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A Predictive 3D Multi-Scale Model of Biliary Fluid Dynamics in the Liver Lobule

Authors: K. Meyer, O. Ostrenko, G. Bourantas, H. Morales-Navarrete, N. Porat-Shliom, F. Segovia-Miranda, H. Nonaka, A. Ghaemi, J. M. Verbavatz, L. Brusch, I. Sbalzarini, Y. Kalaidzidis, R. Weigert, M. Zerial

PubMed ID: 28330614

Date Published: 24th Mar 2017

Projects: Showcase LIAM (Liver Image Analysis Based Model)

Journal: Cell Syst

Citation: Cell Syst. 2017 Mar 15. pii: S2405-4712(17)30052-2. doi: 10.1016/j.cels.2017.02.008.

Scales: Liver lobule

Abstract (Expand)

Bile, the central metabolic product of the liver, is transported by the bile canaliculi network. The impairment of bile flow in cholestatic liver diseases has urged a demand for insights into its ...

Created: 25th Jul 2017 at 13:19

Use of Fibonacci numbers in lipidomics - Enumerating various classes of fatty acids

Authors: S. Schuster, M. Fichtner, S. Sasso

PubMed ID: 28071669

Date Published: 11th Jan 2017

Projects: Showcase Steatosis

Journal: Sci Rep

Citation: Sci Rep. 2017 Jan 10;7:39821. doi: 10.1038/srep39821.

Scales: Cell

Abstract (Expand)

In lipid biochemistry, a fundamental question is how the potential number of fatty acids increases with their chain length. Here, we show that it grows according to the famous Fibonacci numbers when ...

Created: 24th Jun 2017 at 17:16

Quantification of Hepatic Vascular and Parenchymal Regeneration in Mice

Authors: Chichi Xie, Lars Ole Schwen, Weiwei Wei, Andrea Schenk, Sara Zafarnia, Felix Gremse, Uta Dahmen

DOI: 10.1371/journal.pone.0160581

Date Published: 5th Aug 2016

Projects: D4: Regeneration and Liver Size, E3: Horizontal integration on organ scale

Journal: PLoS ONE

Citation: PLoS ONE 11(8) : e0160581

Scales: Liver

Abstract (Expand)

Background. Liver regeneration consists of cellular proliferation leading to parenchymal and vascular growth. This study complements previous studies on cellular proliferation and weight recovery by ...

Created: 26th May 2017 at 09:10 Last updated: 26th May 2017 at 09:12

Model-Based Characterization of Inflammatory Gene Expression Patterns of Activated Macrophages

Authors: Julia Rex, Ute Albrecht, Christian Ehlting, Maria Thomas, Ulrich M. Zanger, Oliver Sawodny, Dieter Häussinger, Michael Ederer, Ronny Feuer, Johannes G. Bode

DOI: 10.1371/journal.pcbi.1005018

Date Published: 27th Jul 2016

Projects: B1: Intercellular communication of hepatocytes and macrophages

Journal: PLoS Comput Biol

Citation: PLoS Comput Biol 12(7) : e1005018

Scales: Cell and Intercellular

Abstract (Expand)

Macrophages are cells with remarkable plasticity. They integrate signals from their microenvironment leading to context-dependent polarization into classically (M1) or alternatively (M2) activated ...

Created: 23rd Nov 2016 at 13:29 Last updated: 23rd Nov 2016 at 13:32

Intrahepatic Size Regulation in a Surgical Model: Liver Resection-Induced Liver Regeneration Counteracts the Local Atrophy following Simultaneous Portal Vein Ligation

Authors: Weiwei Wei, Tianjiao Zhang, Haoshu Fang, Olaf Dirsch, Andrea Schenk, André Homeyer, Felix Gremse, Sara Zafarnia, Utz Settmacher, Uta Dahmen

DOI: 10.1159/000446875

Date Published: 5th Jul 2016

Projects: D4: Regeneration and Liver Size, E3: Horizontal integration on organ scale

Journal: Eur Surg Res

Citation: Eur Surg Res 57(1-2) : 125

Scales: Liver

Abstract (Expand)

Background/Aim: Liver size regulation is based on the balance between hepatic regeneration and atrophy. To achieve a better understanding of intrahepatic size regulation, we explored the size regulation ...

Created: 26th May 2017 at 10:43 Last updated: 26th May 2017 at 10:45

Establishment of a rat model: Associating liver partition with portal vein ligation for staged hepatectomy

Authors: Weiwei Wei, Tianjiao Zhang, Sara Zafarnia, Andrea Schenk, Chichi Xie, Chunyi Kan, Olaf Dirsch, Utz Settmacher, Uta Dahmen

DOI: 10.1016/j.surg.2015.12.005

Date Published: 1st May 2016

Projects: D4: Regeneration and Liver Size, E3: Horizontal integration on organ scale

Journal: Surgery

Citation: Surgery 159(5) : 1299

Scales: Liver

Abstract (Expand)

BACKGROUND: We adapted the anatomically oriented parenchyma-preserving resection technique for associating liver partition with portal vein ligation (PVL) for staged hepatectomy (ALPPS) in rats and ...

Created: 26th May 2017 at 10:46 Last updated: 26th May 2017 at 10:47

Mechanistically linked serum miRNAs distinguish between drug induced and fatty liver disease of different grades

Authors: Z. Liu, Y. Wang, J. Borlak, W. Tong

PubMed ID: 27045805

Date Published: 6th Apr 2016

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

Journal: Sci Rep

Citation: Sci Rep. 2016 Apr 5;6:23709. doi: 10.1038/srep23709.

Scales: Liver

Abstract (Expand)

Hepatic steatosis is characterised by excessive triglyceride accumulation in the form of lipid droplets (LD); however, mechanisms differ in drug induced (DIS) and/or non-alcoholic fatty liver disease ...

Created: 18th May 2016 at 10:50

Zonated Quantification of Steatosis in an Entire Mouse Liver

Authors: Lars Ole Schwen, André Homeyer, Michael Schwier, Uta Dahmen, Olaf Dirsch, Arne Schenk, Lars Kuepfer, Tobias Preusser, Andrea Schenk

DOI: 10.1016/j.compbiomed.2016.04.004

Date Published: 1st Apr 2016

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, Showcase Steatosis

Journal: Computers in Biology and Medicine

Citation: Computers in Biology and Medicine

Scales: Cell, Liver lobule, Liver and Organism

Abstract (Expand)

Many physiological processes and pathological conditions in livers are spatially heterogeneous, forming patterns at the lobular length scale or varying across the organ. Steatosis, a common liver disease ...

Created: 13th Apr 2016 at 15:13 Last updated: 13th Apr 2016 at 15:16

Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse

Authors: J. Zhang, K. He, L. Cai, Y. C. Chen, Y. Yang, Q. Shi, T. F. Woolf, W. Ge, L. Guo, J. Borlak, W. Tong

PubMed ID: 27000539

Date Published: 24th Mar 2016

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

Journal: Chem Biol Interact

Citation: Chem Biol Interact. 2016 Mar 19. pii: S0009-2797(16)30089-8. doi: 10.1016/j.cbi.2016.03.019.

Scales: Cell

Abstract (Expand)

Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of ...

Created: 18th May 2016 at 10:56

Immunogenomics reveal molecular circuits of diclofenac induced liver injury in mice

Authors: E. H. Lee, J. H. Oh, S. Selvaraj, S. M. Park, M. S. Choi, R. Spanel, S. Yoon, J. Borlak

PubMed ID: 26934552

Date Published: 5th Mar 2016

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

Journal: Oncotarget

Citation: Oncotarget. 2016 Feb 25. doi: 10.18632/oncotarget.7698.

Scales: Liver

Abstract (Expand)

Diclofenac is a non-steroidal anti-inflammatory drug and its use can be associated with severe adverse reactions, notably myocardial infarction, stroke and drug-induced liver injury (DILI). In pursue ...

Created: 18th May 2016 at 10:52

Coordinating Role of RXRα in Downregulating Hepatic Detoxification during Inflammation Revealed by Fuzzy-Logic Modeling

Authors: Roland Keller, Marcus Klein, Maria Thomas, Andreas Dräger, Ute Metzger, Markus F. Templin, Thomas O. Joos, Wolfgang E. Thasler, Andreas Zell, Ulrich M. Zanger

DOI: 10.1371/journal.pcbi.1004431

Date Published: 4th Jan 2016

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

Journal: PLoS Comput Biol

Citation: PLoS Comput Biol 12(1) : e1004431

Scales: Cell

Abstract (Expand)

During various inflammatory processes circulating cytokines including IL-6, IL-1β, and TNFα elicit a broad and clinically relevant impairment of hepatic detoxification that is based on the downregulation ...

Created: 7th Jan 2016 at 15:20 Last updated: 7th Jan 2016 at 15:24

Visualization of Vascular and Parenchymal Regeneration after 70% Partial Hepatectomy in Normal Mice

Authors: Chichi Xie, Weiwei Wei, Andrea Schenk, Lars Ole Schwen, Sara Zafarnia, Michael Schwier, Felix Gremse, Isabel Jank, Olaf Dirsch, Uta Dahmen

DOI: 10.3791/53935

Date Published: 2016

Projects: D1: Regulation of Blood Flow and Perfusion in the Liver, D4: Regeneration and Liver Size, E3: Horizontal integration on organ scale, E4: Vertical integration across biological scales

Journal: JoVE

Citation: JoVE (115)

Scales: Liver

Abstract (Expand)

A modified silicone injection procedure was used for visualization of the hepatic vascular tree. This procedure consisted of in-vivo injection of the silicone compound, via a 26 G catheter, into the ...

Created: 14th Sep 2016 at 10:17 Last updated: 14th Sep 2016 at 10:20

The evolution of standards and data management practices in systems biology

Authors: N. J. Stanford, K. Wolstencroft, M. Golebiewski, R. Kania, N. Juty, C. Tomlinson, S. Owen, S. Butcher, H. Hermjakob, N. Le Novere, W. Mueller, J. Snoep, C. Goble

PubMed ID: 26700851

Date Published: 25th Dec 2015

Projects: F1: The data management system, Virtual Liver

Journal: Mol Syst Biol

Citation: Mol Syst Biol. 2015 Dec 23;11(12):851. doi: 10.15252/msb.20156053.

Scales: Not specified

Abstract:

Not specified

Created: 8th Jan 2016 at 09:38

SBMLsqueezer 2: context-sensitive creation of kinetic equations in biochemical networks

Authors: Andreas Dräger, Daniel C Zielinski, Roland Keller, Matthias Rall, Johannes Eichner, Bernhard O Palsson, Andreas Zell

DOI: 10.1186/s12918-015-0212-9

Date Published: 1st Dec 2015

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

Journal: BMC Syst Biol

Citation: BMC Syst Biol 9(1) : 389

Scales: Cell and Intercellular

Abstract (Expand)

Background: The size and complexity of published biochemical network reconstructions are steadily increasing, expanding the potential scale of derived computational models. However, the construction ...

Created: 16th Nov 2015 at 15:27 Last updated: 16th Nov 2015 at 15:29

Intrahepatic Vascular Anatomy in Rats and Mice—Variations and Surgical Implications

Authors: Constanze Sänger, Andrea Schenk, Lars Ole Schwen, Lei Wang, Felix Gremse, Sara Zafarnia, Fabian Kiessling, Chichi Xie, Weiwei Wei, Beate Richter, Olaf Dirsch, Uta Dahmen

DOI: 10.1371/journal.pone.0141798

Date Published: 30th Nov 2015

Projects: D1: Regulation of Blood Flow and Perfusion in the Liver, D4: Regeneration and Liver Size, E3: Horizontal integration on organ scale, E4: Vertical integration across biological scales

Journal: PLoS ONE

Citation: PLoS ONE 10(11) : e0141798

Scales: Liver

Abstract (Expand)

Introduction The intra-hepatic vascular anatomy in rodents, its variations and corresponding supplying and draining territories in respect to the lobar structure of the liver have not been described. ...

Created: 13th Jan 2016 at 08:00 Last updated: 13th Jan 2016 at 08:03

Pathobiochemical signatures of cholestatic liver disease in bile duct ligated mice

Authors: K. Abshagen, M. Konig, A. Hoppe, I. Muller, M. Ebert, H. Weng, H. G. Holzhutter, U. M. Zanger, J. Bode, B. Vollmar, M. Thomas, S. Dooley

PubMed ID: 26589287

Date Published: 20th Nov 2015

Projects: A1: Cellular metabolism, A2: Integration of Signalling Pathways in Hepatocellular Response, A3: Crosslinking signalling metabolism and hepatocyte polarisation, B: Communication of Hepatocytes and Non-Parenchymal Liver Cells, C: Liver lobule level, D: Whole organ level

Journal: BMC Syst Biol

Citation: BMC Syst Biol. 2015 Nov 20;9(1):83.

Scales: Cell, Liver lobule and Liver

Abstract (Expand)

BACKGROUND: Disrupted bile secretion leads to liver damage characterized by inflammation, fibrosis, eventually cirrhosis, and hepatocellular cancer. As obstructive cholestasis often progresses insidiously, ...

Created: 23rd Nov 2015 at 07:41

Evaluation of multiple mechanism-based toxicity endpoints in primary cultured human hepatocytes for the identification of drugs with clinical hepatotoxicity: Results from 152 marketed drugs with known liver injury profiles

Authors: J. Zhang, U. Doshi, A. Suzuki, C. W. Chang, J. Borlak, A. P. Li, W. Tong

PubMed ID: 26581450

Date Published: 20th Nov 2015

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions

Journal: Chem Biol Interact

Citation: Chem Biol Interact. 2015 Nov 12. pii: S0009-2797(15)30110-1. doi: 10.1016/j.cbi.2015.11.008.

Scales: Cell

Abstract (Expand)

We report here the results of a collaborative research program to develop a robust and reliable in vitro system to allow an accurate definition of the drug-induced liver injury (DILI) potential of new ...

Created: 30th Dec 2015 at 10:41

The Therapeutic Promise of Mesenchymal Stem Cells for Liver Restoration

Authors: B. Christ, S. Bruckner, S. Winkler

PubMed ID: 26476857

Date Published: 22nd Oct 2015

Projects: C6: Organization and function of the sinusoidal system and the liver lob...

Journal: Trends Mol Med

Citation: Trends Mol Med. 2015 Nov;21(11):673-86. doi: 10.1016/j.molmed.2015.09.004. Epub 2015 Oct 22.

Scales: Liver

Abstract (Expand)

Hepatocyte transplantation aims to provide a functional substitution of liver tissue lost due to trauma or toxins. Chronic liver diseases are associated with inflammation, deterioration of tissue ...

Created: 11th Nov 2015 at 11:21

Virtual pathway explorer (viPEr) and pathway enrichment analysis tool (PEANuT): creating and analyzing focus networks to identify cross-talk between molecules and pathways

Authors: M. Garmhausen, F. Hofmann, V. Senderov, M. Thomas, B. A. Kandel, B. H. Habermann

PubMed ID: 26467653

Date Published: 14th Oct 2015

Projects: A1.3: Identification of crucial metabolic processes during hepatocyte pr..., A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato..., A3.5: The impact of cell polarity on metabolism detoxification and endoc..., C2: Organization of the sinusoidal system and the liver lobule - referen..., C5: Structural changes and functional consequences of the liver lobular/..., C6: Organization and function of the sinusoidal system and the liver lob...

Journal: BMC Genomics

Citation: BMC Genomics. 2015 Oct 14;16(1):790. doi: 10.1186/s12864-015-2017-z.

Scales: Not specified

Abstract (Expand)

BACKGROUND: Interpreting large-scale studies from microarrays or next-generation sequencing for further experimental testing remains one of the major challenges in quantitative biology. Combining ...

Created: 18th Dec 2015 at 12:55

Optimality in the zonation of ammonia detoxification in rodent liver

Authors: M. Bartl, M. Pfaff, A. Ghallab, D. Driesch, S. G. Henkel, J. G. Hengstler, S. Schuster, C. Kaleta, R. Gebhardt, S. Zellmer, P. Li

PubMed ID: 26438405

Date Published: 5th Oct 2015

Projects: C3: Zonation of metabolism and its regulation

Journal: Arch Toxicol

Citation: Arch Toxicol. 2015 Nov;89(11):2069-78. doi: 10.1007/s00204-015-1596-4. Epub 2015 Oct 5.

Scales: Cell, Intercellular and Liver lobule

Abstract (Expand)

The rodent liver eliminates toxic ammonia. In mammals, three enzymes (or enzyme systems) are involved in this process: glutaminase, glutamine synthetase and the urea cycle enzymes, represented by ...

Created: 11th Dec 2015 at 09:07

Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics

Authors: M. G. Mooij, A. T. Nies, C. A. Knibbe, E. Schaeffeler, D. Tibboel, M. Schwab, S. N. de Wildt

PubMed ID: 26410689

Date Published: 28th Sep 2015

Projects: G2: Clinical Translation to Non-Invasive Volunteer Setting, G3: Clinical Translation to Pharmaceutical Drug Development

Journal: Clin Pharmacokinet

Citation: Clin Pharmacokinet. 2015 Sep 26.

Scales: Not specified

Abstract (Expand)

Membrane transporters play an essential role in the transport of endogenous and exogenous compounds, and consequently they mediate the uptake, distribution, and excretion of many drugs. The clinical ...

Created: 17th Dec 2015 at 11:53

Causes of upregulation of glycolysis in lymphocytes upon stimulation. A comparison with other cell types

Authors: H. Stark, M. Fichtner, R. Konig, S. Lorkowski, S. Schuster

PubMed ID: 26382968

Date Published: 14th Sep 2015

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

Journal: Biochimie

Citation: Biochimie. 2015 Nov;118:185-94. doi: 10.1016/j.biochi.2015.09.017. Epub 2015 Sep 14.

Scales: Cell

Abstract (Expand)

In this review, we revisit the metabolic shift from respiration to glycolysis in lymphocytes upon activation, which is known as the Warburg effect in tumour cells. We compare the situation in lymphocytes ...

Created: 11th Dec 2015 at 16:06

Heritability of metoprolol and torsemide pharmacokinetics

Authors: J. Matthaei, J. Brockmoller, M. V. Tzvetkov, D. Sehrt, C. Sachse-Seeboth, J. B. Hjelmborg, S. Moller, U. Halekoh, U. Hofmann, M. Schwab, R. Kerb

PubMed ID: 26344676

Date Published: 8th Sep 2015

Projects: G2: Clinical Translation to Non-Invasive Volunteer Setting, G3: Clinical Translation to Pharmaceutical Drug Development

Journal: Clin Pharmacol Ther

Citation: Clin Pharmacol Ther. 2015 Sep 7. doi: 10.1002/cpt.258.

Scales: Not specified

Abstract (Expand)

Genetic variation in the pharmacokinetics of metoprolol and torsemide due to polymorphisms in CYP2D6, CYP2C9, and OATP1B1 has been extensively studied. However, it is still unknown how much of the ...

Created: 17th Dec 2015 at 11:46

Specifications of Standards in Systems and Synthetic Biology

Authors: F. Schreiber, G. D. Bader, M. Golebiewski, M. Hucka, B. Kormeier, N. Le Novere, C. Myers, D. Nickerson, B. Sommer, D. Waltemath, S. Weise

PubMed ID: 26528556

Date Published: 4th Sep 2015

Projects: F1: The data management system, Virtual Liver

Journal: J Integr Bioinform

Citation: J Integr Bioinform. 2015 Sep 4;12(2):258. doi: 10.2390/biecoll-jib-2015-258.

Scales: Not specified

Abstract (Expand)

Standards shape our everyday life. From nuts and bolts to electronic devices and technological processes, standardised products and processes are all around us. Standards have technological and economic ...

Created: 17th Dec 2015 at 09:15

LEMming: A Linear Error Model to Normalize Parallel Quantitative Real-Time PCR (qPCR) Data as an Alternative to Reference Gene Based Methods

Authors: R. Feuer, S. Vlaic, J. Arlt, O. Sawodny, U. Dahmen, U. M. Zanger, M. Thomas

PubMed ID: 26325269

Date Published: 1st Sep 2015

Journal: PLoS One

Citation: PLoS One. 2015 Sep 1;10(9):e0135852. doi: 10.1371/journal.pone.0135852. eCollection 2015.

Scales: Cell

Abstract (Expand)

BACKGROUND: Gene expression analysis is an essential part of biological and medical investigations. Quantitative real-time PCR (qPCR) is characterized with excellent sensitivity, dynamic range, ...

Created: 17th Sep 2015 at 10:13

Comparative Analysis and Functional Characterization of HC-AFW1 Hepatocarcinoma Cells: CYP Expression and Induction by Nuclear Receptor Agonists

Authors: A. Braeuning, M. Thomas, U. Hofmann, S. Vetter, E. Zeller, B. Petzuch, J. Johanning, W. Schroth, T. S. Weiss, U. M. Zanger, M. Schwarz

PubMed ID: 26310804

Date Published: 28th Aug 2015

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

Journal: Drug Metab Dispos

Citation: Drug Metab Dispos. 2015 Aug 26. pii: dmd.115.064667.

Scales: Cell

Abstract (Expand)

Enzymatic conversion of most xenobiotic compounds is accomplished by hepatocytes in the liver, which are also an important target for the manifestation of the toxic effects of foreign compounds. Most ...

Created: 17th Sep 2015 at 10:17

Mouse white adipose tissue-derived mesenchymal stem cells gain pericentral and periportal hepatocyte features after differentiation in vitro, which are preserved in vivo after hepatic transplantation

Authors: S. Winkler, M. Hempel, S. Bruckner, F. Mallek, A. Weise, T. Liehr, H. M. Tautenhahn, M. Bartels, B. Christ

PubMed ID: 26235702

Date Published: 19th Aug 2015

Projects: C6: Organization and function of the sinusoidal system and the liver lob...

Journal: Acta Physiol (Oxf)

Citation: Acta Physiol (Oxf). 2015 Oct;215(2):89-104. doi: 10.1111/apha.12560. Epub 2015 Aug 19.

Scales: Liver lobule

Abstract (Expand)

AIM: Mesenchymal stem cells may differentiate into hepatocyte-like cells in vitro and in vivo. Therefore, they are considered a novel cell resource for the treatment of various liver diseases. Here, ...

Created: 11th Nov 2015 at 11:22

SDA 7: A modular and parallel implementation of the simulation of diffusional association software

Authors: Michael Martinez, Neil J. Bruce, Julia Romanowska, Daria B. Kokh, Musa Ozboyaci, Xiaofeng Yu, Mehmet Ali Öztürk, Stefan Richter, Rebecca C. Wade

DOI: 10.1002/jcc.23971

Date Published: 5th Aug 2015

Projects: A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato...

Journal: J. Comput. Chem.

Citation: J. Comput. Chem. 36(21) : 1631

Scales: Cell

Abstract (Expand)

The simulation of diffusional association (SDA) Brownian dynamics software package has been widely used in the study of biomacromolecular association. Initially developed to calculate bimolecular ...

Created: 18th Sep 2015 at 11:12 Last updated: 18th Sep 2015 at 12:36

Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation

Authors: Nadinath B. Nillegoda, Janine Kirstein, Anna Szlachcic, Mykhaylo Berynskyy, Antonia Stank, Florian Stengel, Kristin Arnsburg, Xuechao Gao, Annika Scior, Ruedi Aebersold, D. Lys Guilbride, Rebecca C. Wade, Richard I. Morimoto, Matthias P. Mayer, Bernd Bukau

DOI: 10.1038/nature14884

Date Published: 5th Aug 2015

Projects: A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato...

Journal: Nature

Citation: Nature 524(7564) : 247

Scales: Organism

Abstract (Expand)

Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states. Healthy metazoan cells effectively eliminate intracellular protein aggregates, ...

Created: 18th Sep 2015 at 13:35 Last updated: 18th Sep 2015 at 13:41

Variability in hepatic expression of organic anion transporter 7/SLC22A9, a novel pravastatin uptake transporter: impact of genetic and regulatory factors

Authors: A. Emami Riedmaier, O. Burk, B. A. van Eijck, E. Schaeffeler, K. Klein, S. Fehr, S. Biskup, S. Muller, S. Winter, U. M. Zanger, M. Schwab, A. T. Nies

PubMed ID: 26239079

Date Published: 5th Aug 2015

Projects: G2: Clinical Translation to Non-Invasive Volunteer Setting, G3: Clinical Translation to Pharmaceutical Drug Development

Journal: Pharmacogenomics J

Citation: Pharmacogenomics J. 2015 Aug 4. doi: 10.1038/tpj.2015.55.

Scales: Not specified

Abstract (Expand)

Human organic anion transporter 7 (OAT7, SLC22A9) is a hepatic transport protein poorly characterized so far. We therefore sought to identify novel OAT7 substrates and factors contributing to variable ...

Created: 17th Dec 2015 at 11:49

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

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

SEEK: a systems biology data and model management platform

Authors: K. Wolstencroft, S. Owen, O. Krebs, Q. Nguyen, N. J. Stanford, M. Golebiewski, A. Weidemann, M. Bittkowski, L. An, D. Shockley, J. L. Snoep, W. Mueller, C. Goble

PubMed ID: 26160520

Date Published: 11th Jul 2015

Projects: F1: The data management system, Virtual Liver

Journal: BMC Syst Biol

Citation: BMC Syst Biol. 2015 Jul 11;9:33. doi: 10.1186/s12918-015-0174-y.

Scales: Not specified

Abstract (Expand)

BACKGROUND: Systems biology research typically involves the integration and analysis of heterogeneous data types in order to model and predict biological processes. Researchers therefore require tools ...

Created: 7th Aug 2015 at 11:48

The truncated splice variant of peroxisome proliferator-activated receptor alpha, PPARalpha-tr, autonomously regulates proliferative and pro-inflammatory genes

Authors: M. Thomas, C. Bayha, K. Klein, S. Muller, T. S. Weiss, M. Schwab, U. M. Zanger

PubMed ID: 26122096

Date Published: 30th Jun 2015

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

Journal: BMC Cancer

Citation: BMC Cancer. 2015 Jun 30;15:488. doi: 10.1186/s12885-015-1500-x.

Scales: Not specified

Abstract (Expand)

BACKGROUND: The peroxisome proliferator-activated receptor alpha (PPARalpha) controls lipid/energy homeostasis and inflammatory responses. The truncated splice variant PPARalpha-tr was suggested to ...

Created: 17th Sep 2015 at 10:19

webSDA: a web server to simulate macromolecular diffusional association

Authors: Xiaofeng Yu, Michael Martinez, Annika L. Gable, Jonathan C. Fuller, Neil J. Bruce, Stefan Richter, Rebecca C. Wade

DOI: 10.1093/nar/gkv335

Date Published: 30th Jun 2015

Projects: F3: Kinetic data handling

Journal: Nucleic Acids Res

Citation: Nucleic Acids Res 43(W1) : W220

Scales: Cell

Abstract (Expand)

Macromolecular interactions play a crucial role in biological systems. Simulation of diffusional association (SDA) is a software for carrying out Brownian dynamics simulations that can be used to study ...

Created: 18th Sep 2015 at 13:33 Last updated: 18th Sep 2015 at 13:34

libRoadRunner: A High Performance SBML Simulation and Analysis Library

Authors: Endre T Somogyi, Jean-Marie Bouteiller, James A Glazier, Matthias König, J Kyle Medley, Maciej H Swat, Herbert M Sauro

PubMed ID: 26085503

Date Published: 19th Jun 2015

Projects: No Projects

Journal: Bioinformatics

Citation: Bioinformatics :

Scales: Not specified

Abstract (Expand)

This paper presents libRoadRunner, an extensible, high-performance, cross-platform, open-source software library for the simulation and analysis of models expressed using Systems Biology Markup Language ...

Created: 1st Jul 2015 at 16:00

JSBML 1.0: providing a smorgasbord of options to encode systems biology models

Authors: N. Rodriguez, A. Thomas, L. Watanabe, I. Y. Vazirabad, V. Kofia, H. F. Gomez, F. Mittag, J. Matthes, J. Rudolph, F. Wrzodek, E. Netz, A. Diamantikos, J. Eichner, R. Keller, C. Wrzodek, S. Frohlich, N. E. Lewis, C. J. Myers, N. Le Novere, B. O. Palsson, M. Hucka, A. Drager

PubMed ID: 26079347

Date Published: 17th Jun 2015

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

Journal: Bioinformatics

Citation: Bioinformatics :

Scales: Cell, Intercellular, Liver lobule, Liver and Organism

Abstract (Expand)

JSBML, the official pure Java programming library for the SBML format, has evolved with the advent of different modeling formalisms in systems biology and their ability to be exchanged and represented ...

Created: 22nd Jun 2015 at 17:56

Is laboratory medicine ready for the era of personalized medicine? A survey addressed to laboratory directors of hospitals/academic schools of medicine in Europe

Authors: F. Malentacchi, I. Mancini, I. Brandslund, P. Vermeersch, M. Schwab, J. Marc, R. H. van Schaik, G. Siest, E. Theodorsson, M. Pazzagli, C. Di Resta

PubMed ID: 26036226

Date Published: 4th Jun 2015

Projects: G2: Clinical Translation to Non-Invasive Volunteer Setting, G3: Clinical Translation to Pharmaceutical Drug Development

Journal: Drug Metabol Personal Ther

Citation: Drug Metabol Personal Ther. 2015 Jun;30(2):121-8. doi: 10.1515/dmdi-2015-0012.

Scales: Not specified

Abstract (Expand)

Developments in "-omics" are creating a paradigm shift in laboratory medicine leading to personalized medicine. This allows the increase in diagnostics and therapeutics focused on individuals ...

Created: 17th Dec 2015 at 11:44

Tools for visualization and analysis of molecular networks, pathways, and -omics data

Authors: J. M. Villaveces, P. Koti, B. H. Habermann

PubMed ID: 26082651

Date Published: 4th Jun 2015

Journal: Adv Appl Bioinform Chem

Citation: Adv Appl Bioinform Chem. 2015 Jun 4;8:11-22. doi: 10.2147/AABC.S63534. eCollection 2015.

Scales: Not specified

Abstract (Expand)

Biological pathways have become the standard way to represent the coordinated reactions and actions of a series of molecules in a cell. A series of interconnected pathways is referred to as a biological ...

Created: 18th Dec 2015 at 12:57

Fast and accurate identification of fat droplets in histological images

Authors: André Homeyer, Andrea Schenk, Janine Arlt, Uta Dahmen, Olaf Dirsch, Horst K. Hahn

DOI: 10.1016/j.cmpb.2015.05.009

Date Published: 1st Jun 2015

Projects: D4: Regeneration and Liver Size, Showcase Steatosis

Journal: Computer Methods and Programs in Biomedicine

Citation: Computer Methods and Programs in Biomedicine

Scales: Cell, Liver lobule and Liver

Abstract (Expand)

Background and objective: The accurate identification of fat droplets is a prerequisite for the automatic quantification of steatosis in histological images. A major challenge in this regard is the ...

Created: 25th Jun 2015 at 09:02 Last updated: 29th Jun 2015 at 09:38

Hepatocyte fate upon TGF-β challenge is determined by the matrix environment

Authors: Christoph Meyer, Roman Liebe, Katja Breitkopf-Heinlein, Yan Liu, Alexandra Müller, Pia Rakoczy, Maria Thomas, Honglei Weng, Anastasia Bachmann, Matthias Ebert, Steven Dooley

PubMed ID: 25982745

Date Published: 20th May 2015

Projects: A2.2: Regulation of pro-apoptotic and anti-apoptotic responses in hepato..., A3.3: Hepatocyte polarity

Journal: Differentiation

Citation: Differentiation :

Scales: Cell

Abstract (Expand)

Primary hepatocytes are a versatile tool to investigate all aspects of liver function, and frequently used in drug development and testing. Upon TGF-β challenge, hepatocytes either undergo an epithelial ...

Created: 17th Jun 2015 at 09:09

Computational Approaches for Studying Drug Binding Kinetics

Authors: Julia Romanowska, Daria B. Kokh, Jonathan C. Fuller, Rebecca C. Wade

DOI: 10.1002/9783527673025.ch11

Date Published: 11th May 2015

Projects: F3: Kinetic data handling

Book: Thermodynamics and Kinetics of Drug Binding

Citation: Methods and Principles in Medicinal Chemistry : 211

Scales: Cell

Abstract (Expand)

The binding kinetics of a drug to its macromolecular receptor can be of key importance for its overall efficacy. Thus, there is a need for methods to compute and predict kinetic parameters for drug-receptor ...

Created: 18th Sep 2015 at 13:23 Last updated: 18th Sep 2015 at 13:26

Drug-Induced liver injury: interactions between drug properties and host factors

Authors: Minjun Chen, Ayako Suzuki, Jürgen Borlak, Raúl J Andrade, M Isabel Lucena

PubMed ID: 25912521

Date Published: 29th Apr 2015

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions, A3.6: Transcription factor network and links to metabolism in NAFLD

Journal: J. Hepatol.

Citation: J. Hepatol. :

Scales: Not specified

Abstract (Expand)

Idiosyncratic drug-induced liver injury (DILI) is a common cause for drug withdrawal from the market and although infrequent, DILI can result in serious clinical outcomes including acute liver failure ...

Created: 5th May 2015 at 09:06

Disentangling the Complexity of HGF Signaling by Combining Qualitative and Quantitative Modeling

Authors: Lorenza A. D’Alessandro, Regina Samaga, Tim Maiwald, Seong-Hwan Rho, Sandra Bonefas, Andreas Raue, Nao Iwamoto, Alexandra Kienast, Katharina Waldow, Rene Meyer, Marcel Schilling, Jens Timmer, Steffen Klamt, Ursula Klingmüller

DOI: 10.1371/journal.pcbi.1004192

Date Published: 23rd Apr 2015

Projects: A2.1: Multi-level regulation of signalling pathways important for primin..., A2.3: Cross-talk and distinct properties of growth factor signalling reg..., A2.4: Linking signalling pathways regulating liver regeneration and orga..., A2: Integration of Signalling Pathways in Hepatocellular Response, A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato..., A3.4: Linking signalling to metabolic functions, E1: Integration on the cellular level, Showcase HGF and Regeneration

Journal: PLoS Comput Biol

Citation: PLoS Comput Biol 11(4) : e1004192

Scales: Cell

Abstract (Expand)

Signaling pathways are characterized by crosstalk, feedback and feedforward mechanisms giving rise to highly complex and cell-context specific signaling networks. Dissecting the underlying relations ...

Created: 5th May 2015 at 13:29 Last updated: 22nd May 2015 at 08:57

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

Functional characterization of common protein variants in the efflux transporter ABCC11 and identification of T546M as functionally damaging variant

Authors: R. Arlanov, T. Lang, G. Jedlitschky, E. Schaeffeler, T. Ishikawa, M. Schwab, A. T. Nies

PubMed ID: 25896536

Date Published: 22nd Apr 2015

Projects: G2: Clinical Translation to Non-Invasive Volunteer Setting, G3: Clinical Translation to Pharmaceutical Drug Development

Journal: Pharmacogenomics J

Citation: Pharmacogenomics J. 2015 Apr 21. doi: 10.1038/tpj.2015.27.

Scales: Not specified

Abstract (Expand)

Multidrug resistance protein 8 (ABCC11) is an efflux transporter for anionic lipophilic compounds, conferring resistance to antiviral and anticancer agents like 5-fluorouracil (5-FU). ABCC11 missense ...

Created: 17th Dec 2015 at 11:41

Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature

Authors: S. Wolking, E. Schaeffeler, H. Lerche, M. Schwab, A. T. Nies

PubMed ID: 25860377

Date Published: 11th Apr 2015

Projects: G2: Clinical Translation to Non-Invasive Volunteer Setting, G3: Clinical Translation to Pharmaceutical Drug Development

Journal: Clin Pharmacokinet

Citation: Clin Pharmacokinet. 2015 Jul;54(7):709-35. doi: 10.1007/s40262-015-0267-1.

Scales: Not specified

Abstract (Expand)

ATP-binding cassette transporter B1 (ABCB1; P-glycoprotein; multidrug resistance protein 1) is an adenosine triphosphate (ATP)-dependent efflux transporter located in the plasma membrane of many different ...

Created: 17th Dec 2015 at 11:51

Activating and Inhibitory Functions of WNT/β-catenin in the Induction of Cytochromes P450 by Nuclear Receptors in HepaRG Cells

Authors: Maria Thomas, Christine Bayha, Silvia Vetter, Ute Hofmann, Michael Schwarz, Ulrich M Zanger, Albert Braeuning

PubMed ID: 25824487

Date Published: 1st Apr 2015

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

Journal: Mol. Pharmacol.

Citation: Mol. Pharmacol. :

Scales: Cell

Abstract (Expand)

The WNT/β-catenin signaling pathway has been identified as an important endogenous regulator of hepatic cytochrome P450 (CYP) expression in mouse liver. In particular, it is involved in the regulation ...

Created: 7th Apr 2015 at 14:00

Mathematical modelling of fluid transport and its regulation at multiple scales

Authors: Osvaldo Chara, Lutz Brusch

DOI: 10.1016/j.biosystems.2015.02.004

Date Published: 1st Apr 2015

Projects: A3.3: Hepatocyte polarity, A3.5: The impact of cell polarity on metabolism detoxification and endoc..., Showcase LIAM (Liver Image Analysis Based Model)

Journal: Biosystems

Citation: Biosystems 130 : 1

Scales: Cell and Liver lobule

Abstract (Expand)

Living matter equals water, to a first approximation, and water transport across barriers such as membranes and epithelia is vital. Water serves two competing functions. On the one hand, it is the ...

Created: 30th Apr 2015 at 15:04 Last updated: 30th Apr 2015 at 15:08

Dysregulated serum response factor triggers formation of hepatocellular carcinoma

Authors: Stefan Ohrnberger, Abhishek Thavamani, Albert Braeuning, Daniel B. Lipka, Milen Kirilov, Robert Geffers, Stella E. Authenrieth, Michael Römer, Andreas Zell, Michael Bonin, Michael Schwarz, Günther Schütz, Peter Schirmacher, Christoph Plass, Thomas Longerich, Alfred Nordheim

DOI: 10.1002/hep.27539

Date Published: 1st Mar 2015

Projects: C6: Organization and function of the sinusoidal system and the liver lob...

Journal: Hepatology

Citation: Hepatology 61(3) : 979

Scales: Cell, Intercellular and Liver lobule

Abstract (Expand)

The ubiquitously expressed transcriptional regulator serum response factor (SRF) is controlled by both Ras/MAPK (mitogen-activated protein kinase) and Rho/actin signaling pathways, which are frequently ...

Created: 14th Dec 2015 at 15:12 Last updated: 14th Dec 2015 at 15:15

Proteome mapping of epidermal growth factor induced hepatocellular carcinomas identifies novel cell metabolism targets and mitogen activated protein kinase signalling events

Authors: Jürgen Borlak, Prashant Singh, Giuseppe Gazzana

PubMed ID: 25872475

Date Published: 25th Feb 2015

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

Journal: BMC Genomics

Citation: BMC Genomics 16: 124

Scales: Cell

Abstract (Expand)

Hepatocellular carcinoma (HCC) is on the rise and the sixth most common cancer worldwide. To combat HCC effectively research is directed towards its early detection and the development of targeted ...

Created: 5th May 2015 at 13:29

Promoting Coordinated Development of Community-Based Information Standards for Modeling in Biology: The COMBINE Initiative

Authors: Michael Hucka, David P. Nickerson, Gary D. Bader, Frank T. Bergmann, Jonathan Cooper, Emek Demir, Alan Garny, Martin Golebiewski, Chris J. Myers, Falk Schreiber, Dagmar Waltemath, Nicolas Le NovÃ¨re

DOI: 10.3389/fbioe.2015.00019

Date Published: 24th Feb 2015

Projects: F1: The data management system, Virtual Liver

Journal: Front. Bioeng. Biotechnol.

Citation: Front. Bioeng. Biotechnol. 3

Scales: Not specified

Abstract (Expand)

The Computational Modeling in Biology Network (COMBINE) is a consortium of groups involved in the development of open community standards and formats used in computational modeling in biology. COMBINE’s ...

Created: 25th Feb 2015 at 12:58 Last updated: 25th Feb 2015 at 13:01

Pathological implications of cadherin zonation in mouse liver

Authors: M. Hempel, A. Schmitz, S. Winkler, O. Kucukoglu, S. Bruckner, C. Niessen, B. Christ

PubMed ID: 25687506

Date Published: 17th Feb 2015

Projects: C6: Organization and function of the sinusoidal system and the liver lob...

Journal: Cell Mol Life Sci

Citation: Cell Mol Life Sci. 2015 Jul;72(13):2599-612. doi: 10.1007/s00018-015-1861-y. Epub 2015 Feb 17.

Scales: Liver lobule

Abstract (Expand)

Both acute and chronic liver diseases are associated with ample re-modeling of the liver parenchyma leading to functional impairment, which is thus obviously the cause or the consequence of the disruption ...

Created: 11th Nov 2015 at 11:12

Zonation of hepatic fatty acid metabolism - The diversity of its regulation and the benefit of modeling

Authors: J Schleicher, C Tokarski, E Marbach, M Matz-Soja, S Zellmer, R Gebhardt, S Schuster

PubMed ID: 25677822

Date Published: 14th Feb 2015

Projects: C3: Zonation of metabolism and its regulation

Journal: Biochim. Biophys. Acta

Citation: Biochim. Biophys. Acta :

Scales: Intercellular and Liver lobule

Abstract (Expand)

A pronounced heterogeneity between hepatocytes in subcellular structure and enzyme activities was discovered more than 50years ago and initiated the idea of metabolic zonation. In the last decades ...

Created: 26th Feb 2015 at 09:40

Computational prediction of molecular pathogen-host interactions based on dual transcriptome data

Authors: Sylvie Schulze, Sebastian G. Henkel, Dominik Driesch, Reinhard Guthke, JÃ¶rg Linde

DOI: 10.3389/fmicb.2015.00065

Date Published: 6th Feb 2015

Projects: Virtual Liver

Journal: Front. Microbiol.

Citation: Front. Microbiol. 6

Scales: Cell and Intercellular

Abstract:

Not specified

Created: 11th Feb 2015 at 08:18 Last updated: 11th Feb 2015 at 08:24

A Quick Guide for Building a Successful Bioinformatics Community

Authors: Aidan Budd, Manuel Corpas, Michelle D. Brazas, Jonathan C. Fuller, Jeremy Goecks, Nicola J. Mulder, Magali Michaut, B. F. Francis Ouellette, Aleksandra Pawlik, Niklas Blomberg

DOI: 10.1371/journal.pcbi.1003972

Date Published: 5th Feb 2015

Projects: No Projects

Journal: PLoS Comput Biol

Citation: PLoS Comput Biol 11(2) : e1003972

Scales: Not specified

Abstract (Expand)

“Scientific community” refers to a group of people collaborating together on scientific-research-related activities who also share common goals, interests, and values. Such communities play a key role ...

Created: 9th Feb 2015 at 13:55 Last updated: 9th Feb 2015 at 14:06

Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation

Authors: Hai Li, Qiang Xia, Bo Zeng, Shu-Ting Li, Heng Liu, Qi Li, Jun Li, Shu-Yin Yang, Xiao-Jun Dong, Ting Gao, Stefan Munker, Yan Liu, Roman Liebe, Feng Xue, Qi-Gen Li, Xiao-Song Chen, Qiang Liu, Hui Zeng, Ji-Yao Wang, Qing Xie, Qin-Hua Meng, Jie-Fei Wang, Peter R Mertens, Frank Lammert, Manfred V Singer, Steven Dooley, Matthias P A Ebert, De-Kai Qiu, Tai-Ling Wang, Hong-Lei Weng

PubMed ID: 25646889

Date Published: 4th Feb 2015

Projects: C5: Structural changes and functional consequences of the liver lobular/...

Journal: J. Hepatol.

Citation: J. Hepatol. :

Scales: Liver and Organism

Abstract:

Distinguishing between acute on chronic liver failure (ACLF) and decompensated liver cirrhosis is difficult due to a lack of pathological evidence.

Created: 17th Jun 2015 at 09:18

Human sterol regulatory element-binding protein 1a contributes significantly to hepatic lipogenic gene expression

Authors: Andreas Bitter, Andreas K Nüssler, Wolfgang E Thasler, Kathrin Klein, Ulrich M Zanger, Matthias Schwab, Oliver Burk

PubMed ID: 25634759

Date Published: 30th Jan 2015

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions, A3.4: Linking signalling to metabolic functions, B5: Cell-cell communication influences detoxifying functions in hepatocytes, G2: Clinical Translation to Non-Invasive Volunteer Setting, G3: Clinical Translation to Pharmaceutical Drug Development, Showcase Steatosis

Journal: Cell. Physiol. Biochem.

Citation: Cell. Physiol. Biochem. 35(2): 803-15

Scales: Not specified

Abstract (Expand)

Sterol regulatory element-binding protein (SREBP) 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform ...

Created: 7th Apr 2015 at 14:59

Ten Simple Rules for Organizing an Unconference

Authors: Aidan Budd, Holger Dinkel, Manuel Corpas, Jonathan C. Fuller, Laura Rubinat, Damien P. Devos, Pierre H. Khoueiry, Konrad U. Förstner, Fotis Georgatos, Francis Rowland, Malvika Sharan, Janos X. Binder, Tom Grace, Karyn Traphagen, Adam Gristwood, Natasha T. Wood

DOI: 10.1371/journal.pcbi.1003905

Date Published: 29th Jan 2015

Projects: No Projects

Journal: PLoS Comput Biol

Citation: PLoS Comput Biol 11(1) : e1003905

Scales: Not specified

Abstract:

Not specified

Created: 2nd Feb 2015 at 14:43 Last updated: 2nd Feb 2015 at 14:47

Smad7 regulates compensatory hepatocyte proliferation in damaged mouse liver and positively relates to better clinical outcome in human hepatocellular carcinoma

Authors: Teng Feng, Johanna Dzieran, Xing Gu, Silke Marhenke, Arndt Vogel, Keigo Machida, Thomas S Weiss, Petra Ruemmele, Otto Kollmar, Patrick Hoffmann, Friedrich Grässer, Heike Allgayer, Jasmin Fabian, Hong Lei Weng, Andreas Teufel, Thorsten Maass, Christoph Meyer, Ulrich Lehmann, Cheng Zhu, Peter R Mertens, Chun Fang Gao, Steven Dooley, Nadja M Meindl-Beinker

PubMed ID: 25602745

Date Published: 21st Jan 2015

Projects: A2.1: Multi-level regulation of signalling pathways important for primin..., B2.3: Effect of hepatic stellate cells on hepatocyte polarity and transd...

Journal: Clin. Sci.

Citation: Clin. Sci. 128(11): 761-74

Scales: Liver

Abstract (Expand)

Transforming growth factor β (TGF-β) is cytostatic towards damage-induced compensatory hepatocyte proliferation. This function is frequently lost during hepatocarcinogenesis, thereby switching the TGF-β ...

Created: 17th Jun 2015 at 11:08

GPU-Accelerated Sparse Matrix-Matrix Multiplication by Iterative Row Merging

Authors: Felix Gremse, Andreas Höfter, Lars Ole Schwen, Fabian Kiessling, Uwe Naumann

DOI: 10.1137/130948811

Date Published: 8th Jan 2015

Projects: D3: Inflammation and Regeneration: the whole organ

Journal: SIAM J. Sci. Comput.

Citation: SIAM J. Sci. Comput. 37(1) : C54

Scales: Organism

Abstract (Expand)

We present an algorithm for general sparse matrix-matrix multiplication (SpGEMM) on many-core architectures, such as GPUs. SpGEMM is implemented by iterative row merging, similar to merge sort, except ...

Created: 26th Jan 2015 at 16:56 Last updated: 26th Jan 2015 at 17:01

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

Oncostatin M regulates SOCS3 mRNA stability via the MEK-ERK1/2-pathway independent of p38(MAPK)/MK2

Authors: Christian Ehlting, Oliver Böhmer, Maximilian J Hahnel, Maria Thomas, Ulrich M Zanger, Matthias Gaestel, Wolfram T Knoefel, Jan Schulte Am Esch, Dieter Häussinger, Johannes G Bode

PubMed ID: 25562430

Date Published: 7th Jan 2015

Projects: A1.3: Identification of crucial metabolic processes during hepatocyte pr..., A2.1: Multi-level regulation of signalling pathways important for primin..., A2.3: Cross-talk and distinct properties of growth factor signalling reg..., A2.4: Linking signalling pathways regulating liver regeneration and orga..., A: Cellular level

Journal: Cell. Signal.

Citation: Cell. Signal. :

Scales: Not specified

Abstract (Expand)

The induction of suppressor of cytokine signalling (SOCS)3 expression context dependently involves regulation of SOCS3 transcript stability as previously demonstrated for MAPK activated protein kinase ...

Created: 7th Jan 2015 at 14:25

Mathematical Modelling suggests Differential Impact of β-TrCP Paralogues on Wnt/β-catenin Signalling Dynamics

Authors: Uwe Benary, Bente Kofahl, Andreas Hecht, Jana Wolf

DOI: 10.1111/febs.13204

Date Published: 2015

Projects: A2.5: Integration of insulin and Wnt signalling in hepatocytes, B2.2: Importance of Wnt- and Hedgehog factors for hepatic stellate cells...

Journal: FEBS J

Citation: FEBS J : n/a

Scales: Cell

Abstract (Expand)

The Wnt/β-catenin signalling pathway is involved in the regulation of a multitude of cellular processes by controlling the concentration of the transcriptional regulator β-catenin. Proteasomal degradation ...

Created: 20th Jan 2015 at 07:51 Last updated: 20th Jan 2015 at 07:52

Implementation of systems theory in liver cancer research

Authors: Federico Pinna, Kai Breuhahn

DOI: 10.2217/hep.14.29

Date Published: 2015

Projects: A2.1: Multi-level regulation of signalling pathways important for primin..., A2.4: Linking signalling pathways regulating liver regeneration and orga...

Journal: Hepatic Oncology

Citation: Hepatic Oncology 2(1) : 9

Scales: Cell and Intercellular

Abstract:

Not specified

Created: 20th Jan 2015 at 13:49 Last updated: 20th Jan 2015 at 13:52

Unraveling liver complexity from molecular to organ level: Challenges and perspectives

Authors: L.A. D'Alessandro, S. Hoehme, A. Henney, D. Drasdo, U. Klingmüller

DOI: 10.1016/j.pbiomolbio.2014.11.005

Date Published: 2015

Projects: A2.1: Multi-level regulation of signalling pathways important for primin..., A2.3: Cross-talk and distinct properties of growth factor signalling reg..., A2.4: Linking signalling pathways regulating liver regeneration and orga..., C5: Structural changes and functional consequences of the liver lobular/..., E1: Integration on the cellular level, Interleukin-6 signalling, Showcase HGF and Regeneration

Journal: Progress in Biophysics and Molecular Biology

Citation: Progress in Biophysics and Molecular Biology 117(1) : 78

Scales: Not specified

Abstract (Expand)

Biological responses are determined by information processing at multiple and highly interconnected scales. Within a tissue the individual cells respond to extracellular stimuli by regulating intracellular ...

Created: 6th Apr 2015 at 12:17 Last updated: 9th Jun 2015 at 10:40

Multi-bio and multi-scale systems biology

Authors: Adriano Henney, Peter Hunter, Andrew McCulloch, Denis Noble

DOI: 10.1016/j.pbiomolbio.2015.03.001

Date Published: 2015

Projects: No Projects

Journal: Progress in Biophysics and Molecular Biology

Citation: Progress in Biophysics and Molecular Biology 117(1) : 1

Scales: Not specified

Abstract:

Not specified

Created: 6th Apr 2015 at 12:20 Last updated: 6th Apr 2015 at 12:21

Interleukin-1β Enhances FasL-Induced Caspase-3/-7 Activity without Increasing Apoptosis in Primary Mouse Hepatocytes

Authors: Anna Lutz, Julia Sanwald, Maria Thomas, Ronny Feuer, Oliver Sawodny, Michael Ederer, Christoph Borner, Matjaz Humar, Irmgard Merfort

DOI: 10.1371/journal.pone.0115603

Date Published: 31st Dec 2014

Projects: A2.2: Regulation of pro-apoptotic and anti-apoptotic responses in hepato...

Journal: PLoS ONE

Citation: PLoS ONE 9(12) : e115603

Scales: Cell

Abstract (Expand)

Sustained inflammation may increase the susceptibility of hepatocytes to apoptotic cell death and therefore exacerbate liver damage. Here we report that the pro-inflammatory cytokine IL-1β sensitizes ...

Created: 23rd Jan 2015 at 09:58 Last updated: 23rd Jan 2015 at 10:00

COMBINE archive and OMEX format: one file to share all information to reproduce a modeling project

Authors: Frank T Bergmann, Richard Adams, Stuart Moodie, Jonathan Cooper, Mihai Glont, Martin Golebiewski, Michael Hucka, Camille Laibe, Andrew K Miller, David P Nickerson, Brett G Olivier, Nicolas Rodriguez, Herbert M Sauro, Martin Scharm, Stian Soiland-Reyes, Dagmar Waltemath, Florent Yvon, Nicolas Le Novère

PubMed ID: 25494900

Date Published: 14th Dec 2014

Projects: F1: The data management system

Journal: BMC Bioinformatics

Citation: BMC Bioinformatics 15(1): 369

Scales: Not specified

Abstract (Expand)

BackgroundWith the ever increasing use of computational models in the biosciences, the need to share models and reproduce the results of published studies efficiently and easily is becoming more ...

Created: 9th Jan 2015 at 15:06

A Systematic Comparison of the Impact of Inflammatory Signaling on ADME Gene Expression and Activity in Primary Human Hepatocytes and HepaRG Cells

Authors: Marcus Klein, Maria Thomas, Ute Hofmann, Daniel Seehofer, Georg Damm, Ulrich M Zanger

PubMed ID: 25480923

Date Published: 7th Dec 2014

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

Journal: Drug Metab. Dispos.

Citation: Drug Metab. Dispos. :

Scales: Not specified

Abstract (Expand)

Inflammatory processes are associated with compromised metabolism and elimination of drugs in the liver, largely mediated by proinflammatory cytokines, such as interleukin-6 (IL-6). The HepaRG cell ...

Created: 7th Dec 2014 at 10:17

Whole genome transcript profiling of drug induced steatosis in rats reveals a gene signature predictive of outcome

Authors: Nishika Sahini, Saravanakumar Selvaraj, Jürgen Borlak

PubMed ID: 25470483

Date Published: 3rd Dec 2014

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

Journal: PLoS ONE

Citation: PLoS ONE 9(12): e114085

Scales: Liver

Abstract (Expand)

Drug induced steatosis (DIS) is characterised by excess triglyceride accumulation in the form of lipid droplets (LD) in liver cells. To explore mechanisms underlying DIS we interrogated the publically ...

Created: 29th Jan 2015 at 14:53

Data collection as a barrier to personalized medicine

Authors: David Zakim, Matthias Schwab

PubMed ID: 25479798

Date Published: 2nd Dec 2014

Projects: G3: Clinical Translation to Pharmaceutical Drug Development

Journal: Trends Pharmacol. Sci.

Citation: Trends Pharmacol. Sci. 36(2): 68-71

Scales: Not specified

Abstract (Expand)

Basic life science research holds the promise of personalizing medical care. However, translation steps from the laboratory to the bedside are not trivial. Results from clinical research are difficult ...

Created: 7th Apr 2015 at 14:54

SBMLSimulator: A Java Tool for Model Simulation and Parameter Estimation in Systems Biology

Authors: Alexander Dörr, Roland Keller, Andreas Zell, Andreas Dräger

DOI: 10.3390/computation2040246

Date Published: 1st Dec 2014

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

Journal: Computation

Citation: Computation 2(4) : 246

Scales: Cell and Intercellular

Abstract (Expand)

The identification of suitable model parameters for biochemical reactions has been recognized as a quite difficult endeavor. Parameter values from literature or experiments can often not directly be ...

Created: 14th Jan 2015 at 15:05 Last updated: 10th Jun 2015 at 18:36

LigDig: a web server for querying ligand-protein interactions

Authors: J. C. Fuller, M. Martinez, S. Henrich, A. Stank, S. Richter, R. C. Wade

DOI: 10.1093/bioinformatics/btu784

Date Published: 29th Nov 2014

Projects: A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato..., F3: Kinetic data handling

Journal: Bioinformatics

Citation: Bioinformatics

Scales: Cell

Abstract (Expand)

Summary: LigDig is a webserver designed to answer questions that previously required several independent queries to diverse data-sources. It also performs basic manipulations and analyses of the ...

Created: 6th Dec 2014 at 18:03 Last updated: 6th Dec 2014 at 18:07

Fluorescence based cell counting in collagen monolayer cultures of primary hepatocytes

Authors: C Priesnitz, S Sperber, R Garg, M Orsini, F Noor

PubMed ID: 25424145

Date Published: 26th Nov 2014

Projects: A1: Cellular metabolism, C3: Zonation of metabolism and its regulation

Journal: Cytotechnology

Citation: Cytotechnology :

Scales: Cell

Abstract (Expand)

Accurate determination of cell number is essential for the quantitative description of biological processes. The changes should be related to a measurable reference e.g. in the case of cell culture, ...

Created: 14th Jan 2015 at 16:17

Stratified medicine for the use of antidiabetic medication in treatment of type II diabetes and cancer: where do we go from here

Authors: A Emami-Riedmaier, E Schaeffeler, A T Nies, K Mörike, M Schwab

PubMed ID: 25418285

Date Published: 25th Nov 2014

Projects: G3: Clinical Translation to Pharmaceutical Drug Development

Journal: J. Intern. Med.

Citation: J. Intern. Med. 277(2): 235-47

Scales: Not specified

Abstract (Expand)

At present, the global diabetes epidemic is affecting 347 million individuals, 90% of whom are diagnosed with type II diabetes mellitus (T2DM). T2DM is commonly treated with more than one type of ...

Created: 7th Apr 2015 at 14:50

Isolation, characterization, and cultivation of human hepatocytes and non-parenchymal liver cells

Authors: Elisa Pfeiffer, Victoria Kegel, Katrin Zeilinger, Jan G Hengstler, Andreas K Nüssler, Daniel Seehofer, Georg Damm

PubMed ID: 25394621

Date Published: 15th Nov 2014

Projects: C2: Organization of the sinusoidal system and the liver lobule - referen..., CTU Liver bank

Journal: Exp. Biol. Med. (Maywood)

Citation: Exp. Biol. Med. (Maywood) :

Scales: Cell and Intercellular

Abstract (Expand)

Primary human hepatocytes (PHH) are considered to be the gold standard for in vitro testing of xenobiotic metabolism and hepatotoxicity. However, PHH cultivation in 2D mono-cultures leads to dedifferentiation ...

Created: 5th Jan 2015 at 13:19

Algorithmically generated rodent hepatic vascular trees in arbitrary detail

Authors: Lars Ole Schwen, Weiwei Wei, Felix Gremse, Josef Ehling, Lei Wang, Uta Dahmen, Tobias Preusser

DOI: 10.1016/j.jtbi.2014.10.026

Date Published: 1st Nov 2014

Projects: D1: Regulation of Blood Flow and Perfusion in the Liver, E3: Horizontal integration on organ scale, E4: Vertical integration across biological scales

Journal: Journal of Theoretical Biology

Citation: Journal of Theoretical Biology

Scales: Liver

Abstract (Expand)

Physiologically realistic geometric models of the vasculature in the liver are indispensable for modelling hepatic blood flow, the main connection between the liver and the organism. Current in vivo ...

Created: 17th Nov 2014 at 10:07 Last updated: 17th Nov 2014 at 10:12

The virtual liver: state of the art and future perspectives

Authors: Dirk Drasdo, Johannes Bode, Uta Dahmen, Olaf Dirsch, Steven Dooley, Rolf Gebhardt, Ahmed Ghallab, Patricio Godoy, Dieter Häussinger, Seddik Hammad, Stefan Hoehme, Hermann-Georg Holzhütter, Ursula Klingmüller, Lars Kuepfer, Jens Timmer, Marino Zerial, Jan G. Hengstler

DOI: 10.1007/s00204-014-1384-6

Date Published: 21st Oct 2014

Projects: No Projects

Journal: Arch Toxicol

Citation: Arch Toxicol

Scales: Not specified

Abstract:

Not specified

Created: 7th Nov 2014 at 15:06 Last updated: 7th Nov 2014 at 15:06

Nuclear Expression of the Deubiquitinase CYLD Is Associated with Improved Survival in Human Hepatocellular Carcinoma

Authors: Stefan Welte, Toni Urbanik, Christin Elßner, Nicole Kautz, Bruno Christian Koehler, Nina Waldburger, Justo Lorenzo Bermejo, Federico Pinna, Karl-Heinz Weiss, Peter Schemmer, Dirk Jaeger, Thomas Longerich, Kai Breuhahn, Henning Schulze-Bergkamen

DOI: 10.1371/journal.pone.0110591

Date Published: 16th Oct 2014

Projects: A2.1: Multi-level regulation of signalling pathways important for primin...

Journal: PLoS ONE

Citation: PLoS ONE 9(10) : e110591

Scales: Cell

Abstract:

Not specified

Created: 20th Jan 2015 at 13:44 Last updated: 20th Jan 2015 at 13:46

WISP1 is a novel adipokine linked to inflammation in obesity

Authors: Veronica Murahovschi, Olga Pivovarova, Iryna Ilkavets, Renata M Dmitrieva, Stephanie Döcke, Farnaz Keyhani-Nejad, Özlem Gögebakan, Martin Osterhoff, Margrit Kemper, Silke Hornemann, Mariya Markova, Nora Klöting, Martin Stockmann, Martin O Weickert, Valeria Lamounier-Zepter, Peter Neuhaus, Alexandra Konradi, Steven Dooley, Christian von Loeffelholz, Matthias Blüher, Andreas F H Pfeiffer, Natalia Rudovich

PubMed ID: 25281430

Date Published: 3rd Oct 2014

Projects: C5: Structural changes and functional consequences of the liver lobular/...

Journal: Diabetes

Citation: Diabetes 64(3): 856-66

Scales: Organism

Abstract (Expand)

WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the secreted extracellular matrix-associated proteins of the CCN family and a target gene of the Wingless-type (WNT) ...

Created: 17th Jun 2015 at 09:29

Evolutionary game theory: cells as players

Authors: Sabine Hummert, Katrin Bohl, David Basanta, Andreas Deutsch, Sarah Werner, Günter Theißen, Anja Schroeter, Stefan Schuster

PubMed ID: 25270362

Date Published: 2nd Oct 2014

Projects: No Projects

Journal: Mol Biosyst

Citation: Mol Biosyst 10(12): 3044-65

Scales: Not specified

Abstract (Expand)

In two papers we review game theory applications in biology below the level of cognitive living beings. It can be seen that evolution and natural selection replace the rationality of the actors ...

Created: 3rd Dec 2014 at 20:25

How predictive quantitative modelling of tissue organisation can inform liver disease pathogenesis

Authors: Dirk Drasdo, Stefan Hoehme, Jan G. Hengstler

DOI: 10.1016/j.jhep.2014.06.013

Date Published: 1st Oct 2014

Projects: C: Liver lobule level

Journal: Journal of Hepatology

Citation: Journal of Hepatology 61(4) : 951

Scales: Not specified

Abstract:

Not specified

Created: 7th Nov 2014 at 15:09 Last updated: 7th Nov 2014 at 15:09

The Virtual Liver Network: systems understanding from bench to bedside

Author: Adriano Henney

DOI: 10.4155/FMC.14.127

Date Published: 1st Oct 2014

Projects: No Projects

Journal: Future Medicinal Chemistry

Citation: Future Medicinal Chemistry 6(16) : 1735

Scales: Not specified

Abstract:

Not specified

Created: 28th Nov 2014 at 17:48

Evolutionary game theory: molecules as players

Authors: Katrin Bohl, Sabine Hummert, Sarah Werner, David Basanta, Andreas Deutsch, Stefan Schuster, Günter Theißen, Anja Schroeter

PubMed ID: 25248454

Date Published: 25th Sep 2014

Projects: No Projects

Journal: Mol Biosyst

Citation: Mol Biosyst 10(12): 3066-74

Scales: Not specified

Abstract (Expand)

In this and an accompanying paper we review the use of game theoretical concepts in cell biology and molecular biology. This review focuses on the subcellular level by considering viruses, genes, and ...

Created: 3rd Dec 2014 at 20:29

Modeling function-perfusion behavior in liver lobules including tissue, blood, glucose, lactate and glycogen by use of a coupled two-scale PDE-ODE approach

Authors: T Ricken, D Werner, H G Holzhütter, M König, U Dahmen, O Dirsch

PubMed ID: 25236798

Date Published: 19th Sep 2014

Projects: A1: Cellular metabolism, C: Liver lobule level, E: Model integration

Journal: Biomech Model Mechanobiol

Citation: Biomech Model Mechanobiol 14(3): 515-36

Scales: Cell and Liver lobule

Abstract (Expand)

This study focuses on a two-scale, continuum multicomponent model for the description of blood perfusion and cell metabolism in the liver. The model accounts for a spatial and time depending ...

Created: 30th Jun 2015 at 07:09

Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms

Authors: Andreas Bitter, Petra Rümmele, Kathrin Klein, Benjamin A Kandel, Jessica K Rieger, Andreas K Nüssler, Ulrich M Zanger, Michael Trauner, Matthias Schwab, Oliver Burk

PubMed ID: 25182422

Date Published: 3rd Sep 2014

Projects: A3.4: Linking signalling to metabolic functions, B5: Cell-cell communication influences detoxifying functions in hepatocytes, G1: Clinical Translation to Invasively Characterized Patients, G3: Clinical Translation to Pharmaceutical Drug Development, Showcase Steatosis

Journal: Arch. Toxicol.

Citation: Arch. Toxicol. :

Scales: Cell, Intercellular and Liver lobule

Abstract (Expand)

In addition to its well-characterized role in the regulation of drug metabolism and transport by xenobiotics, pregnane X receptor (PXR) critically impacts on lipid homeostasis. In mice, both ligand-dependent ...

Created: 5th Dec 2014 at 12:44

Treatment of NASH with human mesenchymal stem cells in the immunodeficient mouse

Authors: Sandra Winkler, Bruno Christ

PubMed ID: 25173373

Date Published: 1st Sep 2014

Projects: C6: Organization and function of the sinusoidal system and the liver lob..., Showcase Steatosis

Journal: Methods Mol. Biol.

Citation: Methods Mol. Biol. 1213: 51-6

Scales: Cell and Liver

Abstract (Expand)

Nonalcoholic steatohepatitis (NASH) as a severe form of nonalcoholic liver diseases (NAFLD) is one of the prominent liver diseases worldwide. Under favoring conditions it may progress into liver cirrhosis ...

Created: 15th Jan 2015 at 10:47

The many faces of Hedgehog signalling in the liver: Recent progress reveals striking cellular diversity and the importance of microenvironments

Authors: Madlen Matz-Soja, Rolf Gebhardt

PubMed ID: 25152210

Date Published: 26th Aug 2014

Projects: A: Cellular level

Journal: J. Hepatol.

Citation: J. Hepatol. :

Scales: Not specified

Abstract:

Not specified

Created: 1st Dec 2014 at 15:54

On Calculation of the Electrostatic Potential of a Phosphatidylinositol Phosphate-Containing Phosphatidylcholine Lipid Membrane Accounting for Membrane Dynamics

Authors: Jonathan C. Fuller, Michael Martinez, Rebecca C. Wade

DOI: 10.1371/journal.pone.0104778

Date Published: 20th Aug 2014

Projects: A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato...

Journal: PLoS ONE

Citation: PLoS ONE 9(8) : e104778

Scales: Cell

Abstract (Expand)

Many signaling events require the binding of cytoplasmic proteins to cell membranes by recognition of specific charged lipids, such as phosphoinositol-phosphates. As a model for a protein-membrane ...

Created: 20th Aug 2014 at 19:55 Last updated: 20th Aug 2014 at 19:57

Foxf1 SiRNA Delivery to Hepatic Stellate Cells by DBTC Lipoplex Formulations Ameliorates Fibrosis in Livers of Bile Duct Ligated Mice

Authors: Kerstin Abshagen, Malte Brensel, Berit Genz, Kira Roth, Maria Thomas, Volker Fehring, Ute Schaeper, Brigitte Vollmar

PubMed ID: 25619889

Date Published: 11th Aug 2014

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

Journal: Curr Gene Ther

Citation: Curr Gene Ther :

Scales: Cell

Abstract (Expand)

Activation of hepatic stellate cells (HSCs) is a key event in pathogenesis of liver fibrosis and represents an orchestral interplay of inhibiting and activating transcription factors like forkhead box ...

Created: 27th Jan 2015 at 10:19

Cause and cure of sloppiness in ordinary differential equation models

Authors: Christian Tönsing, Jens Timmer, Clemens Kreutz

PubMed ID: 25215847

Date Published: 11th Aug 2014

Projects: A2.5: Integration of insulin and Wnt signalling in hepatocytes, A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato..., B2.1: Hepatic stellate cells as source and target for hepatocellular gro...

Journal: Phys Rev E Stat Nonlin Soft Matter Phys

Citation: Phys Rev E Stat Nonlin Soft Matter Phys 90(2): 023303

Scales: Cell

Abstract (Expand)

Data-based mathematical modeling of biochemical reaction networks, e.g., by nonlinear ordinary differential equation (ODE) models, has been successfully applied. In this context, parameter estimation ...

Created: 30th Jan 2015 at 15:58

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

morFeus: a web-based program to detect remotely conserved orthologs using symmetrical best hits and orthology network scoring

Authors: Ines Wagner, Michael Volkmer, Malvika Sharan, Jose M Villaveces, Felix Oswald, Vineeth Surendranath, Bianca H Habermann

PubMed ID: 25096057

Date Published: 6th Aug 2014

Projects: A1.3: Identification of crucial metabolic processes during hepatocyte pr..., A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato..., A3.5: The impact of cell polarity on metabolism detoxification and endoc..., A3: Crosslinking signalling metabolism and hepatocyte polarisation, C2: Organization of the sinusoidal system and the liver lobule - referen..., C5: Structural changes and functional consequences of the liver lobular/..., C6: Organization and function of the sinusoidal system and the liver lob...

Journal: BMC Bioinformatics

Citation: BMC Bioinformatics 15(1): 263

Scales: Not specified

Abstract (Expand)

Searching the orthologs of a given protein or DNA sequence is one of the most important and most commonly used Bioinformatics methods in Biology. Programs like BLAST or the orthology search engine ...

Created: 11th Aug 2014 at 16:33

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

Clinical Translation in the Virtual Liver Network

Authors: L Kuepfer, R Kerb, A M Henney

DOI: 10.1038/psp.2014.25

Date Published: 30th Jul 2014

Projects: G: Clinical translation

Journal: CPT: pharmacomet. syst. pharmacol.

Citation: CPT: pharmacomet. syst. pharmacol. 3(7) : e127

Scales: Organism

Abstract:

Not specified

Created: 13th Aug 2014 at 19:07 Last updated: 13th Aug 2014 at 19:12

Liver zonation: Novel aspects of its regulation and its impact on homeostasis

Authors: Rolf Gebhardt, Madlen Matz-Soja

PubMed ID: 25024605

Date Published: 16th Jul 2014

Projects: C3: Zonation of metabolism and its regulation, Virtual Liver

Journal: World J. Gastroenterol.

Citation: World J. Gastroenterol. 20(26): 8491-504

Scales: Cell, Intercellular and Liver lobule

Abstract (Expand)

Liver zonation, the spatial separation of the immense spectrum of different metabolic pathways along the liver sinusoids, is fundamental for proper functioning of this organ. Recent progress in elucidating ...

Created: 26th Jan 2015 at 09:50

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

Explanted diseased livers - a possible source of metabolic competent primary human hepatocytes

Authors: Moritz Kleine, Marc Riemer, Till Krech, Daphne DeTemple, Mark D Jäger, Frank Lehner, Michael P Manns, Jürgen Klempnauer, Jürgen Borlak, Hueseyin Bektas, Florian W R Vondran

PubMed ID: 24999631

Date Published: 7th Jul 2014

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

Journal: PLoS ONE

Citation: PLoS ONE 9(7): e101386

Scales: Cell

Abstract (Expand)

Being an integral part of basic, translational and clinical research, the demand for primary human hepatocytes (PHH) is continuously growing while the availability of tissue resection material for the ...

Created: 10th Jul 2014 at 12:09

Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells

Authors: Berit Genz, Maria Thomas, Brigitte M Pützer, Marcin Siatkowski, Georg Fuellen, Brigitte Vollmar, Kerstin Abshagen

PubMed ID: 24995995

Date Published: 6th Jul 2014

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

Journal: Exp. Cell Res.

Citation: Exp. Cell Res. :

Scales: Cell

Abstract (Expand)

Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular ...

Created: 7th Jul 2014 at 20:27

Targeting Nuclear Receptors with Lentivirus-Delivered Small RNAs in Primary Human Hepatocytes

Authors: Maria Thomas, Jessica K Rieger, Benjamin A Kandel, Kathrin Klein, Ulrich M Zanger

PubMed ID: 25012546

Date Published: 1st Jul 2014

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

Journal: Cell. Physiol. Biochem.

Citation: Cell. Physiol. Biochem. 33(6): 2003-2013

Scales: Not specified

Abstract (Expand)

Background: RNA interference (RNAi) has tremendous potential for investigating gene function and for developing new therapies. Primary human hepatocytes (PHH) are the "gold standard" for ...

Created: 14th Jul 2014 at 13:17

A model integration approach linking signalling and gene-regulatory logic with kinetic metabolic models

Authors: A. Ryll, J. Bucher, A. Bonin, S. Bongard, E. Gonçalves, J. Saez-Rodriguez, J. Niklas, S. Klamt

DOI: 10.1016/j.biosystems.2014.07.002

Date Published: 1st Jul 2014

Projects: A1: Cellular metabolism, A2.5: Integration of insulin and Wnt signalling in hepatocytes, A2: Integration of Signalling Pathways in Hepatocellular Response, A3.4: Linking signalling to metabolic functions, A3.6: Transcription factor network and links to metabolism in NAFLD, A: Cellular level, Showcase Steatosis, Virtual Liver

Journal: Biosystems

Citation: Biosystems

Scales: Cell

Abstract (Expand)

Systems biology has to increasingly cope with large- and multi-scale biological systems. Many successful in silico representations and simulations of various cellular modules proved mathematical modelling ...

Created: 6th Aug 2014 at 07:36 Last updated: 6th Aug 2014 at 07:50

Modelling proteasome and proteasome regulator activities

Authors: Juliane Liepe, Herman-Georg Holzhütter, Peter M Kloetzel, Michael P H Stumpf, Michele Mishto

PubMed ID: 24970232

Date Published: 28th Jun 2014

Projects: No Projects

Journal: Biomolecules

Citation: Biomolecules 4(2): 585-99

Scales: Not specified

Abstract (Expand)

Proteasomes are key proteases involved in a variety of processes ranging from the clearance of damaged proteins to the presentation of antigens to CD8+ T-lymphocytes. Which cleavage sites are used ...

Created: 6th Jan 2015 at 09:32

A testing strategy to predict risk for drug-induced liver injury in humans using high-content screen assays and the 'rule-of-two' model

Authors: Minjun Chen, Chun-Wei Tung, Qiang Shi, Lei Guo, Leming Shi, Hong Fang, Jürgen Borlak, Weida Tong

PubMed ID: 24958025

Date Published: 11th Jun 2014

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions

Journal: Arch. Toxicol.

Citation: Arch. Toxicol. 88(7): 1439-49

Scales: Cell

Abstract (Expand)

Drug-induced liver injury (DILI) is a major cause of drug failures in both the preclinical and clinical phase. Consequently, improving prediction of DILI at an early stage of drug discovery will reduce ...

Created: 28th Jun 2014 at 16:37

Concomitant use of tamoxifen and endoxifen in postmenopausal early breast cancer: prediction of plasma levels by physiologically-based pharmacokinetic modeling

Authors: Kristin Dickschen, Thomas Eissing, Thomas Mürdter, Matthias Schwab, Stefan Willmann, Georg Hempel

PubMed ID: 24936398

Date Published: 5th Jun 2014

Projects: G3: Clinical Translation to Pharmaceutical Drug Development

Journal: Springerplus

Citation: Springerplus 3: 285

Scales: Not specified

Abstract (Expand)

To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism ...

Created: 7th Apr 2015 at 14:48

Predicting idiosyncratic drug-induced liver injury - some recent advances

Authors: Minjun Chen, Jürgen Borlak, Weida Tong

PubMed ID: 24857265

Date Published: 27th May 2014

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions

Journal: Expert Rev Gastroenterol Hepatol

Citation: Expert Rev Gastroenterol Hepatol : 1-3

Scales: Liver

Abstract (Expand)

Drug-induced liver injury (DILI) is a major challenge for the pharmaceutical industry, regulatory authorities, and clinicians. It is usually categorized into 'intrinsic' and 'idiosyncratic', ...

Created: 28th Jun 2014 at 16:40

Isoniazid mediates the CYP2B6*6 genotype-dependent interaction between efavirenz and antituberculosis drug therapy through mechanism-based inactivation of CYP2A6

Authors: Michael H Court, Fawziah E Almutairi, David J Greenblatt, Suwagmani Hazarika, Hongyan Sheng, Kathrin Klein, Ulrich M Zanger, Joanne Bourgea, Christopher J Patten, Awewura Kwara

PubMed ID: 24820076

Date Published: 12th May 2014

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

Journal: Antimicrob. Agents Chemother.

Citation: Antimicrob. Agents Chemother. 58(7): 4145-52

Scales: Not specified

Abstract (Expand)

Efavirenz is commonly used to treat patients coinfected with human immunodeficiency virus and tuberculosis. Previous clinical studies have observed paradoxically elevated efavirenz plasma concentrations ...

Created: 8th Dec 2014 at 09:49

Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

Authors: Sandra Winkler, Erawan Borkham-Kamphorst, Peggy Stock, Sandra Brückner, Matthias Dollinger, Ralf Weiskirchen, Bruno Christ

PubMed ID: 24786317

Date Published: 3rd May 2014

Projects: C4: Disturbance of liver lobule organization in NAFLD, C6: Organization and function of the sinusoidal system and the liver lob..., G: Clinical translation, Showcase Steatosis

Journal: Exp. Cell Res.

Citation: Exp. Cell Res. :

Scales: Cell and Liver

Abstract (Expand)

Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver ...

Created: 19th May 2014 at 20:13

Protocols for staining of bile canalicular and sinusoidal networks of human, mouse and pig livers, three-dimensional reconstruction and quantification of tissue microarchitecture by image processing and analysis

Authors: Seddik Hammad, Stefan Hoehme, Adrian Friebel, Iris von Recklinghausen, Amnah Othman, Brigitte Begher-Tibbe, Raymond Reif, Patricio Godoy, Tim Johann, Amruta Vartak, Klaus Golka, Petru O. Bucur, Eric Vibert, Rosemarie Marchan, Bruno Christ, Steven Dooley, Christoph Meyer, Iryna Ilkavets, Uta Dahmen, Olaf Dirsch, Jan Böttger, Rolf Gebhardt, Dirk Drasdo, Jan G. Hengstler

DOI: 10.1007/s00204-014-1243-5

Date Published: 1st May 2014

Projects: C2: Organization of the sinusoidal system and the liver lobule - referen..., C5: Structural changes and functional consequences of the liver lobular/..., C6: Organization and function of the sinusoidal system and the liver lob..., CTU Confocal microscopy, CTU Image Processing

Journal: Arch Toxicol

Citation: Arch Toxicol 88(5) : 1161

Scales: Liver lobule and Liver

Abstract:

Not specified

Created: 7th Nov 2014 at 15:11 Last updated: 7th Nov 2014 at 15:11

Integrated metabolic spatial-temporal model for the prediction of ammonia detoxification during liver damage and regeneration

Authors: Freimut Schliess, Stefan Hoehme, Sebastian G. Henkel, Ahmed Ghallab, Dominik Driesch, Jan Böttger, Reinhard Guthke, Michael Pfaff, Jan G. Hengstler, Rolf Gebhardt, Dieter Häussinger, Dirk Drasdo, Sebastian Zellmer

DOI: 10.1002/hep.27136

Date Published: 1st May 2014

Projects: A1.1: Central liver metabolism and its regulation under nutritional chal..., A2.1: Multi-level regulation of signalling pathways important for primin..., A2.4: Linking signalling pathways regulating liver regeneration and orga..., A3.4: Linking signalling to metabolic functions

Journal: Hepatology

Citation: Hepatology : n/a

Scales: Not specified

Abstract:

Not specified

Created: 7th Nov 2014 at 15:12 Last updated: 7th Nov 2014 at 15:12

Data extraction for the reaction kinetics database SABIO-RK

Authors: Ulrike Wittig, Renate Kania, Meik Bittkowski, Elina Wetsch, Lei Shi, Lenneke Jong, Martin Golebiewski, Maja Rey, Andreas Weidemann, Isabel Rojas, Wolfgang Müller

DOI: 10.1016/j.pisc.2014.02.004

Date Published: 1st May 2014

Projects: F3: Kinetic data handling

Journal: Perspectives in Science

Citation: Perspectives in Science 1(1-6) : 33

Scales: Not specified

Abstract (Expand)

SABIO-RK (http://sabio.h-its.org/) is a web-accessible, manually curated database that has been established as a resource for biochemical reactions and their kinetic properties with a focus on supporting ...

Created: 3rd Feb 2015 at 10:55 Last updated: 3rd Feb 2015 at 11:03

Human bone marrow mesenchymal stem cell-derived hepatocytes improve the mouse liver after acute acetaminophen intoxication by preventing progress of injury

Authors: Peggy Stock, Sandra Brückner, Sandra Winkler, Matthias M Dollinger, Bruno Christ

PubMed ID: 24758938

Date Published: 25th Apr 2014

Projects: A1: Cellular metabolism, C6: Organization and function of the sinusoidal system and the liver lob..., G: Clinical translation, Showcase HGF and Regeneration

Journal: Int J Mol Sci

Citation: Int J Mol Sci 15(4): 7004-28

Scales: Liver lobule and Liver

Abstract (Expand)

Mesenchymal stem cells from human bone marrow (hMSC) have the potential to differentiate into hepatocyte-like cells in vitro and continue to maintain important hepatocyte functions in vivo after ...

Created: 19th May 2014 at 20:04

The transcription factor CHOP, a central component of the transcriptional regulatory network induced upon CCl4 intoxication in mouse liver, is not a critical mediator of hepatotoxicity

Authors: Gisela Campos, Wolfgang Schmidt-Heck, Ahmed Ghallab, Katharina Rochlitz, Larissa Pütter, Danilo B Medinas, Claudio Hetz, Agata Widera, Cristina Cadenas, Brigitte Begher-Tibbe, Raymond Reif, Georgia Günther, Agapios Sachinidis, Jan G Hengstler, Patricio Godoy

PubMed ID: 24748426

Date Published: 20th Apr 2014

Projects: C2: Organization of the sinusoidal system and the liver lobule - referen..., C6: Organization and function of the sinusoidal system and the liver lob..., Showcase HGF and Regeneration

Journal: Arch. Toxicol.

Citation: Arch. Toxicol. 88(6): 1267-80

Scales: Not specified

Abstract (Expand)

Since xenobiotics enter the organism via the liver, hepatocytes must cope with numerous perturbations, including modifications of proteins leading to endoplasmic reticulum stress (ER-stress). This ...

Created: 20th Jan 2015 at 13:25

How useful are clinical liver function tests in in-vitro human hepatotoxicity assays

Authors: Jürgen Borlak, Anil Chougule, Prafull Kumar Singh

PubMed ID: 24685772

Date Published: 2nd Apr 2014

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions

Journal: Toxicol In Vitro

Citation: Toxicol In Vitro :

Scales: Cell

Abstract (Expand)

In preclinical hepatotoxicity testing cell based assays are frequently employed. However, prediction of clinical drug induced liver injury (DILI) remains a major challenge. Here we examined the usefulness ...

Created: 4th Apr 2014 at 16:13

How Does a Single Cell Know When the Liver Has Reached Its Correct Size?

Authors: Nadine Hohmann, Wei Weiwei, Uta Dahmen, Olaf Dirsch, Andreas Deutsch, Anja Voss-Böhme

DOI: 10.1371/journal.pone.0093207

Date Published: 1st Apr 2014

Projects: D4: Regeneration and Liver Size

Journal: PLoS ONE

Citation: PLoS ONE 9(4) : e93207

Scales: Intercellular, Liver lobule and Liver

Abstract (Expand)

The liver is a multi-functional organ that regulates major physiological processes and that possesses a remarkable regeneration capacity. After loss of functional liver mass the liver grows back to its ...

Created: 24th Apr 2014 at 14:21 Last updated: 24th Apr 2014 at 14:26

Potential Roles of Bone Morphogenetic Protein (BMP)-9 in Human Liver Diseases

Authors: Blanca Herrera, Steven Dooley, Katja Breitkopf-Heinlein

PubMed ID: 24670474

Date Published: 29th Mar 2014

Projects: A2.2: Regulation of pro-apoptotic and anti-apoptotic responses in hepato..., A2.3: Cross-talk and distinct properties of growth factor signalling reg..., A3.3: Hepatocyte polarity, B2.1: Hepatic stellate cells as source and target for hepatocellular gro..., B2.3: Effect of hepatic stellate cells on hepatocyte polarity and transd..., Showcase HGF and Regeneration, Showcase LPS and Inflammation

Journal: Int J Mol Sci

Citation: Int J Mol Sci 15(4): 5199-220

Scales: Not specified

Abstract (Expand)

Bone morphogenetic proteins (BMP-2 to BMP-15) belong to the Transforming Growth Factor (TGF)-β superfamily and, besides their well-documented roles during embryogenesis and bone formation, some of them ...

Created: 31st Mar 2014 at 11:18

Meeting report from the fourth meeting of the Computational Modeling in Biology Network (COMBINE)

Authors: Dagmar Waltemath, Frank T. Bergmann, Claudine Chaouiya, Tobias Czauderna, Padraig Gleeson, Carole Goble, Martin Golebiewski, Michael Hucka, Nick Juty, Olga Krebs, Nicolas Le Novère, Huaiyu Mi, Ion I. Moraru, Chris J. Myers, David Nickerson, Brett G. Olivier, Nicolas Rodriguez, Falk Schreiber, Lucian Smith, Fengkai Zhang, Eric Bonnet

DOI: 10.4056/sigs.5279417

Date Published: 15th Mar 2014

Projects: F1: The data management system

Journal: Stand. Genomic Sci.

Citation: Stand. Genomic Sci. 9(3) : 1285

Scales: Not specified

Abstract (Expand)

The Computational Modeling in Biology Network (COMBINE) is an initiative to coordinate the development of community standards and formats in computational systems biology and related fields. This report ...

Created: 3rd Feb 2015 at 11:07 Last updated: 3rd Feb 2015 at 11:12

Spatio-Temporal Simulation of First Pass Drug Perfusion in the Liver

Authors: Lars Ole Schwen, Markus Krauss, Christoph Niederalt, Felix Gremse, Fabian Kiessling, Andrea Schenk, Tobias Preusser, Lars Kuepfer

DOI: 10.1371/journal.pcbi.1003499

Date Published: 13th Mar 2014

Projects: D1: Regulation of Blood Flow and Perfusion in the Liver, E3: Horizontal integration on organ scale, E4: Vertical integration across biological scales, G3: Clinical Translation to Pharmaceutical Drug Development

Journal: PLoS Comput Biol

Citation: PLoS Comput Biol 10(3) : e1003499

Scales: Liver and Organism

Abstract (Expand)

The liver is the central organ for detoxification of xenobiotics in the body. In pharmacokinetic modeling, hepatic metabolization capacity is typically quantified as hepatic clearance computed as ...

Created: 14th Mar 2014 at 09:13 Last updated: 14th Mar 2014 at 09:28

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

Estimating Dose Painting Effects in Radiotherapy: A Mathematical Model

Authors: Juan Carlos López Alfonso, Nick Jagiella, Luis Núñez, Miguel A. Herrero, Dirk Drasdo

DOI: 10.1371/journal.pone.0089380

Date Published: 26th Feb 2014

Projects: No Projects

Journal: PLoS ONE

Citation: PLoS ONE 9(2) : e89380

Scales: Not specified

Abstract:

Not specified

Created: 7th Nov 2014 at 15:14 Last updated: 7th Nov 2014 at 15:14

Hepatic Hedgehog signaling contributes to the regulation of IGF1 and IGFBP1 serum levels

Authors: Madlen Matz-Soja, Susanne Aleithe, Eugenia Marbach, Jan Böttger, Katrin Arnold, Wolfgang Schmidt-Heck, Jürgen Kratzsch, Rolf Gebhardt

PubMed ID: 24548465

Date Published: 18th Feb 2014

Projects: Virtual Liver

Journal: Cell Commun. Signal

Citation: Cell Commun. Signal 12(1): 11

Scales: Organism

Abstract (Expand)

Hedgehog signaling plays an important role in embryonic development, organogenesis and cancer. In the adult liver, Hedgehog signaling in non-parenchymal cells has been found to play a role in certain ...

Created: 11th Mar 2014 at 14:51

Toward predictive models for drug-induced liver injury in humans: are we there yet

Authors: Minjun Chen, Halil Bisgin, Lillian Tong, Huixiao Hong, Hong Fang, Jürgen Borlak, Weida Tong

PubMed ID: 24521015

Date Published: 14th Feb 2014

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions

Journal: Biomark Med

Citation: Biomark Med 8(2): 201-13

Scales: Liver

Abstract (Expand)

Drug-induced liver injury (DILI) is a frequent cause for the termination of drug development programs and a leading reason of drug withdrawal from the marketplace. Unfortunately, the current preclinical ...

Created: 28th Jun 2014 at 16:31

KEGGViewer, a BioJS component to visualize KEGG Pathways

Authors: Jose M Villaveces, Rafael C Jimenez, Bianca H Habermann

PubMed ID: 24715980

Date Published: 13th Feb 2014

Projects: No Projects

Journal: F1000Res

Citation: F1000Res 3: 43

Scales: Not specified

Abstract (Expand)

Signaling pathways provide essential information on complex regulatory processes within the cell. They are moreover widely used to interpret and integrate data from large-scale studies, such as expression ...

Created: 11th Aug 2014 at 16:29

PsicquicGraph, a BioJS component to visualize molecular interactions from PSICQUIC servers

Authors: Jose M Villaveces, Rafael C Jimenez, Bianca H Habermann

PubMed ID: 25075287

Date Published: 13th Feb 2014

Projects: A1.3: Identification of crucial metabolic processes during hepatocyte pr..., A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato..., A3.5: The impact of cell polarity on metabolism detoxification and endoc..., A3: Crosslinking signalling metabolism and hepatocyte polarisation, C2: Organization of the sinusoidal system and the liver lobule - referen..., C5: Structural changes and functional consequences of the liver lobular/..., C6: Organization and function of the sinusoidal system and the liver lob...

Journal: F1000Res

Citation: F1000Res 3: 44

Scales: Not specified

Abstract (Expand)

Protein interaction networks have become an essential tool in large-scale data analysis, integration, and the visualization of high-throughput data in the context of complex cellular networks. Many ...

Created: 11th Aug 2014 at 16:31

Morpheus: a user-friendly modeling environment for multiscale and multicellular systems biology

Authors: J. Starruss, W. d. Back, L. Brusch, A. Deutsch

DOI: 10.1093/bioinformatics/btt772

Date Published: 17th Jan 2014

Projects: A3.3: Hepatocyte polarity, A3: Crosslinking signalling metabolism and hepatocyte polarisation, B2.3: Effect of hepatic stellate cells on hepatocyte polarity and transd..., B3: Intercellular communication through cell adhesion, B: Communication of Hepatocytes and Non-Parenchymal Liver Cells, C2: Organization of the sinusoidal system and the liver lobule - referen..., C5: Structural changes and functional consequences of the liver lobular/..., C6: Organization and function of the sinusoidal system and the liver lob..., E2: Integration on the liver lobule scale: Image processing and mathemat..., E3: Horizontal integration on organ scale, E: Model integration, Showcase LIAM (Liver Image Analysis Based Model), Virtual Liver

Journal: Bioinformatics

Citation: Bioinformatics

Scales: Cell, Intercellular and Liver lobule

Abstract (Expand)

Summary: Morpheus is a modeling environment for the simulation and integration of cell-based models with ordinary differential equations and reaction-diffusion systems. It allows rapid development of ...

Created: 20th Jan 2014 at 15:49 Last updated: 20th Jan 2014 at 16:16

The apoptotic pore on mitochondria: are we breaking through or still stuck

Authors: C Borner, D W Andrews

PubMed ID: 24413197

Date Published: 15th Jan 2014

Projects: No Projects

Journal: Cell Death Differ.

Citation: Cell Death Differ. 21(2): 187-91

Scales: Not specified

Abstract:

Not specified

Created: 22nd Jan 2014 at 15:13

Unbiased RNAi screen for hepcidin regulators links hepcidin suppression to the proliferative Ras/RAF and the nutrient-dependent mTOR signaling pathways

Authors: Katarzyna Mleczko-Sanecka, Franziska Roche, Ana Rita da Silva, Debora Call, Flavia D'Alessio, Anan Ragab, Philip E Lapinski, Ramesh Ummanni, Ulrike Korf, Christopher Oakes, Georg Damm, Lorenza A D'Alessandro, Ursula Klingmüeller, Philip D King, Michael Boutros, Matthias W Hentze, Martina U Muckenthaler

PubMed ID: 24385536

Date Published: 5th Jan 2014

Projects: A3.4: Linking signalling to metabolic functions, B1.3: Linking modulation of iron metabolism with the impact of macrophag...

Journal: Blood

Citation: Blood :

Scales: Cell and Intercellular

Abstract (Expand)

The hepatic hormone hepcidin is a key regulator of systemic iron metabolism. Its expression is largely regulated by two signaling pathways, the 'iron-regulated' bone morphogenetic protein ...

Created: 14th Jan 2014 at 12:06

A Novel Mitochondrial MAVS/Caspase-8 Platform Links RNA Virus-Induced Innate Antiviral Signaling to Bax/Bak-Independent Apoptosis

Authors: Souhayla El Maadidi, Laura Faletti, Birgit Berg, Christin Wenzl, Katrin Wieland, Zhijian J Chen, Ulrich Maurer, Christoph Borner

PubMed ID: 24391214

Date Published: 3rd Jan 2014

Projects: No Projects

Journal: J. Immunol.

Citation: J. Immunol. 192(3): 1171-83

Scales: Not specified

Abstract (Expand)

Semliki Forest virus (SFV) requires RNA replication and Bax/Bak for efficient apoptosis induction. However, cells lacking Bax/Bak continue to die in a caspase-dependent manner. In this study, we show ...

Created: 22nd Jan 2014 at 15:15

A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis

Authors: Guillem Casanovas, Anashua Banerji, Flavia d'Alessio, Martina U Muckenthaler, Stefan Legewie

PubMed ID: 24391488

Date Published: 2nd Jan 2014

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

Journal: PLoS Comput. Biol.

Citation: PLoS Comput. Biol. 10(1): e1003421

Scales: Cell

Abstract (Expand)

Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated ...

Created: 14th Jan 2014 at 11:56

SEE: structured representation of scientific evidence in the biomedical domain using Semantic Web techniques

Authors: Christian Bölling, Michael Weidlich, Hermann-Georg Holzhütter

DOI: 10.1186/2041-1480-5-S1-S1

Date Published: 2014

Projects: F2: The Liver Knowledge Base (LKB)

Journal: J Biomed Sem

Citation: J Biomed Sem 5(Suppl 1) : S1

Scales: Not specified

Abstract (Expand)

Background Accounts of evidence are vital to evaluate and reproduce scientific findings and integrate data on an informed basis. Currently, such accounts are often inadequate, unstandardized and ...

Created: 17th Jun 2014 at 13:09 Last updated: 17th Jun 2014 at 13:13

Enabling multiscale modeling in systems medicine

Authors: Olaf Wolkenhauer, Charles Auffray, Olivier Brass, Jean Clairambault, Andreas Deutsch, Dirk Drasdo, Francesco Gervasio, Luigi Preziosi, Philip Maini, Anna Marciniak-Czochra, Christina Kossow, Lars Kuepfer, Katja Rateitschak, Ignacio Ramis-Conde, Benjamin Ribba, Andreas Schuppert, Rod Smallwood, Georgios Stamatakos, Felix Winter, Helen Byrne

DOI: 10.1186/gm538

Date Published: 2014

Projects: No Projects

Journal: Genome Med

Citation: Genome Med 6(3) : 21

Scales: Not specified

Abstract:

Not specified

Created: 7th Nov 2014 at 15:10 Last updated: 7th Nov 2014 at 15:10

Mathematical Modeling of Regenerative Processes

Authors: Osvaldo Chara, Elly M. Tanaka, Lutz Brusch

DOI: 10.1016/B978-0-12-391498-9.00011-5

Date Published: 2014

Projects: A3.3: Hepatocyte polarity, A3.5: The impact of cell polarity on metabolism detoxification and endoc..., B2.3: Effect of hepatic stellate cells on hepatocyte polarity and transd..., B3: Intercellular communication through cell adhesion, C2: Organization of the sinusoidal system and the liver lobule - referen..., C5: Structural changes and functional consequences of the liver lobular/..., C6: Organization and function of the sinusoidal system and the liver lob..., D4: Regeneration and Liver Size, Showcase LIAM (Liver Image Analysis Based Model)

Book: Mechanisms of Regeneration

Citation: Current Topics in Developmental Biology 108 : 283

Scales: Not specified

Abstract:

Not specified

Created: 22nd Jan 2015 at 16:09 Last updated: 22nd Jan 2015 at 16:11

TFpredict and SABINE: Sequence-Based Prediction of Structural and Functional Characteristics of Transcription Factors

Authors: Johannes Eichner, Florian Topf, Andreas Dräger, Clemens Wrzodek, Dierk Wanke, Andreas Zell

DOI: 10.1371/journal.pone.0082238

Date Published: 12th Dec 2013

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

Journal: PLoS ONE

Citation: PLoS ONE 8(12) : e82238

Scales: Cell and Intercellular

Abstract (Expand)

One of the key mechanisms of transcriptional control are the specific connections between transcription factors (TF) and cis-regulatory elements in gene promoters. The elucidation of these specific ...

Created: 17th Nov 2015 at 12:27 Last updated: 17th Nov 2015 at 12:28

Determinants of Cell-to-Cell Variability in Protein Kinase Signaling

Authors: Matthias Jeschke, Stephan Baumgärtner, Stefan Legewie

PubMed ID: 24339758

Date Published: 5th Dec 2013

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: PLoS Comput. Biol.

Citation: PLoS Comput. Biol. 9(12): e1003357

Scales: Not specified

Abstract (Expand)

Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein ...

Created: 20th Jan 2014 at 16:29

Dynamics of VEGF matrix-retention in vascular network patterning

Authors: A Köhn-Luque, W de Back, Y Yamaguchi, K Yoshimura, M A Herrero, T Miura

DOI: 10.1088/1478-3975/10/6/066007

Date Published: 1st Dec 2013

Projects: B2.3: Effect of hepatic stellate cells on hepatocyte polarity and transd..., B3: Intercellular communication through cell adhesion, C2: Organization of the sinusoidal system and the liver lobule - referen..., C5: Structural changes and functional consequences of the liver lobular/...

Journal: Phys. Biol.

Citation: Phys. Biol. 10(6) : 066007

Scales: Intercellular

Abstract (Expand)

Vascular endothelial growth factor (VEGF) is a central regulator of blood vessel morphogenesis, although its role in patterning of endothelial cells into vascular networks is not fully understood. It ...

Created: 24th Jan 2014 at 13:54 Last updated: 24th Jan 2014 at 13:57

No activation of human PXR by hyperforin-related phloroglucinols

Authors: Benjamin A Kandel, Sean Ekins, Kristina Leuner, Wolfgang E Thasler, Christian Harteneck, Ulrich M Zanger

PubMed ID: 24259679

Date Published: 22nd Nov 2013

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

Journal: J. Pharmacol. Exp. Ther.

Citation: J. Pharmacol. Exp. Ther. :

Scales: Not specified

Abstract (Expand)

The acylated phloroglucinol, hyperforin, the main active ingredient of St John's wort, exerts anti-depressant properties via indirect inhibition of serotonin reuptake by selectively activating the ...

Created: 8th Jan 2014 at 13:53

Genetics, epigenetics and regulation of drug metabolizing cytochrome P450 enzymes

Authors: Ulrich M Zanger, Kathrin Klein, Maria Thomas, Jessica K Rieger, Roman Tremmel, Benjamin A Kandel, Marcus Klein, Tarek Magdy

PubMed ID: 24196843

Date Published: 8th Nov 2013

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

Journal: Clin. Pharmacol. Ther.

Citation: Clin. Pharmacol. Ther. :

Scales: Not specified

Abstract (Expand)

Of 57 functional human cytochromes P450 (CYP) about a dozen liver-expressed, highly variable forms are responsible for the biotransformation of most drugs. Owing to numerous genetic and non-genetic ...

Created: 8th Jan 2014 at 13:58

A fat option for the pig: Hepatocytic differentiated mesenchymal stem cells for translational research

Authors: Sandra Brückner, Hans-Michael Tautenhahn, Sandra Winkler, Peggy Stock, Matthias Dollinger, Bruno Christ

PubMed ID: 24200501

Date Published: 4th Nov 2013

Projects: C6: Organization and function of the sinusoidal system and the liver lob..., Showcase Steatosis

Journal: Exp. Cell Res.

Citation: Exp. Cell Res. 321(2): 267-75

Scales: Cell and Liver

Abstract (Expand)

Study background: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which ...

Created: 10th Feb 2014 at 17:22

Challenges for an enzymatic reaction kinetics database

Authors: Ulrike Wittig, Maja Rey, Renate Kania, Meik Bittkowski, Lei Shi, Martin Golebiewski, Andreas Weidemann, Wolfgang Müller, Isabel Rojas

PubMed ID: 24165050

Date Published: 30th Oct 2013

Projects: F3: Kinetic data handling, F: Data management

Journal: FEBS J.

Citation: FEBS J. :

Scales: Not specified

Abstract (Expand)

The scientific literature contains a tremendous amount of kinetic data describing the dynamic behaviour of biochemical reactions over time. These data are needed for computational modelling to create ...

Created: 27th Nov 2013 at 13:21

Manganese superoxide dismutase is reduced in the liver of male but not female humans and rodents with non-alcoholic fatty liver disease

Authors: Sabrina Krautbauer, Kristina Eisinger, Madeleine Lupke, Josef Wanninger, Petra Ruemmele, Yvonne Hader, Thomas S Weiss, Christa Buechler

PubMed ID: 24161595

Date Published: 22nd Oct 2013

Projects: A1.1: Central liver metabolism and its regulation under nutritional chal..., A3.6: Transcription factor network and links to metabolism in NAFLD

Journal: Exp. Mol. Pathol.

Citation: Exp. Mol. Pathol. 95(3): 330-5

Scales: Cell, Liver and Organism

Abstract (Expand)

Non-alcoholic fatty liver disease (NAFLD) is among the most common liver diseases. Oxidative stress is one of the pathogenic mechanisms contributing to the progression of simple fatty liver to non-alcoholic ...

Created: 30th Jan 2014 at 16:27

Zonation of nitrogen and glucose metabolism gene expression upon acute liver damage in mouse

Authors: Shahrouz Ghafoory, Katja Breitkopf-Heinlein, Qi Li, Catharina Scholl, Steven Dooley, Stefan Wölfl

PubMed ID: 24147127

Date Published: 17th Oct 2013

Projects: C5: Structural changes and functional consequences of the liver lobular/..., Showcase HGF and Regeneration

Journal: PLoS ONE

Citation: PLoS ONE 8(10): e78262

Scales: Not specified

Abstract (Expand)

Zonation of metabolic activities within specific structures and cell types is a phenomenon of liver organization and ensures complementarity of variant liver functions like protein production, glucose ...

Created: 5th Feb 2014 at 12:26

Phosphorylation of the Smo tail is controlled by membrane localisation and is dispensable for clustering

Authors: A. P. Kupinski, I. Raabe, M. Michel, D. Ail, L. Brusch, T. Weidemann, C. Bokel

DOI: 10.1242/jcs.128926

Date Published: 11th Oct 2013

Projects: A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato...

Journal: Journal of Cell Science

Citation: Journal of Cell Science 126(20) : 4684

Scales: Cell

Abstract (Expand)

The Hedgehog (Hh) signalling cascade is highly conserved and involved in development and disease throughout evolution. Nevertheless, in comparison with other pathways, our mechanistic understanding of ...

Created: 24th Jan 2014 at 14:15 Last updated: 24th Jan 2014 at 14:21

Human parenchymal and non-parenchymal liver cell isolation, culture and characterization

Authors: Georg Damm, Elisa Pfeiffer, Britta Burkhardt, Jan Vermehren, Andreas K. Nüssler, Thomas S. Weiss

DOI: 10.1007/s12072-013-9475-7

Date Published: 1st Oct 2013

Projects: CTU SOP Hepatic stellate cells, human, CTU SOP Human Hepatocytes, CTU SOP Kupffer cells/macrophages, human, CTU SOP Liver sinusoidal endothelial cells, human

Journal: Hepatol Int

Citation: Hepatol Int 7(4) : 951

Scales: Cell

Abstract:

Not specified

Created: 30th Jan 2014 at 16:52 Last updated: 30th Jan 2014 at 16:54

Lessons learned from quantitative dynamical modeling in systems biology

Authors: Andreas Raue, Marcel Schilling, Julie Bachmann, Andrew Matteson, Max Schelke, Daniel Kaschek, Sabine Hug, Clemens Kreutz, Brian D Harms, Fabian J Theis, Ursula Klingmüller, Jens Timmer

PubMed ID: 24098642

Date Published: 30th Sep 2013

Projects: A2.3: Cross-talk and distinct properties of growth factor signalling reg..., A2.5: Integration of insulin and Wnt signalling in hepatocytes, A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato...

Journal: PLoS ONE

Citation: PLoS ONE 8(9): e74335

Scales: Cell

Abstract (Expand)

Due to the high complexity of biological data it is difficult to disentangle cellular processes relying only on intuitive interpretation of measurements. A Systems Biology approach that combines ...

Created: 14th Jan 2014 at 11:35

Serum acute phase reactants hallmark healthy individuals at risk for acetaminophen-induced liver injury

Authors: Jürgen Borlak, Bijon Chatterji, Kishor B Londhe, Paul B Watkins

PubMed ID: 24070255

Date Published: 27th Sep 2013

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions, CTU Proteomics

Journal: Genome Med

Citation: Genome Med 5(9): 86

Scales: Liver and Organism

Abstract (Expand)

Acetaminophen (APAP) is a commonly used analgesic. However, its use is associated with drug induced liver injury (DILI). It is a prominent cause of acute liver failure, with APAP hepatotoxicity far ...

Created: 22nd Oct 2013 at 11:09 Last updated: 24th Oct 2013 at 16:14

Isolation of human hepatocytes by a two-step collagenase perfusion procedure

Authors: Serene M L Lee, Celine Schelcher, Maresa Demmel, Maria Hauner, Wolfgang E Thasler

PubMed ID: 24056912

Date Published: 24th Sep 2013

Projects: A: Cellular level, B: Communication of Hepatocytes and Non-Parenchymal Liver Cells, CTUs, Show cases, Virtual Liver

Journal: J Vis Exp

Citation: J Vis Exp (79):

Scales: Cell

Abstract (Expand)

The liver, an organ with an exceptional regeneration capacity, carries out a wide range of functions, such as detoxification, metabolism and homeostasis. As such, hepatocytes are an important model for ...

Created: 13th Jan 2014 at 15:48

ABCC11/MRP8 polymorphisms affect 5-fluorouracil-induced severe toxicity and hepatic expression

Authors: Tarek Magdy, Rudolf Arlanov, Stefan Winter, Thomas Lang, Kathrin Klein, Yu Toyoda, Toshihisa Ishikawa, Matthias Schwab, Ulrich M Zanger

PubMed ID: 24024896

Date Published: 13th Sep 2013

Projects: A3.4: Linking signalling to metabolic functions, G1: Clinical Translation to Invasively Characterized Patients, G2: Clinical Translation to Non-Invasive Volunteer Setting, G3: Clinical Translation to Pharmaceutical Drug Development, G4: Whole-Body Detoxification in Mouse Models

Journal: Pharmacogenomics

Citation: Pharmacogenomics 14(12): 1433-48

Scales: Not specified

Abstract (Expand)

Because 5-fluorodeoxyuridine monophosphate (5-FdUMP), an anabolic active metabolite of 5-fluorouracil (5-FU), is a substrate of MRP8 (encoded by ABCC11), we investigated whether ABCC11 polymorphisms ...

Created: 8th Jan 2014 at 14:01

Implications of enzyme deficiencies on mitochondrial energy metabolism and reactive oxygen species formation of neurons involved in rotenone-induced Parkinson's disease: a model-based analysis

Authors: Nikolaus Berndt, Herrmann-Georg Holzhütter, Sascha Bulik

PubMed ID: 23937586

Date Published: 12th Sep 2013

Projects: A1.1: Central liver metabolism and its regulation under nutritional chal..., A1.2: Detoxification in hepatocytes challenged by steatotic conditions

Journal: FEBS J.

Citation: FEBS J. 280(20): 5080-93

Scales: Not specified

Abstract (Expand)

Steadily growing experimental evidence suggests that mitochondrial dysfunction plays a key role in the age-dependent impairment of nerve cells underlying several neurodegenerative diseases. In particular, ...

Created: 20th Jan 2014 at 10:41

What can we learn from Einstein and Arrhenius about the optimal flow of our blood

Authors: Stefan Schuster, Heiko Stark

PubMed ID: 24021886

Date Published: 8th Sep 2013

Projects: C3: Zonation of metabolism and its regulation

Journal: Biochim. Biophys. Acta

Citation: Biochim. Biophys. Acta 1840(1): 271-6

Scales: Organism

Abstract (Expand)

The oxygen flow in humans and other higher animals depends on the erythrocyte-to-blood volume ratio, the hematocrit. Since it is physiologically favourable when the flow of oxygen transport is maximum ...

Created: 4th Feb 2014 at 09:02

Detecting and removing inconsistencies between experimental data and signaling network topologies using integer linear programming on interaction graphs

Authors: Ioannis N Melas, Regina Samaga, Leonidas G Alexopoulos, Steffen Klamt

PubMed ID: 24039561

Date Published: 5th Sep 2013

Projects: A2.3: Cross-talk and distinct properties of growth factor signalling reg...

Journal: PLoS Comput. Biol.

Citation: PLoS Comput. Biol. 9(9): e1003204

Scales: Cell

Abstract (Expand)

Cross-referencing experimental data with our current knowledge of signaling network topologies is one central goal of mathematical modeling of cellular signal transduction networks. We present a new ...

Created: 13th Dec 2013 at 17:20

A theoretical study of lipid accumulation in the liver-implications for nonalcoholic fatty liver disease

Authors: J Schleicher, R Guthke, U Dahmen, O Dirsch, H G Holzhuetter, S Schuster

PubMed ID: 23999488

Date Published: 4th Sep 2013

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

Journal: Biochim. Biophys. Acta

Citation: Biochim. Biophys. Acta 1841(1): 62-69

Scales: Cell

Abstract (Expand)

A hallmark of the nonalcoholic fatty liver disease is the accumulation of lipids. We developed a mathematical model of the hepatic lipid dynamics to simulate the fate of fatty acids in hepatocytes. Our ...

Created: 23rd Oct 2013 at 14:55 Last updated: 24th Oct 2013 at 16:14

Quantitative structure-activity relationship models for predicting drug-induced liver injury based on FDA-approved drug labeling annotation and using a large collection of drugs

Authors: Minjun Chen, Huixiao Hong, Hong Fang, Reagan Kelly, Guangxu Zhou, Jürgen Borlak, Weida Tong

PubMed ID: 23997115

Date Published: 31st Aug 2013

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions

Journal: Toxicol. Sci.

Citation: Toxicol. Sci. 136(1): 242-9

Scales: Liver

Abstract (Expand)

Drug-induced liver injury (DILI) is one of the leading causes of the termination of drug development programs. Consequently, identifying the risk of DILI in humans for drug candidates during the early ...

Created: 19th Jan 2014 at 17:57

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

Comparative analysis of TGF-beta/Smad signaling dependent cytostasis in human hepatocellular carcinoma cell lines

Authors: J. Dzieran, J. Fabian, T. Feng, C. Coulouarn, I. Ilkavets, A. Kyselova, K. Breuhahn, S. Dooley, N. M. Meindl-Beinker

PubMed ID: 23991075

Date Published: 22nd Aug 2013

Projects: A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato...

Journal: PLoS One

Citation: PLoS One. 2013 Aug 22;8(8):e72252. doi: 10.1371/journal.pone.0072252. eCollection 2013.

Scales: Not specified

Abstract (Expand)

Hepatocellular carcinoma (HCC) is a major public health problem due to increased incidence, late diagnosis and limited treatment options. TGF-beta is known to provide cytostatic signals during early ...

Created: 27th Jul 2015 at 07:19

Assessment of hepatic detoxification activity: proposal of an improved variant of the (13)c-methacetin breath test

Authors: Hermann-Georg Holzhütter, Johan Friso Lock, Pouria Taheri, Sascha Bulik, Andrean Goede, Martin Stockmann

PubMed ID: 23967104

Date Published: 15th Aug 2013

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions, E4: Vertical integration across biological scales

Journal: PLoS ONE

Citation: PLoS ONE 8(8): e70780

Scales: Not specified

Abstract (Expand)

Breath tests based on the administration of a (13)C-labeled drug and subsequent monitoring of (13)CO2 in the breath (quantified as DOB - delta over baseline) liberated from the drug during hepatic ...

Created: 9th Sep 2013 at 15:13 Last updated: 24th Oct 2013 at 16:14

Systems genetics of hepatocellular damage in vivo and in vitro: identification of a critical network on chromosome 11 in mouse

Authors: Roman Liebe, Rabea A Hall, Robert W Williams, Steven Dooley, Frank Lammert

PubMed ID: 23943854

Date Published: 13th Aug 2013

Projects: A2.1: Multi-level regulation of signalling pathways important for primin..., A2.2: Regulation of pro-apoptotic and anti-apoptotic responses in hepato..., Showcase LPS and Inflammation

Journal: Physiol. Genomics

Citation: Physiol. Genomics 45(20): 931-9

Scales: Not specified

Abstract (Expand)

Quantitative trait locus (QTL) mapping is a powerful method to find modifier loci that influence disease risk and progression without prior knowledge of underlying genetic mechanisms. The aim of this ...

Created: 6th Dec 2013 at 09:19

Out of balance--systemic iron homeostasis in iron-related disorders

Authors: Andrea U Steinbicker, Martina U Muckenthaler

PubMed ID: 23917168

Date Published: 7th Aug 2013

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

Journal: Nutrients

Citation: Nutrients 5(8): 3034-61

Scales: Cell, Intercellular and Organism

Abstract (Expand)

Iron is an essential element in our daily diet. Most iron is required for the de novo synthesis of red blood cells, where it plays a critical role in oxygen binding to hemoglobin. Thus, iron deficiency ...

Created: 20th Jan 2014 at 11:06

Chemerin is highly expressed in hepatocytes and is induced in non-alcoholic steatohepatitis liver

Authors: Sabrina Krautbauer, Josef Wanninger, Kristina Eisinger, Yvonne Hader, Michael Beck, Andrea Kopp, Andreas Schmid, Thomas S Weiss, Christoph Dorn, Christa Buechler

PubMed ID: 23906870

Date Published: 29th Jul 2013

Projects: A1.1: Central liver metabolism and its regulation under nutritional chal..., A3.6: Transcription factor network and links to metabolism in NAFLD, CTU SOP Human Hepatocytes, Show cases

Journal: Exp. Mol. Pathol.

Citation: Exp. Mol. Pathol. 95(2): 199-205

Scales: Cell and Liver

Abstract (Expand)

Chemerin is a recently described adipokine whose adipose tissue and serum levels are increased in obesity. Chemerin is expressed in the liver, and here, expression of chemerin has been studied in liver ...

Created: 30th Jan 2014 at 17:11

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

DNA methylation of the SLC16A3 promoter regulates expression of the human lactate transporter MCT4 in renal cancer with consequences for clinical outcome

Authors: Pascale Fisel, Stephan Kruck, Stefan Winter, Jens Bedke, Jörg Hennenlotter, Anne T Nies, Marcus Scharpf, Falko Fend, Arnulf Stenzl, Matthias Schwab, Elke Schaeffeler

PubMed ID: 23881922

Date Published: 23rd Jul 2013

Projects: B5: Cell-cell communication influences detoxifying functions in hepatocytes, G3: Clinical Translation to Pharmaceutical Drug Development

Journal: Clin. Cancer Res.

Citation: Clin. Cancer Res. 19(18): 5170-81

Scales: Not specified

Abstract (Expand)

The monocarboxylate transporter 4 (MCT4) is a metabolic target in tumor biology because it mediates lactate transport across membranes resulting in antiapoptotic effects. Cell experiments support the ...

Created: 20th Jan 2014 at 14:16

Nrf2 activates augmenter of liver regeneration (ALR) via antioxidant response element and links oxidative stress to liver regeneration

Authors: Rania Dayoub, Arndt Vogel, Jutta Schuett, Madeleine Lupke, Susannah M Spieker, Nadja Kettern, Eberhard Hildt, Michael Melter, Thomas S Weiss

PubMed ID: 23887691

Date Published: 23rd Jul 2013

Projects: A2.1: Multi-level regulation of signalling pathways important for primin..., CTU SOP Human Hepatocytes

Journal: Mol. Med.

Citation: Mol. Med. 19: 237-44

Scales: Cell and Liver

Abstract (Expand)

Liver regeneration can be impaired by permanent oxidative stress and activation of nuclear factor erythroid 2-related factor 2 (Nrf2), known to regulate the cellular antioxidant response, and has been ...

Created: 30th Jan 2014 at 17:06

Evaluation of 41 candidate gene variants for obesity in the EPIC-potsdam cohort by multi-locus stepwise regression

Authors: Sven Knüppel, Klaus Rohde, Karina Meidtner, Dagmar Drogan, Hermann-Georg Holzhütter, Heiner Boeing, Eva Fisher

PubMed ID: 23874820

Date Published: 12th Jul 2013

Projects: No Projects

Journal: PLoS ONE

Citation: PLoS ONE 8(7): e68941

Scales: Not specified

Abstract (Expand)

Obesity has become a leading preventable cause of morbidity and mortality in many parts of the world. It is thought to originate from multiple genetic and environmental determinants. The aim of the ...

Created: 20th Jan 2014 at 10:28

Apoptosis induced by the fungal pathogen gliotoxin requires a triple phosphorylation of Bim by JNK

Authors: A Geissler, F Haun, D O Frank, K Wieland, M M Simon, M Idzko, R J Davis, U Maurer, C Borner

PubMed ID: 23832115

Date Published: 5th Jul 2013

Projects: No Projects

Journal: Cell Death Differ.

Citation: Cell Death Differ. 20(10): 1317-29

Scales: Not specified

Abstract (Expand)

We previously reported that gliotoxin (GT), the major virulence factor of the mold Aspergillus fumigatus causing invasive aspergillosis (IA) in immunocompromised patients, induces apoptosis in a ...

Created: 22nd Jan 2014 at 15:18

GRN2SBML: Automated encoding and annotation of inferred gene regulatory networks complying with SBML

Authors: S. Vlaic, B. Hoffmann, P. Kupfer, M. Weber, A. Drager

DOI: 10.1093/bioinformatics/btt370

Date Published: 26th Jun 2013

Projects: A3.4: Linking signalling to metabolic functions, A3.6: Transcription factor network and links to metabolism in NAFLD

Journal: Bioinformatics

Citation: Bioinformatics 29(17) : 2216

Scales: Cell

Abstract (Expand)

Summary: GRN2SBML automatically encodes gene regulatory networks derived from several inference tools in SBML. Providing a graphical user interface, the networks can be annotated via the SOAP-based ...

Created: 1st Jul 2013 at 23:57 Last updated: 24th Oct 2013 at 16:14

Modeling approaches for qualitative and semi-quantitative analysis of cellular signaling networks

Authors: Regina Samaga, Steffen Klamt

PubMed ID: 23803171

Date Published: 26th Jun 2013

Projects: A2.3: Cross-talk and distinct properties of growth factor signalling reg...

Journal: Cell Commun. Signal

Citation: Cell Commun. Signal 11(1): 43

Scales: Cell

Abstract (Expand)

A central goal of systems biology is the construction of predictive models of bio-molecular networks. Cellular networks of moderate size have been modeled successfully in a quantitative way based on ...

Created: 13th Dec 2013 at 17:23

Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape

Authors: Jerome Gilleron, William Querbes, Anja Zeigerer, Anna Borodovsky, Giovanni Marsico, Undine Schubert, Kevin Manygoats, Sarah Seifert, Cordula Andree, Martin Stöter, Hila Epstein-Barash, Ligang Zhang, Victor Koteliansky, Kevin Fitzgerald, Eugenio Fava, Marc Bickle, Yannis Kalaidzidis, Akin Akinc, Martin Maier, Marino Zerial

PubMed ID: 23792630

Date Published: 23rd Jun 2013

Projects: A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato...

Journal: Nat. Biotechnol.

Citation: Nat. Biotechnol. 31(7): 638-46

Scales: Cell, Intercellular and Liver

Abstract (Expand)

Delivery of short interfering RNAs (siRNAs) remains a key challenge in the development of RNA interference (RNAi) therapeutics. A better understanding of the mechanisms of siRNA cellular uptake, ...

Created: 15th Jul 2013 at 11:10 Last updated: 24th Oct 2013 at 16:14

Practical quantification of necrosis in histological whole-slide images

Authors: André Homeyer, Andrea Schenk, Janine Arlt, Uta Dahmen, Olaf Dirsch, Horst K Hahn

PubMed ID: 23796718

Date Published: 21st Jun 2013

Projects: CTU Image Processing, D4: Regeneration and Liver Size

Journal: Comput Med Imaging Graph

Citation: Comput Med Imaging Graph 37(4): 313-22

Scales: Liver lobule and Liver

Abstract (Expand)

Since the histological quantification of necrosis is a common task in medical research and practice, we evaluate different image analysis methods for quantifying necrosis in whole-slide images. In a ...

Created: 7th Nov 2013 at 08:56

TNFα-induced lysosomal membrane permeability is downstream of MOMP and triggered by caspase-mediated NDUFS1 cleavage and ROS formation

Authors: Jisen Huai, F-Nora Vögtle, Lars Jöckel, Yunbo Li, Thomas Kiefer, Jean-Ehrland Ricci, Christoph Borner

PubMed ID: 23788428

Date Published: 20th Jun 2013

Projects: No Projects

Journal: J. Cell. Sci.

Citation: J. Cell. Sci. 126(Pt 17): 4015-25

Scales: Not specified

Abstract (Expand)

When NF-κB activation or protein synthesis is inhibited, tumor necrosis factor alpha (TNFα) can induce apoptosis through Bax- and Bak-mediated mitochondrial outer membrane permeabilization (MOMP) leading ...

Created: 22nd Jan 2014 at 15:18

Isolation and hepatocyte differentiation of mesenchymal stem cells from porcine bone marrow--"surgical waste" as a novel MSC source

Authors: S Brückner, H-M Tautenhahn, S Winkler, P Stock, S Jonas, M Dollinger, B Christ

PubMed ID: 23769107

Date Published: 19th Jun 2013

Projects: C6: Organization and function of the sinusoidal system and the liver lob..., G: Clinical translation, Showcase Steatosis

Journal: Transplant. Proc.

Citation: Transplant. Proc. 45(5): 2056-8

Scales: Organism

Abstract (Expand)

Mesenchymal stem cells (MSC) isolated from bone marrow and differentiated into hepatocyte-like cells have increasingly gained attention for clinical cell therapy of liver diseases because of their high ...

Created: 19th Nov 2013 at 11:47

Expression variability of absorption, distribution, metabolism, excretion-related microRNAs in human liver: influence of nongenetic factors and association with gene expression

Authors: Jessica K Rieger, Kathrin Klein, Stefan Winter, Ulrich M Zanger

PubMed ID: 23733276

Date Published: 3rd Jun 2013

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

Journal: Drug Metab. Dispos.

Citation: Drug Metab. Dispos. 41(10): 1752-62

Scales: Not specified

Abstract (Expand)

Genes that are important for the detoxification of drugs and other xenobiotics show a high degree of interindividual variation attributable to regulation by diverse genetic, nongenetic, and epigenetic ...

Created: 8th Jan 2014 at 14:05

Alkyne lipids as substrates for click chemistry-based in vitro enzymatic assays

Authors: Anne Gaebler, Robin Milan, Leon Straub, Dominik Hoelper, Lars Kuerschner, Christoph Thiele

PubMed ID: 23709689

Date Published: 23rd May 2013

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

Journal: J. Lipid Res.

Citation: J. Lipid Res. 54(8): 2282-90

Scales: Not specified

Abstract (Expand)

Click chemistry is evolving as a powerful tool in biological applications because it allows the sensitive and specific detection of compounds with alkyne or azido groups. Here we describe the use of ...

Created: 6th Jan 2014 at 11:19

Profile likelihood in systems biology

Authors: Clemens Kreutz, Andreas Raue, Daniel Kaschek, Jens Timmer

PubMed ID: 23581573

Date Published: 9th May 2013

Journal: FEBS J.

Citation: FEBS J. 280(11): 2564-71

Scales: Not specified

Abstract (Expand)

Inferring knowledge about biological processes by a mathematical description is a major characteristic of Systems Biology. To understand and predict system's behavior the available experimental ...

Created: 14th Jan 2014 at 11:37

Metabolic Gradients as Key Regulators in Zonation of Tumor Energy Metabolism: A Tissue-scale Model Based Study

Authors: Matthias König, Hermann-Georg Holzhütter, Nikolaus Berndt

PubMed ID: 23589477

Date Published: 17th Apr 2013

Projects: C3: Zonation of metabolism and its regulation

Journal: Biotechnol J

Citation: Biotechnol J 8(9): 1058-69

Scales: Not specified

Abstract (Expand)

Characteristics of many tumor types are the reprogramming of metabolism and the occurrence of regional hypoxia. In this work we investigated the hypothesis that metabolic reprogramming in combination ...

Created: 6th May 2013 at 09:31 Last updated: 24th Oct 2013 at 16:14

Excemplify: a flexible template based solution, parsing and managing data in spreadsheets for experimentalists

Authors: L. Shi, L. Jong, U. Wittig, P. Lucarelli, M. Stepath, S. Mueller, L. A. D'Alessandro, U. Klingmuller, W. Muller

PubMed ID: 23549603

Date Published: 3rd Apr 2013

Projects: F1: The data management system

Journal: J Integr Bioinform

Citation: J Integr Bioinform. 2013 Apr 3;10(2):220. doi: 10.2390/biecoll-jib-2013-220.

Scales: Not specified

Abstract (Expand)

In systems biology, quantitative experimental data is the basis of building mathematical models. In most of the cases, they are stored in Excel files and hosted locally. To have a public database for ...

Created: 7th Aug 2015 at 12:16

Bridging the layers: towards integration of signal transduction, regulation and metabolism into mathematical models

Authors: Emanuel Gonçalves, Joachim Bucher, Anke Ryll, Jens Niklas, Klaus Mauch, Steffen Klamt, Miguel Rocha, Julio Saez-Rodriguez

PubMed ID: 23525368

Date Published: 26th Mar 2013

Projects: A2.5: Integration of insulin and Wnt signalling in hepatocytes, A3.4: Linking signalling to metabolic functions, A3.6: Transcription factor network and links to metabolism in NAFLD, A: Cellular level, E: Model integration, Virtual Liver

Journal: Mol Biosyst

Citation: Mol Biosyst 9(7): 1576-83

Scales: Cell, Liver and Organism

Abstract (Expand)

Mathematical modelling is increasingly becoming an indispensable tool for the study of cellular processes, allowing their analysis in a systematic and comprehensive manner. In the vast majority of the ...

Created: 3rd Jun 2013 at 16:37 Last updated: 24th Oct 2013 at 16:14

A Discriminative Approach for Unsupervised Clustering of DNA Sequence Motifs

Authors: Philip Stegmaier, Alexander Kel, Edgar Wingender, Jürgen Borlak

DOI: 10.1371/journal.pcbi.1002958

Date Published: 21st Mar 2013

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

Journal: PLoS Comput Biol

Citation: PLoS Comput Biol 9(3) : e1002958

Scales: Cell

Abstract (Expand)

Algorithmic comparison of DNA sequence motifs is a problem in bioinformatics that has received increased attention during the last years. Its main applications concern characterization of potentially ...

Created: 28th Mar 2013 at 11:59 Last updated: 24th Oct 2013 at 16:14

Iron regulatory proteins control a mucosal block to intestinal iron absorption

Authors: Bruno Galy, Dunja Ferring-Appel, Christiane Becker, Norbert Gretz, Hermann-Josef Gröne, Klaus Schümann, Matthias W Hentze

PubMed ID: 23523353

Date Published: 21st Mar 2013

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

Journal: Cell Rep

Citation: Cell Rep 3(3): 844-57

Scales: Not specified

Abstract (Expand)

Mammalian iron metabolism is regulated systemically by the hormone hepcidin and cellularly by iron regulatory proteins (IRPs) that orchestrate a posttranscriptional regulatory network. Through ...

Created: 14th Jan 2014 at 14:38

Biggest challenges in bioinformatics

Authors: Jonathan C Fuller, Pierre Khoueiry, Holger Dinkel, Kristoffer Forslund, Alexandros Stamatakis, Joseph Barry, Aidan Budd, Theodoros G Soldatos, Katja Linssen, Abdul Mateen Rajput

DOI: 10.1038/embor.2013.34

Date Published: 15th Mar 2013

Projects: F: Data management

Journal: EMBO Rep

Citation: EMBO Rep 14(4) : 302

Scales: Not specified

Abstract (Expand)

The third Heidelberg Unseminars in Bioinformatics (HUB) was held on 18th October 2012, at Heidelberg University, Germany. HUB brought together around 40 bioinformaticians from academia and industry to ...

Created: 13th Jan 2014 at 15:08 Last updated: 13th Jan 2014 at 15:14

The High Energy Demand of Neuronal Cells Caused by Passive Leak Currents is Not a Waste of Energy

Authors: Nikolaus Berndt, Hermann-Georg Holzhütter

PubMed ID: 23479331

Date Published: 13th Mar 2013

Projects: No Projects

Journal: Cell Biochem. Biophys.

Citation: Cell Biochem Biophys. 67(2):527-35

Scales: Not specified

Abstract (Expand)

It is estimated that maintenance of the resting potential of neurons consumes between 15 % (in gray matter) and 44 % (in fully myelinated white matter) of the brain's total energy budget [1]. This ...

Created: 6th May 2013 at 09:24 Last updated: 24th Oct 2013 at 16:14

Novel CYP2B6 enzyme variants in a Rwandese population: functional characterization and assessment of in silico prediction tools

Authors: Robert Radloff, Alain Gras, Ulrich M Zanger, Cécile Masquelier, Karthik Arumugam, Jean-Claude Karasi, Vic Arendt, Carole Seguin-Devaux, Kathrin Klein

PubMed ID: 23418033

Date Published: 11th Mar 2013

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

Journal: Hum. Mutat.

Citation: Hum. Mutat. 34(5): 725-34

Scales: Not specified

Abstract (Expand)

Cytochrome P450 CYP2B6 is a highly polymorphic enzyme that metabolizes numerous drugs, pesticides, and environmental toxins. Sequence analysis of a Rwandese population identified eight functionally ...

Created: 13th Jan 2014 at 10:17

Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance

Authors: Ulrich M Zanger, Kathrin Klein

PubMed ID: 23467454

Date Published: 5th Mar 2013

Projects: A3.4: Linking signalling to metabolic functions

Journal: Front Genet

Citation: Front Genet 4: 24

Scales: Not specified

Abstract (Expand)

Cytochrome P450 2B6 (CYP2B6) belongs to the minor drug metabolizing P450s in human liver. Expression is highly variable both between individuals and within individuals, owing to non-genetic factors, ...

Created: 8th Jan 2014 at 14:10

A community-driven global reconstruction of human metabolism

Authors: Ines Thiele, Neil Swainston, Ronan M T Fleming, Andreas Hoppe, Swagatika Sahoo, Maike K Aurich, Hulda Haraldsdottir, Monica L Mo, Ottar Rolfsson, Miranda D Stobbe, Stefan G Thorleifsson, Rasmus Agren, Christian Bölling, Sergio Bordel, Arvind K Chavali, Paul Dobson, Warwick B Dunn, Lukas Endler, David Hala, Michael Hucka, Duncan Hull, Daniel Jameson, Neema Jamshidi, Jon J Jonsson, Nick Juty, Sarah Keating, Intawat Nookaew, Nicolas Le Novère, Naglis Malys, Alexander Mazein, Jason A Papin, Nathan D Price, Evgeni Selkov, Martin I Sigurdsson, Evangelos Simeonidis, Nikolaus Sonnenschein, Kieran Smallbone, Anatoly Sorokin, Johannes H G M van Beek, Dieter Weichart, Igor Goryanin, Jens Nielsen, Hans V Westerhoff, Douglas B Kell, Pedro Mendes, Bernhard Ø Palsson

PubMed ID: 23455439

Date Published: 3rd Mar 2013

Projects: A1.1: Central liver metabolism and its regulation under nutritional chal..., A1.2: Detoxification in hepatocytes challenged by steatotic conditions, A1.3: Identification of crucial metabolic processes during hepatocyte pr...

Journal: Nat. Biotechnol.

Citation: Nat. Biotechnol. 31(5): 419-25

Scales: Not specified

Abstract (Expand)

Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', ...

Created: 19th Mar 2013 at 12:53 Last updated: 24th Oct 2013 at 16:15

Abnormal body iron distribution and erythropoiesis in a novel mouse model with inducible gain of iron regulatory protein (IRP)-1 function

Authors: D Casarrubea, L Viatte, T Hallas, A Vasanthakumar, R S Eisenstein, K Schümann, M W Hentze, B Galy

PubMed ID: 23455710

Date Published: 1st Mar 2013

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

Journal: J. Mol. Med.

Citation: J. Mol. Med. 91(7): 871-81

Scales: Not specified

Abstract (Expand)

Disorders of iron metabolism account for some of the most common human diseases. Cellular iron homeostasis is maintained by iron regulatory proteins (IRP)-1 and 2 through their binding to cis-regulatory ...

Created: 14th Jan 2014 at 14:40

Differently Saturated Fatty Acids Can Be Differentiated by (31)P NMR Subsequent to Derivatization with 2-Chloro-4,4,5,5-tetramethyldioxaphospholane: A Cautionary Note

Authors: Mandy Eibisch, Thomas Riemer, Beate Fuchs, Jürgen Schiller

PubMed ID: 23414224

Date Published: 26th Feb 2013

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

Journal: J. Agric. Food Chem.

Citation: J. Agric. Food Chem. 61(11): 2696-700

Scales: Not specified

Abstract (Expand)

The analysis of free fatty acid (FFA) mixtures is a very important but, even nowadays, challenging task. This particularly applies as the so far most commonly used technique-gas chromatography/mass ...

Created: 6th Jan 2014 at 13:54

Pharmacogenomics of Cytochrome P450 3A4: Recent Progress Toward the "Missing Heritability" Problem

Authors: Kathrin Klein, Ulrich M Zanger

PubMed ID: 23444277

Date Published: 25th Feb 2013

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

Journal: Front Genet

Citation: Front Genet 4: 12

Scales: Not specified

Abstract (Expand)

CYP3A4 is the most important drug metabolizing enzyme in adult humans because of its prominent expression in liver and gut and because of its broad substrate specificity, which includes drugs from most ...

Created: 8th Jan 2014 at 14:16

Hedgehog signalling pathway in adult liver: a major new player in hepatocyte metabolism and zonation

Authors: Madlen Matz-Soja, Amalya Hovhannisyan, Rolf Gebhardt

PubMed ID: 23433827

Date Published: 21st Feb 2013

Projects: Virtual Liver

Journal: Med. Hypotheses

Citation: Med. Hypotheses 80(5): 589-94

Scales: Liver

Abstract (Expand)

Metabolic Zonation, i.e. the heterogeneous distribution of different metabolic pathways in different zones of the lobules, forms the basis of proper function of the liver in metabolic homeostasis and ...

Created: 4th Feb 2014 at 08:09

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

System-wide identification of RNA-binding proteins by interactome capture

Authors: Alfredo Castello, Rastislav Horos, Claudia Strein, Bernd Fischer, Katrin Eichelbaum, Lars M Steinmetz, Jeroen Krijgsveld, Matthias W Hentze

PubMed ID: 23411631

Date Published: 14th Feb 2013

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

Journal: Nat Protoc

Citation: Nat Protoc 8(3): 491-500

Scales: Not specified

Abstract (Expand)

Owing to their preeminent biological functions, the repertoire of expressed RNA-binding proteins (RBPs) and their activity states are highly informative about cellular systems. We have developed a novel ...

Created: 14th Jan 2014 at 14:41

A Unifying Ontology to Integrate Histological and Clinical Observations for Drug-Induced Liver Injury

Authors: Yuping Wang, Zhi Lin, Zhichao Liu, Stephen Harris, Reagan Kelly, Jie Zhang, Weigong Ge, Minjun Chen, Jürgen Borlak, Weida Tong

PubMed ID: 23395088

Date Published: 12th Feb 2013

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions

Journal: Am. J. Pathol.

Citation: Am. J. Pathol. 182(4): 1180-7

Scales: Liver

Abstract (Expand)

Drug-induced liver injury (DILI) may present any morphologic characteristic of acute or chronic liver disease with no standardized terminology in place. Defining lexemes of DILI histopathology would ...

Created: 5th Mar 2013 at 16:36 Last updated: 24th Oct 2013 at 16:15

The Liver Toxicity Knowledge Base: A Systems Approach to a Complex End Point

Authors: M Chen, J Zhang, Y Wang, Z Liu, R Kelly, G Zhou, H Fang, J Borlak, W Tong

PubMed ID: 23486446

Date Published: 25th Jan 2013

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions

Journal: Clin. Pharmacol. Ther.

Citation: Clin. Pharmacol. Ther. 93(5): 409-12

Scales: Cell

Abstract:

Not specified

Created: 15th Mar 2013 at 14:16 Last updated: 24th Oct 2013 at 16:15

A multi-scale modeling framework for individualized, spatiotemporal prediction of drug effects and toxicological risk

Authors: Juan G Diaz Ochoa, Joachim Bucher, Alexandre R R Péry, José M Zaldivar Comenges, Jens Niklas, Klaus Mauch

PubMed ID: 23346056

Date Published: 22nd Jan 2013

Projects: No Projects

Journal: Front Pharmacol

Citation: Front Pharmacol 3: 204

Scales: Not specified

Abstract (Expand)

In this study, we focus on a novel multi-scale modeling approach for spatiotemporal prediction of the distribution of substances and resulting hepatotoxicity by combining cellular models, a 2D liver ...

Created: 4th Feb 2013 at 11:46 Last updated: 24th Oct 2013 at 16:15

Molecular Interactions between NAFLD and Xenobiotic Metabolism

Authors: Adviti Naik, Aleš Belič, Ulrich M Zanger, Damjana Rozman

PubMed ID: 23346097

Date Published: 22nd Jan 2013

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions, A3.4: Linking signalling to metabolic functions, A3.6: Transcription factor network and links to metabolism in NAFLD, G1: Clinical Translation to Invasively Characterized Patients, Showcase Steatosis

Journal: Front Genet

Citation: Front Genet 4: 2

Scales: Not specified

Abstract (Expand)

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, is a complex multifactorial disease characterized by metabolic deregulations that include accumulation ...

Created: 8th Jan 2014 at 14:35

Caveolin-1 abrogates TGF-β mediated hepatocyte apoptosis

Authors: C Meyer, Y Liu, A Kaul, I Peipe, S Dooley

PubMed ID: 23328673

Date Published: 19th Jan 2013

Projects: A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato..., A3.3: Hepatocyte polarity

Journal: Cell Death Dis

Citation: Cell Death Dis 4: e466

Scales: Cell

Abstract (Expand)

Transforming growth factor (TGF)-β has a dual role in liver, providing cytostatic effects during liver damage and regeneration, as well as carcinogenic functions in malignant transformation and ...

Created: 23rd Jan 2013 at 17:53 Last updated: 24th Oct 2013 at 16:15

Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation

Authors: Ulrich M Zanger, Matthias Schwab

PubMed ID: 23333322

Date Published: 16th Jan 2013

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions, A3.4: Linking signalling to metabolic functions, B5: Cell-cell communication influences detoxifying functions in hepatocytes, G1: Clinical Translation to Invasively Characterized Patients, G2: Clinical Translation to Non-Invasive Volunteer Setting, G3: Clinical Translation to Pharmaceutical Drug Development, G4: Whole-Body Detoxification in Mouse Models

Journal: Pharmacol. Ther.

Citation: Pharmacol. Ther. 138(1): 103-41

Scales: Not specified

Abstract (Expand)

Cytochromes P450 (CYP) are a major source of variability in drug pharmacokinetics and response. Of 57 putatively functional human CYPs only about a dozen enzymes, belonging to the CYP1, 2, and 3 families, ...

Created: 8th Jan 2014 at 14:40

Genetics is a major determinant of expression of the human hepatic uptake transporter OATP1B1, but not of OATP1B3 and OATP2B1

Authors: Anne T Nies, Mikko Niemi, Oliver Burk, Stefan Winter, Ulrich M Zanger, Bruno Stieger, Matthias Schwab, Elke Schaeffeler

PubMed ID: 23311897

Date Published: 11th Jan 2013

Projects: A3.4: Linking signalling to metabolic functions, B5: Cell-cell communication influences detoxifying functions in hepatocytes, G1: Clinical Translation to Invasively Characterized Patients, G2: Clinical Translation to Non-Invasive Volunteer Setting, G3: Clinical Translation to Pharmaceutical Drug Development, G4: Whole-Body Detoxification in Mouse Models

Journal: Genome Med

Citation: Genome Med 5(1): 1

Scales: Not specified

Abstract (Expand)

ABSTRACT: BACKGROUND: Organic anion transporting polypeptide (OATP) 1B1, OATP1B3, and OATP2B1 (encoded by SLCO1B1, SLCO1B3, SLCO2B1) mediate the hepatic uptake of endogenous compounds like bile acids ...

Created: 16th Jan 2013 at 09:16 Last updated: 24th Oct 2013 at 16:15

Direct Transcriptional Regulation of Human Hepatic Cytochrome P450 3A4 (CYP3A4) by Peroxisome Proliferator-Activated Receptor Alpha (PPARα)

Authors: Maria Thomas, Oliver Burk, Britta Klumpp, Benjamin A Kandel, Georg Damm, Thomas S Weiss, Kathrin Klein, Matthias Schwab, Ulrich M Zanger

PubMed ID: 23295386

Date Published: 9th Jan 2013

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions, A3.4: Linking signalling to metabolic functions, B5: Cell-cell communication influences detoxifying functions in hepatocytes, G1: Clinical Translation to Invasively Characterized Patients, G2: Clinical Translation to Non-Invasive Volunteer Setting, Showcase Steatosis

Journal: Mol. Pharmacol.

Citation: Mol. Pharmacol. 83(3): 709-18

Scales: Cell

Abstract (Expand)

The nuclear receptor peroxisome proliferator-activated receptor (PPAR)α is primarily known as a regulator of fatty acid metabolism, energy balance, and inflammation, but there is evidence suggesting a ...

Created: 9th Jan 2013 at 15:04 Last updated: 24th Oct 2013 at 16:15

Bone morphogenetic protein-9 (BMP-9) induces epithelial to mesenchymal transition (EMT) in hepatocellular carcinoma cells

Authors: Qi Li, Xing Gu, Honglei Weng, Shahrouz Ghafoory, Yan Liu, Teng Feng, Johanna Dzieran, Li Li, Iryna Ilkavets, Marianna Kruithof-de Julio, Stefan Munker, Alexander Marx, Albrecht Piiper, Eduardo Augusto Alonso, Norbert Gretz, Chunfang Gao, Stefan Wölfl, Steven Dooley, Katja Breitkopf-Heinlein

PubMed ID: 23281849

Date Published: 4th Jan 2013

Projects: A2.3: Cross-talk and distinct properties of growth factor signalling reg..., A3.3: Hepatocyte polarity, B2.1: Hepatic stellate cells as source and target for hepatocellular gro..., B2.3: Effect of hepatic stellate cells on hepatocyte polarity and transd...

Journal: Cancer Sci.

Citation: Cancer Sci. 104(3): 398-408

Scales: Cell

Abstract (Expand)

80 - 90% of primary liver cancer cases originate from hepatocellular carcinoma (HCC), which has been regarded as the fifth most common cancer and the third most fatal reason responsible for cancer-related ...

Created: 18th Jan 2013 at 10:41 Last updated: 24th Oct 2013 at 16:15

Metformin and cancer: from the old medicine cabinet to pharmacological pitfalls and prospects

Authors: Arian Emami Riedmaier, Pascale Fisel, Anne T Nies, Elke Schaeffeler, Matthias Schwab

PubMed ID: 23277337

Date Published: 2nd Jan 2013

Projects: G1: Clinical Translation to Invasively Characterized Patients, G2: Clinical Translation to Non-Invasive Volunteer Setting, G3: Clinical Translation to Pharmaceutical Drug Development, G4: Whole-Body Detoxification in Mouse Models

Journal: Trends Pharmacol. Sci.

Citation: Trends Pharmacol. Sci. 34(2): 126-35

Scales: Not specified

Abstract (Expand)

Metformin is a biguanide derivative used in the treatment of type II diabetes (T2D) and one of the world's most widely prescribed drugs. Owing to its safety profile, it has been recently promoted ...

Created: 8th Jan 2013 at 10:08 Last updated: 24th Oct 2013 at 16:15

Distinct dedifferentiation processes affect caveolin-1 expression in hepatocytes

Authors: Christoph Meyer, Johanna Dzieran, Yan Liu, Felizitas Schindler, Stefan Munker, Alexandra Müller, Cédric Coulouarn, Steven Dooley

DOI: 10.1186/1478-811X-11-6

Date Published: 2013

Projects: A3.3: Hepatocyte polarity

Journal: Cell Commun Signal

Citation: Cell Commun Signal 11(1) : 6

Scales: Cell

Abstract:

Not specified

Created: 23rd Jan 2013 at 17:57 Last updated: 24th Oct 2013 at 16:15

A Mechanistic, Model-Based Approach to Safety Assessment in Clinical Development

Authors: J Lippert, M Brosch, O von Kampen, M Meyer, H.-U Siegmund, C Schafmayer, T Becker, B Laffert, L Goerlitz, S Schreiber, PJ Neuvonen, M Niemi, J Hampe, L Kuepfer

DOI: 10.1038/psp.2012.22

Date Published: 2013

Projects: G3: Clinical Translation to Pharmaceutical Drug Development, G: Clinical translation

Journal: CPT: pharmacomet. syst. pharmacol.

Citation: CPT: pharmacomet. syst. pharmacol. 2(1) : e21

Scales: Not specified

Abstract:

Not specified

Created: 28th Jan 2013 at 09:55 Last updated: 24th Oct 2013 at 16:15

Precise generation of systems biology models from KEGG pathways

Authors: Clemens Wrzodek, Finja Büchel, Manuel Ruff, Andreas Dräger, Andreas Zell

DOI: 10.1186/1752-0509-7-15

Date Published: 2013

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

Journal: BMC Syst Biol

Citation: BMC Syst Biol 7(1) : 15

Scales: Cell and Intercellular

Abstract (Expand)

Background: The KEGG PATHWAY database provides a plethora of pathways for a diversity of organisms. All pathway components are directly linked to other KEGG databases, such as KEGG COMPOUND or KEGG ...

Created: 23rd Feb 2013 at 23:19 Last updated: 24th Oct 2013 at 16:15

Modeling Wnt/β-Catenin Target Gene Expression in APC and Wnt Gradients Under Wild Type and Mutant Conditions

Authors: Uwe Benary, Bente Kofahl, Andreas Hecht, Jana Wolf

DOI: 10.3389/fphys.2013.00021

Date Published: 2013

Projects: A2.5: Integration of insulin and Wnt signalling in hepatocytes, B2.2: Importance of Wnt- and Hedgehog factors for hepatic stellate cells...

Journal: Front. Physiol.

Citation: Front. Physiol. 4

Scales: Cell

Abstract (Expand)

The Wnt/β-catenin pathway is involved in the regulation of a multitude of physiological processes by controlling the differential expression of target genes. In certain tissues such as the adult liver, ...

Created: 27th Feb 2013 at 10:06 Last updated: 24th Oct 2013 at 16:15

The systems biology simulation core algorithm

Authors: Roland Keller, Alexander Dörr, Akito Tabira, Akira Funahashi, Michael J Ziller, Richard Adams, Nicolas Rodriguez, Nicolas Le Novère, Noriko Hiroi, Hannes Planatscher, Andreas Zell, Andreas Dräger

DOI: 10.1186/1752-0509-7-55

Date Published: 2013

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

Journal: BMC Syst Biol

Citation: BMC Syst Biol 7(1) : 55

Scales: Cell, Intercellular, Liver lobule, Liver and Organism

Abstract (Expand)

Background With the increasing availability of high dimensional time course data for metabolites, genes, and fluxes, the mathematical description of dynamical systems has become an essential aspect of ...

Created: 9th Jul 2013 at 04:12 Last updated: 24th Oct 2013 at 16:15

Metabolic Networks

Authors: Andreas Dräger, Hannes Planatscher

DOI: 10.1007/978-1-4419-9863-7_1277

Date Published: 2013

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

Book: Encyclopedia of Systems Biology

Citation: Encyclopedia of Systems Biology : 1249

Scales: Cell

Abstract (Expand)

Metabolic networks are interconnected pathways of biochemical reactions within living cells through which building blocks or compounds necessary for cellular functioning are assembled (anabolism) or ...

Created: 15th Aug 2013 at 23:34 Last updated: 23rd Jul 2015 at 13:38

Parameter Estimation, Metabolic Network Modeling

Authors: Andreas Dräger, Hannes Planatscher

DOI: 10.1007/978-1-4419-9863-7_1174

Date Published: 2013

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

Book: Encyclopedia of Systems Biology

Citation: Encyclopedia of Systems Biology : 1627

Scales: Cell

Abstract (Expand)

Metabolic networks can mathematically be modeled as a differential equation system. These models consist of a stoichiometric matrix, a modulation matrix, and a vector of reaction rates. The mathematical ...

Created: 15th Aug 2013 at 23:37 Last updated: 23rd Jul 2015 at 13:38

Using Bayesian-PBPK modeling for assessment of inter-individual variability and subgroup stratification

Authors: Markus Krauss, Rolf Burghaus, Jörg Lippert, Mikko Niemi, Pertti Neuvonen, Andreas Schuppert, Stefan Willmann, Lars Kuepfer, Linus Görlitz

DOI: 10.1186/2193-9616-1-6

Date Published: 2013

Projects: G: Clinical translation

Journal: In Silico Pharmacol

Citation: In Silico Pharmacol 1(1) : 6

Scales: Liver and Organism

Abstract (Expand)

Purpose Inter-individual variability in clinical endpoints and occurrence of potentially severe adverse effects represent an enormous challenge in drug development at all phases of (pre-)clinical ...

Created: 16th Sep 2013 at 13:50 Last updated: 24th Oct 2013 at 16:15

Path2Models: large-scale generation of computational models from biochemical pathway maps

Authors: Finja Büchel, Nicolas Rodriguez, Neil Swainston, Clemens Wrzodek, Tobias Czauderna, Roland Keller, Florian Mittag, Michael Schubert, Mihai Glont, Martin Golebiewski, Martijn van Iersel, Sarah Keating, Matthias Rall, Michael Wybrow, Henning Hermjakob, Michael Hucka, Douglas B Kell, Wolfgang Müller, Pedro Mendes, Andreas Zell, Claudine Chaouiya, Julio Saez-Rodriguez, Falk Schreiber, Camille Laibe, Andreas Dräger, Nicolas Le Novère

DOI: 10.1186/1752-0509-7-116

Date Published: 2013

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

Journal: BMC Syst Biol

Citation: BMC Syst Biol 7(1) : 116

Scales: Cell and Intercellular

Abstract (Expand)

Background Systems biology projects and omics technologies have led to a growing number of biochemical pathway models and reconstructions. However, the majority of these models are still created de ...

Created: 4th Nov 2013 at 16:48 Last updated: 4th Nov 2013 at 16:54

SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools

Authors: Claudine Chaouiya, Duncan Berenguier, Sarah M Keating, Aurelien Naldi, Martijn P van Iersel, Nicolas Rodriguez, Andreas Dräger, Finja Büchel, Thomas Cokelaer, Bryan Kowal, Benjamin Wicks, Emanuel Gonçalves, Julien Dorier, Michel Page, Pedro T Monteiro, Axel von Kamp, Ioannis Xenarios, Hidde de Jong, Michael Hucka, Steffen Klamt, Denis Thieffry, Nicolas Le Novère, Julio Saez-Rodriguez, Tomá¿ Helikar

DOI: 10.1186/1752-0509-7-135

Date Published: 2013

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

Journal: BMC Syst Biol

Citation: BMC Syst Biol 7(1) : 135

Scales: Cell and Intercellular

Abstract (Expan