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385 Publications visible to you, out of a total of 385
ECM1 stabilizes matrix deposited latent TGF-β to maintain liver homeostasis and prevent fibrogenesis

Abstract

Not specified

Authors: S Hammad, W Fan, T Liu, W Chen, K Gould, T Longerich, I Haußer-Siller, J Hou, J Jia, B Sun, S Dooely

Date Published: 2019

Publication Type: Not specified

Basic Phenotypes of Endocytic System Recognized by Independent Phenotypes Analysis of a High-throughput Genomic Screen

Abstract (Expand)

High-content screens (HCS) using chemical and genomic interference based on light microscopy and quantitative image analysis yielded a large amount of multi-parametric (MP) phenotypic data. Such data-sets … hold great promise for the understanding of cellular mechanisms by systems biology. However, extracting functional information from data-sets, such as links between cellular processes and the functions of unknown genes, remains challenging. The limitation of HCS analysis lies in the complexity of cellular organization. Here, we assumed that cellular processes have a modular structure, and deconvolved the MP data into separate signals from different cellular modules by Blind Source Separation. We applied a combination of quantitative MP image analysis (QMPIA) and Independent Component Analysis (ICA) to an image-based HCS of endocytosis, the process whereby cells uptake molecules from the outside and distribute them to different sub-cellular organelles. We named our approach Independent Phenotypes Analysis (IPA). Phenotypic traits revealed by IPA are interpretable in terms of perturbation of specific endosomal populations (e.g. specific cargo, specific molecular markers) and of specific functional modules (early stages of endocytosis, recycling, cell cycle, etc.). The profile of perturbation of each gene in such basic phenotypic coordinates intrinsically suggest its possible mode of action.

Authors: Unknown, Kseniia Nikitina, Sandra Segeletz, Michael Kuhn, Yannis Kalaidzidis, Marino Zerial

Date Published: 2019

Publication Type: InProceedings

Pipe-3D: A Pipeline Based on Immunofluorescence, 3D Confocal Imaging, Reconstructions, and Morphometry for Biliary Network Analysis in Cholestasis

Abstract

Not specified

Authors: Amruta Damle-Vartak, Brigitte Begher-Tibbe, Georgia Gunther, Fabian Geisler, Nachiket Vartak, Jan G. Hengstler

Date Published: 2019

Publication Type: Book

Lean Patients with Non-Alcoholic Fatty Liver Disease Have a Severe Histological Phenotype Similar to Obese Patients.

Abstract (Expand)

A small proportion of lean patients develop non-alcoholic fatty liver disease (NAFLD). We aimed to report the histological picture of lean NAFLD in comparison to overweight and obese NAFLD patients. … Biopsy and clinical data from 466 patients diagnosed with NAFLD were stratified to groups according to body mass index (BMI): lean (BMI </= 25.0 kg/m(2), n confirmed to be appropriate = 74), overweight (BMI > 25.0 </= 30.0 kg/m(2), n = 242) and obese (BMI > 30.0 kg/m(2), n = 150). Lean NAFLD patients had a higher rate of lobular inflammation compared to overweight patients (12/74; 16.2% vs. 19/242; 7.9%; p = 0.011) but were similar to obese patients (25/150; 16.7%). Ballooning was observed in fewer overweight patients (38/242; 15.7%) compared to lean (19/74; 25.7%; p = 0.014) and obese patients (38/150; 25.3%; p = 0.006). Overweight patients had a lower rate of portal and periportal fibrosis (32/242; 13.2%) than lean (19/74; 25.7%; p = 0.019) and obese patients (37/150; 24.7%; p = 0.016). The rate of cirrhosis was higher in lean patients (6/74; 8.1%) compared to overweight (4/242; 1.7%; p = 0.010) and obese patients (3/150; 2.0% p = 0.027). In total, 60/466; 12.9% patients were diagnosed with non-alcoholic steatohepatitis (NASH). The rate of NASH was higher in lean (14/74; 18.9% p = 0.01) and obese (26/150; 17.3%; p = 0.007) compared to overweight patients (20/242; 8.3%)). Among lean patients, fasting glucose, INR and use of thyroid hormone replacement therapy were independent predictors of NASH in a multivariate model. Lean NAFLD patients were characterized by a severe histological picture similar to obese patients but are more progressed compared to overweight patients. Fasting glucose, international normalized ratio (INR) and the use of thyroid hormone replacement may serve as indicators for NASH in lean patients.

Authors: L. Denkmayr, A. Feldman, L. Stechemesser, S. K. Eder, S. Zandanell, M. Schranz, M. Strasser, U. Huber-Schonauer, S. Buch, J. Hampe, B. Paulweber, C. Lackner, H. Haufe, K. Sotlar, C. Datz, E. Aigner

Date Published: 17th Dec 2018

Publication Type: Journal

Liquid-crystal organization of liver tissue

Abstract

Not specified

Authors: Hernan Morales-Navarrete, Hidenori Nonaka, Andre Scholich, Fabian Segovia-Miranda, Walter de Back, Kirstin Meyer, Roman L Bogorad, Victor Koteliansky, Lutz Brusch, Yannis Kalaidzidis, Frank Julicher, Benjamin M. Friedrich, Marino Zerial

Date Published: 13th Dec 2018

Publication Type: Not specified

Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control

Abstract

Not specified

Authors: Mario Brosch, Kathrin Kattler, Alexander Herrmann, Witigo von Schönfels, Karl Nordström, Daniel Seehofer, Georg Damm, Thomas Becker, Sebastian Zeissig, Sophie Nehring, Fabian Reichel, Vincent Moser, Raghavan Veera Thangapandi, Felix Stickel, Gustavo Baretton, Christoph Röcken, Michael Muders, Madlen Matz-Soja, Michael Krawczak, Gilles Gasparoni, Hella Hartmann, Andreas Dahl, Clemens Schafmayer, Jörn Walter, Jochen Hampe

Date Published: 1st Dec 2018

Publication Type: Not specified

Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control

Abstract (Expand)

A deeper epigenomic understanding of spatial organization of cells in human tissues is an important challenge. Here we report the first combined positional analysis of transcriptomes and methylomes … across three micro-dissected zones (pericentral, intermediate and periportal) of human liver. We identify pronounced anti-correlated transcriptional and methylation gradients including a core of 271 genes controlling zonated metabolic and morphogen networks and observe a prominent porto-central gradient of DNA methylation at binding sites of 46 transcription factors. The gradient includes an epigenetic and transcriptional Wnt signature supporting the concept of a pericentral hepatocyte regeneration pathway under steady-state conditions. While donors with non-alcoholic fatty liver disease show consistent gene expression differences corresponding to the severity of the disease across all zones, the relative zonated gene expression and DNA methylation patterns remain unchanged. Overall our data provide a wealth of new positional insights into zonal networks controlled by epigenetic and transcriptional gradients in human liver.

Authors: Mario Brosch, Kathrin Kattler, Alexander Herrmann, Witigo von Schönfels, Karl Nordström, Daniel Seehofer, Georg Damm, Thomas Becker, Sebastian Zeissig, Sophie Nehring, Fabian Reichel, Vincent Moser, Raghavan Veera Thangapandi, Felix Stickel, Gustavo Baretton, Christoph Röcken, Michael Muders, Madlen Matz-Soja, Michael Krawczak, Gilles Gasparoni, Hella Hartmann, Andreas Dahl, Clemens Schafmayer, Jörn Walter, Jochen Hampe

Date Published: 1st Dec 2018

Publication Type: Not specified

3D visualization of the biliary tree by X-ray phase-contrast computed tomography

Abstract

Not specified

Author: Amruta Damle-Vartak

Date Published: 1st Dec 2018

Publication Type: Not specified

Prospective Assessment of Liver Function by an Enzymatic Liver Function Test to Estimate Short-Term Survival in Patients with Liver Cirrhosis.

Abstract (Expand)

BACKGROUND: MELD attempts to objectively predict the risk of mortality of patients with liver cirrhosis and is commonly used to prioritize organ allocation. Despite the usefulness of the MELD, updated … metrics could further improve the accuracy of estimates of survival. AIMS: To assess and compare the prognostic ability of an enzymatic (13)C-based liver function test (LiMAx) and distinct markers of liver function to predict 3-month mortality of patients with chronic liver failure. METHODS: We prospectively investigated liver function of 268 chronic liver failure patients without hepatocellular carcinoma. Primary study endpoint was liver-related death within 3 months of follow-up. Prognostic values were calculated using Cox proportional hazards and logistic regression analysis. RESULTS: The Cox proportional hazard model indicated that LiMAx (p < 0.001) and serum creatinine values (p < 0.001) were the significant parameters independently associated with the risk of liver failure-related death. Logistic regression analysis revealed LiMAx and serum creatinine to be independent predictors of mortality. Areas under the receiver-operating characteristic curves for MELD (0.86 [0.80-0.92]) and for a combined score of LiMAx and serum creatinine (0.83 [0.76-0.90]) were comparable. CONCLUSIONS: Apart from serum creatinine levels, enzymatic liver function measured by LiMAx was found to be an independent predictor of short-term mortality risk in patients with liver cirrhosis. A risk score combining both determinants allows reliable prediction of short-term prognosis considering actual organ function. Trial Registration Number (German Clinical Trials Register) # DRKS00000614.

Authors: M. Jara, T. Dziodzio, M. Malinowski, K. Luttgert, R. Nikolov, P. V. Ritschl, R. Ollinger, J. Pratschke, M. Stockmann

Date Published: 9th Nov 2018

Publication Type: Not specified

ABCB4 Gene Aberrations in Human Liver Disease: An Evolving Spectrum

Abstract

Not specified

Authors: Matthias Reichert, Frank Lammert

Date Published: 24th Oct 2018

Publication Type: Not specified

Analytical challenges in human plasma lipidomics: A winding path towards the truth

Abstract (Expand)

Human plasma lipidome has been extensively studied in many pathophysiological contexts with the hope of identifying biomarkers for early diagnostics and monitoring the progression and treatment of a … broad spectrum of diseases. However, despite remarkable progress in lipidomics technologies, the concordance of lipidomics measurements between independent laboratories remains limited and not fulfilling the criteria of common laboratory diagnostics. Here we highlighted a few critical aspects of epidemiological studies of the plasma lipidome, including the selection of study cohorts, collection of plasma samples as well as extraction, identification and quantification of lipids. We argue that reporting the abundances of plasma lipids as molar concentrations is a key turning point during the transition of research lipidomics into a common tool of clinical diagnostics.

Authors: Olga Vvedenskaya, Yuting Wang, Jacobo Miranda Ackerman, Oskar Knittelfelder, Andrej Shevchenko

Date Published: 20th Oct 2018

Publication Type: Not specified

Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis

Abstract (Expand)

OBJECTIVES: Variants in patatin-like phospholipase domain-containing 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), and membrane bound O-acyltransferase domain containing …g 7 (MBOAT7; rs641738) are risk factors for the development of alcohol-related cirrhosis. Within this population, PNPLA3 rs738409 is also an established risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to explore possible risk associations of TM6SF2 rs58542926 and MBOAT7 rs641738 with HCC. METHODS: Risk variants in PNPLA3, TM6SF2, and MBOAT7 were genotyped in 751 cases with alcohol-related cirrhosis and HCC and in 1165 controls with alcohol-related cirrhosis without HCC. Association with the risk of developing HCC was analyzed using multivariate logistic regression. RESULTS: The development of HCC was independently associated with PNPLA3 rs738409 (ORadjusted 1.84 [95% CI 1.55-2.18], p = 1.85 × 10-12) and TM6SF2 rs58542926 (ORadjusted 1.66 [1.30-2.13], p = 5.13 × 10-05), using an additive model, and controlling the sex, age, body mass index, and type 2 diabetes mellitus; the risk associated with carriage of MBOAT7 rs641738 (ORadjusted 1.04 [0.88-1.24], p = 0.61) was not significant. The population-attributable fractions were 43.5% for PNPLA3 rs738409, 11.5% for TM6SF2 rs58542926, and 49.9% for the carriage of both the variants combined. CONCLUSIONS: Carriage of TM6SF2 rs58542926 is an additional risk factor for the development of HCC in people with alcohol-related cirrhosis. Carriage of both PNPLA3 rs738409 and TM6SF2 rs58542926 accounts for half of the attributable risk for HCC in this population. Genotyping will allow for more precise HCC risk-stratification of patients with alcohol-related cirrhosis, and genotype-guided screening algorithms would optimize patient care.

Authors: Felix Stickel, Stephan Buch, Hans Dieter Nischalke, Karl Heinz Weiss, Daniel Gotthardt, Janett Fischer, Jonas Rosendahl, Astrid Marot, Mona Elamly, Markus Casper, Frank Lammert, Andrew McQuillin, Steffen Zopf, Ulrich Spengler, Silke Marhenke, Martha M. Kirstein, Arndt Vogel, Florian Eyer, Johann von Felden, Henning Wege, Thorsten Buch, Clemens Schafmayer, Felix Braun, Pierre Deltenre, Thomas Berg, Marsha Y. Morgan, Jochen Hampe

Date Published: 1st Oct 2018

Publication Type: Not specified

Focused scores enable reliable discrimination of small differences in steatosis.

Abstract (Expand)

BACKGROUND: Automated image analysis enables quantitative measurement of steatosis in histological images. However, spatial heterogeneity of steatosis can make quantitative steatosis scores unreliable. … To improve the reliability, we have developed novel scores that are "focused" on steatotic tissue areas. METHODS: Focused scores use concepts of tile-based hotspot analysis in order to compute statistics about steatotic tissue areas in an objective way. We evaluated focused scores on three data sets of images of rodent liver sections exhibiting different amounts of dietary-induced steatosis. The same evaluation was conducted with the standard steatosis score computed by most image analysis methods. RESULTS: The standard score reliably discriminated large differences in steatosis (intraclass correlation coefficient ICC = 0.86), but failed to discriminate small (ICC = 0.54) and very small (ICC = 0.14) differences. With an appropriate tile size, mean-based focused scores reliably discriminated large (ICC = 0.92), small (ICC = 0.86) and very small (ICC = 0.83) differences. Focused scores based on high percentiles showed promise in further improving the discrimination of very small differences (ICC = 0.93). CONCLUSIONS: Focused scores enable reliable discrimination of small differences in steatosis in histological images. They are conceptually simple and straightforward to use in research studies.

Authors: A. Homeyer, S. Hammad, L. O. Schwen, U. Dahmen, H. Hofener, Y. Gao, S. Dooley, A. Schenk

Date Published: 20th Sep 2018

Publication Type: Not specified

Tomoelastography Paired With T2* Magnetic Resonance Imaging Detects Lupus Nephritis With Normal Renal Function.

Abstract (Expand)

OBJECTIVES: The aim of this study was to test multiparametric magnetic resonance imaging including blood oxygen level-dependent (BOLD) imaging by T2* mapping, magnetic resonance elastography (MRE) by … tomoelastography, and diffusion-weighted imaging (DWI) for detecting nephropathy in patients with lupus nephritis (LN). METHODS: Forty-one subjects (25 patients with LN and 16 age- and sex-matched healthy volunteers; LN: mean age, 47.3 +/- 14.8 years; 22 female subjects; volunteers: mean age, 43.9 +/- 11.6 years; 13 female subjects) were prospectively enrolled. The LN group was further divided into subgroups with normal (LN-nRF, GFR > 90 mL/min per 1.73 m) and compromised renal function (LN-cRF, GFR < 90 mL/min per 1.73 m). All subjects were examined by multifrequency MRE, BOLD imaging, and DWI, yielding shear wave speed (SWS; in meter per second), T2* relaxation times (in millisecond), and apparent diffusion coefficient (ADC; in millimeter square per second), respectively. Renal subregional analysis was performed for the medulla (ME), inner cortex (CoI), and outer cortex (CoO). Imaging markers were correlated to clinical parameters such as GFR and protein-to-urine creatinine ratio. Cutoffs and area under the receiver operating curve (AUROC) were computed to test diagnostic performances. RESULTS: Compared with CoI and CoO, LN-nRF predominantly affects ME tissue (SWS: -7%, P < 0.01; T2*: +9%, P < 0.05; ADC: -5%, P = 0.27). Detection of LN-nRF was better with MRE compared with BOLD imaging and DWI (AUROC = 0.81, 0.76, not significant), whereas pairing MRE with T2* further increased diagnostic power (AUROC = 0.91). Disease progression was associated with reduction of SWS also in CoI (LN-nRF, 3.04 +/- 0.38 m/s; LN-cRF, 2.60 +/- 0.26 m/s; p = 0.013), allowing distinction of LN-nRF from LN-cRF (AUROC = 0.83). Diffusion-weighted imaging was only sensitive to LN-cRF in ME tissue (ADC, -12%; P < 0.05). CONCLUSIONS: Lupus nephritis with normal renal function first arises in MRE and BOLD images within ME tissue, progressing to CoI tissue once renal function becomes impaired and diffusion of tissue water changes.

Authors: S. R. Marticorena Garcia, M. Grossmann, A. Bruns, M. Durr, H. Tzschatzsch, B. Hamm, J. Braun, I. Sack, J. Guo

Date Published: 18th Sep 2018

Publication Type: Journal

The Diurnal Timing of Starvation Differently Impacts Murine Hepatic Gene Expression and Lipid Metabolism – A Systems Biology Analysis Using Self-Organizing Maps

Abstract

Not specified

Authors: Christiane Rennert, Sebastian Vlaic, Eugenia Marbach-Breitrück, Carlo Thiel, Susanne Sales, Andrej Shevchenko, Rolf Gebhardt, Madlen Matz-Soja

Date Published: 10th Sep 2018

Publication Type: Not specified

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