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Search Results: 1 - 10 of 404348 matches for " Roman Müllenbach "
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Nuclear Receptor Variants in Liver Disease
Roman Müllenbach,Susanne N. Weber,Frank Lammert
Journal of Lipids , 2012, DOI: 10.1155/2012/934707
Abstract: This review aims to provide a snapshot of the actual state of knowledge on genetic variants of nuclear receptors (NR) involved in regulating important aspects of liver metabolism. It recapitulates recent evidence for the application of NR in genetic diagnosis of monogenic (“Mendelian”) liver disease and their use in clinical diagnosis. Genetic analysis of multifactorial liver diseases such as viral hepatitis or fatty liver disease identifies key players in disease predisposition and progression. Evidence from these analyses points towards a role of NR polymorphisms in common diseases, linking regulatory networks to complex and variable phenotypes. The new insights into NR variants also offer perspectives and cautionary advice for their use as handles towards diagnosis and treatment. 1. Introduction Systematically, genetic analysis with regard to disease onset and progression can be separated into pre- and post-hoc examination of monogenic or polygenic diseases. Monogenic (“Mendelian”) diseases are caused by a single gene defect and follow relatively straightforward inheritance patterns. The most prominent of these disorders are rather rare, often severe, and characterized by early onset. Genetic testing for monogenic liver disease in symptomatic patients is based on known disease-associated gene variants, thereby confirming the genetic etiology and sometimes allowing prediction of disease progression [1]. In contrast, polygenic diseases such as fatty liver disease and gallstones result from combinations of multiple gene variants and environmental factors, all of which play a role in disease initiation and progression [2]. The assessment of predisposition towards polygenic disease is based on sequence analysis of known contributory genes and construction of “polygenic risk scores” from variants of these genes [1]. Still in its infancy, personal genome information might eventually be able to predict a variety of risks associated with an individual’s lifestyle such as fatty food and alcohol consumption, as well as susceptibility to infectious diseases such as infection with hepatitis B or C virus. 2. Nuclear Receptors Nuclear receptors (NRs) are a subclass of regulatory molecules that orchestrate gene transcription in response to the presence or absence of specific ligands. Due to these functional requirements, they are characterized by the presence of a ligand-binding and a DNA-binding domain. NRs represent a central point of interaction between environment and gene regulation. They are the “hinge” connecting endogenous and environmental stimuli, that is,
A frequent variant in the human bile salt export pump gene ABCB11 is associated with hepatitis C virus infection, but not liver stiffness in a German population
Roman Müllenbach, Susanne N Weber, Marcin Krawczyk, Vincent Zimmer, Christoph Sarrazin, Frank Lammert, Frank Günhage
BMC Gastroenterology , 2012, DOI: 10.1186/1471-230x-12-63
Abstract: ABCB11 c.1331?T?>?C genotype was determined by allelic discrimination assay in 649 HCV infected cases and 413 controls. Overall, 444 cases were staged for fibrotic progression by measurement of liver stiffness.Homo- or heterozygous presence of the frequent [C] allele was associated with HCV positivity (OR?=?1.41, CI?=?1.02 - 1.95, p?=?0.037). No association was detectable between the ABCB11 c.1331?T?>?C genotype and increased liver stiffness.Our data confirm that homozygous presence of the major [C] allele of ABCB11 c.1331?T?>?C is a genetic susceptibility factor for HCV infection, but not for liver fibrosis.
Decreased Levels of Active SMAD2 Correlate with Poor Prognosis in Gastric Cancer
Yijun Wu, Qi Li, Xinhui Zhou, Jiren Yu, Yunchuan Mu, Stefan Munker, Chengfu Xu, Zhe Shen, Roman Müllenbach, Yan Liu, Li Li, Norbert Gretz, Derek Zieker, Jun Li, Kouichi Matsuzaki, Youming Li, Steven Dooley, Honglei Weng
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0035684
Abstract: Background TGF-β plays a dual role in the progression of human cancer. During the early stages of carcinogenesis, TGF-β functions as a tumor suppressor. During the late stages of tumor development, however, TGF-β can promote tumor growth and metastasis. A shift in Smad2/3 phosphorylation from the carboxy terminus to linker sites is a key event determining biological function of TGF-β in colorectal and hepatocellular carcinoma. In the present study, we investigated the potential role of differential Smad2/3 phosphorylation in gastric adenocarcinoma. Methodology Immunohistochemical staining with anti-P-Smad2/3C and P-Smad2/3L antibodies was performed on 130 paraffin-embedded gastric adenocarcinoma specimens. The relationship between P-Smad2/3C and P-Smad2/3L immunohistochemical score and clinicopathologic characteristics of patients was analyzed. Real time PCR was used to measure mRNA expression of Smad2 and Smad3 in cancer and surrounding non-tumor tissue. Principal Findings No significant P-Smad2L and/or P-Smad3L positive staining was detected in the majority of specimens (positive staining in 18/130 samples). Positive P-Smad2/3L staining was not associated with a decrease in carboxyterminal phosphorylation staining. Loss of P-Smad2C remarkably correlated with depth of tumor infiltration and poor differentiation of cancer cells in patients with gastric cancer. No correlation was detectable between P-Smad3C and clinicopathologic characteristics of gastric adenocarcinoma. However, co-staining analysis revealed that P-Smad3C co-localised with α-SMA and collagen I in gastric cancer cells, indicating a potential link between P-Smad3C and epithelial-to-mesenchymal transition of cancer. Real time PCR demonstrated reduced mRNA expression of Smad2 in gastric cancer when compared with surrounding non-tumor tissue in 15/16 patients. Conclusions Loss of P-Smad2C tightly correlated with cancer invasion and poor differentiation in gastric cancer. Contrary to colorectal and hepatocellular carcinoma, canonical carboxy-terminal phosphorylation, but not linker phosphorylation, of Smad2 is critical for gastric cancer.
Morpho-Anatomical pecularities of the resistance of different Magnolia L. species under introduction in Forest-steppe and Woodland of Ukraine
Roman M. Palagecha
Modern Phytomorphology , 2012,
Abstract: It has been established that the peculiarities of the formation of ground and strengthening tissues of annual shoots of different magnolias species influence significantly on the processes of their successful wintering under the introduction in the O.V. Fomin Botanical Garden of Kyiv National University.
Eco-Balancing as a Guideline for Environmentally Sound Regional Planning Supported by GIS Applications
ROMAN J. M. LENZ
Romanian Review of Regional Studies , 2005,
Abstract: During the last several years, environmental impact assessment, regional or spatial planning, and environmental balancing seem to develop similarities, e.g. joint basic methodological approaches such as the use of environmental indicators, the focus on same environmental goods such air, water, soil, flora/fauna, etc. (Lenz 1999). Especially GIS-based software systems show their multiple applications in these fields.After a short introduction about the central role of indicators in transdisciplinary problem solving processes, experiences from a set of regional environmental (or eco) balances show a wide range of advantages as well as disadvantages in the context of the widespread use of GIS-based planning tools. Relying on concepts and examples for the spatial eco-balances in the district of Pfaffenhofen (Upper Bavaria, Germany; cf. Lenz 1997) and the municipality of Mulfingen (Hohenlohe, Germany) - both of them related to the concept of environmental indicators of the Advisory Board of Environmental Affairs of the Federal Republic of Germany (SRU 1994) and the Federal Environmental Agency (UBA 1995) - we can show GIS-based information systems of a high practical relevancy. On the basis of the GIS software ArcView, the data base management system Access, and html scripts, we developed environmental information systems to balance environmental effects in a map scale of 1:5,000 - 1:50,000, in order to provide the administration with tools for an environmentally sound and sustainable development of their area (Lenz 1997, 1999, Beuttler et al. 1999). The spatial distribution of land use types, solar energy potential, area consumption and drinking water consumption for the municipality of Mulfingen are highlighted in this paper. Still, the practical use of the systems seems to be limited due to the lack of computer skills among the administrators – even after programming graphical user interfaces for the indicator “drinking water consumption”-, as well as due to widely distributed and hard-to-access data and information sources.
Upper bounds for the number of orbital topological types of planar polynomial vector fields "modulo limit cycles"
Roman M. Fedorov
Mathematics , 2004, DOI: 10.1134/S0081543806030126
Abstract: The paper deals with planar polynomial vector fields. We aim to estimate the number of orbital topological equivalence classes for the fields of degree n. An evident obstacle for this is the second part of Hilbert's 16th problem. To circumvent this obstacle we introduce the notion of equivalence modulo limit cycles. This paper is the continuation of the author's paper in [Mosc. Math. J. 1 (2001), no. 4] where the lower bound of the form 2^{cn^2} has been obtained. Here we obtain the upper bound of the same form. We also associate an equipped planar graph to every planar polynomial vector field, this graph is a complete invariant for orbital topological classification of such fields.
Frobenius manifold structures on the spaces of abelian integrals
Roman M. Fedorov
Mathematics , 2007, DOI: 10.1016/j.geomphys.2010.10.015
Abstract: Frobenius manifold structures on the spaces of abelian integrals were constructed by I. Krichever. We use D-modules, deformation theory, and homological algebra to give a coordinate-free description of these structures. It turns out that the tangent sheaf multiplication has a cohomological origin, while the Levi-Civita connection is related to 1-dimensional isomonodromic deformations.
Irregular Wakimoto modules and the Casimir connection
Roman M. Fedorov
Mathematics , 2008, DOI: 10.1007/s00029-010-0019-x
Abstract: We study some non-highest weight modules over an affine Kac-Moody algebra at non-critical level. Roughly speaking, these modules are non-commutative localizations of some non-highest weight "vacuum" modules. Using free field realization, we embed some rings of differential operators in endomorphism rings of our modules. These rings of differential operators act on a localization of the space of coinvariants of any module over the Kac-Moody algebra with respect to a certain level subalgebra. In a particular case this action is identified with the Casimir connection.
Existence and behavior of asymmetric traveling wave solutions to thin film equation
Roman M. Taranets
Mathematics , 2008,
Abstract: We proved the existence and uniqueness of a traveling wave solution to the thin film equation with a Navier slip condition at the liquid-solid interface. We obtain explicit lower and upper bounds for the solution and an absolute error estimate of approximation of a solution to the thin films equation by the traveling-wave solution.
Algebraic and hamiltonian approaches to isostokes deformations
Roman M. Fedorov
Mathematics , 2004, DOI: 10.1007/s00031-005-1107-4
Abstract: We study a generalization of the isomonodromic deformation to the case of connections with irregular singularities. We call this generalization Isostokes Deformation. A new deformation parameter arises: one can deform the formal normal forms of connections at irregular points. We study this part of the deformation, giving an algebraic description. Then we show how to use loop groups and hypercohomology to write explicit hamiltonians. We work on an arbitrary complete algebraic curve, the structure group is an arbitrary semisimiple group.
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