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Imprinted Zac1 in neural stem cells

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World Journal of Stem Cells 2015年第2期7卷 300-314页

作者： Guillaume Daniel Udo Schmidt-Edelkraut dietmar spengler Anke Hoffmann Max Planck Institute of Psychiatry Translational Research

Neural stem cells(NSCs) and imprinted genes play an important role in brain development. On historical grounds, these two determinants have been largely studied independently of each other. Recent evidence suggests, however, that NSCs can reset select genomic imprints to prevent precocious depletion of the stem cell reservoir. Moreover, imprinted genes like the transcriptional regulator Zac1 can fine tune neuronal vs astroglial differentiation of NSCs. Zac1 binds in a sequence-specific manner to pro-neuronal and imprinted genes to confer transcriptional regulation and furthermore coregulates members of the p53-family in NSCs. At the genome scale, Zac1 is a central hub of an imprinted gene network comprising genes with animportant role for NSC quiescence, proliferation and differentiation. Overall, transcriptional, epigenomic, and genomic mechanisms seem to coordinate the functional relationships of NSCs and imprinted genes from development to maturation, and possibly aging.

关键词： Zac1 Cell fate decisions Neural stem cells Genomic imprinting Igf2-H19 Dlk1 p57 Kip2 Necdin Differentiation Imprinted gene networks

Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism

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World Journal of Biological Chemistry 2015年第3期6卷 95-109页

作者： Anke Hoffmann dietmar spengler Max Planck Institute of Psychiatry Translational Research

Transient neonatal diabetes mellitus 1(TNDM1) is a rare genetic disorder representing with severe neonatal hyperglycaemia followed by remission within one and a half year and adolescent relapse with type 2 diabetes in half of the patients. Genetic defects in TNDM1 comprise uniparental isodisomy of chromosome 6, duplication of the minimal TNDM1 locus at 6q24, or relaxation of genomically imprinted ZAC1 /HYMAI. Whereas the function of HYMAI, a non-coding m RNA, is still unidentified, biochemical and molecular studies show that zinc finger protein 1 regulating apoptosis and cell cycle arrest(ZAC1) behaves as a factor with versatile transcriptional functions dependent on binding to specific GC-rich DNA motives and interconnected regulation of recruited coactivator activities. Genome-wide expression profiling enabled the isolation of a number of Zac1 target genes known to regulate different aspects of β-cell function and peripheral insulin sensitivity. Among these, upregulation of Pparγ and Tcf4 impairs insulinsecretion and β-cell proliferation. Similarly, Zac1-mediated upregulation of Socs3 may attenuate β-cell proliferation and survival by inhibition of growth factor signalling. Additionally, Zac1 directly represses Pac1 and Rasgrf1 with roles in insulin secretion and β-cell proliferation. Collectively, concerted dysregulation of these target genes could contribute to the onset and course of TNDM1. Interestingly, Zac1 overexpression in β-cells spares the effects of stimulatory G-protein signaling on insulin secretion and raises the prospect for tailored treatments in relapsed TNDM1 patients. Overall, these results suggest that progress on the molecular and cellular foundations of monogenetic forms of diabetes can advance personalized therapy in addition to deepening the understanding of insulin and glucose metabolism in general.

关键词： Diabetes mellitus ZAC1 Transient neonatal diabetes mellitus 1 Genomic imprinting Insulin Glucose Target genes Tailored therapy

A ROBUST DISCRETIZATION OF THE REISSNER-MINDLIN PLATE WITH ARBITRARY POLYNOMIAL DEGREE

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Journal of Computational Mathematics 2020年第1期38卷 1-13页

作者： dietmar Gallistl Mira Schedensack Friedrich-Schiller-Universitdt Jena 07737 JenaGermany Universitat Leipzig PF 10092004009 LeipzigGermany

A numerical scheme for the Reissner-Mindlin plate model is *** method is based on a discrete Helmholtz decomposition and can be viewed as a generalization of the nonconforming finite element scheme of Arnold and Falk[SIAM ***.,26(6):1276-1290,1989].The two unknowns in the discrete formulation are the in-plane rotations and the gradient of the vertical *** decomposition of the discrete shear variable leads to equivalence with the usual Stokes system with penalty term plus two Poisson equations and the proposed method is equivalent to a stabilized discretization of the Stokes system that generalizes the Mini *** method is proved to satisfy a best-approximation result which is robust with respect to the thickness parameter t.

关键词： Reissner-Mindlin plate Nonconforming finite element Discrete Helmholtz decomposition Robustness

BRAIN INJURY BIOMECHANICS IN REAL WORLD VEHICLE ACCIDENT USING MATHEMATICAL MODELS

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Chinese Journal of Mechanical Engineering 2008年第4期21卷 81-86页

作者： YANG Jikuang XU Wei OTTE dietmar State Key Laboratory of Advanced Design and Manufacture for Vehicle Body Hunan University Changsha 410082 China Accident Research Unit Medical University HannoverHannover D-30623 Germany

This paper aims at investigating brain injury mechanisms and predicting head injuries in real world accidents. For this purpose, a 3D human head finite element model （HBM-head） was developed based on head-brain anatomy. The HBM head model was validated with two experimental tests. Then the head finite element（FE） model and a multi-body system （MBS） model were used to carry out reconstructions of real world vehicle-pedestrian accidents and brain injuries. The MBS models were used for calculating the head impact conditions in vehicle impacts. The HBM-head model was used for calculating the injury related physical parameters, such as intracranial pressure, stress, and strain. The calculated intracranial pressure and strain distribution were correlated with the injury outcomes observed from accidents. It is shown that this model can predict the intracranial biomechanical response and calculate the injury related physical parameters. The head FE model has good biofidelity and will be a valuable tool for the study of injury mechanisms and the tolerance level of the brain.

关键词： Skull-brain FE model Head injury Real-world vehicle accident

The Fingerprint of Global Warming in the Tropical Pacific

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Advances in Atmospheric Sciences 2016年第4期33卷 I0001-I0002页

作者： Noel KEENLYSIDE dietmar DOMMENGET Geophysical Institute University of Bergen/Bjerknes Center for Climate Research Bergen 5007 Norway Nansen Environmental and Remote Sensing Center/Bjerknes Center for Climate Research Bergen 5006 Norway ARC Centre of Excellence for Climate System Science School of Earth Atmosphere and Environment Monash University Clayton VIC Australia

The impacts of global warming will be felt most strongly at regional scales. However, great uncertainties exist in climate change projections at these scales, limiting our ability to provide useful information for the planning and implementation of appropriate adaptation measures. Thus, there is an urgent need to reduce these uncertainties.

关键词： EPSW The Fingerprint of Global Warming in the Tropical Pacific

Subsidence history and forming mechanism of anomalous tectonic subsidence in the Bozhong depression, Bohaiwan basin

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Science China Earth Sciences 2007年第9期50卷 1310-1318页

作者： MüLLER R. dietmar School of Geosciences University of Sydney Sydney NSW 2006 Australia

The Bozhong depression of the Bohaiwan basin belongs to a family of extensional basins in East China, but is quite different from other parts of the basin. The Cenozoic subsidence of the depression is controlled by a combination of lithospheric thinning and polycyclic strike-slip movements. Three episodic rifts have been identified, i.e. Paleocence-early Eocene, middle-late Eocene and Oligocene age. The depression underwent syn-rift and post-rift stages, but two episodic dextral movement events of the strike-slip faults modify the subsidence of the Bozhong depression since the Oligocene. The early dextral movement of the Tan-Lu fault associated with crustal extension resulted in accelerated subsidence during the time of deposition of the Dongying Formation with a maximum thickness of 4000 m. A late reactivation of dextral movement of the Tan-Lu fault began in late Miocene (about 12 Ma), which resulted in the intense subsidence of Minghuazhen Formation and Quaternary. In addition, dynamic mantle convection-driven topography also accelerated the post-rift anomalous subsidence since the Miocene (24.6 Ma). Our results indicate that the primary control on rapid subsidence both during the rift and post-rift stages in the Bozhong depression originates from a combination of multiple episodic crustal extension and polycyclic dextral movements of strike-slip faults, and dynamic topography.

关键词： tectonic subsidence strike-slip dynamic topography Bozhong depression Bohaiwan basin

Melatonin, circadian rhythms and glaucoma: current perspective

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Neural Regeneration Research 2022年第8期17卷 1759-1760页

作者： Denis Gubin dietmar Weinert Chronobiology&Chronomedicine Laboratory Medical UniversityTyumen/Department of BiologyMedical UniversityTyumen/Tyumen Cardiology Research CenterTomsk National Research Medical CenterRussian Academy of ScienceTomskRussia Institute of Biology/Zoology Martin Luther UniversityHalle-WittenbergGermany

Primary open-angle glaucoma as a causal factor for circadian disruption:Living by the clock,in alignment with external time cues is an important condition for human health and *** changes in the ambient light serve as a key factor to synchronize the endogenously generated circadian *** retina perceives the photic signals and transmits them to the central body clock,the suprachiasmatic nuclei(SCN),via the retinohypothalamic tract.

关键词： ambient alignment Periodic

SATURATION AND RELIABLE HIERARCHICAL A POSTERIORI MORLEY FINITE ELEMENT ERROR CONTROL

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Journal of Computational Mathematics 2018年第6期36卷 833-844页

作者： Carsten Carstensen dietmar Gallistl Yunqing Huang Humboldt-Universitat zu Berlin Institut fiir Mathematik Unter den Linden 6 10099 Berlin Germany Department of Applied Mathematics University of Twente P.O. Box 217 7500 AE Enschede Institute for Computational and Applied Mathematics and Hunan Key Laboratory for Computation & Simulation in Science & Engineering Xiangtan University Xiangtan 411105 China

This paper proves the saturation assumption for the nonconforming Morley finite ele- ment discretization of the biharmonic equation. This asserts that the error of the Morley approximation under uniform refinement is strictly reduced by a contraction factor smaller than one up to explicit higher-order data approximation terms. The refinement has at least to bisect any edge such as red refinement or 3-bisections on any triangle. This justifies a hierarchical error estimator for the Morley finite element method, which simply compares the discrete solutions of one mesh and its red-refinement. The related adaptive mesh-refining strategy performs optimally in numerical experiments. A remark for Crouzeix-Raviart nonconforming finite element error control is included.

关键词： Saturation Hierarchical error estimation Finite element Nonconforming Biharmonie Morley Kirchhoff plate Crouzeix-Raviart

Between Scylla and Charybdis:The role of the human immune system in the pathogenesis of hepatitis C

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World Journal of Gastroenterology 2013年第44期19卷 7852-7866页

作者： Ulrich spengler Hans Dieter Nischalke Jacob Nattermann Christian P Strassburg Department of Internal Medicine 1 University of Bonn 53105 Bonn Germany

Hepatitis C virus(HCV)frequently elicits only mild immune responses so that it can often establish chronic *** this case HCV antigens persist and continue to stimulate the immune *** persistence then leads to profound changes in the infected host’s immune responsiveness,and eventually contributes to the pathology of chronic *** topic highlight summarizes changes associated with chronic hepatitis C concerning innate immunity(interferons,natural killer cells),adaptive immune responses(immunoglobulins,T cells,and mechanisms of immune regulation(regulatory T cells).Our overview clarifies that a strong anti-HCV immune response is frequently associated with acute severe tissue *** chronic hepatitis C,however,the effector arms of the immune system either become refractory to activation or take over regulatory *** together these changes in immunity may lead to persistent liver damage and ***,effector arms of the immune system will not only be considered with respect to antiviral defence but also as pivotal mechanisms of inflammation,necrosis and progression to ***,avoiding Scylla-a strong,sustained antiviral immune response with inital tissue damage-takes the infected host to virus-triggered immunopathology,which ultimately leads to cirrhosis and liver cancerthe realm of Charybdis.

关键词： Natural killer cells CD4+ T helper cells Regulatory T cells Interferon Hepatitis C Hepatic stellate cells Hepatocytes Immunoglobulin Retinoic acid inducible gene-I Toll like receptors