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Innate immune recognition and modulation in hepatitis D virus infection

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World Journal of Gastroenterology 2020年第21期26卷 2781-2791页

作者： stephanie Jung Sebastian Maximilian Altstetter Ulrike Protzer Institute of Virology Technical University of Munich/Helmholtz Zentrum MünchenMunich D-81675Germany German Center for Infection Research(DZIF) Munich Partner SiteMunich D-81675Germany

hepatitis D virus(hDV)is a global health threat with more than 15 million humans *** treatment options are largely unsatisfactory leaving chronically infected humans at high risk to develop liver cirrhosis and hepatocellular *** is the only human satellite virus *** encodes only two proteins,and requires hepatitis B virus(hBV)envelope protein expression for productive virion release and spread of the *** hDV could evolve and why hBV was selected as a helper virus remains *** the discovery of Na+-taurocholate co-transporting polypeptide as the essential uptake receptor for hBV and hDV,we are beginning to understand the interactions of hDV and the immune *** hBV is mostly regarded a stealth virus,that escapes innate immune recognition,hBV-hDV coinfection is characterized by a strong innate immune *** RNA sensor melanoma differentiation antigen 5 has been reported to recognize hDV RNA replication and activate innate *** immunity,however,seems not to impair hDV replication while it inhibits *** this review,we describe what is known up-to-date about the interplay between hBV as a helper and hDV’s immune evasion strategy and identify where additional research is required.

关键词： hepatitis D virus hepatitis B virus Innate immunity Pathogen-associated molecular pattern molecules Immune evasion Immunosuppression

Determination of safe mud window considering time-dependent variations of temperature and pore pressure:Analytical and numerical approaches

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Journal of Rock Mechanics and Geotechnical Engineering 2017年第5期9卷 900-911页

作者： Alireza Gholilou Pouria Behnoud far stephanie Vialle Mahyar Madadi Western Australian School of Mines Curtin University Department of Petroleum Engineering Amirkabir University of Technology

Wellbore stability is a key to have a successful drilling *** stresses are the main factors affecting wellbore instability and associated problems in drilling *** stresses are significantly impacted by pore pressure variation and thermal stresses in the *** order to address wellbore instability problems,it is important to investigate the mechanisms of rockefluid interaction with respect to thermal and mechanical *** order to understand the induced stresses,different mathematical models have been *** this study,the field equations governing the problem have been derived based on the thermo-poroelastic theory and solved analytically in Laplace *** results are transferred to time domain using Fourier inverse *** difference method is also utilized to validate the *** pressure and temperature distributions around the wellbore have been focused and ***,induced radial and tangential stresses for different cases of cooling and heating of formation are *** addition,the differences between thermo-poroelastic and poroelastic models in situation of permeable and impermeable wellbores are *** is observed that cooling and pore pressure distribution reinforce the induced radial *** cooling can be a tool to control and reduce tangential stress induced due to invasion of drilling *** the next step,safe mud window is obtained using Mohr-Coulomb,Mogi-Coulomb,and modified Lade failure criteria for different *** and pore pressure distributions do not change the minimum allowable wellbore pressure ***,upper limit of mud window is sensitive to induced stresses and it seems vital to consider changes in temperature and pore pressure to avoid any *** widest and narrowest mud windows are proposed by modified Lade and Mohr-Coulomb failure criteria,respectively.

关键词： Mud window Thermo-poroelastic theory Time-dependence Fourier series Induced stresses

Competitive Contribution of Catalyst and Adsorption Roles of TiO_2 on the Degradation of AO7 Dye During Plasma Treatment

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Plasma Science and Technology 2013年第9期15卷 915-922页

作者： Nabila hADDOU Moufok Redounae GhEZZAR Fatiha ABDELMALEK stephanie OGNIER Ahmed ADDOU Laboratory of Science and Technical Environment and Valorization University of Mostaganem Laboratory of Process Engineering and Surface Treatment National School of ChemistryUniversity of Pierre and Marie Curie

In order to investigate the role of TiO2 during plasma treatment, the degradation of the dye AO7 has been studied by gliding arc discharge in the presence of a TiO2 catalyst （CGAD）. The results revealed that the adsorption of the dye on TiO2 is a physical adsorption in accordance with Langmuir isotherm, with a constant of adsorption KL ： 0.52 mg/L and a maximum adsorption capacity b = 18.1 mg/g. The temperature variation of the reaction medium made it possible to consider thermodynamic parameters. Indeed, the adsorption is exothermic （enthalpy： △h 〈 0）, and spontaneous （free enthalpy： △G 〈 0）. The negative entropy （△S 〈 0） confirms the affinity of the dye molecules for TiO2. 20 min of CGAD treatment in the pres- ence of an optimal quantity of TiO2 （2 g/L enabled us to bleach the solution of AO7 （100 μM） completely. The discoloration rate with and without the addition of TiO2 was 100% and 28%, respectively. 40 additional minutes of treatment allowed a total abatement of the chemical oxy- gen demand. The elimination of AO7 molecules during the plasma-catalytic treatment follows Langmuir-hinshelwood （L-h） model kinetics. According to this model, the speed constant is kr = 14.97 mg-L-1 ·min-1 and the adsorption coefficient is KL-h= 0.010 L/mg. The latter being negligible compared to kr, adsorption is therefore weakly performed during the plasma treatment.

关键词： adsorption catalysis AO7 gliding arc discharge TiO_2 degradation

Ictal semiology,functional anatomy and multimodal diagnostic in patients with insular epilepsies

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Acta Epileptologica 2019年第1期1卷 49-58页

作者： hermann Stefan stephanie Gollwitzer Department of Neurology BiomagnetismUniversity Hospital Erlangen10SchwabachanlageD-91054 ErlangenGermany. Department of Neurology Epilepsy CenterUniversity Hospital ErlangenErlangenGermany.

Background:The insula is a hidden part in the cerebral *** epilepsy is underrecognized and it bears a special risk for misdiagnosis with regard to nonepileptic seizures or wrong localization of epileptic *** presentations:The manuscript describes 2 cases with ictal semiology of paresthesia and pain followed by hyperkinetic movements,noninvasive findings of source localization and/or invasive SEEG ***:Magnetic source imaging,ictal SPECT as noninvasive and invasive recordings with depth electrodes(SEEG)can provide important preoperative information for the involvement of insular and periinsular regions in focal pharmacoresistant *** optimal use of these methods presupposes extensive knowledge of ictal semiology and other clinical *** clinical localization hypothesis can be optimally proofed by SEEG exploration.

关键词： Insular epilepsy Ictal semiology Source localization MEG/EEG SEEG

TOWARDS A hUMAN DIGNITy BASED APPROACh TO FOOD SECURITy： LESSONS FROM ChINA AND INDIA

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Frontiers of Law in China-Selected Publications from Chinese Universities 2016年第2期11卷 243-265页

作者： Nandini Ramanujam stephanie Chow Faculty of Law McGill University Centre of human Rights and Legal Pluralism at McGill University MontrealCanada

Despite almost halving the proportion of the world＇s undernourished over the past two and half decades, the number of undernourished people in the world remains staggeringly high. Efforts to address the global state of food insecurity must target China and India, which are home to the world＇s highest and second highest number of undernourished people. This article analyzes the comparative experiences of tackling food security in China and India and adopts an inter-disciplinary approach, which melds legal, economic, and human perspectives to food security. Both China and India have made concerted efforts to improve food security of vulnerable populations in the past three decades. These efforts have historically focused on actively promoting grain production, which has been largely successful in achieving grain self-sufficiency and securing adequate availability of food for their populations. however, the contemporary challenges to food security are now increasingly driven by unsustainable dietary patterns and are exacerbated by growing populations, increasing wealth, and the globalization of food supply chains. As a result, the cause of food insecurity is no longer fundamentally about food supply, but rather about the extent to which marginalized populations are empowered with the rights, freedoms, and capabilities that enable them to attain healthy and productive lives. China and India apply markedly different approaches to address the issue of people＇s access to food. In India, the right to food movement has gained momentum through the work of civil society actors and there is now a legal right to food. In contrast, in China the right to food is neither stipulated in Chinese law nor referenced to in the official policy rhetoric as the country seeks to ensure access to food by focusing on poverty alleviation more generally through an income transfer program and a non-food based, social safety net to help the poor. At the same time, the Chinese population＇s high edu

关键词： food security human dignity human capabilities right to food

Farnesylcysteine Lyase Regulation of Abscisic Arabidopsis is Involved in Negative Acid Signaling in

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Molecular Plant 2010年第1期3卷 143-155页

作者： David h. huizinga Ryan Denton Kelly G. Koehler Ashley Tomasello Lyndsay Wood stephanie E. Sen Dring N. Crowell Department of Biology Indiana University-Purdue University Indianapolis 723 West Michigan Street Indianapolis IN 46202 USA Department of Chemistry Indiana University-Purdue University Indianapolis 402 N. Blackford Street Indianapolis IN 46202 USA Department of Chemistry The College of New Jersey 2000 Pennington Road Ewing NJ 08628 USA Department of Biological Sciences Idaho State University 650 Memorial Drive Pocatello ID 83209 USA

The Arabidopsis FCLy gene encodes a specific farnesylcysteine （FC） lyase, which is responsible for the oxidative metabolism of FC to farnesal and cysteine. In addition, fcly mutants with quantitative decreases in FC lyase activity exhibit an enhanced response to ABA. however, the enzymological properties of the FCLy-encoded enzyme and its precise role in ABA signaling remain unclear. here, we show that recombinant Arabidopsis FC lyase expressed in insect cells exhib- its high selectivity for FC as a substrate and requires FAD and molecular oxygen for activity. Arabidopsis FC lyase is also shown to undergo post-translational N-glycosylation. FC, which is a competitive inhibitor of isoprenylcysteine methyltransferase （ICMT）, accumulates in fcly mutants. Moreover, the enhanced response of fcly mutants to ABA is reversed by ICMToverexpression. These observations support the hypothesis that the ABA hypersensitive phenotype of fcly plants is the result of FC accumulation and inhibition of ICMT.

关键词： hormone biology primary metabolism seed biology stomata membrane proteins Arabidopsis.

Identification and characterization of a novel bipartite nuclear localization signal in the hepatitis B virus polymerase

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World Journal of Gastroenterology 2013年第44期19卷 8000-8010页

作者： Joachim Lupberger stephanie Schaedler Alexander Peiran Eberhard hildt Department of Medicine Ⅱ University of Freiburg D-79106 Freiburg Germany Inserm U748 Strasbourg France Division of Virology University Goettingen37073 Goettingen Germany Division of Virology Paul-Ehrlich-InstituteD-63325 Langen Germany

AIM: To characterize the nuclear import of hepatitis B virus (hBV) polymerase (P) and its relevance for the viral life cycle.METhODS: Sequence analysis was performed to predict functional motives within P. Phosphorylation of P was analyzed by in vitro phosphorylation. Phosphorylation site and nuclear localization signal (NLS) were destroyed by site directed mutagenesis. Functionality of the identified NLS was analyzed by confocal fluorescence microscopy and characterizing the karyopherin binding. Relevance of the structural motives for viral life cycle was studied by infection of primary Tupaia hepatocytes with hBV.RESULTS: We identified by sequence alignment and functional experiments a conserved bipartite NLS containing a casein kinase II (CKII) phosphorylation site located within the terminal protein domain (TP) of the hBV polymerase. Inhibition of CKII impairs the functionality of this NLS and thereby prevents the nuclear import of the polymerase. Binding of the import factor karyopherin-α2 to the polymerase depends on its CKII-mediated phosphorylation of the bipartite NLS. In hBV-infected primary Tupaia hepatocytes CKII inhibition in the early phase (post entry phase) of the infection process prevents the establishment of the infection.CONCLUSION: Based on these data it is suggested that during hBV infection the final import of the genome complex into the nucleus is mediated by a novel bipartite NLS localized in the TP domain of hBV polymerase.

关键词： hepatitis B virus Nuclear localization signal Casein kinase II Trafficking Replication

Changes in structure and functional properties of whey proteins induced by high hydrostatic pressure:A review

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Frontiers of Chemical Science and Engineering 2009年第4期3卷 436-442页

作者： Xiaoming LIU Jia NING stephanie CLARK State Key Laboratory of Food Science and Technology and School of Food Science and Technology Jiangnan UniversityWuxi 214122China Department of Food Science and human Nutrition Iowa State UniversityAmesIA 50011-1061USA

high hydrostatic pressure(hhP)is an alternative technology to heat processing for food product *** does not cause environmental pollution and eliminates the use of chemical additives in food *** review covers the research conducted to understand the effect of hhP on structure and functional properties of whey *** this paper,the mechanism underlying pressure-induced changes inβ-lactoglobulin andα-lactabumin is also discussed and how they related to functional properties such as hydrophobicity,foam stability,and flavor-binding capacity.

关键词： high hydrostatic pressure whey protein functional properties structure

A CK2-RNF4 interplay coordinates non-canonical SUMOylation and degradation of nuclear receptor FXR

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Journal of Molecular Cell Biology 2017年第3期9卷 195-208页

作者： stephanie Bilodeau Veronique Caron Jonathan Gagnon Alexandre Kuftedjian Andre Tremblay Research Center CHU Sainte-Justine Montreal Quebec H3T 1C5 Canada Department of Biochemistry and Molecular Medicine Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada Department of Obstetrics & Gynecology Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada

Farnesoid X receptor （FXR） is a ligand-activated nuclear receptor that plays a central role in regulating genes involved in bile acid homeostasis, and fat and glucose metabolism. here, we demonstrate a post-translational interplay between FXR phosphoryl- ation, SUMOylation, and ubiquitination that directs the receptor into an activation-degradation pathway in hepatocytes. We iden- tify a non-canonical SUMOylation motif termed pSuM that conjugates SUM02 at Lys-325 of FXR under the direct control of casein kinase 2 （CK2）, which provides the required negative charge for Ubc9 and PIAS1 to perform SUMOylation, by phosphorylating Ser-327. Lys-325 SUMOylation is indispensable to the promotion of efficient ligand activation and transcriptional coactivation of FXR. Constitutive pSuM activation using a phospho-mimic Ser-327 mutant or catalytic CK2 expression strongly induces SUM02 conjugation, which directs FXR ubiquitination and proteasome-dependent degradation. We also determine that such SUMOylation-dependent ubiquitination of FXR is mediated by the E3 ubiquitin ligase RNF4, which is required to achieve maximal induction of FXR and optimal up- or downregulation of responsive genes involved in bile acid homeostasis and liver regeneration. Our findings identify a highly regulated atypical SUMO conjugation motif that serves to coordinate FXR transcriptional compe- tence, thereby expanding the intricate dynamics of the SUMOylation process used by incoming signals to govern metabolic gene regulation.

关键词： farnesoid receptor SUMOylation ubiquitination 26S proteasome bile acid