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Search Results: 1 - 10 of 375 matches for " Beate Sodeik? "
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Improper Tagging of the Non-Essential Small Capsid Protein VP26 Impairs Nuclear Capsid Egress of Herpes Simplex Virus
Claus-Henning Nagel, Katinka D?hner, Anne Binz, Rudolf Bauerfeind, Beate Sodeik
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0044177
Abstract: To analyze the subcellular trafficking of herpesvirus capsids, the small capsid protein has been labeled with different fluorescent proteins. Here, we analyzed the infectivity of several HSV1(17+) strains in which the N-terminal region of the non-essential small capsid protein VP26 had been tagged at different positions. While some variants replicated with similar kinetics as their parental wild type strain, others were not infectious at all. Improper tagging resulted in the aggregation of VP26 in the nucleus, prevented efficient nuclear egress of viral capsids, and thus virion formation. Correlative fluorescence and electron microscopy showed that these aggregates had sequestered several other viral proteins, but often did not contain viral capsids. The propensity for aggregate formation was influenced by the type of the fluorescent protein domain, the position of the inserted tag, the cell type, and the progression of infection. Among the tags that we have tested, mRFPVP26 had the lowest tendency to induce nuclear aggregates, and showed the least reduction in replication when compared to wild type. Our data suggest that bona fide monomeric fluorescent protein tags have less impact on proper assembly of HSV1 capsids and nuclear capsid egress than tags that tend to dimerize. Small chemical compounds capable of inducing aggregate formation of VP26 may lead to new antiviral drugs against HSV infections.
Cryo Electron Tomography of Herpes Simplex Virus during Axonal Transport and Secondary Envelopment in Primary Neurons
Iosune Ibiricu,Juha T. Huiskonen,Katinka D?hner,Frank Bradke,Beate Sodeik,Kay Grünewald
PLOS Pathogens , 2011, DOI: 10.1371/journal.ppat.1002406
Abstract: During herpes simplex virus 1 (HSV1) egress in neurons, viral particles travel from the neuronal cell body along the axon towards the synapse. Whether HSV1 particles are transported as enveloped virions as proposed by the ‘married’ model or as non-enveloped capsids suggested by the ‘separate’ model is controversial. Specific viral proteins may form a recruitment platform for microtubule motors that catalyze such transport. However, their subviral location has remained elusive. Here we established a system to analyze herpesvirus egress by cryo electron tomography. At 16 h post infection, we observed intra-axonal transport of progeny HSV1 viral particles in dissociated hippocampal neurons by live-cell fluorescence microscopy. Cryo electron tomography of frozen-hydrated neurons revealed that most egressing capsids were transported independently of the viral envelope. Unexpectedly, we found not only DNA-containing capsids (cytosolic C-capsids), but also capsids lacking DNA (cytosolic A-/B-capsids) in mid-axon regions. Subvolume averaging revealed lower amounts of tegument on cytosolic A-/B-capsids than on C-capsids. Nevertheless, all capsid types underwent active axonal transport. Therefore, even few tegument proteins on the capsid vertices seemed to suffice for transport. Secondary envelopment of capsids was observed at axon terminals. On their luminal face, the enveloping vesicles were studded with typical glycoprotein-like spikes. Furthermore, we noted an accretion of tegument density at the concave cytosolic face of the vesicle membrane in close proximity to the capsids. Three-dimensional analysis revealed that these assembly sites lacked cytoskeletal elements, but that filamentous actin surrounded them and formed an assembly compartment. Our data support the ‘separate model’ for HSV1 egress, i.e. progeny herpes viruses being transported along axons as subassemblies and not as complete virions within transport vesicles.
Plus- and Minus-End Directed Microtubule Motors Bind Simultaneously to Herpes Simplex Virus Capsids Using Different Inner Tegument Structures
Kerstin Radtke,Daniela Kieneke,André Wolfstein,Kathrin Michael,Walter Steffen,Tim Scholz,Axel Karger,Beate Sodeik
PLOS Pathogens , 2010, DOI: 10.1371/journal.ppat.1000991
Abstract: Many viruses depend on host microtubule motors to reach their destined intracellular location. Viral particles of neurotropic alphaherpesviruses such as herpes simplex virus 1 (HSV1) show bidirectional transport towards the cell center as well as the periphery, indicating that they utilize microtubule motors of opposing directionality. To understand the mechanisms of specific motor recruitment, it is necessary to characterize the molecular composition of such motile viral structures. We have generated HSV1 capsids with different surface features without impairing their overall architecture, and show that in a mammalian cell-free system the microtubule motors dynein and kinesin-1 and the dynein cofactor dynactin could interact directly with capsids independent of other host factors. The capsid composition and surface was analyzed with respect to 23 structural proteins that are potentially exposed to the cytosol during virus assembly or cell entry. Many of these proteins belong to the tegument, the hallmark of all herpesviruses located between the capsid and the viral envelope. Using immunoblots, quantitative mass spectrometry and quantitative immunoelectron microscopy, we show that capsids exposing inner tegument proteins such as pUS3, pUL36, pUL37, ICP0, pUL14, pUL16, and pUL21 recruited dynein, dynactin, kinesin-1 and kinesin-2. In contrast, neither untegumented capsids exposing VP5, VP26, pUL17 and pUL25 nor capsids covered by outer tegument proteins such as vhs, pUL11, ICP4, ICP34.5, VP11/12, VP13/14, VP16, VP22 or pUS11 bound microtubule motors. Our data suggest that HSV1 uses different structural features of the inner tegument to recruit dynein or kinesin-1. Individual capsids simultaneously accommodated motors of opposing directionality as well as several copies of the same motor. Thus, these associated motors either engage in a tug-of-war or their activities are coordinately regulated to achieve net transport either to the nucleus during cell entry or to cytoplasmic membranes for envelopment during assembly.
The Herpes Simplex Virus Protein pUL31 Escorts Nucleocapsids to Sites of Nuclear Egress, a Process Coordinated by Its N-Terminal Domain
Christina Funk?,Melanie Ott?,Verena Raschbichler?,Claus-Henning Nagel?,Anne Binz?,Beate Sodeik,Rudolf Bauerfeind?,Susanne M. Bailer
PLOS Pathogens , 2015, DOI: 10.1371/journal.ppat.1004957
Abstract: Progeny capsids of herpesviruses leave the nucleus by budding through the nuclear envelope. Two viral proteins, the membrane protein pUL34 and the nucleo-phosphoprotein pUL31 form the nuclear egress complex that is required for capsid egress out of the nucleus. All pUL31 orthologs are composed of a diverse N-terminal domain with 1 to 3 basic patches and a conserved C-terminal domain. To decipher the functions of the N-terminal domain, we have generated several Herpes simplex virus mutants and show here that the N-terminal domain of pUL31 is essential with basic patches being critical for viral propagation. pUL31 and pUL34 entered the nucleus independently of each other via separate routes and the N-terminal domain of pUL31 was required to prevent their premature interaction in the cytoplasm. Unexpectedly, a classical bipartite nuclear localization signal embedded in this domain was not required for nuclear import of pUL31. In the nucleus, pUL31 associated with the nuclear envelope and newly formed capsids. Viral mutants lacking the N-terminal domain or with its basic patches neutralized still associated with nucleocapsids but were unable to translocate them to the nuclear envelope. Replacing the authentic basic patches with a novel artificial one resulted in HSV1(17+)Lox-UL31-hbpmp1mp2, that was viable but delayed in nuclear egress and compromised in viral production. Thus, while the C-terminal domain of pUL31 is sufficient for the interaction with nucleocapsids, the N-terminal domain was essential for capsid translocation to sites of nuclear egress and a coordinated interaction with pUL34. Our data indicate an orchestrated sequence of events with pUL31 binding to nucleocapsids and escorting them to the inner nuclear envelope. We propose a common mechanism for herpesviral nuclear egress: pUL31 is required for intranuclear translocation of nucleocapsids and subsequent interaction with pUL34 thereby coupling capsid maturation with primary envelopment.
Prevalence of Wild-Type Butyrylcholinesterase Genotype in Patients with Alzheimer’s Dementia  [PDF]
Beate Mueller, Georg Adler
World Journal of Neuroscience (WJNS) , 2015, DOI: 10.4236/wjns.2015.53019
Abstract: Approximately, two-thirds patients with Alzheimer’s disease (AD) are reported to have homozygous wild-type butyrylcholinesterase (BuChE) gene expression. It is associated with a higher rate of hydrolysis of acetylcholine, which ultimately leads to increase in the levels of BuChE in advanced stages of the disease. Rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and BuChE, might be of additional benefit in patients with AD with wild-type BuChE allele.
The Renin-Angiotensin System in the Development of Salt-Sensitive Hypertension in Animal Models and Humans
Beate Rassler
Pharmaceuticals , 2010, DOI: 10.3390/ph3040940
Abstract: Hypertension is still one of the major causes of death from cardiovascular failure. Increased salt intake may aggravate the rise in blood pressure and the development of consequential damage of the heart, the vessels and other organs. The general necessity of restricted salt intake regardless of blood pressure or salt sensitivity has been a matter of debate over the past decades. This review summarizes the main pathogenic mechanisms of hypertension and salt sensitivity in rat models, particularly in the spontaneously hypertensive rat (SHR), and in patients with essential hypertension (EH). Although SHRs are commonly considered to be salt-resistant, there is much evidence that salt loading may deteriorate blood pressure and cardiovascular function even in these animals. Similarly, EH is not a homogenous disorder – some patients, but not all, exhibit pronounced salt sensitivity. The renin-angiotensin system (RAS) plays a key role in the regulation of blood pressure and salt and fluid homeostasis and thus is one of the main targets of antihypertensive therapy. This review focuses on the contribution of the RAS to the pathogenesis of salt-sensitive hypertension in SHRs and patients with EH.
Organizaciones sociales y anclaje territorial Escenarios y componentes de la transformación socioterritorial y local en Venezuela
Cuadernos del Cendes , 2008,
Abstract: in latin america, social movements and organizations engage in a struggle for better living conditions, demanding more participation in public policies, from and in their territories. for the democratization of society, the socioterritorial anchoring of social organizations is very important. this article examines if in the venezuelan case new public spaces are being built in the microlocal level, based on the practices of communitarian organizations. the analysis of organizations such as communal councils and health committees shows achievements, difficulties and contradictions in which their communitarian practices are embedded. the difficult construction of institutionalized public spaces for the exercise of a citizenship anchored in the socioterritorial realm has begun in venezuela.
Bibliotheken und Portale - ein überblick / Libraries and portals - a survey
Guba, Beate
GMS Medizin-Bibliothek-Information , 2006,
Abstract: Initially a definition of the term portal is given by which the main functionalities of portals are described. Furthermore a distinction is made between two different types of portals: a) Subject-oriented information portals and b) MyLibrary portals. The progress in this area and future tendencies are illustrated by various examples. This article focuses on the scientific context, public libraries are excluded.
Review: Lewis A. Dexter (2006). Elite and Specialized Interviewing. With a New Introduction by Alan Ware and Martín Sánchez-Jankowski Review: Lewis A. Dexter (2006). Elite and Specialized Interviewing. With a New Introduction by Alan Ware and Martín Sánchez-Jankowski Rese a: Lewis A. Dexter (2006). Elite and Specialized Interviewing. With a New Introduction by Alan Ware and Martín Sánchez-Jankowski
Beate Littig
Forum : Qualitative Social Research , 2008,
Abstract: Der Eigenverlag des European Consortium for Political Research (ECPR) besorgte 2006 in der Reihe ECPR Classics die Neuauflage des Buches "Elite and Specialized Interviewing" des Politikwissenschaftlers L.A. DEXTER, das zuerst 1969 erschienen ist. Eliteinterviews sind in DEXTERs Verst ndnis nicht-standardisierte, offene Interviews mit Angeh rigen der politischen oder wirtschaftlichen Elite, die es den Befragten erm glichen, ihre eigenen Relevanzen darzulegen. Was heute als Gemeinplatz qualitativer Sozialforschung gilt, kann zur Zeit der Ersterscheinung von DEXTERs Buch und unter der Vorherrschaft quantitativer Sozialforschung als methodische Innovation angesehen werden. DEXTERs Buch, das weniger ein Methodenbuch als ein Essay über seine umfangreichen Erfahrungen mit dem Interviewen von Eliten ist, enth lt vielf ltige praktische Hinweise für das Interviewen von Eliten, die nach wie vor gültig sind. Sie betreffen sowohl die gegenw rtig prim r englischsprachige Literatur über Eliteinterviews als auch das vergleichbare deutschsprachige Interviewen von ExpertInnen. Insofern kann das Buch zurecht als Klassiker bezeichnet werden, auch wenn die methodologischen und methodischen überlegungen qualitativer Sozialforschung inzwischen differenzierter und methodenkritischer sind. URN: urn:nbn:de:0114-fqs080151 The European Consortium for Political Research (ECPR) republished in 2006 the book of the political scientist L.A. DEXTER on "Elite and Specialized Interviewing." According to DEXTER the main characteristic of this type of interviews is non-standardized treatment. Through this the interviewee is given the chance to present his or her own relevance with regard to the topic and situation at stake. What seems to be self-evident in the context of qualitative social research today—the importance of the interviewee's definition of the situation and the topic at stake—can be regarded as an innovation in the 1970ies considering the predominance of quantitative social research. DEXTER's essay gives a broad variety of hints of how to approach and practically interview elites, which are still up-to-date. Thus the book can be labeled as a classic, despite the fact that the methodological reflections about qualitative social research, including elite interviewing or as in the German-speaking context expert interviews have become much more detailed and divers. URN: urn:nbn:de:0114-fqs080151 El Consorcio Europeo para la Investigación Política (ECPR, por sus siglas en inglés) reeditó en 2006 el libro del politólogo L.A. DEXTER sobre "Elite and Specialized Interviewing". De acuer
Interviews mit Eliten – Interviews mit ExpertInnen: Gibt es Unterschiede? Interviews with the Elite and with Experts. Are There Any Differences? Entrevistas con élites y con expertos. Existen diferencias?
Beate Littig
Forum : Qualitative Social Research , 2008,
Abstract: Vergleicht man die überwiegend deutschsprachige Literatur zu Experteninterviews mit den internationalen Beitr gen zu Eliteninterviews, fallen mehr Gemeinsamkeiten als Unterschiede auf. Thematisiert werden hier wie dort die gro en Zugangsprobleme und Spezifika der Interaktionssituation und der Gespr chsführung. Auch bei der jeweiligen Definition der Zielgruppen der Interviews (ExpertInnen und Eliten) gibt es überschneidungen, wenn auch nicht Deckungsgleichheit. Der Beitrag diskutiert die Gemeinsamkeiten und Unterschiede von beiden methodischen Ans tzen und will so zu einer Pr zisierung der Methodologie des Experteninterviews beitragen. Er endet mit einem wissenssoziologisch begründeten Pl doyer dafür, (professionelle) Funktionseliten aufgrund ihrer Machtpositionen als eine spezifische Gruppe von ExpertInnen zu betrachten. Methodologisch betrachtet sind ExpertInnen (und somit auch Eliten) aufgrund ihres spezifischen Deutungs- und Handlungswissens für die sozial- und politikwissenschaftlich orientierte Forschung bedeutsam. Konsequenterweise sind dann Interviews mit Eliten, die auf die Generierung expliziten wie impliziten, professionellen oder berufsbezogenen Wissens abzielen, als Experteninterviews anzusehen. URN: urn:nbn:de:0114-fqs0803161 A comparison of the predominantly German-language literature on expert interviews in international articles on interviewing the elite reveals more commonalities than differences. Similar issues are discussed in both, such as the problems of gaining access to these groups, and the specifics of interaction and interviewing. Although not identical, the respective target group definitions (experts and the elite) for such interviews overlap. This article discusses the commonalities and differences in these two methodological approaches, thereby contributing to a more detailed specification of the methodology of expert interviews. It concludes with an appeal based on the sociology of knowledge that the (professional) functional elite—given their positions of power—be considered as a specific group of experts. From a methodological perspective and as a result of their specific background knowledge ("know why") and know-how, experts (and thus also the elite) are of relevance to social and political science research. Consequently, interviews with the elite aimed at generating explicit, tacit, professional or occupational knowledge should be seen as expert interviews. URN: urn:nbn:de:0114-fqs0803161 Una comparación de la literatura preferentemente en alemán sobre entrevistas a expertos y de artículos internacionales sobre la entr
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