Eimeria bovis infection modulates endothelial host cell cholesterol metabolism for successful replication

During first merogony Eimeria bovis forms large macromeronts in endothelial host cells containing >120 000 merozoites I. During multiplication, large amounts of cholesterol are indispensable for the enormous offspring membrane production. Cholesterol auxotrophy was proven for other apicomplexan parasites. Consequently they scavenge cholesterol from their host cell apparently in a parasite-specific manner. We here analyzed the influence of E. bovis infection on endothelial host cell cholesterol metabolism and found considerable differences to other coccidian parasites. Overall, free cholesterol significantly accumulated in E. bovis infected host cells. Furthermore, a striking increase of lipid droplet formation was observed within immature macromeronts. Artificial host cell lipid droplet enrichment significantly improved E. bovis merozoite I production confirming the key role of lipid droplet contents for optimal parasite proliferation. The transcription of several genes being involved in both, cholesterol de novo biosynthesis and low density lipoprotein-(LDL) mediated uptake, was significantly up-regulated at a time in infected cells suggesting a simultaneous exploitation of these two cholesterol acquisition pathways. E. bovis scavenges LDL-derived cholesterol apparently through significantly increased levels of surface LDL receptor abundance and LDL binding to infected cells. Consequently, LDL supplementation significantly improved parasite replication. The up-regulation of the oxidized LDL receptor 1 furthermore identified this scavenger receptor as a key molecule in parasite-triggered LDL uptake. Moreover, cellular cholesterol processing was altered in infected cells as indicated by up-regulation of cholesterol-25-hydroxylase and sterol O-acyltransferase. Overall, these results show that E. bovis considerably exploits the host cell cholesterol metabolism to guarantee its massive intracellular growth and replication

Činjenje nacije u carstvima: pojava Turske i Austrije

This article examines nation-building in relation to education and educational institutions, taking two former big players in European politics in the wake of the First World War as examples: the Ottoman Empire and the Habsburg Empire. The Habsburg Empire is examined by focusing particularly on textbooks around and after 1918, comparing them with each other and understanding them as major tools for spreading national ideas within state school. As will be shown, the idea of an Austrian nation can hardly be found, neither before nor immediately after the break of 1918, in the sense of the ideology of a nation-state. On the other hand, the Ottoman Empire is being examined as an example for doing nation in a process of transformation of social structures within non-western societies through western-style schools, thus contributing to nationally substantiating the Republic of Turkey. This article examines the imperial foundations of these two nation-states and how they and the preceding empires dealt with the modern concept of nation and nationalism.U ovom članku ispituje se izgrađivanje nacije u vezi s obrazovanjem i obrazovnim institucijama, na primjeru dva bivša velika aktera u europskoj politici nakon Prvog svjetskog rata: Otomanskog Carstvu i Habsburškog Carstva. Habsburško Carstvo promatra se prvenstveno kroz poseban fokus na udžbenike u 1918. godini i periodu nakon nje, uspoređujući ih međusobno i razumijevajući ih kao glavne alate širenja nacionalnih ideja unutar državnih škola. Kako će biti pokazano, ideja austrijske nacije u smislu ideologije nacionalne države teško se može naći, kako prije, tako i neposredno nakon sloma 1918. godine. S druge strane, Otomansko Carstvo ispituje se kao primjer činjenja nacije u procesu transformacije društvenih struktura unutar ne-zapadnih društava, kroz škole zapadnjačkoga stila te stoga doprinosi nacionalnom ostvarenju Republike Turske. U ovom članku istražuju se imperijalne osnove ove dvije nacionalne države i način na koji su se one i prijašnja carstva bavili modernim konceptom nacije i nacionalizma

Joint Pricing and Inventory Control under Reference Price Effects

In this work, we address the problem of simultaneously determining a pricing and inventory replenishment strategy under reference price effects. This reference price effect models the fact that consumers not only react sensitively to the current price, but also to deviations from a reference price formed on the basis of past purchases. Immediate effects of price reductions on profits have to be weighted against the resulting losses in future periods. By providing an analytical analysis and numerical simulations we study how the additional dynamics of the consumers’ willingness to pay affect an optimal pricing and inventory control model and whether a simple policy such as a base-stock-list-price policy holds in such a setting

Oxytocin impedes the effect of the word blindness post-hypnotic suggestion on Stroop task performance.

The ability to enhance sensitivity to relevant (post)hypnotic suggestions has implications for creating clinically informed analogues of psychological and neuropsychological conditions and for the use of hypnotic interventions in psychological and medical conditions. The aim of this study was to test the effect of oxytocin inhalation on a post-hypnotic suggestion that previously has been shown to improve the selectivity of attention in the Stroop task. In a double-blind placebo-controlled between-subjects study, medium hypnotizable individuals performed the Stroop task under normal conditions and when they had been given a post-hypnotic suggestion that they would perceive words as meaningless symbols. In line with previous research, Stroop interference was substantially reduced by the suggestion in the placebo condition. However, contrary to expectations, oxytocin impeded the effect of the word blindness suggestion on performance. The results are explained in terms of the requirement for the re-implementation of the word blindness suggestion on a trial-by-trial basis and the need to sustain activation of the suggestion between trials. The findings contrast with a recent study showing a beneficial effect of oxytocin on sensitivity to (post)hypnotic suggestions but are consistent with findings showing a detrimental effect of oxytocin on memory processes

Reversible translocation of acyl-CoA:cholesterol acyltransferase (ACAT) between the endoplasmic reticulum and vesicular structures

The enzyme acyl-CoA:cholesterol acyltransferase (ACAT) is normally localized in the endoplasmic reticulum (ER) where it can esterify cholesterol for storage in lipid droplets and/or the formation of lipoproteins. Here, we report that ACAT can translocate from the ER into vesicular structures in response to different ACAT inhibitors. The translocation was fast (within minutes), reversible and occurred in different cell types. Interestingly, oleic acid was able to fasten the re-translocation from vesicles back into the reticular ER network. The process of ACAT translocation could also be induced by cyclodextrins, cholesterol, lanosterol (but not 4-cholestene-3 one), 25-hydroxycholesterol, and by certain stress stimuli such as hyperosmolarity (sucrose treatment), temperature change, or high-density cultivation. In vitro esterification showed that ACAT remains fully active after it has been translocated to vesicles in response to hyperosmotic sucrose treatment of the cells. The translocation process was not accompanied by changes in the electrophoretic mobility of ACAT, even after chemical crosslinking. Interestingly, the protein synthesis inhibitor cycloheximide showed a stimulating effect on ACAT activity and prevented the translocation of ACAT from the ER into vesicles

Plasma membrane cholesterol as a regulator of human and rodent P2X7 receptor activation and sensitization.

P2X7 receptors are nonselective cation channels gated by high extracellular ATP, but with sustained activation, receptor sensitization occurs, whereby the intrinsic pore dilates, making the cell permeable to large organic cations, which eventually leads to cell death. P2X7 receptors associate with cholesterol-rich lipid rafts, but it is unclear how this affects the properties of the receptor channel. Here we show that pore-forming properties of human and rodent P2X7 receptors are sensitive to perturbations of cholesterol levels. Acute depletion of cholesterol with 5 mm methyl-β-cyclodextrin (MCD) caused a substantial increase in the rate of agonist-evoked pore formation, as measured by the uptake of ethidium dye, whereas cholesterol loading inhibited this process. Patch clamp analysis of P2X7 receptor currents carried by Na(+) and N-methyl-D-glucamine (NMDG(+)) showed enhanced activation and current facilitation following cholesterol depletion. This contrasts with the inhibitory effect of methyl-β-cyclodextrin reported for other P2X subtypes. Mutational analysis suggests the involvement of an N-terminal region and a proximal C-terminal region that comprises multiple cholesterol recognition amino acid consensus (CRAC) motifs, in the cholesterol sensitivity of channel gating. These results reveal cholesterol as a negative regulator of P2X7 receptor pore formation, protecting cells from P2X7-mediated cell death.This work was supported by the Biotechnology and Biological Sciences Research Council (BB/F001320/1), the David James Studentship, Department of Pharmacology, University of Cambridge and the Marshall Scholarship.This paper was originally published in The Journal of Biological Chemistry (Robinson LE, Shridar M, Smith P, Murrell-Lagnado RD, The Journal of Biological Chemistry 2014, 289, 46, 31983–31994, doi:10.1074/jbc.M114.574699

Vergleich dreier Masterstudiengänge in Library and Information Science (LIS) an Hochschulen des United Kingdom und ihre potentielle Eignung als weiterführende Qualifikation aus der Perspektive einer Studentin des Bachelorstudiengangs „Bibliothekswesen“ der Fachhochschule Köln

Diese Arbeit stellt drei Masterstudiengänge des Bereichs Library and Information Science an Hochschulen des United Kingdom vor und überprüft sie auf ihre Eignung als weiterführende Qualifikation für die Absolventen des Bachelorstudiengangs „Bibliothekswesen“ der Fachhochschule Köln. Durch Darstellung der europäischen Studienstrukturen seit Beginn des Bologna-Prozesses werden zunächst die Rahmenbedingungen für ein Auslandsstudium verdeutlicht. Als Grundlage für die spätere Beurteilung der Masterstudiengänge wird anschließend der Bachelorstudiengang „Bibliothekswesen“ unter Zuhilfenahme des Modulbuchs und der Prüfungsordnung vorgestellt und ein Profil für die Absolventen entwickelt. Nach einem allgemeinen Überblick über die Hochschulausbildung im United Kingdom und die LIS-Ausbildung im Speziellen, wird der Berufsverband Chartered Institute of Library and Information Professionals und seine Aufgabe im Bereich Akkreditierung vorgestellt. Im Hauptteil werden anhand selbsterstellter Kriterien drei Studiengänge aus England, Wales und Schottland ausgewählt und anhand der Informationen der Internetseiten der Hochschulen beschrieben. Abschließend werden die Studiengänge, ebenfalls mittels selbstgewählter Kriterien, auf ihre Eignung als weiterführende Qualifikation überprüft

Stripes — A Conceptual Operating System User Interface

Perinteiset käyttöjärjestelmien graafiset käyttöliittymät suunniteltiin vuosikym- meniä sitten ja ovat muodostuneet osaksi jokapäiväistä elämäämme. Viime vuosien tietoteknillinen kehitys ja tietokoneiden muuttuneet käyttötarpeet ovat tuoneet esille nykyisten käyttöliittymien heikkoudet. Tämä lopputyö esittää vaihtoehtoisen käyttöliit- tymätoteutuksen, nimeltään Juovat, joka painottaa käytettävyyttä, yksinkertaisuutta, tuotteliaisuutta ja muita käyttäjäkeskeisiä arvoja. Työ kattaa ja analysoi nykyisten käyttöliittymien historian sekä viime vuosien tärkeimmät innovaatiot. Alan tutkiminen helpottaa nykyisten käyttöliittymien heik- kouksien ja vahvuuksien kartoittamisessa sekä auttaa muodostamaan selkeät kriteerit suunnitellulle käyttöliittymätoteutukselle. Juovat-käyttöliittymän kokonaisvaltainen suunnittelu ja useat yksityiskohdat esitel- lään seikkaperäisesti. Toimivuutta analysoidaan vertaamalla toteutuksen vahvuuksia ja heikkouksia olemassa oleviin käyttöliittymiin sekä testaamalla käytännön toimivuutta prototyypin avulla. Lopuksi testituloksia peilataan alkuperäisiin suunnittelukritee- reihin ja pohditaan työn onnistumista.Traditional computer operating system graphical user interfaces were designed decades ago have since become an integral part of our everyday lives. While fundamentally excellent, recent changes in the industry and use cases for computers are exposing the weaknesses in the implementations of current operating system user interfaces. This thesis is an attempt to propose an alternative, modernized user interface design — entitled Stripes — based on usability, simplicity, productivity, and other design guidelines. The history and recent innovative additions to the current implementations of WIMP- based operating system user interfaces are outlined and analyzed. This contextual mapping of the field helps in identifying key problems and strengths of modern computer user interfaces, and, in addition to the aforementioned guidelines, form a basis for the design of the proposed concept. The fundamental design choices, as well as several details of Stripes are described and explained. Its theoretical improvements and disadvantages over current user interface implementations are first discussed, then tested with the help of an interactive proto- type. The favorable and critical test outcomes are described in detail, and reflected against the original design guidelines of the concept. Finally, conclusions on the success of the proposed interface are provided

Evaluation von ausgewählten Altmetrics-Diensten für den Einsatz an wissenschaftlichen Bibliotheken

Der Wandel der wissenschaftlichen Kommunikation durch die Verlagerung ins Internet hat neue Formen wissenschaftlichen Outputs hervorgebracht, für deren Evaluation die klassischen bibliometrischen Indikatoren und Verfahren nicht mehr ausreichen. Neben traditionellen Indikatoren haben sich seit wenigen Jahren alternative Metriken, sogenannte Altmetrics, entwickelt. Diese messen die Wahrnehmung über die klassische Zitation hinaus und werten Erwähnungen in sozialen Medien und weiterer webbasierter Wissenschaftskommunikation aus. Diese Arbeit beschreibt die Möglichkeiten des Einsatzes von Altmetrics an wissenschaftlichen Bibliotheken. Dabei wird zunächst die Entwicklung der Bibliometrie und deren Anwendung in Bibliotheken, u.a. anhand einiger Beispiele, dargestellt. Nach einer kurzen Definition werden Potentiale und Grenzen der Altmetrics erläutert, einzelne Anbieter von Altmetrics-Diensten vorgestellt sowie potentielle bibliothekarische Anwendungsfälle geschildert. Zur Beurteilung konkreter Einsatzmöglichkeiten von Altmetrics-Diensten werden zwei Tools ausgewählt und anhand von selbsterstellten Kriterien analysiert und beurteilt

Poesie, Philosophie und Malerei : Ästhetisch-philosophische Studien zu Joseph von Eichendorff und Otto Weininger

Print-on-demand: https://www.bod.de/buchshop/poesie-philosophie-und-malerei-georg-gimpl-978375629675