143 research outputs found
Asymmetric dimethylarginine is transported by the mitochondrial carrier SLC25A2
Asymmetric dimethyl l-arginine (ADMA) is generated within cells and in mitochondria when proteins with dimethylated arginine residues are degraded. The aim of this study was to identify the carrier protein(s) that transport ADMA across the inner mitochondrial membrane. It was found that the recombinant, purified mitochondrial solute carrier SLC25A2 when reconstituted into liposomes efficiently transports ADMA in addition to its known substrates arginine, lysine, and ornithine and in contrast to the other known mitochondrial amino acid transporters SLC25A12, SLC25A13, SLC25A15, SLC25A18, SLC25A22, and SLC25A29. The widely expressed SLC25A2 transported ADMA across the liposomal membrane in both directions by both unidirectional transport and exchange against arginine or lysine. The SLC25A2-mediated ADMA transport followed first-order kinetics, was nearly as fast as the transport of the best SLC25A2 substrates known so far, and was highly specific as symmetric dimethylarginine (SDMA) was not transported at all. Furthermore, ADMA inhibited SLC25A2 activity with an inhibition constant of 0.38 ± 0.04 mM, whereas SDMA inhibited it poorly. We propose that a major function of SLC25A2 is to export ADMA from mitochondria missing the mitochondrial ADMA-metabolizing enzyme AGXT2. There is evidence that ADMA can also be imported into mitochondria, e.g., in kidney proximal tubulus cells, to be metabolized by AGXT2. SLC25A2 may also mediate this transport function
A framework for describing the influence of service organisation and delivery on participation in fetal anomaly screening in England
Objective. The aim of this research was to explore the influence of service organisation and delivery on providers and users’ interactions and decision-making in the context of Down’s syndrome screening. Methods. A qualitative descriptive study involving online interviews conducted with a purposive sample of 34 community midwives, 35 pregnant women, and 15 partners from two maternity services in different health districts in England. Data were analysed using a combination of grounded theory principles and content analysis and a framework was developed. Results. The main emerging concepts were organisational constraints, power, routinisation, and tensions. Providers were concerned about being time-limited that encouraged routine, minimal information-giving and lacked skills to check users’ understanding. Users reported their participation was influenced by providers’ attitudes, the ambience of the environment, asymmetric power relations, and the offer and perception of screening as a routine test. Discordance between the national programme’s policy of nondirective informed choice and providers’ actions of recommending and arranging screening appointments was unexpected. Additionally, providers and users differing perceptions of emotional effects of information, beliefs, and expectations created tensions within them, between them, and in the antenatal environment. Conclusions. A move towards a social model of care may be beneficial to empower service users and create less tension for providers and users
Absolute rate constants for the reactions of some arylchlorocarbenes with acetic acid
PT: J; CR: CLOSS GL, 1968, TOP STEREOCHEM, V3, P193 CLOSS GL, 1976, J AM CHEM SOC, V98, P8190 EISENTHAL KB, 1980, J AM CHEM SOC, V102, P6563 GRAHAM WH, 1965, J AM CHEM SOC, V87, P4396 GRILLER D, 1982, J AM CHEM SOC, V104, P5549 HADEL LM, UNPUB CHEM PHYS LETT KIRMSE W, 1971, CARBENE CHEM, CH7 LIU MTH, 1972, CAN J CHEM, V50, P3009 NAGAI Y, 1962, B CHEM SOC JPN, V35, P132 SCAIANO JC, 1980, J AM CHEM SOC, V102, P7747 TURRO NJ, 1980, J AM CHEM SOC, V102, P7576 WONG PC, 1981, CHEM PHYS LETT, V83, P69 WONG PC, 1981, J AM CHEM SOC, V103, P5934 WONG PC, 1982, J AM CHEM SOC, V104, P5106 ZUPANCIC JJ, 1980, J AM CHEM SOC, V102, P5958 ZUPANCIC JJ, 1981, J AM CHEM SOC, V103, P2423 ZUPANCIC JJ, 1981, J AM CHEM SOC, V103, P944; NR: 17; TC: 17; J9: J ORG CHEM; PG: 2; GA: QM675Source type: Electronic(1
La historia como suspenso: la representación del tiempo en Heinrich von Ofterdingen de Novalis (Friedrich von Hardenberg)
Revista con referatoFil: Closs, Marina. Universidad Nacional de General Sarmiento. Instituto del Desarrollo Humano; Argentina.Fil: Closs, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.En este artículo, analizaremos algunas de las distintas aproximaciones a la representación del tiempo en Heinrich von Ofterdingende Novalis (1772-1801), buscando no excluirlas entre sí, sino combinarlas en el espíritu ecléctico que pregona el mismo autor en su obra. En Heinrich von Ofterdingen, Novalis intenta hacer coincidir la representación de un tiempo objetivo y exterior con uno subjetivo e interior, reuniendo los dos géneros discursivos que en su época se relacionan a estas dos formas de representación: la historia y la novela. En la “novela mitológica” que planea escribir Novalis, las categorías de novela e historia confluyen y, al mismo tiempo, se redefinen. Para complejizar aún más esta fusión, Novalis toma como herramientas los géneros de la mitología y el Märchen, por medio de los cuales proyecta una representación del tiempo desprendido de su linealidad objetiva, pero también de su inmanencia subjetiva. En Heinrich von Ofterdingen, Novalis asume la búsqueda de una confluencia entre novela e historia, sujeto y objeto, interioridad y mundo exterior que emerge también en las notas y fragmentos en los que define su estética.In this article, we will analyze some of the different approaches to the representation of time in Heinrich von Ofterdingende Novalis (1772-1801), seeking not to exclude them from each other, but to combine them in the eclectic spirit that preaches the same author in his work. In Heinrich von Ofterdingen, Novalis attempts to coincide the representation of an objective and exterior time with a subjective and interior one, bringing together the two discursive genres that in his time are related to these two forms of representation: history and novel. In the “mythological novel” that Novalis plans to write, the categories of novel and history converge and, at the same time, are redefined. To further complete this fusion, Novalis takes as tools the genres of mythology and Märchen, by means of which he projects a representation of time detached from its objective linearity, but also from its subjective inmanence. In Heinrich von Ofterdingen, Novalis takes on the search for a confluence between novel and story, subject and object, interiority and external world that also emerges in the notes and fragments that define its aesthetics.Neste artigo, analisaremos algumas das fronteiras aproximadas à representação do tempo em Heinrich von Ofterdingende Novalis (1772-1801), buscando não excluí-las entre si, combinando-as no espírito ecléctico que pregou o mesmo autor em sua obra. En Heinrich von Ofterdingen, Novalis tentou fazer coincidir a representação de um tempo objetivo e exterior com um subjetivo e interior, reunindo os dois gêneros discursivos que em sua época se relacionavam a estas duas formas de representação: a história e a novela. Na “novela mitológica” que Novalis escreveu, as categorias de novela e história se fundiram e, ao mesmo tempo, foram redefinidas. Para completar ainda mais esta fusão, Novalis toma como herramientas os gêneros da mitologia e do Märchen, por meio de quais deles projeta uma representação do tempo desprendida de sua linearidade objetiva, mas também de sua inmanência subjetiva. Em Heinrich von Ofterdingen, Novalis assume a busca de uma confluência entre novela e história, assunto e objeto, interioridade e mundo exterior que emerge também nas notas e fragmentos nos que definem sua estética
Posttranslationale Regulation der Transportaktivität humaner kationischer Aminosäuretransporter (human cationic aminoacid transporter: hCATs)
Cells depend on transporters for communication, interaction, and the selective uptake of nutrients and other molecules. Despite their importance, the intricate regulatory mecha-nisms that govern transporter activity and surface expression are not fully understood for many of these vital membrane proteins. This work investigated the post-translational regulation of human cationic amino acid transporters (hCATs) by protein kinase C (PKC) involving Rho-GTPases (Cdc42, Rac1, and RhoA) and other potentially involved proteins.
The central finding of the work is that both PKC and Rho-GTPases, especially Cdc42, play a crucial role in modulating the transport activity of all four hCAT isoforms. Activation of PKC leads to a significant reduction in arginine uptake by the hCATs. This effect was demonstrated in Xenopus laevis oocytes as a model system and various human cell lines. Interestingly, the reduced arginine uptake is caused by the altered membrane localization of the transporters (induced endocytosis).
An important aspect of this work is the investigation of the interplay of Rho-GTPases in regulating hCAT transporters showing the involvement of these GTPases in adapting transporter activity to meet cellular arginine demand. The results suggest that the simul-taneous activation of PKC and Rho-GTPases could lead to complex regulation of hCAT transporters, involving a reduced localization of the transporters in the plasma mem-brane.
The importance of membrane localization for the function of hCAT transporters was par-ticularly emphasized in this work. Understanding the mechanisms that regulate mem-brane proteins, especially transporter proteins, is of central importance, as they represent both targets and sensors for the cell's environment.
In summary, this research makes an important contribution to understanding the com-plex regulation of amino acid transporters, especially hCATs. The results show that PKC and Rho-GTPases play a crucial role in modulating transport activity and that membrane localization of the transporters is an important factor for their function. The interaction between PKC and Rho-GTPases could represent a finely tuned system that controls amino acid uptake as needed.In dieser Arbeit wurde die posttranslationale Regulation der kationischen Aminosäuret-ransporter (hCATs) durch Proteinkinase C (PKC) unter Beteiligung der Rho-GTPasen (Cdc42, Rac1 und RhoA) und anderen potenziellen beteiligten Proteinen untersucht.
Zentrale Erkenntnis der Arbeit ist, dass sowohl PKC als auch Rho-GTPasen, insbesondere Cdc42, eine entscheidende Rolle bei der Modulation der Transportaktivität aller vier hCAT-Isoformen spielen. Die Aktivierung von PKC führt zu einer signifikanten Reduktion der Argininaufnahme durch die hCATs. Dieser Effekt konnte sowohl im Modellsystem der Xenopus-Oocyten als auch in verschiedenen humanen Zelllinien nachgewiesen werden. Interessanterweise wird die verminderte Argininaufnahme durch die veränderte Memb-ranlokalisation der Transporter (wahrscheinlich induzierte Endozytose) verursacht.
Ein weiterer wichtiger Aspekt der Arbeit ist die Untersuchung des Zusammenspiels von Rho-GTPasen bei der Regulation der hCAT-Transporter. Die Aktivierung von Rho-GTPasen z.B. durch EGF, deutet auf eine Beteiligung dieser GTPasen bei der Regulation der Trans-portaktivität hin. Die Ergebnisse legen nahe, dass die gleichzeitige Aktivierung von PKC und Rho-GTPasen zu einer komplexen Regulation der hCAT-Transporter führt, die sich in einer reduzierten Oberflächenexpression der Transporter äußert.
Die Bedeutung der Membranlokalisation für die Funktion der hCAT-Transporter wurde in dieser Arbeit besonders hervorgehoben. Es ist von zentraler Bedeutung, die Mechanismen zu verstehen, die die Membranproteine, insbesondere die Transporterproteine, regulie-ren, da sie sowohl Angriffspunkte als auch Sensoren für die Umgebung der Zelle darstel-len.
Zusammenfassend lässt sich sagen, dass diese Forschungsarbeit einen wichtigen Beitrag zum Verständnis der komplexen Regulation von Aminosäuretransportern, insbesondere der hCATs, leistet. Die Ergebnisse zeigen, dass PKC und Rho-GTPasen eine entscheidende Rolle bei der Modulation der Transportaktivität spielen und dass die Membranlokalisati-on der Transporter ein wichtiger Faktor für ihre Funktion ist. Die Interaktion zwischen PKC und Rho-GTPasen könnte ein fein abgestimmtes System darstellen, das die Aminosäu-reaufnahme bedarfsgerecht steuert.XIX, 162 Seiten ; Illustrationen, Diagramm
History as suspense: The representation of time in Novalis’ Heinrich von Ofterdingen
En este artículo, analizaremos algunas de las distintas aproximaciones a la representación del tiempo en Heinrich von Ofterdingende Novalis (1772-1801), buscando no excluirlas entre sí, sino combinarlas en el espíritu ecléctico que pregona el mismo autor en su obra. En Heinrich von Ofterdingen, Novalis intenta hacer coincidir la representación de un tiempo objetivo y exterior con uno subjetivo e interior, reuniendo los dos géneros discursivos que en su época se relacionan a estas dos formas de representación: la historia y la novela. En la “novela mitológica” que planea escribir Novalis, las categorías de novela e historia confluyen y, al mismo tiempo, se redefinen. Para complejizar aún más esta fusión, Novalis toma como herramientas los géneros de la mitología y el Märchen, por medio de los cuales proyecta una representación del tiempo desprendido de su linealidad objetiva, pero también de su inmanencia subjetiva. En Heinrich von Ofterdingen, Novalis asume la búsqueda de una confluencia entre novela e historia, sujeto y objeto, interioridad y mundo exterior que emerge también en las notas y fragmentos en los que define su estética.In this article, we will analyze some of the different approaches to the representation of time in Novalis' Heinrich von Ofterdingen, seeking not to exclude them from each other, but to combine them in the eclectic spirit proclaimed by the author himself in his work. In Heinrich von Ofterdingen, Novalis tries to make the representation of an objective and exterior time coincide with a subjective and interior one, bringing together the two discursive genres that in his time are related to these two forms of representation: history and novel. In the "mythological novel" that Novalis plans to write, the categories of novel and history converge and, at the same time, are redefined. To further complexify this fusion, Novalis takes as his tools the genres of mythology and Märchen, by means of which he projects a representation of time detached from its objective linearity, but also from its subjective immanence. In Heinrich von Ofterdingen, Novalis assumes the ambitious search for a confluence between novel and history, subject and object, interiority and external world also referred to in the notes and fragments in which he defines his aesthetics.Fil: Closs, Marina. Universidad Nacional de General Sarmiento. Instituto del Desarrollo Humano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Time-resolved and low-temperature absorption spectroscopic studies on 10-silaanthracen-9(10H)-ylidene
PT: J; CR: BRAUER BE, 1982, J AM CHEM SOC, V104, P6814 CARMAN RM, 1968, TETRAHEDRON LETT, P2723 CLOSS GL, 1966, J CHEM PHYS, V44, P413 CLOSS GL, 1976, J AM CHEM SOC, V98, P8190 EISENTHAL KB, 1980, J AM CHEM SOC, V102, P6563 GRILLER D, 1982, J AM CHEM SOC, V104, P6813 HAYASHI H, 1980, B CHEM SOC JPN, V53, P1519 MASUHARA H, 1968, B CHEM SOC JPN, V41, P2319 MASUHARA H, 1971, B CHEM SOC JPN, V44, P38 MORITANI I, 1968, J AM CHEM SOC, V90, P5918 RICHIE A, 1965, CHEM BER, V98, P3627 SEKIGUCHI A, 1982, B CHEM SOC JPN, V55, P1675 SEKIGUCHI A, 1982, TETRAHEDRON LETT, V23, P4095 WONG PC, 1981, J AM CHEM SOC, V103, P5934 WONG PC, 1982, J AM CHEM SOC, V104, P5106 ZUPANCIC JJ, 1980, J AM CHEM SOC, V102, P5958 ZUPANCIC JJ, 1981, J AM CHEM SOC, V103, P2423 ZUPANCIC JJ, 1981, J AM CHEM SOC, V103, P944; NR: 18; TC: 7; J9: CHEM LETT; PG: 4; GA: RB995Source type: Electronic(1
The rationale for a wider concept of Inclusive Education for teacher education: A case-study of Serbia
Teacher education for inclusive education (IE) is recognized as vital for improving quality and equity in education globally. In the Western Balkan countries it is also part of the transition process towards joining the European Union and has attracted international funding for IE-related projects. A key finding from research funded by the European Training Foundation, carried out by the authors as members of a seven-country research team in 2009-2010, was that the prevailing local understanding of IE was very narrow. In this article we hypothesize the reasons for this finding. We use a case study of school and teacher education systems in Serbia to explore how this understanding has constrained the development of IE and associated teacher education and limited the efficacy of some recent internationally supported developments. We identify both challenges and possible ways forward for teacher education for IE based on promoting a concept of IE that is both collaboratively agreed and comprehensive. © 2012 UNESCO IBE
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