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Selected AbstractsMalondialdehyde modification of myelin oligodendrocyte glycoprotein leads to increased immunogenicity and encephalitogenicityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007Maja Wållberg Abstract Self proteins may become autoantigenic through structural modification. We studied malondialdehydation of recombinant rat (rr) myelin oligodendrocyte glycoprotein (MOG), an autoantigen in multiple sclerosis. Malondialdehyde (MDA) modification changed protein weight and charge, the location of these adducts being mapped by Fourier transform ion cyclotron resonance. Molecular modelling revealed significant differences in the MDA-rrMOG three-dimensional structure. DBA/1 mice immunised with MDA-rrMOG developed greater proliferative responses and more severe experimental autoimmune encephalomyelitis than mice immunised with unmodified rrMOG. MDA-rrMOG was taken up more effectively by antigen-presenting cells (APC), at least partially through scavenger receptors. Exposure to MDA-rrMOG led to increased expression of IL-23, IL-12 and IL-12R, indicating a role not only for increased antigen uptake but also for activation of APC. We thus provide biochemical, structural, immunological and clinical data that suggest that the post-translationally modified form of this myelin autoantigen is a more relevant form of the molecule. [source] Interleukin-15 is not required for the induction or maintenance of orally induced peripheral toleranceIMMUNOLOGY, Issue 3 2004Owain R. Millington Summary Orally induced tolerance is a physiologically relevant form of peripheral tolerance, which is believed to be important for the prevention of pathological immune responses in the gut. Of several mechanisms proposed to mediate oral tolerance, one that has received much attention recently is the concept of regulatory CD4+ T cells. As recent studies have suggested that interleukin (IL)-15 may be important for the differentiation and maintenance of regulatory CD4+ T cells, we have examined the role of IL-15 in oral tolerance, using a soluble form of the IL-15 receptor (sIL-15R) which blocks the biological effects of IL-15 in vivo. Oral tolerance induced by feeding mice ovalbumin (OVA) in a low-dose regimen believed to induce regulatory T cell activity was not affected by the administration of sIL-15R during either the induction or maintenance phase of tolerance. Thus, oral tolerance does not involve an IL-15-dependent mechanism. [source] Human spastin has multiple microtubule-related functionsJOURNAL OF NEUROCHEMISTRY, Issue 5 2005Sara Salinas Abstract Hereditary spastic paraplegias (HSPs) are neurodegenerative diseases caused by mutations in more than 20 genes, which lead to progressive spasticity and weakness of the lower limbs. The most frequently mutated gene causing autosomal dominant HSP is SPG4, which encodes spastin, a protein that belongs to the family of ATPases associated with various cellular activities (AAAs). A number of studies have suggested that spastin regulates microtubule dynamics. We have studied the ATPase activity of recombinant human spastin and examined the effect of taxol-stabilized microtubules on this activity. We used spastin translated from the second ATG and provide evidence that this is the physiologically relevant form. We showed that microtubules enhance the ATPase activity of the protein, a property also described for katanin, an AAA of the same spastin subgroup. Furthermore, we demonstrated that human spastin has a microtubule-destabilizing activity and can bundle microtubules in vitro, providing new insights into the molecular pathogenesis of HSP. [source] Estimating the Causal Effects of Media Coverage on Policy-Specific KnowledgeAMERICAN JOURNAL OF POLITICAL SCIENCE, Issue 1 2009Jason Barabas Policy facts are among the most relevant forms of knowledge in a democracy. Although the mass media seem like an obvious source of policy-specific information, past research in this area has been plagued by design and methodological problems that have hindered causal inferences. Moreover, few studies include measures of media content, preventing researchers from being able to say what it is about media coverage that influences learning. We advance the literature by employing a simple but underutilized approach for estimating the causal effects of news coverage. Drawing upon a unique collection of cross-sectional survey data, we make within-survey/within-subjects comparisons under conditions of high and low media coverage. We show how the volume, breadth, and prominence of news media coverage increase policy-specific knowledge above and beyond common demographic factors. [source] Engineering the prion protein using chemical synthesisCHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2001H.L. Ball Abstract: In recent years, the technology of solid-phase peptide synthesis (SPPS) has improved to the extent that chemical synthesis of small proteins may be a viable complementary strategy to recombinant expression. We have prepared several modified and wild-type prion protein (PrP) polypeptides, of up to 112 residues, that demonstrate the flexibility of a chemical approach to protein synthesis. The principal event in prion disease is the conformational change of the normal, ,-helical cellular protein (PrPC) into a ,-sheet-rich pathogenic isoform (PrPSc). The ability to form PrPSc in transgenic mice is retained by a 106 residue ,mini-prion' (PrP106), with the deletions 23,88 and 141,176. Synthetic PrP106 (sPrP106) and a His-tagged analog (sPrP106HT) have been prepared successfully using a highly optimized Fmoc chemical methodology involving DCC/HOBt activation and an efficient capping procedure with N -(2-chlorobenzyloxycarbonyloxy) succinimide. A single reversed-phase purification step gave homogeneous protein, in excellent yield. With respect to its conformational and aggregational properties and its response to proteinase digestion, sPrP106 was indistinguishable from its recombinant analog (rPrP106). Certain sequences that proved to be more difficult to synthesize using the Fmoc approach, such as bovine (Bo) PrP(90,200), were successfully prepared using a combination of the highly activated coupling reagent HATU and t -Boc chemistry. To mimic the glycosylphosphatidyl inositol (GPI) anchor and target sPrP to cholesterol-rich domains on the cell surface, where the conversion of PrPC is believed to occur, a lipophilic group or biotin, was added to an orthogonally side-chain-protected Lys residue at the C-terminus of sPrP sequences. These groups enabled sPrP to be immobilized on either the cell surface or a streptavidin-coated ELISA plate, respectively, in an orientation analogous to that of membrane-bound, GPI-anchored PrPC. The chemical manipulation of such biologically relevant forms of PrP by the introduction of point mutations or groups that mimic post-translational modifications should enhance our understanding of the processes that cause prion diseases and may lead to the chemical synthesis of an infectious agent. [source] The Role of Indigenous Peoples in Guatemalan Political Advertisements: An Ethnographic Content AnalysisCOMMUNICATION, CULTURE & CRITIQUE, Issue 3 2010Colleen Connolly-Ahern This study investigates the current status of indigenous peoples within Guatemalan society, as articulated in one of the most relevant forms of modern communication, political advertising, and defined by one of the most relevant forms of self-expression to the indigenous peoples of Guatemala, the traje. Using ethnographic content analysis, the study examines the roles and characterizations of indigenous people in 67 television commercials from across the Guatemalan political spectrum. Results indicate that indigenous people are most often seen as "crowd members," and are never given important roles, such as "candidate endorser" or "undecided voter." Overall, wearing traje is associated with helplessness and separateness. The commercials of Q'iché Maya candidate Rigoberta Menchú exhibited many of the same characteristics of other candidates. Le rôle des peuples autochtones dans les publicités politiques guatémaltèques : une analyse de contenu ethnographique Colleen Connolly-Ahern & Antoni Castells i Talens Cette étude explore le statut actuel des peuples autochtones dans la société guatémaltèque, telle qu'elle est articulée dans l'une des formes les plus appropriées de communication moderne, les publicités politiques, et telle que définie par l'une des formes d'expression des peuples autochtones du Guatemala les plus pertinentes, le «traje». Par une analyse de contenu ethnographique, l'étude explore les rôles et les représentations des peuples autochtones dans 67 publicités télévisées couvrant le spectre politique du Guatemala. Les résultats indiquent que les peuples autochtones sont le plus souvent vus comme des «membres de la foule». Ils n'ont jamais de rôles importants comme celui de «partisan d'un candidat» ou d'«électeur indécis'. Dans l'ensemble, le port du «traje» est associéà l'impuissance et à la différence. Les publicités de la candidate maya k'iche' Rigoberta Menchú présentaient plusieurs des mêmes caractéristiques que celles des autres candidats. El Rol de las Personas Indígenas en la Publicidad Política de Guatemala: Un Análisis de Contenido Etnográfico Colleen Connolly-Ahern & Antoni Castells i Talens Advertising and Public Relations College of Communications, Penn State University, State College, PA 16802, USA Resumen Este estudio investiga el estado corriente de las personas indígenas dentro de la sociedad Guatemalteca, articulado en una de las formas más relevantes de la comunicación moderna, la publicidad política, y definido por una de las formas más relevantes de auto expresión de las personas Indígenas de Guatemala, el traje. Usando un análisis de contenido etnográfico, este estudio examina los roles y las caracterizaciones de las personas indígenas en 67 comerciales de televisión a través del espectro político Guatemalteco. Los resultados indican que las personas indígenas son vistas más a menudo como "miembros de la multitud'' y nunca se les da roles importantes tales como ,,el candidato de la representación'' o ,,el votante indeciso. '' En general, el uso del traje está asociado con la impotencia y la separación. Los comerciales de la candidata Q'ich,e Maya Rigoberta Menchú exhibieron muchas de las mismas características de los otros candidatos. [source] |