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| 2. |
- Cheng, Fang, et al.
(författare)
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Copper-dependent co-internalization of the prion protein and glypican-1.
- 2006
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Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 98:5, s. 1445-1457
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate chains have been found to be associated with amyloid deposits in a number of diseases including transmissible spongiform encephalopathies. Diverse lines of evidence have linked proteoglycans and their glycosaminoglycan chains, and especially heparan sulfate, to the metabolism of the prion protein isoforms. Glypicans are a family of glycosylphosphatidylinositol-anchored, heparan sulfate-containing, cell-associated proteoglycans. Cysteines in glypican-1 can become nitrosylated by endogenously produced nitric oxide. When glypican-1 is exposed to a reducing agent, such as ascorbate, nitric oxide is released and autocatalyses deaminative cleavage of heparan sulfate chains. These processes take place while glypican-1 recycles via a non-classical, caveolin-associated pathway. We have previously demonstrated that prion protein provides the Cu2+ ions required to nitrosylate thiol groups in the core protein of glypican-1. By using confocal immunofluorescence microscopy and immunomagnetic techniques, we now show that copper induces co-internalization of prion protein and glypican-1 from the cell surface to perinuclear compartments. We find that prion protein is controlling both the internalization of glypican-1 and its nitric oxide-dependent autoprocessing. Silencing glypican-1 expression has no effect on copper-stimulated prion protein endocytosis, but in cells expressing a prion protein construct lacking the copper binding domain internalization of glypican-1 is much reduced and autoprocessing is abrogated. We also demonstrate that heparan sulfate chains of glypican-1 are poorly degraded in prion null fibroblasts. The addition of either Cu2+ ions, nitric oxide donors, ascorbate or ectopic expression of prion protein restores heparan sulfate degradation. These results indicate that the interaction between glypican-1 and Cu2+-loaded prion protein is required both for co-internalization and glypican-1 self-pruning.
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| 3. |
- Kaplan, Anders, et al.
(författare)
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An Automated Method for Scanning LC−MS Data Sets for Significant Peptides and Proteins, Including Quantitative Profiling and Interactive Confirmation : An Automated Method for Scanning LC−MS Data Sets for Significant Peptides and Proteins, Including Quantitative Profiling and Interactive Confirmation
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:7, s. 2888-2895
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Tidskriftsartikel (refereegranskat)abstract
- Differential quantification of proteins and peptides by LC-MS is a promising method to acquire knowledge about biological processes, and for finding drug targets and biomarkers. However, differential protein analysis using LC-MS has been held back by the lack of suitable software tools. Large amounts of experimental data are easily generated in protein and peptide profiling experiments, but data analysis is time-consuming and labor-intensive. Here, we present a fully automated method for scanning LC-MS/MS data for biologically significant peptides and proteins, including support for interactive confirmation and further profiling. By studying peptide mixtures of known composition, we demonstrate that peptides present in different amounts in different groups of samples can be automatically screened for using statistical tests. A linear response can be obtained over almost 3 orders of magnitude, facilitating further profiling of peptides and proteins of interest. Furthermore, we apply the method to study the changes of endogenous peptide levels in mouse brain striatum after administration of reserpine, a classical model drug for inducing Parkinson disease symptoms.
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| 4. |
- Lindqvist, Christina, 1975-
(författare)
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L'influence translinguistique dans l'interlangue française : Étude de la production orale d'apprenants plurilingues
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present study concerns cross-linguistic influence in the spoken French of multilingual learners. The main purpose is to investigate to what degree, and in what manner, previously acquired languages (L1, L2(s)) influence the target language, L3. Given the fact that the study only concerns spoken interlanguage, it makes use of a psycholinguistic perspective, which takes models of oral production into account. The analysis is divided into two main parts. The first concerns the oral production of 30 Swedish learners of French, who fall into three groups according to their previous exposure to French: beginners, secondary school students and university students. The results show that proficiency in the L3 is crucial in at least two ways. First, there is a correlation between the level of proficiency in the L3 and the number of instances of cross-linguistic influence in that the least advanced learners produce the highest number of cross-linguistic lexemes, whereas the most advanced learners produce the lowest number. Second, the level of proficiency in the L3 is decisive for the number of background languages (L1, L2) used during oral production in L3: the lower the proficiency in the L3, the more background languages are used, and vice versa. The second part of the analysis contains six case studies of learners with partly different L1s and L2s. It focuses on the roles of the background languages during conversation in L3 and on the factors contributing to the attribution of these roles. The results point at both similarities and differences between the learners with respect to the roles of the background languages. A result common to all the learners is the use of Swedish L1/L2 and English L1 as an instrumental language, i.e. a language used rather strategically with a communicative purpose. The use of these languages in this function seems to be due to the fact that Swedish and English are shared languages between the learner and the interlocutor.
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| 5. |
- Rosenberg, David, 1957-
(författare)
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Psychiatric disability in the community : Surveying the social landscape in the post-deinstitutional era
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation presents a discussion of life in the community for people experiencing psychiatric disabilities in the post-deinstitutional era, with the goal of developing knowledge that can suggest a focus for planning more relevant services and supports. While evaluations of deinsitutionalization have focused on possibilities for providing community, rather than hospital-based services for these individuals, the intention was to support a participatory life in the community, a life defined by much more than just care and treatment. The Mental Health Care Reform of 1995 in Sweden paved the way for this more community-based view of needs related to psychiatric disabilities, as local social services became responsible for supports to a participatory life, “like all others”. The general aim of this dissertation was to explore and analyze the results of a series of surveys of psychiatric disability, in order to develop knowledge of the social context of the lives which individuals experiencing these disabilities live in the community. More specifically, the aim was to;• describe contacts/interactions between these individuals and the societal organisations with which they seek services or support.• describe characteristics and needs of the individuals identified in these studies as expressed by representatives of the helping system and users who participated in the studies.• develop knowledge of the mechanisms involved in these patterns of seeking support by exploring and analyzing the empirical results within the context of theoretical (social) approaches to understanding psychiatric disability.The findings of this research are based on an analysis of the quantitative and qualitative results of three studies involving seven municipalities in northern Sweden. Of the 2385 individuals who personnel identified as meeting the criteria for a serious psychiatric disability, approximately half did not have active contact with the formal mental health system. They did however seek services, supports and opportunities that they saw as relevant to their lives and needs as community members. These included health, housing and financial assistance as well as opportunities for education and employment. Various mechanisms operating in the community, including stigmatizing attitudes, exclusionary practices and organizational systems and rules, were seen by respondents as obstacles to these individuals developing meaningful and participatory roles.Social approaches, when utilized to explore and understand issues regarding psychiatric disability in the community, support a focus on the social landscape in which ndividuals experience disability-related needs, as well as the dynamics of the disability experience. While in the deinstitutional era, needs were assessed relative to the individual’s relationship to the psychiatric care system, in the post-deinstitutional era, they should be assessed from a participation-relative perspective, where their position as community member, rather than as patient or client, describes the social location of need. Specialized support to general community resources and services in addition to psychiatrically defined supports, would likely reach many, especially younger individuals who might otherwise become seriously disabled.
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| 6. |
- Rosenberg, David, et al.
(författare)
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The Social Location of Need. Surveying Psychiatric Disability in the Community
- 2008
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Ingår i: Scandinavian Journal of Disability Research. - 1501-7419. ; Vol 11:In print, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- The majority of studies related to the needs of individuals with psychiatric disabilities focus on their meeting with the traditional mental health system. Environmentally relative conceptions of disability have only shown limited success in expanding the views of the field of community psychiatry to include social and organisational contexts. Swedish disability policy emphasises the individual's ability to participate in community life and may therefore be said to reflect a social approach to disability, in contrast to an exclusively medical perspective that focuses on deficits and the individual's need for psychiatrically defined services. In this study, inventories of need for people with psychiatric disabilities were completed for three municipalities. Results indicated that these individuals resist psychiatrically defined categories as they seek supports based on their own experiences of need in the community.
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| 7. |
- Rosenberg, David, 1957-, et al.
(författare)
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The social location of need – surveying psychiatric disability in the community
- 2009
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Ingår i: Scandinavian Journal of Disability Research. - : Taylor & Francis. - 1501-7419 .- 1745-3011. ; 11:1, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- The majority of studies related to the needs of individuals with psychiatric disabilities focus on their meeting with, and use of, the traditional mental health system. Environmentally relative conceptions of disability have only shown limited success in expanding the views of the field of community psychiatry to include social and organizational contexts. Swedish disability policy emphasizes the individual's ability to participate in community life and may therefore be said to reflect a social approach to disability, in contrast to an exclusively medical perspective that focuses on deficits and the individual's need for psychiatrically defined services. In this study, inventories of need for people with psychiatric disabilities, a legislated responsibility of the social service system in Sweden, were completed for three municipalities. Results indicated that these individuals resist psychiatrically defined categories as they seek supports based on their own experience of need in the community.
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