Inom dagens musikklimat har DJ:andet och dess utövare kommit att ta en allt större plats. Mycket av den musik som produceras och spelas i offentligheten har rötter i denna kultur. Dock så lyser den med sin frånvaro inom musikundervisningen i skolan. Detta examensarbete syftar till att undersöka hur DJ:ande kan inkluderas i musikundervisningen på gymnasiet. Sex kvalitativa intervjuer med yrkesverksamma DJ:s i Stockholmsområdet genomfördes för att undersöka vilka kunskaper som är viktiga och om DJ:ande kan fungera som ett pedagogiskt verktyg. Även diskjockeyns roll inom populärmusiken undersöks och vilka kurser inom ämnet musik på gymnasiet som bäst lämpar sig för integration av DJ:ande. Resultatet visar att DJ:ande har en central roll inom populärmusikens utveckling, speciellt från 1970-talet och framåt. DJ:ande kan inkluderas inom kurser i ämnet musik på gymnasiet men lämpar sig mindre bra som pedagogiskt verktyg. Förmågan att läsa ett dansgolv och att ha en stor kunskap om musikaliska verk är viktiga kunskaper för DJ:s.

Projektet handlar om hur jag har lärt mig grunderna för att kunna DJ:a techno. Detta innebär bland annat att i realtid överlagra och sammanfoga ljudkällor för att skapa en musikalisk helhet. Under denna process har jag lärt mig om olika mixningstekniker, hård- och mjukvara, repertoar samt både DJ:andet och technons historia. Detta har i sin tur väckt tankar om hur jag i framtiden kan använda DJ:ande som ett redskap inom musikundervisning och som ett yrke. Projektet har konkret resulterat i en mixtape som finns tillängligt via det tryckta exemplaret samt en spelning på en privat fest.

Parkinson’s disease (PD) is a common neurodegenerative disorder symptomatically characterized by motor dysfunction caused by the selective loss of nigral dopamine neurons within midbrain. The pathogenesis of PD remains unclear. Although, originally thought to be sporadic, about ten percent of PD is familial. The recent elucidation of mutations in genes linked to the disease has offered potential for new animal models and understanding of PD pathogenesis. DJ-1 and LRRK2 are genes linked to autosomal recessive juvenile-onset PD and autosomal-dominant late onset PD, respectively. How mutations in these two genes leads to PD remains uncertain and is plagued by poor murine models that do not recapitulate the human condition. The following dissertation attempts to characterize both mouse and fly models of DJ-1 and LRRK2 mediated PD and elucidate other genetic modifiers that may contribute to PD. Firstly, the DJ-1 null mouse model, which lacks cell death, was improved by backcrossing to a pure C57-Bl6 background. These DJ-1 null mice display a robust and progressive unilateral-to-bilateral loss of nigral neurons accompanied by motor deficits in aged mice. Secondly, a large scale screen was performed in Drosophila to determine genes that modify mutant LRRK2 toxicity in both the eye and dopaminergic neurons of the fly. The screen revealed 36 genetic interactors that either suppressed or enhanced LRRK2 induced cell death in the fly. One of these interactors was SCAR (human WAVE-2). Due to the role WAVE-2 is known to have in immune cell phagocytic function, we demonstrate that LRRK2 deficient/G2019S murine myeloid cells have impaired/enhanced phagocytic activity which is correlated with a decrease/increase in WAVE-2 protein, respectively. We furthermore suggest that LRRK2 and WAVE-2 may bind directly and that LRRK2 phosphorylates WAVE-2 to maintain its stability. Finally, as a proof of concept, we constructed a novel animal model of LRRK2 in flies by limiting LRRK2 over expression to central phagocytes of the Drosophila brain. This causes lifespan deficits and motor dysfunction that can be rescued by down-regulation of SCAR. Collectively, this body of work helped create the first germ-line, genetic model of PD that recapitulates nigral loss and elucidated LRRK2 interactors in the fly. Furthermore, we demonstrate that one of these interactors mediated LRRK2’s modulation of phagocytic activity that may contribute to the pathogenesis of PD.

Parkinson’s disease (PD) is the most common movement neurodegenerative disease affecting approximately 1% of the population over 60. Though originally thought to be sporadic in nature, a genetic component is increasingly being linked to the disease. Of these genes, mutations in DJ-1 (PARK7) cause early onset autosomal recessive PD. Initial workup of the DJ-1 protein has suggested that it may act in the cell by combatting oxidative stress though the mechanism by which it does so is unclear. Thus, though much work has attempted to elucidate a function at the biochemical, cellular and organismal level, the overt physiological role of DJ-1 remains elusive. In this dissertation, we explore the mechanisms through which DJ-1 confers neuroprotection, particularly in the case of oxidative stress insult. We demonstrate that DJ-1 acts through the pro-survival protein AKT to accomplish its neuroprotective function. Moreover, we note that DJ-1 likely serves its role as an antioxidant through the NRF2 master antioxidant regulator pathway a pathway that is, itself, likely to be regulated by AKT. Together, our results demonstrate that neuroprotection by DJ-1 is done through a signaling pathway involving both AKT and NRF2 and that disruption of the former in PD likely results in abolishing this signaling pathway. Finally, to generate a better animal model of PD, we demonstrate that backcrossing DJ-1 null mice - which originally did not demonstrate any gross histopathological or behavioral phenotypes – display unilateral dopaminergic degeneration that progresses to bilateral degeneration with aging, a feature reminiscent of classical PD progression. Collectively, this thesis takes a two-sided approach to address the biochemical and physiological functions of DJ-1 within the cell and the mouse in hopes of elucidating mechanisms of neuronal death to devise better translational therapies.

No description available.

Parkinson’s disease (PD) is the most common movement neurodegenerative disease affecting approximately 1% of the population over 60. Though originally thought to be sporadic in nature, a genetic component is increasingly being linked to the disease. Of these genes, mutations in DJ-1 (PARK7) cause early onset autosomal recessive PD. Initial workup of the DJ-1 protein has suggested that it may act in the cell by combatting oxidative stress though the mechanism by which it does so is unclear. Thus, though much work has attempted to elucidate a function at the biochemical, cellular and organismal level, the overt physiological role of DJ-1 remains elusive. In this dissertation, we explore the mechanisms through which DJ-1 confers neuroprotection, particularly in the case of oxidative stress insult. We demonstrate that DJ-1 acts through the pro-survival protein AKT to accomplish its neuroprotective function. Moreover, we note that DJ-1 likely serves its role as an antioxidant through the NRF2 master antioxidant regulator pathway a pathway that is, itself, likely to be regulated by AKT. Together, our results demonstrate that neuroprotection by DJ-1 is done through a signaling pathway involving both AKT and NRF2 and that disruption of the former in PD likely results in abolishing this signaling pathway. Finally, to generate a better animal model of PD, we demonstrate that backcrossing DJ-1 null mice - which originally did not demonstrate any gross histopathological or behavioral phenotypes – display unilateral dopaminergic degeneration that progresses to bilateral degeneration with aging, a feature reminiscent of classical PD progression. Collectively, this thesis takes a two-sided approach to address the biochemical and physiological functions of DJ-1 within the cell and the mouse in hopes of elucidating mechanisms of neuronal death to devise better translational therapies.

Oxidative stress and mutations in DJ-1, a redox sensitive protein, are linked to Parkinson's Disease. The protective mechanism of DJ-1 is unclear. I hypothesized that: 1) DJ-1 mediates protection by translocating to mitochondria after oxidative stress and, 2) when DJ-1 is downregulated, apoptotic pathways regulated by calcineurin are also downregulated. In PC12 cells and rat cortical neurons, oxidative stress resulted in the upregulation of DJ-1 and increased DJ-1 in the nucleus, but did not increase mitochondrial translocation of DJ-1. In cortical neurons and wildtype mouse embryonic fibroblasts, H2O2 induced cleavage of CnA into an inactive fragment. DJ-1 knockout fibroblasts had less nuclear localization of the transcription factor NFATc4, a substrate of calcineurin involved in apoptosis. H2O2 increased CnA cleavage in DJ-1 knockout fibroblasts, but NFATc4 localization was unchanged. These results suggest that the downregulation of apoptotic pathways regulated by calcineurin may be a compensatory response to the downregulation of DJ-1.

Oxidative stress and mutations in DJ-1, a redox sensitive protein, are linked to Parkinson's Disease. The protective mechanism of DJ-1 is unclear. I hypothesized that: 1) DJ-1 mediates protection by translocating to mitochondria after oxidative stress and, 2) when DJ-1 is downregulated, apoptotic pathways regulated by calcineurin are also downregulated. In PC12 cells and rat cortical neurons, oxidative stress resulted in the upregulation of DJ-1 and increased DJ-1 in the nucleus, but did not increase mitochondrial translocation of DJ-1. In cortical neurons and wildtype mouse embryonic fibroblasts, H2O2 induced cleavage of CnA into an inactive fragment. DJ-1 knockout fibroblasts had less nuclear localization of the transcription factor NFATc4, a substrate of calcineurin involved in apoptosis. H2O2 increased CnA cleavage in DJ-1 knockout fibroblasts, but NFATc4 localization was unchanged. These results suggest that the downregulation of apoptotic pathways regulated by calcineurin may be a compensatory response to the downregulation of DJ-1.

The following thesis explores the conditions of possibility for remix culture through the work of Paul D. Miller, a.k.a. Dj Spooky that Subliminal Kid. Beginning with the impact and vertigo of Dj Spooky's language and practice, it explores the reciprocal relation of media to language in the construction of the proper (property) and the author (authority). The context of Dj Spooky as a conceptual artist and the material of his book, Rhythm Science , provides the setting and scenario for extended readings of the paradoxes and cultural effects of remix culture, including the relation of writing to djing, practices of incorporative media, tactics of digital email, combat over copyright, and the sampling of the archive. The formalization of these effects is outlined by writing in-between the theories of Gilles Deleuze and Jacques Derrida. This formalization signals the advent of the network over the territory, the form over the content, the formal over the expressive (while nonetheless recognising the distinction, persistence and difference of these terms). It argues that remix culture regenerates and redefines the parameters of the author and the proper through technological and political forces that nonetheless retain their structures of power. The conduit and context of this formal, paradoxical transformation are the cultural forces of global and digital networks, which is here defined as the "oceanic network."

Parkinson’s disease (PD) is the most common movement neurodegenerative disease affecting approximately 1% of the population over 60. Though originally thought to be sporadic in nature, a genetic component is increasingly being linked to the disease. Of these genes, mutations in DJ-1 (PARK7) cause early onset autosomal recessive PD. Initial workup of the DJ-1 protein has suggested that it may act in the cell by combatting oxidative stress though the mechanism by which it does so is unclear. Thus, though much work has attempted to elucidate a function at the biochemical, cellular and organismal level, the overt physiological role of DJ-1 remains elusive. In this dissertation, we explore the mechanisms through which DJ-1 confers neuroprotection, particularly in the case of oxidative stress insult. We demonstrate that DJ-1 acts through the pro-survival protein AKT to accomplish its neuroprotective function. Moreover, we note that DJ-1 likely serves its role as an antioxidant through the NRF2 master antioxidant regulator pathway a pathway that is, itself, likely to be regulated by AKT. Together, our results demonstrate that neuroprotection by DJ-1 is done through a signaling pathway involving both AKT and NRF2 and that disruption of the former in PD likely results in abolishing this signaling pathway. Finally, to generate a better animal model of PD, we demonstrate that backcrossing DJ-1 null mice - which originally did not demonstrate any gross histopathological or behavioral phenotypes – display unilateral dopaminergic degeneration that progresses to bilateral degeneration with aging, a feature reminiscent of classical PD progression. Collectively, this thesis takes a two-sided approach to address the biochemical and physiological functions of DJ-1 within the cell and the mouse in hopes of elucidating mechanisms of neuronal death to devise better translational therapies.