14,515 research outputs found

    Rethinking live electronic music: a DJ perspective

    No full text
    The author critiques the conventional understanding of live electronic music through empirical research on his own DJ practice and investigates others working in the field. In reviewing the opinions of theorists and practitioners in both the live electronic music genre and DJ-ing he argues against the body/machine dialectic that has determined much of the thinking in the former. The author forms a notion of the DJ as a real-time composer working beyond traditional binary distinctions who brings the human body and machine into a mutual relationship. Through practice-led research he charts an investigation beginning in physical human gesture and culminating in digital machine repetition. He concludes that mechanical and digital repetition do not obscure human agency in the production of live works and that this concern is imaginary

    Characterisation of DJ1 (PARK7) in human brain: possible involvement in idiopathic Parkinson's disease and other neurodegenerative disorders

    No full text
    Mutations in the DJ‐1 gene can induce the development of early‐onset Parkinson's disease (PD) through a loss of protein function. Currently any possible role for DJ‐1 in sporadic PD remains undetermined. To address this, we have studied the characteristics and activities of DJ‐1 in post‐mortem human brain tissue in order to gain insights into its contribution to the development of PD and other neurodegenerative disorders. Western blotting revealed DJ‐1 protein expression to be reduced in several brain regions associated with PD pathology including nigra, striatum and frontal cortex. Similarly levels of DJ‐1 mRNA were also shown to also be lower in PD striatum and frontal cortex suggesting a transcriptional regulation of protein expression in human brain. Further analysis of DJ‐1 gene expression showed PD related changes to be variable throughout the brain, with regions like the amygdala and entorhinal cortex displaying an up‐regulation. DJ‐1 protein was also shown to undergo increased oxidation in PD cases, highlighting the elevated oxidative stress conditions in PD. By using immunoprecipitation to investigate a possible role for DJ‐1 as an in vivo regulator of translation, we found DJ‐1 protein associates with RNA transcripts for selenoproteins, PTEN/Akt pathway components and mitochondrial subunits of complex 1. Protein levels for a number of these transcripts were altered in PD tissue without any parallel change in mRNA levels. DJ‐1 is reportedly involved in a diverse range of cellular activities and its proclivity to associate with multiple RNA species provides a simple biochemical mechanism for this. Moreover it demonstrates that under conditions of elevated oxidative stress, DJ‐1 can instigate a rapid and compartmentalised up‐regulation of pro‐survival proteins in a transcriptionally independent manner. Analysis of DJ‐1 in tauopathies showed co‐localisation with 3R and 4R tau, implicating a possible chaperone function for DJ‐1. Unlike in PD, no altered expression of DJ‐1 mRNA and protein was observed

    DJ-1 knockdown in BV-2 microglia cells enhances LPS-induced death of co-cultured SH-SY5Y neuronal cells.

    No full text
    In the co-culture device, control vector- or DJ-1 shRNA-transfected BV-2 cells were cultured in the upper inserts, while SH-SY5Y cells were cultured in the lower plate wells. Cell viability of SH-SY5Y was evaluated by using MTT assay (A) and methylene blue assay (B). Note that LPS (300 ng/ml, for 18 hours) reduced viability of neuronal cells, which was further decreased by co-culture with DJ-1-knockdown BV-2 cells. The viability was markedly decreased in co-culture with DJ-1-knockdown BV-2 cells and LPS treatment, which can be antagonized by IFN-γ and/or I-TAC neutralizing antibody. Data were normalized as percentage of mean neuron number in the co-culture without any treatment (con) and presented as mean ± S.E.M. (n = 4–5 for each group) * p<0.05, # p<0.05 as compared with DJ-1-knockdown BV-2 cells with LPS treatment.</p

    DJ-1 knockdown increases LPS-induced cytokine expression in BV-2 microglia cells via NF-κB pathways.

    No full text
    (A) Western blots showed the knockdown of DJ-1 in BV-2 cells by stably transfecting cells with plasmids encoding DJ-1 shRNA as compared with control PLKO vector. (B) Immunoblotting showed that treatment of LPS (300 ng/ml) increased the phosphorylation of IκB-α, degradation of IκB-α and p65 nuclear translocation, which was enhanced in DJ-1 knockdown BV-2 cells. (C) Luciferase reporter assay showed that LPS stimulation for 4 hours enhanced the NF-κB promoter activity in DJ-1 knockdown cells. (D) mRNA expression (6 hours after LPS) and (E) protein secretion levels (24 hours after LPS) of IFN-γ and I-TAC were increased by LPS in BV-2 cells and conditioned medium (CM) respectively, and were further enhanced by DJ-1 knockdown. The elevated expression and secretion of cytokine can be antagonized by treating cells with NF-κB inhibitors PDTC and JSH-23. Data were normalized as percentage of mean basal level in group of control vector (con) and presented as mean ± S.E.M. (n = 4–5 for each group) * p<0.05, # p<0.05 as compared between conditions with and without inhibitor treatment, which were either with or without LPS stimulation.</p

    Mini-gene DJ-1,3A (DJ-1 CT161-175) blocks the interaction between DJ-1 and DAT.

    No full text
    <p>(A) Co-expression of the DJ-1,3A mini-gene blocks the physical interaction between DJ-1 and DAT. Co-immunoprecipitation of DAT with DJ-1 was performed by incubating 500 μg of solubilized HEK-293T cells that were co-transfected with DAT, DJ-1, and either pcDNA3 or DJ-1,3A. Western blot reveals that the DAT/DJ-1 interaction is blocked by the addition of DJ-1,3A mini-gene. (B) 2.5 μg of HEK-293T lysates were run on SDS-PAGE and immunoblotted with DAT, DJ-1 or β-tubulin. (C) Quantification of co-immunoprecipitation of DAT with DJ-1 in HEK-293T cells co-transfected with pcDNA3 or the DJ-1,3A mini-gene* P<0.05, t-test. n = 7. (D) Mini-gene DJ-1,3A blocks the functional interaction between DJ-1 and DAT. [<sup>3</sup>H] DA uptake was measured in HEK-293T cells that were co-expressing the DJ-1,3A mini-gene. DJ-1-mediated increase in DAT-mediated [<sup>3</sup>H] DA uptake was blocked with the co-expression of mini-gene encoding DJ-1,3A but does not alter the uptake in cells only transfected with DAT. (* P<0.05, significantly different from DAT/pcD group; # P<0.05, significantly different from DAT/DJ-1 group; one-way ANOVA post hoc Tukey test, n = 3). (E) Quantification of DAT cell surface localization using a cell-based ELISA. HEK-293T cells co-expressing DAT and DJ-1 exhibit an approximate 30% increase in DAT cell surface localization compared with cells co-transfected with DAT and pcDNA3, an effect blocked by the co-expression of the DJ-1,3A mini-gene (** P<0.01 compared to DAT/p3 group; one-way ANOVA, post hoc Tukey test, n = 6).</p

    Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction

    No full text
    DJ-1 is linked to an early-onset autosomal recessive Parkinson&apos;s disease (PD) characterized primarily by selective loss of dopaminergic (DA) neurons, which results in motor disturbances. However, our understanding on how mutations in DJ-I are related to PD is unclear. Here, we isolated the DJ-1 orthologue, DJ-1 beta, in Drosophila and characterized its expression and loss-of-function mutants. We observed its strongest expression in the adult stage of development and ubiquitous expression in the larval brain. Our homozygous mutants showed severe defects in locomotor ability without loss of DA neurons, consistent with the previous mice DJ-1 mutant studies ([Goldberg, M.S., Pisani, A., Haburcak, M., Vortherms, T.A., Kitada, T., Costa, C., Tong, Y., Martella, G., Tscherter, A., Martins, A., et al., 2005. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45, 489-496.]; [Kiln, R.H., Smith, P.D., Aleyasin, H., Hayley, S., Mount, M.P., Pownall, S., Wakeham, A., You-Ten, A.J., Kalia, S.K., Home, P., Westaway, D., Lozano. A.M., Anisman, H., Park, D.S., Mak, T.W., 2005. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and oxidative stress. Proc. Natl. Acad. Sci. USA 102, 5215-5220.]; [Chen, L., Cagniard, B., Mathews, T., Jones, S., Koh, H.C., Ding, Y., Carvey, P.M., Ling, Z., Kang, U.J., Zhuang, X., 2005. Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J. Biol. Chem. 280, 21418-21426.]). The locomotor activity of DJ-1 beta mutants was further decreased by paraquat-induced oxidative stress. Moreover, we found that Drosophila DJ-1 is prominently localized in mitochondria, suggesting that DJ-1 functions as a protector against oxidative stress in mitochondria. (c) 2005 Elsevier B. V. All rights reserved

    Structural basis for the interaction between DJ-1 and Bcl-XL

    No full text
    DJ-1 is a multifunctional protein associated with Parkinson's disease (PD) and tumorigenesis. In response to ultraviolet B (UVB) irradiation, DJ-1 is translocated into the mitochondria, and its interaction with the mitochondrial protein Bcl-XL protects cells against death. In this study, we characterized the molecular interaction between DJ-1 and Bcl-XL by NMR spectroscopy. The NMR chemical shift perturbation data demonstrated that the oxidized but not the reduced form of DJ-1 binds to the predominantly hydrophobic groove surrounded by the BH1?BH3 domains in Bcl-XL. In addition, our results showed that the C-terminal α8-helix peptide (Cpep) of DJ-1 binds to the pro-apoptotic BH3 peptide-binding hydrophobic groove in Bcl-XL and, thus, acts as a Bcl-XL-binding motif. In combination with the NMR chemical shift perturbation data, a refined structural model of the Bcl-XL/DJ-1 Cpep complex revealed that the binding mode is remarkably similar to that of other Bcl-XL/pro-apoptotic BH3 peptide complexes. Taken together, our results provide a structural basis for the binding mechanism between DJ-1 and Bcl-XL, which will contribute to molecular understanding of the role of mitochondrial DJ-1 in Bcl-XL regulation in response to oxidative stress. ⓒ 2017 Elsevier Inc.

    hpDJ: An automated DJ with floorshow feedback

    No full text
    Many radio stations and nightclubs employ Disk-Jockeys (DJs) to provide a continuous uninterrupted stream or “mix” of dance music, built from a sequence of individual song-tracks. In the last decade, commercial pre-recorded compilation CDs of DJ mixes have become a growth market. DJs exercise skill in deciding an appropriate sequence of tracks and in mixing 'seamlessly' from one track to the next. Online access to large-scale archives of digitized music via automated music information retrieval systems offers users the possibility of discovering many songs they like, but the majority of consumers are unlikely to want to learn the DJ skills of sequencing and mixing. This paper describes hpDJ, an automatic method by which compilations of dance-music can be sequenced and seamlessly mixed by computer, with minimal user involvement. The user may specify a selection of tracks, and may give a qualitative indication of the type of mix required. The resultant mix can be presented as a continuous single digital audio file, whether for burning to CD, or for play-out from a personal playback device such as an iPod, or for play-out to rooms full of dancers in a nightclub. Results from an early version of this system have been tested on an audience of patrons in a London nightclub, with very favourable results. Subsequent to that experiment, we designed technologies which allow the hpDJ system to monitor the responses of crowds of dancers/listeners, so that hpDJ can dynamically react to those responses from the crowd. The initial intention was that hpDJ would monitor the crowd’s reaction to the song-track currently being played, and use that response to guide its selection of subsequent song-tracks tracks in the mix. In that version, it’s assumed that all the song-tracks existed in some archive or library of pre-recorded files. However, once reliable crowd-monitoring technology is available, it becomes possible to use the crowd-response data to dynamically “remix” existing song-tracks (i.e, alter the track in some way, tailoring it to the response of the crowd) and even to dynamically “compose” new song-tracks suited to that crowd. Thus, the music played by hpDJ to any particular crowd of listeners on any particular night becomes a direct function of that particular crowd’s particular responses on that particular night. On a different night, the same crowd of people might react in a different way, leading hpDJ to create different music. Thus, the music composed and played by hpDJ could be viewed as an “emergent” property of the dynamic interaction between the computer system and the crowd, and the crowd could then be viewed as having collectively collaborated on composing the music that was played on that night. This en masse collective composition raises some interesting legal issues regarding the ownership of the composition (i.e.: who, exactly, is the author of the work?), but revenue-generating businesses can nevertheless plausibly be built from such technologies
    corecore