7 research outputs found

    The Sweater Work / Shop

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    The Sweater Work / Shop is a project focusing on the utilization of DIY, crafts and making techniques in a design context. Setting out to develop a small-scale system, this Thesis explores the possibilities of working with textile waste in new and innovative ways through hands-on making while searching for an alternative to mass consumption. Theoretical research provides relevant and contemporary knowledge about the key areas of DIY, crafts and making, as well as their suggested benefits for the environment, society, individual wellbeing and the human-object relationship. Added to this, an extensive practical research provides deeper insights into these themes, related businesses and local projects, together with applied knowledge about the DIY, crafts and making process in a series of experiments with techniques and materials. An in-depth analysis summarizes the most significant problems and opportunities learned by application of the previously mentioned research methods, resulting in the formulation of a design brief for the practical prototype. The prototype itself is a small mobile kiosk to show, make and sell. It visualizes the process of un-knitting old garments, making recycled yarns and then knitting new products from these yarns. It serves both as a workstation and a small shop, therefore the title of this Thesis: The Sweater Work / Shop. This prototype is combined with an alternative pricing system, offering customized products for a lower price, and thereby creating value through engagement of the customer and the story of the making process instead of monetary investments. In the end, a real-life trial proved, that customized products offer a good balance of involvement; allowing even those who don’t want to craft, DIY or make to participate and benefit from some of the positive aspects of DIY, crafts and making

    Epigenome Microarray Platform for Proteome-Wide Dissection of Chromatin-Signaling Networks

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    Knowledge of protein domains that function as the biological effectors for diverse post-translational modifications of histones is critical for understanding how nuclear and epigenetic programs are established. Indeed, mutations of chromatin effector domains found within several proteins are associated with multiple human pathologies, including cancer and immunodeficiency syndromes. To date, relatively few effector domains have been identified in comparison to the number of modifications present on histone and non-histone proteins. Here we describe the generation and application of human modified peptide microarrays as a platform for high-throughput discovery of chromatin effectors and for epitope-specificity analysis of antibodies commonly utilized in chromatin research. Screening with a library containing a majority of the Royal Family domains present in the human proteome led to the discovery of TDRD7, JMJ2C, and MPP8 as three new modified histone-binding proteins. Thus, we propose that peptide microarray methodologies are a powerful new tool for elucidating molecular interactions at chromatin

    Differential Cooperation between Heterochromatin Protein HP1 Isoforms and MyoD in Myoblasts*S⃞

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    Mechanisms of transcriptional repression are important during cell differentiation. Mammalian heterochromatin protein 1 isoforms HP1α, HP1β, and HP1γ play important roles in the regulation of chromatin structure and function. We explored the possibility of different roles for the three HP1 isoforms in an integrated system, skeletal muscle terminal differentiation. In this system, terminal differentiation is initiated by the transcription factor MyoD, whose target genes remain mainly silent until myoblasts are induced to differentiate. Here we show that HP1α and HP1β isoforms, but not HP1γ, interact with MyoD in myoblasts. This interaction is direct, as shown using recombinant proteins in vitro. A gene reporter assay revealed that HP1α and HP1β, but not HP1γ, inhibit MyoD transcriptional activity, suggesting a model in which MyoD could serve as a bridge between nucleosomes and chromatin-binding proteins such as HDACs and HP1. Chromatin immunoprecipitation assays show a preferential recruitment of HP1 proteins on MyoD target genes in proliferating myoblasts. Finally, modulation of HP1 protein level impairs MyoD target gene expression and muscle terminal differentiation. Together, our data show a nonconventional interaction between HP1 and a tissue-specific transcription factor, MyoD. In addition, they strongly suggest that HP1 isoforms play important roles during muscle terminal differentiation in an isoform-dependent manner

    Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer

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    Two major mechanisms have been causally implicated in the establishment of cellular senescence: the activation of the DNA damage response (DDR) pathway and the formation of senescence-associated heterochromatic foci (SAHF). Here we show that in human fibroblasts resistant to premature p16(INK4a) induction, SAHF are preferentially formed following oncogene activation but are not detected during replicative cellular senescence or on exposure to a variety of senescence-inducing stimuli. Oncogene-induced SAHF formation depends on DNA replication and ATR (ataxia telangiectasia and Rad3-related). Inactivation of ATM (ataxia telangiectasia mutated) or p53 allows the proliferation of oncogene-expressing cells that retain increased heterochromatin induction. In human cancers, levels of heterochromatin markers are higher than in normal tissues, and are independent of the proliferative index or stage of the tumours. Pharmacological and genetic perturbation of heterochromatin in oncogene-expressing cells increase DDR signalling and lead to apoptosis. In vivo, a histone deacetylase inhibitor (HDACi) causes heterochromatin relaxation, increased DDR, apoptosis and tumour regression. These results indicate that heterochromatin induced by oncogenic stress restrains DDR and suggest that the use of chromatin-modifying drugs in cancer therapies may benefit from the study of chromatin and DDR status of tumours
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