Leveraging affect: mobilizing enthusiasm and the co-production of the musical economy

This chapter considers the promises and problems of fandom and enthusiasm within capitalism, with particular reference to rise of crowdsourcing as a means of mobilising fan enthusiasm to fund new creative projects, with a particular focus on the music industry. Crowdfunding has emerged as an alternative way of funding projects caused by the more cautious investments of record companies, and is the latest development here firms and companies have sought to harness the affect and emotions of fans. However, although crowdfunding may tap new sources of money, the process is not without its costs, both in terms of the demands placed on its users and of being able to navigate a system that requires reserves of social, cultural and financial capital

A critique of the hypothesis that CA repeats are primary targets of neuronal MeCP2

The DNA-binding protein MeCP2 is reported to bind methylated cytosine in CG and CA motifs in genomic DNA, but it was recently proposed that arrays of tandemly repeated CA containing either methylated or hydroxymethylated cytosine are the primary targets for MeCP2 binding and function. Here we investigated the predictions of this hypothesis using a range of published datasets. We failed to detect enrichment of cytosine modification at genomic CA repeat arrays in mouse brain regions and found no evidence for preferential MeCP2 binding at CA repeats. Moreover, we did not observe a correlation between the CA repeat density near genes and their degree of transcriptional deregulation when MeCP2 was absent. Our results do not provide support for the hypothesis that CA repeats are key mediators of MeCP2 function. Instead, we found that CA repeats are subject to CAC methylation to a degree that is typical of the surrounding genome and contribute modestly to MeCP2-mediated modulation of gene expression in accordance with their content of this canonical target motif

Educating for Indigenous health equity: An international consensus statement

The determinants of health inequities between Indigenous and non-Indigenous populations include factors amenable to medical education’s influence, for example, the competence of the medical workforce to provide effective and equitable care to Indigenous populations. Medical education institutions have an important role to play in eliminating these inequities. However, there is evidence that medical education is not adequately fulfilling this role, and in fact may be complicit in perpetuating inequities. This article seeks to examine the factors underpinning medical education’s role in Indigenous health inequity, in order to inform interventions to address these factors. The authors developed a consensus statement that synthesizes evidence from research, evaluation, and the collective experience of an international research collaboration including experts in Indigenous medical education. The statement describes foundational processes that limit Indigenous health development in medical education and articulates key principles that can be applied at multiple levels to advance Indigenous health equity. The authors recognize colonization, racism, and privilege as fundamental determinants of Indigenous health that are also deeply embedded in Western medical education. In order to contribute effectively to Indigenous health development, medical education institutions must engage in decolonization processes and address racism and privilege at curricular and institutional levels. Indigenous health curricula must be formalized and comprehensive, and must be consistently reinforced in all educational environments. Institutions’ responsibilities extend to advocacy for health system and broader societal reform to reduce and eliminate health inequities. These activities must be adequately resourced and underpinned by investment in infrastructure and Indigenous leadership

PAR-CLIP data indicate that Nrd1-Nab3-dependent transcription termination regulates expression of hundreds of protein coding genes in yeast

Background Nrd1 and Nab3 are essential sequence-specific yeast RNA binding proteins that function as a heterodimer in the processing and degradation of diverse classes of RNAs. These proteins also regulate several mRNA coding genes; however, it remains unclear exactly what percentage of the mRNA component of the transcriptome these proteins control. To address this question, we used the pyCRAC software package developed in our laboratory to analyze CRAC and PAR-CLIP data for Nrd1-Nab3-RNA interactions. Results We generated high-resolution maps of Nrd1-Nab3-RNA interactions, from which we have uncovered hundreds of new Nrd1-Nab3 mRNA targets, representing between 20 and 30% of protein-coding transcripts. Although Nrd1 and Nab3 showed a preference for binding near 5′ ends of relatively short transcripts, they bound transcripts throughout coding sequences and 3′ UTRs. Moreover, our data for Nrd1-Nab3 binding to 3′ UTRs was consistent with a role for these proteins in the termination of transcription. Our data also support a tight integration of Nrd1-Nab3 with the nutrient response pathway. Finally, we provide experimental evidence for some of our predictions, using northern blot and RT-PCR assays. Conclusions Collectively, our data support the notion that Nrd1 and Nab3 function is tightly integrated with the nutrient response and indicate a role for these proteins in the regulation of many mRNA coding genes. Further, we provide evidence to support the hypothesis that Nrd1-Nab3 represents a failsafe termination mechanism in instances of readthrough transcription.</p

Cfp1 integrates both CpG content and gene activity for accurate H3K4me3 deposition in embryonic stem cells

Trimethylation of histone H3 Lys 4 (H3K4me3) is a mark of active and poised promoters. The Set1 complex is responsible for most somatic H3K4me3 and contains the conserved subunit CxxC finger protein 1 (Cfp1), which binds to unmethylated CpGs and links H3K4me3 with CpG islands (CGIs). Here we report that Cfp1 plays unanticipated roles in organizing genome-wide H3K4me3 in embryonic stem cells. Cfp1 deficiency caused two contrasting phenotypes: drastic loss of H3K4me3 at expressed CGI-associated genes, with minimal consequences for transcription, and creation of “ectopic” H3K4me3 peaks at numerous regulatory regions. DNA binding by Cfp1 was dispensable for targeting H3K4me3 to active genes but was required to prevent ectopic H3K4me3 peaks. The presence of ectopic peaks at enhancers often coincided with increased expression of nearby genes. This suggests that CpG targeting prevents “leakage” of H3K4me3 to inappropriate chromatin compartments. Our results demonstrate that Cfp1 is a specificity factor that integrates multiple signals, including promoter CpG content and gene activity, to regulate genome-wide patterns of H3K4me3

Leveraging affect: mobilizing enthusiasm and the co-production of the musical economy

This chapter considers the promises and problems of fandom and enthusiasm within capitalism, with particular reference to rise of crowdsourcing as a means of mobilising fan enthusiasm to fund new creative projects, with a particular focus on the music industry. Crowdfunding has emerged as an alternative way of funding projects caused by the more cautious investments of record companies, and is the latest development here firms and companies have sought to harness the affect and emotions of fans. However, although crowdfunding may tap new sources of money, the process is not without its costs, both in terms of the demands placed on its users and of being able to navigate a system that requires reserves of social, cultural and financial capital