Promoting circular economy transition: A study about perceptions and awareness by different stakeholders groups

Abstract The interest into Circular Economy (CE), mainly emerged recently in response to climate change, environmental damage, and the limits of a linear economy, requires a deeper investigation on how the concept and its transition process are perceived in the society. In the present explorative study (questionnaire survey), we evaluate the perception and level of awareness of three stakeholder groups with a good knowledge on CE concept and governance of the transition process, specifically: Researchers, Economists, and Administrators. The three samples contain stakeholders from EU and non-EU countries. We developed primarily a comprehensive literature review on CE perceptions and awareness useful for the design of the questionnaire, the comparison of the results and in overall for creating a wider framework of analysis and interpretation of the current CE transition. The questionnaire has been tested on one of the three samples (Researchers) and then replicated on the other two ones (Economists and Administrators). The results of the survey shows that the three groups perceive CE as a "zero waste economy" (Administrators) and in wider terms as a model for re-design our present state of economy and society in a more regenerative manner (Researchers and Economists). Administrators seem more focused on utilizing CE for economic growth and job creation while Researchers and Economists mainly expect receiving environmental benefits from the CE transition. The three groups share a common vision of CE at its initial stage of the transition process in agree with the relevant literature. In that, a more successful advance of CE depends on the governance of the process by key actors and instruments. Researchers emphasize a more holistic top-down approach while Economists and Administrators expect a bottom-up approach guided by the civil society (companies and citizens/consumers). However, these results complement each other's as all the actors are relevant for fostering CE and a mixed set of instruments is needed. Moreover, given that implementation of CE is costly for consumers and companies, the political intervention has a leading role in this initial phase also in disseminating a positive and sustainable image of CE concept and model. At this regard the support of CE research to such intervention is highly important to develop a CE path in line with all the three principles of sustainable development, the desired outcome of the society and capable of facing the current unprecedent environmental challenges

Regulatory architecture of the RCA gene cluster captures an intragenic TAD boundary, CTCF-Mediated chromatin looping and a long-range intergenic enhancer

The Regulators of Complement Activation (RCA) gene cluster comprises several tandemly arranged genes with shared functions within the immune system. RCA members, such as complement receptor 2 (CR2), are well-established susceptibility genes in complex autoimmune diseases. Altered expression of RCA genes has been demonstrated at both the functional and genetic level, but the mechanisms underlying their regulation are not fully characterised. We aimed to investigate the structural organisation of the RCA gene cluster to identify key regulatory elements that influence the expression of CR2 and other genes in this immunomodulatory region. Using 4C, we captured extensive CTCF-mediated chromatin looping across the RCA gene cluster in B cells and showed these were organised into two topologically associated domains (TADs). Interestingly, an inter-TAD boundary was located within the CR1 gene at a well-characterised segmental duplication. Additionally, we mapped numerous gene-gene and gene-enhancer interactions across the region, revealing extensive co-regulation. Importantly, we identified an intergenic enhancer and functionally demonstrated this element upregulates two RCA members (CR2 and CD55) in B cells. We have uncovered novel, long-range mechanisms whereby autoimmune disease susceptibility may be influenced by genetic variants, thus highlighting the important contribution of chromatin topology to gene regulation and complex genetic disease.This work was supported by the National Institutes of Health [R01 AI24717 to JH], the Australian Government Research Training Program Scholarship at the University of Western Australia [to JC and JSC], the Spanish Government [BFU2016-74961-P to JG-S] and an institutional grant Unidad de Excelencia María de Maeztu [MDM-206-0687 to the Department of Gene Regulation and Morphogenesis, Centro Andaluz de Biología del Desarrol]

MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, enhancing the viral infection of Burkitt lymphoma cells.

MYC is an oncogenic transcription factor dysregulated in about half of total human tumors. While transcriptomic studies reveal more than 1000 genes regulated by MYC, a much smaller fraction of genes is directly transactivated by MYC. Virtually all Burkitt lymphoma (BL) carry chromosomal translocations involving MYC oncogene. Most endemic BL and a fraction of sporadic BL are associated with Epstein-Barr virus (EBV) infection. The currently accepted mechanism is that EBV is the BL-causing agent inducing MYC translocation. Herein we show that the EBV receptor, CR2 (also called CD21), is a direct MYC target gene. This is based on several pieces of evidence: MYC induces CR2 expression in both proliferating and arrested cells and in the absence of protein synthesis, binds the CR2 promoter and transactivates CR2 in an E-box-dependent manner. Moreover, using mice with conditional MYC ablation we show that MYC induces CR2 in primary B cells. Importantly, modulation of MYC levels directly correlates with EBV's ability of infection in BL cells. Altogether, in contrast to the widely accepted hypothesis for the correlation between EBV and BL, we propose an alternative hypothesis in which MYC dysregulation could be the first event leading to the subsequent EBV infection.S

Transcriptional effects of a lupus-associated polymorphism in the 5' untranslated region (UTR) of human complement receptor 2 (CR2/CD21)

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic component that determines risk. A common three single-nucleotide polymorphism (SNP) haplotype of the complement receptor 2 (CR2) gene has been associated with increased risk of SLE (Wu et al., 2007; Douglas et al., 2009), and a less common haplotype consisting of the major allele at SNP1 and minor alleles at SNP2 and 3 confers protection (Douglas et al., 2009). SNP1 (rs3813946), which is located in the 5' untranslated region (UTR) of the CR2 gene, altered transcriptional activity of a CR2 promoter-luciferase reporter gene construct transiently transfected into a B cell line (Wu et al., 2007) and had an independent effect in the protective haplotype (Douglas et al., 2009). In this study, we show that this SNP alters transcriptional activity in a transiently transfected non B-cell line as well as in stably transfected cell lines, supporting its relevance in vivo. Furthermore, the allele at this SNP affects chromatin accessibility of the surrounding sequence and transcription factor binding. These data confirm the effects of rs3813946 on CR2 transcription, identifying the 5' UTR to be a novel regulatory element for the CR2 gene in which variation may alter gene function and modify the development of lupus