Drama teacher education, partnerships for transforming the future: Exploring the concepts of building a Guild of Drama Educators

Focus: The concept of drama teacher education as catalyst for creating communities of drama educators– drama education as an induction into a community of drama educator

Elevated interferon-stimulated gene transcription in peripheral blood mononuclear cells occurs in patients infected with genotype 1 but not genotype 3 hepatitis C virus

Hepatitis C virus (HCV) can be classified into seven distinct genotypes that are associated with differing pathologies and respond differently to antiviral therapy. In the UK, genotype 1 and 3 are present in approximately equal proportions. Chronic infection with HCV genotype 3 is associated with increased liver steatosis and reduced peripheral total cholesterol levels, which potentially influences peripheral immune responses. To understand these differences, we investigated host gene transcription in peripheral blood mononuclear cells by microarray and quantitative PCR in patients with genotype 1 (n = 22) or genotype 3 infection (n = 22) and matched healthy controls (n = 15). Enrichment of genes involved in immune response and inflammatory pathways were present in patients infected with HCV genotype 1; however, no differences in genes involved in lipid or cholesterol metabolism were detected. This genotype-specific induction of genes is unrelated to IL28B genotype or previous treatment failure. Our data support the hypothesis that genotype 1 infection drives a skewed Type I interferon response and provides a foundation for future investigations into the host–pathogen interactions that underlie the genotype-specific clinical outcomes of chronic HCV infection

Non cell autonomous upregulation of CDKN2 transcription linked to progression of chronic hepatitis C disease

Chronic hepatitis C virus infection (C-HC) is associated with higher mortality arising from hepatic and extrahepatic disease. This may be due to accelerated biological aging; however, studies in C-HC have thus far been based solely on telomere length as a biomarker of aging (BoA). In this study, we have evaluated CDKN2 locus transcripts as alternative BoAs in C-HC. Our results suggest that C-HC induces non-cell-autonomous senescence and accelerates biological aging. The CDKN2 locus may provide a link between C-HC and increased susceptibility to age-associated diseases and provides novel biomarkers for assessing its impact on aging processes in man

Navigating the grey: Experiences of incremental cannabis reform in Australia

Introduction and Aims: There have been many changes to cannabis laws across the globe, some dramatic but more often incremental. This study explored the experiences after an incremental cannabis law reform in the Australian Capital Territory, Australia. Method: Semi-structured interviews (n = 30) were conducted in March and April 2021, 14 months after the introduction of cannabis law reform, with people aged 18 and over who had grown and/or consumed cannabis in the previous 12 months. Participants were asked about recent and past cannabis use, growing cannabis and changes to their practices after the introduction of the legislation. Results: Incremental cannabis law change resulted in regulatory grey areas. How people interpreted and navigated such grey areas were connected to their relative privileges, circumstances and histories. Those who were highly policed were more likely to experience the grey areas negatively. Those who were not highly policed found the grey areas confusing or ‘half-arse’ (insufficiently executed), but mostly experienced the new laws positively through new cannabis cultivation or perceived reduction in stigma and fear of arrest. Those with self-identified privilege were unconcerned with grey areas of the legislation. Discussion and Conclusion: Incremental policy change can result in grey areas that require some navigation. Vulnerable populations appear less likely to experience the full benefits of such incremental drug law reform. It is vital to attend to the inequities that can arise from incremental law reform so that positive experiences are shared across the population regardless of relative privilege

Established Tables and Emergent Huddles: Exploring the Processes of Participation Associated With the Policy Changes to Opioid Pharmacotherapy Treatment in Australia in the Context of COVID-19

In this paper we document and analyze emergent participatory processes in drug policy, focusing on the relations between established modes of engagement and emergent participatory formats. We do this through analysis of a case example, attending to policy changes to opioid pharmacotherapy treatment in the context of COVID-19 in Australia. Semistructured interviews (n = 22) were undertaken between August 2020 and March 2021 with people closely involved in the recent policy changes and discussions surrounding opioid pharmacotherapy treatment in Australia. The analysis of the interview accounts followed work which has forged relational, co-productionist and materialist understandings of participation. Two figures of participation were encountered in the interview accounts: the tables of participation and the huddles of participation. The tables seemingly represented a standardized set of bureaucratic mechanisms for the inclusion of the “voices” of people who use drugs. The huddles emerged as a responsive and less coherent set of ad hoc participatory collectives in the context of rapid policy changes during COVID-19. Instead of viewing emergence as distinct from existing participatory formats, emergence was conceptualized ecologically in this article—that is in relation to established forms of participation. As the institutionally mandated tables served the basis for the emergent huddles of participation in this case study, it demonstrates that even the most foreclosed participatory structures can adapt and be responsive to evolving situations of need, perhaps also in ordinary times and not just in emergency conditions

Broad anti-hepatitis C virus (HCV) antibody responses are associated with improved clinical disease parameters in chronic HCV infection

During hepatitis C virus (HCV) infection broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glycoproteins are generated in many individuals. It is unclear if these antibodies play a protective or a pathogenic role during chronic infection. In this study, we investigated whether bNAb responses in individuals with chronic infection were associated with differences in clinical presentation. Patient-derived purified serum IgG was used to assess the breadth of HCV E1E2 binding and neutralization activity of HCV pseudoparticles. Two panels were compared, bearing viral envelope proteins representing either an inter-genotype or an intra-genotype (gt) 1 group. We found that HCV viral load was negatively associated with strong cross-genotypic E1E2 binding (P=0.03). Overall we observed only modest correlation between total E1E2 binding and neutralizing ability. The breadth of inter-genotype neutralization did not correlate with any clinical parameters, however, analysis of individuals with gt 1 HCV infection (n=20), using an intra-genotype pseudoparticle panel, found a strong association between neutralization breadth and reduced liver fibrosis (P=0.006). Broad bNAb response in our chronic cohort was associated with a single nucleotide polymorphism (SNP) in the HLA-DQB1 gene (P=0.038) as previously reported in an acute cohort. Furthermore bNAbs in these individuals targeted more than one region of E2 neutralizing epitopes as assessed through cross-competition of patient bNAbs with well-characterized E2 antibodies. We conclude that bNAb responses in chronic gt1 infection are associated with lower rates of fibrosis and host genetics may play a role in the ability to raise such responses. IMPORTANCE: Globally there are 130-150 million people with chronic HCV infection. Typically the disease is progressive and is a major cause of severe liver cirrhosis and hepatocellular carcinoma. While it is known that neutralizing antibodies have a role in spontaneous clearance during acute infection, little is known about their role in chronic infection. In the present work we investigate the antibody response in a cohort of chronically infected individuals and find that a broad neutralizing antibody response is protective, with reduced levels of liver fibrosis and cirrhosis. We also find an association with SNPs in class II HLA genes and the presence of a broad neutralizing response indicating that antigen presentation may be important for production of HCV neutralizing antibodies

Bidirectional lipid droplet velocities are controlled by differential binding strengths of HCV Core DII protein

Host cell lipid droplets (LD) are essential in the hepatitis C virus (HCV) life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two-photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein’s lipid binding domain II (DII-core) induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV

Emerging climate-driven disturbance processes: Widespread mortality associated with snow-to-rain transitions across 10° of latitude and half the range of a climate-threatened conifer

Climate change is causing rapid changes to forest disturbance regimes worldwide. While the consequences of climate change for existing disturbance processes, like fires, are relatively well studied, emerging drivers of disturbance such as snow loss and subsequent mortality are much less documented. As the climate warms, a transition from winter snow to rain in high latitudes will cause significant changes in environmental conditions such as soil temperatures, historically buffered by snow cover. The Pacific coast of North America is an excellent test case, as mean winter temperatures are currently at the snow–rain threshold and have been warming for approximately 100 years post-Little Ice Age. Increased mortality in a widespread tree species in the region has been linked to warmer winters and snow loss. Here, we present the first high-resolution range map of this climate-sensitive species, Callitropsis nootkatensis (yellow-cedar), and document the magnitude and location of observed mortality across Canada and the United States. Snow cover loss related mortality spans approximately 10° latitude (half the native range of the species) and 7% of the overall species range and appears linked to this snow–rain transition across its range. Mortality is commonly >70% of basal area in affected areas, and more common where mean winter temperatures is at or above the snow–rain threshold (>0 °C mean winter temperature). Approximately 50% of areas with a currently suitable climate for the species (< 2 °C) are expected to warm beyond that threshold by the late 21st century. Regardless of climate change scenario, little of the range which is expected to remain suitable in the future (e.g., a climatic refugia) is in currently protected landscapes (<1–9%). These results are the first documentation of this type of emerging climate disturbance and highlight the difficulties of anticipating novel disturbance processes when planning for conservation and management.Ye