Methyltransferase Dnmt3a upregulates HDAC9 to deacetylate the kinase TBK1 for activation of antiviral innate immunity

The DNA methyltransferase Dnmt3a has high expression in terminally differentiated macrophages; however, its role in innate immunity remains unknown. Here we report that deficiency in Dnmt3a selectively impaired the production of type I interferons triggered by pattern-recognition receptors (PRRs), but not that of the proinflammatory cytokines TNF and IL-6. Dnmt3a-deficient mice exhibited enhanced susceptibility to viral challenge. Dnmt3a did not directly regulate the transcription of genes encoding type I interferons; instead, it increased the production of type I interferons through an epigenetic mechanism by maintaining high expression of the histone deacetylase HDAC9. In turn, HDAC9 directly maintained the deacetylation status of the key PRR signaling molecule TBK1 and enhanced its kinase activity. Our data add mechanistic insight into the crosstalk between epigenetic modifications and post-translational modifications in the regulation of PRR signaling and activation of antiviral innate immune responses

Moving from victim blaming to an appreciative inquiry : exploring quality of life in care homes

This paper highlights the need for researchers to work across disciplinary boundaries in order to capture the complexity that care practitioners have to engage with everyday in care home settings. Drawing on findings from a literature review on the complexity of loss in continuing care institutions for older people, the case is made for less victim blaming and more appreciative approaches to research. The way this thinking informed the development of a further literature review on quality of life in care homes (My Home Life) is discussed. Findings from this second study are shared by illustrating key messages with quotes from older residents, relatives and staff living, visiting and working in care homes. These best practice messages focus on: transition into a care home; working to help residents maintain their identity; creating community within care homes; shared decision-making; health and health services; end-of-life care; keeping the workforce fit for purpose, and promoting positive culture. The importance of collaborative working in both research and practice is discussed. The paper is likely to be of interest to all those concerned with improving and developing evidence-based practice in the care home sector, including users and service providers, managers, commissioners and inspectors, policy-makers, researchers and teachersPeer reviewe

Habitat simplification increases the impact of a freshwater invasive fish

Biodiversity continues to decline at a range of spatial scales and there is an urgent requirement to understand how multiple drivers interact in causing such declines. Further, we require methodologies that can facilitate predictions of the effects of such drivers in the future. Habitat degradation and biological invasions are two of the most important threats to biodiversity and here we investigate their combined effects, both in terms of understanding and predicting impacts on native species. The predatory largemouth bass Micropterus salmoides is one of the World’s Worst Invaders, causing declines in native prey species, and its introduction often coincides with habitat simplification. We investigated the predatory functional response, as a measure of ecological impact, of juvenile largemouth bass in artificial vegetation over a range of habitat complexities (high, intermediate, low and zero). Prey, the female guppy Poecilia reticulata, were representative of native fish. As habitats became less complex, significantly more prey were consumed, since, even although attack rates declined, reduced handling times resulted in higher maximum feeding rates by bass. At all levels of habitat complexity, bass exhibited potentially population de-stabilising Type II functional responses, with no emergence of more stabilising Type III functional responses as often occurs in predator-prey relationships in complex habitats. Thus, habitat degradation and simplification potentially exacerbate the impact of this invasive species, but even highly complex habitats may ultimately not protect native species. The utilisation of functional responses under varying environmental contexts provides a method for the understanding and prediction of invasive species impacts.National Research Foundation. South Afric

Aging populations and rural places: impacts on and innovations in land use planning

Recent demographic trends highlight the increased prevalence of older populations in rural America. The trends result from multiple demographic patterns, such as being ‘left behind’ as younger residents leave rural areas and the migration of older adults drawn to rural areas for amenity or lifestyle considerations. Policies aimed toward keeping older adults in their homes as long as feasible (the ‘aging in place’ movement) means Americans are residents in their communities for longer periods of time but with potential growing needs for assistance. The spatial and institutional organization of rural areas coincides to create significant challenges for an aging population. Rural areas lack many essential services for an older population, particularly health care. Transportation in rural areas is highly automobile-dependent, yet older adults face challenges with driving. Additionally, demographic trends indicate that older adults have fewer family members living near them. This chapter highlights innovations in land use planning and service provision for an aging population, emphasizing housing affordability and availability, multi-modal transportation options, recreational opportunities, and environmental sustainability. The chapter also describes governance issues shown to have success for organizations and land use planning agencies moving toward planning for an aging population