Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation

Background: Spinocerebellar ataxia type 28 (SCA28) is a dominantly inherited neurodegenerative disease caused by pathogenic variants in AFG3L2. The AFG3L2 protein is a subunit of mitochondrial m-AAA complexes involved in protein quality control. Objective of this study was to determine the molecular mechanisms of SCA28, which has eluded characterisation to date. Methods: We derived SCA28 patient fibroblasts carrying different pathogenic variants in the AFG3L2 proteolytic domain (missense: the newly identified p.F664S and p.M666T, p.G671R, p.Y689H and a truncating frameshift p.L556fs) and analysed multiple aspects of mitochondrial physiology. As reference of residual m-AAA activity, we included SPAX5 patient fibroblasts with homozygous p.Y616C pathogenic variant, AFG3L2 +/\ue2 ' HEK293 T cells by CRISPR/Cas9-genome editing and Afg3l2 \ue2 '/\ue2 ' murine fibroblasts. Results: We found that SCA28 cells carrying missense changes have normal levels of assembled m-AAA complexes, while the cells with a truncating pathogenic variant had only half of this amount. We disclosed inefficient mitochondrial fusion in SCA28 cells caused by increased OPA1 processing operated by hyperactivated OMA1. Notably, we found altered mitochondrial proteostasis to be the trigger of OMA1 activation in SCA28 cells, with pharmacological attenuation of mitochondrial protein synthesis resulting in stabilised levels of OMA1 and OPA1 long forms, which rescued mitochondrial fusion efficiency. Secondary to altered mitochondrial morphology, mitochondrial calcium uptake resulted decreased in SCA28 cells. Conclusion: Our data identify the earliest events in SCA28 pathogenesis and open new perspectives for therapy. By identifying similar mitochondrial phenotypes between SCA28 cells and AFG3L2 +/- cells, our results support haploinsufficiency as the mechanism for the studied pathogenic variants

Factors Influencing Households’ Intention to Adopt Solar PV : A Systematic Review

Rising energy needs, concerns of energy security, mitigating greenhouse gas emissions, climate change phenomenon and a push to utilize indigenous sources for energy generation purposes has encouraged the use of solar photovoltaics (PV). The technological advancements of the recent past, improvement in technologies’ performance, reduction in the prices, policy and regulatory support, and its applicability at household level has made solar energy as a preferred form of energy generation. However, despite its rapid diffusion, it is widely believed that its current application is insignificant compared to its potential. This leads us to ask why solar PV has not been adopted to the level it should have. The existing literature has highlighted a number of factors affecting solar PV adoption. This paper systematically reviews the literature to identify the factors that have been instrumental to solar PV adoption. By exploring the Scopus database, this research identifies 39 articles matching the study objectives. Findings of this research will help academics, technology companies and policymakers in understanding the factors influencing the process and proposing solutions to address these.©2020 Springer. This is a post-peer-review, pre-copyedit version of an article published in Advances in Human Factors, Business Management and Leadership. AHFE 2020. The final authenticated version is available online at: http://dx.doi.org/10.1007/978-3-030-50791-6_36fi=vertaisarvioitu|en=peerReviewed

The technology of the middle class: Understanding the fulfilment of adoption intentions in Queensland's rapid uptake residential solar photovoltaics market

Residential solar photovoltaics (PV), a once niche technology reliant on direct regulatory support to stimulate its adoption, has progressively become more competitive because of economies of learning and scale in production. Given its extraordinary market growth, a better understanding of the various market and social factors affecting residential consumers’ PV purchasing decisions is required for policy makers to create efficient support mechanisms, by industry participants to better target marketing activities, and for more informed planning of centralised electricity generation and network infrastructure development. This paper reports on an analysis of the behavioural drivers of households as decision-making units fulfilling an intention to adopt PV. Drawing upon Rogers’ diffusion of innovation theory and using a logistic regression choice model, the actual outcomes of the residential PV market are examined in the state of Queensland, Australia. A recent survey of more than 8000 households is used to investigate the difference in demographic and motivational factors among households with the stated intention to purchase PV with those that have already adopted the technology. Our findings suggest that PV is the technology of the middle class. This reasoning is made based on surveyees’ stated concerns over rising electricity bills and survey data which indicates that economic life events have a significant influence over perceptions of affordability. Households need to be concerned with rising electricity bills to be motivated to adopt PV, but must also have access to sufficient capital to afford its upfront cost. Familiarity with the technology appeared to reduce adoption motivations based on self-sufficiency and intentions to go off grid

Seeing the value of experiential knowledge through COVID-19

Seeing the entwinement of social and epistemic challenges through COVID, we discuss the perils of simplistic appeals to ‘follow the science’. A hardened scientism risks excarbating social conflict and fueling conspiracy beliefs. Instead, we see an opportunity to devise more inclusive medical knowledge practices through endorsing experiential knowledge alongside traditional evidence types