Therapeutic strategies for C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia

Purpose of review An intronic G4C2 expansion mutation in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Although there are currently no treatments for this insidious, fatal disease, intense research has led to promising therapeutic strategies, which will be discussed here. Recent findings Therapeutic strategies for C9-ALS/FTD have primarily focused on reducing the toxic effects of mutant expansion RNAs or the dipeptide repeat proteins (DPRs). The pathogenic effects of G4C2 expansion transcripts have been targeted using approaches aimed at promoting their degradation, inhibiting nuclear export or silencing transcription. Other promising strategies include immunotherapy to reduce the DPRs themselves, reducing RAN translation, removing the repeats using DNA or RNA editing and manipulation of downstream disease-altered stress granule pathways. Finally, understanding the molecular triggers that lead to pheno-conversion may lead to opportunities that can delay symptomatic disease onset. Summary A large body of evidence implicates RAN-translated DPRs as a main driver of C9-ALS/FTD. Promising therapeutic strategies for these devastating diseases are being rapidly developed with several approaches already in or approaching clinical trials

Contributing to sustainable community livelihoods: corporate social responsibility programmes of resource companies

Many rural communities in Australia are looking to arrest population decline and secure their future viability. This article examines how resource companies contribute towards building sustainable community livelihoods through corporate social responsibility (CSR) programmes. The study uses structuration theory to explore how human agency combines with key structural processes to create CSR with long-term benefits. Data collection includes semi-structured interviews with employees from 25 Australian resource companies and relevant stakeholders. The study identifies three main CSR approaches reflecting how companies support community livelihoods: minimalist-financial, shared-value, and corporate citizenship models. These approaches are shaped by company values and culture, effectiveness of CSR policies and human capacity. The study highlights the importance of resource companies developing links with local organisations to facilitate livelihood approaches. Overall, the capacity for rural communities to access long-term opportunities from resource development is highly variable, symptomatic of a broader lack of strategic direction for rural development.Anne Elizabeth Fordham, Guy M. Robinson, Boyd Dirk Blackwell and Jen Clear

Emerging organic contaminants in groundwater

Emerging organic contaminants (ECs) are compounds now being found in groundwater from agricultural, urban sources that were previously not detectable, or thought to be significant. ECs include pesticides and degradates, pharmaceuticals, industrial compounds, personal care products, fragrances, water treatment by-products, flame retardants and surfactants, as well as ‘life-style’ compounds such as caffeine and nicotine. ECs may have adverse effects on aquatic ecosystems and human health. Frequently detected ECs include the anti-epileptic drug carbamazepine, the antibiotic sulfamethoxazole, the anti-inflammatories ibuprofen and diclofenac, and caffeine, as well as pesticide degradates. This means there will be challenges in the future in order to address these ECs and to minimise their impact on drinking water and ecosystems. In the coming decades, more ECs are likely to have environmental standards defined, and therefore a better understanding of environmental behaviour remains a priority