Hyperosmotic stress induces cell-dependent aggregation of α-synuclein.

The aggregation of alpha-synuclein (α-syn) is a pathological feature of a number of neurodegenerative conditions, including Parkinson's disease. Genetic mutations, abnormal protein synthesis, environmental stress, and aging have all been implicated as causative factors in this process. The importance of water in the polymerisation of monomers, however, has largely been overlooked. In the present study, we highlight the role of hyperosmotic stress in inducing human α-syn to aggregate in cells in vitro, through rapid treatment of the cells with three different osmolytes: sugar, salt and alcohol. This effect is cell-dependent and not due to direct protein-osmolyte interaction, and is specific for α-syn when compared to other neurodegeneration-related proteins, such as Tau or Huntingtin. This new property of α-syn not only highlights a unique aspect of its behaviour which may have some relevance for disease states, but may also be useful as a screening test for compounds to inhibit the aggregation of α-syn in vitro.Funding was by the DDPDgenes, Rosetree Trust, Wellcome Trust PhD Program for Clinicians, the Danish Council for Independent Research | Natural Sciences (FNU-11-113326), the Stem Cell Institute and Wellcome Trust-MRC funded Cambridge Stem Cell Institute and an NIHR award of a Biomedical Research Centre for Addenbrooke’s Hospital/University of Cambridge. RA Barker is an NIHR Senior Investigator

Sleepwalking into lock-in? Avoiding wrongs to future people in the governance of solar radiation management research

This paper argues for two ways in which we can avoid the reckless endangerment of future people in the governance of solar radiation management (SRM) research, which could happen through lock-in to SRM deployment from research. SRM research is at an early stage, one at which the mechanisms of lock-in could start to operate. However, lock-in fit to endanger future people could be slowed or stopped through targeted governance. This paper argues that governance of SRM research that does not include provisions to detect, slow, or stop lock-in fails the test of an intergenerationally adequate precautionary principle, and that research governed without these provisions cannot itself be justified as a precaution against the impacts of climate change

Crying out for help with root exudates : adaptive mechanisms by which stressed plants assemble health-promoting soil microbiomes

Plants employ immunological and ecological strategies to resist biotic stress. Recent evidence suggests that plants adapt to biotic stress by changing their root exudation chemistry to assemble health-promoting microbiomes. This so-called ‘cry-for-help’ hypothesis provides a mechanistic explanation for previously characterized soil feedback responses to plant disease, such as the development of disease-suppressing soils upon successive cultivations of take all-infected wheat. Here, we divide the hypothesis into individual stages and evaluate the evidence for each component. We review how plant immune responses modify root exudation chemistry, as well as what impact this has on microbial activities, and the subsequent plant responses to these activities. Finally, we review the ecological relevance of the interaction, along with its translational potential for future crop protection strategies

Gold nanoparticles explore cells: cellular uptake and their use as intracellular probes

Understanding uptake of nanomaterials by cells and their use for intracellular sensing is important for studying their interaction and toxicology as well as for obtaining new biological insight. Here, we investigate cellular uptake and intracellular dynamics of gold nanoparticles and demonstrate their use in reporting chemical information from the endocytotic pathway and cytoplasm. The intracellular gold nanoparticles serve as probes for surface-enhanced Raman spectroscopy (SERS) allowing for biochemical characterisation of their local environment. In particular, in this work we compare intracellular SERS using non-functionalised and functionalised nanoparticles in their ability to segregate different but closely related cell phenotypes. The results indicate that functionalised gold nanoparticles are more efficient in distinguishing between different types of cells. Our studies pave the way for understanding the uptake of gold nanoparticles and their utilisation for SERS to give rise to a greater biochemical understanding in cell-based therapies