19 research outputs found

    A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration.

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    NAD metabolism regulates diverse biological processes, including ageing, circadian rhythm and axon survival. Axons depend on the activity of the central enzyme in NAD biosynthesis, nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2), for their maintenance and degenerate rapidly when this activity is lost. However, whether axon survival is regulated by the supply of NAD or by another action of this enzyme remains unclear. Here we show that the nucleotide precursor of NAD, nicotinamide mononucleotide (NMN), accumulates after nerve injury and promotes axon degeneration. Inhibitors of NMN-synthesising enzyme NAMPT confer robust morphological and functional protection of injured axons and synapses despite lowering NAD. Exogenous NMN abolishes this protection, suggesting that NMN accumulation within axons after NMNAT2 degradation could promote degeneration. Ectopic expression of NMN deamidase, a bacterial NMN-scavenging enzyme, prolongs survival of injured axons, providing genetic evidence to support such a mechanism. NMN rises prior to degeneration and both the NAMPT inhibitor FK866 and the axon protective protein Wld(S) prevent this rise. These data indicate that the mechanism by which NMNAT and the related Wld(S) protein promote axon survival is by limiting NMN accumulation. They indicate a novel physiological function for NMN in mammals and reveal an unexpected link between new strategies for cancer chemotherapy and the treatment of axonopathies

    Material efficiency: providing material services with less material production.

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    Material efficiency, as discussed in this Meeting Issue, entails the pursuit of the technical strategies, business models, consumer preferences and policy instruments that would lead to a substantial reduction in the production of high-volume energy-intensive materials required to deliver human well-being. This paper, which introduces a Discussion Meeting Issue on the topic of material efficiency, aims to give an overview of current thinking on the topic, spanning environmental, engineering, economics, sociology and policy issues. The motivations for material efficiency include reducing energy demand, reducing the emissions and other environmental impacts of industry, and increasing national resource security. There are many technical strategies that might bring it about, and these could mainly be implemented today if preferred by customers or producers. However, current economic structures favour the substitution of material for labour, and consumer preferences for material consumption appear to continue even beyond the point at which increased consumption provides any increase in well-being. Therefore, policy will be required to stimulate material efficiency. A theoretically ideal policy measure, such as a carbon price, would internalize the externality of emissions associated with material production, and thus motivate change directly. However, implementation of such a measure has proved elusive, and instead the adjustment of existing government purchasing policies or existing regulations-- for instance to do with building design, planning or vehicle standards--is likely to have a more immediate effect

    Material efficiency: A white paper

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    For most materials used to provide buildings, infrastructure, equipment and products, global stocks are still sufficient to meet anticipated demand, but the environmental impacts of materials production and processing, particularly those related to energy, are rapidly becoming critical. These impacts can be ameliorated to some extent by the ongoing pursuit of efficiencies within existing processes, but demand is anticipated to double in the next 40 years, and this will lead to an unacceptable increase in overall impacts unless the total requirement for material production and processing is reduced. This is the goal of material efficiency, and this paper aims to stimulate interest in the area. Four major strategies for reducing material demand through material efficiency are discussed: longer-lasting products; modularisation and remanufacturing; component re-use; designing products with less material. In industrialised nations, these strategies have had little attention, because of economic, regulatory and social barriers, which are each examined. However, evidence from waste management and the pursuit of energy efficiency suggests that these barriers might be overcome, and an outline of potential mechanisms for change is given. In bringing together insights into material efficiency from a wide range of disciplines, the paper presents a set of 20 open questions for future work

    The energy required to produce materials: constraints on energy-intensity improvements, parameters of demand.

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    In this paper, we review the energy requirements to make materials on a global scale by focusing on the five construction materials that dominate energy used in material production: steel, cement, paper, plastics and aluminium. We then estimate the possibility of reducing absolute material production energy by half, while doubling production from the present to 2050. The goal therefore is a 75 per cent reduction in energy intensity. Four technology-based strategies are investigated, regardless of cost: (i) widespread application of best available technology (BAT), (ii) BAT to cutting-edge technologies, (iii) aggressive recycling and finally, and (iv) significant improvements in recycling technologies. Taken together, these aggressive strategies could produce impressive gains, of the order of a 50-56 per cent reduction in energy intensity, but this is still short of our goal of a 75 per cent reduction. Ultimately, we face fundamental thermodynamic as well as practical constraints on our ability to improve the energy intensity of material production. A strategy to reduce demand by providing material services with less material (called 'material efficiency') is outlined as an approach to solving this dilemma

    Industry 1.61803: the transition to an industry with reduced material demand fit for a low carbon future

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    Arising from a discussion meeting in September 2016, this editorial introduces a special issue on the transition to a future industrial system with greatly reduced demand for material production and attempts to synthesize the main findings. The motivation for such a transition is to reduce industrial greenhouse gas emissions, but unlike previous industrial transformations, there are no major stakeholders who will pursue the change for their own immediate benefit. The special issue, therefore, explores the means by which such a transition could be brought about. The editorial presents an overview of the opportunities identified in the papers of the volume, presents examples of actions that can be taken today to begin the process of change and concludes with an agenda for research that might support a rapid acceleration in the rate of change

    DyNeuMo Mk-2: an investigational circadian-locked neuromodulator with responsive stimulation for applied chronobiology

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    Deep brain stimulation (DBS) for Parkinson's disease, essential tremor and epilepsy is an established palliative treatment. DBS uses electrical neuromodulation to suppress symptoms. Most current systems provide a continuous pattern of fixed stimulation, with clinical follow-ups to refine settings constrained to normal office hours. An issue with this management strategy is that the impact of stimulation on circadian, i.e. sleep-wake, rhythms is not fully considered; either in the device design or in the clinical follow-up. Since devices can be implanted in brain targets that couple into the reticular activating network, impact on wakefulness and sleep can be significant. This issue will likely grow as new targets are explored, with the potential to create entraining signals that are uncoupled from environmental influences. To address this issue, we have designed a new brain-machine-interface for DBS that combines a slow-adaptive circadian-based stimulation pattern with a fast-acting pathway for responsive stimulation, demonstrated here for seizure management. In preparation for first-in-human research trials to explore the utility of multi-timescale automated adaptive algorithms, design and prototyping was carried out in line with ISO risk management standards, ensuring patient safety. The ultimate aim is to account for chronobiology within the algorithms embedded in brain-machine-interfaces and in neuromodulation technology more broadly
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