Morphologic and functional correlates of synaptic pathology in the cathepsin D knockout mouse model of congenital neuronal ceroid lipofuscinosis

Mutations in the cathepsin D (CTSD) gene cause an aggressive neurodegenerative disease (congenital neuronal ceroid lipofuscinosis) that leads to early death. Recent evidence suggests that presynaptic abnormalities play a major role in the pathogenesis of CTSD deficiencies. To identify the early events that lead to synaptic alterations, we investigated synaptic ultrastructure and function in pre-symptomatic CTSD knock-out (Ctsd(−/−)) mice. Electron microscopy revealed that there were significantly greater numbers of readily releasable synaptic vesicles present in Ctsd(−/−) mice than in wild-type control mice as early as postnatal day 16. The size of this synaptic vesicle pool continued to increase with disease progression in the hippocampus and thalamus of the Ctsd(−/−) mice. Electrophysiology revealed a markedly decreased frequency of miniature excitatory postsynaptic currents (EPSCs) with no effect on pair-pulse modulation of the evoked EPSPs in the hippocampus of Ctsd(−/−) mice. The reduced miniature EPSC frequency was observed before the appearance of epilepsy or any morphological sign of synaptic degeneration. Taken together, the data indicate that CTSD is required for normal synaptic function, and that a failure in synaptic trafficking or recycling may be an early and important pathological mechanism in Ctsd(−/−) mice; these presynaptic abnormalities may initiate synaptic degeneration in advance of subsequent neuronal loss

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Responsible research in industry RRI

The Responsible-Industry project aims at exploring how the adoption of the RRI (Responsible Research and Innovation) principles can help private corporations to conduct their research and innovation (R&I) activities responsively. Responsible Research and Innovation (RRI) is, in fact, an inclusive approach to ensure that societal actors work together during the whole research and innovation (R&I) process, to better align both the process and outcomes of R&I with the values, needs and expectations of European society. RRI builds on a strong commitment of European Commission policies to stimulate greater responsiveness of science and innovation towards society’s needs. Until now, RRI has been primary focused on publicly funded research. For maximum uptake of RRI, it is important to advance the adoption of RRI in both the private and public sectors. For this reason, the European Commission envisages wider application of RRI to industry. This objective could be facilitated by enlarging CSR (Corporate Social Responsibility) policies to take into account peculiar aspects of research and innovation processes. The CSR and RRI concepts share the objective of integrating social, environmental, ethical, human rights and consumer concerns into the enterprise business operations and to max-imize the creation of shared value for shareholders and stakeholders and society at large. Social and environmental impacts are increasingly complex and companies need new ways to address this challenge. There is also a growing need for companies to demonstrate that they are ethically, socially and environmentally responsible. There are in fact several recent examples of new emerging technologies, which have been contested by the society because societal impacts and ethical aspects were not adequately taken into consideration in the development of new products and processes. Considerable investments made to develop these innovations were wasted. In this context, the Responsible Industry Project specifically aims to integrate principles and methodologies of RRI into the research and innovation processes developed by industries active in the domain of ICT for an ageing society. The ICT - related tools and services for an ageing population constitute a maturing technology and market with huge growth potential, combining several aspects relevant for RRI. In particular: • The research field is rapidly moving and challenging, because ICT are enablers of innovative and sometimes futuristic solutions • The market area is targeted to vulnerable groups of the population, thus significant ethical and social issues must be addressed during product development • The target group is heterogeneous and having cultural differences • The market is still in its infancy, and novel specific R&I and business models are under development, thus providing opportunities for RRI approaches to be tested. To this purpose, a “Framework for the Implementation of RRI” has been set up by the Responsible Industry Project to provide strategic options and recommendations for industrial actors engaged in research and innovation to pursue responsible practices and behaviours in developing devices, products and services in the above said field. Adopting RRI will generate numerous benefits for companies. These include: • Strengthening links with customers and end-users • Enhancing the company’s reputation • Decreasing business risks and unintended consequences • Strengthening public trust in the safety of products • Increasing acceptability of products • Adopting an environmentally friendly profile As a result, the company reputation will be enhanced with positive impact on its medium-term competitiveness/profitability, so improving the bottom line and the company value. In order to achieve these goals, responsi-bility should become an integral part of the company culture and mission, a real change of thinking should be pursued