The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43

The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function

Opinion on 'Responsible Dual Use' Political, Security, Intelligence and Military Research of Concern in Neuroscience and Neurotechnology

Current and newly emerging insights and technologies arising from research in brain sciences increase capabilities to access, assess and affect thought, emotion and behaviour. While much of this research and development is directed towards clinical use, it also has applications in other settings, notably in the political, security, intelligence and military (PSIM) domains. This is often referred to in terms of ‘Dual Use’. Many of these potential uses raise important social and ethical questions which demand the attention of all those involved in the research, administration, management and regulation of neuroscience research and related technological developments, including those in information and communication technologies (ICT) and robotics. In this Opinion, we suggest that we can increase our ability to identify which programmes and projects of research, development and innovation are ‘of concern’ by applying the principles of Responsible Research and Innovation (RRI) to the concept of ‘dual use’ and distinguishing between ‘responsible’ and ‘irresponsible’ systems of research and technological development. We therefore use the term ‘dual use research of concern’ (DURC) to refer to neuroscience research and technological innovations, and brain inspired developments in information and communication technologies, for use in the political, security, intelligence and military domains, which are either directly of concern because of their potential for use in ways that threaten the peace, health, safety, security and well-being of citizens, or are undertaken without responsible regard to such potential uses. To ensure ongoing attention to these issues, the Opinion proposes recommendations for the Human Brain Project, the European Union and the wider neuroscience and ICT community

Interest representation in the EU: an open and structured dialogue?

Since 1992, the European Commission has sought to build ‘An Open and Structured Dialogue’ with interest groups, and since 2001 a broader ‘Dialogue with Civil Society’. A core feature of this dialogue involves instruments of transparency, and pluralism, with funding to ensure the presence of a wide range of voices. Consultation procedures provide for a ‘marketplace of ideas’ which simulate political competition and contestation, with a ‘voice but not a vote’, and which are supposed to provide for answerability by the European Commission for its policy choices. The European Commission also selects its allies to support its regulatory proposals, with NGOs frequent allies as well as firms and business sectors supporting higher standards. The EU’s fragmented decision-making system helps to provide a naturally pluralist environment, although some recent research suggests that NGOs are more likely to be successful in securing their policy goals than business organizations. NGOs work mostly in coalitions, with the size of coalition a factor in lobbying success. The saliency of issues is another substantial feature of variation in lobbying success and where NGOs can raise the contention of issues they can bring wider participation in EU issues

Interest Groups, NGOs or Civil Society Organisations? The Framing of Non-State Actors in the EU

Scholars have used varying terminology for describing non-state entities seeking to influence public policy or work with the EU’s institutions. This paper argues that the use of this terminology is not and should not be random, as different ‘frames’ come with different normative visions about the role(s) of these entities in EU democracy. A novel bibliometric analysis of 780 academic publications between 1992 and 2020 reveals that three frames stand out: The interest group frame, the NGO frame, as well as the civil society organisation frame; a number of publications also use multiple frames. This article reveals the specific democratic visions contained in these frames, including a pluralist view for interest groups; a governance view for NGOs as ‘third sector’ organisations, and participatory and deliberative democracy contributions for civil society organisations. The use of these frames has dynamically changed over time, with ‘interest groups’ on the rise. The results demonstrate the shifting focus of studies on non-state actors in the EU and consolidation within the sub-field; the original visions of European policy-makers emerging from the 2001 White Paper on governance may only partially come true

Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie

Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome

Vaccine development is essential for pandemic preparedness. We previously conducted a Phase 1 clinical trial of the vector vaccine candidate MVA-MERS-S against the Middle East respiratory syndrome coronavirus (MERS-CoV), expressing its full spike glycoprotein (MERS-CoV-S), as a homologous two-dose regimen (Days 0 and 28). Here, we evaluate a third vaccination with MVA-MERS-S in a subgroup of trial participants one year after primary immunization. A booster vaccination with MVA-MERS-S is safe and well-tolerated. Both binding and neutralizing anti-MERS-CoV antibody titers increase substantially in all participants and exceed maximum titers observed after primary immunization more than 10-fold. We identify four immunogenic IgG epitopes, located in the receptor-binding domain (RBD, n=1) and the S2 subunit (n=3) of MERS-CoV-S. The level of baseline anti-human coronavirus antibody titers does not impact the generation of anti-MERS-CoV antibody responses. Our data support the rationale of a booster vaccination with MVA-MERS-S and encourage further investigation in larger trials

Cyberdreams: visualizing music in extended reality

From the visual music films of the twentieth century to the Video Jockey (VJ) performances seen at the latest electronic dance music festivals, there is an extensive body of artistic work that seeks to visualize sound and music. The form that these visualizations take has been shaped significantly by the capabilities of available technologies; thus, we have seen a transition from paint to film; from hand-drawn animations to motion-graphics; and from analog to digital projection systems. In the twenty-first century, visualizations of music are now possible with extended reality (XR) technologies such as virtual reality (VR), augmented/mixed reality (AR/MR), and related forms of multi-projection environment such as fulldome. However, the successful design of visual music and VJ performances using XR technologies requires us to consider the compositional approaches that can be used by artists and designers. To investigate this area, this chapter will begin with an analysis of existing work that visualizes music using XR technologies. This will allow us to consider the spectrum of existing design approaches, and provide a commentary on the possibilities and limitations of the respective technologies. Following this, the chapter will provide an in-depth discussion of Weinel’s practice-led research, which extends from work exhibited at the Carbon Meets Silicon exhibitions held at Wrexham Glyndŵr University (2015, 2017), and includes AR paintings, VJ performances, and a VR application: Cyberdream VR. Through the discussion of these works, the chapter will demonstrate possible compositional principles for visualizing music across media ranging from paint to XR, enabling the realization of work that reinforces the conceptual meanings associated with music