FLow and Benthic ECology 4D – FLOWBEC – an overview

This work is funded by NERC/DEFRA (grants NE/J004332/1, NE/J004308/1, NE/J004200/1, NE/J004359/1, NE/J004316/1, NE/J004219/1, NE/J00426X/1, NE/J004294/1). We also like to acknowledge OpenHydro Ltd and Atlantis Resources Ltd for allowing the placement of the FLOWBEC frame in close proximity to their installations at EMEC, and Marine Scotland Science for their support developing and deploying the FLOWBEC frame.Publisher PD

Financial Constraints, Innovation Performance and Sectoral Disaggregation

How do the effects of financial constraints on innovation performance vary by sector and firm characteristics? This paper uses innovation survey data from 11 European countries to examine the heterogeneity of these effects. Our results suggest that the impact of direct measures of financial barriers differs in production and service sectors, and also by the firm's export orientation. In particular, financial constraints appear to have more pronounced negative effects in the production sector than in the service sector. Among different types of firms, the response to financial constraints seems to be stronger for non-exporters

The P323L Substitution in the SARS-CoV-2 Polymerase (NSP12) Confers a Selective Advantage During Infection

BACKGROUND: The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure. RESULTS: Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323. CONCLUSIONS: These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions

An ALS-Linked Mutant SOD1 Produces a Locomotor Defect Associated with Aggregation and Synaptic Dysfunction When Expressed in Neurons of Caenorhabditis elegans

The nature of toxic effects exerted on neurons by misfolded proteins, occurring in a number of neurodegenerative diseases, is poorly understood. One approach to this problem is to measure effects when such proteins are expressed in heterologous neurons. We report on effects of an ALS-associated, misfolding-prone mutant human SOD1, G85R, when expressed in the neurons of Caenorhabditis elegans. Stable mutant transgenic animals, but not wild-type human SOD1 transgenics, exhibited a strong locomotor defect associated with the presence, specifically in mutant animals, of both soluble oligomers and insoluble aggregates of G85R protein. A whole-genome RNAi screen identified chaperones and other components whose deficiency increased aggregation and further diminished locomotion. The nature of the locomotor defect was investigated. Mutant animals were resistant to paralysis by the cholinesterase inhibitor aldicarb, while exhibiting normal sensitivity to the cholinergic agonist levamisole and normal muscle morphology. When fluorescently labeled presynaptic components were examined in the dorsal nerve cord, decreased numbers of puncta corresponding to neuromuscular junctions were observed in mutant animals and brightness was also diminished. At the EM level, mutant animals exhibited a reduced number of synaptic vesicles. Neurotoxicity in this system thus appears to be mediated by misfolded SOD1 and is exerted on synaptic vesicle biogenesis and/or trafficking

Pain and other symptoms of CRPS can be increased by ambiguous visual stimuli - An exploratory study

Background: Visual disturbance, visuo-spatial difficulties, and exacerbations of pain associated with these, have been reported by some patients with Complex Regional Pain Syndrome (CRPS). Aims: We investigated the hypothesis that some visual stimuli (i.e. those which produce ambiguous perceptions) can induce pain and other somatic sensations in people with CRPS. Methods: Thirty patients with CRPS, 33 with rheumatology conditions and 45 healthy controls viewed two images: a bistable spatial image and a control image. For each image participants recorded the frequency of percept change in 1 min and reported any changes in somatosensation. Results: 73% of patients with CRPS reported increases in pain and/or sensory disturbances including changes in perception of the affected limb, temperature and weight changes and feelings of disorientation after viewing the bistable image. Additionally, 13% of the CRPS group responded with striking worsening of their symptoms which necessitated task cessation. Subjects in the control groups did not report pain increases or somatic sensations. Conclusions: It is possible to worsen the pain suffered in CRPS, and to produce other somatic sensations, by means of a visual stimulus alone. This is a newly described finding. As a clinical and research tool, the experimental method provides a means to generate and exacerbate somaesthetic disturbances, including pain, without moving the affected limb and causing nociceptive interference. This may be particularly useful for brain imaging studies. © 2010 Published by Elsevier Ltd. on behalf of European Federation of International Association for the Study of Pain Chapters

What is 'Open'? An Economic Analysis of Open Institutions

By examining several different types of open institutions including open source software, open science, open square and (open) urban planning, this paper presents a general analysis of open institutional structure that is complementary to traditional proprietary mode. We argue that open institutions, in whatever forms, are essentially about decentralized production of a collective good (or “commons”) that relies on voluntary collaboration of highly variable human-related input. In addition to providing a general definition of open institutional structure, we submit there are two necessary conditions for open institutions. The first is the integration of consumers into production. The second condition is that the efficiency gain from “production” commons is the objective and the tragedy of anticommons becomes a serious problem. In this sense, open institutions represent a positive approach toward externality and uncertainty