188 research outputs found

    Enantioselective Synthesis and Application of N-stereogenic Ammonium Cations

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    Enantioselective synthesis is vital in the construction of many biologically and commercially relevant molecules. Despite having potentially wide-ranging applications, routes to synthesise enriched heteroatomic stereocentres have received less consideration than carbon-based analogues. The use of nitrogen as a stereocentre is commonly neglected due to its ability to readily pyramidally invert at room temperature, enabled by quantum tunnelling. In 1899, Pope and Peachy achieved the first successful resolution of a quaternary ammonium salt, establishing a conformationally and configurationally stable nitrogen stereocentre. However despite this, a general enantioselective methodology to access these stereogenic elements remained elusive until recently. Novel work by our group pioneered the enantioselective synthesis of N-stereocentres as the sole stereogenic element in a molecule. This methodology was made possible through the integration of a supramolecular recognition event and in situ racemisation within a crystallisation-induced asymmetric transformation (CIAT). The supramolecular recognition was facilitated by 1,1′-bi-2-naphthol (BINOL), which played a crucial role in orchestrating the molecular interactions and directing the desired stereochemical outcome. To better explore the utility of the CIAT and increase both the scope and application of this methodology, initially the the supramolecular recognition phenomenon is investigated on a diverse library of achiral ammonium salts. The salts form ternary complexes with BINOL, which serve as supramolecular recognition units in solution. These recognition units assemble into a dynamic and flexible hydrogen-bonded network of (R)-BINOLs and counterions. Subsequently, this network is abstracted into the solid phase, manifesting as a crystalline helical host that encapsulates ammonium cations. These hosts create discrete isostructures, adapting to offer a suitable multipoint recognition environment for the cation to which they are presented. Remarkably, quaternary ammonium cation complexes access a lower energy solid-state compared to their less substituted counterparts, resulting in their selective abstraction from solution, even under aqueous conditions. This discovery challenges selectivity based on hydrogen bonding ability and cation-p interaction strength, marking a potential paradigm shift in the field through use of the solid state. Due to the significance of the crystalline state to a CIAT-like methodology any manipulation of its morphology has pronounced effects on the products synthesised. As such, it was established that consideration of both solvent selection and the enantiopurity of the chiral resolving agent is imperative to precisely control the solid-state end-point of the recognition process. Leveraging an improved understanding of solid-state recognition phenomenon, this study integrates knowledge into the enantioselective methodology, shedding light on the influence of isostructure selection on enantiopurity. Furthermore, empirical observations on ammonium salt·BINOL complexes reveal that positioning steric bulk in close proximity to the stereocentre and minimising functionality on substituent groups are important factors in enhancing enantioselectivity. Analysis of the thermodynamic parameters dictating enantiomer selection in microcrystalline solids illuminates how the stereoselectivity is dictated through multiple mechanisms based on diastereomeric interactions in the solid-state. The study also reports a chiral High Performance Liquid Chromatography (HPLC) methodology to determine the enrichment levels of the newly synthesised ammonium salts. Finally, a newly synthesised ammonium salt (Nallyl, N-methyl, N-phenylacetyl anilinium bromide) was successfully applied to direct the stereochemistry of a substituted atropoisomeric scaffold, showcasing its potential as valuable tool for precise control over molecular chirality in complex chemical structures

    Re-examination of the rainbow trout (Oncorhynchus mykiss) immune response to flagellin : Yersinia ruckeri flagellin is a potent activator of acute phase proteins, anti-microbial peptides and pro-inflammatory cytokines in vitro

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    Acknowledgements E.W. was supported by a PhD studentship from the Ministry of Science and Technology of Thailand and Mahasarakham University. T.W. received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland), that is funded by the Scottish Funding Council (grant reference HR09011). This research was also funded by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (grant agreement No. 311993 TARGETFISH).Peer reviewedPostprin

    Molecular studies on the fish pathogen Yersinia ruckeri

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    Yersinia ruckeri is the aetiological agent of enteric redmouth (ERM), a disease of salmonids, notably rainbow trout (Oncorhynchus mykiss, Walbaum). Until the 1990s, prophylaxis was achieved using a formalin-inactivated whole-cell vaccine of a motile (= flagellin producing) Y. ruckeri strain. However, outbreaks of ERM have since occurred in vaccinated livestock which heralded the emergence of a new biogroup. In addition to giving a negative result for the Voges–Proskauer (VP) reaction and the production of an extracellular lipase, strains responsible for the majority of these new outbreaks in vaccinated stock were non-motile and unable to produce detectable flagellin. It was the aim of this study to determine what protective role flagellin may have towards Y. ruckeri infection, both as a component of the whole-cell vaccine and as a vaccine in itself (i.e. sub-unit vaccine). Results showed that protection against bacterial challenge, either with a motile or non-motile Y. ruckeri strain, was not entirely dependent on the presence of flagellin within the whole-cell vaccine. On the other hand, administering native flagellin (50 μg/fish) via intraperitoneal injection (without adjuvant) resulted in excellent levels of protection (relative percent survival = 100%) against challenge 28 days postvaccination with a flagellin-producing (YR1) or flagellin-devoid (R1) Y. ruckeri strain. Use of recombinant flagellin (r-flagellin) as a vaccine again confirmed the protective properties against challenge with both YR1 and R1 strains, even at lower concentrations i.e. 10 μg/fish. Protection was also conferred after a relatively short period of time (14 days) without any detrimental effect on health or weight of the fish. Thus flagellin has the potential to be an efficacious, non-specific sub-unit vaccine for rainbow trout. Analysis of whole cell proteins by SDS-PAGE from both motile and non-motile isolates demonstrated that highly virulent EX5 isolates which caused disease in vaccinated livestock were overexpressing a 30 to 40 kDa protein. 2D SDS-PAGE and Maldi-tof mass spectrometry identified this protein as outer membrane protein A (OmpA). However, attempts to disrupt the gene encoding the OmpA protein (ompA) using transposon mutagenesis and PCR screening failed to isolate a mutant with a transposon within the gene of interest (ompA::Tn-RL27)

    Conflicting Evolutionary Pressures on Human Cognition: A Case Study of Autism

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    The current dominant view is that the evolutionary pressures leading to our large brain sizes were predominantly social. This study investigates the effects of both technical and social pressures on our cognitive evolution, to determine whether the pressures were more complex than social theories allow. This is assessed both between hominin species and within our species. Between species effects are determined by evaluating the evolution of human cognition in 4 stages. Archaeological evidence of behaviour and changes in brain structure are presented for each stage. This allows specializations to be identified, and permits us to suggest whether specialization in each species was in response to social pressures, or a more complex pattern of both technical and social pressures. The results of this evaluation support a more complex pattern of evolutionary pressures. Within species effects are assessed, using Autism Spectrum Condition (ASC) as an example of an alternate, more technically focused, adaptive strategy. This condition accentuates technical behavioural traits which would be advantageous to a Palaeolithic population. The genetics of the condition show that it is highly heritable, was likely present prior to 200 ka, and under positive selection. Thus, these technical traits must have had an impact on past populations. A survey is conducted to assess whether characteristics and components of autism would influence individual’s engagement with material culture, in particular art. The results provide an example of how individuals with enhanced technical traits within our species may have affected our cultural evolution. Thus, the role of technical pressures in our evolution and how they relate to social pressures requires more attention

    Local Box Adjacency Algorithms for Cylindrical Algebraic Decompositions

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    AbstractWe describe new algorithms for determining the adjacencies between zero-dimensional cells and those one-dimensional cells that are sections (not sectors) in cylindrical algebraic decompositions (cad). Such adjacencies constitute a basis for determining all other cell adjacencies. Our new algorithms are local, being applicable to a specified 0D cell and the 1D cells described by specified polynomials. Particularly efficient algorithms are given for the 0D cells in spaces of dimensions two, three and four. Then an algorithm is given for a space of arbitrary dimension. This algorithm may on occasion report failure, but it can then be repeated with a modified isolating interval and a likelihood of success

    Nocturnal pollination: An overlooked ecosystem service vulnerable to environmental change

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    © 2020 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and the Royal Society of Biology and distributed under the Creative Commons Attribution License 4.0 (CC BY). Existing assessments of the ecosystem service of pollination have been largely restricted to diurnal insects, with a particular focus on generalist foragers such as wild and honey bees. As knowledge of how these plant-pollinator systems function, their relevance to food security and biodiversity, and the fragility of these mutually beneficial interactions increases, attention is diverting to other, less well-studied pollinator groups. One such group are those that forage at night. In this review, we document evidence that nocturnal species are providers of pollination services (including pollination of economically valuable and culturally important crops, as well as wild plants of conservation concern), but highlight how little is known about the scale of such services. We discuss the primary mechanisms involved in night-time communication between plants and insect pollen-vectors, including floral scent, visual cues (and associated specialized visual systems), and thermogenic sensitivity (associated with thermogenic flowers). We highlight that these mechanisms are vulnerable to direct and indirect disruption by a range of anthropogenic drivers of environmental change, including air and soil pollution, artificial light at night, and climate change. Lastly, we highlight a number of directions for future research that will be important if nocturnal pollination services are to be fully understood and ultimately conserved

    How Do We Explain ‛Autistic Traits’ in European Upper Palaeolithic Art?

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    Traits in Upper Palaeolithic art which are also seen in the work of talented artists with autism, including an exceptional realism, remain to be explained. Debate over explanations has been heated, ranging from such art having been created by individuals with autism spectrum conditions, to being influenced by such individuals, to being a product of the use of psychotropic drugs. Here we argue that 'autistic traits' in art, such as extreme realism, are the product of local processing bias or detail focus. The significance of local processing bias has implications for our understanding of Upper Palaeolithic society

    Autism spectrum conditions affect preferences in valued personal possessions

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    Although autism has been characterised as a disorder certain selective advantages of autism have been identified which may represent a selective trade-off for reduced ‘folk psychology’ and provide a potential explanation for the incorporation of autism genes in the human evolutionary past. Such potential trade-off skills remain to be explored in terms of selectively advantageous or disadvantageous behaviours in the distant past however. Here we present the results of an analysis of the relationship between AQ (autism quotient) and attitudes to valued personal possessions on the basis of a study of 550 participants. We find that individuals with autism have a reduced tendency to value and preserve objects as reminders of relationships/attachment figures and place a greater value on the direct practical function of their personal possessions. The latter strategy may have been more selectively advantageous in certain contexts whilst less advantageous in others in the distant evolutionary past

    Aquinas and Solovyov: Unified Christian ontological-epistemology in critique of epistemic reductivism

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    Modern positivism reduced ‘being to knowing’, considering being as cognitively inaccessible and its study as meaningless. In recent ‘scientistic’ scholarship, these presuppositions have found new life. However, Christian ontologically founded epistemology is concerned by this dismissal of being. In search of an ecumenical response, this work attempts a multi-patrimonial Christian, philosophical counterargument to reductive anti-metaphysical epistemology. A comparative analysis between the ontological epistemologies of Saint Thomas Aquinas (as representative of the Mediaeval Occidental Christian tradition) and Vladimir Solovyov (a modern, eastern Christian philosopher-theologian) is made. In this contrast, it is argued that a harmonic Christian philosophical voice is evident. In both Western and Eastern approaches, the causal complexity of being – by the fact that being is – implores the philosopher for a unified account, in contradiction to anti-metaphysical reductivism in any of its forms. Intradisciplinary and/or interdisciplinary implications: Bringing the Christian metaphysics and epistemology of Aquinas and Solovyov into conversation, which the author has not seen done in other literature, this work brings together Epistemology and Metaphysics, leading to a unified practical application in the critique of issue within contemporary Philosophy of Science, scientism

    Continuous-variable quantum digital signatures over insecure channels

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    Funding: The authors gratefully acknowledge the support from the Scottish Universities Physics Alliance (SUPA) and the Engineering and Physical Sciences Research Council (EPSRC).Digital signatures ensure the integrity of a classical message and the authenticity of its sender. Despite their far-reaching use in modern communication, currently used signature schemes rely on computational assumptions and will be rendered insecure by a quantum computer. We present a quantum digital signatures (QDS) scheme whose security is instead based on the impossibility of perfectly and deterministically distinguishing between quantum states. Our continuous-variable (CV) scheme relies on phase measurement of a distributed alphabet of coherent states and allows for secure message authentication against a quantum adversary performing collective beamsplitter and entangling-cloner attacks. Crucially, in the CV setting we allow for an eavesdropper on the quantum channels and yet retain shorter signature lengths than previous protocols with no eavesdropper. This opens up the possibility to implement CV QDS alongside existing CV quantum key distribution platforms with minimal modification.Publisher PDFPeer reviewe
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