153 research outputs found

    Editorial

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    Sharenting in a socially distanced world

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    For www.parenting.digital, Claire Bessant, Emma Nottingham and Marion Oswald discuss the impact of COVID-19 on family use of technology and the encouragement that families are receiving from businesses, schools, the media and others to share images of their personal life during lockdown. Are the COVID-19 response measures altering public attitudes and cultures towards the sharing of data and information about children? What are the possible future implications for children’s privacy

    Enantioselective copper-catalysed reductive Michael cyclisations

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    Hydrometalation of α,ÎČ-unsaturated carbonyl compounds provides access to reactive metal enolates, which can then be trapped by a suitable electrophile. The coppercatalysed reductive aldol reaction involves hydrometalation of an α,ÎČ-unsaturated carbonyl compound, followed by an inter- or intramolecular aldol reaction. While there have been numerous examples of copper-catalysed reductive aldol reactions reported in the literature, the corresponding reductive Michael reaction has been relatively understudied. Herein, the copper-catalysed reductive Michael cyclisation of substrates containing two α,ÎČ-unsaturated carbonyl moieties is described. A range of structurally and electronically diverse substrates were prepared by various different methods. Both α,ÎČ-unsaturated ketones and esters underwent cyclisation, in the presence of a copper catalyst, a bisphosphine ligand, and a stoichiometric reductant, to afford 5- and 6- membered carbocyclic and heterocyclic products, with good-to-excellent levels of diastereo- and enantiocontrol. Furthermore, the diastereochemical outcome of these reactions is dependent on the specific reaction conditions used

    Deciphering the Anti-Aflatoxinogenic Properties of Eugenol Using a Large-Scale q-PCR Approach

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    Produced by several species of Aspergillus, Aflatoxin B1 (AFB1) is a carcinogenic mycotoxin contaminating many crops worldwide. The utilization of fungicides is currently one of the most common methods; nevertheless, their use is not environmentally or economically sound. Thus, the use of natural compounds able to block aflatoxinogenesis could represent an alternative strategy to limit food and feed contamination. For instance, eugenol, a 4-allyl-2-methoxyphenol present in many essential oils, has been identified as an anti-aflatoxin molecule. However, its precise mechanism of action has yet to be clarified. The production of AFB1 is associated with the expression of a 70 kB cluster, and not less than 21 enzymatic reactions are necessary for its production. Based on former empirical data, a molecular tool composed of 60 genes targeting 27 genes of aflatoxin B1 cluster and 33 genes encoding the main regulatory factors potentially involved in its production, was developed. We showed that AFB1 inhibition in Aspergillus flavus following eugenol addition at 0.5 mM in a Malt Extract Agar (MEA) medium resulted in a complete inhibition of the expression of all but one gene of the AFB1 biosynthesis cluster. This transcriptomic effect followed a down-regulation of the complex composed by the two internal regulatory factors, AflR and AflS. This phenomenon was also influenced by an over-expression of veA and mtfA, two genes that are directly linked to AFB1 cluster regulation

    Deciphering the genetic control of innate and adaptive immune responses in pig: a combined genetic and genomic study

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    Improving animal robustness and resistance to pathogens by adding health criteria in selection schemes is one of the challenging objectives of the next decade. In order to better understand the genetic control of immunity in French Large White pigs, we have launched a program combining genetic and genomic studies not focussing on any particular pathogen. Animals recorded for production traits were scored for a wide range of immunity parameters three weeks after vaccination against Mycoplasma hyopneumoniae: i) total white blood cells and lymphocyte counts and proportions of various leucocyte subsets including cells harbouring IgM, γΎTCR, CD4/CD8, CD16/CD2 and CD16/CD172a/MHCII, ii) innate immune response parameters (phagocytosis and in vitro production of IL1B, IL6, IL8, TNF, IL12 and IFNαafter blood stimulation), iii) adaptive immune response parameters (lymphocyte proliferation, in vitro production of IL2, IL4, IL10 and IFNÎł after blood stimulation, total IgG, IgA, IgM and specific IgG levels) and iv) two acute phase proteins (C-reactive protein and haploglobin). Across traits, heritability estimates reached 0.4 on average (se=0.1) and 42 of the 54 measured parameters showed moderate to high heritabilities (≄0.2), confirming that many parameters are under genetic control and could be included in selection protocols. Functional analyses revealed that the blood transcriptome is informative for part of the immunity traits and should provide relevant phenotypic information to better characterize some immunity traits

    Transcriptome analysis of porcine PBMCs after in vitro stimulation by LPS or PMA/ionomycin using an expression array targeting the pig immune response

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    <p>Abstract</p> <p>Background</p> <p>Designing sustainable animal production systems that better balance productivity and resistance to disease is a major concern. In order to address questions related to immunity and resistance to disease in pig, it is necessary to increase knowledge on its immune system and to produce efficient tools dedicated to this species.</p> <p>Results</p> <p>A long-oligonucleotide-based chip referred to as SLA-RI/NRSP8-13K was produced by combining a generic set with a newly designed SLA-RI set that targets all annotated loci of the pig major histocompatibility complex (MHC) region (SLA complex) in both orientations as well as immunity genes outside the SLA complex.</p> <p>The chip was used to study the immune response of pigs following stimulation of porcine peripheral blood mononuclear cells (PBMCs) with lipopolysaccharide (LPS) or a mixture of phorbol myristate acetate (PMA) and ionomycin for 24 hours. Transcriptome analysis revealed that ten times more genes were differentially expressed after PMA/ionomycin stimulation than after LPS stimulation. LPS stimulation induced a general inflammation response with over-expression of SAA1, pro-inflammatory chemokines IL8, CCL2, CXCL5, CXCL3, CXCL2 and CCL8 as well as genes related to oxidative processes (SOD2) and calcium pathways (S100A9 and S100A12). PMA/ionomycin stimulation induced a stronger up-regulation of T cell activation than of B cell activation with dominance toward a Th1 response, including IL2, CD69 and TNFRSF9 (tumor necrosis factor receptor superfamily, member 9) genes. In addition, a very intense repression of THBS1 (thrombospondin 1) was observed. Repression of MHC class I genes was observed after PMA/ionomycin stimulation despite an up-regulation of the gene cascade involved in peptide processing. Repression of MHC class II genes was observed after both stimulations. Our results provide preliminary data suggesting that antisense transcripts mapping to the SLA complex may have a role during immune response.</p> <p>Conclusion</p> <p>The SLA-RI/NRSP8-13K chip was found to accurately decipher two distinct immune response activations of PBMCs indicating that it constitutes a valuable tool to further study immunity and resistance to disease in pig. The transcriptome analysis revealed specific and common features of the immune responses depending on the stimulation agent that increase knowledge on pig immunity.</p

    Considerations for defining+80 Da mass shifts in mass spectrometry-based proteomics: phosphorylation and beyond

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    Post-translational modifications (PTMs) are ubiquitous and key to regulating protein function. Understanding the dynamics of individual PTMs and their biological roles requires robust characterisation. Mass spectrometry (MS) is the method of choice for the identification and quantification of protein modifications. This article focusses on the MS-based analysis of those covalent modifications that induce a mass shift of +80 Da, notably phosphorylation and sulfation, given the challenges associated with their discrimination and pinpointing the sites of modification on a polypeptide chain. Phosphorylation in particular is highly abundant, dynamic and can occur on numerous residues to invoke specific functions, hence robust characterisation is crucial to understanding biological relevance. Showcasing our work in the context of other developments in the field, we highlight approaches for enrichment and site localisation of phosphorylated (canonical and non-canonical) and sulfated peptides, as well as modification analysis in the context of intact proteins (top down proteomics) to explore combinatorial roles. Finally, we discuss the application of native ion-mobility MS to explore the effect of these PTMs on protein structure and ligand binding

    Observing Data-Driven Approaches to Covid-19: Reflections from a Distributed, Remote, Interdisciplinary Research Project

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    The Observatory for Monitoring Data-Driven Approaches to Covid-19 (OMDDAC) is an Arts and Humanities Research Council funded research project investigating data-driven approaches to Covid-19, focused upon legal, ethical, policy and operational challenges. The project is a collaboration between Northumbria University (Law School, Department of Computing and Information Sciences, Department of Mathematics) and the Royal United Services Institute, a defence and security think-tank, and aims to carry out integrated interdisciplinary research, regarded as the most challenging type of interdisciplinarity but where the outputs can be the most impactful. Due to the constraints of the pandemic, the project has been carried out in a fully distributed and remote manner, with some team members never having met in person. The subject of the research is continually changing and developing, creating unique project management issues, with the impact of the pandemic pervasive in the lives of the researchers. This article takes the form of a series of reflections from the points of view of individual project researchers – the specialist legal researcher, the think-tank Co-Investigator, the post-doctoral researcher, statistical and data science researchers, and the Principal Investigator – and organised under two main themes - project management and internal communication; and methodologies/interdisciplinary research. We thus draw out lessons for future remote and distributed research, focused upon interdisciplinarity, the benefits and challenges of remote research methodologies, and issues of collegiality. Finally, we warn that it will be a false economy for universities and funders to assume that research projects can continue to be conducted in a mainly remote manner and therefore, that budgetary savings can be made by reducing time allocations, travel and academic networking
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