119 research outputs found

    Los Cromberger y los impresos enviados a las colonias españolas en América durante la primera mitad del siglo XVI, con una coda filipina

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    Se ha supuesto que la principal dinastía de impresores, editores y libreros de la Sevilla de la primera mitad del siglo XVI, los Cromberger, envió remesas de libros a las colonias españolas en América. En este artículo se cuestiona esta suposición, analizando documentos conservados en archivos españoles y americanos así como algunas ediciones cromberguianas. Se examina una noticia recién descubierta sobre la primera colección de libros importante llevada a las islas Filipinas

    The influence of nicotinamide on the development of neurons

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    This document is the Accepted Manuscript version of a published work that appeared in final form in Journal of Neurology, Neurosurgery and Psychiatry. To access the final edited and published work see http://dx.doi.org/10.1136/jnnp-2014-309236.199A major challenge in translating the promise of stem cell therapies to treat a myriad of neurodegenerative disorders is to rapidly and efficiently direct pluripotent stem cells to generate differentiated neurons. The application of active vitamin metabolites known to function in embryonic development and maintenance in the adult brain such as retinoic acid (vitamin A), ascorbic acid (vitamin C) and calcitriol (vitamin D3) have proven effective in current in-vitro differentiation protocols. Therefore, in this study we investigated whether the biologically active vitamin B3 metabolite, nicotinamide could enhance the differentiation of mouse embryonic stem cells, cultured as monolayers, into mature neurons at either early or late stages of development. Interestingly, nicotinamide elicited a dose-responsive increase in the percentage of neurons when added at an early developmental stage to the cells undergoing differentiation (days 0–7). Nicotinamide (10 mM) increased the proportion of ÎČ-III tubulin positive neurons by two fold and concomitantly decreased the total number of cells in culture, measured by quantification of 4â€Č, 6-diamidino-2-phenylindole positive cells. This effect could result from induction of cell-cycle exit and/or selective cell death in non-neural populations. Higher levels of nicotinamide (20 mM) induced cytoxicity and cell death. This study supports previous evidence that vitamins and their metabolites can efficiently direct stem cells into neurons. Current work is focusing on the effect of nicotinamide on the process of neural induction and whether nicotinamide influences the generation of particular neuronal subtypes implicated in neurodegenerative diseases, specifically focusing on midbrain dopamine neurons; towards a therapy for Parkinson's disease

    Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells

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    Emerging evidence indicates that a strong relationship exists between brain regenerative therapies and nutrition. Early life nutrition plays an important role during embryonic brain development, and there are clear consequences to an imbalance in nutritional factors on both the production and survival of mature neuronal populations and the infant’s risk of diseases in later life. Our research and that of others suggest that vitamins play a fundamental role in the formation of neurons and their survival. There is a growing body of evidence that nicotinamide, the water-soluble amide form of vitamin B3, is implicated in the conversion of pluripotent stem cells to clinically relevant cells for regenerative therapies. This study investigated the ability of nicotinamide to promote the development of mature catecholaminergic neuronal populations (associated with Parkinson’s disease) from mouse embryonic stem cells, as well as investigating the underlying mechanisms of nicotinamide’s action. Nicotinamide selectively enhanced the production of tyrosine hydroxylase-expressing neurons and serotonergic neurons from mouse embryonic stem cell cultures (Sox1GFP knock-in 46C cell line). A 5-Ethynyl-2®-deoxyuridine (EdU) assay ascertained that nicotinamide, when added in the initial phase, reduced cell proliferation. Nicotinamide drove tyrosine hydroxylase-expressing neuron differentiation as effectively as an established cocktail of signalling factors, reducing the proliferation of neural progenitors and accelerating neuronal maturation, neurite outgrowth and neurotransmitter expression. These novel findings show that nicotinamide enhanced and enriched catecholaminergic differentiation and inhibited cell proliferation by directing cell cycle arrest in mouse embryonic stem cell cultures, thus driving a critical neural proliferation-to-differentiation switch from neural progenitors to neurons. Further research into the role of vitamin metabolites in embryogenesis will significantly advance cell-based regenerative medicine, and help realize their role as crucial developmental signalling molecules in brain development

    Television news and the symbolic criminalisation of young people

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    This is an Author's Accepted Manuscript of an article published in Journalism Studies, 9(1), 75 - 90, 2008, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/14616700701768105.This essay combines quantitative and qualitative analysis of six UK television news programmes. It seeks to analyse the representation of young people within broadcast news provision at a time when media representations, political discourse and policy making generally appear to be invoking young people as something of a folk devil or a locus for moral panics. The quantitative analysis examines the frequency with which young people appear as main actors across a range of different subjects and analyses the role of young people as news sources. It finds a strong correlation between young people and violent crime. A qualitative analysis of four “special reports” or backgrounders on channel Five's Five News explores the representation of young people in more detail, paying attention to contradictions and tensions in the reports, the role of statistics in crime reporting, the role of victims of crime and the tensions between conflicting news frames.Arts and Humanities Research Counci

    Recording the heart beat of cattle using a differential system of optically pumped magnetometers

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    Livestock farming occupies about 30% of the Earth’s habitable surface area with a global value around £1 trillion. This important economic entity relies to a large extend on the health and wellbeing of the animals involved. Besides economic pressure there is also a growing interest of the consumer in the ethical keeping of livestock. Seeking physiological parameters that allow a close assessment of animal wellbeing has identified the animals’ heart beat as a possible parameter to monitor. The electric signal of the heart muscle excitation and relaxation does also carry a magnetic field component. Reading the magnetic field to query heart beat information does avoid the need for contact electrodes. We use two QuSpin Total Field Magnetometers (QTFM¼) in a differential set-up to cancel common mode noise. Using the background noise to time-shift the two signals we optimize signal to noise ratio and record the magnetic heart signal over a noise floor close to 1 pT Hz-1/2 in the 1–100 Hz frequency band. By means of a correlation search algorithm we retrieve the heart rate and the shape of the magnetic heart excitation. Comparison to electro cardiograms shows good correlation

    Mosquito saliva enhances virus infection through sialokinin-dependent vascular leakage

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    Viruses transmitted by Aedes mosquitoes are an increasingly important global cause of disease. Defining common determinants of host susceptibility to this large group of het-erogenous pathogens is key for informing the rational design of panviral medicines. Infection of the vertebrate host with these viruses is enhanced by mosquito saliva, a complex mixture of salivary-gland-derived factors and microbiota. We show that the enhancement of infection by saliva was dependent on vascular function and was independent of most antisaliva immune responses, including salivary microbiota. Instead, the Aedes gene product sialokinin mediated the enhancement of virus infection through a rapid reduction in endothelial barrier integrity. Sialokinin is unique within the insect world as having a vertebrate-like tachykinin sequence and is absent from Anopheles mosquitoes, which are incompetent for most arthropod-borne viruses, whose saliva was not proviral and did not induce similar vascular permeability. Therapeutic strategies targeting sialokinin have the potential to limit disease severity following infection with Aedes mosquito-borne viruses.</p

    Tissue registration and exploration user interfaces in support of a human reference atlas

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    Seventeen international consortia are collaborating on a human reference atlas (HRA), a comprehensive, high-resolution, three-dimensional atlas of all the cells in the healthy human body. Laboratories around the world are collecting tissue specimens from donors varying in sex, age, ethnicity, and body mass index. However, harmonizing tissue data across 25 organs and more than 15 bulk and spatial single-cell assay types poses challenges. Here, we present software tools and user interfaces developed to spatially and semantically annotate ( register ) and explore the tissue data and the evolving HRA. A key part of these tools is a common coordinate framework, providing standard terminologies and data structures for describing specimen, biological structure, and spatial data linked to existing ontologies. As of April 22, 2022, the registration user interface has been used to harmonize and publish data on 5,909 tissue blocks collected by the Human Biomolecular Atlas Program (HuBMAP), the Stimulating Peripheral Activity to Relieve Conditions program (SPARC), the Human Cell Atlas (HCA), the Kidney Precision Medicine Project (KPMP), and the Genotype Tissue Expression project (GTEx). Further, 5,856 tissue sections were derived from 506 HuBMAP tissue blocks. The second exploration user interface enables consortia to evaluate data quality, explore tissue data spatially within the context of the HRA, and guide data acquisition. A companion website is at https://cns-iu.github.io/HRA-supporting-information/

    Recording the Heart Beat of Cattle using a Gradiometer System of Optically Pumped Magnetometers

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    Monitoring of heart rate has the potential to provide excellent data for the remote monitoring of animals, and heart rate has been associated with stress, pyrexia, pain and illness in animals. However monitoring of heart rate in domesticated animals is difficult as it entails the restraint of the animal (which may in turn affect heart rate), and the application of complex monitoring equipment that is either invasive or not practical to implement under commercial farm conditions. Therefore accurate non-invasive automated remote monitoring of heart rate has not been possible in domesticated animals. Biomagnetism associated with muscle and nerve action provides a promising emerging field in medical sensing, but it is currently confined to magnetically-shielded clinical environments. In this study, we use biomagnetic sensing on commercial dairy cattle under farm conditions as a model system to show proof-of-principle for non-contact magnetocardiography (MCG) outside a controlled laboratory environment. By arranging magnetometers in a differential set-up and using purpose-built low-noise electronics, we are able to suppress common mode noise and successfully record the heart rate, the heart beat intervals and the heart beat amplitude. Comparing the MCG signal with simultaneous data recorded using a conventional electrocardiogram (ECG) allowed alignment of the two signals, and was able to match features of the ECG including the P-wave, the QRS complex and the T-wave. This study has shown the potential for MCG to be developed as a non-contact method for the assessment of heart rate and other cardiac attributes in adult dairy cattle. Whilst this study using an animal model showed the capabilities of un-shielded MCG, these techniques also suggest potentially exciting opportunities in human cardiac medicine outside hospital environments

    Simultaneous Analysis of All SNPs in Genome-Wide and Re-Sequencing Association Studies

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    Testing one SNP at a time does not fully realise the potential of genome-wide association studies to identify multiple causal variants, which is a plausible scenario for many complex diseases. We show that simultaneous analysis of the entire set of SNPs from a genome-wide study to identify the subset that best predicts disease outcome is now feasible, thanks to developments in stochastic search methods. We used a Bayesian-inspired penalised maximum likelihood approach in which every SNP can be considered for additive, dominant, and recessive contributions to disease risk. Posterior mode estimates were obtained for regression coefficients that were each assigned a prior with a sharp mode at zero. A non-zero coefficient estimate was interpreted as corresponding to a significant SNP. We investigated two prior distributions and show that the normal-exponential-gamma prior leads to improved SNP selection in comparison with single-SNP tests. We also derived an explicit approximation for type-I error that avoids the need to use permutation procedures. As well as genome-wide analyses, our method is well-suited to fine mapping with very dense SNP sets obtained from re-sequencing and/or imputation. It can accommodate quantitative as well as case-control phenotypes, covariate adjustment, and can be extended to search for interactions. Here, we demonstrate the power and empirical type-I error of our approach using simulated case-control data sets of up to 500 K SNPs, a real genome-wide data set of 300 K SNPs, and a sequence-based dataset, each of which can be analysed in a few hours on a desktop workstation
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