26 research outputs found

    Feline leukaemia virus: half a century since its discovery

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    In the early 1960s, Professor William (Bill) F.H. Jarrett was presented with a timeGÇôspace cluster of cats with lymphoma identified by a local veterinary practitioner, Harry Pfaff, and carried out experiments to find if the condition might be caused by a virus, similar to lymphomas noted previously in poultry and mice. In 1964, the transmission of lymphoma in cats and the presence of virus-like particles that resembled GÇÿthe virus of murine leukaemiasGÇÖ in the induced tumours were reported in Nature. These seminal studies initiated research on feline leukaemia virus (FeLV) and launched the field of feline retrovirology. This review article considers the way in which some of the key early observations made by Bill Jarrett and his coworkers have developed in subsequent years and discusses progress that has been made in the field since FeLV was first discovered

    Posthuman literacies: young children moving in time, place and more-than-human worlds.

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    This paper examines the potential of posthumanism to enable a reconceptualization of young children’s literacies from the starting point of movement and sound in the more-than-human world. We propose movement as communicative practice that always occurs as a more complex entanglement of relations within more-than-human worlds. Through our analysis, an understanding of sound emerged as a more-than-human practice that encompasses children’s linguistic and non-linguistic utterances, and which occurs through, with, alongside movement. This paper draws on data from two different research studies; in the first two year old children in the UK banged on drums and marched in a museum. In the second study, two young children in Australia chose sites for their own research and produce a range of emergent literacies from vocalisation and ongoing stories to installations. We present examples of ways in which speaking, gesturing and sounding, as emergent literacy practices, were not so much about transmitting information or intentionally designed signs, but about embodied and sensory experiences in which communication about and in place occurred through the body being and moving in place. This paper contributes to the field of posthuman early childhood literacies by foregrounding movement as central to in-the-moment becoming. Movement and sound exist beyond parameters of human perception, within a flat ontology (MacLure, 2013) in which humans are decentred and everything exists on the same plane, in constant motion. Starting from movement in order to conceptualise literacy offers, therefore, an expanded field of inquiry into early childhood literacy. In the multimodal literacy practices analysed in this paper, meaning and world emerge simultaneously, offering new forms of literacy and representation and suggesting possibilities for defining or conceptualising literacy in ways that resist anthropocentric or logocentric framings

    Identification of novel subgroup a variants with enhanced receptor binding and replicative capacity in primary isolates of anaemogenic strains of feline leukaemia virus

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    <b>BACKGROUND:</b> The development of anaemia in feline leukaemia virus (FeLV)-infected cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C arises from the subgroup that is transmitted, FeLV-A, through alterations in the amino acid sequence of the receptor binding domain (RBD) of the envelope glycoprotein that result in a shift in the receptor usage and the cell tropism of the virus. The factors that influence the transition from subgroup A to subgroup C remain unclear, one possibility is that a selective pressure in the host drives the acquisition of mutations in the RBD, creating A/C intermediates with enhanced abilities to interact with the FeLV-C receptor, FLVCR. In order to understand further the emergence of FeLV-C in the infected cat, we examined primary isolates of FeLV-C for evidence of FeLV-A variants that bore mutations consistent with a gradual evolution from FeLV-A to FeLV-C.<p></p> <b>RESULTS:</b> Within each isolate of FeLV-C, we identified variants that were ostensibly subgroup A by nucleic acid sequence comparisons, but which bore mutations in the RBD. One such mutation, N91D, was present in multiple isolates and when engineered into a molecular clone of the prototypic FeLV-A (Glasgow-1), enhanced replication was noted in feline cells. Expression of the N91D Env on murine leukaemia virus (MLV) pseudotypes enhanced viral entry mediated by the FeLV-A receptor THTR1 while soluble FeLV-A Env bearing the N91D mutation bound more efficiently to mouse or guinea pig cells bearing the FeLV-A and -C receptors. Long-term in vitro culture of variants bearing the N91D substitution in the presence of anti-FeLV gp70 antibodies did not result in the emergence of FeLV-C variants, suggesting that additional selective pressures in the infected cat may drive the subsequent evolution from subgroup A to subgroup C.<p></p> <b>CONCLUSIONS:</b> Our data support a model in which variants of FeLV-A, bearing subtle differences in the RBD of Env, may be predisposed towards enhanced replication in vivo and subsequent conversion to FeLV-C. The selection pressures in vivo that drive the emergence of FeLV-C in a proportion of infected cats remain to be established

    Trayectorias y desafíos de la historiografía de los museos de historia natural en América Del Sur

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    Powerful tools of interchange and circulation of data and specimens, Natural History museums constituted themselves in several Latin-American countries, such as Argentine and Brazil as privileged loci of epistemic infrastructure since the nineteenth century. The museums gathered huge amounts of collections of surveys of territories and people, always proposed as comprehensive, ultimate and exhaustive endeavors, which made those institutions face the challenges of not only storing and displayng the collections and specimens but also how to order the latter in archives and catalogues that would make them intelligible. Problematizing issues already present in the nowadays consistent literature, including the Latin-American contribution, on museums, the paper discusses among other themes, the acritical identification between museums and the representation of nations and the recurrent notion of museums as place of memory. It proposes as a challenge to the new generation of scholar to ponder how to write these histories incorporating their human and non-human agents as well as the set of events and circunstances that generated their sucesses and failures.En el siglo XIX los museos de historia natural de América del Sur se constituyeron en instrumentos clave para el intercambio y la circulación de datos y especímenes y, en ese sentido, en loci privilegiados de la infraestructura de las ciencias y del saber. Almacenaron tal cantidad de objetos y colecciones que los organizadores de estas instituciones se enfrentaron al problema de cómo guardarlos y exhibirlos dándoles un orden que pudiera entenderse. Por eso, los museos no pueden separarse de la historia del papel, del archivo y de los catálogos. Este artículo repasa algunas cuestiones de la historiografía producida en las últimas décadas, discutiendo, entre otras cosas, la identificación acrítica entre museos, memoria y representación de la nación. A su vez, propone el desafío de cómo escribir la historia de los museos incorporando los agentes humanos y no humanos y el conjunto de circunstancias que sustentan sus éxitos y fracasos

    WHO informal consultation on regulatory considerations for evaluation of the quality, safety and efficacy of RNA-based prophylactic vaccines for infectious diseases, 20-22 April 2021

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    This paper presents the key outcomes of the above WHO informal consultation with global stakeholders including regulatory authorities, vaccine developers and manufacturers, academia and other international health organizations and institutions involved in the development, evaluation and use of messenger RNA (mRNA) vaccines. The aim of the consultation was to further clarify the main principles to be presented in an upcoming WHO guidance document on the regulatory considerations in evaluating the quality, safety and efficacy of mRNA prophylactic vaccines for infectious diseases. This WHO guidance document is intended to facilitate global mRNA vaccine development and regulatory convergence in the assessment of such vaccines. The urgent need to develop such a document as a new WHO written standard is outlined in this report along with the key scientific and regulatory challenges. A number of key conclusions are provided at the end of this report along with an update on the steps taken following this meeting

    FRET Analysis of Ionic-Strength Sensors using Time-Resolved Fluorescence

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    Ionic strength influences many aspects of the cell such as cell volume, catalytic activities of enzymes, protein activities, and protein-protein interactions. A family of genetically encoded novel ionic strength sensors has been developed to quantify the ionic strength in vivo. These ionic strength sensors consist of a single polypeptide chain that is made up of mCerulean (a cyan fluorescent protein) connected to mCitrine (a yellow fluorescent protein) via a basic α-helix (enriched in either lysine or arginine residues), a short flexible hinge, and an acidic α-helix (enriched in either aspartate or glutamate residues). These sensors are capable of undergoing fluorescence resonance energy transfer (FRET). The two α-helices are electrostatically attracted to each other, and they become less so as the ionic strength of the environment surrounding the sensor increases due to electrostatic screening. The increase in the intramolecular distance between donor, mCerulean, and acceptor, mCitrine, causes a decrease in the energy transferred. E6G2, which has uncharged α-helices and thus insensitive to ionic strength changes, is used as a control. To quantify the effects of ionic strength as a function of potassium chloride concentration, fluorescence lifetime is used to assess energy transfer between mCerulean and mCitrine. In addition to determining the sensitivity of these protein sensors, these experiments serve as a critical control for the single molecule approach of using fluorescence correlation spectroscopic measurements of molecular brightness as a measure of energy transfer efficiency. The combination of fluorescence lifetime and fluorescence correlation spectroscopy approaches will be useful tools for our long-term goal, which is to dynamically map ionic strength changes in living cells.Department of Chemistry & Biochemistry, University of Minnesota Duluth Swenson College of Science and Engineering, University of Minnesota Duluth Swenson Family Foundation University of Minnesota Grant-in-Aid University of Minnesota Duluth Chancellor's Small Grant Minnesota Supercomputing Institute (MSI) at the University of Minnesota Netherlands Organization for Scientific Research Vidi Gran

    Charge Immobilization of Skeletal Muscle Na+ Channels: Role of Residues in the Inactivation Linker

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    We investigated structural determinants of fast inactivation and deactivation in sodium channels by comparing ionic flux and charge movement in skeletal muscle channels, using mutations of DIII-DIV linker charges. Charge altering and substituting mutations at K-1317, K-1318 depolarized the g(V) curve but hyperpolarized the h∞ curve. Charge reversal and substitution at this locus reduced the apparent voltage sensitivity of open- and closed-state fast inactivation. These effects were not observed with charge reversal at E-1314, E-1315. Mutations swapping or neutralizing the negative cluster at 1314, 1315 and the positive cluster at 1317, 1318 indicated that local interactions dictate the coupling of activation to fast inactivation. Gating charge was immobilized before channel entry into fast inactivation in hNaV1.4 but to a lesser extent in mutations at K-1317, K-1318. These results suggest that charge is preferentially immobilized in channels inactivating from the open state. Recovery of gating charge proceeded with a single, fast phase in the double mutation K-1317R, K-1318R. This mutation also partially uncoupled recovery from deactivation. Our findings indicate that charged residues near the fast inactivation “particle” allosterically interact with voltage sensors to control aspects of gating in sodium channels

    Viajando pelo campo e pelas coleções: aspectos de uma controvérsia paleontológica Fieldtrips and collections: aspects of a Paleontology controversy

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    O campo, os museus, as coleções e os catálogos entrelaçam-se nas redes de relações estabelecidas entre os naturalistas que desenvolveram suas carreiras na construção das ciências paleontológicas no Brasil e na Argentina, na transição para o século XX. Localmente situada, a terra incognita - a Patagônia argentina do início do século - foi palco de diversas controvérsias científicas. Estas marcaram tanto a consolidação das ciências paleontológicas na atual América Latina como a cooperação científica estabelecida entre Hermann von Ihering (1850-1930), diretor do Museu Paulista, de São Paulo, entre 1894 e 1915, e Florentino Ameghino (1854-1911), o naturalista argentino que foi uma referência em sua época, na paleontologia sul-americana de mamíferos.<br>Fieldtrips, museums, collections and catalogues intermingle in a net of relations established among naturalists who developed their careers as the building up of paleontology in Brazil and in Argentina took place from the second half of the nineteenth century on. At the beginning of the twentieth century, Argentinean Patagonia - terra incognita - was the scenery of several controversial scientific issues, which characterize not only the development of Paleontology-related sciences in Latin America, but also the scientific cooperation between Hermann von Ihering (1850 -1930), director of Museu Paulista in São Paulo from 1894 to 1915, and Florentino Ameghino (1854 -1911), an Argentinean naturalist who became a reference for science in his days as to mammal paleontology in South-America
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