341 research outputs found

    Intrecci linguistici. Lingue e dialetti italiani tra i giovani italoamericani nella grande area di New York

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    Da quando furono introdotti dai primi immigrati che si insediarono sul suolo americano, la lingua e i dialetti italiani negli Stati Uniti si sono continuamente trasformati. Sui comportamenti linguistici degli emigrati italiani all\u2019estero incisero fattori di natura sociale, culturale, geografica ed economica, nonch\ue9 le diverse ondate migratorie. In particolare, nelle comunit\ue0 italoamericane, la lingua e i dialetti italiani andarono a comporre un continuum linguistico che si accompagn\uf2 all\u2019inglese secondo combinazioni diverse e con un variegato ventaglio di forme. Questo saggio si propone di ripercorrere le tappe che hanno segnato questi cambiamenti, analizzando alcune ricerche svolte a partire dagli anni Ottanta nonch\ue9 i dati della condizione in cui versa attualmente la lingua italiana negli Stati Uniti. Vengono, inoltre, presentati i risultati legati all\u2019uso della lingua e dei dialetti, frutto di una survey condotta nel 2013 su un campione di giovani italoamericani residenti nella grande area di New York. Nonostante le differenze tra le diverse generazioni d\u2019immigrazione dei giovani partecipanti allo studio, emerge come vi sia, soprattutto nelle nuove generazioni di italoamericani, una tendenza alla ripresa di interesse verso la lingua delle origini e i dialetti, espressa anche attraverso la volont\ue0 di trasmetterla ai propri figli

    In vitro inhibition of monkeypox virus production and spread by Interferon-β

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    <p>Abstract</p> <p>Background</p> <p>The <it>Orthopoxvirus </it>genus contains numerous virus species that are capable of causing disease in humans, including variola virus (the etiological agent of smallpox), monkeypox virus, cowpox virus, and vaccinia virus (the prototypical member of the genus). Monkeypox is a zoonotic disease that is endemic in the Democratic Republic of the Congo and is characterized by systemic lesion development and prominent lymphadenopathy. Like variola virus, monkeypox virus is a high priority pathogen for therapeutic development due to its potential to cause serious disease with significant health impacts after zoonotic, accidental, or deliberate introduction into a naïve population.</p> <p>Results</p> <p>The purpose of this study was to investigate the prophylactic and therapeutic potential of interferon-β (IFN-β) for use against monkeypox virus. We found that treatment with human IFN-β results in a significant decrease in monkeypox virus production and spread <it>in vitro</it>. IFN-β substantially inhibited monkeypox virus when introduced 6-8 h post infection, revealing its potential for use as a therapeutic. IFN-β induced the expression of the antiviral protein MxA in infected cells, and constitutive expression of MxA was shown to inhibit monkeypox virus infection.</p> <p>Conclusions</p> <p>Our results demonstrate the successful inhibition of monkeypox virus using human IFN-β and suggest that IFN-β could potentially serve as a novel safe therapeutic for human monkeypox disease.</p

    HIV-1 Nef Employs Two Distinct Mechanisms to Modulate Lck Subcellular Localization and TCR Induced Actin Remodeling

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    The Nef protein acts as critical factor during HIV pathogenesis by increasing HIV replication in vivo via the modulation of host cell vesicle transport and signal transduction processes. Recent studies suggested that Nef alters formation and function of immunological synapses (IS), thereby modulating exogenous T-cell receptor (TCR) stimulation to balance between partial T cell activation required for HIV-1 spread and prevention of activation induced cell death. Alterations of IS function by Nef include interference with cell spreading and actin polymerization upon TCR engagement, a pronounced intracellular accumulation of the Src kinase Lck and its reduced IS recruitment. Here we use a combination of Nef mutagenesis and pharmacological inhibition to analyze the relative contribution of these effects to Nef mediated alterations of IS organization and function on TCR stimulatory surfaces. Inhibition of actin polymerization and IS recruitment of Lck were governed by identical Nef determinants and correlated well with Nef's association with Pak2 kinase activity. In contrast, Nef mediated Lck endosomal accumulation was separable from these effects, occurred independently of Pak2, required integrity of the microtubule rather than the actin filament system and thus represents a distinct Nef activity. Finally, reduction of TCR signal transmission by Nef was linked to altered actin remodeling and Lck IS recruitment but did not require endosomal Lck rerouting. Thus, Nef affects IS function via multiple independent mechanisms to optimize virus replication in the infected host

    Molecular Design, Functional Characterization and Structural Basis of a Protein Inhibitor Against the HIV-1 Pathogenicity Factor Nef

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    Increased spread of HIV-1 and rapid emergence of drug resistance warrants development of novel antiviral strategies. Nef, a critical viral pathogenicity factor that interacts with host cell factors but lacks enzymatic activity, is not targeted by current antiviral measures. Here we inhibit Nef function by simultaneously blocking several highly conserved protein interaction surfaces. This strategy, referred to as “wrapping Nef”, is based on structure-function analyses that led to the identification of four target sites: (i) SH3 domain interaction, (ii) interference with protein transport processes, (iii) CD4 binding and (iv) targeting to lipid membranes. Screening combinations of Nef-interacting domains, we developed a series of small Nef interacting proteins (NIs) composed of an SH3 domain optimized for binding to Nef, fused to a sequence motif of the CD4 cytoplasmic tail and combined with a prenylation signal for membrane association. NIs bind to Nef in the low nM affinity range, associate with Nef in human cells and specifically interfere with key biological activities of Nef. Structure determination of the Nef-inhibitor complex reveals the molecular basis for binding specificity. These results establish Nef-NI interfaces as promising leads for the development of potent Nef inhibitors

    Mammal-Like Organization of the Avian Midbrain Central Gray and a Reappraisal of the Intercollicular Nucleus

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    In mammals, rostrocaudal columns of the midbrain periaqueductal gray (PAG) regulate diverse behavioral and physiological functions, including sexual and fight-or-flight behavior, but homologous columns have not been identified in non-mammalian species. In contrast to mammals, in which the PAG lies ventral to the superior colliculus and surrounds the cerebral aqueduct, birds exhibit a hypertrophied tectum that is displaced laterally, and thus the midbrain central gray (CG) extends mediolaterally rather than dorsoventrally as in mammals. We therefore hypothesized that the avian CG is organized much like a folded open PAG. To address this hypothesis, we conducted immunohistochemical comparisons of the midbrains of mice and finches, as well as Fos studies of aggressive dominance, subordinance, non-social defense and sexual behavior in territorial and gregarious finch species. We obtained excellent support for our predictions based on the folded open model of the PAG and further showed that birds possess functional and anatomical zones that form longitudinal columns similar to those in mammals. However, distinguishing characteristics of the dorsal/dorsolateral PAG, such as a dense peptidergic innervation, a longitudinal column of neuronal nitric oxide synthase neurons, and aggression-induced Fos responses, do not lie within the classical avian CG, but in the laterally adjacent intercollicular nucleus (ICo), suggesting that much of the ICo is homologous to the dorsal PAG

    Precise determination of the mass of the Higgs boson and tests of compatibility of its couplings with the standard model predictions using proton collisions at 7 and 8 TeV

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    Observation of the diphoton decay of the Higgs boson and measurement of its properties

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    Study of double parton scattering using W+2-jet events in proton-proton collisions at √s=7 TeV

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    Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

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