10 research outputs found

    Fossil CO2 emissions of all world countries - 2018 Report

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    The Emissions Database for Global Atmospheric Research provides time series of CO2 emissions for all world countries from 1970 until 2017. In this report, fossil CO2 emissions are presented for the period 1990-2017 as well as the per capita and per GDP trends.JRC.C.5-Air and Climat

    Stability and expression levels of HLA-C on the cell membrane modulate HIV-1 infectivity

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    HLA-C expression is associated with a differential ability to control HIV-1 infection. Higher HLA-C levels may lead to a better control of HIV-1 infection through both a higher efficiency of antigen presentation to cytotoxic T lymphocytes (CTLs), as well as the triggering of activating Killer Immunoglobulin like receptors (KIR) on NK-cells, whereas lower levels may provide a poor HIV-1 control and a rapid progression toward AIDS.We characterized the relative amount of HLA-C heterotrimers (heavy chain/\u3b22m/peptide) and HLA-C free heavy chains on PBMC from healthy blood donors harboring both alleles with stable or unstable binding to \u3b22m/peptide. We analyzed the stability of HLA-C heterotrimers of different allotypes and the infectivity of HIV-1 virions produced by PBMC with various allotypes.We observed significant differences in HLA-C heterotrimers stability and in expression levels. We found that R5 HIV-1 virions produced by PBMC harboring unstable HLA-C alleles were more infectious than those produced by PBMC carrying the stable variants.We propose that HIV-1 infectivity might depend both on the amounts of HLA-C molecules and on their stability as trimeric complex. According to this model, individuals with low expressed HLA-C alleles and unstable binding to \u3b22m/peptide might have a worse control of HIV-1 infection and an intrinsically higher capacity to support viral replication.IMPORTANCE Following HIV-1 infection, some people advance rapidly toward AIDS while others have a slow disease progression. HLA-C, a molecule involved in immunity, is a key determinant of HIV-1 control.Here we reveal how HLA-C variants contribute to modulate viral infectivity. HLA-C is present on the cell surface in two different conformations: the immunologically active conformation is part of a complex that includes \u3b22-microglobulin/peptide; the other conformation is not bound to \u3b22-microglobulin/peptide and can associate with HIV-1, increasing its infectivity. Individuals with HLA-C variants with a predominance of immunologically active conformations would display a stronger immunity against HIV-1, a reduced viral infectivity and an effective control of HIV-1 infection, while subjects with HLA-C variants that easily dissociate from \u3b22-microglobulin/peptide would have a reduced immunological response to HIV-1 and produce more infectious virions.This study provides new information that could be useful to design novel vaccine strategies and therapeutic approaches against HIV-1

    HIV-1-Associated Neurocognitive Disorders: Is HLA-C Binding Stability to β2-Microglobulin a Missing Piece of the Pathogenetic Puzzle?

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    AIDS dementia complex (ADC) and HIV-associated neurocognitive disorders (HAND) are complications of HIV-1 infection. Viral infections are risk factors for the development of neurodegenerative disorders. Aging is associated with low-grade inflammation in the brain, i.e., the inflammaging. The molecular mechanisms linking immunosenescence, inflammaging and the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease, are largely unknown. ADC and HAND share some pathological features with AD and may offer some hints on the relationship between viral infections, neuroinflammation, and neurodegeneration. β2-microglobulin (β2m) is an important pro-aging factor that interferes with neurogenesis and worsens cognitive functions. Several studies published in the 80–90s reported high levels of β2m in the cerebrospinal fluid of patients with ADC. High levels of β2m have also been detected in AD. Inflammatory diseases in elderly people are associated with polymorphisms of the MHC-I locus encoding HLA molecules that, by associating with β2m, contribute to cellular immunity. We recently reported that HLA-C, no longer associated with β2m, is incorporated into HIV-1 virions, determining an increase in viral infectivity. We also documented the presence of HLA-C variants more or less stably linked to β2m. These observations led us to hypothesize that some variants of HLA-C, in the presence of viral infections, could determine a greater release and accumulation of β2m, which in turn, may be involved in triggering and/or sustaining neuroinflammation. ADC is the most severe form of HAND. To explore the role of HLA-C in ADC pathogenesis, we analyzed the frequency of HLA-C variants with unstable binding to β2m in a group of patients with ADC. We found a higher frequency of unstable HLA-C alleles in ADC patients, and none of them was harboring stable HLA-C alleles in homozygosis. Our data suggest that the role of HLA-C variants in ADC/HAND pathogenesis deserves further studies. If confirmed in a larger number of samples, this finding may have practical implication for a personalized medicine approach and for developing new therapies to prevent HAND. The exploration of HLA-C variants as risk factors for AD and other neurodegenerative disorders may be a promising field of study

    Discrepanza apparente di tipizzazione HLA nel reclutamento di un donatore di cellule staminali emopoietiche afferente al Centro Donatori di Verona (CD VR01)

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    20. Discrepanza apparente di tipizzazione HLA nel reclutamento di un donatore di cellule staminali ematopoietiche afferente al Centro Donatori di Verona (CD VR01)\u201

    Fossil CO2 and GHG emissions of all world countries

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    The Paris Agreement plans global stocktakes, to which the UNFCCC greenhouse gas (GHG) emission inventories are the primary input. To complete this picture, the Emissions Database for Global Atmospheric Research provides for all world countries emission time series from 1970 until 2018 for CO2 and until 2015 for non-CO2 GHGs.JRC.C.5-Air and Climat

    Key role of sequencing to trace hepatitis a viruses circulating in Italy during a large multi-country European foodborne outbreak in 2013

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    Background. Foodborne Hepatitis A Virus (HAV) outbreaks are being recognized as an emerging public health problem in industrialized countries. In 2013 three foodborne HAV outbreaks occurred in Europe and one in USA. During the largest of the three European outbreaks, most cases occurred in Italy (>1,200 cases as of March 31, 2014). A national Task Force was established at the beginning of the outbreak by the Ministry of Health. Mixed frozen berries were early demonstrated to be the source of infection by the identity of viral sequences in patients and in food. In the present study the molecular characterization of HAV isolates from 355 Italian cases is reported. Methods. Molecular characterization was carried out by PCR/sequencing (VP1/2A region), comparison with reference strains and phylogenetic analysis. Results. A unique strain was responsible for most characterized cases (235/355, 66.1%). Molecular data had a key role in tracing this outbreak, allowing 110 out of the 235 outbreak cases (46.8%) to be recognized in absence of any other link. The data also showed background circulation of further unrelated strains, both autochthonous and travel related, whose sequence comparison highlighted minor outbreaks and small clusters, most of them unrecognized on the basis of epidemiological data. Phylogenetic analysis showed most isolates from travel related cases clustering with reference strains originating from the same geographical area of travel. Conclusions. In conclusion, the study documents, in a real outbreak context, the crucial role of molecular analysis in investigating an old but re-emerging pathogen. Improving the molecular knowledge of HAV strains, both autochthonous and circulating in countries from which potentially contaminated foods are imported, will become increasingly important to control outbreaks by supporting trace back activities, aiming to identify the geographical source(s) of contaminated food, as well as public health interventions
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