1,125 research outputs found

    Analysis of a fragmentary diatom record from Lake Van (Turkey) reveals substantial lake-level variability during previous interglacials MIS7 and MIS5e

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    Ancient lake sediments provide opportunities to reconstruct aquatic ecosystems during previous interglacials. In the summer of 2010, the ICDP project PALEOVAN drilled a complete succession of the lacustrine sedimentary sequence deposited during the last ~600,000 years in Lake Van, eastern Anatolia (Turkey). Previous palaeolimnological analysis of the Lake Van sediment record has shown diatoms to be absent over most of the sequence apart from a short interval during the Holocene. Here, we demonstrate the preservation of additional fragmentary diatom records during Marine Isotope Stage (MIS) 7 (243,000–191,000 years ago; Lisiecki and Raymo in Paleoceanography 20:PA1003, 2005; Jouzel et al. in Science 317:793–796, 2007) and MIS5e (130,000–116,000 years ago; Lisiecki and Raymo 2005; Jouzel et al. 2007), each spanning no more than a few thousand years. Although brief, the presence of contrasting diatom assemblages between these two interglacials provide a snapshot of varying water depth and, by inference, climate. Analysis of MIS7e samples suggests that lake water levels were low after a period when the lake was open (i.e., high lake levels with the presence of an outflow present), resulting in higher salinities and possibly less stable bottom waters, which switched between anoxic and oxic states more frequently. By contrast, the diatom assemblages during MIS5e are characteristic of fresh, relatively nutrient rich waters. This suggests that lake levels were high, that the lake was hydrologically open with an outlet, and that the bottom waters were anoxic for long periods of time. Furthermore, our palaeoconductivity estimates and modelling of the past lake volumes with respect to its salt content support the presence of an outflow

    Profiling of Glycan Receptors for Minute Virus of Mice in Permissive Cell Lines Towards Understanding the Mechanism of Cell Recognition

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    The recognition of sialic acids by two strains of minute virus of mice (MVM), MVMp (prototype) and MVMi (immunosuppressive), is an essential requirement for successful infection. To understand the potential for recognition of different modifications of sialic acid by MVM, three types of capsids, virus-like particles, wild type empty (no DNA) capsids, and DNA packaged virions, were screened on a sialylated glycan microarray (SGM). Both viruses demonstrated a preference for binding to 9-O-methylated sialic acid derivatives, while MVMp showed additional binding to 9-O-acetylated and 9-O-lactoylated sialic acid derivatives, indicating recognition differences. The glycans recognized contained a type-2 Galβ1-4GlcNAc motif (Neu5Acα2-3Galβ1-4GlcNAc or 3′SIA-LN) and were biantennary complex-type N-glycans with the exception of one. To correlate the recognition of the 3′SIA-LN glycan motif as well as the biantennary structures to their natural expression in cell lines permissive for MVMp, MVMi, or both strains, the N- and O-glycans, and polar glycolipids present in three cell lines used for in vitro studies, A9 fibroblasts, EL4 T lymphocytes, and the SV40 transformed NB324K cells, were analyzed by MALDI-TOF/TOF mass spectrometry. The cells showed an abundance of the sialylated glycan motifs recognized by the viruses in the SGM and previous glycan microarrays supporting their role in cellular recognition by MVM. Significantly, the NB324K showed fucosylation at the non-reducing end of their biantennary glycans, suggesting that recognition of these cells is possibly mediated by the Lewis X motif as in 3′SIA-LeX identified in a previous glycan microarray screen

    Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding

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    The surface envelope glycoprotein (SU) of Human immunodeficiency virus type 1 (HIV-1), gp120SU plays an essential role in virus binding to target CD4+ T-cells and is a major vaccine target. Gp120 has remarkably high levels of N-linked glycosylation and there is considerable evidence that this “glycan shield” can help protect the virus from antibody-mediated neutralization. In recent years, however, it has become clear that gp120 glycosylation can also be included in the targets of recognition by some of the most potent broadly neutralizing antibodies. Knowing the site-specific glycosylation of gp120 can facilitate the rational design of glycopeptide antigens for HIV vaccine development. While most prior studies have focused on glycan analysis of recombinant forms of gp120, here we report the first systematic glycosylation site analysis of gp120 derived from virions produced by infected T lymphoid cells and show that a single site is exclusively substituted with complex glycans. These results should help guide the design of vaccine immunogens

    Health Product Risk Communication: Is the message getting through?

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    Risk communication is an important component of improving the health and safety of Canadians. For numerous departments and agencies at all levels of government, as well as public and private organizations, effective risk communication can protect Canadians from preventable hazards. The Minister of Health, on behalf of Health Canada (the Sponsor), asked the Council of Canadian Academies (the Council) to provide an evidence-based and authoritative assessment of the state of knowledge on measurement and evaluation of health risk communication. This assessment focuses on identifying tools, evaluation methods, gaps in the literature, and barriers and facilitators to carrying out successful communication and evaluation activities. Specifically, this assessment examines the following questions: How can the effectiveness of health risk communications be measured and evaluated? • What types of instruments/tools are currently available for health risk communication? • What methodological best practices can be used to evaluate the reach, use and benefit of health risk communication? • What research could be done to inform the measurement of the effectiveness of risk communications? • What are the existing barriers to effective risk communications and what best practices exist to address these challenges? To address the charge, the Council assembled a multi-disciplinary panel of 11 experts (the Panel) from Canada and abroad. The Panel’s composition reflected a balance of expertise, experience, and demonstrated leadership in academic, clinical, and regulatory fields. Each member served as an informed individual, rather than as a representative of a particular discipline, patron, organization, or region

    Evidences for a quasi 60-year North Atlantic Oscillation since 1700 and its meaning for global climate change

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    The North Atlantic Oscillation (NAO) obtained using instrumental and documentary proxy predictors from Eurasia is found to be characterized by a quasi 60-year dominant oscillation since 1650. This pattern emerges clearly once the NAO record is time integrated to stress its comparison with the temperature record. The integrated NAO (INAO) is found to well correlate with the length of the day (since 1650) and the global surface sea temperature record HadSST2 and HadSST3 (since 1850). These findings suggest that INAO can be used as a good proxy for global climate change, and that a 60-year cycle exists in the global climate since at least 1700. Finally, the INAO ~60-year oscillation well correlates with the ~60- year oscillations found in the historical European aurora record since 1700, which suggests that this 60-year dominant climatic cycle has a solar-astronomical origin

    Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

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    The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

    Viral Decay Kinetics in the Highly Active Antiretroviral Therapy-Treated Rhesus Macaque Model of AIDS

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    To prevent progression to AIDS, persons infected with human immunodeficiency virus type 1 (HIV-1) must remain on highly active antiretroviral therapy (HAART) indefinitely since this modality does not eradicate the virus. The mechanisms involved in viral persistence during HAART are poorly understood, but an animal model of HAART could help elucidate these mechanisms and enable studies of HIV-1 eradication strategies. Due to the specificity of non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for HIV-1, we have used RT-SHIV, a chimeric virus of simian immunodeficiency virus with RT from HIV-1. This virus is susceptible to NNRTIs and causes an AIDS-like disease in rhesus macaques. In this study, two groups of HAART-treated, RT-SHIV-infected macaques were analyzed to determine viral decay kinetics. In the first group, viral loads were monitored with a standard TaqMan RT-PCR assay with a limit of detection of 50 viral RNA copies per mL. Upon initiation of HAART, viremia decayed in a bi-phasic manner with half-lives of 1.7 and 8.5 days, respectively. A third phase was observed with little further decay. In the second group, the macaques were followed longitudinally with a more sensitive assay utilizing ultracentrifugation to concentrate virus from plasma. Bi-phasic decay of viral RNA was also observed in these animals with half-lives of 1.8 and 5.8 days. Viral loads in these animals during a third phase ranged from 2–58 RNA copies/mL, with little decay over time. The viral decay kinetics observed in these macaques are similar to those reported for HIV-1 infected humans. These results demonstrate that low-level viremia persists in RT-SHIV-infected macaques despite a HAART regimen commonly used in humans
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