284 research outputs found

    Geochemistry of and alteration phases in martian lherzolite Y-793605

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    We have done preliminary SEM characterization of alteration phases on an exterior and an interior chip of martian lherzolite Yamato-793605,and have performed instrumental and radiochemical neutron activation analyses of a glass-poor and a glass-rich interior sample of the rock for a suite of 31 major and trace elements. To date, we have identified silica (containing minor amounts of S, K, Fe, Al), K-Fe-sulfate (probably jarosite) and Fe-phosphate as alteration phases in Y-793605. Of these, the silica and K-Fe-sulfate are likely terrestrial weathering products. Other evidence of alteration consists of what appear to be partly decomposed Ca-phosphate grains, which were probably originally igneous grains. No carbonates or Ca-sulfates have been identified as yet, and none of the alteration phases we have identified are unambiguously of martian origin. Compositionally, Y-793605 is very similar to the other two martian lherzolites ALHA77005 and LEW 88516. Our sample of Y-793605 is lower in the incompatible lithophile trace elements, such as the REE, than the average of either ALHA77005 or LEW 88516,but is within the ranges of individual analyses for ALHA77005. Y-793605 is a partial cumulate like the other lherzolites, but our sample contained less of a trapped melt component

    Cholesterol Secosterol Aldehydes Induce Amyloidogenesis and Dysfunction of Wild-Type Tumor Protein p53

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    SummaryEpidemiologic and clinical evidence points to an increased risk for cancer when coupled with chronic inflammation. However, the molecular mechanisms that underpin this interrelationship remain largely unresolved. Herein we show that the inflammation-derived cholesterol 5,6-secosterol aldehydes, atheronal-A (KA) and -B (ALD), but not the polyunsaturated fatty acid (PUFA)-derived aldehydes 4-hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE), induce misfolding of wild-type p53 into an amyloidogenic form that binds thioflavin T and Congo red dyes but cannot bind to a consensus DNA sequence. Treatment of lung carcinoma cells with KA and ALD leads to a loss of function of extracted p53, as determined by the analysis of extracted nuclear protein and in activation of p21. Our results uncover a plausible chemical link between inflammation and cancer and expand the already pivotal role of p53 dysfunction and cancer risk

    Evolution and rapid spread of a reassortant A(H3N2) virus that predominated the 2017-2018 influenza season

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    The 2017-2018 North American influenza season caused more hospitalizations and deaths than any year since the 2009 H1N1 pandemic. The majority of recorded influenza infections were caused by A(H3N2) viruses, with most of the virus's North American diversity falling into the A2 clade. Within A2, we observe a subclade which we call A2/re that rose to comprise almost 70 per cent of A(H3N2) viruses circulating in North America by early 2018. Unlike most fast-growing clades, however, A2/re contains no amino acid substitutions in the hemagglutinin (HA) segment. Moreover, hemagglutination inhibition assays did not suggest substantial antigenic differences between A2/re viruses and viruses sampled during the 2016-2017 season. Rather, we observe that the A2/re clade was the result of a reassortment event that occurred in late 2016 or early 2017 and involved the combination of the HA and PB1 segments of an A2 virus with neuraminidase (NA) and other segmentsa virus from the clade A1b. The success of this clade shows the need for antigenic analysis that targets NA in addition to HA. Our results illustrate the potential for non-HA drivers of viral success and necessitate the need for more thorough tracking of full viral genomes to better understand the dynamics of influenza epidemics

    Antiviral responses by swine primary bronchoepithelial cells are limited compared to human bronchoepithelial cells following influenza virus infection

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    Swine generate reassortant influenza viruses because they can be simultaneously infected with avian and human influenza; however, the features that restrict influenza reassortment in swine and human hosts are not fully understood. Type I and III interferons (IFNs) act as the first line of defense against influenza virus infection of respiratory epithelium. To determine if human and swine have different capacities to mount an antiviral response the expression of IFN and IFN-stimulated genes (ISG) in normal human bronchial epithelial (NHBE) cells and normal swine bronchial epithelial (NSBE) cells was evaluated following infection with human (H3N2), swine (H1N1), and avian (H5N3, H5N2, H5N1) influenza A viruses. Expression of IFNλ and ISGs were substantially higher in NHBE cells compared to NSBE cells following H5 avian influenza virus infection compared to human or swine influenza virus infection. This effect was associated with reduced H5 avian influenza virus replication in human cells at late times post infection. Further, RIG-I expression was lower in NSBE cells compared to NHBE cells suggesting reduced virus sensing. Together, these studies identify key differences in the antiviral response between human and swine respiratory epithelium alluding to differences that may govern influenza reassortment

    Antigenic characterization of highly pathogenic avian influenza A(H5N1) viruses with chicken and ferret antisera reveals clade-dependent variation in hemagglutination inhibition profiles.

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    Highly pathogenic avian influenza (HPAI) A(H5N1) viruses pose a significant economic burden to the poultry industry worldwide and have pandemic potential. Poultry vaccination against HPAI A(H5N1) viruses has been an important component of HPAI control measures and has been performed in Vietnam since 2005. To systematically assess antigenic matching of current vaccines to circulating field variants, we produced a panel of chicken and ferret antisera raised against historical and contemporary Vietnamese reference viruses representing clade variants that were detected between 2001 and 2014. The antisera were used for hemagglutination inhibition (HI) assays to generate data sets for analysis by antigenic cartography, allowing for a direct comparison of results from chicken or ferret antisera. HI antigenic maps, developed with antisera from both hosts, revealed varying patterns of antigenic relationships and clustering of viruses that were dependent on the clade of viruses analyzed. Antigenic relationships between existing poultry vaccines and circulating field viruses were also aligned with in vivo protection profiles determined by previously reported vaccine challenge studies. Our results establish the feasibility and utility of HPAI A(H5N1) antigenic characterization using chicken antisera and support further experimental and modeling studies to investigate quantitative relationships between genetic variation, antigenic drift and correlates of poultry vaccine protection in vivo

    The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening

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    Aims/hypothesis: Young children who develop multiple autoantibodies (mAbs) are at very high risk for type 1 diabetes. We assessed whether a population with mAbs detected by screening is also at very high risk, and how risk varies according to age, type of autoantibodies and metabolic status. Methods: Type 1 Diabetes TrialNet Pathway to Prevention participants with mAbs (n = 1815; age, 12.35 ± 9.39 years; range, 1-49 years) were analysed. Type 1 diabetes risk was assessed according to age, autoantibody type/number (insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], insulinoma-associated antigen-2 autoantibodies [IA-2A] or zinc transporter 8 autoantibodies [ZnT8A]) and Index60 (composite measure of fasting C-peptide, 60 min glucose and 60 min C-peptide). Cox regression and cumulative incidence curves were utilised in this cohort study. Results: Age was inversely related to type 1 diabetes risk in those with mAbs (HR 0.97 [95% CI 0.96, 0.99]). Among participants with 2 autoantibodies, those with GADA had less risk (HR 0.35 [95% CI 0.22, 0.57]) and those with IA-2A had higher risk (HR 2.82 [95% CI 1.76, 4.51]) of type 1 diabetes. Those with IAA and GADA had only a 17% 5 year risk of type 1 diabetes. The risk was significantly lower for those with Index60 <1.0 (HR 0.23 [95% CI 0.19, 0.30]) vs those with Index60 values ≥1.0. Among the 12% (225/1815) ≥12.0 years of age with GADA positivity, IA-2A negativity and Index60 <1.0, the 5 year risk of type 1 diabetes was 8%. Conclusions/interpretation: Type 1 diabetes risk varies substantially according to age, autoantibody type and metabolic status in individuals screened for mAbs. An appreciable proportion of older children and adults with mAbs appear to have a low risk of progressing to type 1 diabetes at 5 years. With this knowledge, clinical trials of type 1 diabetes prevention can better target those most likely to progress

    Summary distribution of slides and earth flows

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    Future movement of slides and earth flows is most likely to occur within the delineated parts of the landscape where these landslides have previously moved. OPEN-FILE REPORT 97-745 C 1997 This report is preliminary and has not been reviewed for conformity with U.S. Geological Survey editorial standards or with the Norm American Stratigraphic Code. Any use of trade, product, or firm names is for descriptive purposes only and does not imply endorsement by the U.S. Government. This database, identified as &apos;Summary Distribution of Slides and Earth Flows in the San Francisco Bay Region, California&apos;, has been approved for release and publication by the Director of the USGS. Although this database has been reviewed and is substantially complete, the USGS reserves the right to revise the data pursuant to further analysis and review. This database is released on condition that neither the USGS nor the U.S. Government may be held liable for any damages resulting from it use

    Characterization of Uncultivable Bat Influenza Virus Using a Replicative Synthetic Virus

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    Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARSCoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn’t attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses

    Concord Companions: Margaret Fuller, Friendship, and Desire

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    In this paper, we examine the rhetoric of friendship and desire in mid-nineteenth-century American writing. We begin by looking at Emerson's essay on friendship and Thoreau's poem "Sympathy" (1840) to provide a context for reading Margaret Fuller's fascinating texts on samesex bonds between women. Of particular interest to us is Fuller's translation of Elizabeth von Arnim's Die Gunderode (1840), a collection of letters between Arnim and the German Romantic poet Karoline von Gunderode which provides compelling insights into the early to mid-nineteenth-century continuum between female friendship and same-sex desire. We situate this translation alongside Fuller's own female friendships and expressions of love for women, more specifically her declarations of love to Anna Barker and, later, to George Sand. This latter relationship, we suggest, was a source of admiration and anxiety, for Sand's cross-dressing and fluid sense of gender identity was simultaneously celebrated and condemned in Fuller's Women in the Nineteenth Century (1843)
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