26 research outputs found

    Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas

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    Integrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them were frequently silenced by epigenetic mechanisms. Notably, the pattern of genetic and epigenetic inactivation differed among B-NHL subtypes. Thus, the P53-inducible PIG7/LITAF was silenced by homozygous deletion in primary mediastinal B-cell lymphoma and by promoter hypermethylation in germinal center lymphoma, the proapoptotic BIM gene presented homozygous deletion in mantle cell lymphoma and promoter hypermethylation in Burkitt lymphoma, the proapoptotic BH3-only NOXA was mutated and preferentially silenced in diffuse large B-cell lymphoma, and INK4c/P18 was silenced by biallelic mutation in mantle-cell lymphoma. Our microarray strategy has identified novel candidate tumor suppressor genes inactivated by genetic and epigenetic mechanisms that substantially vary among the B-NHL subtypes

    Autoantibodies against type I IFNs in patients with life-threatening COVID-19

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    Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

    Pervasive gaps in Amazonian ecological research

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    Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

    7-Gons and genus three hyperelliptic curves

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    In this paper, we will give a general but completely elementary description for hyperelliptic curves of genus three whose Jacobian varieties have endomorphisms by the real cyclotomic field ℚ(ζ7 + ζ̄7). We study the algebraic correspondences on these curves which are lifts of algebraic correspondences on a conic in P2 associated with Poncelet 7-gons. These correspondences induce endomorphisms φ on the Jacobians which satisfy φ3+φ2-2φ-1=0. Moreover, we study Humbert\u27s modular equations which characterize the curves of genus three having these real multiplications. © 2012 Springer-Verlag
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