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Träfflista för sökning "WFRF:(Hansen Karina K.) "

Search: WFRF:(Hansen Karina K.)

  • Result 11-12 of 12
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11.
  • Wessel, Jennifer, et al. (author)
  • Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
  • 2015
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • Journal article (peer-reviewed)abstract
    • Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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12.
  • Brem, Jürgen, et al. (author)
  • Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors
  • 2022
  • In: Nature Chemistry. - : Springer Nature. - 1755-4330 .- 1755-4349. ; 14:1, s. 15-24
  • Journal article (peer-reviewed)abstract
    • Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-β-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential β-lactamase stable β-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.
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  • Result 11-12 of 12
Type of publication
journal article (11)
research review (1)
Type of content
peer-reviewed (12)
Author/Editor
Franks, Paul W. (7)
Pedersen, Oluf (7)
Hansen, Torben (7)
Deloukas, Panos (6)
Schulze, Matthias B. (6)
Meidtner, Karina (6)
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Wareham, Nicholas J. (6)
Kuusisto, Johanna (6)
Laakso, Markku (6)
McCarthy, Mark I (6)
Bork-Jensen, Jette (6)
Linneberg, Allan (6)
Grarup, Niels (6)
Ridker, Paul M. (6)
Chasman, Daniel I. (6)
Langenberg, Claudia (6)
Boehnke, Michael (6)
Mohlke, Karen L (6)
Thorleifsson, Gudmar (6)
Thorsteinsdottir, Un ... (6)
Stefansson, Kari (6)
Rotter, Jerome I. (6)
Hattersley, Andrew T (6)
Gustafsson, Stefan (6)
Loos, Ruth J F (6)
Hayward, Caroline (6)
Gudnason, Vilmundur (6)
Zeggini, Eleftheria (6)
Lange, Leslie A. (6)
Boeing, Heiner (5)
Salomaa, Veikko (5)
Lind, Lars (5)
Brandslund, Ivan (5)
Scott, Robert A (5)
Jorgensen, Torben (5)
Zhao, Wei (5)
Rasheed, Asif (5)
Saleheen, Danish (5)
Yaghootkar, Hanieh (5)
Mahajan, Anubha (5)
Walker, Mark (5)
Luan, Jian'an (5)
Kee, Frank (5)
Karpe, Fredrik (5)
Peloso, Gina M. (5)
Kovacs, Peter (5)
Zhao, Jing Hua (5)
Fornage, Myriam (5)
Uitterlinden, André ... (5)
Polasek, Ozren (5)
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University
Uppsala University (10)
Lund University (8)
Umeå University (5)
Karolinska Institutet (4)
University of Gothenburg (3)
Swedish University of Agricultural Sciences (2)
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Stockholm University (1)
Linköping University (1)
Swedish Museum of Natural History (1)
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Language
English (12)
Research subject (UKÄ/SCB)
Medical and Health Sciences (9)
Natural sciences (6)

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