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  1. Article: Mutations and polymorphisms of the gene of the major human blood protein, serum albumin

    Minchiotti, Lorenzo / Galliano, Monica / Kragh-Hansen, Ulrich / Peters, Theodore Jr

    Human mutation. 2008 Aug., v. 29, no. 8

    2008  

    Abstract: We have tabulated the 77 currently known mutations of the familiar human blood protein, serum albumin (ALB). A total of 65 mutations result in bisalbuminemia. Physiological and structural effects of these mutations are included where observed. Most of ... ...

    Abstract We have tabulated the 77 currently known mutations of the familiar human blood protein, serum albumin (ALB). A total of 65 mutations result in bisalbuminemia. Physiological and structural effects of these mutations are included where observed. Most of the changes are benign. The majority of them were detected upon clinical electrophoretic studies, as a result of a point mutation of a charged amino acid residue. Three were discovered by their strong binding of thyroxine or triiodothyronine. A total of 12 of the tabulated mutations result in analbuminemia, defined as a serum albumin concentration of <1 g/L. These were generally detected upon finding a low albumin concentration in patients with mild edema, and involve either splicing errors negating translation or premature stop codons producing truncated albumin molecules. A total of nine mutations, five of those with analbuminemia and four resulting in variants modified near the C-terminal end, cause frameshifts. Allotypes from three of the point mutations become N-glycosylated and one C-terminal frameshift mutation shows O-glycosylation. Hum Mutat 0,1-10, 2008.
    Language English
    Dates of publication 2008-08
    Size p. 1007-1016.
    Publishing place Wiley Subscription Services, Inc., A Wiley Company
    Document type Article
    ZDB-ID 1126646-6
    ISSN 1098-1004 ; 1059-7794
    ISSN (online) 1098-1004
    ISSN 1059-7794
    DOI 10.1002/humu.20754
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Increased Iron Absorption in Uroporphyrin-Treated Rats

    Weaver, Gary A. / Franck, Christopher A. / Harris, Mark D. / Peters, Jr, Theodore

    Digestion - International Journal of Gastroenterology

    1991  Volume 49, Issue 3, Page(s) 151–155

    Abstract: Rats were given 59Fe (28 μg) together with doses of 0, 2 and 200 μg of uroporphyrin III in paired observations. Absorption of 59Fe was determined by comparing whole body counts of the rats 30 min and 7 days after dosing. Prior treatment with 200 μg of ... ...

    Abstract Rats were given 59Fe (28 μg) together with doses of 0, 2 and 200 μg of uroporphyrin III in paired observations. Absorption of 59Fe was determined by comparing whole body counts of the rats 30 min and 7 days after dosing. Prior treatment with 200 μg of uroporphyrin twice daily for 3 days was associated with significantly increased 59Fe absorption of 6.2% compared to the absorption of 4.6% without uroporphyrin (control) and 4.6% with a 2-μg dose (p < 0.05).
    Keywords Porphyria cutanea tarda ; Iron absorption ; Uroporphyrin ; Porphyrin
    Language English
    Publisher S. Karger AG
    Publishing place Basel
    Publishing country Switzerland
    Document type Article ; Online
    ZDB-ID 1712-7
    ISSN 1421-9867 ; 0012-2823 ; 0012-2823
    ISSN (online) 1421-9867
    ISSN 0012-2823
    DOI 10.1159/000200714
    Database Karger publisher's database

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  3. Article: Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization.

    Sevcik, Molly A / Ghilardi, Joseph R / Peters, Christopher M / Lindsay, Theodore H / Halvorson, Kyle G / Jonas, Beth M / Kubota, Kazufumi / Kuskowski, Michael A / Boustany, Leila / Shelton, David L / Mantyh, Patrick W

    Pain

    2005  Volume 115, Issue 1-2, Page(s) 128–141

    Abstract: Bone cancer pain can be difficult to control, as it appears to be driven simultaneously by inflammatory, neuropathic and tumorigenic mechanisms. As nerve growth factor (NGF) has been shown to modulate inflammatory and neuropathic pain states, we focused ... ...

    Abstract Bone cancer pain can be difficult to control, as it appears to be driven simultaneously by inflammatory, neuropathic and tumorigenic mechanisms. As nerve growth factor (NGF) has been shown to modulate inflammatory and neuropathic pain states, we focused on a novel NGF sequestering antibody and demonstrated that two administrations of this therapy in a mouse model of bone cancer pain produces a profound reduction in both ongoing and movement-evoked bone cancer pain-related behaviors that was greater than that achieved with acute administration of 10 or 30 mg/kg of morphine. This therapy also reduced several neurochemical changes associated with peripheral and central sensitization in the dorsal root ganglion and spinal cord, whereas the therapy did not influence disease progression or markers of sensory or sympathetic innervation in the skin or bone. Mechanistically, the great majority of sensory fibers that innervate the bone are CGRP/TrkA expressing fibers, and if the sensitization and activation of these fibers is blocked by anti-NGF therapy there would not be another population of nociceptors, such as the non-peptidergic IB4/RET-IR nerve fibers, to take their place in signaling nociceptive events.
    MeSH term(s) Animals ; Antibodies, Monoclonal/administration & dosage ; Biomarkers/metabolism ; Femoral Neoplasms/complications ; Femoral Neoplasms/diagnosis ; Femoral Neoplasms/drug therapy ; Male ; Mice ; Mice, Inbred C3H ; Nerve Growth Factor/immunology ; Nociceptors/drug effects ; Nociceptors/metabolism ; Pain/diagnosis ; Pain/etiology ; Pain/prevention & control ; Peripheral Nerves/drug effects ; Peripheral Nerves/metabolism ; Sarcoma/complications ; Sarcoma/diagnosis ; Sarcoma/drug therapy ; Spinal Cord/drug effects ; Spinal Cord/metabolism ; Treatment Outcome ; Tumor Cells, Cultured
    Chemical Substances Antibodies, Monoclonal ; Biomarkers ; Nerve Growth Factor (9061-61-4)
    Language English
    Publishing date 2005-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1016/j.pain.2005.02.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Tumor-induced injury of primary afferent sensory nerve fibers in bone cancer pain.

    Peters, Christopher M / Ghilardi, Joseph R / Keyser, Cathy P / Kubota, Kazufumi / Lindsay, Theodore H / Luger, Nancy M / Mach, David B / Schwei, Matthew J / Sevcik, Molly A / Mantyh, Patrick W

    Experimental neurology

    2005  Volume 193, Issue 1, Page(s) 85–100

    Abstract: Bone is the most common site of chronic pain in patients with metastatic cancer. What remains unclear are the mechanisms that generate this pain and why bone cancer pain can be so severe and refractory to treatment with opioids. Here we show that ... ...

    Abstract Bone is the most common site of chronic pain in patients with metastatic cancer. What remains unclear are the mechanisms that generate this pain and why bone cancer pain can be so severe and refractory to treatment with opioids. Here we show that following injection and confinement of NCTC 2472 osteolytic tumor cells within the mouse femur, tumor cells sensitize and injure the unmyelinated and myelinated sensory fibers that innervate the marrow and mineralized bone. This tumor-induced injury of sensory nerve fibers is accompanied by an increase in ongoing and movement-evoked pain behaviors, an upregulation of activating transcription factor 3 (ATF3) and galanin by sensory neurons that innervate the tumor-bearing femur, upregulation of glial fibrillary acidic protein (GFAP) and hypertrophy of satellite cells surrounding sensory neuron cell bodies within the ipsilateral dorsal root ganglia (DRG), and macrophage infiltration of the DRG ipsilateral to the tumor-bearing femur. Similar neurochemical changes have been described following peripheral nerve injury and in other non-cancerous neuropathic pain states. Chronic treatment with gabapentin did not influence tumor growth, tumor-induced bone destruction or the tumor-induced neurochemical reorganization that occurs in sensory neurons or the spinal cord, but it did attenuate both ongoing and movement-evoked bone cancer-related pain behaviors. These results suggest that even when the tumor is confined within the bone, a component of bone cancer pain is due to tumor-induced injury to primary afferent nerve fibers that innervate the tumor-bearing bone. Tumor-derived, inflammatory, and neuropathic mechanisms may therefore be simultaneously driving this chronic pain state.
    MeSH term(s) Afferent Pathways/chemistry ; Afferent Pathways/pathology ; Animals ; Bone Neoplasms/complications ; Bone Neoplasms/pathology ; Male ; Mice ; Mice, Inbred C3H ; Neurons, Afferent/chemistry ; Neurons, Afferent/pathology ; Pain/etiology ; Pain/pathology ; Polyneuropathies/etiology ; Polyneuropathies/pathology
    Language English
    Publishing date 2005-05
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 207148-4
    ISSN 1090-2430 ; 0014-4886
    ISSN (online) 1090-2430
    ISSN 0014-4886
    DOI 10.1016/j.expneurol.2004.11.028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: New filovirus disease classification and nomenclature.

    Kuhn, Jens H / Adachi, Takuya / Adhikari, Neill K J / Arribas, Jose R / Bah, Ibrahima Elhadj / Bausch, Daniel G / Bhadelia, Nahid / Borchert, Matthias / Brantsæter, Arne Broch / Brett-Major, David M / Burgess, Timothy H / Chertow, Daniel S / Chute, Christopher G / Cieslak, Theodore J / Colebunders, Robert / Crozier, Ian / Davey, Richard T / de Clerck, Hilde / Delgado, Rafael /
    Evans, Laura / Fallah, Mosoka / Fischer, William A / Fletcher, Tom E / Fowler, Robert A / Grünewald, Thomas / Hall, Andy / Hewlett, Angela / Hoepelman, Andy I M / Houlihan, Catherine F / Ippolito, Giuseppe / Jacob, Shevin T / Jacobs, Michael / Jakob, Robert / Jacquerioz, Frederique A / Kaiser, Laurent / Kalil, Andre C / Kamara, Rashidatu F / Kapetshi, Jimmy / Klenk, Hans-Dieter / Kobinger, Gary / Kortepeter, Mark G / Kraft, Colleen S / Kratz, Thomas / Bosa, Henry S Kyobe / Lado, Marta / Lamontagne, François / Lane, H Cliff / Lobel, Leslie / Lutwama, Julius / Lyon, G Marshall / Massaquoi, Moses B F / Massaquoi, Thomas A / Mehta, Aneesh K / Makuma, Vital Mondonge / Murthy, Srinivas / Musoke, Tonny Seikikongo / Muyembe-Tamfum, Jean-Jacques / Nakyeyune, Phiona / Nanclares, Carolina / Nanyunja, Miriam / Nsio-Mbeta, Justus / O'Dempsey, Tim / Pawęska, Janusz T / Peters, Clarence J / Piot, Peter / Rapp, Christophe / Renaud, Bertrand / Ribner, Bruce / Sabeti, Pardis C / Schieffelin, John S / Slenczka, Werner / Soka, Moses J / Sprecher, Armand / Strong, James / Swanepoel, Robert / Uyeki, Timothy M / van Herp, Michel / Vetter, Pauline / Wohl, David A / Wolf, Timo / Wolz, Anja / Wurie, Alie H / Yoti, Zabulon

    Nature reviews. Microbiology

    2019  Volume 17, Issue 5, Page(s) 261–263

    MeSH term(s) Filoviridae/classification ; Filoviridae/pathogenicity ; Filoviridae Infections/classification ; Hemorrhagic Fever, Ebola/classification ; Humans ; World Health Organization
    Language English
    Publishing date 2019-03-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2139054-X
    ISSN 1740-1534 ; 1740-1526
    ISSN (online) 1740-1534
    ISSN 1740-1526
    DOI 10.1038/s41579-019-0187-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention.

    Wang, Zhe / Emmerich, Andrew / Pillon, Nicolas J / Moore, Tim / Hemerich, Daiane / Cornelis, Marilyn C / Mazzaferro, Eugenia / Broos, Siacia / Ahluwalia, Tarunveer S / Bartz, Traci M / Bentley, Amy R / Bielak, Lawrence F / Chong, Mike / Chu, Audrey Y / Berry, Diane / Dorajoo, Rajkumar / Dueker, Nicole D / Kasbohm, Elisa / Feenstra, Bjarke /
    Feitosa, Mary F / Gieger, Christian / Graff, Mariaelisa / Hall, Leanne M / Haller, Toomas / Hartwig, Fernando P / Hillis, David A / Huikari, Ville / Heard-Costa, Nancy / Holzapfel, Christina / Jackson, Anne U / Johansson, Åsa / Jørgensen, Anja Moltke / Kaakinen, Marika A / Karlsson, Robert / Kerr, Kathleen F / Kim, Boram / Koolhaas, Chantal M / Kutalik, Zoltan / Lagou, Vasiliki / Lind, Penelope A / Lorentzon, Mattias / Lyytikäinen, Leo-Pekka / Mangino, Massimo / Metzendorf, Christoph / Monroe, Kristine R / Pacolet, Alexander / Pérusse, Louis / Pool, Rene / Richmond, Rebecca C / Rivera, Natalia V / Robiou-du-Pont, Sebastien / Schraut, Katharina E / Schulz, Christina-Alexandra / Stringham, Heather M / Tanaka, Toshiko / Teumer, Alexander / Turman, Constance / van der Most, Peter J / Vanmunster, Mathias / van Rooij, Frank J A / van Vliet-Ostaptchouk, Jana V / Zhang, Xiaoshuai / Zhao, Jing-Hua / Zhao, Wei / Balkhiyarova, Zhanna / Balslev-Harder, Marie N / Baumeister, Sebastian E / Beilby, John / Blangero, John / Boomsma, Dorret I / Brage, Soren / Braund, Peter S / Brody, Jennifer A / Bruinenberg, Marcel / Ekelund, Ulf / Liu, Ching-Ti / Cole, John W / Collins, Francis S / Cupples, L Adrienne / Esko, Tõnu / Enroth, Stefan / Faul, Jessica D / Fernandez-Rhodes, Lindsay / Fohner, Alison E / Franco, Oscar H / Galesloot, Tessel E / Gordon, Scott D / Grarup, Niels / Hartman, Catharina A / Heiss, Gerardo / Hui, Jennie / Illig, Thomas / Jago, Russell / James, Alan / Joshi, Peter K / Jung, Taeyeong / Kähönen, Mika / Kilpeläinen, Tuomas O / Koh, Woon-Puay / Kolcic, Ivana / Kraft, Peter P / Kuusisto, Johanna / Launer, Lenore J / Li, Aihua / Linneberg, Allan / Luan, Jian'an / Vidal, Pedro Marques / Medland, Sarah E / Milaneschi, Yuri / Moscati, Arden / Musk, Bill / Nelson, Christopher P / Nolte, Ilja M / Pedersen, Nancy L / Peters, Annette / Peyser, Patricia A / Power, Christine / Raitakari, Olli T / Reedik, Mägi / Reiner, Alex P / Ridker, Paul M / Rudan, Igor / Ryan, Kathy / Sarzynski, Mark A / Scott, Laura J / Scott, Robert A / Sidney, Stephen / Siggeirsdottir, Kristin / Smith, Albert V / Smith, Jennifer A / Sonestedt, Emily / Strøm, Marin / Tai, E Shyong / Teo, Koon K / Thorand, Barbara / Tönjes, Anke / Tremblay, Angelo / Uitterlinden, Andre G / Vangipurapu, Jagadish / van Schoor, Natasja / Völker, Uwe / Willemsen, Gonneke / Williams, Kayleen / Wong, Quenna / Xu, Huichun / Young, Kristin L / Yuan, Jian Min / Zillikens, M Carola / Zonderman, Alan B / Ameur, Adam / Bandinelli, Stefania / Bis, Joshua C / Boehnke, Michael / Bouchard, Claude / Chasman, Daniel I / Smith, George Davey / de Geus, Eco J C / Deldicque, Louise / Dörr, Marcus / Evans, Michele K / Ferrucci, Luigi / Fornage, Myriam / Fox, Caroline / Garland, Theodore / Gudnason, Vilmundur / Gyllensten, Ulf / Hansen, Torben / Hayward, Caroline / Horta, Bernardo L / Hyppönen, Elina / Jarvelin, Marjo-Riitta / Johnson, W Craig / Kardia, Sharon L R / Kiemeney, Lambertus A / Laakso, Markku / Langenberg, Claudia / Lehtimäki, Terho / Marchand, Loic Le / Magnusson, Patrik K E / Martin, Nicholas G / Melbye, Mads / Metspalu, Andres / Meyre, David / North, Kari E / Ohlsson, Claes / Oldehinkel, Albertine J / Orho-Melander, Marju / Pare, Guillaume / Park, Taesung / Pedersen, Oluf / Penninx, Brenda W J H / Pers, Tune H / Polasek, Ozren / Prokopenko, Inga / Rotimi, Charles N / Samani, Nilesh J / Sim, Xueling / Snieder, Harold / Sørensen, Thorkild I A / Spector, Tim D / Timpson, Nicholas J / van Dam, Rob M / van der Velde, Nathalie / van Duijn, Cornelia M / Vollenweider, Peter / Völzke, Henry / Voortman, Trudy / Waeber, Gérard / Wareham, Nicholas J / Weir, David R / Wichmann, Heinz-Erich / Wilson, James F / Hevener, Andrea L / Krook, Anna / Zierath, Juleen R / Thomis, Martine A I / Loos, Ruth J F / Hoed, Marcel den

    Nature genetics

    2022  Volume 54, Issue 9, Page(s) 1332–1344

    Abstract: Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide ... ...

    Abstract Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type II
    MeSH term(s) Actinin/genetics ; Cross-Sectional Studies ; Exercise/physiology ; Genome-Wide Association Study ; Humans ; Leisure Activities ; Sedentary Behavior
    Chemical Substances ACTN3 protein, human ; Actinin (11003-00-2)
    Language English
    Publishing date 2022-09-07
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-022-01165-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Book ; Online: Intercomparison of NO2, O4, O3 and HCHO slant column measurements by MAX-DOAS and zenith-sky UV–visible spectrometers during CINDI-2

    Kreher, Karin / Roozendael, Michel / Hendrick, Francois / Apituley, Arnoud / Dimitropoulou, Ermioni / Frieß, Udo / Richter, Andreas / Wagner, Thomas / Lampel, Johannes / Abuhassan, Nader / Ang, Li / Anguas, Monica / Bais, Alkis / Benavent, Nuria / Bösch, Tim / Bognar, Kristof / Borovski, Alexander / Bruchkouski, Ilya / Cede, Alexander /
    Chan, Ka Lok / Donner, Sebastian / Drosoglou, Theano / Fayt, Caroline / Finkenzeller, Henning / Garcia-Nieto, David / Gielen, Clio / Gómez-Martín, Laura / Hao, Nan / Henzing, Bas / Herman, Jay R. / Hermans, Christian / Hoque, Syedul / Irie, Hitoshi / Jin, Junli / Johnston, Paul / Khayyam Butt, Junaid / Khokhar, Fahim / Koenig, Theodore K. / Kuhn, Jonas / Kumar, Vinod / Liu, Cheng / Ma, Jianzhong / Merlaud, Alexis / Mishra, Abhishek K. / Müller, Moritz / Navarro-Comas, Monica / Ostendorf, Mareike / Pazmino, Andrea / Peters, Enno / Pinardi, Gaia / Pinharanda, Manuel / Piters, Ankie / Platt, Ulrich / Postylyakov, Oleg / Prados-Roman, Cristina / Puentedura, Olga / Querel, Richard / Saiz-Lopez, Alfonso / Schönhardt, Anja / Schreier, Stefan F. / Seyler, André / Sinha, Vinayak / Spinei, Elena / Strong, Kimberly / Tack, Frederik / Tian, Xin / Tiefengraber, Martin / Tirpitz, Jan-Lukas / Gent, Jeroen / Volkamer, Rainer / Vrekoussis, Mihalis / Wang, Shanshan / Wang, Zhuoru / Wenig, Mark / Wittrock, Folkard / Xie, Pinhua H. / Xu, Jin / Yela, Margarita / Zhang, Chengxin / Zhao, Xiaoyi

    eISSN: 1867-8548

    2020  

    Abstract: In September 2016, 36 spectrometers from 24 institutes measured a number of key atmospheric pollutants for a period of 17 d during the Second Cabauw Intercomparison campaign for Nitrogen Dioxide measuring Instruments (CINDI-2) that took place at Cabauw, ... ...

    Abstract In September 2016, 36 spectrometers from 24 institutes measured a number of key atmospheric pollutants for a period of 17 d during the Second Cabauw Intercomparison campaign for Nitrogen Dioxide measuring Instruments (CINDI-2) that took place at Cabauw, the Netherlands (51.97 ∘ N, 4.93 ∘ E). We report on the outcome of the formal semi-blind intercomparison exercise, which was held under the umbrella of the Network for the Detection of Atmospheric Composition Change (NDACC) and the European Space Agency (ESA). The three major goals of CINDI-2 were (1) to characterise and better understand the differences between a large number of multi-axis differential optical absorption spectroscopy (MAX-DOAS) and zenith-sky DOAS instruments and analysis methods, (2) to define a robust methodology for performance assessment of all participating instruments, and (3) to contribute to a harmonisation of the measurement settings and retrieval methods. This, in turn, creates the capability to produce consistent high-quality ground-based data sets, which are an essential requirement to generate reliable long-term measurement time series suitable for trend analysis and satellite data validation. The data products investigated during the semi-blind intercomparison are slant columns of nitrogen dioxide ( NO 2 ), the oxygen collision complex ( O 4 ) and ozone ( O 3 ) measured in the UV and visible wavelength region, formaldehyde (HCHO) in the UV spectral region, and NO 2 in an additional (smaller) wavelength range in the visible region. The campaign design and implementation processes are discussed in detail including the measurement protocol, calibration procedures and slant column retrieval settings. Strong emphasis was put on the careful alignment and synchronisation of the measurement systems, resulting in a unique set of measurements made under highly comparable air mass conditions. The CINDI-2 data sets were investigated using a regression analysis of the slant columns measured by each instrument and for each of the target data products. The slope and intercept of the regression analysis respectively quantify the mean systematic bias and offset of the individual data sets against the selected reference (which is obtained from the median of either all data sets or a subset), and the rms error provides an estimate of the measurement noise or dispersion. These three criteria are examined and for each of the parameters and each of the data products, performance thresholds are set and applied to all the measurements. The approach presented here has been developed based on heritage from previous intercomparison exercises. It introduces a quantitative assessment of the consistency between all the participating instruments for the MAX-DOAS and zenith-sky DOAS techniques.
    Subject code 333
    Language English
    Publishing date 2020-05-06
    Publishing country de
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

    Gordon, David E / Hiatt, Joseph / Bouhaddou, Mehdi / Rezelj, Veronica V / Ulferts, Svenja / Braberg, Hannes / Jureka, Alexander S / Obernier, Kirsten / Guo, Jeffrey Z / Batra, Jyoti / Kaake, Robyn M / Weckstein, Andrew R / Owens, Tristan W / Gupta, Meghna / Pourmal, Sergei / Titus, Erron W / Cakir, Merve / Soucheray, Margaret / McGregor, Michael /
    Cakir, Zeynep / Jang, Gwendolyn / O'Meara, Matthew J / Tummino, Tia A / Zhang, Ziyang / Foussard, Helene / Rojc, Ajda / Zhou, Yuan / Kuchenov, Dmitry / Hüttenhain, Ruth / Xu, Jiewei / Eckhardt, Manon / Swaney, Danielle L / Fabius, Jacqueline M / Ummadi, Manisha / Tutuncuoglu, Beril / Rathore, Ujjwal / Modak, Maya / Haas, Paige / Haas, Kelsey M / Naing, Zun Zar Chi / Pulido, Ernst H / Shi, Ying / Barrio-Hernandez, Inigo / Memon, Danish / Petsalaki, Eirini / Dunham, Alistair / Marrero, Miguel Correa / Burke, David / Koh, Cassandra / Vallet, Thomas / Silvas, Jesus A / Azumaya, Caleigh M / Billesbølle, Christian / Brilot, Axel F / Campbell, Melody G / Diallo, Amy / Dickinson, Miles Sasha / Diwanji, Devan / Herrera, Nadia / Hoppe, Nick / Kratochvil, Huong T / Liu, Yanxin / Merz, Gregory E / Moritz, Michelle / Nguyen, Henry C / Nowotny, Carlos / Puchades, Cristina / Rizo, Alexandrea N / Schulze-Gahmen, Ursula / Smith, Amber M / Sun, Ming / Young, Iris D / Zhao, Jianhua / Asarnow, Daniel / Biel, Justin / Bowen, Alisa / Braxton, Julian R / Chen, Jen / Chio, Cynthia M / Chio, Un Seng / Deshpande, Ishan / Doan, Loan / Faust, Bryan / Flores, Sebastian / Jin, Mingliang / Kim, Kate / Lam, Victor L / Li, Fei / Li, Junrui / Li, Yen-Li / Li, Yang / Liu, Xi / Lo, Megan / Lopez, Kyle E / Melo, Arthur A / Moss, Frank R / Nguyen, Phuong / Paulino, Joana / Pawar, Komal Ishwar / Peters, Jessica K / Pospiech, Thomas H / Safari, Maliheh / Sangwan, Smriti / Schaefer, Kaitlin / Thomas, Paul V / Thwin, Aye C / Trenker, Raphael / Tse, Eric / Tsui, Tsz Kin Martin / Wang, Feng / Whitis, Natalie / Yu, Zanlin / Zhang, Kaihua / Zhang, Yang / Zhou, Fengbo / Saltzberg, Daniel / Hodder, Anthony J / Shun-Shion, Amber S / Williams, Daniel M / White, Kris M / Rosales, Romel / Kehrer, Thomas / Miorin, Lisa / Moreno, Elena / Patel, Arvind H / Rihn, Suzannah / Khalid, Mir M / Vallejo-Gracia, Albert / Fozouni, Parinaz / Simoneau, Camille R / Roth, Theodore L / Wu, David / Karim, Mohd Anisul / Ghoussaini, Maya / Dunham, Ian / Berardi, Francesco / Weigang, Sebastian / Chazal, Maxime / Park, Jisoo / Logue, James / McGrath, Marisa / Weston, Stuart / Haupt, Robert / Hastie, C James / Elliott, Matthew / Brown, Fiona / Burness, Kerry A / Reid, Elaine / Dorward, Mark / Johnson, Clare / Wilkinson, Stuart G / Geyer, Anna / Giesel, Daniel M / Baillie, Carla / Raggett, Samantha / Leech, Hannah / Toth, Rachel / Goodman, Nicola / Keough, Kathleen C / Lind, Abigail L / Klesh, Reyna J / Hemphill, Kafi R / Carlson-Stevermer, Jared / Oki, Jennifer / Holden, Kevin / Maures, Travis / Pollard, Katherine S / Sali, Andrej / Agard, David A / Cheng, Yifan / Fraser, James S / Frost, Adam / Jura, Natalia / Kortemme, Tanja / Manglik, Aashish / Southworth, Daniel R / Stroud, Robert M / Alessi, Dario R / Davies, Paul / Frieman, Matthew B / Ideker, Trey / Abate, Carmen / Jouvenet, Nolwenn / Kochs, Georg / Shoichet, Brian / Ott, Melanie / Palmarini, Massimo / Shokat, Kevan M / García-Sastre, Adolfo / Rassen, Jeremy A / Grosse, Robert / Rosenberg, Oren S / Verba, Kliment A / Basler, Christopher F / Vignuzzi, Marco / Peden, Andrew A / Beltrao, Pedro / Krogan, Nevan J

    Science (New York, N.Y.)

    2020  Volume 370, Issue 6521

    Abstract: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and ...

    Abstract The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.
    MeSH term(s) COVID-19/metabolism ; Conserved Sequence ; Coronavirus Nucleocapsid Proteins/genetics ; Coronavirus Nucleocapsid Proteins/metabolism ; Cryoelectron Microscopy ; Host Microbial Interactions ; Humans ; Mitochondrial Membrane Transport Proteins/genetics ; Mitochondrial Membrane Transport Proteins/metabolism ; Mitochondrial Precursor Protein Import Complex Proteins ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Protein Conformation ; Protein Interaction Maps ; Severe acute respiratory syndrome-related coronavirus/metabolism ; SARS-CoV-2/metabolism ; Severe Acute Respiratory Syndrome/metabolism
    Chemical Substances Coronavirus Nucleocapsid Proteins ; Mitochondrial Membrane Transport Proteins ; Mitochondrial Precursor Protein Import Complex Proteins ; Phosphoproteins ; TOMM70 protein, human ; nucleocapsid phosphoprotein, SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-10-15
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abe9403
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

    Gordon, David E. / Hiatt, Joseph / Bouhaddou, Mehdi / Rezelj, Veronica V. / Ulferts, Svenja / Braberg, Hannes / Jureka, Alexander S. / Obernier, Kirsten / Guo, Jeffrey Z. / Batra, Jyoti / Kaake, Robyn M. / Weckstein, Andrew R. / Owens, Tristan W. / Gupta, Meghna / Pourmal, Sergei / Titus, Erron W. / Cakir, Merve / Soucheray, Margaret / McGregor, Michael /
    Cakir, Zeynep / Jang, Gwendolyn / O’Meara, Matthew J. / Tummino, Tia A. / Zhang, Ziyang / Foussard, Helene / Rojc, Ajda / Zhou, Yuan / Kuchenov, Dmitry / Hüttenhain, Ruth / Xu, Jiewei / Eckhardt, Manon / Swaney, Danielle L. / Fabius, Jacqueline M. / Ummadi, Manisha / Tutuncuoglu, Beril / Rathore, Ujjwal / Modak, Maya / Haas, Paige / Haas, Kelsey M. / Naing, Zun Zar Chi / Pulido, Ernst H. / Shi, Ying / Barrio-Hernandez, Inigo / Memon, Danish / Petsalaki, Eirini / Dunham, Alistair / Marrero, Miguel Correa / Burke, David / Koh, Cassandra / Vallet, Thomas / Silvas, Jesus A. / Azumaya, Caleigh M. / Billesbølle, Christian / Brilot, Axel F. / Campbell, Melody G. / Diallo, Amy / Dickinson, Miles Sasha / Diwanji, Devan / Herrera, Nadia / Hoppe, Nick / Kratochvil, Huong T. / Liu, Yanxin / Merz, Gregory E. / Moritz, Michelle / Nguyen, Henry C. / Nowotny, Carlos / Puchades, Cristina / Rizo, Alexandrea N. / Schulze-Gahmen, Ursula / Smith, Amber M. / Sun, Ming / Young, Iris D. / Zhao, Jianhua / Asarnow, Daniel / Biel, Justin / Bowen, Alisa / Braxton, Julian R. / Chen, Jen / Chio, Cynthia M. / Chio, Un Seng / Deshpande, Ishan / Doan, Loan / Faust, Bryan / Flores, Sebastian / Jin, Mingliang / Kim, Kate / Lam, Victor L. / Li, Fei / Li, Junrui / Li, Yen-Li / Li, Yang / Liu, Xi / Lo, Megan / Lopez, Kyle E. / Melo, Arthur A. / Moss, Frank R. / Nguyen, Phuong / Paulino, Joana / Pawar, Komal Ishwar / Peters, Jessica K. / Pospiech, Thomas H. / Safari, Maliheh / Sangwan, Smriti / Schaefer, Kaitlin / Thomas, Paul V. / Thwin, Aye C. / Trenker, Raphael / Tse, Eric / Tsui, Tsz Kin Martin / Wang, Feng / Whitis, Natalie / Yu, Zanlin / Zhang, Kaihua / Zhang, Yang / Zhou, Fengbo / Saltzberg, Daniel / Hodder, Anthony J. / Shun-Shion, Amber S. / Williams, Daniel M. / White, Kris M. / Rosales, Romel / Kehrer, Thomas / Miorin, Lisa / Moreno, Elena / Patel, Arvind H. / Rihn, Suzannah / Khalid, Mir M. / Vallejo-Gracia, Albert / Fozouni, Parinaz / Simoneau, Camille R. / Roth, Theodore L. / Wu, David / Karim, Mohd Anisul / Ghoussaini, Maya / Dunham, Ian / Berardi, Francesco / Weigang, Sebastian / Chazal, Maxime / Park, Jisoo / Logue, James / McGrath, Marisa / Weston, Stuart / Haupt, Robert / Hastie, C. James / Elliott, Matthew / Brown, Fiona / Burness, Kerry A. / Reid, Elaine / Dorward, Mark / Johnson, Clare / Wilkinson, Stuart G. / Geyer, Anna / Giesel, Daniel M. / Baillie, Carla / Raggett, Samantha / Leech, Hannah / Toth, Rachel / Goodman, Nicola / Keough, Kathleen C. / Lind, Abigail L. / Klesh, Reyna J. / Hemphill, Kafi R. / Carlson-Stevermer, Jared / Oki, Jennifer / Holden, Kevin / Maures, Travis / Pollard, Katherine S. / Sali, Andrej / Agard, David A. / Cheng, Yifan / Fraser, James S. / Frost, Adam / Jura, Natalia / Kortemme, Tanja / Manglik, Aashish / Southworth, Daniel R. / Stroud, Robert M. / Alessi, Dario R. / Davies, Paul / Frieman, Matthew B. / Ideker, Trey / Abate, Carmen / Jouvenet, Nolwenn / Kochs, Georg / Shoichet, Brian / Ott, Melanie / Palmarini, Massimo / Shokat, Kevan M. / García-Sastre, Adolfo / Rassen, Jeremy A. / Grosse, Robert / Rosenberg, Oren S. / Verba, Kliment A. / Basler, Christopher F. / Vignuzzi, Marco / Peden, Andrew A. / Beltrao, Pedro / Krogan, Nevan J.

    Science

    2020  , Page(s) eabe9403

    Abstract: The COVID-19 (Coronavirus disease-2019) pandemic, caused by the SARS-CoV-2 coronavirus, is a significant threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and ... ...

    Abstract The COVID-19 (Coronavirus disease-2019) pandemic, caused by the SARS-CoV-2 coronavirus, is a significant threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and MERS-CoV. Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analysis for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 Orf9b, an interaction we structurally characterized using cryo-EM. Combining genetically-validated host factors with both COVID-19 patient genetic data and medical billing records identified important molecular mechanisms and potential drug treatments that merit further molecular and clinical study.
    Keywords Multidisciplinary ; covid19
    Language English
    Publisher American Association for the Advancement of Science (AAAS)
    Publishing country us
    Document type Article ; Online
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abe9403
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

    Sampson, Joshua N / Wheeler, William A / Yeager, Meredith / Panagiotou, Orestis / Wang, Zhaoming / Berndt, Sonja I / Lan, Qing / Abnet, Christian C / Amundadottir, Laufey T / Figueroa, Jonine D / Landi, Maria Teresa / Mirabello, Lisa / Savage, Sharon A / Taylor, Philip R / De Vivo, Immaculata / McGlynn, Katherine A / Purdue, Mark P / Rajaraman, Preetha / Adami, Hans-Olov /
    Ahlbom, Anders / Albanes, Demetrius / Amary, Maria Fernanda / An, She-Juan / Andersson, Ulrika / Andriole, Gerald / Andrulis, Irene L / Angelucci, Emanuele / Ansell, Stephen M / Arici, Cecilia / Armstrong, Bruce K / Arslan, Alan A / Austin, Melissa A / Baris, Dalsu / Barkauskas, Donald A / Bassig, Bryan A / Becker, Nikolaus / Benavente, Yolanda / Benhamou, Simone / Berg, Christine / Van Den Berg, David / Bernstein, Leslie / Bertrand, Kimberly A / Birmann, Brenda M / Black, Amanda / Boeing, Heiner / Boffetta, Paolo / Boutron-Ruault, Marie-Christine / Bracci, Paige M / Brinton, Louise / Brooks-Wilson, Angela R / Bueno-de-Mesquita, H Bas / Burdett, Laurie / Buring, Julie / Butler, Mary Ann / Cai, Qiuyin / Cancel-Tassin, Geraldine / Canzian, Federico / Carrato, Alfredo / Carreon, Tania / Carta, Angela / Chan, John K C / Chang, Ellen T / Chang, Gee-Chen / Chang, I-Shou / Chang, Jiang / Chang-Claude, Jenny / Chen, Chien-Jen / Chen, Chih-Yi / Chen, Chu / Chen, Chung-Hsing / Chen, Constance / Chen, Hongyan / Chen, Kexin / Chen, Kuan-Yu / Chen, Kun-Chieh / Chen, Ying / Chen, Ying-Hsiang / Chen, Yi-Song / Chen, Yuh-Min / Chien, Li-Hsin / Chirlaque, María-Dolores / Choi, Jin Eun / Choi, Yi Young / Chow, Wong-Ho / Chung, Charles C / Clavel, Jacqueline / Clavel-Chapelon, Françoise / Cocco, Pierluigi / Colt, Joanne S / Comperat, Eva / Conde, Lucia / Connors, Joseph M / Conti, David / Cortessis, Victoria K / Cotterchio, Michelle / Cozen, Wendy / Crouch, Simon / Crous-Bou, Marta / Cussenot, Olivier / Davis, Faith G / Ding, Ti / Diver, W Ryan / Dorronsoro, Miren / Dossus, Laure / Duell, Eric J / Ennas, Maria Grazia / Erickson, Ralph L / Feychting, Maria / Flanagan, Adrienne M / Foretova, Lenka / Fraumeni, Joseph F / Freedman, Neal D / Beane Freeman, Laura E / Fuchs, Charles / Gago-Dominguez, Manuela / Gallinger, Steven / Gao, Yu-Tang / Gapstur, Susan M / Garcia-Closas, Montserrat / García-Closas, Reina / Gascoyne, Randy D / Gastier-Foster, Julie / Gaudet, Mia M / Gaziano, J Michael / Giffen, Carol / Giles, Graham G / Giovannucci, Edward / Glimelius, Bengt / Goggins, Michael / Gokgoz, Nalan / Goldstein, Alisa M / Gorlick, Richard / Gross, Myron / Grubb, Robert / Gu, Jian / Guan, Peng / Gunter, Marc / Guo, Huan / Habermann, Thomas M / Haiman, Christopher A / Halai, Dina / Hallmans, Goran / Hassan, Manal / Hattinger, Claudia / He, Qincheng / He, Xingzhou / Helzlsouer, Kathy / Henderson, Brian / Henriksson, Roger / Hjalgrim, Henrik / Hoffman-Bolton, Judith / Hohensee, Chancellor / Holford, Theodore R / Holly, Elizabeth A / Hong, Yun-Chul / Hoover, Robert N / Horn-Ross, Pamela L / Hosain, G M Monawar / Hosgood, H Dean / Hsiao, Chin-Fu / Hu, Nan / Hu, Wei / Hu, Zhibin / Huang, Ming-Shyan / Huerta, Jose-Maria / Hung, Jen-Yu / Hutchinson, Amy / Inskip, Peter D / Jackson, Rebecca D / Jacobs, Eric J / Jenab, Mazda / Jeon, Hyo-Sung / Ji, Bu-Tian / Jin, Guangfu / Jin, Li / Johansen, Christoffer / Johnson, Alison / Jung, Yoo Jin / Kaaks, Rudolph / Kamineni, Aruna / Kane, Eleanor / Kang, Chang Hyun / Karagas, Margaret R / Kelly, Rachel S / Khaw, Kay-Tee / Kim, Christopher / Kim, Hee Nam / Kim, Jin Hee / Kim, Jun Suk / Kim, Yeul Hong / Kim, Young Tae / Kim, Young-Chul / Kitahara, Cari M / Klein, Alison P / Klein, Robert J / Kogevinas, Manolis / Kohno, Takashi / Kolonel, Laurence N / Kooperberg, Charles / Kricker, Anne / Krogh, Vittorio / Kunitoh, Hideo / Kurtz, Robert C / Kweon, Sun-Seog / LaCroix, Andrea / Lawrence, Charles / Lecanda, Fernando / Lee, Victor Ho Fun / Li, Donghui / Li, Haixin / Li, Jihua / Li, Yao-Jen / Li, Yuqing / Liao, Linda M / Liebow, Mark / Lightfoot, Tracy / Lim, Wei-Yen / Lin, Chien-Chung / Lin, Dongxin / Lindstrom, Sara / Linet, Martha S / Link, Brian K / Liu, Chenwei / Liu, Jianjun / Liu, Li / Ljungberg, Börje / Lloreta, Josep / Di Lollo, Simonetta / Lu, Daru / Lund, Eiluv / Malats, Nuria / Mannisto, Satu / Le Marchand, Loic / Marina, Neyssa / Masala, Giovanna / Mastrangelo, Giuseppe / Matsuo, Keitaro / Maynadie, Marc / McKay, James / McKean-Cowdin, Roberta / Melbye, Mads / Melin, Beatrice S / Michaud, Dominique S / Mitsudomi, Tetsuya / Monnereau, Alain / Montalvan, Rebecca / Moore, Lee E / Mortensen, Lotte Maxild / Nieters, Alexandra / North, Kari E / Novak, Anne J / Oberg, Ann L / Offit, Kenneth / Oh, In-Jae / Olson, Sara H / Palli, Domenico / Pao, William / Park, In Kyu / Park, Jae Yong / Park, Kyong Hwa / Patiño-Garcia, Ana / Pavanello, Sofia / Peeters, Petra H M / Perng, Reury-Perng / Peters, Ulrike / Petersen, Gloria M / Picci, Piero / Pike, Malcolm C / Porru, Stefano / Prescott, Jennifer / Prokunina-Olsson, Ludmila / Qian, Biyun / Qiao, You-Lin / Rais, Marco / Riboli, Elio / Riby, Jacques / Risch, Harvey A / Rizzato, Cosmeri / Rodabough, Rebecca / Roman, Eve / Roupret, Morgan / Ruder, Avima M / Sanjose, Silvia de / Scelo, Ghislaine / Schned, Alan / Schumacher, Fredrick / Schwartz, Kendra / Schwenn, Molly / Scotlandi, Katia / Seow, Adeline / Serra, Consol / Serra, Massimo / Sesso, Howard D / Setiawan, Veronica Wendy / Severi, Gianluca / Severson, Richard K / Shanafelt, Tait D / Shen, Hongbing / Shen, Wei / Shin, Min-Ho / Shiraishi, Kouya / Shu, Xiao-Ou / Siddiq, Afshan / Sierrasesúmaga, Luis / Sihoe, Alan Dart Loon / Skibola, Christine F / Smith, Alex / Smith, Martyn T / Southey, Melissa C / Spinelli, John J / Staines, Anthony / Stampfer, Meir / Stern, Marianna C / Stevens, Victoria L / Stolzenberg-Solomon, Rachael S / Su, Jian / Su, Wu-Chou / Sund, Malin / Sung, Jae Sook / Sung, Sook Whan / Tan, Wen / Tang, Wei / Tardón, Adonina / Thomas, David / Thompson, Carrie A / Tinker, Lesley F / Tirabosco, Roberto / Tjønneland, Anne / Travis, Ruth C / Trichopoulos, Dimitrios / Tsai, Fang-Yu / Tsai, Ying-Huang / Tucker, Margaret / Turner, Jenny / Vajdic, Claire M / Vermeulen, Roel C H / Villano, Danylo J / Vineis, Paolo / Virtamo, Jarmo / Visvanathan, Kala / Wactawski-Wende, Jean / Wang, Chaoyu / Wang, Chih-Liang / Wang, Jiu-Cun / Wang, Junwen / Wei, Fusheng / Weiderpass, Elisabete / Weiner, George J / Weinstein, Stephanie / Wentzensen, Nicolas / White, Emily / Witzig, Thomas E / Wolpin, Brian M / Wong, Maria Pik / Wu, Chen / Wu, Guoping / Wu, Junjie / Wu, Tangchun / Wu, Wei / Wu, Xifeng / Wu, Yi-Long / Wunder, Jay S / Xiang, Yong-Bing / Xu, Jun / Xu, Ping / Yang, Pan-Chyr / Yang, Tsung-Ying / Ye, Yuanqing / Yin, Zhihua / Yokota, Jun / Yoon, Ho-Il / Yu, Chong-Jen / Yu, Herbert / Yu, Kai / Yuan, Jian-Min / Zelenetz, Andrew / Zeleniuch-Jacquotte, Anne / Zhang, Xu-Chao / Zhang, Yawei / Zhao, Xueying / Zhao, Zhenhong / Zheng, Hong / Zheng, Tongzhang / Zheng, Wei / Zhou, Baosen / Zhu, Meng / Zucca, Mariagrazia / Boca, Simina M / Cerhan, James R / Ferri, Giovanni M / Hartge, Patricia / Hsiung, Chao Agnes / Magnani, Corrado / Miligi, Lucia / Morton, Lindsay M / Smedby, Karin E / Teras, Lauren R / Vijai, Joseph / Wang, Sophia S / Brennan, Paul / Caporaso, Neil E / Hunter, David J / Kraft, Peter / Rothman, Nathaniel / Silverman, Debra T / Slager, Susan L / Chanock, Stephen J / Chatterjee, Nilanjan

    Journal of the National Cancer Institute

    2015  Volume 107, Issue 12, Page(s) djv279

    Abstract: Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms ( ...

    Abstract Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.
    Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.
    Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.
    Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
    MeSH term(s) Adult ; Aged ; Asian People/genetics ; Asian People/statistics & numerical data ; Bone Neoplasms/genetics ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Kidney Neoplasms/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Lung Neoplasms/etiology ; Lung Neoplasms/genetics ; Lymphoma, Large B-Cell, Diffuse/genetics ; Male ; Middle Aged ; Neoplasms/etiology ; Neoplasms/genetics ; Osteosarcoma/genetics ; Polymorphism, Single Nucleotide ; Smoking/adverse effects ; Testicular Neoplasms/genetics ; Tissue Array Analysis ; Urinary Bladder Neoplasms/etiology ; Urinary Bladder Neoplasms/genetics ; White People/genetics ; White People/statistics & numerical data
    Language English
    Publishing date 2015-10-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2992-0
    ISSN 1460-2105 ; 0027-8874 ; 0198-0157
    ISSN (online) 1460-2105
    ISSN 0027-8874 ; 0198-0157
    DOI 10.1093/jnci/djv279
    Database MEDical Literature Analysis and Retrieval System OnLINE

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