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  • 1
    Publication Date: 2002-04-20
    Description: Thromboxane (Tx) A2 is a vasoconstrictor and platelet agonist. Aspirin affords cardioprotection through inhibition of TxA2 formation by platelet cyclooxygenase (COX-1). Prostacyclin (PGI2) is a vasodilator that inhibits platelet function. Here we show that injury-induced vascular proliferation and platelet activation are enhanced in mice that are genetically deficient in the PGI2 receptor (IP) but are depressed in mice genetically deficient in the TxA2 receptor (TP) or treated with a TP antagonist. The augmented response to vascular injury was abolished in mice deficient in both receptors. Thus, PGI2 modulates platelet-vascular interactions in vivo and specifically limits the response to TxA2. This interplay may help explain the adverse cardiovascular effects associated with selective COX-2 inhibitors, which, unlike aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), inhibit PGI2 but not TxA2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheng, Yan -- Austin, Sandra C -- Rocca, Bianca -- Koller, Beverly H -- Coffman, Thomas M -- Grosser, Tilo -- Lawson, John A -- FitzGerald, Garret A -- HL 54500/HL/NHLBI NIH HHS/ -- HL 62250/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2002 Apr 19;296(5567):539-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Experimental Therapeutics, 153 Johnson Pavilion, 3620 Hamilton Walk, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6084, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11964481" target="_blank"〉PubMed〈/a〉
    Keywords: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology ; Animals ; *Carotid Artery Injuries/pathology ; Carotid Artery, Common/cytology/drug effects/physiology ; Cell Division ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/adverse effects/therapeutic use ; Endothelium, Vascular/cytology/drug effects/*physiology ; Epoprostenol/metabolism/*physiology ; Humans ; Isoenzymes/antagonists & inhibitors ; Lactones/adverse effects/therapeutic use ; Male ; Membrane Proteins ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Muscle, Smooth, Vascular/cytology/drug effects/physiology ; Naphthalenes ; *Platelet Activation/drug effects ; Platelet Aggregation/drug effects ; Propionates ; Prostaglandin-Endoperoxide Synthases ; Receptors, Epoprostenol ; Receptors, Prostaglandin/physiology ; Receptors, Thromboxane/antagonists & inhibitors/genetics/physiology ; Sulfones ; Tetrahydronaphthalenes/pharmacology ; Thromboxane A2/*physiology ; Tunica Intima/cytology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2010-04-07
    Description: Within the circulatory system, blood flow regulates vascular remodelling, stimulates blood stem cell formation, and has a role in the pathology of vascular disease. During vertebrate embryogenesis, vascular patterning is initially guided by conserved genetic pathways that act before circulation. Subsequently, endothelial cells must incorporate the mechanosensory stimulus of blood flow with these early signals to shape the embryonic vascular system. However, few details are known about how these signals are integrated during development. To investigate this process, we focused on the aortic arch (AA) blood vessels, which are known to remodel in response to blood flow. By using two-photon imaging of live zebrafish embryos, we observe that flow is essential for angiogenesis during AA development. We further find that angiogenic sprouting of AA vessels requires a flow-induced genetic pathway in which the mechano-sensitive zinc finger transcription factor klf2a induces expression of an endothelial-specific microRNA, mir-126, to activate Vegf signalling. Taken together, our work describes a novel genetic mechanism in which a microRNA facilitates integration of a physiological stimulus with growth factor signalling in endothelial cells to guide angiogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914488/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914488/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nicoli, Stefania -- Standley, Clive -- Walker, Paul -- Hurlstone, Adam -- Fogarty, Kevin E -- Lawson, Nathan D -- DK32520/DK/NIDDK NIH HHS/ -- R01 CA107454/CA/NCI NIH HHS/ -- R01 CA107454-05/CA/NCI NIH HHS/ -- R01 HL079266/HL/NHLBI NIH HHS/ -- R01 HL079266-05/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Apr 22;464(7292):1196-200. doi: 10.1038/nature08889. Epub 2010 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20364122" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aorta, Thoracic/*embryology ; Endothelial Cells/metabolism ; Gene Expression Regulation, Developmental ; *Hemodynamics ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Kruppel-Like Transcription Factors/metabolism ; Membrane Proteins/genetics/metabolism ; Mice ; MicroRNAs/genetics/*metabolism ; NIH 3T3 Cells ; *Neovascularization, Physiologic ; Regional Blood Flow/physiology ; *Signal Transduction ; Vascular Endothelial Growth Factor A/*metabolism ; Zebrafish/blood/embryology/*genetics ; Zebrafish Proteins/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2006-07-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mendelson, Joseph R 3rd -- Lips, Karen R -- Gagliardo, Ronald W -- Rabb, George B -- Collins, James P -- Diffendorfer, James E -- Daszak, Peter -- Ibanez D, Roberto -- Zippel, Kevin C -- Lawson, Dwight P -- Wright, Kevin M -- Stuart, Simon N -- Gascon, Claude -- da Silva, Helio R -- Burrowes, Patricia A -- Joglar, Rafael L -- La Marca, Enrique -- Lotters, Stefan -- du Preez, Louis H -- Weldon, Che -- Hyatt, Alex -- Rodriguez-Mahecha, Jose Vicente -- Hunt, Susan -- Robertson, Helen -- Lock, Brad -- Raxworthy, Christopher J -- Frost, Darrel R -- Lacy, Robert C -- Alford, Ross A -- Campbell, Jonathan A -- Parra-Olea, Gabriela -- Bolanos, Federico -- Domingo, Jose Joaquin Calvo -- Halliday, Tim -- Murphy, James B -- Wake, Marvalee H -- Coloma, Luis A -- Kuzmin, Sergius L -- Price, Mark Stanley -- Howell, Kim M -- Lau, Michael -- Pethiyagoda, Rohan -- Boone, Michelle -- Lannoo, Michael J -- Blaustein, Andrew R -- Dobson, Andy -- Griffiths, Richard A -- Crump, Martha L -- Wake, David B -- Brodie, Edmund D Jr -- New York, N.Y. -- Science. 2006 Jul 7;313(5783):48.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Zoo Atlanta, 800 Cherokee Avenue SE, Atlanta, GA 30315, USA. jmendelson@zooatlanta.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16825553" target="_blank"〉PubMed〈/a〉
    Keywords: *Amphibians ; Animals ; *Biodiversity ; Chytridiomycota ; Conservation of Natural Resources ; Ecosystem ; *International Agencies ; International Cooperation ; Mycoses/veterinary ; Population Dynamics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2007-04-14
    Description: The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rhesus Macaque Genome Sequencing and Analysis Consortium -- Gibbs, Richard A -- Rogers, Jeffrey -- Katze, Michael G -- Bumgarner, Roger -- Weinstock, George M -- Mardis, Elaine R -- Remington, Karin A -- Strausberg, Robert L -- Venter, J Craig -- Wilson, Richard K -- Batzer, Mark A -- Bustamante, Carlos D -- Eichler, Evan E -- Hahn, Matthew W -- Hardison, Ross C -- Makova, Kateryna D -- Miller, Webb -- Milosavljevic, Aleksandar -- Palermo, Robert E -- Siepel, Adam -- Sikela, James M -- Attaway, Tony -- Bell, Stephanie -- Bernard, Kelly E -- Buhay, Christian J -- Chandrabose, Mimi N -- Dao, Marvin -- Davis, Clay -- Delehaunty, Kimberly D -- Ding, Yan -- Dinh, Huyen H -- Dugan-Rocha, Shannon -- Fulton, Lucinda A -- Gabisi, Ramatu Ayiesha -- Garner, Toni T -- Godfrey, Jennifer -- Hawes, Alicia C -- Hernandez, Judith -- Hines, Sandra -- Holder, Michael -- Hume, Jennifer -- Jhangiani, Shalini N -- Joshi, Vandita -- Khan, Ziad Mohid -- Kirkness, Ewen F -- Cree, Andrew -- Fowler, R Gerald -- Lee, Sandra -- Lewis, Lora R -- Li, Zhangwan -- Liu, Yih-Shin -- Moore, Stephanie M -- Muzny, Donna -- Nazareth, Lynne V -- Ngo, Dinh Ngoc -- Okwuonu, Geoffrey O -- Pai, Grace -- Parker, David -- Paul, Heidie A -- Pfannkoch, Cynthia -- Pohl, Craig S -- Rogers, Yu-Hui -- Ruiz, San Juana -- Sabo, Aniko -- Santibanez, Jireh -- Schneider, Brian W -- Smith, Scott M -- Sodergren, Erica -- Svatek, Amanda F -- Utterback, Teresa R -- Vattathil, Selina -- Warren, Wesley -- White, Courtney Sherell -- Chinwalla, Asif T -- Feng, Yucheng -- Halpern, Aaron L -- Hillier, Ladeana W -- Huang, Xiaoqiu -- Minx, Pat -- Nelson, Joanne O -- Pepin, Kymberlie H -- Qin, Xiang -- Sutton, Granger G -- Venter, Eli -- Walenz, Brian P -- Wallis, John W -- Worley, Kim C -- Yang, Shiaw-Pyng -- Jones, Steven M -- Marra, Marco A -- Rocchi, Mariano -- Schein, Jacqueline E -- Baertsch, Robert -- Clarke, Laura -- Csuros, Miklos -- Glasscock, Jarret -- Harris, R Alan -- Havlak, Paul -- Jackson, Andrew R -- Jiang, Huaiyang -- Liu, Yue -- Messina, David N -- Shen, Yufeng -- Song, Henry Xing-Zhi -- Wylie, Todd -- Zhang, Lan -- Birney, Ewan -- Han, Kyudong -- Konkel, Miriam K -- Lee, Jungnam -- Smit, Arian F A -- Ullmer, Brygg -- Wang, Hui -- Xing, Jinchuan -- Burhans, Richard -- Cheng, Ze -- Karro, John E -- Ma, Jian -- Raney, Brian -- She, Xinwei -- Cox, Michael J -- Demuth, Jeffery P -- Dumas, Laura J -- Han, Sang-Gook -- Hopkins, Janet -- Karimpour-Fard, Anis -- Kim, Young H -- Pollack, Jonathan R -- Vinar, Tomas -- Addo-Quaye, Charles -- Degenhardt, Jeremiah -- Denby, Alexandra -- Hubisz, Melissa J -- Indap, Amit -- Kosiol, Carolin -- Lahn, Bruce T -- Lawson, Heather A -- Marklein, Alison -- Nielsen, Rasmus -- Vallender, Eric J -- Clark, Andrew G -- Ferguson, Betsy -- Hernandez, Ryan D -- Hirani, Kashif -- Kehrer-Sawatzki, Hildegard -- Kolb, Jessica -- Patil, Shobha -- Pu, Ling-Ling -- Ren, Yanru -- Smith, David Glenn -- Wheeler, David A -- Schenck, Ian -- Ball, Edward V -- Chen, Rui -- Cooper, David N -- Giardine, Belinda -- Hsu, Fan -- Kent, W James -- Lesk, Arthur -- Nelson, David L -- O'brien, William E -- Prufer, Kay -- Stenson, Peter D -- Wallace, James C -- Ke, Hui -- Liu, Xiao-Ming -- Wang, Peng -- Xiang, Andy Peng -- Yang, Fan -- Barber, Galt P -- Haussler, David -- Karolchik, Donna -- Kern, Andy D -- Kuhn, Robert M -- Smith, Kayla E -- Zwieg, Ann S -- 062023/Wellcome Trust/United Kingdom -- R01 HG002939/HG/NHGRI NIH HHS/ -- U54 HG003068/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):222-34.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. agibbs@bcm.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431167" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research ; *Evolution, Molecular ; Female ; Gene Duplication ; Gene Rearrangement ; Genetic Diseases, Inborn ; Genetic Variation ; *Genome ; Humans ; Macaca mulatta/*genetics ; Male ; Multigene Family ; Mutation ; Pan troglodytes/genetics ; Sequence Analysis, DNA ; Species Specificity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2009-08-01
    Description: Commensal bacteria in the lower intestine of mammals are 10 times as numerous as the body's cells. We investigated the relative importance of different immune mechanisms in limiting the spread of the intestinal microbiota. Here, we reveal a flexible continuum between innate and adaptive immune function in containing commensal microbes. Mice deficient in critical innate immune functions such as Toll-like receptor signaling or oxidative burst production spontaneously produce high-titer serum antibodies against their commensal microbiota. These antibody responses are functionally essential to maintain host-commensal mutualism in vivo in the face of innate immune deficiency. Spontaneous hyper-activation of adaptive immunity against the intestinal microbiota, secondary to innate immune deficiency, may clarify the underlying mechanisms of inflammatory diseases where immune dysfunction is implicated.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730530/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730530/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Slack, Emma -- Hapfelmeier, Siegfried -- Stecher, Barbel -- Velykoredko, Yuliya -- Stoel, Maaike -- Lawson, Melissa A E -- Geuking, Markus B -- Beutler, Bruce -- Tedder, Thomas F -- Hardt, Wolf-Dietrich -- Bercik, Premysl -- Verdu, Elena F -- McCoy, Kathy D -- Macpherson, Andrew J -- AI56363/AI/NIAID NIH HHS/ -- CA105001/CA/NCI NIH HHS/ -- R01 CA105001/CA/NCI NIH HHS/ -- U19 AI056363/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):617-20. doi: 10.1126/science.1172747.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada. andrew.macpherson@insel.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644121" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Bacterial/biosynthesis/blood/*immunology ; Bacteremia/immunology/microbiology ; Bacteria/growth & development/*immunology/isolation & purification ; Bacterial Infections/immunology/microbiology ; CD4-Positive T-Lymphocytes/immunology ; Colony Count, Microbial ; Enterococcus faecalis/growth & development/immunology/isolation & purification ; Escherichia coli K12/growth & development/immunology/isolation & purification ; Germ-Free Life ; Immunity ; *Immunity, Innate ; Intestinal Mucosa/immunology/*microbiology ; Intestines/immunology/*microbiology ; Lymphoid Tissue/microbiology ; Mice ; Mice, Inbred C57BL ; Permeability ; Respiratory Burst ; Signal Transduction ; Specific Pathogen-Free Organisms ; Spleen/microbiology ; Toll-Like Receptors/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2010-05-08
    Description: Dicer is a central enzyme in microRNA (miRNA) processing. We identified a Dicer-independent miRNA biogenesis pathway that uses Argonaute2 (Ago2) slicer catalytic activity. In contrast to other miRNAs, miR-451 levels were refractory to dicer loss of function but were reduced in MZago2 (maternal-zygotic) mutants. We found that pre-miR-451 processing requires Ago2 catalytic activity in vivo. MZago2 mutants showed delayed erythropoiesis that could be rescued by wild-type Ago2 or miR-451-duplex but not by catalytically dead Ago2. Changing the secondary structure of Dicer-dependent miRNAs to mimic that of pre-miR-451 restored miRNA function and rescued developmental defects in MZdicer mutants, indicating that the pre-miRNA secondary structure determines the processing pathway in vivo. We propose that Ago2-mediated cleavage of pre-miRNAs, followed by uridylation and trimming, generates functional miRNAs independently of Dicer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093307/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093307/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cifuentes, Daniel -- Xue, Huiling -- Taylor, David W -- Patnode, Heather -- Mishima, Yuichiro -- Cheloufi, Sihem -- Ma, Enbo -- Mane, Shrikant -- Hannon, Gregory J -- Lawson, Nathan D -- Wolfe, Scot A -- Giraldez, Antonio J -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-38/CA/NCI NIH HHS/ -- R01 GM081602/GM/NIGMS NIH HHS/ -- R01 GM081602-01/GM/NIGMS NIH HHS/ -- R01 GM081602-02/GM/NIGMS NIH HHS/ -- R01 GM081602-03/GM/NIGMS NIH HHS/ -- R01 GM081602-03S1/GM/NIGMS NIH HHS/ -- R01 GM081602-04/GM/NIGMS NIH HHS/ -- R01 GM101108/GM/NIGMS NIH HHS/ -- R01 HL093766/HL/NHLBI NIH HHS/ -- R01 HL093766-04/HL/NHLBI NIH HHS/ -- R01GM081602-03/03S1/GM/NIGMS NIH HHS/ -- R01HL093766/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jun 25;328(5986):1694-8. doi: 10.1126/science.1190809. Epub 2010 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20448148" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Biocatalysis ; Embryo, Nonmammalian/metabolism ; Embryonic Development ; Erythropoiesis ; Eukaryotic Initiation Factor-2/genetics/*metabolism ; Humans ; MicroRNAs/*chemistry/*metabolism ; Models, Biological ; Morphogenesis ; Nucleic Acid Conformation ; RNA Precursors/metabolism ; RNA Processing, Post-Transcriptional ; Recombinant Proteins/metabolism ; Ribonuclease III/metabolism ; Zebrafish/embryology/genetics/*metabolism ; Zebrafish Proteins/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2004-11-20
    Description: Female gender affords relative protection from cardiovascular disease until the menopause. We report that estrogen acts on estrogen receptor subtype alpha to up-regulate the production of atheroprotective prostacyclin, PGI2, by activation of cyclooxygenase 2 (COX-2). This mechanism restrained both oxidant stress and platelet activation that contribute to atherogenesis in female mice. Deletion of the PGI2 receptor removed the atheroprotective effect of estrogen in ovariectomized female mice. This suggests that chronic treatment of patients with selective inhibitors of COX-2 could undermine protection from cardiovascular disease in premenopausal females.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Egan, Karine M -- Lawson, John A -- Fries, Susanne -- Koller, Beverley -- Rader, Daniel J -- Smyth, Emer M -- Fitzgerald, Garret A -- HL62250/HL/NHLBI NIH HHS/ -- HL70128/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2004 Dec 10;306(5703):1954-7. Epub 2004 Nov 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Translational Medicine and Therapeutics, University of Pennsylvania, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15550624" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antioxidants/metabolism ; Arteriosclerosis/metabolism/pathology/*prevention & control ; Cardiovascular Diseases/chemically induced ; Cells, Cultured ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/adverse effects/pharmacology ; Epoprostenol/biosynthesis/metabolism/*physiology ; Estradiol/pharmacology ; Estrogen Receptor alpha/metabolism ; Female ; Hydrogen Peroxide/pharmacology ; Isoenzymes/*metabolism ; Lactones/adverse effects/pharmacology ; Lipid Peroxidation ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Smooth, Vascular/drug effects/metabolism ; Myocytes, Smooth Muscle/cytology/drug effects/metabolism ; Ovariectomy ; Oxidative Stress ; Platelet Activation ; Prostaglandin-Endoperoxide Synthases/*metabolism ; Receptors, Epoprostenol/genetics/physiology ; Receptors, LDL/genetics/physiology ; Sex Characteristics ; Sulfones/adverse effects/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2011-06-10
    Description: Haematopoietic stem cells (HSCs) are a self-renewing population of cells that continuously replenish all blood and immune cells during the lifetime of an individual. HSCs are used clinically to treat a wide array of diseases, including acute leukaemias and congenital blood disorders, but obtaining suitable numbers of cells and finding immune-compatible donors remain serious problems. These difficulties have led to an interest in the conversion of embryonic stem cells or induced pluripotent stem cells into HSCs, which is not possible using current methodologies. To accomplish this goal, it is critical to understand the native mechanisms involved in the specification of HSCs during embryonic development. Here we demonstrate in zebrafish that Wnt16 controls a novel genetic regulatory network required for HSC specification. Non-canonical signalling by Wnt16 is required for somitic expression of the Notch ligands deltaC (dlc) and deltaD (dld), and these ligands are, in turn, required for the establishment of definitive haematopoiesis. Notch signalling downstream of Dlc and Dld is earlier than, and distinct from, known cell-autonomous requirements for Notch, strongly suggesting that novel Notch-dependent relay signal(s) induce the first HSCs in parallel to other established pathways. Our results demonstrate that somite-specific gene expression is required for the production of haemogenic endothelium.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304471/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304471/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clements, Wilson K -- Kim, Albert D -- Ong, Karen G -- Moore, John C -- Lawson, Nathan D -- Traver, David -- R01 DK074482/DK/NIDDK NIH HHS/ -- R01 DK074482-05/DK/NIDDK NIH HHS/ -- R01-DK074482/DK/NIDDK NIH HHS/ -- R01-HL093467/HL/NHLBI NIH HHS/ -- England -- Nature. 2011 Jun 8;474(7350):220-4. doi: 10.1038/nature10107.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0380, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21654806" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Lineage ; Hematopoiesis ; Hematopoietic Stem Cells/*cytology/*metabolism ; Intracellular Signaling Peptides and Proteins ; Ligands ; Membrane Proteins/metabolism ; Nerve Tissue Proteins/metabolism ; Phenotype ; Receptors, Notch/*metabolism ; *Signal Transduction ; Somites/cytology/*metabolism ; Wnt Proteins/deficiency/genetics/*metabolism ; Zebrafish/*metabolism ; Zebrafish Proteins/deficiency/genetics/*metabolism
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2015-09-30
    Description: Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of 〉90% of cancer-related mortality. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are initiated by stem-like cells that proliferate and differentiate to produce advanced metastatic disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648562/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648562/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawson, Devon A -- Bhakta, Nirav R -- Kessenbrock, Kai -- Prummel, Karin D -- Yu, Ying -- Takai, Ken -- Zhou, Alicia -- Eyob, Henok -- Balakrishnan, Sanjeev -- Wang, Chih-Yang -- Yaswen, Paul -- Goga, Andrei -- Werb, Zena -- CA136717/CA/NCI NIH HHS/ -- CA180039/CA/NCI NIH HHS/ -- K23 HL116657/HL/NHLBI NIH HHS/ -- R01 CA136717/CA/NCI NIH HHS/ -- R01 CA180039/CA/NCI NIH HHS/ -- England -- Nature. 2015 Oct 1;526(7571):131-5. doi: 10.1038/nature15260. Epub 2015 Sep 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy, University of California, San Francisco, California 94143, USA. ; Department of Medicine, University of California, San Francisco, California 94143, USA. ; Department of Cell and Tissue Biology, University of California, San Francisco, California 94143, USA. ; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan. ; Department of Cell and Molecular Biology, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26416748" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/drug therapy/genetics/*pathology ; Cell Cycle/drug effects ; Cell Differentiation/drug effects/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Separation ; Cell Transformation, Neoplastic/drug effects/pathology ; Cyclin-Dependent Kinases/antagonists & inhibitors ; Disease Models, Animal ; *Disease Progression ; Epithelial Cells/drug effects/pathology ; Epithelial-Mesenchymal Transition/genetics ; Flow Cytometry ; Gene Expression Profiling ; Genes, myc/genetics ; Humans ; Mesoderm/metabolism/pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Metastasis/drug therapy/*pathology ; Neoplastic Stem Cells/drug effects/metabolism/*pathology ; *Single-Cell Analysis ; Xenograft Model Antitumor Assays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2011-01-29
    Description: 'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060778/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060778/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Locke, Devin P -- Hillier, LaDeana W -- Warren, Wesley C -- Worley, Kim C -- Nazareth, Lynne V -- Muzny, Donna M -- Yang, Shiaw-Pyng -- Wang, Zhengyuan -- Chinwalla, Asif T -- Minx, Pat -- Mitreva, Makedonka -- Cook, Lisa -- Delehaunty, Kim D -- Fronick, Catrina -- Schmidt, Heather -- Fulton, Lucinda A -- Fulton, Robert S -- Nelson, Joanne O -- Magrini, Vincent -- Pohl, Craig -- Graves, Tina A -- Markovic, Chris -- Cree, Andy -- Dinh, Huyen H -- Hume, Jennifer -- Kovar, Christie L -- Fowler, Gerald R -- Lunter, Gerton -- Meader, Stephen -- Heger, Andreas -- Ponting, Chris P -- Marques-Bonet, Tomas -- Alkan, Can -- Chen, Lin -- Cheng, Ze -- Kidd, Jeffrey M -- Eichler, Evan E -- White, Simon -- Searle, Stephen -- Vilella, Albert J -- Chen, Yuan -- Flicek, Paul -- Ma, Jian -- Raney, Brian -- Suh, Bernard -- Burhans, Richard -- Herrero, Javier -- Haussler, David -- Faria, Rui -- Fernando, Olga -- Darre, Fleur -- Farre, Domenec -- Gazave, Elodie -- Oliva, Meritxell -- Navarro, Arcadi -- Roberto, Roberta -- Capozzi, Oronzo -- Archidiacono, Nicoletta -- Della Valle, Giuliano -- Purgato, Stefania -- Rocchi, Mariano -- Konkel, Miriam K -- Walker, Jerilyn A -- Ullmer, Brygg -- Batzer, Mark A -- Smit, Arian F A -- Hubley, Robert -- Casola, Claudio -- Schrider, Daniel R -- Hahn, Matthew W -- Quesada, Victor -- Puente, Xose S -- Ordonez, Gonzalo R -- Lopez-Otin, Carlos -- Vinar, Tomas -- Brejova, Brona -- Ratan, Aakrosh -- Harris, Robert S -- Miller, Webb -- Kosiol, Carolin -- Lawson, Heather A -- Taliwal, Vikas -- Martins, Andre L -- Siepel, Adam -- Roychoudhury, Arindam -- Ma, Xin -- Degenhardt, Jeremiah -- Bustamante, Carlos D -- Gutenkunst, Ryan N -- Mailund, Thomas -- Dutheil, Julien Y -- Hobolth, Asger -- Schierup, Mikkel H -- Ryder, Oliver A -- Yoshinaga, Yuko -- de Jong, Pieter J -- Weinstock, George M -- Rogers, Jeffrey -- Mardis, Elaine R -- Gibbs, Richard A -- Wilson, Richard K -- G0501331/Medical Research Council/United Kingdom -- HG002238/HG/NHGRI NIH HHS/ -- HG002385/HG/NHGRI NIH HHS/ -- MC_U137761446/Medical Research Council/United Kingdom -- P01 AG022064/AG/NIA NIH HHS/ -- R01 GM059290/GM/NIGMS NIH HHS/ -- R01 GM59290/GM/NIGMS NIH HHS/ -- R01 HG002939/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG003079-08/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2011 Jan 27;469(7331):529-33. doi: 10.1038/nature09687.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Genome Center at Washington University, Washington University School of Medicine, 4444 Forest Park Avenue, Saint Louis, Missouri 63108, USA. dlocke@wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21270892" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Centromere/genetics ; Cerebrosides/metabolism ; Chromosomes ; Evolution, Molecular ; Female ; Gene Rearrangement/genetics ; Genetic Speciation ; *Genetic Variation ; Genetics, Population ; Genome/*genetics ; Humans ; Male ; Phylogeny ; Pongo abelii/*genetics ; Pongo pygmaeus/*genetics ; Population Density ; Population Dynamics ; Species Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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