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  • 1
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    Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-03-25
    Description: Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. However, cGMP stimulation alone is limited by counter-adaptions including PDE upregulation. Furthermore, although PDE5A regulates nitric-oxide-generated cGMP, nitric oxide signalling is often depressed by heart disease. PDEs controlling natriuretic-peptide-coupled cGMP remain uncertain. Here we show that cGMP-selective PDE9A (refs 7, 8) is expressed in the mammalian heart, including humans, and is upregulated by hypertrophy and cardiac failure. PDE9A regulates natriuretic-peptide- rather than nitric-oxide-stimulated cGMP in heart myocytes and muscle, and its genetic or selective pharmacological inhibition protects against pathological responses to neurohormones, and sustained pressure-overload stress. PDE9A inhibition reverses pre-established heart disease independent of nitric oxide synthase (NOS) activity, whereas PDE5A inhibition requires active NOS. Transcription factor activation and phosphoproteome analyses of myocytes with each PDE selectively inhibited reveals substantial differential targeting, with phosphorylation changes from PDE5A inhibition being more sensitive to NOS activation. Thus, unlike PDE5A, PDE9A can regulate cGMP signalling independent of the nitric oxide pathway, and its role in stress-induced heart disease suggests potential as a therapeutic target.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376609/" 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/PMC4376609/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Dong I -- Zhu, Guangshuo -- Sasaki, Takashi -- Cho, Gun-Sik -- Hamdani, Nazha -- Holewinski, Ronald -- Jo, Su-Hyun -- Danner, Thomas -- Zhang, Manling -- Rainer, Peter P -- Bedja, Djahida -- Kirk, Jonathan A -- Ranek, Mark J -- Dostmann, Wolfgang R -- Kwon, Chulan -- Margulies, Kenneth B -- Van Eyk, Jennifer E -- Paulus, Walter J -- Takimoto, Eiki -- Kass, David A -- HHSN268201000032C/HL/NHLBI NIH HHS/ -- HL-07227/HL/NHLBI NIH HHS/ -- HL-089297/HL/NHLBI NIH HHS/ -- HL-093432/HL/NHLBI NIH HHS/ -- HL-119012/HL/NHLBI NIH HHS/ -- HL089847/HL/NHLBI NIH HHS/ -- HL105993/HL/NHLBI NIH HHS/ -- HL68891/HL/NHLBI NIH HHS/ -- N01HV28180/HL/NHLBI NIH HHS/ -- P01 HL107153/HL/NHLBI NIH HHS/ -- R01 HL089297/HL/NHLBI NIH HHS/ -- R01 HL089847/HL/NHLBI NIH HHS/ -- R01 HL093432/HL/NHLBI NIH HHS/ -- R01 HL105993/HL/NHLBI NIH HHS/ -- R01 HL111198/HL/NHLBI NIH HHS/ -- R01 HL119012/HL/NHLBI NIH HHS/ -- T32 HL007227/HL/NHLBI NIH HHS/ -- England -- Nature. 2015 Mar 26;519(7544):472-6. doi: 10.1038/nature14332. Epub 2015 Mar 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA. ; Advanced Medical Research Laboratories, Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa 227-0033, Japan. ; Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. ; 1] Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA [2] Heart Institute and Advanced Clinical Biosystems Research Institute, Cedar Sinai Medical Center, 8700 Beverly Blvd, AHSP A9229 Los Angeles, California 90048, USA. ; Department of Physiology, Institute of Bioscience and Biotechnology, BK21 plus Graduate Program, Kangwon National University College of Medicine, Chuncheon 200-701, Korea. ; Department of Pharmacology, University of Vermont, Burlington, Vermont 05405, USA. ; Department of Medicine, Division of Cardiovascular Medicine, Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25799991" target="_blank"〉PubMed〈/a〉
    Keywords: 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & ; inhibitors/deficiency/genetics/*metabolism ; Animals ; Aortic Valve Stenosis/complications ; Cardiomegaly/drug therapy/*enzymology/etiology/*metabolism ; Cyclic GMP/*metabolism ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Muscle Cells/enzymology ; Myocardium/enzymology ; Natriuretic Peptides/metabolism ; *Nitric Oxide/metabolism ; Nitric Oxide Synthase ; Phosphodiesterase Inhibitors/pharmacology/therapeutic use ; Pressure ; Signal Transduction/drug effects ; Stress, Physiological ; Up-Regulation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Decadal climatological trends of aerosol optical parameters over three different environments in South Korea (2012)
    Wiley
    Details
    Publication Date: 2012-08-16
    Description: Decadal climatology of aerosol optical parameters derived from Moderate Resolution Imaging Spectroradiometer (MODIS) on board Terra satellite has been analysed during past decade (February 2000 to February 2010) over three different environments in South Korea. Seoul, a continental urban station showed a significant decadal decrease of around 22% in aerosol optical depth (AOD) at 550 nm during observational period. The corresponding decrease in AOD found to be 18.7% over Busan, a coastal station. However Jeju, a volcanically sedimented island station in Korea showed negligible changes in AOD (1.4%). Fine mode fraction (FMF) and Angstrom exponent (ANG) parameters also showed a significant decadal reduction, indicating the decrease in fine mode aerosols, which are majorly produced due to anthropogenic activities in land areas. On analysing the decadal trends in seasonal climatology, it is found that aerosol parameters in general were showing a decreasing trend in different seasons except during spring. The decadal trend in meteorological parameters did not show a perfect alignment with aerosol trends. This suggests that the decadal decrease in aerosols could be mainly attributed to reduction in anthropogenic aerosol emissions. The surface temperature over the stations showed a significant increase of 8% to 11%. This study suggests that, in spite of positive effects in pollution perspective, the reduced AOD may in part contribute the increasing trend of surface temperature. Copyright © 2012 Royal Meteorological Society
    Print ISSN: 0899-8418
    Electronic ISSN: 1097-0088
    Topics: Geosciences , Physics
    Published by Wiley
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  • 3
    Electronic Resource
    Electronic Resource
    A new detector assembly for conversion electrons and X-rays from Mossbauer effect
    Amsterdam : Elsevier
    Nuclear Instruments and Methods 120 (1974), S. 23-28 
    Details
    ISSN: 0029-554X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0029-554X(74)90100-1
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  • 4
    Electronic Resource
    Electronic Resource
    NMR linewidth study of a latex interpenetrating network (1991)
    Springer
    Colloid & polymer science 269 (1991), S. 227-241 
    Details
    ISSN: 1435-1536
    Keywords: Latex ; structure ; NMR spectroscopy ; interpenetrating network ; NMR linewidth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Polymer structure developed in latex particles has been investigated by measuring the temperature dependence of the carbon magnetic resonance (CMR) peak linewidths. Interpenetrating polymer networks (IPN) were formed by a continuous-addition emulsion polymerization process, in which a crosslinked seed particle was the site for formation of a linear second-stage polymer. Morphology was controlled by the level of crosslinking in the seed stage. The two polymers of the composite particle differ in their glass-transition temperatures by 100°C. By heating the particles to 50°C above the glass-transition temperature of the softer polymer, which formed the continuous network phase of this composite, it was possible to observe its CMR spectrum independently of the other polymer. The temperature dependence of the linewidth varied with the structure of the network. This was characterized by limiting linewidth behavior at both low and high temperature, which systematically varied as a function of the degree of mixing the two phases. Differential scanning calorimetry and electron microscopy corroborated the morphology change observed with the linewidth data. The influence of a diluent, present during formation of the network stage, was also examined with this CMR approach.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665496
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  • 5
    Electronic Resource
    Electronic Resource
    Effects of silver and potassium ions on ion exchange in float glass (1992)
    Springer
    Journal of materials science 27 (1992), S. 2908-2913 
    Details
    ISSN: 1573-4803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The variation of optical and mechanical properties in ion-exchanged glasses was investigated. Ion exchange was carried out in KNO3, NaNO3 melts and their mixed melts with AgNO3. The glasses used were soda-lime-silicate glasses produced by the float process. In order to analyse the effects of ion exchange, colour variation for optical properties, bending strength, surface microhardness and softening point for mechanical properties, and resistivity for electrical properties, were measured. In the optical properties, silver ions play an important role in colouring, ion exchange in the mixed melt of KNO3 and AgNO3, and additional heat treatment in air made it possible to obtain a range of colours from yellow to reddish-brown. Bending strength was increased by five times over the values of the parent glasses, surface microhardness was increased about 50 kg mm−2, and the softening point was increased linearly with the amount of ion exchange resulting from ion exchange in the KNO3 melt, because the potassium ion plays a great role in strengthening in the mechanical properties. On the other hand, in the mixed melt of KNO3 and AgNO3, bending strength and surface microhardness were increased slightly in contrast with the KNO3 melt, and the softening point decreased on increasing the amount of ion exchange.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01154099
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  • 6
    Electronic Resource
    Electronic Resource
    The formation of “inverted” core-shell latexes (1983)
    New York : Wiley-Blackwell
    Journal of Polymer Science: Polymer Chemistry Edition 21 (1983), S. 147-154 
    Details
    ISSN: 0360-6376
    Keywords: Physics ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: It has been found that when hydrophobic monomers are polymerized in the presence of highly hydrophilic polymer seed particles, the second-stage hydrophobic polymers form cores surrounded by the first-stage hydrophilic polymers, resulting in “inverted” core-shell latexes. The formation of core-shell morphology by this inversion process has been found to be dependent on the hydrophilicity and molecular weight of the first-stage hydrophilic polymers and the extent of phase separation between the two polymers involved. Particle morphology has been examined by electron microscopy, surface acid titration, alkali swelling of particles, and surface reactivity.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/pol.1983.170210115
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  • 7
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    Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy (2014)
    National Academy of Sciences
    Details
    Publication Date: 2014-01-22
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation (2016)
    Springer Nature
    Details
    Publication Date: 2016-03-25
    Description: Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation Cell Death and Disease 7, e2158 (March 2016). doi:10.1038/cddis.2015.410 Authors: H J Lee, J M Ryu, Y H Jung, K H Lee, D I Kim & H J Han
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 9
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    CATH FunFHMMer web server: protein functional annotations using functional family assignments (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-02
    Description: The widening function annotation gap in protein databases and the increasing number and diversity of the proteins being sequenced presents new challenges to protein function prediction methods. Multidomain proteins complicate the protein sequence–structure–function relationship further as new combinations of domains can expand the functional repertoire, creating new proteins and functions. Here, we present the FunFHMMer web server, which provides Gene Ontology (GO) annotations for query protein sequences based on the functional classification of the domain-based CATH-Gene3D resource. Our server also provides valuable information for the prediction of functional sites. The predictive power of FunFHMMer has been validated on a set of 95 proteins where FunFHMMer performs better than BLAST, Pfam and CDD. Recent validation by an independent international competition ranks FunFHMMer as one of the top function prediction methods in predicting GO annotations for both the Biological Process and Molecular Function Ontology. The FunFHMMer web server is available at http://www.cathdb.info/search/by_funfhmmer .
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency (2016)
    Oxford University Press
    Details
    Publication Date: 2016-02-20
    Description: Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. Interestingly, SSCs express key pluripotency genes such as Oct4, Sox2, Klf4 and Myc . Therefore, molecular dissection of mSSC reprogramming may provide clues about novel endogenous reprogramming or pluripotency regulatory factors. Our comparative transcriptome analysis of mSSCs and induced pluripotent stem cells (iPSCs) suggests that they have similar pluripotency states but are reprogrammed via different transcriptional pathways. We identified 53 genes as putative pluripotency regulatory factors using an integrated systems biology approach. We demonstrated a selected candidate, Positive cofactor 4 ( Pc4 ), can enhance the efficiency of somatic cell reprogramming by promoting and maintaining transcriptional activity of the key reprograming factors. These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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