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  • 1
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    Unmasking the S-phase-promoting potential of cyclin B1 (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-05-10
    Description: In higher eukaryotes, the S phase and M phase of the cell cycle are triggered by different cyclin-dependent kinases (CDKs). For example, in frog egg extracts, Cdk1-cyclin B catalyzes entry into mitosis but cannot trigger DNA replication. Two hypotheses can explain this observation: Either Cdk1-cyclin B fails to recognize the key substrates of its S-phase-promoting counterparts, or its activity is somehow regulated to prevent it from activating DNA synthesis. Here, we show that Cdk1-cyclin B1 has cryptic S-phase-promoting abilities that can be unmasked by relocating it from the cytoplasm to the nucleus and moderately stimulating its activity. Subcellular localization of vertebrate CDKs and the control of their activity are thus critical factors for determining their specificity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moore, Jonathan D -- Kirk, Jane A -- Hunt, Tim -- New York, N.Y. -- Science. 2003 May 9;300(5621):987-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12738867" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; CDC2 Protein Kinase/*metabolism ; Cell Cycle Proteins/metabolism/pharmacology ; Cell Extracts ; Cell Nucleus/metabolism ; Chromatin/metabolism ; Cyclin B/*metabolism/pharmacology ; Cyclin B1 ; DNA/biosynthesis ; *DNA Replication ; Enzyme Activation ; Mitosis ; Nuclear Envelope/metabolism ; Nuclear Localization Signals ; Ovum ; Protein Kinases/metabolism ; Recombinant Fusion Proteins ; *S Phase ; Transfection ; Xenopus ; cdc25 Phosphatases/metabolism/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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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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  • 3
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    Whole-body scanning PCR; a highly sensitive method to study the biodistribution of mRNAs, noncoding RNAs and therapeutic oligonucleotides (2013)
    Oxford University Press
    Details
    Publication Date: 2013-08-28
    Description: Efficient tissue-specific delivery is a crucial factor in the successful development of therapeutic oligonucleotides. Screening for novel delivery methods with unique tissue-homing properties requires a rapid, sensitive, flexible and unbiased technique able to visualize the in vivo biodistribution of these oligonucleotides. Here, we present whole body scanning PCR, a platform that relies on the local extraction of tissues from a mouse whole body section followed by the conversion of target-specific qPCR signals into an image. This platform was designed to be compatible with a novel RT-qPCR assay for the detection of siRNAs and with an assay suitable for the detection of heavily chemically modified oligonucleotides, which we termed Chemical-Ligation qPCR (CL-qPCR). In addition to this, the platform can also be used to investigate the global expression of endogenous mRNAs and non-coding RNAs. Incorporation of other detection systems, such as aptamers, could even further expand the use of this technology.
    Keywords: Nucleic acid amplification, Cell biology, RNA characterisation and manipulation
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Damage-tolerant nanotwinned metals with nanovoids under radiation environments (2015)
    Springer Nature
    Details
    Publication Date: 2015-04-26
    Description: Article Materials that are tolerant to radiation damage are important for use in nuclear reactors or the storage of nuclear materials. Here, the authors show that pre-introduced nanovoids in nanotwinned copper improve self-healing of the material and therefore enhance its radiation tolerance. Nature Communications doi: 10.1038/ncomms8036 Authors: Y. Chen, K Y. Yu, Y. Liu, S. Shao, H. Wang, M. A. Kirk, J. Wang, X. Zhang
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 5
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    Observation of Lobes near the X Point in Resonant Magnetic Perturbation Experiments on MAST (2012)
    American Physical Society (APS)
    Details
    Publication Date: 2012-06-21
    Description: Author(s): A. Kirk, J. Harrison, Yueqiang Liu, E. Nardon, I. T. Chapman, P. Denner, and the MAST team The application of nonaxisymmetric resonant magnetic perturbations (RMPs) with a toroidal mode number n =6 in the MAST tokamak produces a significant reduction in plasma energy loss associated with type-I edge localized modes (ELMs), the first such observation with n 〉3 . During the ELM mitigated st... [Phys. Rev. Lett. 108, 255003] Published Wed Jun 20, 2012
    Keywords: Plasma and Beam Physics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
    Published by American Physical Society (APS)
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  • 6
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    A census of dense cores in the Taurus L1495 cloud from the Herschel Gould Belt Survey (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-17
    Description: We present a catalogue of dense cores in a ~4° x 2° field of the Taurus star-forming region, inclusive of the L1495 cloud, derived from Herschel SPIRE and PACS observations in the 70 μm, 160 μm, 250 μm, 350 μm, and 500 μm continuum bands. Estimates of mean dust temperature and total mass are derived using modified blackbody fits to the spectral energy distributions. We detect 525 starless cores of which ~10–20 per cent are gravitationally bound and therefore presumably prestellar. Our census of unbound objects is ~85 per cent complete for M 〉 0.015 M in low-density regions ( A V 5 mag), while the bound (prestellar) subset is ~85 per cent complete for M 〉 0.1 M overall. The prestellar core mass function (CMF) is consistent with lognormal form, resembling the stellar system initial mass function, as has been reported previously. All of the inferred prestellar cores lie on filamentary structures whose column densities exceed the expected threshold for filamentary collapse, in agreement with previous reports. Unlike the prestellar CMF, the unbound starless CMF is not lognormal, but instead is consistent with a power-law form below 0.3 M and shows no evidence for a low-mass turnover. It resembles previously reported mass distributions for CO clumps at low masses ( M 0.3 M ). The volume density PDF, however, is accurately lognormal except at high densities. It is consistent with the effects of self-gravity on magnetized supersonic turbulence. The only significant deviation from lognormality is a high-density tail which can be attributed unambiguously to prestellar cores.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 7
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    Host adaptation and unexpected symbiont partners enable reef-building corals to tolerate extreme temperatures (2016)
    Wiley
    Details
    Publication Date: 2016-02-12
    Description: Understanding the potential for coral adaptation to warming seas is complicated by interactions between symbiotic partners that define stress responses and the difficulties of tracking selection in natural populations. To overcome these challenges, we characterised the contribution of both animal host and symbiotic algae to thermal tolerance in corals that have already experienced considerable warming on par with end-of-century projections for most coral reefs. Thermal responses in Platygyra daedalea corals from the hot Persian Gulf where summer temperatures reach 36°C were compared with conspecifics from the milder Sea of Oman. Persian Gulf corals had higher rates of survival at elevated temperatures (33 and 36°C) in both the non-symbiotic larval stage (32-49% higher) and the symbiotic adult life-stage (51% higher). Additionally, Persian Gulf hosts had fixed greater potential to mitigate oxidative stress (31-49% higher) and their Symbiodinium partners had better retention of photosynthetic performance under elevated temperature (up to 161% higher). Superior thermal tolerance of Persian Gulf versus Sea of Oman corals was maintained after 6-months acclimatisation to a common ambient environment and was underpinned by genetic divergence in both the coral host and symbiotic algae. In P. daedalea host samples, genome-wide SNP variation clustered into two discrete groups corresponding with Persian Gulf and Sea of Oman sites. Symbiodinium within host tissues predominantly belonged to ITS2 rDNA type C3 in the Persian Gulf and type D1a in the Sea of Oman contradicting patterns of Symbiodinium thermal tolerance from other regions. Our findings provide evidence that genetic adaptation of both host and Symbiodinium has enabled corals to cope with extreme temperatures in the Persian Gulf. Thus, the persistence of coral populations under continued warming will likely be determined by evolutionary rates in both, rather than single, symbiotic partners. This article is protected by copyright. All rights reserved.
    Print ISSN: 1354-1013
    Electronic ISSN: 1365-2486
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Geography
    Published by Wiley
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  • 8
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    Rotor Dynamics of Flywheel Energy Storage Systems (1991)
    American Society of Mechanical Engineers
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    Publication Date: 1991-02-01
    Description: This paper deals with the dynamic analysis of the magnetic bearing stack system. The stack consists of a single flywheel supported by two magnetic bearings. To model the system, the dynamic equations of a magnetically suspended flywheel are derived. Next, the four control systems controlling the four degrees-of-freedom of the stack are incorporated into the model. The resulting dynamic equations are represented as first-order differential equations in a matrix form. A computer simulation program was then used to simulate the working of the magnetic bearing stack. Real time plots from the simulation are used to show the effect of dynamic coupling on torque response. Frequency response is used to determine the resonance frequencies of the stack system. It is found that system stability depends on flywheel speed. On the basis of the above results suggestions are made to improve stability and allow the stack to be spun beyond 60,000 rpm.
    Print ISSN: 0199-6231
    Electronic ISSN: 1528-8986
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Published by American Society of Mechanical Engineers
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  • 9
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    Flywheel energy storage. II - Magnetically suspended superflywheel (1977)
    In:  Other Sources
    Details
    Publication Date: 2011-08-17
    Description: This article, the second of a two part paper, describes the general design requirements for a flywheel energy storage system. A new superflywheel energy storage system, using a spokeless, magnetically suspended, composite material pierced disk rotor is proposed. The new system is configured around a permanent magnet ('flux biased') magnetic suspension system with active control in the radial direction and passive control in the axial direction. The storage ring is used as a moving rotor and electronic commutation of stationary armature coils is proposed. There is no mechanical contact with the rotating ring and long life and low run down losses are projected. A discussion of major components for a 10 kwh system is presented.
    Keywords: ENERGY PRODUCTION AND CONVERSION
    Type: International Journal of Mechanical Sciences; 19; 4, 19; 1977
    Format: text
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    NASA TECHNICAL REPORTS
  • 10
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    Magnetically suspended flywheel system study (1984)
    In:  CASI
    Details
    Publication Date: 2016-06-07
    Description: A program to study the application of a graphite/epoxy, magnetically suspended, pierced disk flywheel for the combined function of spacecraft attitude control and energy storage (ACES) is described. Past achievements of the program include design and analysis computer codes for the flywheel rotor, a magnetically suspended flywheel model, and graphite/epoxy rotor rings that were successfully prestressed via interference assembly. All hardware successfully demonstrated operation of the necessary subsystems which form a complete ACES design. Areas of future work include additional rotor design research, system definition and control strategies, prototype development, and design/construction of a UM/GSFC spin test facility. The results of applying design and analysis computer codes to a magnetically suspended interference assembled rotor show specific energy densities of 42 Wh/lb (92.4 Wh/kg) are obtained for a 1.6 kWh system.
    Keywords: SPACECRAFT PROPULSION AND POWER
    Type: NASA. Langley Research Center An Assessment of Integrated Flywheel System Technol.; p 307-328
    Format: application/pdf
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    NASA TECHNICAL REPORTS
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