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  • Astrophysics  (5)
  • Male  (3)
  • CC 4
  • Lasers and Masers
  • 2010-2014  (9)
  • 2000-2004
  • 2011  (9)
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  • 2010-2014  (9)
  • 2000-2004
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  • 1
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    Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-11-04
    Description: Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells. Senescent cells accumulate in various tissues and organs with ageing and have been hypothesized to disrupt tissue structure and function because of the components they secrete. However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16(Ink4a), to design a novel transgene, INK-ATTAC, for inducible elimination of p16(Ink4a)-positive senescent cells upon administration of a drug. Here we show that in the BubR1 progeroid mouse background, INK-ATTAC removes p16(Ink4a)-positive senescent cells upon drug treatment. In tissues--such as adipose tissue, skeletal muscle and eye--in which p16(Ink4a) contributes to the acquisition of age-related pathologies, life-long removal of p16(Ink4a)-expressing cells delayed onset of these phenotypes. Furthermore, late-life clearance attenuated progression of already established age-related disorders. These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468323/" 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/PMC3468323/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, Darren J -- Wijshake, Tobias -- Tchkonia, Tamar -- LeBrasseur, Nathan K -- Childs, Bennett G -- van de Sluis, Bart -- Kirkland, James L -- van Deursen, Jan M -- AG13925/AG/NIA NIH HHS/ -- CA96985/CA/NCI NIH HHS/ -- P30 DK050456/DK/NIDDK NIH HHS/ -- R01 AG013925/AG/NIA NIH HHS/ -- R01 AG013925-14/AG/NIA NIH HHS/ -- R01 CA096985/CA/NCI NIH HHS/ -- R01 CA096985-10/CA/NCI NIH HHS/ -- England -- Nature. 2011 Nov 2;479(7372):232-6. doi: 10.1038/nature10600.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22048312" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/cytology/drug effects/pathology ; Aging/drug effects/*physiology ; Animals ; Bone Marrow Cells/cytology/drug effects ; Cell Aging/drug effects/*physiology ; Cell Count ; Cell Cycle Proteins ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16/*metabolism ; Eye/cytology/drug effects/pathology ; Female ; Gene Expression ; Genotype ; Longevity/drug effects/physiology ; Male ; Mice ; Mice, Transgenic ; Muscle, Skeletal/cytology/drug effects/pathology ; Phenotype ; Progeria/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Tacrolimus/analogs & derivatives/pharmacology ; Time Factors ; Weaning
    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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    A synthetic homing endonuclease-based gene drive system in the human malaria mosquito (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-04-22
    Description: Genetic methods of manipulating or eradicating disease vector populations have long been discussed as an attractive alternative to existing control measures because of their potential advantages in terms of effectiveness and species specificity. The development of genetically engineered malaria-resistant mosquitoes has shown, as a proof of principle, the possibility of targeting the mosquito's ability to serve as a disease vector. The translation of these achievements into control measures requires an effective technology to spread a genetic modification from laboratory mosquitoes to field populations. We have suggested previously that homing endonuclease genes (HEGs), a class of simple selfish genetic elements, could be exploited for this purpose. Here we demonstrate that a synthetic genetic element, consisting of mosquito regulatory regions and the homing endonuclease gene I-SceI, can substantially increase its transmission to the progeny in transgenic mosquitoes of the human malaria vector Anopheles gambiae. We show that the I-SceI element is able to invade receptive mosquito cage populations rapidly, validating mathematical models for the transmission dynamics of HEGs. Molecular analyses confirm that expression of I-SceI in the male germline induces high rates of site-specific chromosomal cleavage and gene conversion, which results in the gain of the I-SceI gene, and underlies the observed genetic drive. These findings demonstrate a new mechanism by which genetic control measures can be implemented. Our results also show in principle how sequence-specific genetic drive elements like HEGs could be used to take the step from the genetic engineering of individuals to the genetic engineering of populations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093433/" 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/PMC3093433/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Windbichler, Nikolai -- Menichelli, Miriam -- Papathanos, Philippos Aris -- Thyme, Summer B -- Li, Hui -- Ulge, Umut Y -- Hovde, Blake T -- Baker, David -- Monnat, Raymond J Jr -- Burt, Austin -- Crisanti, Andrea -- CA133831/CA/NCI NIH HHS/ -- RL1 CA133831/CA/NCI NIH HHS/ -- RL1 CA133831-01/CA/NCI NIH HHS/ -- RL1 CA133831-02/CA/NCI NIH HHS/ -- RL1 CA133831-03/CA/NCI NIH HHS/ -- RL1 CA133831-04/CA/NCI NIH HHS/ -- RL1 CA133831-05/CA/NCI NIH HHS/ -- RL1 GM084433/GM/NIGMS NIH HHS/ -- RL1 GM084433-01/GM/NIGMS NIH HHS/ -- RL1 GM084433-02/GM/NIGMS NIH HHS/ -- RL1 GM084433-03/GM/NIGMS NIH HHS/ -- RL1 GM084433-04/GM/NIGMS NIH HHS/ -- RL1 GM084433-05/GM/NIGMS NIH HHS/ -- T32 CA080416/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 May 12;473(7346):212-5. doi: 10.1038/nature09937. Epub 2011 Apr 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Imperial College London, Department of Life Sciences, South Kensington Campus, London, SW7 2AZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21508956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Anopheles gambiae/*genetics ; Deoxyribonucleases, Type II Site-Specific/genetics ; Female ; Genes, Reporter/genetics ; *Genetic Engineering ; Genotype ; Insect Vectors/*genetics ; Male ; Molecular Sequence Data ; Mosquito Control/*methods ; Saccharomyces cerevisiae Proteins/genetics
    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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    Distinct physiological and behavioural functions for parental alleles of imprinted Grb10 (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-01-29
    Description: Imprinted genes, defined by their preferential expression of a single parental allele, represent a subset of the mammalian genome and often have key roles in embryonic development, but also postnatal functions including energy homeostasis and behaviour. When the two parental alleles are unequally represented within a social group (when there is sex bias in dispersal and/or variance in reproductive success), imprinted genes may evolve to modulate social behaviour, although so far no such instance is known. Predominantly expressed from the maternal allele during embryogenesis, Grb10 encodes an intracellular adaptor protein that can interact with several receptor tyrosine kinases and downstream signalling molecules. Here we demonstrate that within the brain Grb10 is expressed from the paternal allele from fetal life into adulthood and that ablation of this expression engenders increased social dominance specifically among other aspects of social behaviour, a finding supported by the observed increase in allogrooming by paternal Grb10-deficient animals. Grb10 is, therefore, the first example of an imprinted gene that regulates social behaviour. It is also currently alone in exhibiting imprinted expression from each of the parental alleles in a tissue-specific manner, as loss of the peripherally expressed maternal allele leads to significant fetal and placental overgrowth. Thus Grb10 is, so far, a unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, owing to actions of the two parental alleles in different tissues.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031026/" 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/PMC3031026/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garfield, Alastair S -- Cowley, Michael -- Smith, Florentia M -- Moorwood, Kim -- Stewart-Cox, Joanne E -- Gilroy, Kerry -- Baker, Sian -- Xia, Jing -- Dalley, Jeffrey W -- Hurst, Laurence D -- Wilkinson, Lawrence S -- Isles, Anthony R -- Ward, Andrew -- 093875/Wellcome Trust/United Kingdom -- G0300415/Medical Research Council/United Kingdom -- G0300415(66812)/Medical Research Council/United Kingdom -- G11786/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2011 Jan 27;469(7331):534-8. doi: 10.1038/nature09651.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology & Biochemistry and Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath BA2 7AY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21270893" target="_blank"〉PubMed〈/a〉
    Keywords: *Alleles ; Animals ; Behavior, Animal/*physiology ; Central Nervous System/embryology ; Female ; GRB10 Adaptor Protein/*genetics/*metabolism ; Gene Expression Regulation, Developmental ; Genomic Imprinting/*genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; Social Dominance
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Searching for Soft Relativistic Jets in Core-Collapse Supernovae with the IceCube Optical Follow-up Program (2011)
    In:  CASI
    Details
    Publication Date: 2019-07-12
    Description: Context. Transient neutrino sources such as Gamma-Ray Bursts (GRBs) and Supernovae (SNe) are hypothesized to emit bursts of high-energy neutrinos on a time-scale of 〈 or approx.100 s. While GRB neutrinos would be produced in high relativistic jets, core-collapse SNe might host soft-relativistic jets, which become stalled in the outer layers of the progenitor star leading to an efficient production of high-energy neutrinos. Aims. To increase the sensitivity to these neutrinos and identify their sources, a low-threshold optical follow-up program for neutrino multiplets detected with the IceCube observatory has been implemented. Methods. If a neutrino multiplet, i.e. two or more neutrinos from the same direction within 100 s, is found by IceCube a trigger is sent to the Robotic Optical Transient Search Experiment, ROTSE. The 4 ROTSE telescopes immediately start an observation program of the corresponding region of the sky in order to detect an optical counterpart to the neutrino events. Results. No statistically significant excess in the rate of neutrino multiplets has been observed and furthermore no coincidence with an optical counterpart was found. Conclusions. The search allows, for the first time, to set stringent limits on current models predicting a high-energy neutrino flux from soft relativistic hadronic jets in core-collapse SNe. We conclude that a sub-population of SNe with typical Lorentz boost factor and jet energy of 10 and 3 x 10(exp 51) erg, respectively, does not exceed 4:2% at 90% confidence.
    Keywords: Astrophysics
    Type: GSFC.JA.5925.2012
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  • 5
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    Testing Gravitational Physics with Space-based Gravitational-wave Observations (2011)
    In:  CASI
    Details
    Publication Date: 2019-07-19
    Description: Gravitational wave observations provide exceptional and unique opportunities for precision tests of gravitational physics, as predicted by general relativity (GR). Space-based gravitational wave measurements, with high signal-to-noise ratios and large numbers of observed events may provide the best-suited gravitational-wave observations for testing GR with unprecedented precision. These observations will be especially useful in testing the properties of gravitational waves and strong-field aspects of the theory which are less relevant in other observations. We review the proposed GR test based on observations of massive black hole mergers, extreme mass ratio inspirals, and galactic binary systems.
    Keywords: Astrophysics
    Type: GSFC.ABS.5948.2012 , Workshop for Gravitational-Wave Mission Architectural Concepts/Maritime Institute; Dec 20, 2011 - Dec 21, 2011; Linthicum, MD; United States
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  • 6
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    Searches for Periodic Neutrino Emission from Binary Systems with 22 and 40 Strings of IceCube (2011)
    In:  CASI
    Details
    Publication Date: 2019-07-12
    Description: Recent observations of GeV /TeV photon emission from several X-ray binaries have sparked a renewed interest in these objects as galactic particle accelerators. In spite of the available multi-wavelength data, their acceleration mechanisms are not determined, and the nature of the accelerated particles (hadrons or leptons) is unknown. While much evidence favors leptonic emission, it is very likely that a hadronic component is also accelerated in the jets of these binary systems. The observation of neutrino emission would be clear evidence for the presence of a hadronic component in the outflow of these sources. In this paper we look for periodic neutrino emission from binary systems. Such modulation, observed in the photon flux, would be caused by the geometry of these systems. The results of two searches are presented that differ in the treatment of the spectral shape and phase of the emission. The 'generic' search allows parameters to vary freely and best fit values, in a 'model-dependent' search, predictions are used to constrain these parameters. We use the IceCube data taken from May 31, 2007 to April 5, 2008 with its 22-string configuration, and from April 5, 2008 and May 20, 2009 with its 40-string configuration. For the generic search and the 40 string sample, we find that the most significant source in the catalog of 7 binary stars is Cygnus X-3 with a 1.8% probability after trials (2.10" sigma one-sided) of being produced by statistical fluctuations of the background. The model-dependent method tested a range of system geometries - the inclination and the massive star's disk size - for LS I+61 deg 303, no significant excess was found.
    Keywords: Astrophysics
    Type: GSFC.JA.5866.2012
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  • 7
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    New Concepts for Space-Based Gravitational Wave Missions (2011)
    In:  CASI
    Details
    Publication Date: 2019-07-12
    Description: The most astrophysically interesting sources in the gravitational wave spectrum lie in the low-frequency band (0.0001 - 1 Hz), which is only accessible from space. For two decades, the LISA concept has been the leading contender for a detector in this band. Despite a strong recommendation from Astro2010, there is strong motivation to find a less expensive concept, even at the loss of some science. We are searching for a lower cost mission concept by examining alternate orbits, less-capable measurement concepts, radically different implementations of the measurement concept and other cost-saving ideas. We report the results of our searches to date, and summarize the analyses behind them.
    Keywords: Astrophysics
    Type: GSFC.ABS.4428.2011
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  • 8
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    Geoscience Laser Altimetry System (GLAS) Loop Heat Pipe Anomaly and On Orbit Testing (2011)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: The Geoscience Laser Altimetry System (GLAS) is the sole instrument on the ICESat Satellite. On day 230 of 2003, the GLAS Component Loop Heat Pipe (CLHP) entered a slow circulation mode that resulted in the main electronics box reaching its hot safing temperature, after which the entire instrument was turned off. The CLHP had a propylene working fluid and was actively temperature controlled via a heater on the compensation chamber. The slow circulation mode happened right after a planned propulsive yaw maneuver with the spacecraft. It took several days to recover the CLHP and ensure that it was still operational. The recovery occurred after the entire instrument was cooled to survival temperatures and the CLHP compensation chamber cycled on a survival heater. There are several theories as to why this slow circulation mode exhibited itself, including: accumulation of Non-Condensible Gas (NCG), the secondary wick being under designed or improperly implemented, or an expanded (post-launch) leak across the primary wick. Each of these is discussed in turn, and the secondary wick performance is identified as the most likely source of the anomalous behavior. After the anomaly, the CLHP was controlled to colder temperatures to improve its performance (as the surface tension increases with lower temperature, as does the volume of liquid in the compensation chamber) and only precursor pulses occurred later in the mission. After GLAS s last laser failed, in late 2009, a decision was made to conduct engineering tests of both LHPs to try and duplicate this flight anomaly. The engineering tests consisted of control setpoint changes, sink changes, and one similar propulsive Yaw maneuver. The only test that showed any similar anomaly precursors on the CLHP was the propulsive maneuver followed by a setpoint increase. The ICESat Satellite was placed in a decaying orbit and ended its mission on August 30, 2010 in Barents Sea.
    Keywords: Lasers and Masers
    Type: GSFC.CP.4806.2011 , 41st International Conference on Environmental Systems; Jul 17, 2011 - Jul 21, 2011; Portland, OR; United States
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  • 9
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    The Atacama Cosmology Telescope: High-Resolution Sunyaev-Zel'dovich Array Observations of ACT SZE-Selected Clusters from the Equatorial Strip (2011)
    In:  CASI
    Details
    Publication Date: 2019-07-19
    Description: We present follow-up observations with the Sunyaev-Zel'dovich Array (SZA) of optically-confirmed galaxy clusters found in the equatorial survey region of the Atacama Cosmology Telescope (ACT): ACT-CL J0022-0036, ACT-CL J2051+0057, and ACT-CL J2337+0016. ACT-CL J0022-0036 is a newly-discovered, massive (10(exp 15) Msun), high-redshift (z=0.81) cluster revealed by ACT through the Sunyaev-Zel'dovich effect (SZE). Deep, targeted observations with the SZA allow us to probe a broader range of cluster spatial scales, better disentangle cluster decrements from radio point source emission, and derive more robust integrated SZE flux and mass estimates than we can with ACT data alone. For the two clusters we detect with the SZA we compute integrated SZE signal and derive masses from the SZA data only. ACT-CL J2337+0016, also known as Abell 2631, has archival Chandra data that allow an additional X-ray-based mass estimate. Optical richness is also used to estimate cluster masses and shows good agreement with the SZE and X-ray-based estimates. Based on the point sources detected by the SZA in these three cluster fields and an extrapolation to ACT's frequency, we estimate that point sources could be contaminating the SZE decrement at the less than = 20% level for some fraction of clusters.
    Keywords: Astrophysics
    Type: GSFC.ABS.5635.2011
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