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  • 2010-2014  (163)
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  • 1
    Publikationsdatum: 2011-02-16
    Beschreibung: Analytical Chemistry DOI: 10.1021/ac102769j
    Print ISSN: 0003-2700
    Digitale ISSN: 1520-6882
    Thema: Chemie und Pharmazie
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2011-04-27
    Beschreibung: Affinity reagents that bind to specific molecular targets are an essential tool for both diagnostics and targeted therapeutics. There is a particular need for advanced technologies for the generation of reagents that specifically target cell-surface markers, because transmembrane proteins are notoriously difficult to express in recombinant form. We have previously shown that microfluidics offers many advantages for generating affinity reagents against purified protein targets, and we have now significantly extended this approach to achieve successful in vitro selection of T7 phage-displayed peptides that recognize markers expressed on live, adherent cells within a microfluidic channel. As a model, we have targeted neuropilin-1 (NRP-1), a membrane-bound receptor expressed at the surface of human prostate carcinoma cells that plays central roles in angiogenesis, cell migration, and invasion. We show that, compared to conventional biopanning methods, microfluidic selection enables more efficient discovery of peptides with higher affinity and specificity by providing controllable and reproducible means for applying stringent selection conditions against minimal amounts of target cells without loss. Using our microfluidic system, we isolate peptide sequences with superior binding affinity and specificity relative to the well known NRP-1-binding RPARPAR peptide. As such microfluidic systems can be used with a wide range of biocombinatorial libraries and tissue types, we believe that our method represents an effective approach toward efficient biomarker discovery from patient samples.
    Print ISSN: 0027-8424
    Digitale ISSN: 1091-6490
    Thema: Biologie , Medizin , Allgemeine Naturwissenschaft
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Publikationsdatum: 2014-11-02
    Beschreibung: We exploit data from the Pan-Andromeda Archaeological Survey (PAndAS) to study the extended structures of M31's dwarf elliptical companions, NGC 147 and NGC 185. Our wide-field, homogeneous photometry allows us to construct deep colour–magnitude diagrams which reach down to ~3 mag below the red giant branch (RGB) tip. We trace the stellar components of the galaxies to surface brightness of μ g  ~ 32 mag arcsec –2 and show that they have much larger extents (~5 kpc radii) than previously recognized. While NGC 185 retains a regular shape in its peripheral regions, NGC 147 exhibits pronounced isophotal twisting due to the emergence of symmetric tidal tails. We fit single Sérsic models to composite surface brightness profiles constructed from diffuse light and star counts and find that NGC 147 has an effective radius almost three times that of NGC 185. In both cases, the effective radii that we calculate are larger by a factor of ~2 compared to most literature values. We also calculate revised total magnitudes of M g  = –15.36 ± 0.04 for NGC 185 and M g  = –16.36 ± 0.04 for NGC 147. Using photometric metallicities computed for RGB stars, we find NGC 185 to exhibit a metallicity gradient of [Fe/H] ~ –0.15 dex kpc –1 over the radial range 0.125–0.5 deg. On the other hand, NGC 147 exhibits almost no metallicity gradient, ~–0.02 dex kpc –1 from 0.2 to 0.6 deg. The differences in the structure and stellar populations in the outskirts of these systems suggest that tidal influences have played an important role in governing the evolution of NGC 147.
    Print ISSN: 0035-8711
    Digitale ISSN: 1365-2966
    Thema: Physik
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Publikationsdatum: 2014-06-20
    Beschreibung: We report the discovery of 59 globular clusters (GCs) and two candidate GCs in a search of the halo of M31, primarily via visual inspection of Canada–France–Hawaii Telescope/MegaCam imagery from the Pan-Andromeda Archaeological Survey (PAndAS). The superior quality of these data also allows us to check the classification of remote objects in the Revised Bologna Catalogue (RBC), plus a subset of GC candidates drawn from Sloan Digital Sky Survey (SDSS) imaging. We identify three additional new GCs from the RBC, and confirm the GC nature of 11 SDSS objects (8 of which appear independently in our remote halo catalogue); the remaining 188 candidates across both lists are either foreground stars or background galaxies. Our new catalogue represents the first uniform census of GCs across the M31 halo – we find clusters to the limit of the PAndAS survey area at projected radii of up to R proj  ~ 150 kpc. Tests using artificial clusters reveal that detection incompleteness cuts in at luminosities below M V  = –6.0; our 50 per cent completeness limit is M V   –4.1. We construct a uniform set of PAndAS photometric measurements for all known GCs outside R proj  = 25 kpc, and any new GCs within this radius. With these data, we update results from Huxor et al., investigating the luminosity function (LF), colours and effective radii of M31 GCs with a particular focus on the remote halo. We find that the GCLF is clearly bimodal in the outer halo ( R proj  〉 30 kpc), with the secondary peak at M V  ~ –5.5. We argue that the GCs in this peak have most likely been accreted along with their host dwarf galaxies. Notwithstanding, we also find, as in previous surveys, a substantial number of GCs with above-average luminosity in the outer M31 halo – a population with no clear counterpart in the Milky Way.
    Print ISSN: 0035-8711
    Digitale ISSN: 1365-2966
    Thema: Physik
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Publikationsdatum: 2014-07-01
    Beschreibung: We present a detailed kinematic analysis of the outer halo globular cluster system of the Andromeda galaxy (M31). Our basis for this is a set of new spectroscopic observations for 78 clusters lying at projected distances between R proj  ~ 20–140 kpc from the M31 centre. These are largely drawn from the recent Pan-Andromeda Archaeological Survey globular cluster catalogue; 63 of our targets have no previous velocity data. Via a Bayesian maximum likelihood analysis, we find that globular clusters with R proj  〉 30 kpc exhibit coherent rotation around the minor optical axis of M31, in the same direction as more centrally located globular clusters, but with a smaller amplitude of 86 ± 17 km s –1 . There is also evidence that the velocity dispersion of the outer halo globular cluster system decreases as a function of projected distance from the M31 centre, and that this relation can be well described by a power law of index –0.5. The velocity dispersion profile of the outer halo globular clusters is quite similar to that of the halo stars, at least out to the radius up to which there is available information on the stellar kinematics. We detect and discuss various velocity correlations amongst subgroups of globular clusters that lie on stellar debris streams in the M31 halo. Many of these subgroups are dynamically cold, exhibiting internal velocity dispersions consistent with zero. Simple Monte Carlo experiments imply that such configurations are unlikely to form by chance, adding weight to the notion that a significant fraction of the outer halo globular clusters in M31 have been accreted alongside their parent dwarf galaxies. We also estimate the M31 mass within 200 kpc via the Tracer Mass Estimator (TME), finding (1.2–1.6) ± 0.2 10 12 M . This quantity is subject to additional systematic effects due to various limitations of the data, and assumptions built in into the TME. Finally, we discuss our results in the context of formation scenarios for the M31 halo.
    Print ISSN: 0035-8711
    Digitale ISSN: 1365-2966
    Thema: Physik
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Publikationsdatum: 2010-09-25
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferguson, Charles D -- Marburger, Lindsey E -- Farmer, J Doyne -- Makhijani, Arjun -- England -- Nature. 2010 Sep 23;467(7314):391-3. doi: 10.1038/467391a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Federation of American Scientists, Washington, DC 20036, USA. cferguson@fas.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20864972" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Conservation of Energy Resources/economics/*trends ; Electricity ; Fossil Fuels/economics/utilization ; Nuclear Power Plants/economics/*statistics & numerical data ; United States
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Publikationsdatum: 2012-12-14
    Beschreibung: Ventral tegmental area (VTA) dopamine neurons in the brain's reward circuit have a crucial role in mediating stress responses, including determining susceptibility versus resilience to social-stress-induced behavioural abnormalities. VTA dopamine neurons show two in vivo patterns of firing: low frequency tonic firing and high frequency phasic firing. Phasic firing of the neurons, which is well known to encode reward signals, is upregulated by repeated social-defeat stress, a highly validated mouse model of depression. Surprisingly, this pathophysiological effect is seen in susceptible mice only, with no apparent change in firing rate in resilient individuals. However, direct evidence--in real time--linking dopamine neuron phasic firing in promoting the susceptible (depression-like) phenotype is lacking. Here we took advantage of the temporal precision and cell-type and projection-pathway specificity of optogenetics to show that enhanced phasic firing of these neurons mediates susceptibility to social-defeat stress in freely behaving mice. We show that optogenetic induction of phasic, but not tonic, firing in VTA dopamine neurons of mice undergoing a subthreshold social-defeat paradigm rapidly induced a susceptible phenotype as measured by social avoidance and decreased sucrose preference. Optogenetic phasic stimulation of these neurons also quickly induced a susceptible phenotype in previously resilient mice that had been subjected to repeated social-defeat stress. Furthermore, we show differences in projection-pathway specificity in promoting stress susceptibility: phasic activation of VTA neurons projecting to the nucleus accumbens (NAc), but not to the medial prefrontal cortex (mPFC), induced susceptibility to social-defeat stress. Conversely, optogenetic inhibition of the VTA-NAc projection induced resilience, whereas inhibition of the VTA-mPFC projection promoted susceptibility. Overall, these studies reveal novel firing-pattern- and neural-circuit-specific mechanisms of depression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554860/" 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/PMC3554860/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chaudhury, Dipesh -- Walsh, Jessica J -- Friedman, Allyson K -- Juarez, Barbara -- Ku, Stacy M -- Koo, Ja Wook -- Ferguson, Deveroux -- Tsai, Hsing-Chen -- Pomeranz, Lisa -- Christoffel, Daniel J -- Nectow, Alexander R -- Ekstrand, Mats -- Domingos, Ana -- Mazei-Robison, Michelle S -- Mouzon, Ezekiell -- Lobo, Mary Kay -- Neve, Rachael L -- Friedman, Jeffrey M -- Russo, Scott J -- Deisseroth, Karl -- Nestler, Eric J -- Han, Ming-Hu -- F31 MH095425/MH/NIMH NIH HHS/ -- F32 MH096464/MH/NIMH NIH HHS/ -- K99 MH094405/MH/NIMH NIH HHS/ -- R01 MH092306/MH/NIMH NIH HHS/ -- R25 GM064118/GM/NIGMS NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- T32 MH087004/MH/NIMH NIH HHS/ -- T32 MH096678/MH/NIMH NIH HHS/ -- England -- Nature. 2013 Jan 24;493(7433):532-6. doi: 10.1038/nature11713. Epub 2012 Dec 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Systems Therapeutics, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235832" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Depression/etiology/*physiopathology ; Dopaminergic Neurons/*metabolism ; Food Preferences ; Male ; Mesencephalon/*cytology ; Mice ; Neural Pathways ; Nucleus Accumbens/physiology ; Optogenetics ; Phenotype ; Prefrontal Cortex/physiology ; *Social Behavior ; Stress, Psychological/complications/*physiopathology ; Sucrose/administration & dosage ; Time Factors ; Ventral Tegmental Area/physiology
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
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    Unbekannt
    Nature Publishing Group (NPG)
    Publikationsdatum: 2011-03-25
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferguson, Charles D -- England -- Nature. 2011 Mar 24;471(7339):411. doi: 10.1038/471411a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Federation of American Scientists, Washington DC, USA. cferguson@fas.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21430730" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Conservation of Energy Resources/economics/*methods/statistics & numerical ; data/*trends ; *Internationality ; Japan ; Nuclear Energy/economics/*statistics & numerical data ; Nuclear Power Plants/economics/standards/*supply & distribution/*utilization ; Public Opinion ; Radioactive Hazard Release/prevention & control ; Tsunamis
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Publikationsdatum: 2014-11-11
    Beschreibung: beta-catenin is a multi-functional protein that has an important role in the mature central nervous system; its dysfunction has been implicated in several neuropsychiatric disorders, including depression. Here we show that in mice beta-catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a key brain reward region, an effect mediated by D2-type medium spiny neurons. Using genome-wide beta-catenin enrichment mapping, we identify Dicer1-important in small RNA (for example, microRNA) biogenesis--as a beta-catenin target gene that mediates resilience. Small RNA profiling after excising beta-catenin from nucleus accumbens in the context of chronic stress reveals beta-catenin-dependent microRNA regulation associated with resilience. Together, these findings establish beta-catenin as a critical regulator in the development of behavioural resilience, activating a network that includes Dicer1 and downstream microRNAs. We thus present a foundation for the development of novel therapeutic targets to promote stress resilience.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257892/" 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/PMC4257892/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dias, Caroline -- Feng, Jian -- Sun, Haosheng -- Shao, Ning Yi -- Mazei-Robison, Michelle S -- Damez-Werno, Diane -- Scobie, Kimberly -- Bagot, Rosemary -- LaBonte, Benoit -- Ribeiro, Efrain -- Liu, XiaoChuan -- Kennedy, Pamela -- Vialou, Vincent -- Ferguson, Deveroux -- Pena, Catherine -- Calipari, Erin S -- Koo, Ja Wook -- Mouzon, Ezekiell -- Ghose, Subroto -- Tamminga, Carol -- Neve, Rachael -- Shen, Li -- Nestler, Eric J -- P50 MH096890/MH/NIMH NIH HHS/ -- R00 MH094405/MH/NIMH NIH HHS/ -- England -- Nature. 2014 Dec 4;516(7529):51-5. doi: 10.1038/nature13976. Epub 2014 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; Department of Psychiatry, University of Texas Southwestern, Dallas, Texas 75390, USA. ; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383518" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adaptation, Physiological/genetics ; Animals ; DEAD-box RNA Helicases/*genetics/metabolism ; Depression/physiopathology ; Gene Expression Profiling ; *Gene Expression Regulation ; Genome-Wide Association Study ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs/*genetics/metabolism ; Neurons/metabolism ; *Resilience, Psychological ; Ribonuclease III/*genetics/metabolism ; Signal Transduction ; Stress, Physiological/*genetics ; beta Catenin/genetics/*metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Publikationsdatum: 2012-10-09
    Beschreibung: Brain-derived neurotrophic factor (BDNF) is a key positive regulator of neural plasticity, promoting, for example, the actions of stimulant drugs of abuse such as cocaine. We discovered a surprising opposite role for BDNF in countering responses to chronic morphine exposure. The suppression of BDNF in the ventral tegmental area (VTA) enhanced the ability of morphine to increase dopamine (DA) neuron excitability and promote reward. In contrast, optical stimulation of VTA DA terminals in nucleus accumbens (NAc) completely reversed the suppressive effect of BDNF on morphine reward. Furthermore, we identified numerous genes in the NAc, a major target region of VTA DA neurons, whose regulation by BDNF in the context of chronic morphine exposure mediated this counteractive function. These findings provide insight into the molecular basis of morphine-induced neuroadaptations in the brain's reward circuitry.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547365/" 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/PMC3547365/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koo, Ja Wook -- Mazei-Robison, Michelle S -- Chaudhury, Dipesh -- Juarez, Barbara -- LaPlant, Quincey -- Ferguson, Deveroux -- Feng, Jian -- Sun, Haosheng -- Scobie, Kimberly N -- Damez-Werno, Diane -- Crumiller, Marshall -- Ohnishi, Yoshinori N -- Ohnishi, Yoko H -- Mouzon, Ezekiell -- Dietz, David M -- Lobo, Mary Kay -- Neve, Rachael L -- Russo, Scott J -- Han, Ming-Hu -- Nestler, Eric J -- K99 MH094405/MH/NIMH NIH HHS/ -- P01 DA008227/DA/NIDA NIH HHS/ -- R01 DA014133/DA/NIDA NIH HHS/ -- R01 MH092306/MH/NIMH NIH HHS/ -- T32 MH087004/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2012 Oct 5;338(6103):124-8. doi: 10.1126/science.1222265.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23042896" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Brain-Derived Neurotrophic Factor/genetics/*physiology ; Dopamine/metabolism ; Dopaminergic Neurons/*drug effects/physiology ; Gene Expression Regulation ; Gene Knockdown Techniques ; Gene Knockout Techniques ; Male ; Mice ; Mice, Inbred C57BL ; Morphine/*pharmacology ; Morphine Dependence/genetics/*physiopathology ; Nucleus Accumbens/drug effects/physiopathology ; Photic Stimulation ; Receptor, trkB/genetics/physiology ; Ventral Tegmental Area/*drug effects/physiology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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