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  • 1
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    Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-11-26
    Description: Ghrelin is a gastric peptide hormone that stimulates weight gain in vertebrates. The biological activities of ghrelin require octanoylation of the peptide on Ser(3), an unusual posttranslational modification that is catalyzed by the enzyme ghrelin O-acyltransferase (GOAT). Here, we describe the design, synthesis, and characterization of GO-CoA-Tat, a peptide-based bisubstrate analog that antagonizes GOAT. GO-CoA-Tat potently inhibits GOAT in vitro, in cultured cells, and in mice. Intraperitoneal administration of GO-CoA-Tat improves glucose tolerance and reduces weight gain in wild-type mice but not in ghrelin-deficient mice, supporting the concept that its beneficial metabolic effects are due specifically to GOAT inhibition. In addition to serving as a research tool for mapping ghrelin actions, GO-CoA-Tat may help pave the way for clinical targeting of GOAT in metabolic diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068526/" 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/PMC3068526/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barnett, Brad P -- Hwang, Yousang -- Taylor, Martin S -- Kirchner, Henriette -- Pfluger, Paul T -- Bernard, Vincent -- Lin, Yu-yi -- Bowers, Erin M -- Mukherjee, Chandrani -- Song, Woo-Jin -- Longo, Patti A -- Leahy, Daniel J -- Hussain, Mehboob A -- Tschop, Matthias H -- Boeke, Jef D -- Cole, Philip A -- P01 CA016519/CA/NCI NIH HHS/ -- P01 CA016519-35/CA/NCI NIH HHS/ -- P30 DK079637/DK/NIDDK NIH HHS/ -- P60 DK079637/DK/NIDDK NIH HHS/ -- P60 DK079637-05/DK/NIDDK NIH HHS/ -- R01 DK081472/DK/NIDDK NIH HHS/ -- R01 DK081472-01A1/DK/NIDDK NIH HHS/ -- R01 DK081472-02/DK/NIDDK NIH HHS/ -- R01 DK081472-03/DK/NIDDK NIH HHS/ -- R01 GM062437/GM/NIGMS NIH HHS/ -- R01 GM062437-04/GM/NIGMS NIH HHS/ -- R01 GM062437-11/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 17;330(6011):1689-92. doi: 10.1126/science.1196154. Epub 2010 Nov 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21097901" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Acyltransferases/*antagonists & inhibitors ; Animals ; Cell Survival/drug effects ; Drug Design ; Enzyme Inhibitors/chemical synthesis/*pharmacology/toxicity ; Ghrelin/deficiency/genetics/*metabolism ; Glucose/*metabolism ; Glucose Tolerance Test ; HeLa Cells ; Homeostasis ; Humans ; Insulin/metabolism ; Ion Channels/metabolism ; Islets of Langerhans/drug effects/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondrial Proteins/metabolism ; Peptides/chemical synthesis/*pharmacology/toxicity ; Weight Gain/*drug effects
    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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    A designed supramolecular protein assembly with in vivo enzymatic activity (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-12-20
    Description: The generation of new enzymatic activities has mainly relied on repurposing the interiors of preexisting protein folds because of the challenge in designing functional, three-dimensional protein structures from first principles. Here we report an artificial metallo-beta-lactamase, constructed via the self-assembly of a structurally and functionally unrelated, monomeric redox protein into a tetrameric assembly that possesses catalytic zinc sites in its interfaces. The designed metallo-beta-lactamase is functional in the Escherichia coli periplasm and enables the bacteria to survive treatment with ampicillin. In vivo screening of libraries has yielded a variant that displays a catalytic proficiency [(k(cat)/K(m))/k(uncat)] for ampicillin hydrolysis of 2.3 x 10(6) and features the emergence of a highly mobile loop near the active site, a key component of natural beta-lactamases to enable substrate interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Woon Ju -- Tezcan, F Akif -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1525-8. doi: 10.1126/science.1259680.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0356, USA. ; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0356, USA. tezcan@ucsd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525249" target="_blank"〉PubMed〈/a〉
    Keywords: Ampicillin/*chemistry/pharmacology ; Catalysis ; Catalytic Domain ; Crystallography, X-Ray ; *Directed Molecular Evolution ; Escherichia coli/drug effects/enzymology ; Hydrolysis ; Metalloproteins/*chemistry/genetics ; Mutation ; Periplasm/enzymology ; *Protein Engineering ; Protein Folding ; Protein Structure, Secondary ; Substrate Specificity ; Zinc/*chemistry ; beta-Lactamases/*chemistry/genetics
    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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  • 3
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    Analysis of Human Disturbance and Ecological Security Evolution in Oasis in Arid Area Based on LUCC: A Case Study of Oasis in the Northern Tianshan Mountain Slope Economic Zone (2017)
    Institute of Physics (IOP)
    Details
    Publication Date: 2017-07-22
    Description: Oases in arid areas are environmentally and economically vulnerable regions. Study on ecological security of oases in arid areas is of great significance to the stability and the economic development of oases. Based on Land Use/Land Cover data in 1965, 1980, 1995, 2005 and 2015, the study analyze the temporal and spatial changes in human disturbance and ecological security of oases in the Northern Tianshan Mountain Slope Economic Zone (NTMSEZ) in recent 50 years by establishing the ecological security index (ESI) through human disturbance index and landscape vulnerability index. The results showed that: in recent 50 years, the human disturbance of the NTMSEZ has been increased to current moderate human impacts. Urban construction, oasis expansion and farmland reclamation are the main factors of the increment. The human disturbance in Urumchi, Shihezi, Kuitun, Miquan and Changji is higher than that in other oases and that in core areas of oasis is higher than other areas. The ESI...
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
    Published by Institute of Physics (IOP)
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  • 4
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    Temporal and Spatial Variations of Vegetation Cover in Xinjiang from 2002 to 2015 and Their Response to Climate (2017)
    Institute of Physics (IOP)
    Details
    Publication Date: 2017-07-22
    Description: In this paper, the dataset of normalized difference vegetation indexes (NDVIs) in the arid region in Xinjiang from 2002 to 2015 as well as the climate data from 52 meteorological stations are utilized and the temporal and spatial variations of NDVI in recent years and their response to temperature and precipitation are analyzed in combination with various methods such as the maximum value analysis, correlation analysis and spatial analysis. It is concluded that in the past 14 years, the annual maximum NDVIs of Xinjiang presented a moderate rising tendency; Under the influence of the global background, the temperature and precipitation also showed different degrees of increase, which showed a significant increase in temperature. The annual maximum NDVI had a significant correlation with the annual precipitation (correlation coefficient: 0.634), but no obvious correlation was identified between the annual maximum NDVI and the annual average temperature (correlation coefficient: 0....
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
    Published by Institute of Physics (IOP)
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  • 5
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    Determination of an acoustic reflection coefficient at the inlet of a model gas turbine combustor for power generation (2017)
    Institute of Physics (IOP)
    Details
    Publication Date: 2017-01-24
    Description: A phenomenon that potentially influences the reliability of power generation systems is the presence of thermo-acoustic oscillations in the combustion chamber of a land- based gas turbine. To develop specific measures that prevent the instability, it is essential to predict and/or evaluate the underlying physics of the thermo-acoustics, which requires the acoustic boundary condition at the exit of the burner, that is, at the inlet of the combustor. Here we report a procedure for calculating acoustic reflection coefficients at the burner exit by utilizing two microphone method (TMM) for dynamic pressure signals. The procedure has been verified by comparing its results with reported ones and further successfully employed to determine the acoustic boundary condition of the burner of a partially-premixed model gas turbine combustor.
    Print ISSN: 1757-8981
    Electronic ISSN: 1757-899X
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by Institute of Physics (IOP)
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  • 6
    Electronic Resource
    Electronic Resource
    Germination response of Orobanche seeds subjected to conditioning temperature, water potential and growth regulator treatments (2005)
    Oxford, UK : Blackwell Science Ltd
    Weed research 45 (2005), S. 0 
    Details
    ISSN: 1365-3180
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Broomrapes (Orobanche spp.) are parasitic weeds that cause significant losses of crop yield. Experiments were conducted to investigate the seed response to the artificial germination stimulant GR24 in three species of Orobanche subjected to preconditioning under various temperatures, water potentials and with plant growth regulators. The highest germination percentages were observed in Orobanche ramosa, Orobanche aegyptiaca and Orobanche minor seeds conditioned at 18°C for 7 days followed by germination stimulation at 18°C. With the increase of the conditioning period (7, 14, 21 and 28 days), the germination percentage of O. ramosa and O. aegyptiaca progressively decreased. When conditioned at −2 MPa, the germination percentage was lower than at 0 and −1 MPa, especially at 13 and 28°C. Orobanche minor seeds could retain relatively high germination if conditioned at 18, 23 or 28°C, even after significantly extended conditioning periods (up to 84 days). GA3 (30–100 mg L−1), norflurazon and fluridone (10–100 mg L−1), and brassinolide (0.5–1.0 mg L−1) increased seed germination, while 0.01 mg L−1 uniconazole significantly reduced germination rates of all three Orobanche spp. The promotional effects of GA3 and norflurazon and the inhibitory effect of uniconazole were evident, even when they were treated for 3 days. Germination of Orobanche seeds was much lower when the unconditioned seeds were directly exposed to GR24 at 10−6 m. This early GR24-induced inhibition was however alleviated or even eliminated by the inclusion of GA3 or norflurazon (10–50 mg L−1) in the conditioning medium. On the contrary, the inclusion of uniconazole increased the inhibitory effect of GR24, particularly in the case of O. ramosa.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3180.2005.00477.x
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    Paper (German National Licenses)
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  • 7
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    Tracking a defined route for O2 migration in a dioxygen-activating diiron enzyme (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-08-22
    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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    Spin dynamics, electronic, and thermal transport properties of two-dimensional CrPS4 single crystal (2016)
    American Institute of Physics (AIP)
    Details
    Publication Date: 2016-01-28
    Description: 2-Dimensional (2D) CrPS 4 single crystals have been grown by the chemical vapor transport method. The crystallographic, magnetic, electronic, and thermal transport properties of the single crystals were investigated by the room-temperature X-ray diffraction, electrical resistivity ρ(T) , specific heat C P (T) , and the electronic spin response (ESR) measurements. CrPS 4 crystals crystallize into a monoclinic structure. The electrical resistivity ρ(T) shows a semiconducting behavior with an energy gap E a  = 0.166 eV. The antiferromagnetic transition temperature is about T N  = 36 K. The spin flipping induced by the applied magnetic field is observed along the c axis. The magnetic phase diagram of CrPS 4 single crystal has been discussed. The extracted magnetic entropy at T N is about 10.8 J/mol K, which is consistent with the theoretical value R ln(2S + 1) for S  = 3 / 2 of the Cr 3+ ion. Based on the mean-field theory, the magnetic exchange constants J 1 and J c corresponding to the interactions of the intralayer and between layers are about 0.143 meV and −0.955 meV are obtained based on the fitting of the susceptibility above T N , which agree with the results obtained from the ESR measurements. With the help of the strain for tuning the magnetic properties, monolayer CrPS 4 may be a promising candidate to explore 2D magnetic semiconductors.
    Print ISSN: 0021-8979
    Electronic ISSN: 1089-7550
    Topics: Physics
    Published by American Institute of Physics (AIP)
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  • 9
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    Stretchable batteries with gradient multilayer conductors (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉Stretchable conductors are essential components in next-generation deformable and wearable electronic devices. The ability of stretchable conductors to achieve sufficient electrical conductivity, however, remains limited under high strain, which is particularly detrimental for charge storage devices. In this study, we present stretchable conductors made from multiple layers of gradient assembled polyurethane (GAP) comprising gold nanoparticles capable of self-assembly under strain. Stratified layering affords control over the composite internal architecture at multiple scales, leading to metallic conductivity in both the lateral and transversal directions under strains of as high as 300%. The unique combination of the electrical and mechanical properties of GAP electrodes enables the development of a stretchable lithium-ion battery with a charge-discharge rate capability of 100 mAh g〈sup〉–1〈/sup〉 at a current density of 0.5 A g〈sup〉–1〈/sup〉 and remarkable cycle retention of 96% after 1000 cycles. The hierarchical GAP nanocomposites afford rapid fabrication of advanced charge storage devices.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
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    Tracking a defined route for O2 migration in a dioxygen-activating diiron enzyme [Chemistry] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-09-07
    Description: For numerous enzymes reactive toward small gaseous compounds, growing evidence indicates that these substrates diffuse into active site pockets through defined pathways in the protein matrix. Toluene/o-xylene monooxygenase hydroxylase is a dioxygen-activating enzyme. Structural analysis suggests two possible pathways for dioxygen access through the α-subunit to the diiron center: a channel or a series of hydrophobic cavities. To distinguish which is utilized as the O2 migration pathway, the dimensions of the cavities and the channel were independently varied by site-directed mutagenesis and confirmed by X-ray crystallography. The rate constants for dioxygen access to the diiron center were derived from the formation rates of a peroxodiiron(III) intermediate, generated upon treatment of the diiron(II) enzyme with O2. This reaction depends on the concentration of dioxygen to the first order. Altering the dimensions of the cavities, but not the channel, changed the rate of dioxygen reactivity with the enzyme. These results strongly suggest that voids comprising the cavities in toluene/o-xylene monooxygenase hydroxylase are not artifacts of protein packing/folding, but rather programmed routes for dioxygen migration through the protein matrix. Because the cavities are not fully connected into the diiron active center in the enzyme resting state, conformational changes will be required to facilitate dioxygen access to the diiron center. We propose that such temporary opening and closing of the cavities may occur in all bacterial multicomponent monooxygenases to control O2 consumption for efficient catalysis. Our findings suggest that other gas-utilizing enzymes may employ similar structural features to effect substrate passage through a protein matrix.
    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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