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  • 1
    Publication Date: 2014-03-29
    Description: Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATalpha allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033833/" 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/PMC4033833/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Annaluru, Narayana -- Muller, Heloise -- Mitchell, Leslie A -- Ramalingam, Sivaprakash -- Stracquadanio, Giovanni -- Richardson, Sarah M -- Dymond, Jessica S -- Kuang, Zheng -- Scheifele, Lisa Z -- Cooper, Eric M -- Cai, Yizhi -- Zeller, Karen -- Agmon, Neta -- Han, Jeffrey S -- Hadjithomas, Michalis -- Tullman, Jennifer -- Caravelli, Katrina -- Cirelli, Kimberly -- Guo, Zheyuan -- London, Viktoriya -- Yeluru, Apurva -- Murugan, Sindurathy -- Kandavelou, Karthikeyan -- Agier, Nicolas -- Fischer, Gilles -- Yang, Kun -- Martin, J Andrew -- Bilgel, Murat -- Bohutski, Pavlo -- Boulier, Kristin M -- Capaldo, Brian J -- Chang, Joy -- Charoen, Kristie -- Choi, Woo Jin -- Deng, Peter -- DiCarlo, James E -- Doong, Judy -- Dunn, Jessilyn -- Feinberg, Jason I -- Fernandez, Christopher -- Floria, Charlotte E -- Gladowski, David -- Hadidi, Pasha -- Ishizuka, Isabel -- Jabbari, Javaneh -- Lau, Calvin Y L -- Lee, Pablo A -- Li, Sean -- Lin, Denise -- Linder, Matthias E -- Ling, Jonathan -- Liu, Jaime -- Liu, Jonathan -- London, Mariya -- Ma, Henry -- Mao, Jessica -- McDade, Jessica E -- McMillan, Alexandra -- Moore, Aaron M -- Oh, Won Chan -- Ouyang, Yu -- Patel, Ruchi -- Paul, Marina -- Paulsen, Laura C -- Qiu, Judy -- Rhee, Alex -- Rubashkin, Matthew G -- Soh, Ina Y -- Sotuyo, Nathaniel E -- Srinivas, Venkatesh -- Suarez, Allison -- Wong, Andy -- Wong, Remus -- Xie, Wei Rose -- Xu, Yijie -- Yu, Allen T -- Koszul, Romain -- Bader, Joel S -- Boeke, Jef D -- Chandrasegaran, Srinivasan -- 092076/Wellcome Trust/United Kingdom -- GM077291/GM/NIGMS NIH HHS/ -- R01 GM077291/GM/NIGMS NIH HHS/ -- R01 GM090192/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):55-8. doi: 10.1126/science.1249252. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Environmental Health Sciences, Johns Hopkins University (JHU) School of Public Health, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674868" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Chromosomes, Fungal/genetics/metabolism ; DNA, Fungal/genetics ; Genes, Fungal ; Genetic Fitness ; Genome, Fungal ; Genomic Instability ; Introns ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; RNA, Fungal/genetics ; RNA, Transfer/genetics ; Saccharomyces cerevisiae/cytology/*genetics/physiology ; Sequence Analysis, DNA ; Sequence Deletion ; Synthetic Biology/*methods ; Transformation, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2012-02-10
    Description: First identified as histone-modifying proteins, lysine acetyltransferases (KATs) and deacetylases (KDACs) antagonize each other through modification of the side chains of lysine residues in histone proteins. Acetylation of many non-histone proteins involved in chromatin, metabolism or cytoskeleton regulation were further identified in eukaryotic organisms, but the corresponding enzymes and substrate-specific functions of the modifications are unclear. Moreover, mechanisms underlying functional specificity of individual KDACs remain enigmatic, and the substrate spectra of each KDAC lack comprehensive definition. Here we dissect the functional specificity of 12 critical human KDACs using a genome-wide synthetic lethality screen in cultured human cells. The genetic interaction profiles revealed enzyme-substrate relationships between individual KDACs and many important substrates governing a wide array of biological processes including metabolism, development and cell cycle progression. We further confirmed that acetylation and deacetylation of the catalytic subunit of the adenosine monophosphate-activated protein kinase (AMPK), a critical cellular energy-sensing protein kinase complex, is controlled by the opposing catalytic activities of HDAC1 and p300. Deacetylation of AMPK enhances physical interaction with the upstream kinase LKB1, leading to AMPK phosphorylation and activation, and resulting in lipid breakdown in human liver cells. These findings provide new insights into previously underappreciated metabolic regulatory roles of HDAC1 in coordinating nutrient availability and cellular responses upstream of AMPK, and demonstrate the importance of high-throughput genetic interaction profiling to elucidate functional specificity and critical substrates of individual human KDACs potentially valuable for therapeutic applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277212/" 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/PMC3277212/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Yu-yi -- Kiihl, Samara -- Suhail, Yasir -- Liu, Shang-Yun -- Chou, Yi-hsuan -- Kuang, Zheng -- Lu, Jin-ying -- Khor, Chin Ni -- Lin, Chi-Long -- Bader, Joel S -- Irizarry, Rafael -- Boeke, Jef D -- U54 RR 020839/RR/NCRR NIH HHS/ -- U54 RR020839/RR/NCRR NIH HHS/ -- U54 RR020839-09/RR/NCRR NIH HHS/ -- England -- Nature. 2012 Feb 8;482(7384):251-5. doi: 10.1038/nature10804.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan. yuyilin@ntu.edu.tw〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22318606" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/chemistry/genetics/*metabolism ; Acetylation ; Biocatalysis ; Catalytic Domain ; Cell Cycle ; Cell Line ; Cell Line, Tumor ; Histone Deacetylase 1/genetics/*metabolism ; Humans ; Lysine/*metabolism ; Phosphorylation ; Protein Binding ; Protein-Serine-Threonine Kinases/metabolism ; RNA Interference ; Substrate Specificity ; p300-CBP Transcription Factors/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    ISSN: 1572-8838
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Notes: Abstract The current distribution in an aluminium electrolysis cell with a Søderberg anode was calculated to supplement measured data (Part I of this study). A numerical method based on the conservative scheme was used. A 2D cross section of a commercial cell was considered and the electric fields in the anode, cathode and the electrolyte were considered under steady state conditions. Four different approximations of a curvilinear boundary were proposed. The overvoltage for both electrodes was introduced. The current density decreased along the side of the anode from the nominal value 0.8 A cm−2 on the underside to 0.26 A cm−2 in the upper part near the surface of the electrolyte. The calculated current density along the side of the Soderberg anode for all the approximations was compared with the measured data, and the agreement was within 10 to 15%. In the curved part of the anode the differences between measured and calculated values were 20–28%; but in this region the accuracy of the experimental data was in the same range. Also the finite element method was used for the comparison of the calculated current density.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1572-9532
    Keywords: EXACT SOLUTION ; ELECTROMAGNETIC SHOCK WAVE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Einstein-Maxwell spacetimes endowed with twocommuting spacelike Killing vector fields areconsidered. Subject to the hypotheses that one of thetwo null geodesic congruence orthogonal to thetwo-surface generated by the two commuting spacelikeKilling vector fields is shearfree and theelectromagnetic field is non null, it is shown that,with a specific choice of null tetrad, theNewman-Penrose equations together with the Maxwell equations for theclass of spacetime considered may be reduced to asecond-order ode of Sturm-Liouville type, from whichexact solutions of the class of spacetimes consideredmay be constructed. Examples of exact solutions arethen given. Exact solutions with distribution-valuedWeyl curvature describing the scattering ofelectromagnetic shock wave with gravitational impulsiveor shock wave of variable polarisation are also constructed.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1572-8838
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Notes: Abstract A voltage probe was used to determine the current distribution along the sides of the anodes in commercial Søderberg aluminium cells. The current density decreased in the upward direction along the side of the anode from 0.8 A cm−2 on the working face to 0.15–0.28 A cm−2 near the surface of the bath. It was estimated that only 5%–10% of the carbon dust formed in Søderberg cells was generated at the side of the anode, and the rest came from the working face of the anode. About 5% of the total anode consumption took place on the side of the anode, of which ∼3% was caused by air-burning above the bath (electrolyte) level.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0009-3084
    Keywords: Antioxidant activity ; Erythrocyte hemolysis ; Lipophilic vitamin C
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 7
    Publication Date: 2018-06-02
    Description: Introduction High blood pressure (BP) affects over 40% of adults over the age of 25 worldwide and is the leading global risk factor for death or disability. Hypertension is also the most important risk factor for endovascular atherosclerosis, which, when combined with other cardiovascular risk factors, leads to atherosclerotic cardiovascular disease (ASCVD). Statins are one of the most widely used drugs for the prevention of ASCVD. The recently announced study of Heart Outcomes Prevention Evaluation-3 suggests that cholesterol-lowering agents combined with antihypertensive therapy can prevent cardiovascular events and reduce the combined endpoint. We plan to conduct a systematic review and meta-analysis to evaluate whether combined antihypertensive and statin therapy is more beneficial than antihypertensive therapy alone in patients with hypertension without complications. Methods and analysis We will perform a comprehensive search for randomised controlled trials evaluating combined antihypertensive and statin therapy for the treatment of patients with hypertension. The following English electronic databases will be searched: The Cochrane Library, EMBASE and PubMed. Outcomes will be categorised as short-term (≤6 months) or long-term (〉6 months). When evaluating the effects of combined antihypertensive and statin therapy, a short-term outcome is usually defined as a change in BP or lipid levels, while a long-term outcome is usually defined as cardiovascular benefits or risks. The data screening and extraction will be conducted by two different reviewers. The quality of the RCTs will be assessed according to the Cochrane handbook risk of bias tool. Ethics and dissemination This review does not require ethics approval and the results of the meta-analysis will be submitted to a peer-review journal. PROSPERO registration number CRD 42017071935 .
    Keywords: Open access, Cardiovascular medicine
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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