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  • 1
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    Structural insight into precursor tRNA processing by yeast ribonuclease P (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018
    Description: 〈p〉Ribonuclease P (RNase P) is a universal ribozyme responsible for processing the 5'-leader of pre–transfer RNA (pre-tRNA). Here, we report the 3.5-angstrom cryo–electron microscopy structures of 〈i〉Saccharomyces cerevisiae〈/i〉 RNase P alone and in complex with pre-tRNA〈sup〉Phe〈/sup〉. The protein components form a hook-shaped architecture that wraps around the RNA and stabilizes RNase P into a "measuring device" with two fixed anchors that recognize the L-shaped pre-tRNA. A universally conserved uridine nucleobase and phosphate backbone in the catalytic center together with the scissile phosphate and the O3' leaving group of pre-tRNA jointly coordinate two catalytic magnesium ions. Binding of pre-tRNA induces a conformational change in the catalytic center that is required for catalysis. Moreover, simulation analysis suggests a two-metal-ion S〈sub〉N〈/sub〉2 reaction pathway of pre-tRNA cleavage. These results not only reveal the architecture of yeast RNase P but also provide a molecular basis of how the 5'-leader of pre-tRNA is processed by eukaryotic RNase P.〈/p〉
    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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    Structural insight into precursor tRNA processing by yeast ribonuclease P (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018
    Description: 〈p〉Ribonuclease P (RNase P) is a universal ribozyme responsible for processing the 5'-leader of pre-tRNA. Here we report the 3.5-Å cryo-EM structures of 〈i〉Saccharomyces cerevisiae〈/i〉 RNase P alone and in complex with pre-tRNA〈sup〉Phe〈/sup〉. The protein components form a hook-shaped architecture that wraps around the RNA and stabilizes RNase P into a "measuring device" with two fixed anchors that recognize the L-shaped pre-tRNA. A universally conserved uridine nucleobase and phosphate backbone in the catalytic center together with the scissile phosphate and the O3' leaving group of pre-tRNA jointly coordinate two catalytic magnesium ions. Binding of pre-tRNA induces a conformational change in the catalytic center that is required for catalysis. Moreover, simulation analysis suggests a two-metal-ion S〈sub〉N〈/sub〉2 reaction pathway of pre-tRNA cleavage. These results not only reveal the architecture of yeast RNase P but also provide a molecular basis of how the 5'-leader of pre-tRNA is processed by eukaryotic RNase P.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Structural insight into precursor tRNA processing by yeast ribonuclease P (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-11-09
    Description: Ribonuclease P (RNase P) is a universal ribozyme responsible for processing the 5'-leader of pre–transfer RNA (pre-tRNA). Here, we report the 3.5-angstrom cryo–electron microscopy structures of Saccharomyces cerevisiae RNase P alone and in complex with pre-tRNA Phe . The protein components form a hook-shaped architecture that wraps around the RNA and stabilizes RNase P into a "measuring device" with two fixed anchors that recognize the L-shaped pre-tRNA. A universally conserved uridine nucleobase and phosphate backbone in the catalytic center together with the scissile phosphate and the O3' leaving group of pre-tRNA jointly coordinate two catalytic magnesium ions. Binding of pre-tRNA induces a conformational change in the catalytic center that is required for catalysis. Moreover, simulation analysis suggests a two-metal-ion S N 2 reaction pathway of pre-tRNA cleavage. These results not only reveal the architecture of yeast RNase P but also provide a molecular basis of how the 5'-leader of pre-tRNA is processed by eukaryotic RNase P.
    Keywords: Biochemistry, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    A swarm of slippery micropropellers penetrates the vitreous body of the eye (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018
    Description: 〈p〉The intravitreal delivery of therapeutic agents promises major benefits in the field of ocular medicine. Traditional delivery methods rely on the random, passive diffusion of molecules, which do not allow for the rapid delivery of a concentrated cargo to a defined region at the posterior pole of the eye. The use of particles promises targeted delivery but faces the challenge that most tissues including the vitreous have a tight macromolecular matrix that acts as a barrier and prevents its penetration. Here, we demonstrate novel intravitreal delivery microvehicles—slippery micropropellers—that can be actively propelled through the vitreous humor to reach the retina. The propulsion is achieved by helical magnetic micropropellers that have a liquid layer coating to minimize adhesion to the surrounding biopolymeric network. The submicrometer diameter of the propellers enables the penetration of the biopolymeric network and the propulsion through the porcine vitreous body of the eye over centimeter distances. Clinical optical coherence tomography is used to monitor the movement of the propellers and confirm their arrival on the retina near the optic disc. Overcoming the adhesion forces and actively navigating a swarm of micropropellers in the dense vitreous humor promise practical applications in ophthalmology.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    PAC, an evolutionarily conserved membrane protein, is a proton-activated chloride channel (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Severe local acidosis causes tissue damage and pain, and is one of the hallmarks of many diseases including ischemia, cancer, and inflammation. However, the molecular mechanisms of the cellular response to acid are not fully understood. We performed an unbiased RNA interference screen and identified 〈i〉PAC (TMEM206)〈/i〉 as being essential for the widely observed proton-activated Cl〈sup〉–〈/sup〉 (PAC) currents (〈i〉I〈/i〉〈sub〉Cl,H〈/sub〉). Overexpression of human PAC in 〈i〉PAC〈/i〉 knockout cells generated 〈i〉I〈/i〉〈sub〉Cl,H〈/sub〉 with the same characteristics as the endogenous ones. Zebrafish PAC encodes a PAC channel with distinct properties. Knockout of mouse 〈i〉Pac〈/i〉 abolished 〈i〉I〈/i〉〈sub〉Cl,H〈/sub〉 in neurons and attenuated brain damage after ischemic stroke. The wide expression of PAC suggests a broad role for this conserved Cl〈sup〉–〈/sup〉 channel family in physiological and pathological processes associated with acidic pH.〈/p〉
    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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  • 6
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    A swarm of slippery micropropellers penetrates the vitreous body of the eye (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-11-03
    Description: The intravitreal delivery of therapeutic agents promises major benefits in the field of ocular medicine. Traditional delivery methods rely on the random, passive diffusion of molecules, which do not allow for the rapid delivery of a concentrated cargo to a defined region at the posterior pole of the eye. The use of particles promises targeted delivery but faces the challenge that most tissues including the vitreous have a tight macromolecular matrix that acts as a barrier and prevents its penetration. Here, we demonstrate novel intravitreal delivery microvehicles—slippery micropropellers—that can be actively propelled through the vitreous humor to reach the retina. The propulsion is achieved by helical magnetic micropropellers that have a liquid layer coating to minimize adhesion to the surrounding biopolymeric network. The submicrometer diameter of the propellers enables the penetration of the biopolymeric network and the propulsion through the porcine vitreous body of the eye over centimeter distances. Clinical optical coherence tomography is used to monitor the movement of the propellers and confirm their arrival on the retina near the optic disc. Overcoming the adhesion forces and actively navigating a swarm of micropropellers in the dense vitreous humor promise practical applications in ophthalmology.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Antibiotics crisis in China (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hao, Rongzhang -- Zhao, Rongtao -- Qiu, Shaofu -- Wang, Ligui -- Song, Hongbin -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):1100-1. doi: 10.1126/science.348.6239.1100-d. Epub 2015 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China. ; Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China. hongbinsong@263.net.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26045427" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/*analysis ; China ; *Drug Resistance, Bacterial ; Food Contamination/*prevention & control ; Humans ; Livestock ; Meat/analysis ; Swine ; Waste Water/analysis ; Water Pollution/*prevention & control ; Water Supply/analysis
    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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  • 8
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    Anti-parity-time symmetry in diffusive systems (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Various concepts related to parity-time symmetry, including anti–parity-time symmetry, have found broad applications in wave physics. Wave systems are fundamentally described by Hermitian operators, whereas their unusual properties are introduced by incorporation of gain and loss. We propose that the related physics need not be restricted to wave dynamics, and we consider systems described by diffusive dynamics. We study the heat transfer in two countermoving media and show that this system exhibits anti–parity-time symmetry. The spontaneous symmetry breaking results in a phase transition from motionless temperature profiles, despite the mechanical motion of the background, to moving temperature profiles. Our results extend the concepts of parity-time symmetry beyond wave physics and may offer opportunities to manipulate heat and mass transport.〈/p〉
    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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