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Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA 期刊论文
NATURE, 2020, 583 (7814) : 139-+
作者:  Muniz, Juan A.;  Barberena, Diego;  Lewis-Swan, Robert J.;  Young, Dylan J.;  Cline, Julia R. K.;  Rey, Ana Maria;  Thompson, James K.
收藏  |  浏览/下载:55/0  |  提交时间:2020/07/03

MicroRNAs (miRNAs) regulate the levels of translation of messenger RNAs (mRNAs). At present, the major parameter that can explain the selection of the target mRNA and the efficiency of translation repression is the base pairing between the '  seed'  region of the miRNA and its counterpart mRNA(1). Here we use R-1 rho relaxation-dispersion nuclear magnetic resonance(2) and molecular simulations(3) to reveal a dynamic switch-based on the rearrangement of a single base pair in the miRNA-mRNA duplex-that elongates a weak five-base-pair seed to a complete seven-base-pair seed. This switch also causes coaxial stacking of the seed and supplementary helix fitting into human Argonaute 2 protein (Ago2), reminiscent of an active state in prokaryotic Ago(4,5). Stabilizing this transient state leads to enhanced repression of the target mRNA in cells, revealing the importance of this miRNA-mRNA structure. Our observations tie together previous findings regarding the stepwise miRNA targeting process from an initial '  screening'  state to an '  active'  state, and unveil the role of the RNA duplex beyond the seed in Ago2.


Repression of a messenger RNA by a cognate microRNA depends not only on complementary base pairing, but also on the rearrangement of a single base pair, producing a conformation that fits better within the human Ago2 protein.


  
A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes 期刊论文
NATURE, 2020, 582 (7811) : 271-+
作者:  Waszak, Sebastian M.;  Robinson, Giles W.;  Gudenas, Brian L.;  Smith, Kyle S.;  Forget, Antoine;  Kojic, Marija;  Garcia-Lopez, Jesus;  Hadley, Jennifer;  Hamilton, Kayla V.;  Indersie, Emilie;  Buchhalter, Ivo;  Kerssemakers, Jules;  Jaeger, Natalie;  Sharma, Tanvi;  Rausch, Tobias
收藏  |  浏览/下载:39/0  |  提交时间:2020/07/03

Hoxb13 acts as a cofactor of Meis1 in regulating cardiomyocyte maturation and cell cycle, and knockout of both proteins enables regeneration of postnatal cardiac tissue in a mouse model of heart injury.


A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes(1,2) and that Meis1, a three amino acid loop extension (TALE) family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest(3). Here we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can extend the postnatal window of cardiomyocyte proliferation and reactivate the cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and improved left ventricular systolic function following myocardial infarction, as demonstrated by echocardiography and magnetic resonance imaging. Chromatin immunoprecipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204, resulting in its nuclear localization and cell cycle arrest. These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes.


  
In situ NMR metrology reveals reaction mechanisms in redox flow batteries 期刊论文
NATURE, 2020, 579 (7798) : 224-+
作者:  Ma, Jianfei;  You, Xin;  Sun, Shan;  Wang, Xiaoxiao;  Qin, Song;  Sui, Sen-Fang
收藏  |  浏览/下载:39/0  |  提交时间:2020/07/03

Large-scale energy storage is becoming increasingly critical to balancing renewable energy production and consumption(1). Organic redox flow batteries, made from inexpensive and sustainable redox-active materials, are promising storage technologies that are cheaper and less environmentally hazardous than vanadium-based batteries, but they have shorter lifetimes and lower energy density(2,3). Thus, fundamental insight at the molecular level is required to improve performance(4,5). Here we report two in situ nuclear magnetic resonance (NMR) methods of studying redox flow batteries, which are applied to two redox-active electrolytes: 2,6-dihydroxyanthraquinone (DHAQ) and 4,4 '  -((9,10-anthraquinone-2,6-diyl)dioxy) dibutyrate (DBEAQ). In the first method, we monitor the changes in the H-1 NMR shift of the liquid electrolyte as it flows out of the electrochemical cell. In the second method, we observe the changes that occur simultaneously in the positive and negative electrodes in the full electrochemical cell. Using the bulk magnetization changes (observed via the H-1 NMR shift of the water resonance) and the line broadening of the H-1 shifts of the quinone resonances as a function of the state of charge, we measure the potential differences of the two single-electron couples, identify and quantify the rate of electron transfer between the reduced and oxidized species, and determine the extent of electron delocalization of the unpaired spins over the radical anions. These NMR techniques enable electrolyte decomposition and battery self-discharge to be explored in real time, and show that DHAQ is decomposed electrochemically via a reaction that can be minimized by limiting the voltage used on charging. We foresee applications of these NMR methods in understanding a wide range of redox processes in flow and other electrochemical systems.


  
Coherent electrical control of a single high-spin nucleus in silicon 期刊论文
NATURE, 2020, 579 (7798) : 205-+
作者:  Dedoussi, Irene C.;  Eastham, Sebastian D.;  Monier, Erwan;  Barrett, Steven R. H.
收藏  |  浏览/下载:22/0  |  提交时间:2020/07/03

Nuclear spins are highly coherent quantum objects. In large ensembles, their control and detection via magnetic resonance is widely exploited, for example, in chemistry, medicine, materials science and mining. Nuclear spins also featured in early proposals for solid-state quantum computers(1) and demonstrations of quantum search(2) and factoring(3) algorithms. Scaling up such concepts requires controlling individual nuclei, which can be detected when coupled to an electron(4-6). However, the need to address the nuclei via oscillating magnetic fields complicates their integration in multi-spin nanoscale devices, because the field cannot be localized or screened. Control via electric fields would resolve this problem, but previous methods(7-9) relied on transducing electric signals into magnetic fields via the electron-nuclear hyperfine interaction, which severely affects nuclear coherence. Here we demonstrate the coherent quantum control of a single Sb-123 (spin-7/2) nucleus using localized electric fields produced within a silicon nanoelectronic device. The method exploits an idea proposed in 1961(10) but not previously realized experimentally with a single nucleus. Our results are quantitatively supported by a microscopic theoretical model that reveals how the purely electrical modulation of the nuclear electric quadrupole interaction results in coherent nuclear spin transitions that are uniquely addressable owing to lattice strain. The spin dephasing time, 0.1 seconds, is orders of magnitude longer than those obtained by methods that require a coupled electron spin to achieve electrical driving. These results show that high-spin quadrupolar nuclei could be deployed as chaotic models, strain sensors and hybrid spin-mechanical quantum systems using all-electrical controls. Integrating electrically controllable nuclei with quantum dots(11,12) could pave the way to scalable, nuclear- and electron-spin-based quantum computers in silicon that operate without the need for oscillating magnetic fields.


  
Actinide 2-metallabiphenylenes that satisfy Huckel's rule 期刊论文
NATURE, 2020, 578 (7796) : 563-+
作者:  Achar, Yathish Jagadheesh;  Adhil, Mohamood;  Choudhary, Ramveer;  Gilbert, Nick;  Foiani, Marco
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

Aromaticity and antiaromaticity, as defined by Huckel'  s rule, are key ideas in organic chemistry, and are both exemplified in biphenylene(1-3)-a molecule that consists of two benzene rings joined by a four-membered ring at its core. Biphenylene analogues in which one of the benzene rings has been replaced by a different (4n + 2) pi-electron system have so far been associated only with organic compounds(4,5). In addition, efforts to prepare a zirconabiphenylene compound resulted in the isolation of a bis(alkyne) zirconocene complex instead(6). Here we report the synthesis and characterization of, to our knowledge, the first 2-metallabiphenylene compounds. Single-crystal X-ray diffraction studies reveal that these complexes have nearly planar, 11-membered metallatricycles with metrical parameters that compare well with those reported for biphenylene. Nuclear magnetic resonance spectroscopy, in addition to nucleus-independent chemical shift calculations, provides evidence that these complexes contain an antiaromatic cyclobutadiene ring and an aromatic benzene ring. Furthermore, spectroscopic evidence, Kohn-Sham molecular orbital compositions and natural bond orbital calculations suggest covalency and delocalization of the uranium f(2) electrons with the carbon-containing ligand.


The synthesis of uranium- and thorium-containing metallabiphenylenes demonstrates the ability of the actinides to stabilize aromatic/antiaromatic structures where transition metals have failed.


  
The origin of soil organic matter controls its composition and bioreactivity across a mesic boreal forest latitudinal gradient 期刊论文
GLOBAL CHANGE BIOLOGY, 2018, 24 (2) : E458-E473
作者:  Kohl, Lukas;  Philben, Michael;  Edwards, Kate A.;  Podrebarac, Frances A.;  Warren, Jamie;  Ziegler, Susan E.
收藏  |  浏览/下载:9/0  |  提交时间:2019/04/09
bioreactivity  Boreal forest  climate change  moss  nuclear magnetic resonance  Soil organic matter  total hydrolysable amino acids  vegetation  
Final Report: DoE SBIR Phase 2 Low-Cost Small Diameter NMR Technologies for In-Situ Subsurface Characterization and Monitoring 科技报告
来源:US Department of Energy (DOE). 出版年: 2010
作者:  Walsh, David Oliver [Vista Clara Inc., Mukilteo, WA (United States)]
收藏  |  浏览/下载:15/0  |  提交时间:2019/04/05
nuclear magnetic resonance  borehole nmr  direct push  nmr logging  geophysical logging  groundwater  subsurface characterization  microhole nmr  slimhole nmr