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  • 1
    Publication Date: 2018-05-04
    Description: In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that the combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning.
    Keywords: Development, Engineering
    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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  • 2
    Publication Date: 2012-04-12
    Description: Observations with the Venus Express magnetometer and low-energy particle detector revealed magnetic field and plasma behavior in the near-Venus wake that is symptomatic of magnetic reconnection, a process that occurs in Earth's magnetotail but is not expected in the magnetotail of a nonmagnetized planet such as Venus. On 15 May 2006, the plasma flow in this region was toward the planet, and the magnetic field component transverse to the flow was reversed. Magnetic reconnection is a plasma process that changes the topology of the magnetic field and results in energy exchange between the magnetic field and the plasma. Thus, the energetics of the Venus magnetotail resembles that of the terrestrial tail, where energy is stored and later released from the magnetic field to the plasma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, T L -- Lu, Q M -- Baumjohann, W -- Russell, C T -- Fedorov, A -- Barabash, S -- Coates, A J -- Du, A M -- Cao, J B -- Nakamura, R -- Teh, W L -- Wang, R S -- Dou, X K -- Wang, S -- Glassmeier, K H -- Auster, H U -- Balikhin, M -- New York, N.Y. -- Science. 2012 May 4;336(6081):567-70. doi: 10.1126/science.1217013. Epub 2012 Apr 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chinese Academy of Sciences Key Laboratory of Geospace Environment, University of Science and Technology of China, Hefei 230026, China. tielong.zhang@oeaw.ac.at〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22491094" target="_blank"〉PubMed〈/a〉
    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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  • 3
    Publication Date: 2011-11-05
    Description: The mTOR complex 1 (mTORC1) protein kinase is a master growth regulator that is stimulated by amino acids. Amino acids activate the Rag guanosine triphosphatases (GTPases), which promote the translocation of mTORC1 to the lysosomal surface, the site of mTORC1 activation. We found that the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1. The v-ATPase engages in extensive amino acid-sensitive interactions with the Ragulator, a scaffolding complex that anchors the Rag GTPases to the lysosome. In a cell-free system, ATP hydrolysis by the v-ATPase was necessary for amino acids to regulate the v-ATPase-Ragulator interaction and promote mTORC1 translocation. Results obtained in vitro and in human cells suggest that amino acid signaling begins within the lysosomal lumen. These results identify the v-ATPase as a component of the mTOR pathway and delineate a lysosome-associated machinery for amino acid sensing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3211112/" 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/PMC3211112/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zoncu, Roberto -- Bar-Peled, Liron -- Efeyan, Alejo -- Wang, Shuyu -- Sancak, Yasemin -- Sabatini, David M -- AI47389/AI/NIAID NIH HHS/ -- CA103866/CA/NCI NIH HHS/ -- R01 CA103866/CA/NCI NIH HHS/ -- R01 CA103866-07/CA/NCI NIH HHS/ -- R01 CA103866-08/CA/NCI NIH HHS/ -- R37 AI047389/AI/NIAID NIH HHS/ -- R37 AI047389-11/AI/NIAID NIH HHS/ -- R37 AI047389-12/AI/NIAID NIH HHS/ -- R37 AI047389-13/AI/NIAID NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Nov 4;334(6056):678-83. doi: 10.1126/science.1207056.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22053050" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/*metabolism ; Animals ; Cell Line ; Drosophila ; GTP Phosphohydrolases/metabolism ; Humans ; Lysosomes/*metabolism ; Multiprotein Complexes ; Proteins/*metabolism ; RNA Interference ; Signal Transduction ; TOR Serine-Threonine Kinases ; Vacuolar Proton-Translocating ATPases/*metabolism
    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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  • 4
    Publication Date: 2011-08-06
    Description: The modern Indian summer monsoon (ISM) is characterized by exceptionally strong interhemispheric transport, indicating the importance of both Northern and Southern Hemisphere processes driving monsoon variability. Here, we present a high-resolution continental record from southwestern China that demonstrates the importance of interhemispheric forcing in driving ISM variability at the glacial-interglacial time scale as well. Interglacial ISM maxima are dominated by an enhanced Indian low associated with global ice volume minima. In contrast, the glacial ISM reaches a minimum, and actually begins to increase, before global ice volume reaches a maximum. We attribute this early strengthening to an increased cross-equatorial pressure gradient derived from Southern Hemisphere high-latitude cooling. This mechanism explains much of the nonorbital scale variance in the Pleistocene ISM record.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉An, Zhisheng -- Clemens, Steven C -- Shen, Ji -- Qiang, Xiaoke -- Jin, Zhangdong -- Sun, Youbin -- Prell, Warren L -- Luo, Jingjia -- Wang, Sumin -- Xu, Hai -- Cai, Yanjun -- Zhou, Weijian -- Liu, Xiaodong -- Liu, Weiguo -- Shi, Zhengguo -- Yan, Libin -- Xiao, Xiayun -- Chang, Hong -- Wu, Feng -- Ai, Li -- Lu, Fengyan -- New York, N.Y. -- Science. 2011 Aug 5;333(6043):719-23. doi: 10.1126/science.1203752.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Loess and Quaternary Geology, Institute of Earth Environment, Chinese Academy of Sciences, Xi'an 710075, China. anzs@loess.llqg.ac.cn〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21817044" target="_blank"〉PubMed〈/a〉
    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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  • 5
    Publication Date: 2013-02-16
    Description: Allostery is well documented for proteins but less recognized for DNA-protein interactions. Here, we report that specific binding of a protein on DNA is substantially stabilized or destabilized by another protein bound nearby. The ternary complex's free energy oscillates as a function of the separation between the two proteins with a periodicity of ~10 base pairs, the helical pitch of B-form DNA, and a decay length of ~15 base pairs. The binding affinity of a protein near a DNA hairpin is similarly dependent on their separation, which-together with molecular dynamics simulations-suggests that deformation of the double-helical structure is the origin of DNA allostery. The physiological relevance of this phenomenon is illustrated by its effect on gene expression in live bacteria and on a transcription factor's affinity near nucleosomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586787/" 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/PMC3586787/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Sangjin -- Brostromer, Erik -- Xing, Dong -- Jin, Jianshi -- Chong, Shasha -- Ge, Hao -- Wang, Siyuan -- Gu, Chan -- Yang, Lijiang -- Gao, Yi Qin -- Su, Xiao-dong -- Sun, Yujie -- Xie, X Sunney -- DP1 OD000277/OD/NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 15;339(6121):816-9. doi: 10.1126/science.1229223.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23413354" target="_blank"〉PubMed〈/a〉
    Keywords: *Allosteric Regulation ; Base Sequence ; Binding Sites ; DNA, B-Form/*chemistry ; DNA-Binding Proteins/*chemistry ; DNA-Directed RNA Polymerases/chemistry ; Escherichia coli/genetics/metabolism ; Gene Expression ; *Gene Expression Regulation, Bacterial ; Lac Repressors/chemistry ; Molecular Dynamics Simulation ; Nucleosomes/chemistry ; Protein Binding ; Protein Structure, Tertiary ; Receptors, Glucocorticoid/chemistry ; Transcription Factors/*chemistry ; Viral Proteins/chemistry
    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
    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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  • 7
    Publication Date: 2018-11-29
    Description: A plethora of bacterial allosteric transcription factors (aTFs) have been identified to sense a variety of small molecules. Introduction of a novel aTF-based approach to sense diverse small molecules in vitro will signify a broad series of detection applications. Here, we found that aTFs could interact with their nicked DNA binding sites. Building from this new finding, we designed and implemented a novel aTF-based nicked DNA template–assisted signal transduction system (aTF-NAST) by using the competition between aTFs and T4 DNA ligase to bind to the nicked DNA. This aTF-NAST could reliably and modularly transduce the signal of small molecules recognized by aTFs to the ligated DNA signal, thus enabling the small molecules to be measured via various mature and robust DNA detection methods. Coupling this aTF-NAST with three DNA detection methods, we demonstrated nine novel biosensors for the detection of an antiseptic 4-hydroxybenzoic acid, a disease marker uric acid and an antibiotic tetracycline. These biosensors show impressive sensitivity and robustness in real-life analysis, highlighting the great potential of our aTF-NAST for biosensing applications.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 8
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-07
    Description: Mutations in two genes, PKD1 and PKD2 , account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo–electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet noncanonical, transient receptor potential (TRP) channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular half, S6a, resembling pore helix 1 in a typical TRP channel. Three positively charged, cavity-facing residues on S6b may block cation permeation. In addition to the VGIC, a five–transmembrane helix domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins.
    Keywords: Biochemistry, Online Only
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2018-09-15
    Description: Air-stable, lightweight, and electrically conductive polymers are highly desired as the electrodes for next-generation electronic devices. However, the low electrical conductivity and low carrier mobility of polymers are the key bottlenecks that limit their adoption. We demonstrate that the key to addressing these limitations is to molecularly engineer the crystallization and morphology of polymers. We use oxidative chemical vapor deposition (oCVD) and hydrobromic acid treatment as an effective tool to achieve such engineering for conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT). We demonstrate PEDOT thin films with a record-high electrical conductivity of 6259 S/cm and a remarkably high carrier mobility of 18.45 cm 2 V –1 s –1 by inducing a crystallite-configuration transition using oCVD. Subsequent theoretical modeling reveals a metallic nature and an effective reduction of the carrier transport energy barrier between crystallized domains in these thin films. To validate this metallic nature, we successfully fabricate PEDOT-Si Schottky diode arrays operating at 13.56 MHz for radio frequency identification (RFID) readers, demonstrating wafer-scale fabrication compatible with conventional complementary metal-oxide semiconductor (CMOS) technology. The oCVD PEDOT thin films with ultrahigh electrical conductivity and high carrier mobility show great promise for novel high-speed organic electronics with low energy consumption and better charge carrier transport.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 10
    Publication Date: 2018-09-21
    Description: Spatiotemporal instabilities are widespread phenomena resulting from complexity and nonlinearity. In broad-area edge-emitting semiconductor lasers, the nonlinear interactions of multiple spatial modes with the active medium can result in filamentation and spatiotemporal chaos. These instabilities degrade the laser performance and are extremely challenging to control. We demonstrate a powerful approach to suppress spatiotemporal instabilities using wave-chaotic or disordered cavities. The interference of many propagating waves with random phases in such cavities disrupts the formation of self-organized structures such as filaments, resulting in stable lasing dynamics. Our method provides a general and robust scheme to prevent the formation and growth of nonlinear instabilities for a large variety of high-power lasers.
    Keywords: Physics, Applied
    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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