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  • 1
    Publication Date: 2013-10-15
    Description: The biogenic amine transporters (BATs) regulate endogenous neurotransmitter concentrations and are targets for a broad range of therapeutic agents including selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs). Because eukaryotic BATs are recalcitrant to crystallographic analysis, our understanding of the mechanism of these inhibitors and antidepressants is limited. LeuT is a bacterial homologue of BATs and has proven to be a valuable paradigm for understanding relationships between their structure and function. However, because only approximately 25% of the amino acid sequence of LeuT is in common with that of BATs, and as LeuT is a promiscuous amino acid transporter, it does not recapitulate the pharmacological properties of BATs. Indeed, SSRIs and TCAs bind in the extracellular vestibule of LeuT and act as non-competitive inhibitors of transport. By contrast, multiple studies demonstrate that both TCAs and SSRIs are competitive inhibitors for eukaryotic BATs and bind to the primary binding pocket. Here we engineered LeuT to harbour human BAT-like pharmacology by mutating key residues around the primary binding pocket. The final LeuBAT mutant binds the SSRI sertraline with a binding constant of 18 nM and displays high-affinity binding to a range of SSRIs, SNRIs and a TCA. We determined 12 crystal structures of LeuBAT in complex with four classes of antidepressants. The chemically diverse inhibitors have a remarkably similar mode of binding in which they straddle transmembrane helix (TM) 3, wedge between TM3/TM8 and TM1/TM6, and lock the transporter in a sodium- and chloride-bound outward-facing open conformation. Together, these studies define common and simple principles for the action of SSRIs, SNRIs and TCAs on BATs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904662/" 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/PMC3904662/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Hui -- Goehring, April -- Wang, Kevin H -- Penmatsa, Aravind -- Ressler, Ryan -- Gouaux, Eric -- R37 MH070039/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Nov 7;503(7474):141-5. doi: 10.1038/nature12648. Epub 2013 Oct 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24121440" target="_blank"〉PubMed〈/a〉
    Keywords: Antidepressive Agents, Second-Generation/metabolism/*pharmacology ; Antidepressive Agents, Tricyclic/metabolism/*pharmacology ; Bacterial Proteins/antagonists & inhibitors/chemistry/genetics/metabolism ; Binding, Competitive/drug effects ; Biogenic Amines/*metabolism ; Chlorides/metabolism ; Crystallography, X-Ray ; Humans ; Mazindol/metabolism/pharmacology ; Models, Molecular ; Mutation ; Norepinephrine/metabolism ; *Plasma Membrane Neurotransmitter Transport Proteins/antagonists & ; inhibitors/chemistry/genetics/metabolism ; Protein Conformation/drug effects ; Recombinant Fusion Proteins/*chemistry/genetics/metabolism ; Reproducibility of Results ; Serotonin Plasma Membrane Transport Proteins/*chemistry/genetics/*metabolism ; Serotonin Uptake Inhibitors/metabolism/*pharmacology ; Sertraline/metabolism/pharmacology ; Sodium/metabolism ; Structure-Activity Relationship
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  • 2
    Publication Date: 2009-12-17
    Description: Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951497/" 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/PMC3951497/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Ruiqiang -- Fan, Wei -- Tian, Geng -- Zhu, Hongmei -- He, Lin -- Cai, Jing -- Huang, Quanfei -- Cai, Qingle -- Li, Bo -- Bai, Yinqi -- Zhang, Zhihe -- Zhang, Yaping -- Wang, Wen -- Li, Jun -- Wei, Fuwen -- Li, Heng -- Jian, Min -- Li, Jianwen -- Zhang, Zhaolei -- Nielsen, Rasmus -- Li, Dawei -- Gu, Wanjun -- Yang, Zhentao -- Xuan, Zhaoling -- Ryder, Oliver A -- Leung, Frederick Chi-Ching -- Zhou, Yan -- Cao, Jianjun -- Sun, Xiao -- Fu, Yonggui -- Fang, Xiaodong -- Guo, Xiaosen -- Wang, Bo -- Hou, Rong -- Shen, Fujun -- Mu, Bo -- Ni, Peixiang -- Lin, Runmao -- Qian, Wubin -- Wang, Guodong -- Yu, Chang -- Nie, Wenhui -- Wang, Jinhuan -- Wu, Zhigang -- Liang, Huiqing -- Min, Jiumeng -- Wu, Qi -- Cheng, Shifeng -- Ruan, Jue -- Wang, Mingwei -- Shi, Zhongbin -- Wen, Ming -- Liu, Binghang -- Ren, Xiaoli -- Zheng, Huisong -- Dong, Dong -- Cook, Kathleen -- Shan, Gao -- Zhang, Hao -- Kosiol, Carolin -- Xie, Xueying -- Lu, Zuhong -- Zheng, Hancheng -- Li, Yingrui -- Steiner, Cynthia C -- Lam, Tommy Tsan-Yuk -- Lin, Siyuan -- Zhang, Qinghui -- Li, Guoqing -- Tian, Jing -- Gong, Timing -- Liu, Hongde -- Zhang, Dejin -- Fang, Lin -- Ye, Chen -- Zhang, Juanbin -- Hu, Wenbo -- Xu, Anlong -- Ren, Yuanyuan -- Zhang, Guojie -- Bruford, Michael W -- Li, Qibin -- Ma, Lijia -- Guo, Yiran -- An, Na -- Hu, Yujie -- Zheng, Yang -- Shi, Yongyong -- Li, Zhiqiang -- Liu, Qing -- Chen, Yanling -- Zhao, Jing -- Qu, Ning -- Zhao, Shancen -- Tian, Feng -- Wang, Xiaoling -- Wang, Haiyin -- Xu, Lizhi -- Liu, Xiao -- Vinar, Tomas -- Wang, Yajun -- Lam, Tak-Wah -- Yiu, Siu-Ming -- Liu, Shiping -- Zhang, Hemin -- Li, Desheng -- Huang, Yan -- Wang, Xia -- Yang, Guohua -- Jiang, Zhi -- Wang, Junyi -- Qin, Nan -- Li, Li -- Li, Jingxiang -- Bolund, Lars -- Kristiansen, Karsten -- Wong, Gane Ka-Shu -- Olson, Maynard -- Zhang, Xiuqing -- Li, Songgang -- Yang, Huanming -- Wang, Jian -- Wang, Jun -- R01 HG003229/HG/NHGRI NIH HHS/ -- R01 HG003229-05/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Jan 21;463(7279):311-7. doi: 10.1038/nature08696. Epub 2009 Dec 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BGI-Shenzhen, Shenzhen 518083, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010809" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; China ; Conserved Sequence/genetics ; Contig Mapping ; Diet/veterinary ; Dogs ; Evolution, Molecular ; Female ; Fertility/genetics/physiology ; Genome/*genetics ; *Genomics ; Heterozygote ; Humans ; Multigene Family/genetics ; Polymorphism, Single Nucleotide/genetics ; Receptors, G-Protein-Coupled/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Synteny/genetics ; Ursidae/classification/*genetics/physiology
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  • 3
    Publication Date: 2010-03-20
    Description: Quantum mechanics provides a highly accurate description of a wide variety of physical systems. However, a demonstration that quantum mechanics applies equally to macroscopic mechanical systems has been a long-standing challenge, hindered by the difficulty of cooling a mechanical mode to its quantum ground state. The temperatures required are typically far below those attainable with standard cryogenic methods, so significant effort has been devoted to developing alternative cooling techniques. Once in the ground state, quantum-limited measurements must then be demonstrated. Here, using conventional cryogenic refrigeration, we show that we can cool a mechanical mode to its quantum ground state by using a microwave-frequency mechanical oscillator-a 'quantum drum'-coupled to a quantum bit, which is used to measure the quantum state of the resonator. We further show that we can controllably create single quantum excitations (phonons) in the resonator, thus taking the first steps to complete quantum control of a mechanical system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connell, A D -- Hofheinz, M -- Ansmann, M -- Bialczak, Radoslaw C -- Lenander, M -- Lucero, Erik -- Neeley, M -- Sank, D -- Wang, H -- Weides, M -- Wenner, J -- Martinis, John M -- Cleland, A N -- England -- Nature. 2010 Apr 1;464(7289):697-703. doi: 10.1038/nature08967. Epub 2010 Mar 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of California, Santa Barbara, California 93106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237473" target="_blank"〉PubMed〈/a〉
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  • 4
    Publication Date: 2008-03-21
    Description: Equal amounts of matter and antimatter are predicted to have been produced in the Big Bang, but our observable Universe is clearly matter-dominated. One of the prerequisites for understanding this elimination of antimatter is the nonconservation of charge-parity (CP) symmetry. So far, two types of CP violation have been observed in the neutral K meson (K(0)) and B meson (B(0)) systems: CP violation involving the mixing between K(0) and its antiparticle (and likewise for B(0) and ), and direct CP violation in the decay of each meson. The observed effects for both types of CP violation are substantially larger for the B(0) meson system. However, they are still consistent with the standard model of particle physics, which has a unique source of CP violation that is known to be too small to account for the matter-dominated Universe. Here we report that the direct CP violation in charged B(+/-)--〉K(+/-)pi(0) decay is different from that in the neutral B(0) counterpart. The direct CP-violating decay rate asymmetry, (that is, the difference between the number of observed B(-)--〉K(-)pi(0) event versus B(+)--〉K(+) pi(0) events, normalized to the sum of these events) is measured to be about +7%, with an uncertainty that is reduced by a factor of 1.7 from a previous measurement. However, the asymmetry for versus B(0)--〉K(+)pi(-) is at the -10% level. Although it is susceptible to strong interaction effects that need further clarification, this large deviation in direct CP violation between charged and neutral B meson decays could be an indication of new sources of CP violation-which would help to explain the dominance of matter in the Universe.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Belle Collaboration -- Lin, S-W -- Unno, Y -- Hou, W-S -- Chang, P -- Adachi, I -- Aihara, H -- Akai, K -- Arinstein, K -- Aulchenko, V -- Aushev, T -- Aziz, T -- Bakich, A M -- Balagura, V -- Barberio, E -- Bay, A -- Bedny, I -- Bitenc, U -- Bondar, A -- Bozek, A -- Bracko, M -- Browder, T E -- Chang, M-C -- Chao, Y -- Chen, A -- Chen, K-F -- Chen, W T -- Cheon, B G -- Chiang, C-C -- Chistov, R -- Cho, I-S -- Choi, S-K -- Choi, Y -- Choi, Y K -- Cole, S -- Dalseno, J -- Danilov, M -- Dash, M -- Drutskoy, A -- Eidelman, S -- Epifanov, D -- Fratina, S -- Fujikawa, M -- Furukawa, K -- Gabyshev, N -- Goldenzweig, P -- Golob, B -- Ha, H -- Haba, J -- Hara, T -- Hayasaka, K -- Hayashii, H -- Hazumi, M -- Heffernan, D -- Hokuue, T -- Hoshi, Y -- Hsiung, Y B -- Hyun, H J -- Iijima, T -- Ikado, K -- Inami, K -- Ishikawa, A -- Ishino, H -- Itoh, R -- Iwabuchi, M -- Iwasaki, M -- Iwasaki, Y -- Kah, D H -- Kaji, H -- Kataoka, S U -- Kawai, H -- Kawasaki, T -- Kibayashi, A -- Kichimi, H -- Kikutani, E -- Kim, H J -- Kim, S K -- Kim, Y J -- Kinoshita, K -- Korpar, S -- Kozakai, Y -- Krizan, P -- Krokovny, P -- Kumar, R -- Kuo, C C -- Kuzmin, A -- Kwon, Y-J -- Lee, M J -- Lee, S E -- Lesiak, T -- Li, J -- Liu, Y -- Liventsev, D -- Mandl, F -- Marlow, D -- McOnie, S -- Medvedeva, T -- Mimashi, T -- Mitaroff, W -- Miyabayashi, K -- Miyake, H -- Miyazaki, Y -- Mizuk, R -- Mori, T -- Nakamura, T T -- Nakano, E -- Nakao, M -- Nakazawa, H -- Nishida, S -- Nitoh, O -- Noguchi, S -- Nozaki, T -- Ogawa, S -- Ogawa, Y -- Ohshima, T -- Okuno, S -- Olsen, S L -- Ozaki, H -- Pakhlova, G -- Park, C W -- Park, H -- Peak, L S -- Pestotnik, R -- Peters, M -- Piilonen, L E -- Poluektov, A -- Sahoo, H -- Sakai, Y -- Schneider, O -- Schumann, J -- Schwartz, A J -- Seidl, R -- Senyo, K -- Sevior, M E -- Shapkin, M -- Shen, C P -- Shibuya, H -- Shidara, T -- Shinomiya, S -- Shiu, J-G -- Shwartz, B -- Singh, J B -- Sokolov, A -- Somov, A -- Stanic, S -- Staric, M -- Sumisawa, K -- Sumiyoshi, T -- Suzuki, S -- Tajima, O -- Takasaki, F -- Tamura, N -- Tanaka, M -- Tawada, M -- Taylor, G N -- Teramoto, Y -- Tikhomirov, I -- Trabelsi, K -- Uehara, S -- Ueno, K -- Uglov, T -- Uno, S -- Urquijo, P -- Ushiroda, Y -- Usov, Y -- Varner, G -- Varvell, K E -- Vervink, K -- Villa, S -- Wang, C C -- Wang, C H -- Wang, M-Z -- Watanabe, Y -- Wedd, R -- Wicht, J -- Won, E -- Yabsley, B D -- Yamaguchi, A -- Yamashita, Y -- Yamauchi, M -- Yoshida, M -- Yuan, C Z -- Yusa, Y -- Zhang, C C -- Zhang, Z P -- Zhilich, V -- Zhulanov, V -- Zupanc, A -- England -- Nature. 2008 Mar 20;452(7185):332-5. doi: 10.1038/nature06827.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, National Taiwan University, Taipei, 106, Taiwan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18354478" target="_blank"〉PubMed〈/a〉
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  • 5
    Publication Date: 2008-07-18
    Description: Spin systems and harmonic oscillators comprise two archetypes in quantum mechanics. The spin-1/2 system, with two quantum energy levels, is essentially the most nonlinear system found in nature, whereas the harmonic oscillator represents the most linear, with an infinite number of evenly spaced quantum levels. A significant difference between these systems is that a two-level spin can be prepared in an arbitrary quantum state using classical excitations, whereas classical excitations applied to an oscillator generate a coherent state, nearly indistinguishable from a classical state. Quantum behaviour in an oscillator is most obvious in Fock states, which are states with specific numbers of energy quanta, but such states are hard to create. Here we demonstrate the controlled generation of multi-photon Fock states in a solid-state system. We use a superconducting phase qubit, which is a close approximation to a two-level spin system, coupled to a microwave resonator, which acts as a harmonic oscillator, to prepare and analyse pure Fock states with up to six photons. We contrast the Fock states with coherent states generated using classical pulses applied directly to the resonator.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hofheinz, Max -- Weig, E M -- Ansmann, M -- Bialczak, Radoslaw C -- Lucero, Erik -- Neeley, M -- O'Connell, A D -- Wang, H -- Martinis, John M -- Cleland, A N -- England -- Nature. 2008 Jul 17;454(7202):310-4. doi: 10.1038/nature07136.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of California, Santa Barbara, California 93106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18633412" target="_blank"〉PubMed〈/a〉
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  • 6
    Publication Date: 2009-10-23
    Description: The tumour stroma is believed to contribute to some of the most malignant characteristics of epithelial tumours. However, signalling between stromal and tumour cells is complex and remains poorly understood. Here we show that the genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands accelerated the initiation, progression and malignant transformation of mammary epithelial tumours. This was associated with the massive remodelling of the extracellular matrix (ECM), innate immune cell infiltration and increased angiogenesis. Loss of Pten in stromal fibroblasts led to increased expression, phosphorylation (T72) and recruitment of Ets2 to target promoters known to be involved in these processes. Remarkably, Ets2 inactivation in Pten stroma-deleted tumours ameliorated disruption of the tumour microenvironment and was sufficient to decrease tumour growth and progression. Global gene expression profiling of mammary stromal cells identified a Pten-specific signature that was highly represented in the tumour stroma of patients with breast cancer. These findings identify the Pten-Ets2 axis as a critical stroma-specific signalling pathway that suppresses mammary epithelial tumours.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2767301/" 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/PMC2767301/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trimboli, Anthony J -- Cantemir-Stone, Carmen Z -- Li, Fu -- Wallace, Julie A -- Merchant, Anand -- Creasap, Nicholas -- Thompson, John C -- Caserta, Enrico -- Wang, Hui -- Chong, Jean-Leon -- Naidu, Shan -- Wei, Guo -- Sharma, Sudarshana M -- Stephens, Julie A -- Fernandez, Soledad A -- Gurcan, Metin N -- Weinstein, Michael B -- Barsky, Sanford H -- Yee, Lisa -- Rosol, Thomas J -- Stromberg, Paul C -- Robinson, Michael L -- Pepin, Francois -- Hallett, Michael -- Park, Morag -- Ostrowski, Michael C -- Leone, Gustavo -- P01 CA097189/CA/NCI NIH HHS/ -- P01 CA097189-050002/CA/NCI NIH HHS/ -- P01CA097189/CA/NCI NIH HHS/ -- R01 CA053271/CA/NCI NIH HHS/ -- R01 CA085619/CA/NCI NIH HHS/ -- R01 CA085619-05/CA/NCI NIH HHS/ -- R01 CA121275/CA/NCI NIH HHS/ -- R01 CA121275-02/CA/NCI NIH HHS/ -- R01 HD047470/HD/NICHD NIH HHS/ -- R01 HD047470-05/HD/NICHD NIH HHS/ -- R01CA053271/CA/NCI NIH HHS/ -- R01CA85619/CA/NCI NIH HHS/ -- R01HD47470/HD/NICHD NIH HHS/ -- England -- Nature. 2009 Oct 22;461(7267):1084-91. doi: 10.1038/nature08486.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19847259" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic ; Extracellular Matrix/metabolism ; Fibroblasts/*metabolism ; Gene Deletion ; Gene Expression Regulation, Neoplastic ; Humans ; Immunity, Innate ; Mammary Neoplasms, Experimental/metabolism/pathology ; Mice ; Mice, Transgenic ; Neoplasms, Glandular and Epithelial/*metabolism/*pathology ; PTEN Phosphohydrolase/deficiency/genetics/*metabolism ; Proto-Oncogene Protein c-ets-2/deficiency/metabolism ; Stromal Cells/*metabolism
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  • 7
    Publication Date: 2009-09-26
    Description: The measurement process plays an awkward role in quantum mechanics, because measurement forces a system to 'choose' between possible outcomes in a fundamentally unpredictable manner. Therefore, hidden classical processes have been considered as possibly predetermining measurement outcomes while preserving their statistical distributions. However, a quantitative measure that can distinguish classically determined correlations from stronger quantum correlations exists in the form of the Bell inequalities, measurements of which provide strong experimental evidence that quantum mechanics provides a complete description. Here we demonstrate the violation of a Bell inequality in a solid-state system. We use a pair of Josephson phase qubits acting as spin-1/2 particles, and show that the qubits can be entangled and measured so as to violate the Clauser-Horne-Shimony-Holt (CHSH) version of the Bell inequality. We measure a Bell signal of 2.0732 +/- 0.0003, exceeding the maximum amplitude of 2 for a classical system by 244 standard deviations. In the experiment, we deterministically generate the entangled state, and measure both qubits in a single-shot manner, closing the detection loophole. Because the Bell inequality was designed to test for non-classical behaviour without assuming the applicability of quantum mechanics to the system in question, this experiment provides further strong evidence that a macroscopic electrical circuit is really a quantum system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ansmann, Markus -- Wang, H -- Bialczak, Radoslaw C -- Hofheinz, Max -- Lucero, Erik -- Neeley, M -- O'Connell, A D -- Sank, D -- Weides, M -- Wenner, J -- Cleland, A N -- Martinis, John M -- England -- Nature. 2009 Sep 24;461(7263):504-6. doi: 10.1038/nature08363.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of California, Santa Barbara, California 93106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779447" target="_blank"〉PubMed〈/a〉
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  • 8
    Publication Date: 2009-05-05
    Description: Culture is typically viewed as consisting of traits inherited epigenetically, through social learning. However, cultural diversity has species-typical constraints, presumably of genetic origin. A celebrated, if contentious, example is whether a universal grammar constrains syntactic diversity in human languages. Oscine songbirds exhibit song learning and provide biologically tractable models of culture: members of a species show individual variation in song and geographically separated groups have local song dialects. Different species exhibit distinct song cultures, suggestive of genetic constraints. Without such constraints, innovations and copying errors should cause unbounded variation over multiple generations or geographical distance, contrary to observations. Here we report an experiment designed to determine whether wild-type song culture might emerge over multiple generations in an isolated colony founded by isolates, and, if so, how this might happen and what type of social environment is required. Zebra finch isolates, unexposed to singing males during development, produce song with characteristics that differ from the wild-type song found in laboratory or natural colonies. In tutoring lineages starting from isolate founders, we quantified alterations in song across tutoring generations in two social environments: tutor-pupil pairs in sound-isolated chambers and an isolated semi-natural colony. In both settings, juveniles imitated the isolate tutors but changed certain characteristics of the songs. These alterations accumulated over learning generations. Consequently, songs evolved towards the wild-type in three to four generations. Thus, species-typical song culture can appear de novo. Our study has parallels with language change and evolution. In analogy to models in quantitative genetics, we model song culture as a multigenerational phenotype partly encoded genetically in an isolate founding population, influenced by environmental variables and taking multiple generations to emerge.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693086/" 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/PMC2693086/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feher, Olga -- Wang, Haibin -- Saar, Sigal -- Mitra, Partha P -- Tchernichovski, Ofer -- R01 DC004722/DC/NIDCD NIH HHS/ -- R01 DC004722-09/DC/NIDCD NIH HHS/ -- England -- Nature. 2009 May 28;459(7246):564-8. doi: 10.1038/nature07994. Epub 2009 May 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, City College, City University of New York, New York 10031, USA. olcifeher@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19412161" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; *Culture ; Female ; Finches/*physiology ; Instinct ; Learning/physiology ; Male ; *Models, Biological ; Social Isolation ; Vocalization, Animal/*physiology
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  • 9
    Publication Date: 2009-12-18
    Description: In the established model of mammalian cell cycle control, the retinoblastoma protein (Rb) functions to restrict cells from entering S phase by binding and sequestering E2f activators (E2f1, E2f2 and E2f3), which are invariably portrayed as the ultimate effectors of a transcriptional program that commit cells to enter and progress through S phase. Using a panel of tissue-specific cre-transgenic mice and conditional E2f alleles we examined the effects of E2f1, E2f2 and E2f3 triple deficiency in murine embryonic stem cells, embryos and small intestines. We show that in normal dividing progenitor cells E2f1-3 function as transcriptional activators, but contrary to the current view, are dispensable for cell division and instead are necessary for cell survival. In differentiating cells E2f1-3 function in a complex with Rb as repressors to silence E2f targets and facilitate exit from the cell cycle. The inactivation of Rb in differentiating cells resulted in a switch of E2f1-3 from repressors to activators, leading to the superactivation of E2f responsive targets and ectopic cell divisions. Loss of E2f1-3 completely suppressed these phenotypes caused by Rb deficiency. This work contextualizes the activator versus repressor functions of E2f1-3 in vivo, revealing distinct roles in dividing versus differentiating cells and in normal versus cancer-like cell cycles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806193/" 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/PMC2806193/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chong, Jean-Leon -- Wenzel, Pamela L -- Saenz-Robles, M Teresa -- Nair, Vivek -- Ferrey, Antoney -- Hagan, John P -- Gomez, Yorman M -- Sharma, Nidhi -- Chen, Hui-Zi -- Ouseph, Madhu -- Wang, Shu-Huei -- Trikha, Prashant -- Culp, Brian -- Mezache, Louise -- Winton, Douglas J -- Sansom, Owen J -- Chen, Danian -- Bremner, Rod -- Cantalupo, Paul G -- Robinson, Michael L -- Pipas, James M -- Leone, Gustavo -- 5 T32 CA106196-04/CA/NCI NIH HHS/ -- CA098956/CA/NCI NIH HHS/ -- P01CA097189/CA/NCI NIH HHS/ -- R01 CA098956/CA/NCI NIH HHS/ -- R01 CA098956-06A2/CA/NCI NIH HHS/ -- R01CA82259/CA/NCI NIH HHS/ -- R01CA85619/CA/NCI NIH HHS/ -- R01HD04470/HD/NICHD NIH HHS/ -- England -- Nature. 2009 Dec 17;462(7275):930-4. doi: 10.1038/nature08677.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016602" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Apoptosis ; Cell Cycle/genetics/physiology ; *Cell Differentiation ; Cell Proliferation ; E2F Transcription Factors/deficiency/genetics/*metabolism ; E2F1 Transcription Factor/deficiency/genetics/metabolism ; E2F2 Transcription Factor/deficiency/genetics/metabolism ; E2F3 Transcription Factor/deficiency/genetics/metabolism ; Embryo, Mammalian/cytology/metabolism ; Embryonic Stem Cells/*cytology/*metabolism ; Female ; *Gene Expression Regulation ; Intestine, Small/cytology/metabolism ; Mice ; Mice, Transgenic ; Repressor Proteins/deficiency/genetics/*metabolism ; Retinoblastoma Protein/deficiency/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2009-05-30
    Description: The superposition principle is a fundamental tenet of quantum mechanics. It allows a quantum system to be 'in two places at the same time', because the quantum state of a physical system can simultaneously include measurably different physical states. The preparation and use of such superposed states forms the basis of quantum computation and simulation. The creation of complex superpositions in harmonic systems (such as the motional state of trapped ions, microwave resonators or optical cavities) has presented a significant challenge because it cannot be achieved with classical control signals. Here we demonstrate the preparation and measurement of arbitrary quantum states in an electromagnetic resonator, superposing states with different numbers of photons in a completely controlled and deterministic manner. We synthesize the states using a superconducting phase qubit to phase-coherently pump photons into the resonator, making use of an algorithm that generalizes a previously demonstrated method of generating photon number (Fock) states in a resonator. We completely characterize the resonator quantum state using Wigner tomography, which is equivalent to measuring the resonator's full density matrix.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hofheinz, Max -- Wang, H -- Ansmann, M -- Bialczak, Radoslaw C -- Lucero, Erik -- Neeley, M -- O'Connell, A D -- Sank, D -- Wenner, J -- Martinis, John M -- Cleland, A N -- England -- Nature. 2009 May 28;459(7246):546-9. doi: 10.1038/nature08005.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of California, Santa Barbara, California 93106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478780" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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