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  • 1
    Publication Date: 2015-09-10
    Description: Somaclonal variation arises in plants and animals when differentiated somatic cells are induced into a pluripotent state, but the resulting clones differ from each other and from their parents. In agriculture, somaclonal variation has hindered the micropropagation of elite hybrids and genetically modified crops, but the mechanism responsible remains unknown. The oil palm fruit 'mantled' abnormality is a somaclonal variant arising from tissue culture that drastically reduces yield, and has largely halted efforts to clone elite hybrids for oil production. Widely regarded as an epigenetic phenomenon, 'mantling' has defied explanation, but here we identify the MANTLED locus using epigenome-wide association studies of the African oil palm Elaeis guineensis. DNA hypomethylation of a LINE retrotransposon related to rice Karma, in the intron of the homeotic gene DEFICIENS, is common to all mantled clones and is associated with alternative splicing and premature termination. Dense methylation near the Karma splice site (termed the Good Karma epiallele) predicts normal fruit set, whereas hypomethylation (the Bad Karma epiallele) predicts homeotic transformation, parthenocarpy and marked loss of yield. Loss of Karma methylation and of small RNA in tissue culture contributes to the origin of mantled, while restoration in spontaneous revertants accounts for non-Mendelian inheritance. The ability to predict and cull mantling at the plantlet stage will facilitate the introduction of higher performing clones and optimize environmentally sensitive land resources.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ong-Abdullah, Meilina -- Ordway, Jared M -- Jiang, Nan -- Ooi, Siew-Eng -- Kok, Sau-Yee -- Sarpan, Norashikin -- Azimi, Nuraziyan -- Hashim, Ahmad Tarmizi -- Ishak, Zamzuri -- Rosli, Samsul Kamal -- Malike, Fadila Ahmad -- Bakar, Nor Azwani Abu -- Marjuni, Marhalil -- Abdullah, Norziha -- Yaakub, Zulkifli -- Amiruddin, Mohd Din -- Nookiah, Rajanaidu -- Singh, Rajinder -- Low, Eng-Ti Leslie -- Chan, Kuang-Lim -- Azizi, Norazah -- Smith, Steven W -- Bacher, Blaire -- Budiman, Muhammad A -- Van Brunt, Andrew -- Wischmeyer, Corey -- Beil, Melissa -- Hogan, Michael -- Lakey, Nathan -- Lim, Chin-Ching -- Arulandoo, Xaviar -- Wong, Choo-Kien -- Choo, Chin-Nee -- Wong, Wei-Chee -- Kwan, Yen-Yen -- Alwee, Sharifah Shahrul Rabiah Syed -- Sambanthamurthi, Ravigadevi -- Martienssen, Robert A -- R01 GM067014/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Sep 24;525(7570):533-7. doi: 10.1038/nature15365. Epub 2015 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia. ; Orion Genomics, 4041 Forest Park Avenue, St Louis, Missouri 63108, USA. ; United Plantations Berhad, Jendarata Estate, 36009 Teluk Intan, Perak, Malaysia. ; Applied Agricultural Resources Sdn Bhd, No. 11, Jalan Teknologi 3/6, Taman Sains Selangor 1, 47810 Kota Damansara, Petaling Jaya, Selangor, Malaysia. ; FELDA Global Ventures R&D Sdn Bhd, c/o FELDA Biotechnology Centre, PT 23417, Lengkuk Teknologi, 71760 Bandar Enstek, Negeri Sembilan, Malaysia. ; Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26352475" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Alternative Splicing/genetics ; Arecaceae/*genetics/metabolism ; *DNA Methylation ; Epigenesis, Genetic/*genetics ; *Epigenomics ; Fruit/genetics ; Genes, Homeobox/genetics ; Genetic Association Studies ; Genome, Plant/*genetics ; Introns/genetics ; Molecular Sequence Data ; *Phenotype ; Plant Oils/analysis/metabolism ; RNA Splice Sites/genetics ; RNA, Small Interfering/genetics ; Retroelements/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2012-06-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jian -- Jiang, Nan -- England -- Nature. 2012 Jun 20;486(7403):323. doi: 10.1038/486323e.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722181" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; HIV Infections/*epidemiology/*prevention & control ; Health Education/*statistics & numerical data ; Homosexuality, Male/*statistics & numerical data ; Humans ; Male ; *Safe Sex
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2018-11-16
    Description: Purpose: The MEK inhibitor trametinib radiosensitizes KRAS-mutant non–small cell lung cancer (NSCLC) and is being tested clinically with chemoradiation. However, variability in response to trametinib suggests that additional pathways are involved. The mechanism of resistance to trametinib radiosensitization is still unknown. Experimental Design: We used a panel of KRAS -mutant NSCLC cells and tested the radiosensitization effects of trametinib by clonogenic survival assay. Then, we investigated the mechanisms underlying the resistance to the combination therapy through several knockout and overexpression systems. Finally, we validated our findings in syngeneic mouse models in a treatment setting that mimicked the standard of care in the clinic. Results: Radiosensitization by trametinib was effective only in KRAS-LKB1 –mutated cells with wild-type (WT) p53, and we found that restoring LKB1 expression in those cells blocked that sensitization. Trametinib and radiotherapy both induced senescence in a p53-dependent manner, but in WT LKB1 cells, the combination also activated the AMPK-autophagy pathway to rescue damaged cells from senescence. LKB1 -knockout or autophagy inhibition in WT LKB1 cells potentiated trametinib radiosensitization. In syngeneic animal models of Kras -mutant lung tumors, Lkb1 -knockout tumors were resistant to trametinib and chemoradiation given separately, but the combination greatly controlled tumor growth and prolonged survival. Conclusions: The LKB1 mutation in KRAS -mutant NSCLC conferred enhanced radiosensitization in combination with trametinib. The WT LKB1 could activate autophagy through AMPK pathway to induce resistance to the combination of trametinib and radiation. The KRAS-LKB1 mutation could potentially be a biomarker to select patients for trametinib and radiotherapy combination therapy. Clin Cancer Res; 24(22); 5744–56. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 4
    Publication Date: 2018-10-13
    Description: Hydrogen-rich hydrides attract great attention due to recent theoretical ( 1 ) and then experimental discovery of record high-temperature superconductivity in H 3 S [ T c = 203 K at 155 GPa ( 2 )]. Here we search for stable uranium hydrides at pressures up to 500 GPa using ab initio evolutionary crystal structure prediction. Chemistry of the U-H system turned out to be extremely rich, with 14 new compounds, including hydrogen-rich UH 5 , UH 6 , U 2 H 13 , UH 7 , UH 8 , U 2 H 17 , and UH 9 . Their crystal structures are based on either common face-centered cubic or hexagonal close-packed uranium sublattice and unusual H 8 cubic clusters. Our high-pressure experiments at 1 to 103 GPa confirm the predicted UH 7 , UH 8 , and three different phases of UH 5 , raising confidence about predictions of the other phases. Many of the newly predicted phases are expected to be high-temperature superconductors. The highest- T c superconductor is UH 7 , predicted to be thermodynamically stable at pressures above 22 GPa (with T c = 44 to 54 K), and this phase remains dynamically stable upon decompression to zero pressure (where it has T c = 57 to 66 K).
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 5
    Publication Date: 2018-11-03
    Description: Bufalin is a major cardiotonic compound in the traditional Chinese medicine, Chansu, prepared from toad skin secretions. Cell culture studies have suggested an anticancer potential involving multiple cellular processes, including differentiation, apoptosis, senescence, and angiogenesis. In prostate cancer cell models, P53-dependent and independent caspase-mediated apoptosis and androgen receptor (AR) antagonism have been described for bufalin at micromolar concentrations. Because a human pharmacokinetic study indicated that single nanomolar bufalin was safely achievable in the peripheral circulation, we evaluated its cellular activity within range with the AR-positive and P53 wild-type human LNCaP prostate cancer cells in vitro . Our data show that bufalin induced caspase-mediated apoptosis at 20 nmol/L or higher concentration with concomitant suppression of AR protein and its best-known target, PSA and steroid receptor coactivator 1 and 3 (SRC-1, SRC-3). Bufalin exposure induced protein abundance of P53 (not mRNA) and P21CIP1 ( CDKN1A ), G 2 arrest, and increased senescence-like phenotype (SA-galactosidase). Small RNAi knocking down of P53 attenuated bufalin-induced senescence, whereas knocking down of P21CIP1 exacerbated bufalin-induced caspase-mediated apoptosis. In vivo , daily intraperitoneal injection of bufalin (1.5 mg/kg body weight) for 9 weeks delayed LNCaP subcutaneous xenograft tumor growth in NSG SCID mice with a 67% decrease of final weight without affecting body weight. Tumors from bufalin-treated mice exhibited increased phospho-P53 and SA-galactosidase without detectable caspase-mediated apoptosis or suppression of AR and PSA. Our data suggest potential applications of bufalin in therapy of prostate cancer in patients or chemo-interception of prostate precancerous lesions, engaging a selective activation of P53 senescence. Mol Cancer Ther; 17(11); 2341–52. ©2018 AACR .
    Print ISSN: 1535-7163
    Electronic ISSN: 1538-8514
    Topics: Medicine
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  • 6
    Publication Date: 2015-07-25
    Description: Superelastic conducting fibers with improved properties and functionalities are needed for diverse applications. Here we report the fabrication of highly stretchable (up to 1320%) sheath-core conducting fibers created by wrapping carbon nanotube sheets oriented in the fiber direction on stretched rubber fiber cores. The resulting structure exhibited distinct short- and long-period sheath buckling that occurred reversibly out of phase in the axial and belt directions, enabling a resistance change of less than 5% for a 1000% stretch. By including other rubber and carbon nanotube sheath layers, we demonstrated strain sensors generating an 860% capacitance change and electrically powered torsional muscles operating reversibly by a coupled tension-to-torsion actuation mechanism. Using theory, we quantitatively explain the complementary effects of an increase in muscle length and a large positive Poisson's ratio on torsional actuation and electronic properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Z F -- Fang, S -- Moura, F A -- Ding, J N -- Jiang, N -- Di, J -- Zhang, M -- Lepro, X -- Galvao, D S -- Haines, C S -- Yuan, N Y -- Yin, S G -- Lee, D W -- Wang, R -- Wang, H Y -- Lv, W -- Dong, C -- Zhang, R C -- Chen, M J -- Yin, Q -- Chong, Y T -- Zhang, R -- Wang, X -- Lima, M D -- Ovalle-Robles, R -- Qian, D -- Lu, H -- Baughman, R H -- New York, N.Y. -- Science. 2015 Jul 24;349(6246):400-4. doi: 10.1126/science.aaa7952.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Alan G. MacDiarmid NanoTech Institute, University of Texas at Dallas, Richardson, TX 75080, USA. Jiangsu Collaborative Innovation Center of Photovoltaic Science and Engineering, Changzhou University, Changzhou 213164, China. Jiangnan Graphene Research Institute, Changzhou 213149, China. ; Alan G. MacDiarmid NanoTech Institute, University of Texas at Dallas, Richardson, TX 75080, USA. Jiangnan Graphene Research Institute, Changzhou 213149, China. ; Alan G. MacDiarmid NanoTech Institute, University of Texas at Dallas, Richardson, TX 75080, USA. Applied Physics Department, State University of Campinas, Campinas, SP 13081-970, Brazil. ; Jiangsu Collaborative Innovation Center of Photovoltaic Science and Engineering, Changzhou University, Changzhou 213164, China. Micro/Nano Science and Technology Center, Jiangsu University, Zhenjiang 212013, China. ; Alan G. MacDiarmid NanoTech Institute, University of Texas at Dallas, Richardson, TX 75080, USA. ; High-Performance Materials Institute, Florida State University, Tallahassee, FL 32310, USA. ; Applied Physics Department, State University of Campinas, Campinas, SP 13081-970, Brazil. ; Jiangsu Collaborative Innovation Center of Photovoltaic Science and Engineering, Changzhou University, Changzhou 213164, China. Jiangnan Graphene Research Institute, Changzhou 213149, China. ; Jiangnan Graphene Research Institute, Changzhou 213149, China. Institute of Materials Physics, Tianjin University of Technology, Tianjin 300384, China. ; Jiangnan Graphene Research Institute, Changzhou 213149, China. ; School of Astronautics, Northwestern Polytechnical University, Xi'an 710072, China. Department of Mechanical Engineering, University of Texas at Dallas, Richardson, TX 75080, USA. ; Department of Mechanical Engineering, University of Texas at Dallas, Richardson, TX 75080, USA. ; Lintec of America, Nano-Science and Technology Center, Richardson, TX 75081, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26206929" target="_blank"〉PubMed〈/a〉
    Keywords: *Elastic Tissue ; Elasticity ; Electric Capacitance ; *Electronics ; *Muscle, Skeletal ; *Nanotubes, Carbon ; Torsion, Mechanical
    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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  • 7
    Publication Date: 2018-02-01
    Description: Hierarchical VOOH hollow spheres with low crystallinity composed of nanoparticles were prepared by a facile and template-free method, which involved a precipitation of precursor microspheres in aqueous solution at room temperature and subsequent hydrothermal reaction. Quasi-solid-state symmetric and asymmetric supercapacitor (SSC and ASC) devices were fabricated using hierarchical VOOH hollow spheres as the electrodes, and the electrochemical properties of the VOOH//VOOH SSC device and the VOOH//AC ASC device were studied by cyclic voltammetry (CV), galvanostatic charge–discharge (GCD) and electrochemical impedance spectroscopy (EIS). Results demonstrated that the electrochemical performance of the VOOH//AC ASC device was better than that of the VOOH//VOOH SSC device. After 3000 cycles, the specific capacitance of the VOOH//AC ASC device retains 83% of the initial capacitance, while the VOOH//VOOH SSC device retains only 7.7%. Findings in this work proved that hierarchical VOOH hollow spheres could be a promising candidate as an ideal electrode material for supercapacitor devices.
    Keywords: materials science
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 8
    Publication Date: 2018-04-21
    Description: A quantum interface links the stationary qubits in a quantum memory with flying photonic qubits in optical transmission channels and constitutes a critical element for the future quantum internet. Entanglement of quantum interfaces is an important step for the realization of quantum networks. Through heralded detection of photon interference, we generate multipartite entanglement between 25 (or 9) individually addressable quantum interfaces in a multiplexed atomic quantum memory array and confirm genuine 22-partite (or 9-partite) entanglement. This experimental entanglement of a record-high number of individually addressable quantum interfaces makes an important step toward the realization of quantum networks, long-distance quantum communication, and multipartite quantum information processing.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 9
    Publication Date: 2018-06-01
    Description: Thiopurines (eg, 6-mercaptopurine [MP]) are highly efficacious antileukemic agents, but they are also associated with dose-limiting toxicities. Recent studies by us and others have identified inherited NUDT15 deficiency as a novel genetic cause of thiopurine toxicity, and there is a strong rationale for NUDT15- guided dose individualization to preemptively mitigate adverse effects of these drugs. Using CRISPR-Cas9 genome editing, we established a Nudt15 –/– mouse model to evaluate the effectiveness of this strategy in vivo. Across MP dosages, Nudt15 –/– mice experienced severe leukopenia, rapid weight loss, earlier death resulting from toxicity, and more bone marrow hypocellularity compared with wild-type mice. Nudt15 –/– mice also showed excessive accumulation of a thiopurine active metabolite (ie, DNA-incorporated thioguanine nucleotides [DNA-TG]) in an MP dose–dependent fashion, as a plausible cause of increased toxicity. MP dose reduction effectively normalized systemic exposure to DNA-TG in Nudt15 –/– mice and largely eliminated Nudt15 deficiency–mediated toxicity. In 95 children with acute lymphoblastic leukemia, MP dose adjustment also directly led to alteration in DNA-TG levels, the effects of which were proportional to the degree of NUDT15 deficiency. Using leukemia-bearing mice with concordant Nudt15 genotype in leukemia and host, we also confirmed that therapeutic efficacy was preserved in Nudt15 –/– mice receiving a reduced MP dose compared with Nudt15 +/+ counterparts exposed to a standard dose. In conclusion, we demonstrated that NUDT15 genotype–guided MP dose individualization can preemptively mitigate toxicity without compromising therapeutic efficacy.
    Keywords: Lymphoid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 10
    Publication Date: 2018-07-24
    Description: Invasion of erythrocytes by merozoites is required in the life cycle of malarial parasites. Proteins derived from the invasive merozoites are essential ligands for erythrocyte recognition and penetration. In this study, we report a novel protein that possesses a Trx domain-like structure of the thioredoxin family and is expressed on the surface of merozoites of the malaria parasite Plasmodium falciparum . This protein, namely, PfTrx-mero protein, displayed a mutated sequence character at the Trx domain, but with a specific binding activity to human erythrocytes. Specific antibodies to the protein inhibited merozoite invasion into human erythrocytes. Immunization with a homologous protein of Plasmodium berghei strain ANKA also showed significant protection against lethal infection in mice. These results suggested that the novel PfTrx-like-mero protein expressed on the surface of merozoites is an important ligand participating in erythrocyte invasion and a potential vaccine candidate.
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
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