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Nature communications 5388건

  1. [해외논문]   Structural absorption by barbule microstructures of super black bird of paradise feathers   SCI SCIE

    McCoy, Dakota E. (Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138 USA ) , Feo, Teresa (Department of Vertebrate Zoology, MRC-116, National Museum of Natural History, Smithsonian Institution, Washington, DC 20013 USA ) , Harvey, Todd Alan (Department of Ecology and Evolutionary Biology, and Peabody Museum of Natural History, Yale University, New Haven, CT 06520 USA ) , Prum, Richard O. (Department of Ecology and Evolutionary Biology, and Peabody Museum of Natural History, Yale University, New Haven, CT 06520 USA)
    Nature communications v.9 no.1 ,pp. 1 , 2018 ,

    초록

    Many studies have shown how pigments and internal nanostructures generate color in nature. External surface structures can also influence appearance, such as by causing multiple scattering of light (structural absorption) to produce a velvety, super black appearance. Here we show that feathers from five species of birds of paradise (Aves: Paradisaeidae) structurally absorb incident light to produce extremely low-reflectance, super black plumages. Directional reflectance of these feathers (0.05–0.31%) approaches that of man-made ultra-absorbent materials. SEM, nano-CT, and ray-tracing simulations show that super black feathers have titled arrays of highly modified barbules, which cause more multiple scattering, resulting in more structural absorption, than normal black feathers. Super black feathers have an extreme directional reflectance bias and appear darkest when viewed from the distal direction. We hypothesize that structurally absorbing, super black plumage evolved through sensory bias to enhance the perceived brilliance of adjacent color patches during courtship display. Physical structure is known to contribute to the appearance of bird plumage through structural color and specular reflection. Here, McCoy, Feo, and colleagues demonstrate how a third mechanism, structural absorption, leads to low reflectance and super black color in birds of paradise feathers.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

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  2. [해외논문]   Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy   SCI SCIE

    Kirtane, Ameya R. (Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA ) , Abouzid, Omar (Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA ) , Minahan, Daniel (Département Biosciences, Institut National des Sciences Appliquées de Lyon, 20 Avenue Albert Einstein, Villeurbanne, France, 69100 ) , Bensel, Taylor (Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA ) , Hill, Alison L. (Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA ) , Selinger, Christian (Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, 02138, USA ) , Bershteyn, Anna (Institute for Disease Modeling, Bellevue, WA, 98005, USA ) , Craig, Morgan (Institute for Disease Modeling, Bellevue, WA, 98) , Mo, Shirley S. , Mazdiyasni, Hormoz , Cleveland, Cody , Rogner, Jaimie , Lee, Young-Ah Lucy , Booth, Lucas , Javid, Farhad , Wu, Sarah J. , Grant, Tyler , Bellinger, Andrew M. , Nikolic, Boris , Hayward, Alison , Wood, Lowell , Eckhoff, Philip A. , Nowak, Martin A. , Langer, Robert , Traverso, Giovanni
    Nature communications v.9 no.1 ,pp. 2 - 2 , 2018 ,

    초록

    The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug–polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

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  3. [해외논문]   Dynamic metal-ligand coordination for multicolour and water-jet rewritable paper   SCI SCIE

    Ma, Yun (Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications (NUPT), Nanjing, 210023, China ) , She, Pengfei (Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications (NUPT), Nanjing, 210023, China ) , Zhang, Kenneth Yin (Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications (NUPT), Nanjing, 210023, China ) , Yang, Huiran (Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials) , Qin, Yanyan , Xu, Zihan , Liu, Shujuan , Zhao, Qiang , Huang, Wei
    Nature communications v.9 no.1 ,pp. 3 - 3 , 2018 ,

    초록

    Rewritable paper has recently become prevalent in both academic research and marketplace due to the potential environmental advantages, including forest conservation, pollution reduction, energy saving and resource sustainability. However, its real-life applications are limited by a lack of effective strategy to realize multicolour and water-jet printing on rewritable paper with long legible image-lasting times. Herein, we report an effective strategy to construct rewritable paper based on colour or luminescence switching induced by dynamic metal–ligand coordination. This type of rewritable paper can be conveniently utilized for multicolour water-jet printing by using aqueous solutions containing different metal salts as ink. In addition, the printed images on the water-jet rewritable paper can be retained for a long time (> 6 months), which shows great progress compared to previous work. We believe that this type of rewritable paper could be considered as a prototype for multicolour water-jet printing to meet the practical needs.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  4. [해외논문]   Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling   SCI SCIE

    Elia, Josephine (Nemours, du Pont Hospital for Children, Wilmington, 19803, DE, USA. Josephine.Elia@nemours.org ) , Ungal, Grace (Department of Pediatrics Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, 19107, PA, USA. Josephine.Elia@nemours.org ) , Kao, Charlly (Department of Psychiatry Sidney Kimmel Medical College of Thomas Jefferson University, 19107, Philadelphia, USA. Josephine.Elia@nemours.org ) , Ambrosini, Alexander (Drexel University College of Medicine, Philadelphia, 19129, PA, USA ) , De Jesus-Rosario, Nilsa (The Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 19104, PA, USA ) , Larsen, Lene (University of Pennsylvania, Philadelphia, 19104, PA, USA ) , Chiavacci, Rosetta (Department of Psychiatry Sidney Kimmel Medical College of Thomas Jefferson University, 19107, Philadelphia, USA ) , Wang, Tiancheng (Department of Psychiatry Sidney Kimmel Medical College of Thomas Jefferson University, 19107, Philadelphia, USA ) , Kurian, Christine (The Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 19104, PA, USA ) , Titchen, Kanani (The Center for Applied Genomics, The Childre) , Sykes, Brian , Hwang, Sharon , Kumar, Bhumi , Potts, Jacqueline , Davis, Joshua , Malatack, Jeffrey , Slattery, Emma , Moorthy, Ganesh , Zuppa, Athena , Weller, Andrew , Byrne, Enda , Li, Yun R. , Kraft, Walter K. , Hakonarson, Hakon
    Nature communications v.9 no.1 ,pp. 4 - 4 , 2018 ,

    초록

    The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12–17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50–800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 at baseline vs. 2.33 at week 5 (P 

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  5. [해외논문]   VAMPnets for deep learning of molecular kinetics   SCI SCIE

    Mardt, Andreas (Department of Mathematics and Computer Science, Freie Universität Berlin, Arnimallee 6, 14195, Berlin, Germany ) , Pasquali, Luca (Department of Mathematics and Computer Science, Freie Universität Berlin, Arnimallee 6, 14195, Berlin, Germany ) , Wu, Hao (Department of Mathematics and Computer Science, Freie Universität Berlin, Arnimallee 6, 14195, Berlin, Germany ) , Noé (Department of Mathematics and Computer Science, Freie Universität Berlin, Arnimallee 6, 14195, Berlin, Germany. frank.noe@fu-berlin.de) , , Frank
    Nature communications v.9 no.1 ,pp. 5 - 5 , 2018 ,

    초록

    There is an increasing demand for computing the relevant structures, equilibria, and long-timescale kinetics of biomolecular processes, such as protein-drug binding, from high-throughput molecular dynamics simulations. Current methods employ transformation of simulated coordinates into structural features, dimension reduction, clustering the dimension-reduced data, and estimation of a Markov state model or related model of the interconversion rates between molecular structures. This handcrafted approach demands a substantial amount of modeling expertise, as poor decisions at any step will lead to large modeling errors. Here we employ the variational approach for Markov processes (VAMP) to develop a deep learning framework for molecular kinetics using neural networks, dubbed VAMPnets. A VAMPnet encodes the entire mapping from molecular coordinates to Markov states, thus combining the whole data processing pipeline in a single end-to-end framework. Our method performs equally or better than state-of-the-art Markov modeling methods and provides easily interpretable few-state kinetic models.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  6. [해외논문]   Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity   SCI SCIE

    Zhang, Yuan (Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA. yuanzhang@uri.edu ) , Li, Na (Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA. yuanzhang@uri.edu ) , Suh, Heikyung (Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA ) , Irvine, Darrell J. (Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA )
    Nature communications v.9 no.1 ,pp. 6 - 6 , 2018 ,

    초록

    Immunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)−2 generate effective anti-tumor immunity but also elicit serious toxicities, hampering their clinical application. Here we show that combination therapy with anti-CD137 and an IL-2-Fc fusion achieves significant initial anti-tumor activity, but also lethal immunotoxicity deriving from stimulation of circulating leukocytes. To overcome this toxicity, we demonstrate that anchoring IL-2 and anti-CD137 on the surface of liposomes allows these immune agonists to rapidly accumulate in tumors while lowering systemic exposure. In multiple tumor models, immunoliposome delivery achieves anti-tumor activity equivalent to free IL-2/anti-CD137 but with the complete absence of systemic toxicity. Immunoliposomes stimulated tumor infiltration by cytotoxic lymphocytes, cytokine production, and granzyme expression, demonstrating equivalent immunostimulatory effects to the free drugs in the local tumor microenvironment. Thus, surface-anchored particle delivery may provide a general approach to exploit the potent stimulatory activity of immune agonists without debilitating systemic toxicities.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  7. [해외논문]   Trapping IgE in a closed conformation by mimicking CD23 binding prevents and disrupts FcεRI interaction   SCI SCIE

    Jabs, Frederic (Immunological Engineering, Department of Engineering, Aarhus University, 8000, Aarhus, Denmark ) , Plum, Melanie (Institute of Organic Chemistry, Department of Chemistry, University of Hamburg, 20146, Hamburg, Germany ) , Laursen, Nick S. (Immunological Engineering, Department of Engineering, Aarhus University, 8000, Aarhus, Denmark ) , Jensen, Rasmus K. (Department of Molecular Biology and Genetics, Aarhus University, 8000, Aarhus, Denmark. nsl@mbg.au.dk ) , Mølgaard, Brian (Department of Molecular Biology and Genetics, Aarhus University, 8000, Aarhus, Denmark ) , Miehe, Michaela (Immunological Engineering, Department of Engineering, Aarhus University, 8000, Aarhus, Denmark ) , Mandolesi, Marco (Immunological Engineering, Department of Engineering, Aarhus University, 8000, Aarhus, Denmark ) , Rauber, Michè (Immunological Engineering, Department of Engineering, Aarhus University, 8000, Aarhus, Denmark ) , le M. (Clinical & Experimental Allergology, Department of Dermatology and Allergology, Philipps University Marburg, 35043, Marburg, Germany ) , Pfü (Department of Dermatology and Allergology University Medical Center Giessen and M) , tzner, Wolfgang , Jakob, Thilo , Mö , bs, Christian , Andersen, Gregers R. , Spillner, Edzard
    Nature communications v.9 no.1 ,pp. 7 - 7 , 2018 ,

    초록

    Anti-IgE therapeutics interfere with the ability of IgE to bind to its receptors on effector cells. Here we report the crystal structure of an anti-IgE single-domain antibody in complex with an IgE Fc fragment, revealing how the antibody inhibits interactions between IgE and the two receptors FcεRI and CD23. The epitope overlaps only slightly with the FcεRI-binding site but significantly with the CD23-binding site. Solution scattering studies of the IgE Fc reveal that antibody binding induces a half-bent conformation in between the well-known bent and extended IgE Fc conformations. The antibody acts as functional homolog of CD23 and induces a closed conformation of IgE Fc incompatible with FcεRI binding. Notably the antibody displaces IgE from both CD23 and FcεRI, and abrogates allergen-mediated basophil activation and facilitated allergen binding. The inhibitory mechanism might facilitate strategies for the future development of anti-IgE therapeutics for treatment of allergic diseases.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  8. [해외논문]   Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci   SCI SCIE

    Bell, Christopher G. (Department of Twin Research & Genetic Epidemiology, King's College London, ) , Gao, Fei (BGI-Shenzhen, ) , Yuan, Wei (Department of Twin Research & Genetic Epidemiology, King's College London, ) , Roos, Leonie (Department of Twin Research & Genetic Epidemiology, King's College London, ) , Acton, Richard J. (MRC Lifecourse Epidemiology Unit, University of Southampton, ) , Xia, Yudong (BGI-Shenzhen, ) , Bell, Jordana (Department of Twin Research & Genetic Epidemiology, King's College London, ) , Ward, Kirsten (Department of Twin Research & Genetic Epidemiology, King's College London, ) , Mangino, Massimo (Department of Twin Research & Genetic Epidemiology, King's College London, ) , Hysi, Pirro G. (Department of Twin Research & Genetic Epidemiology, King's College London, ) , Wang, Jun (MRC Lifecourse Epidemiology Unit, University of Southampton, ) , Spector, Timothy D. (Department of Twin Research & Genetic Epidemiology, King's College London,)
    Nature communications v.9 no.1 ,pp. 8 , 2018 ,

    초록

    Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites (TFBSs) strongly encoding the DNA methylome. Therefore, genetic polymorphism impacts on the observed epigenome. Furthermore, large genetic variants alter epigenetic signal dosage. Here, we identify DNA methylation variability between GWAS-SNP risk and non-risk haplotypes. In three subsets comprising 3128 MeDIP-seq peripheral-blood DNA methylomes, we find 7173 consistent and functionally enriched Differentially Methylated Regions. 36.8% can be attributed to common non-SNP genetic variants. CpG-SNPs, as well as facilitative TFBS-motifs, are also enriched. Highlighting their functional potential, CpG-SNPs strongly associate with allele-specific DNase-I hypersensitivity sites. Our results demonstrate strong DNA methylation allelic differences driven by obligatory or facilitative genetic effects, with potential direct or regional disease-related repercussions. These allelic variations require disentangling from pure tissue-specific modifications, may influence array studies, and imply underestimated population variability in current reference epigenomes. Genomic polymorphisms affect the epigenome, which in turn influences how epigenome- and genome-wide analysis are interpreted. Here, the authors characterise allelic differences in DNA methylation driven by obligatory or facilitative genetic effects, which may affect disease-related loci.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  9. [해외논문]   Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine   SCI SCIE

    Calipari, Erin S. (Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA ) , Godino, Arthur (Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA ) , Peck, Emily G. (Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA ) , Salery, Marine (Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA ) , Mervosh, Nicholas L. (Department of Psychiatry, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA ) , Landry, Joseph A. (Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA ) , Russo, Scott J. (Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA ) , Hurd, Yasmin L. (Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA ) , Nestler, Eric J. (Fishberg Department of Neur) , Kiraly, Drew D.
    Nature communications v.9 no.1 ,pp. 9 , 2018 ,

    초록

    Cocaine addiction is characterized by dysfunction in reward-related brain circuits, leading to maladaptive motivation to seek and take the drug. There are currently no clinically available pharmacotherapies to treat cocaine addiction. Through a broad screen of innate immune mediators, we identify granulocyte-colony stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations. Here we report that G-CSF potentiates cocaine-induced increases in neural activity in the nucleus accumbens (NAc) and prefrontal cortex. In addition, G-CSF injections potentiate cocaine place preference and enhance motivation to self-administer cocaine, while not affecting responses to natural rewards. Infusion of G-CSF neutralizing antibody into NAc blocks the ability of G-CSF to modulate cocaine's behavioral effects, providing a direct link between central G-CSF action in NAc and cocaine reward. These results demonstrate that manipulating G-CSF is sufficient to alter the motivation for cocaine, but not natural rewards, providing a pharmacotherapeutic avenue to manipulate addictive behaviors without abuse potential. Cocaine addiction is accompanied by dysfunction in neural circuits related to reward, but it is unclear how these adaptations occur. Here, authors identify granulocyte-colony stimulating factor as a potent mediator of cocaine-induced adaptations, and show that it can alter the motivation for cocaine.

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  10. [해외논문]   Inhibition of Poly(A)-binding protein with a synthetic RNA mimic reduces pain sensitization in mice   SCI SCIE

    Barragá (School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080 USA ) , n-Iglesias, Paulino (Department of Biological Sciences, University of Texas Dallas, Richardson, TX 75080 USA ) , Lou, Tzu-Fang (Department of Biological Sciences, University of Texas Dallas, Richardson, TX 75080 USA ) , Bhat, Vandita D. (School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080 USA ) , Megat, Salim (School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080 USA ) , Burton, Michael D. (School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080 USA ) , Price, Theodore J. (Department of Biological Sciences, University of Texas Dallas, Richardson, TX 75080 USA) , Campbell, Zachary T.
    Nature communications v.9 no.1 ,pp. 10 , 2018 ,

    초록

    Nociceptors rely on cap-dependent translation to rapidly induce protein synthesis in response to pro-inflammatory signals. Comparatively little is known regarding the role of the regulatory factors bound to the 3′ end of mRNA in nociceptor sensitization. Poly(A)-binding protein (PABP) stimulates translation initiation by bridging the Poly(A) tail to the eukaryotic initiation factor 4F complex associated with the mRNA cap. Here, we use unbiased assessment of PABP binding specificity to generate a chemically modified RNA-based competitive inhibitor of PABP. The resulting RNA mimic, which we designated as the Poly(A) SPOT-ON, is more stable than unmodified RNA and binds PABP with high affinity and selectivity in vitro. We show that injection of the Poly(A) SPOT-ON at the site of an injury can attenuate behavioral response to pain. Collectively, these results suggest that PABP is integral for nociceptive plasticity. The general strategy described here provides a broad new source of mechanism-based inhibitors for RNA-binding proteins and is applicable for in vivo studies. Poly(A)-binding protein (PABP) is an RNA binding protein with translation function. Here, BarragAn-Iglesias and colleagues devise an RNA mimic that inhibits PABP activity, and show that inhibitors can reduce animal's pain response in vivo when injected locally.

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