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      • Nature-inspired thermo-responsive multifunctional membrane adaptively hybridized with PNIPAm and PPy

        Kim, Hyejeong,Kim, Kiwoong,Lee, Sang Joon Nature Publishing Group 2017 NPG Asia Materials Vol.9 No.10

        <P>Specialized plant tissues, such as the epidermis of a leaf covered with stomata, consist of soft materials with deformability and electrochemical properties to achieve specific functions in response to various environmental stimuli. Stimulus-responsive hydrogels with electrochemical properties are good candidates for imitating such special functionalities in nature and thus have great potential in a wide range of academic and industrial applications. However, hydrogel-incorporated conductive materials are usually mechanically rigid, which limits their application in other fields. In addition, the fabrication technology of structured functional hydrogels has low reproducibility due to the required multistep processing. Here, inspired by nature, specifically the stimulus-responsive functionalities of plants, a new thermo-responsive multifunctional hybrid membrane (HM) is synthesized through the in situ hybridization of conductive poly(pyrrole) (PPy) on a photopolymerized poly(N-isopropylacrylamide) (PNIPAm) matrix. The morphological and electrical properties of the fabricated HM are investigated to characterize various aspects of its multiple functions. In terms of morphology, the HM can be easily fabricated into various structures by smartly utilizing photopolymerization patterning, and it exhibits thermo-responsive deformability. In terms of functionality, it exhibits various electrical and charge responses to thermal stimuli. This simple and efficient fabrication method can be used as a promising platform for fabricating a variety of functional devices.</P>

      • SCISCIE

        Reinvigorating natural product combinatorial biosynthesis with synthetic biology

        Kim, Eunji,Moore, Bradley S,Yoon, Yeo Joon NATURE PUBLISHING GROUP 2015 NATURE CHEMICAL BIOLOGY Vol. No.

        Natural products continue to play a pivotal role in drug-discovery efforts and in the understanding if human health. The ability to extend nature's chemistry through combinatorial biosynthesis—altering functional groups, regiochemistry and scaffold backbones through the manipulation of biosynthetic enzymes—offers unique opportunities to create natural product analogs. Incorporating emerging synthetic biology techniques has the potential to further accelerate the refinement of combinatorial biosynthesis as a robust platform for the diversification of natural chemical drug leads. Two decades after the field originated, we discuss the current limitations, the realities and the state of the art of combinatorial biosynthesis, including the engineering of substrate specificity of biosynthetic enzymes and the development of heterologous expression systems for biosynthetic pathways. We also propose a new perspective for the combinatorial biosynthesis of natural products that could reinvigorate drug discovery by using synthetic biology in combination with synthetic chemistry.

      • Molecular basis of flowering under natural long-day conditions in <i>Arabidopsis</i>

        Song, Young Hun,Kubota, Akane,Kwon, Michael S.,Covington, Michael, F.,Lee, Nayoung,Ella, R. Taagen,Cintró,n, Dianne Laboy,Hwang, Dae Yeon,Akiyama, Reiko,Sarah, K. Hodge,Huang, He,Nguyen, Nhu H. Nature Publishing Group 2018 Nature plants Vol.4 No.10

        <P>Plants sense light and temperature changes to regulate flowering time. Here we show that expression of the <I>Arabidopsis</I> florigen gene, <I>FLOWERING LOCUS T</I> (<I>FT</I>), peaks in the morning during spring, a different pattern than we observe in the lab. Providing our lab growth conditions with a red/far-red light ratio similar to open field conditions and daily temperature oscillation is sufficient to mimic the <I>FT</I> expression and flowering time in natural long days. Under the adjusted growth conditions, key light signaling components, such as phytochrome A (phyA) and EARLY FLOWERING 3 (ELF3), play important roles in morning <I>FT</I> expression. These conditions stabilize CONSTANS (CO) protein, a major <I>FT</I> activator, in the morning, which is likely a critical mechanism for photoperiodic flowering in nature. Refining the parameters of our standard growth conditions to more precisely mimic plant responses in nature can provide a powerful method for improving our understanding of seasonal response.</P>

      • SCISCIESCOPUS

        Direct observation of bond formation in solution with femtosecond X-ray scattering

        Kim, Kyung Hwan,Kim, Jong Goo,Nozawa, Shunsuke,Sato, Tokushi,Oang, Key Young,Kim, Tae Wu,Ki, Hosung,Jo, Junbeom,Park, Sungjun,Song, Changyong,Sato, Takahiro,Ogawa, Kanade,Togashi, Tadashi,Tono, Kensuk Nature Publishing Group, a division of Macmillan P 2015 Nature Vol.518 No.7539

        The making and breaking of atomic bonds are essential processes in chemical reactions. Although the ultrafast dynamics of bond breaking have been studied intensively using time-resolved techniques, it is very difficult to study the structural dynamics of bond making, mainly because of its bimolecular nature. It is especially difficult to initiate and follow diffusion-limited bond formation in solution with ultrahigh time resolution. Here we use femtosecond time-resolved X-ray solution scattering to visualize the formation of a gold trimer complex, [Au(CN)<SUB>2</SUB><SUP>–</SUP>]<SUB>3</SUB> in real time without the limitation imposed by slow diffusion. This photoexcited gold trimer, which has weakly bound gold atoms in the ground state, undergoes a sequence of structural changes, and our experiments probe the dynamics of individual reaction steps, including covalent bond formation, the bent-to-linear transition, bond contraction and tetramer formation with a time resolution of ∼500 femtoseconds. We also determined the three-dimensional structures of reaction intermediates with sub-ångström spatial resolution. This work demonstrates that it is possible to track in detail and in real time the structural changes that occur during a chemical reaction in solution using X-ray free-electron lasers and advanced analysis of time-resolved solution scattering data.

      • IL-10-transduced bone marrow mesenchymal stem cells can attenuate the severity of acute graft-versus-host disease after experimental allogeneic stem cell transplantation

        Min, C-K,Kim, B-G,Park, G,Cho, Bin,Oh, I-H Nature Publishing Group 2007 Bone marrow transplantation Vol.39 No.10

        Recent data suggest that adult mesenchymal stem cells (MSCs) might enhance allogeneic hematopoietic engraftment and prevent graft-versus-host disease (GVHD) owing to their immunosuppressive nature. Using a murine model of acute GVHD, this study examined whether or not the immunosuppressive properties of MSCs could reduce the severity of experimental GVHD. The early injection of MSCs after transplant did not attenuate the severity of acute GVHD. Therefore, this study investigated whether or not the use of IL-10-transduced MSCs (IL-10 MSCs) could reduce the severity of acute GVHD. Lethally irradiated recipients were transplanted and injected with IL-10 MSCs, the MSC-expressing vector alone (vector MSCs), or the diluent (controls), respectively, on day +1. Compared with the vector MSCs or controls, there was a significantly lower mortality in the recipients of the IL-10 MSCs at day 50 after the transplant (percent survival, 0 or 10 vs 70%, P=0.0004 or 0.0064, respectively). The decrease in mortality was confirmed by the semi-quantitative GVHD score (P<0.05), and was associated with decreased serum levels of the pro-inflammatory cytokines, IFN-γ, on day +7 (P=0.015). Therefore, beneficial effects on GVHD were observed when MSCs were engineered to express the anti-inflammatory cytokine, IL-10.Bone Marrow Transplantation (2007) 39, 637–645. doi:10.1038/sj.bmt.1705644; published online 26 March 2007

      • A mechanical metamaterial made from a DNA hydrogel.

        Lee, Jong Bum,Peng, Songming,Yang, Dayong,Roh, Young Hoon,Funabashi, Hisakage,Park, Nokyoung,Rice, Edward J,Chen, Liwei,Long, Rong,Wu, Mingming,Luo, Dan Nature Pub. Group 2012 Nature nanotechnology Vol.7 No.12

        <P>Metamaterials are artificial substances that are structurally engineered to have properties not typically found in nature. To date, almost all metamaterials have been made from inorganic materials such as silicon and copper, which have unusual electromagnetic or acoustic properties that allow them to be used, for example, as invisible cloaks, superlenses or super absorbers for sound. Here, we show that metamaterials with unusual mechanical properties can be prepared using DNA as a building block. We used a polymerase enzyme to elongate DNA chains and weave them non-covalently into a hydrogel. The resulting material, which we term a meta-hydrogel, has liquid-like properties when taken out of water and solid-like properties when in water. Moreover, upon the addition of water, and after complete deformation, the hydrogel can be made to return to its original shape. The meta-hydrogel has a hierarchical internal structure and, as an example of its potential applications, we use it to create an electric circuit that uses water as a switch.</P>

      • Bio-inspired, bioengineered and biomimetic drug delivery carriers

        Yoo, Jin-Wook,Irvine, Darrell J.,Discher, Dennis E.,Mitragotri, Samir Nature Publishing Group, a division of Macmillan P 2011 Nature reviews. Drug discovery Vol.10 No.7

        Synthetic carriers such as polymer and lipid particles often struggle to meet clinical expectations. Natural particulates ?? that range from pathogens to mammalian cells ?? are therefore worth examining in more depth, as they are highly optimized for their specific functions in vivo and possess features that are often desired in drug delivery carriers. With a better understanding of these biological systems, in conjunction with the availability of advanced biotechnology tools that are useful for re-engineering the various natural systems, researchers have started to exploit natural particulates for multiple applications in the delivery of proteins, small interfering RNA and other therapeutic agents. Here, we review the natural drug delivery carriers that have provided the basis and inspiration for new drug delivery systems.

      • ZEITLUPE is a circadian photoreceptor stabilized by GIGANTEA in blue light

        Kim, Woe-Yeon,Fujiwara, Sumire,Suh, Sung-Suk,Kim, Jeongsik,Kim, Yumi,Han, Linqu,David, Karine,Putterill, Joanna,Nam, Hong Gil,Somers, David E. Nature Publishing Group 2007 Nature Vol.449 No.7160

        The circadian clock is essential for coordinating the proper phasing of many important cellular processes. Robust cycling of key clock elements is required to maintain strong circadian oscillations of these clock-controlled outputs. Rhythmic expression of the Arabidopsis thaliana F-box protein ZEITLUPE (ZTL) is necessary to sustain a normal circadian period by controlling the proteasome-dependent degradation of a central clock protein, TIMING OF CAB EXPRESSION 1 (TOC1). ZTL messenger RNA is constitutively expressed, but ZTL protein levels oscillate with a threefold change in amplitude through an unknown mechanism. Here we show that GIGANTEA (GI) is essential to establish and sustain oscillations of ZTL by a direct protein–protein interaction. GI, a large plant-specific protein with a previously undefined molecular role, stabilizes ZTL in vivo. Furthermore, the ZTL–GI interaction is strongly and specifically enhanced by blue light, through the amino-terminal flavin-binding LIGHT, OXYGEN OR VOLTAGE (LOV) domain of ZTL. Mutations within this domain greatly diminish ZTL–GI interactions, leading to strongly reduced ZTL levels. Notably, a C82A mutation in the LOV domain, implicated in the flavin-dependent photochemistry, eliminates blue-light-enhanced binding of GI to ZTL. These data establish ZTL as a blue-light photoreceptor, which facilitates its own stability through a blue-light-enhanced GI interaction. Because the regulation of GI transcription is clock-controlled, consequent GI protein cycling confers a post-translational rhythm on ZTL protein. This mechanism of establishing and sustaining robust oscillations of ZTL results in the high-amplitude TOC1 rhythms necessary for proper clock function.

      • High-harmonic generation by resonant plasmon field enhancement

        Kim, Seungchul,Jin, Jonghan,Kim, Young-Jin,Park, In-Yong,Kim, Yunseok,Kim, Seung-Woo Nature Publishing Group 2008 Nature Vol.453 No.7196

        High-harmonic generation by focusing a femtosecond laser onto a gas is a well-known method of producing coherent extreme-ultraviolet (EUV) light. This nonlinear conversion process requires high pulse intensities, greater than 10<SUP>13</SUP> W cm<SUP>-2</SUP>, which are not directly attainable using only the output power of a femtosecond oscillator. Chirped-pulse amplification enables the pulse intensity to exceed this threshold by incorporating several regenerative and/or multi-pass amplifier cavities in tandem. Intracavity pulse amplification (designed not to reduce the pulse repetition rate) also requires a long cavity. Here we demonstrate a method of high-harmonic generation that requires no extra cavities. This is achieved by exploiting the local field enhancement induced by resonant plasmons within a metallic nanostructure consisting of bow-tie-shaped gold elements on a sapphire substrate. In our experiment, the output beam emitted from a modest femtosecond oscillator (100-kW peak power, 1.3-nJ pulse energy and 10-fs pulse duration) is directly focused onto the nanostructure with a pulse intensity of only 10<SUP>11</SUP> W cm<SUP>-2</SUP>. The enhancement factor exceeds 20 dB, which is sufficient to produce EUV wavelengths down to 47 nm by injection with an argon gas jet. The method could form the basis for constructing laptop-sized EUV light sources for advanced lithography and high-resolution imaging applications.

      • SCISCIESCOPUS

        CtBP3/BARS drives membrane fission in dynamin-independent transport pathways

        Bonazzi, Matteo,Spanò,, Stefania,Turacchio, Gabriele,Cericola, Claudia,Valente, Carmen,Colanzi, Antonino,Kweon, Hee Seok,Hsu, Victor W.,Polishchuck, Elena V.,Polishchuck, Roman S.,Sallese, Miche Nature Publishing Group 2005 NATURE CELL BIOLOGY Vol.7 No.6

        Membrane fission is a fundamental step in membrane transport. So far, the only fission protein machinery that has been implicated in in vivo transport involves dynamin, and functions in several, but not all, transport pathways. Thus, other fission machineries may exist. Here, we report that carboxy-terminal binding protein 3/brefeldin A-ribosylated substrate (CtBP3/BARS) controls fission in basolateral transport from the Golgi to the plasma membrane and in fluid-phase endocytosis, whereas dynamin is not involved in these steps. Conversely, CtBP3/BARS protein is inactive in apical transport to the plasma membrane and in receptor-mediated endocytosis, both steps being controlled by dynamin. This indicates that CtBP3/BARS controls membrane fission in endocytic and exocytic transport pathways, distinct from those that require dynamin.

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