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      • Feeding State, Insulin and NPR-1 Modulate Chemoreceptor Gene Expression via Integration of Sensory and Circuit Inputs

        Gruner, Matthew,Nelson, Dru,Winbush, Ari,Hintz, Rebecca,Ryu, Leesun,Chung, Samuel H.,Kim, Kyuhyung,Gabel, Chrisopher V.,van der Linden, Alexander M. Public Library of Science 2014 PLoS genetics Vol.10 No.10

        <P>Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes in the expression of chemoreceptor genes may underlie some of these food and state-dependent changes in chemosensory behavior, but the mechanisms underlying these expression changes are unknown. Here, we identified a KIN-29 (SIK)-dependent chemoreceptor, <I>srh-234</I>, in <I>C. elegans</I> whose expression in the ADL sensory neuron type is regulated by integration of sensory and internal feeding state signals. We show that in addition to KIN-29, signaling is mediated by the DAF-2 insulin-like receptor, OCR-2 TRPV channel, and NPR-1 neuropeptide receptor. Cell-specific rescue experiments suggest that DAF-2 and OCR-2 act in ADL, while NPR-1 acts in the RMG interneurons. NPR-1-mediated regulation of <I>srh-234</I> is dependent on gap-junctions, implying that circuit inputs regulate the expression of chemoreceptor genes in sensory neurons. Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate <I>srh-234</I> expression. While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate <I>srh-234</I> expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway. Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions.</P><P><B>Author Summary</B></P><P>Animals dramatically modify their chemosensory behaviors to attractive and noxious chemical stimuli when starved. This could allow them to alter and optimize their food-search strategies to increase their survival and reproduction. Changes in the gene expression of chemoreceptors specialized in detecting environmental stimuli is observed in fish, insects and nematodes, and may be a general mechanism underlying the changes in chemosensory behaviors observed in starved animals. To elucidate this mechanism, we have developed an <I>in vivo</I> reporter assay in <I>C. elegans</I> for monitoring the expression of a candidate chemoreceptor gene in a single sensory neuron type, called ADL, as a function of feeding state. Using this reporter assay, we show that sensory inputs into ADL and neural outputs from ADL, as well as inputs from the RMG interneuron, which is electrically connected to ADL, are required to fine-tune expression of chemoreceptor genes in ADL. Sensory and circuit-mediated regulation of chemoreceptor gene expression is dependent on multiple pathways, including the neuropeptide receptor, NPR-1, and the DAF-2 insulin-like receptor. Our results reveal mechanisms underlying chemoreceptor gene expression, and provide insight into how expression changes in chemoreceptor genes may contribute to changes in chemosensory behavior as a function of feeding state.</P>

      • SCOPUS
      • Glass-to-cryogenic-liquid transitions in aqueous solutions suggested by crack healing

        Kim, Chae Un,Tate, Mark W.,Gruner, Sol M. National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.38

        <P><B>Significance</B></P><P>For decades, physicists, physical chemists, and biologists have been tremendously intrigued by the unusual thermodynamic and kinetic properties of supercooled water. Theories have been proposed to account for the properties but these theories remain contentious for lack of experimental evidence. We investigated phase behavior of water at cryogenic temperatures and showed clear experimental evidence that the two cryogenic glassy states of water (high-density amorphous and low-density amorphous) undergo glass-to-cryogenic-liquid transitions and they are thermodynamically separated by a first-order phase transition. The results provide insight into the physical origin of the anomalous properties of supercooled water.</P><P>Observation of theorized glass-to-liquid transitions between low-density amorphous (LDA) and high-density amorphous (HDA) water states had been stymied by rapid crystallization below the homogeneous water nucleation temperature (∼235 K at 0.1 MPa). We report optical and X-ray observations suggestive of glass-to-liquid transitions in these states. Crack healing, indicative of liquid, occurs when LDA ice transforms to cubic ice at 160 K, and when HDA ice transforms to the LDA state at temperatures as low as 120 K. X-ray diffraction study of the HDA to LDA transition clearly shows the characteristics of a first-order transition. Study of the glass-to-liquid transitions in nanoconfined aqueous solutions shows them to be independent of the solute concentrations, suggesting that they represent an intrinsic property of water. These findings support theories that LDA and HDA ice are thermodynamically distinct and that they are continuously connected to two different liquid states of water.</P>

      • SCISCIESCOPUS

        Ordered mesoporous silica nanoparticles with and without embedded iron oxide nanoparticles: structure evolution during synthesis

        Suteewong, Teeraporn,Sai, Hiroaki,Lee, Jinwoo,Bradbury, Michelle,Hyeon, Taeghwan,Gruner, Sol M.,Wiesner, Ulrich Royal Society of Chemistry 2010 Journal of materials chemistry Vol.20 No.36

        <P>This work reports on the structural evolution during room temperature synthesis of hexagonally ordered mesoporous silica nanoparticles with and without embedded iron oxide particles. Oleic acid-capped iron oxide nanoparticles are synthesized and transferred to an aqueous phase using the cationic surfactant, hexadecyltrimethylammonium bromide (CTAB). MCM-41 type silica and composite nanoparticles are fabricated <I>via</I> sol–gel synthesis. Aliquots are taken from the solution during synthesis to capture the particle formation process. Transmission Electron Microscopy (TEM) and Small Angle X-ray Scattering (SAXS) reveal a transition from a disordered to an ordered structure in both synthesis systems. Along with the evolution of structure, iron oxide nanoparticles acting as seeds at the early stages are relocated from the particle centers to the edges. Nitrogen sorption measurements for iron oxide-embedded mesoporous nanoparticles indicate surface areas as high as for the mesoporous silica nanoparticles without iron oxide.</P> <P>Graphic Abstract</P><P>We report on the structural evolution during synthesis of ordered mesoporous silica nanoparticles with and without embedded magnetic nanoparticles. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c0jm01002b'> </P>

      • SCOPUSKCI등재

        Enhanced Stability of LiCoO<sub>2</sub> Cathodes in Lithium-ion Batteries Using Surface Modification by Atomic Layer Deposition

        Jung, Yoon-S.,Cavanagh, Andrew S.,Dillon, Anne C.,Groner, Markus D.,George, Steven M.,Lee, Se-Hee The Korean Ceramic Society 2010 한국세라믹학회지 Vol.47 No.1

        Ultrathin atomic layer deposition (ALD) coatings were found to enhance the performance of lithium-ion batteries (LIBs). Previous studies have demonstrated that $LiCoO_2$ cathode powders coated with metal oxides with thicknesses of $\sim100-1000{\AA}$ grown using wet chemical techniques improved LIB performance. In this study, $LiCoO_2$ powders were coated with conformal $Al_2O_3$ ALD films with thicknesses of only $\sim3-4{\AA}$ established using 2 ALD cycles. The coated $LiCoO_2$ powders exhibited a capacity retention of 89% after 120 charge-discharge cycles in the 3.3~4.5 V (vs. $Li/Li^+$) range. In contrast, the bare $LiCoO_2$ powders displayed only a 45% capacity retention. This dramatic improvement may result from the ultrathin $Al_2O_3$ ALD film acting to minimize Co dissolution or to reduce surface electrolyte reactions.

      • Tracking solvent and protein movement during CO<sub>2</sub> release in carbonic anhydrase II crystals

        Kim, Chae Un,Song, HyoJin,Avvaru, Balendu Sankara,Gruner, Sol M.,Park, SangYoun,McKenna, Robert National Academy of Sciences 2016 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.113 No.19

        <P>Carbonic anhydrases are mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO2/HCO3-. Previously, the X-ray crystal structures of CO2-bound holo (zinc-bound) and apo (zinc-free) human carbonic anhydrase IIs (hCA IIs) were captured at high resolution. Here, we present sequential timeframe structures of holo-[T = 0 s (CO2-bound), 50 s, 3 min, 10 min, 25 min, and 1 h] and apo-hCA IIs [T = 0 s, 50 s, 3 min, and 10 min] during the 'slow' release of CO2. Two active site waters, WDW (deep water) and WDW' (this study), replace the vacated space created on CO2 release, and another water, WI (intermediate water), is seen to translocate to the proton wire position W1. In addition, on the rim of the active site pocket, a water W2' (this study), in close proximity to residue His64 and W2, gradually exits the active site, whereas His64 concurrently rotates from pointing away ('out') to pointing toward ('in') active site rotameric conformation. This study provides for the first time, to our knowledge, structural 'snapshots' of hCA II intermediate states during the formation of the His64-mediated proton wire that is induced as CO2 is released. Comparison of the holo-and apo-hCA II structures shows that the solvent network rearrangements require the presence of the zinc ion.</P>

      • The nuclear factor kappa B (NF-kappa B): a potential therapeutic target for estrogen receptor negative breast cancers.

        Biswas, D K,Dai, S C,Cruz, A,Weiser, B,Graner, E,Pardee, A B National Academy of Sciences 2001 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.98 No.18

        <P>The effect of a kinase inhibitor Go6796 on growth of epidermal growth factor (EGF)-stimulated estrogen receptor negative (ER-) breast cancer cells in vivo and role of nuclear factor kappa B (NF-kappaB) on tumorogenesis have been investigated. This was studied in an animal model by implanting ER- mouse mammary epithelial tumor cells (CSMLO) in syngeneic A-J mice. (i) Local administration of Go6976 an inhibitor of protein kinases C alpha and beta inhibited growth of tumors and caused extensive necrotic degeneration and regression of the tumors without causing any microscopically detectable damage to the vital organs liver and lung. (ii) Stable expression of dominant-negative mutants of the beta subunit (dnIkkbeta) of the inhibitory kappa B (IkappaB) kinase (dnIkk) that selectively blocked activation of NF-kappaB caused loss of tumorigenic potential of CSMLO cells. Stable expression of dnIkkbeta also blocked phorbol 12-myristate 13-acetate (PMA)-induced activation of NF-kappaB and overexpression of cyclin D1, concomitantly with the loss or reduced tumorigenic potential of these cells. Thus, results from in vivo and in vitro experiments strongly suggest the involvement of NF-kappaB in ER- mammary epithelial cell-mediated tumorigenesis. We propose that blocking NF-kappaB activation not only inhibits cell proliferation, but also antagonizes the antiapoptotic role of this transcription factor in ER- breast cancer cells. Thus, NF-kappaB is a potential target for therapy of EGFR family receptor-overexpressing ER- breast cancers.</P>

      • KCI등재

        Enhanced Stability of LiCoO2 Cathodes in Lithium-ion Batteries Using Surface Modification by Atomic Layer Deposition

        정윤석,Andrew S. Cavanagh,Anne C. Dillon,Markus D. Groner,Steven M. George,이세희 한국세라믹학회 2010 한국세라믹학회지 Vol.47 No.1

        Ultrathin atomic layer deposition (ALD) coatings were found to enhance the performance of lithium-ion batteries (LIBs). Previous studies have demonstrated that LiCoO2 cathode powders coated with metal oxides with thicknesses of ~100-1000 Å grown using wet chemical techniques improved LIB performance. In this study, LiCoO2 powders were coated with conformal Al2O3 ALD films with thicknesses of only ~3-4 Å established using 2 ALD cycles. The coated LiCoO2 powders exhibited a capacity retention of 89% after 120 charge-discharge cycles in the 3.3~4.5 V (vs. Li/Li+) range. In contrast, the bare LiCoO2 powders displayed only a 45% capacity retention. This dramatic improvement may result from the ultrathin Al2O3 ALD film acting to minimize Co dissolution or to reduce surface electrolyte reactions.

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