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Sample records for integrin nanoclusters function

  1. Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

    Directory of Open Access Journals (Sweden)

    Barja-Fidalgo C.

    2005-01-01

    Full Text Available Extracellular matrix proteins and cell adhesion receptors (integrins play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

  2. Functional consequences of integrin gene mutations in mice

    DEFF Research Database (Denmark)

    Bouvard, D; Brakebusch, C; Gustafsson, E

    2001-01-01

    Integrins are cell-surface receptors responsible for cell attachment to extracellular matrices and to other cells. The application of mouse genetics has significantly increased our understanding of integrin function in vivo. In this review, we summarize the phenotypes of mice carrying mutant inte...

  3. Straightforward and robust synthesis of monodisperse surface-functionalized gold nanoclusters

    Directory of Open Access Journals (Sweden)

    Silvia Varela-Aramburu

    2016-09-01

    Full Text Available Gold nanoclusters are small (1–3 nm nanoparticles with a high surface area that are useful for biomedical studies and drug delivery. The synthesis of small, surface-functionalized gold nanoclusters is greatly dependent on the reaction conditions. Here, we describe a straightforward, efficient and robust room temperature one-pot synthesis of 2 nm gold nanoclusters using thioglucose as a reducing and stabilizing agent, which was discovered by serendipity. The resultant monodisperse gold nanoclusters are more stable than those generated using some other common methods. The carboxylic acid contained in the stabilizing agent on the cluster surface serves as anchor for nanocluster functionalization. Alternatively, the addition of thiols serves to functionalize the nanoclusters. The resulting non-cytotoxic nanoclusters are taken up by cells and constitute a tuneable platform for biomedical applications including drug delivery.

  4. Formation of functionalized nanoclusters by solvent evaporation and their effect on the physicochemical properties of dental composite resins.

    Science.gov (United States)

    Rodríguez, Henry A; Giraldo, Luis F; Casanova, Herley

    2015-07-01

    The aim of this work was to study the effect of silica nanoclusters (SiNC), obtained by a solvent evaporation method and functionalized by 3-methacryloxypropyltrimethoxysilane (MPS) and MPS+octyltrimethoxysilane (OTMS) (50/50wt/wt), on the rheological, mechanical and sorption properties of urethane dimethylacrylate (UDMA)/triethylenglycol dimethacrylate (TEGDMA) (80/20wt/wt) resins blend. Silica nanoparticles (SiNP) were silanized with MPS or MPS+OTMS (50/50wt/wt) and incorporated in an UDMA-isopropanol mix to produce functionalized silica nanoclusters after evaporating the isopropanol. The effect of functionalized SiNC on resins rheological properties was determined by large and small deformation tests. Mechanical, thermal, sorption and solubility properties were evaluated for composite materials. The UDMA/TEGDMA (80/20wt/wt) resins blend with added SiNC (ca. 350nm) and functionalized with MPS showed a Newtonian flow behavior associated to their spheroidal shape, whereas the resins blend with nanoclusters silanized with MPS+OTMS (50/50wt/wt) (ca. 400nm) showed a shear-thinning behavior due to nanoclusters irregular shape. Composite materials prepared with bare silica nanoclusters showed lower compressive strength than functionalized silica nanoclusters. MPS functionalized nanoclusters showed better mechanical properties but higher water sorption than functionalized nanoclusters with both silane coupling agents, MPS and OTMS. The solvent evaporation method applied to functionalized nanoparticles showed to be an alternative way to the sinterization method for producing nanoclusters, which improved some dental composite mechanical properties and reduced water sorption. The shape of functionalized silica nanoclusters showed to have influence on the rheological properties of SiNC resin suspensions and the mechanical and sorption properties of light cured composites. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  5. Dual antagonists of integrins.

    Science.gov (United States)

    Nadrah, K; Dolenc, M Sollner

    2005-01-01

    The roles of integrins in pathologies have been studied intensively and only partially explained. This has resulted in the development of several nanomolar antagonists to certain integrins. In most cases, the aim was to produce compounds which are highly selective towards specific integrins. This paradigm has recently shifted a little. Targeting two or more integrins with one compound has become a very attractive concept, especially since it has become clear that several severe disorders, such as pathological angiogenesis, cannot be treated just with highly specific integrin antagonists. This review is aimed to elucidate some aspects regarding the design of drugs with dual activity towards integrins. Integrin structure and tissue distribution will first be described, in order to provide the basis for their functions in various pathologies which will follow. Inhibitors of several pairs of integrins will be described.

  6. Glucose oxidase-functionalized fluorescent gold nanoclusters as probes for glucose

    International Nuclear Information System (INIS)

    Xia, Xiaodong; Long, Yunfei; Wang, Jianxiu

    2013-01-01

    Highlights: ► A glucose oxidase/gold nanocluster conjugates formed by etching chemistry. ► Integration of the bioactivities and fluorescence properties within a single unit. ► These conjugates serve as novel fluorescent probe for glucose. -- Abstract: Creation and application of noble metal nanoclusters have received continuous attention. By integrating enzyme activity and fluorescence for potential applications, enzyme-capped metal clusters are more desirable. This work demonstrated a glucose oxidase (an enzyme for glucose)-functionalized gold cluster as probe for glucose. Under physiological conditions, such bioconjugate was successfully prepared by an etching reaction, where tetrakis (hydroxylmethyl) phosphonium-protected gold nanoparticle and thioctic acid-modified glucose oxidase were used as precursor and etchant, respectively. These bioconjugates showed unique fluorescence spectra (λ em max = 650 nm, λ ex max = 507 nm) with an acceptable quantum yield (ca. 7%). Moreover, the conjugated glucose oxidase remained active and catalyzed reaction of glucose and dissolved O 2 to produce H 2 O 2 , which quenched quantitatively the fluorescence of gold clusters and laid a foundation of glucose detection. A linear range of 2.0 × 10 −6 –140 × 10 −6 M and a detection limit of 0.7 × 10 −6 M (S/N = 3) were obtained. Also, another horseradish peroxidase/gold cluster bioconjugate was produced by such general synthesis method. Such enzyme/metal cluster bioconjugates represented a promising class of biosensors for biologically important targets in organelles or cells

  7. Functions of Tenascin-C and Integrin alpha9beta1 in Mediating Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2017-10-01

    AWARD  NUMBER:          W81XWH-16-1-0523 TITLE:  Functions of Tenascin- C and Integrin alpha9beta1 in Mediating Prostate Cancer Bone Metastasis...Prostat Prostate Cancer  Bone Metastasis   5a.  CONTRACT  NUMBER   Functions of Tenascin- C and Integrin alpha9beta1 in Mediating Prostate Cancer...SUPPLEMENTARY  NOTES 14. ABSTRACT The purpose of this work is to dissect mechanisms responsible for interactions between integrin a9b1 and tenascin- C that are

  8. A transmembrane polar interaction is involved in the functional regulation of integrin alpha L beta 2.

    Science.gov (United States)

    Vararattanavech, Ardcharaporn; Chng, Choon-Peng; Parthasarathy, Krupakar; Tang, Xiao-Yan; Torres, Jaume; Tan, Suet-Mien

    2010-05-14

    Integrins are heterodimeric transmembrane (TM) receptors formed by noncovalent associations of alpha and beta subunits. Each subunit contains a single alpha-helical TM domain. Inside-out activation of an integrin involves the separation of its cytoplasmic tails, leading to disruption of alphabeta TM packing. The leukocyte integrin alpha L beta 2 is required for leukocyte adhesion, migration, proliferation, cytotoxic function, and antigen presentation. In this study, we show by mutagenesis experiments that the packing of alpha L beta 2 TMs is consistent with that of the integrin alpha IIb beta 3 TMs. However, molecular dynamics simulations of alpha L beta 2 TMs in lipids predicted a polar interaction involving the side chains of alpha L Ser1071 and beta2 Thr686 in the outer-membrane association clasp (OMC). This is supported by carbonyl vibrational shifts observed in isotope-labeled alpha L beta 2 TM peptides that were incorporated into lipid bilayers. Molecular dynamics studies simulating the separation of alpha L beta 2 tails showed the presence of polar interaction during the initial perturbation of the inner-membrane association clasp. When the TMs underwent further separation, the polar interaction was disrupted. OMC polar interaction is important in regulating the functions of beta2 integrins because mutations that disrupt the OMC polar interaction generated constitutively activated alpha L beta 2, alpha M beta 2, and alpha X beta 2 in 293T transfectants. We also show that the expression of mutant beta2 Thr686Gly in beta2-deficient T cells rescued cell adhesion to intercellular adhesion molecule 1, but the cells showed overt elongated morphologies in response to chemokine stromal-cell-derived factor 1 alpha treatment as compared to wild-type beta2-expressing cells. These two TM polar residues are totally conserved in other members of the beta2 integrins in humans and across different species. Our results provide an example of the stabilizing effect of polar

  9. Catalytic hydrolysis of ammonia borane for hydrogen generation using cobalt nanocluster catalyst supported on polydopamine functionalized multiwalled carbon nanotube

    International Nuclear Information System (INIS)

    Arthur, Ernest Evans; Li, Fang; Momade, Francis W.Y.; Kim, Hern

    2014-01-01

    Hydrogen was generated from ammonia borane complex by hydrolysis using cobalt nanocluster catalyst supported on polydopamine functionalized MWCNTs (multi-walled carbon nanotubes). The impregnation-chemical reduction method was used for the preparation of the supported catalyst. The nanocluster catalyst support was formed by in-situ oxidative polymerization of dopamine on the MWCNTs in alkaline solution at room temperature. The structural and physical–chemical properties of the nanocluster catalyst were characterized by FT-IR (Fourier transform infrared spectroscopy), EDX (energy-dispersive X-ray spectroscopy), SEM (scanning electron microscope), XRD (X-ray diffraction) and TEM (transmission electron microscopy). The nanocluster catalyst showed good catalytic activity for the hydrogen generation from aqueous ammonia borane complex. A reusability test to determine the practical usage of the catalyst was also investigated. The result revealed that the catalyst maintained an appreciable catalytic performance and stability in terms of its reusability after three cycle of reuse for the hydrolysis reaction. Also, the activation energy for the hydrolysis of ammonia borane complex was estimated to be 50.41 kJmol −1 , which is lower than the values of some of the reported catalyst. The catalyst can be considered as a promising candidate in developing highly efficient portable hydrogen generation systems such as PEMFC (proton exchange membrane fuel cells). - Highlights: • Co/Pdop-o-MWCNT (Pdop functionalized MWCNT supported cobalt nanocluster) catalyst was synthesized for hydrogen generation. • It is an active catalyst for hydrogen generation via hydrolysis of ammonia borane. • It showed good stability in terms of reusability for the hydrogen generation

  10. Synthesis of Iron-ferrocyanide functionalized magnetic nanocluster for the removal of cesium

    International Nuclear Information System (INIS)

    Yang, Hee-Man; Jang, Sung-Chan; Lee, Kune Woo; Seo, Bum-Kyoung; Moon, Jei Kwon

    2014-01-01

    In the present study, magnetite nanocluster was synthesized by hydrothermal method, and coated with iron ferrocyanide for the adsorption of cesium in an aqueous solution through simple addition of iron ferrocyanide in acid condition. We describe the morphology, structure, and physical property of these nanoparticles. In addition, their ability to eliminate cesium from water was also evaluated. In this study, we fabricated Iron ferrocyanide immobilized magnetite nanocluster (IFC-MNC) using hydrothermal methods. The CIFC-MNC exhibited easy separation ability from water by an external magnet, and showed a high removal efficiency of cesium in aqueous solutions. Therefore, the IFC-MNC demonstrated good potential for the treatment of water contaminated with radioactive cesium. gnetic nanoadsorbents composed of a magnetic particles core and functional shell, which adsorb the contaminants, has attracted significant attention in environmental remediation owing to their high surface area and unique superparamagnetism. The nuclear accident at the Fukushima Daiichi nuclear power station in 2011 released a huge quantity of radioactive contaminants into the environment. Among these, cesium Cs-137 is the most problematic contaminant due to its long half-life (30.2 years), and high-energy gamma ray (γ-ray) emissions. Among various adsorbents to treat Cs-137 contaminated water, metal ferrocyanides were widely applied to remove the Cs-137 in water. For better separation of metal ferrocyanide from water, recently, our group reported the fabrication of copper ferrocyanide-functionalized magnetic nanoparticles (Cu-FC-EDA-MNPs) using alkoxysilanes, having ethylenediamine (EDA) group, modified Fe 3 O 4 nanoparticles (EDA-MNPs) for the fast and easy magnetic separation of metal ferrocyanide. However, the fabrication method was multistep procedure. Thus, a more simplified fabrication procedure is still desired

  11. Synthesis of Iron-ferrocyanide functionalized magnetic nanocluster for the removal of cesium

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hee-Man; Jang, Sung-Chan; Lee, Kune Woo; Seo, Bum-Kyoung; Moon, Jei Kwon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    In the present study, magnetite nanocluster was synthesized by hydrothermal method, and coated with iron ferrocyanide for the adsorption of cesium in an aqueous solution through simple addition of iron ferrocyanide in acid condition. We describe the morphology, structure, and physical property of these nanoparticles. In addition, their ability to eliminate cesium from water was also evaluated. In this study, we fabricated Iron ferrocyanide immobilized magnetite nanocluster (IFC-MNC) using hydrothermal methods. The CIFC-MNC exhibited easy separation ability from water by an external magnet, and showed a high removal efficiency of cesium in aqueous solutions. Therefore, the IFC-MNC demonstrated good potential for the treatment of water contaminated with radioactive cesium. gnetic nanoadsorbents composed of a magnetic particles core and functional shell, which adsorb the contaminants, has attracted significant attention in environmental remediation owing to their high surface area and unique superparamagnetism. The nuclear accident at the Fukushima Daiichi nuclear power station in 2011 released a huge quantity of radioactive contaminants into the environment. Among these, cesium Cs-137 is the most problematic contaminant due to its long half-life (30.2 years), and high-energy gamma ray (γ-ray) emissions. Among various adsorbents to treat Cs-137 contaminated water, metal ferrocyanides were widely applied to remove the Cs-137 in water. For better separation of metal ferrocyanide from water, recently, our group reported the fabrication of copper ferrocyanide-functionalized magnetic nanoparticles (Cu-FC-EDA-MNPs) using alkoxysilanes, having ethylenediamine (EDA) group, modified Fe{sub 3}O{sub 4} nanoparticles (EDA-MNPs) for the fast and easy magnetic separation of metal ferrocyanide. However, the fabrication method was multistep procedure. Thus, a more simplified fabrication procedure is still desired.

  12. Glucose oxidase-functionalized fluorescent gold nanoclusters as probes for glucose

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Xiaodong [College of Chemistry and Chemical Engineering, Central South University, Changsha 410083 (China); School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201 (China); Long, Yunfei, E-mail: l_yunfei927@163.com [School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201 (China); Wang, Jianxiu, E-mail: jxiuwang@csu.edu.cn [College of Chemistry and Chemical Engineering, Central South University, Changsha 410083 (China)

    2013-04-15

    Highlights: ► A glucose oxidase/gold nanocluster conjugates formed by etching chemistry. ► Integration of the bioactivities and fluorescence properties within a single unit. ► These conjugates serve as novel fluorescent probe for glucose. -- Abstract: Creation and application of noble metal nanoclusters have received continuous attention. By integrating enzyme activity and fluorescence for potential applications, enzyme-capped metal clusters are more desirable. This work demonstrated a glucose oxidase (an enzyme for glucose)-functionalized gold cluster as probe for glucose. Under physiological conditions, such bioconjugate was successfully prepared by an etching reaction, where tetrakis (hydroxylmethyl) phosphonium-protected gold nanoparticle and thioctic acid-modified glucose oxidase were used as precursor and etchant, respectively. These bioconjugates showed unique fluorescence spectra (λ{sub em} {sub max} = 650 nm, λ{sub ex} {sub max} = 507 nm) with an acceptable quantum yield (ca. 7%). Moreover, the conjugated glucose oxidase remained active and catalyzed reaction of glucose and dissolved O{sub 2} to produce H{sub 2}O{sub 2}, which quenched quantitatively the fluorescence of gold clusters and laid a foundation of glucose detection. A linear range of 2.0 × 10{sup −6}–140 × 10{sup −6} M and a detection limit of 0.7 × 10{sup −6} M (S/N = 3) were obtained. Also, another horseradish peroxidase/gold cluster bioconjugate was produced by such general synthesis method. Such enzyme/metal cluster bioconjugates represented a promising class of biosensors for biologically important targets in organelles or cells.

  13. Use of integrin-linked kinase to extend function of encapsulated pancreatic tissue

    International Nuclear Information System (INIS)

    Blanchette, James O; Langer, Steven J; Leinwand, Leslie L; Sahai, Suchit; Topiwala, Pritesh S; Anseth, Kristi S

    2010-01-01

    We have studied the impact of overexpression of an intracellular signaling protein, integrin-linked kinase (ILK), on the survival and function of encapsulated islet tissue used for the treatment of type 1 diabetes. The dimensions of the encapsulated tissue can impact the stresses placed on the tissue and ILK overexpression shows the ability to extend function of dissociated cells as well as intact islets. These results suggest that lost cell-extracellular matrix interactions in cell encapsulation systems can lead to decreased insulin secretion and ILK signaling is a target to overcome this phenomenon. (communication)

  14. Use of integrin-linked kinase to extend function of encapsulated pancreatic tissue

    Energy Technology Data Exchange (ETDEWEB)

    Blanchette, James O [Department of Chemical Engineering, University of South Carolina, Columbia, SC (United States); Langer, Steven J; Leinwand, Leslie L [Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO (United States); Sahai, Suchit; Topiwala, Pritesh S [Biomedical Engineering Program, University of South Carolina, Columbia, SC (United States); Anseth, Kristi S, E-mail: blanchej@cec.sc.ed [Howard Hughes Medical Institute, Boulder, CO (United States)

    2010-12-15

    We have studied the impact of overexpression of an intracellular signaling protein, integrin-linked kinase (ILK), on the survival and function of encapsulated islet tissue used for the treatment of type 1 diabetes. The dimensions of the encapsulated tissue can impact the stresses placed on the tissue and ILK overexpression shows the ability to extend function of dissociated cells as well as intact islets. These results suggest that lost cell-extracellular matrix interactions in cell encapsulation systems can lead to decreased insulin secretion and ILK signaling is a target to overcome this phenomenon. (communication)

  15. The Gain-of-Function Integrin β3 Pro33 Variant Alters the Serotonin System in the Mouse Brain.

    Science.gov (United States)

    Dohn, Michael R; Kooker, Christopher G; Bastarache, Lisa; Jessen, Tammy; Rinaldi, Capria; Varney, Seth; Mazalouskas, Matthew D; Pan, Hope; Oliver, Kendra H; Velez Edwards, Digna R; Sutcliffe, James S; Denny, Joshua C; Carneiro, Ana M D

    2017-11-15

    Engagement of integrins by the extracellular matrix initiates signaling cascades that drive a variety of cellular functions, including neuronal migration and axonal pathfinding in the brain. Multiple lines of evidence link the ITGB3 gene encoding the integrin β3 subunit with the serotonin (5-HT) system, likely via its modulation of the 5-HT transporter (SERT). The ITGB3 coding polymorphism Leu33Pro (rs5918, Pl A2 ) produces hyperactive αvβ3 receptors that influence whole-blood 5-HT levels and may influence the risk for autism spectrum disorder (ASD). Using a phenome-wide scan of psychiatric diagnoses, we found significant, male-specific associations between the Pro33 allele and attention-deficit hyperactivity disorder and ASDs. Here, we used knock-in (KI) mice expressing an Itgb3 variant that phenocopies the human Pro33 variant to elucidate the consequences of constitutively enhanced αvβ3 signaling to the 5-HT system in the brain. KI mice displayed deficits in multiple behaviors, including anxiety, repetitive, and social behaviors. Anatomical studies revealed a significant decrease in 5-HT synapses in the midbrain, accompanied by decreases in SERT activity and reduced localization of SERTs to integrin adhesion complexes in synapses of KI mice. Inhibition of focal adhesion kinase (FAK) rescued SERT function in synapses of KI mice, demonstrating that constitutive active FAK signaling downstream of the Pro32Pro33 integrin αvβ3 suppresses SERT activity. Our studies identify a complex regulation of 5-HT homeostasis and behaviors by integrin αvβ3, revealing an important role for integrins in modulating risk for neuropsychiatric disorders. SIGNIFICANCE STATEMENT The integrin β3 Leu33Pro coding polymorphism has been associated with autism spectrum disorders (ASDs) within a subgroup of patients with elevated blood 5-HT levels, linking integrin β3, 5-HT, and ASD risk. We capitalized on these interactions to demonstrate that the Pro33 coding variation in the murine

  16. Facile Synthesis of Gd-Functionalized Gold Nanoclusters as Potential MRI/CT Contrast Agents

    Directory of Open Access Journals (Sweden)

    Wenjun Le

    2016-04-01

    Full Text Available Multi-modal imaging plays a key role in the earlier detection of disease. In this work, a facile bioinspired method was developed to synthesize Gd-functionalized gold nanoclusters (Gd-Au NCs. The Gd-Au NCs exhibit a uniform size, with an average size of 5.6 nm in dynamic light scattering (DLS, which is a bit bigger than gold clusters (3.74 nm, DLS, while the fluorescent properties of Gd-Au NCs are almost the same as that of Au NCs. Moreover, the Gd-Au NCs exhibit a high longitudinal relaxivity value (r1 of 22.111 s−1 per mM of Gd in phosphate-buffered saline (PBS, which is six times higher than that of commercial Magnevist (A complex of gadolinium with a chelating agent, diethylenetriamine penta-acetic acid, Gd-DTPA, r1 = 3.56 mM−1·s−1. Besides, as evaluated by nano single photon emission computed tomography (SPECT and computed tomography (CT the Gd-Au NCs have a potential application as CT contrast agents because of the Au element. Finally, the Gd-Au NCs show little cytotoxicity, even when the Au concentration is up to 250 μM. Thus, the Gd-Au NCs can act as multi-modal imaging contrast agents.

  17. A novel fluorescent array for mercury (II) ion in aqueous solution with functionalized cadmium selenide nanoclusters

    International Nuclear Information System (INIS)

    Chen Jinlong; Gao Yingchun; Xu, ZhiBing; Wu, GenHua; Chen, YouCun; Zhu, ChangQing

    2006-01-01

    Mono-disperse CdSe nanoclusters have been prepared facilely and functionalized with L-cysteine through two steps by using safe and low cost substances. They are water-soluble and biocompatible. Especially these functionalized quantum dots can be stably soluble in water more than for 30 days, and the intensity of fluorescence and absorbance was decreased less than 15% of fresh prepared CdSe colloids. These functionalized CdSe QDs exhibited strong specific affinity for mercury (II) through QDs interface functional groups. Based on the quenching of fluorescence signals of functionalized CdSe QDs at 530 nm and no obvious wavelength shift or no new emission band in present of Hg (II) at pH 7.75 of phosphate buffer solution, a simple, rapid and specific array for Hg (II) was proposed. In comparison with conventional organic fluorophores, these nanoparticles are brighter, more stable against photobleaching, and do not suffer from blinking. Under optimum conditions, the response of linearly proportional to the concentration of Hg (II) between 0 and 2.0 x 10 -6 mol L -1 , and the limit of detection is 6.0 x 10 -9 mol L -1 . The relative standard deviation of six replicate measurements is 1.8% for 1.0 x 10 -7 mol L -1 Hg (II). The mechanism of reaction is also discussed. The proposed method was successfully applied for Hg (II) detection in four real samples with a satisfactory result that was obtained by cold vapor atomic fluorescence spectrometry (CV-AFS)

  18. The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression.

    Science.gov (United States)

    Patsoukis, Nikolaos; Bardhan, Kankana; Weaver, Jessica D; Sari, Duygu; Torres-Gomez, Alvaro; Li, Lequn; Strauss, Laura; Lafuente, Esther M; Boussiotis, Vassiliki A

    2017-08-22

    Lymphocyte activation requires adhesion to antigen-presenting cells. This is a critical event linking innate and adaptive immunity. Lymphocyte adhesion is accomplished through LFA-1, which must be activated by a process referred to as inside-out integrin signaling. Among the few signaling molecules that have been implicated in inside-out integrin activation in hematopoietic cells are the small guanosine triphosphatase (GTPase) Rap1 and its downstream effector Rap1-interacting molecule (RIAM), a multidomain protein that defined the Mig10-RIAM-lamellipodin (MRL) class of adaptor molecules. Through its various domains, RIAM is a critical node of signal integration for activation of T cells, recruits monomeric and polymerized actin to drive actin remodeling and cytoskeletal reorganization, and promotes inside-out integrin signaling in T cells. As a regulator of inside-out integrin activation, RIAM affects multiple functions of innate and adaptive immunity. The effects of RIAM on cytoskeletal reorganization and integrin activation have implications in cell migration and trafficking of cancer cells. We provide an overview of the structure and interactions of RIAM, and we discuss the implications of RIAM functions in innate and adaptive immunity and cancer. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  19. Mena binds α5 integrin directly and modulates α5β1 function.

    Science.gov (United States)

    Gupton, Stephanie L; Riquelme, Daisy; Hughes-Alford, Shannon K; Tadros, Jenny; Rudina, Shireen S; Hynes, Richard O; Lauffenburger, Douglas; Gertler, Frank B

    2012-08-20

    Mena is an Ena/VASP family actin regulator with roles in cell migration, chemotaxis, cell-cell adhesion, tumor cell invasion, and metastasis. Although enriched in focal adhesions, Mena has no established function within these structures. We find that Mena forms an adhesion-regulated complex with α5β1 integrin, a fibronectin receptor involved in cell adhesion, motility, fibronectin fibrillogenesis, signaling, and growth factor receptor trafficking. Mena bound directly to the carboxy-terminal portion of the α5 cytoplasmic tail via a 91-residue region containing 13 five-residue "LERER" repeats. In fibroblasts, the Mena-α5 complex was required for "outside-in" α5β1 functions, including normal phosphorylation of FAK and paxillin and formation of fibrillar adhesions. It also supported fibrillogenesis and cell spreading and controlled cell migration speed. Thus, fibroblasts require Mena for multiple α5β1-dependent processes involving bidirectional interactions between the extracellular matrix and cytoplasmic focal adhesion proteins.

  20. First-principles study of MoS2 and MoSe2 nanoclusters in the framework of evolutionary algorithm and density functional theory

    Science.gov (United States)

    Hashemi, Zohreh; Rafiezadeh, Shohreh; Hafizi, Roohollah; Hashemifar, S. Javad; Akbarzadeh, Hadi

    2018-04-01

    Evolutionary algorithm is combined with full-potential ab initio calculations to investigate conformational space of (MoS2)n and (MoSe2)n (n = 1-10) nanoclusters and to identify the lowest energy structural isomers of these systems. It is argued that within both BLYP and PBE functionals, these nanoclusters favor sandwiched planar configurations, similar to their ideal planar sheets. The second order difference in total energy (Δ2 E) of the lowest energy isomers is computed to estimate the abundance of the clusters at different sizes and to determine the magic sizes of (MoS2)n and (MoSe2)n nanoclusters. In order to investigate the electronic properties of nanoclusters, their energy gap is calculated by several methods, including hybrid functionals (B3LYP and PBE0), GW approach, and Δ scf method. At the end, the vibrational modes of the lowest lying isomers are calculated by using the force constants method and the IR active modes of the systems are identified. The vibrational spectra are used to calculate the Helmholtz free energy of the systems and then to investigate abundance of the nanoclusters at finite temperatures.

  1. ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function

    DEFF Research Database (Denmark)

    Kawaguchi, Nobuko; Sundberg, Christina; Kveiborg, Marie

    2003-01-01

    -100 from cells overexpressing ADAM12 than from control cells. Collectively, these results show that surface expression of ADAM12 impairs the function of beta1 integrins and, consequently, alters the organization of the actin cytoskeleton and extracellular matrix. These events may be necessary...

  2. Function of Etk in Growth Factor Receptor Signaling to Integrins in Breast Cancer

    National Research Council Canada - National Science Library

    Shimizu, Yoji

    2001-01-01

    The central hypothesis in this IDEA Award is that increased integrin-mediated adhesiveness and migration of breast cancer cells in response to stimulation by the growth factors heregulin beta (HRG beta...

  3. Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function.

    Science.gov (United States)

    Sayedyahossein, Samar; Rudkouskaya, Alena; Leclerc, Valerie; Dagnino, Lina

    2016-02-01

    A functional permeability barrier is essential to prevent the passage of water and electrolytes, macromolecules, and pathogens through the epidermis. This is accomplished in terminally differentiated keratinocytes through formation of a cornified envelope and the assembly of tight intercellular junctions. Integrin-linked kinase (ILK) is a scaffold protein essential for hair follicle morphogenesis and epidermal attachment to the basement membrane. However, the biological functions of ILK in differentiated keratinocytes remain poorly understood. Furthermore, whether ILK is implicated in keratinocyte differentiation and intercellular junction formation has remained an unresolved issue. Here we describe a pivotal role for ILK in keratinocyte differentiation responses to increased extracellular Ca(2+), regulation of adherens and tight junction assembly, and the formation of an outside-in permeability barrier toward macromolecules. In the absence of ILK, the calcium sensing receptor, E-cadherin, and ZO-1 fail to translocate to the cell membrane, through mechanisms that involve abnormalities in microtubules and in RhoA activation. In situ, ILK-deficient epidermis exhibits reduced tight junction formation and increased outside-in permeability to a dextran tracer, indicating reduced barrier properties toward macromolecules. Therefore, ILK is an essential component of keratinocyte differentiation programs that contribute to epidermal integrity and the establishment of its barrier properties. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Redox-Triggered Bonding-Induced Emission of Thiol-Functionalized Gold Nanoclusters for Luminescence Turn-On Detection of Molecular Oxygen.

    Science.gov (United States)

    Ao, Hang; Feng, Hui; Zhao, Mengting; Zhao, Meizhi; Chen, Jianrong; Qian, Zhaosheng

    2017-11-22

    Most optical sensors for molecular oxygen were developed based on the quenching effect of the luminescence of oxygen-sensitive probes; however, the signal turn-off mode of these probes is undesirable to quantify and visualize molecular oxygen. Herein, we report a novel luminescence turn-on detection strategy for molecular oxygen via the specific oxygen-triggered bonding-induced emission of thiol-functionalized gold nanoclusters. Thiol-functionalized gold nanoclusters were prepared by a facile one-step synthesis, and as-prepared gold nanoclusters possess significant aggregation-induced emission (AIE) property. It is the first time to discover the oxygen-triggered bonding-induced emission (BIE) behavior of gold nanoclusters, which results in disulfide-linked covalent bonding assemblies with intensely red luminescence. This specific redox-triggered BIE is capable of quantitatively detecting dissolved oxygen in aqueous solution in a light-up manner, and trace amount of dissolved oxygen at ppb level is achieved based on this detection method. A facile and convenient test strip for oxygen detection was also developed to monitor molecular oxygen in a gas matrix. Covalent bonding-induced emission is proven to be a more efficient way to attain high brightness of AIEgens than a physical aggregation-induced emission process, and provides a more convenient and desirable detection method for molecular oxygen than the previous sensors.

  5. Molecular dynamics and docking simulation of a natural variant of Activated Protein C with impaired protease activity: implications for integrin-mediated antiseptic function.

    Science.gov (United States)

    D'Ursi, Pasqualina; Orro, Alessandro; Morra, Giulia; Moscatelli, Marco; Trombetti, Gabriele; Milanesi, Luciano; Rovida, Ermanna

    2015-01-01

    Activated Protein C (APC) is a multifunctional serine protease, primarily known for its anticoagulant function in the coagulation system. Several studies have already elucidated its role in counteracting apoptosis and inflammation in cells, while significant effort is still ongoing for defining its involvement in sepsis. Earlier literature has shown that the antiseptic function of APC is mediated by its binding to leukocyte integrins, which is due to the presence of the integrin binding motif Arg-Gly-Asp at the N-terminus of the APC catalytic chain. Many natural mutants have been identified in patients with Protein C deficiency diagnosis including a variant of specificity pocket (Gly216Asp). In this work, we present a molecular model of the complex of APC with αVβ3 integrin obtained by protein-protein docking approach. A computational analysis of this variant is hereby presented, based on molecular dynamics and docking simulations, aiming at investigating the effects of the Gly216Asp mutation on the protein conformation and inferring its functional implications. Our study shows that such mutation is likely to impair the protease activity while preserving the overall protein fold. Moreover, superposition of the integrin binding motifs in wild-type and mutant forms suggests that the interaction with integrin can still occur and thus the mutant is likely to retain its antiseptic function related to the neutrophyl integrin binding. Therapeutic applications could result in this APC mutant which retains antiseptic function without anticoagulant side effects.

  6. Frontline Science: Functionally impaired geriatric CAR-T cells rescued by increased α5β1 integrin expression.

    Science.gov (United States)

    Guha, Prajna; Cunetta, Marissa; Somasundar, Ponnandai; Espat, N Joseph; Junghans, Richard P; Katz, Steven C

    2017-08-01

    Chimeric antigen receptor expressing T cells (CAR-T) are a promising form of immunotherapy, but the influence of age-related immune changes on CAR-T production remains poorly understood. We showed that CAR-T cells from geriatric donors (gCAR-T) are functionally impaired relative to CAR-T from younger donors (yCAR-T). Higher transduction efficiencies and improved cell expansion were observed in yCAR-T cells compared with gCAR-T. yCAR-T demonstrated significantly increased levels of proliferation and signaling activation of phosphorylated (p)Erk, pAkt, pStat3, and pStat5. Furthermore, yCAR-T contained higher proportions of CD4 and CD8 effector memory (EM) cells, which are known to have enhanced cytolytic capabilities. Accordingly, yCAR-T demonstrated higher levels of tumor antigen-specific cytotoxicity compared with gCAR-T. Enhanced tumor killing by yCAR-T correlated with increased levels of perforin and granzyme B. yCAR-T had increased α5β1 integrin expression, a known mediator of retroviral transduction. We found that treatment with M-CSF or TGF-β1 rescued the impaired transduction efficiency of the gCAR-T by increasing the α5β1 integrin expression. Neutralization of α5β1 confirmed that this integrin was indispensable for CAR expression. Our study suggests that the increase of α5β1 integrin expression levels enhances CAR expression and thereby improves tumor killing by gCAR-T. © Society for Leukocyte Biology.

  7. Functional single-walled carbon nanotubes based on an integrin αvβ3 monoclonal antibody for highly efficient cancer cell targeting

    International Nuclear Information System (INIS)

    Ou Zhongmin; Wu Baoyan; Xing Da; Zhou Feifan; Wang Huiying; Tang Yonghong

    2009-01-01

    The application of single-walled carbon nanotubes (SWNTs) in the field of biomedicine is becoming an entirely new and exciting topic. In this study, a novel functional SWNT based on an integrin α v β 3 monoclonal antibody was developed and was used for cancer cell targeting in vitro. SWNTs were first modified by phospholipid-bearing polyethylene glycol (PL-PEG). The PL-PEG functionalized SWNTs were then conjugated with protein A. A SWNT-integrin α v β 3 monoclonal antibody system (SWNT-PEG-mAb) was thus constructed by conjugating protein A with the fluorescein labeled integrin α v β 3 monoclonal antibody. In vitro study revealed that SWNT-PEG-mAb presented a high targeting efficiency on integrin α v β 3 -positive U87MG cells with low cellular toxicity, while for integrin α v β 3 -negative MCF-7 cells, the system had a low targeting efficiency, indicating that the high targeting to U87MG cells was due to the specific integrin targeting of the monoclonal antibody. In conclusion, SWNT-PEG-mAb developed in this research is a potential candidate for cancer imaging and drug delivery in cancer targeting therapy.

  8. Genetic analysis of beta1 integrin function: confirmed, new and revised roles for a crucial family of cell adhesion molecules

    DEFF Research Database (Denmark)

    Brakebusch, C; Hirsch, E; Potocnik, A

    1997-01-01

    Integrins are heterodimeric cell adhesion proteins connecting the extracellular matrix to the cytoskeleton and transmitting signals in both directions. These integrins are suggested to be involved in many different biological processes such as growth, differentiation, migration, and cell death. O...

  9. Integrin Signalling

    OpenAIRE

    Schelfaut, Roselien

    2005-01-01

    Integrins are receptors presented on most cells. By binding ligand they can generate signalling pathways inside the cell. Those pathways are a linkage to proteins in the cytosol. It is known that tumor cells can survive and proliferate in the absence of a solid support while normal cells need to be bound to ligand. To understand why tumour cells act that way, we first have to know how ligand-binding to integrins affect the cell. This research field includes studies on activation of proteins b...

  10. Endothelial cell-derived matrix promotes the metabolic functional maturation of hepatocyte via integrin-Src signalling.

    Science.gov (United States)

    Guo, Xinyue; Li, Weihong; Ma, Minghui; Lu, Xin; Zhang, Haiyan

    2017-11-01

    The extracellular matrix (ECM) microenvironment is involved in the regulation of hepatocyte phenotype and function. Recently, the cell-derived extracellular matrix has been proposed to represent the bioactive and biocompatible materials of the native ECM. Here, we show that the endothelial cell-derived matrix (EC matrix) promotes the metabolic maturation of human adipose stem cell-derived hepatocyte-like cells (hASC-HLCs) through the activation of the transcription factor forkhead box protein A2 (FOXA2) and the nuclear receptors hepatocyte nuclear factor 4 alpha (HNF4α) and pregnane X receptor (PXR). Reducing the fibronectin content in the EC matrix or silencing the expression of α5 integrin in the hASC-HLCs inhibited the effect of the EC matrix on Src phosphorylation and hepatocyte maturation. The inhibition of Src phosphorylation using the inhibitor PP2 or silencing the expression of Src in hASC-HLCs also attenuated the up-regulation of the metabolic function of hASC-HLCs in a nuclear receptor-dependent manner. These data elucidate integrin-Src signalling linking the extrinsic EC matrix signals and metabolic functional maturation of hepatocyte. This study provides a model for studying the interaction between hepatocytes and non-parenchymal cell-derived matrix. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  11. Surface mediated assembly of small, metastable gold nanoclusters

    Science.gov (United States)

    Pettibone, John M.; Osborn, William A.; Rykaczewski, Konrad; Talin, A. Alec; Bonevich, John E.; Hudgens, Jeffrey W.; Allendorf, Mark D.

    2013-06-01

    The unique properties of metallic nanoclusters are attractive for numerous commercial and industrial applications but are generally less stable than nanocrystals. Thus, developing methodologies for stabilizing nanoclusters and retaining their enhanced functionality is of great interest. We report the assembly of PPh3-protected Au9 clusters from a heterogeneous mixture into films consisting of sub 3 nm nanocluster assemblies. The depositing nanoclusters are metastable in solution, but the resulting nanocluster assemblies are stabilized indefinitely in air or fresh solvent. The films exhibit distinct structure from Au nanoparticles observed by X-ray diffraction, and film dissolution data support the preservation of small nanoclusters. UV-Vis spectroscopy, electrospray ionization mass spectrometry, X-ray photoelectron spectroscopy and electron microscopy are used to elucidate information regarding the nanocluster formation and assembly mechanism. Preferential deposition of nanocluster assemblies can be achieved on multiple substrates, including polymer, Cr, Si, SiO2, SiNx, and metal-organic frameworks (MOFs). Unlike other vapor phase coating processes, nanocluster assembly on the MIL-68(In) MOF crystal is capable of preferentially coating the external surface and stabilizing the crystal structure in hydrothermal conditions, which should enhance their storage, separation and delivery capabilities.The unique properties of metallic nanoclusters are attractive for numerous commercial and industrial applications but are generally less stable than nanocrystals. Thus, developing methodologies for stabilizing nanoclusters and retaining their enhanced functionality is of great interest. We report the assembly of PPh3-protected Au9 clusters from a heterogeneous mixture into films consisting of sub 3 nm nanocluster assemblies. The depositing nanoclusters are metastable in solution, but the resulting nanocluster assemblies are stabilized indefinitely in air or fresh solvent. The

  12. Leukocyte integrins and their ligand interactions

    Science.gov (United States)

    Hyun, Young-Min; Lefort, Craig T.; Kim, Minsoo

    2010-01-01

    Although critical for cell adhesion and migration during normal immune-mediated reactions, leukocyte integrins are also involved in the pathogenesis of diverse clinical conditions including autoimmune diseases and chronic inflammation. Leukocyte integrins therefore have been targets for anti-adhesive therapies to treat the inflammatory disorders. Recently, the therapeutic potential of integrin antagonists has been demonstrated in psoriasis and multiple sclerosis. However, current therapeutics broadly affect integrin functions and, thus, yield unfavorable side effects. This review discusses the major leukocyte integrins and the anti-adhesion strategies for treating immune diseases. PMID:19184539

  13. Expression and putative function of fibronectin and its receptor (integrin alpha(5)beta(1)) in male and female gametes during bovine fertilization in vitro.

    Science.gov (United States)

    Thys, Mirjan; Nauwynck, Hans; Maes, Dominiek; Hoogewijs, Maarten; Vercauteren, Dries; Rijsselaere, Tom; Favoreel, Herman; Van Soom, Ann

    2009-09-01

    Fibronectin (Fn) is a 440 kDa glycoprotein assumed to participate in sperm-egg interaction in human. Recently, it has been demonstrated that Fn--when present during bovine IVF--strongly inhibits sperm penetration. The present study was conducted firstly to evaluate the expression of Fn and its integrin receptor (alpha(5)beta(1)) on male and female bovine gametes using indirect immunofluorescence and secondly, to determine the function of Fn during bovine IVF. Endogenous Fn was detected underneath the zona pellucida (ZP) and integrin alpha(5) on the oolemma of cumulus-denuded oocytes. Bovine spermatozoa displayed integrin alpha(5) at their equatorial segment after acrosome reaction. We established that the main inhibitory effect of exogenously supplemented Fn was located at the sperm-oolemma binding, with a (concurrent) effect on fusion, and this can probably be attributed to the binding of Fn to spermatozoa at the equatorial segment, as shown by means of Alexa Fluor 488-conjugated Fn. Combining these results, the inhibitory effect of exogenously supplemented Fn seemed to be exerted on the male gamete by binding to the exposed integrin alpha(5)beta(1) receptor after acrosome reaction. The presence of endogenous Fn underneath the ZP together with integrin alpha(5) expression on oolemma and acrosome-reacted (AR) sperm cell surface suggests a 'velcro' interaction between the endogenous Fn ligand and corresponding receptors on both (AR) sperm cell and oolemma, initiating sperm-egg binding.

  14. Tensin stabilizes integrin adhesive contacts in Drosophila.

    Science.gov (United States)

    Torgler, Catherine N; Narasimha, Maithreyi; Knox, Andrea L; Zervas, Christos G; Vernon, Matthew C; Brown, Nicholas H

    2004-03-01

    We report the functional characterization of the Drosophila ortholog of tensin, a protein implicated in linking integrins to the cytoskeleton and signaling pathways. A tensin null was generated and is viable with wing blisters, a phenotype characteristic of loss of integrin adhesion. In tensin mutants, mechanical abrasion is required during wing expansion to cause wing blisters, suggesting that tensin strengthens integrin adhesion. The localization of tensin requires integrins, talin, and integrin-linked kinase. The N-terminal domain and C-terminal PTB domain of tensin provide essential recruitment signals. The intervening SH2 domain is not localized on its own. We suggest a model where tensin is recruited to sites of integrin adhesion via its PTB and N-terminal domains, localizing the SH2 domain so that it can interact with phosphotyrosine-containing proteins, which stabilize the integrin link to the cytoskeleton.

  15. Fetal and adult hematopoietic stem cells require beta1 integrin function for colonizing fetal liver, spleen, and bone marrow

    DEFF Research Database (Denmark)

    Potocnik, A J; Brakebusch, C; Fässler, R

    2000-01-01

    hematolymphoid differentiation potential in vitro and in fetal organ cultures but were unable to seed fetal and adult hematopoietic tissues. Adult beta1 integrin null HSCs isolated from mice carrying loxP-tagged beta1 integrin alleles and ablated for beta1 integrin expression by retroviral cre transduction......Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a prerequisite for the establishment of hematopoiesis during embryogenesis and after bone marrow transplantation. We show that beta1 integrin-deficient HSCs from the para-aortic splanchnopleura and the fetal blood had...

  16. Cluster perturbation theory for calculation of electronic properties of ensembles of metal nanoclusters

    Science.gov (United States)

    Zhumagulov, Yaroslav V.; Krasavin, Andrey V.; Kashurnikov, Vladimir A.

    2018-05-01

    The method is developed for calculation of electronic properties of an ensemble of metal nanoclusters with the use of cluster perturbation theory. This method is applied to the system of gold nanoclusters. The Greens function of single nanocluster is obtained by ab initio calculations within the framework of the density functional theory, and then is used in Dyson equation to group nanoclusters together and to compute the Greens function as well as the electron density of states of the whole ensemble. The transition from insulator state of a single nanocluster to metallic state of bulk gold is observed.

  17. Age-specific function of α5β1 integrin in microglial migration during early colonization of the developing mouse cortex.

    Science.gov (United States)

    Smolders, Sophie Marie-Thérèse; Swinnen, Nina; Kessels, Sofie; Arnauts, Kaline; Smolders, Silke; Le Bras, Barbara; Rigo, Jean-Michel; Legendre, Pascal; Brône, Bert

    2017-07-01

    Microglia, the immune cells of the central nervous system, take part in brain development and homeostasis. They derive from primitive myeloid progenitors that originate in the yolk sac and colonize the brain mainly through intensive migration. During development, microglial migration speed declines which suggests that their interaction with the microenvironment changes. However, the matrix-cell interactions allowing dispersion within the parenchyma are unknown. Therefore, we aimed to better characterize the migration behavior and to assess the role of matrix-integrin interactions during microglial migration in the embryonic brain ex vivo. We focused on microglia-fibronectin interactions mediated through the fibronectin receptor α5β1 integrin because in vitro work indirectly suggested a role for this ligand-receptor pair. Using 2-photon time-lapse microscopy on acute ex vivo embryonic brain slices, we found that migration occurs in a saltatory pattern and is developmentally regulated. Most importantly, there is an age-specific function of the α5β1 integrin during microglial cortex colonization. At embryonic day (E) 13.5, α5β1 facilitates migration while from E15.5, it inhibits migration. These results indicate a developmentally regulated function of α5β1 integrin in microglial migration during colonization of the embryonic brain. © 2017 Wiley Periodicals, Inc.

  18. Probiotic-derived polyphosphate enhances the epithelial barrier function and maintains intestinal homeostasis through integrin-p38 MAPK pathway.

    Directory of Open Access Journals (Sweden)

    Shuichi Segawa

    Full Text Available Probiotics exhibit beneficial effects on human health, particularly in the maintenance of intestinal homeostasis in a complex manner notwithstanding the diversity of an intestinal flora between individuals. Thus, it is highly probable that some common molecules secreted by probiotic and/or commensal bacteria contribute to the maintenance of intestinal homeostasis and protect the intestinal epithelium from injurious stimuli. To address this question, we aimed to isolate the cytoprotective compound from a lactobacillus strain, Lactobacillus brevis SBC8803 which possess the ability to induce cytoprotective heat shock proteins in mouse small intestine. L. brevis was incubated in MRS broth and the supernatant was passed through with a 0.2-µm filter. Caco2/bbe cells were treated with the culture supernatant, and HSP27 expression was evaluated by Western blotting. HSP27-inducible components were separated by ammonium sulfate precipitation, DEAE anion exchange chromatography, gel filtration, and HPLC. Finally, we identified that the HSP27-inducible fraction was polyphosphate (poly P, a simple repeated structure of phosphates, which is a common product of lactobacilli and other bacteria associated with intestinal microflora without any definitive physiological functions. Then, poly P was synthesized by poly P-synthesizing enzyme polyphosphate kinase. The synthesized poly P significantly induced HSP27 from Caco2/BBE cells. In addition, Poly P suppressed the oxidant-induced intestinal permeability in the mouse small intestine and pharmacological inhibitors of p38 MAPK and integrins counteract its protective effect. Daily intrarectal administration of poly P (10 µg improved the inflammation grade and survival rate in 4% sodium dextran sulfate-administered mice. This study, for the first time, demonstrated that poly P is the molecule responsible for maintaining intestinal barrier actions which are mediated through the intestinal integrin β1-p38 MAPK.

  19. Experimental measurements of U60 nanocluster stability in aqueous solution

    Science.gov (United States)

    Flynn, Shannon L.; Szymanowski, Jennifer E. S.; Gao, Yunyi; Liu, Tianbo; Burns, Peter C.; Fein, Jeremy B.

    2015-05-01

    In this study, the aqueous behavior of isolated U60 nanoclusters (K16Li25[UO2(O2)OH]60)-19 was studied under several pH conditions and nanocluster concentrations to determine if the nanoclusters exhibit solid phase buffering behavior or if they exhibit behavior more like aqueous complexes. U60 is a cage cluster consisting of 60 (UO2)(O2)2(OH)2 uranyl polyhedral which share OH and O2 groups with their neighboring uranyl polyhedral, resulting in negatively charged cage clusters whose charge is at least partially offset by K+ and Li+ in the aqueous phase. Batch experiments to monitor nanocluster stability were conducted for 16 days at pH 7.5, 8.0 and 8.5 at nanocluster suspension concentrations of 1.4, 2.8 and 6.0 g/L. The aqueous concentrations of U, Li, and K, determined after 10 kDa molecular weight filtration, achieved steady-state with the nanoclusters within 24 h. The steady-state aqueous U, Li, and K concentrations were independent of solution pH, however they increased with increasing nanocluster concentration, indicating that the nanoclusters do not buffer the aqueous activities as a bulk solid phase would, but exhibit behavior that is more characteristic of dissolved aqueous complexes. The ion activity product (I.A.P.) value was calculated using two approaches: (1) treating the nanoclusters as a solid phase with an activity of one, and (2) treating the nanoclusters as aqueous complexes with a non-unit activity equal to their concentration in solution. The I.A.P. values that were calculated with non-unit activity for the nanoclusters exhibited significantly less variation as a function of nanocluster concentration compared to the I.A.P. values calculated with a nanocluster activity of one. The results yield a calculated log dissociation constant for the U60 nanoclusters of 9.2 + 0.2/-0.3 (1σ). Our findings provide a better understanding of the thermodynamic stability and behavior of U60 nanoclusters in aqueous systems, and can be used to estimate the

  20. Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease

    International Nuclear Information System (INIS)

    Werner, Christian; Boehm, Michael; Friedrich, Erik B.

    2008-01-01

    Number and function of endothelial progenitor cells (EPCs) are down-regulated in patients with coronary artery disease (CAD). Integrin-linked kinase (ILK) is a signal and adaptor protein that regulates survival of mature endothelial cells and vascular development. Here we show that EPC dysfunction in patients with CAD is paralleled by down-regulation of ILK while restoration of ILK expression rescues the migratory defect of CAD-EPCs. Human EPCs transduced with dominant-negative ILK (DN-ILK) display significantly reduced expression of CD34 + /VEGFR-2 + , DiI-Ac-LDL uptake, and Ulex europaeus lectin binding. Mechanistically, DN-ILK-transfected EPCs are characterized by decreased proliferation, while proliferation is increased in wild-type ILK-transfected EPCs. These effects are paralleled by changes in cyclin D1 expression, colony forming units, and cytoskeletal rearrangement. Functionally, ILK is necessary and sufficient for SDF-1-triggered migration and adhesion in EPCs. These data extend current knowledge about the role of ILK in EPC biology and implicate ILK as a therapeutic target in CAD.

  1. Expression and functional importance of collagen-binding integrins, alpha 1 beta 1 and alpha 2 beta 1, on virus-activated T cells

    DEFF Research Database (Denmark)

    Andreasen, Susanne Ø; Thomsen, Allan R; Koteliansky, Victor E

    2003-01-01

    decreased responses were seen upon transfer of alpha(1)-deficient activated/memory T cells. Thus, expression of alpha(1)beta(1) and alpha(2)beta(1) integrins on activated T cells is directly functionally important for generation of inflammatory responses within tissues. Finally, the inhibitory effect......Adhesive interactions are crucial to cell migration into inflammatory sites. Using murine lymphocytic choriomeningitis virus as an Ag model system, we have investigated expression and function of collagen-binding integrins, alpha(1)beta(1) and alpha(2)beta(1), on activated and memory T cells. Using...... this system and MHC tetramers to define Ag-specific T cells, we demonstrate that contrary to being VLAs, expression of alpha(1)beta(1) and alpha(2)beta(1) can be rapidly induced on acutely activated T cells, that expression of alpha(1)beta(1) remains elevated on memory T cells, and that expression of alpha(1...

  2. Research Update: Density functional theory investigation of the interactions of silver nanoclusters with guanine

    Directory of Open Access Journals (Sweden)

    Brandon B. Dale

    2017-05-01

    Full Text Available Bare and guanine-complexed silver clusters Ag n z (n = 2-6; z = 0-2 are examined using density functional theory to elucidate the geometries and binding motifs that are present experimentally. Whereas the neutral systems remain planar in this size range, a 2D-3D transition occurs at Ag 5 + for the cationic system and at Ag 4 2 + for the dicationic system. Neutral silver clusters can bind with nitrogen 3 or with the pi system of the base. However, positively charged clusters interact with nitrogen 7 and the neighboring carbonyl group. Thus, the cationic silver-DNA clusters present experimentally may preferentially interact at these sites.

  3. Molecular interactions in particular Van der Waals nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Jungclas, Hartmut; Schmidt, Lothar [Marburg Univ. (Germany). Chemistry Dept.; Komarov, Viacheslav V.; Popova, Anna M. [Marburg Univ. (Germany). Chemistry Dept.; Lomonosov Moscow State Univ. (Russian Federation). Skobeltzin Inst. of Nuclear Physics

    2017-04-01

    A method is presented to analyse the interaction energies in a nanocluster, which is consisting of three neutral molecules bound by non-covalent long range Van der Waals forces. One of the molecules (M{sub 0}) in the nanocluster has a permanent dipole moment, whereas the two other molecules (M{sub 1} and M{sub 2}) are non-polar. Analytical expressions are obtained for the numerical calculation of the dispersion and induction energies of the molecules in the considered nanocluster. The repulsive forces at short intermolecular distances are taken into account by introduction of damping functions. Dispersion and induction energies are calculated for a nanocluster with a definite geometry, in which the polar molecule M{sub 0} is a linear hydrocarbon molecule C{sub 5}H{sub 10} and M{sub 1} and M{sub 2} are pyrene molecules. The calculations are done for fixed distances between the two pyrene molecules. The results show that the induction energies in the considered three-molecular nanocluster are comparable with the dispersion energies. Furthermore, the sum of induction energies in the substructure (M{sub 0}, M{sub 1}) of the considered nanocluster is much higher than the sum of induction energies in a two-molecular nanocluster with similar molecules (M{sub 0}, M{sub 1}) because of the absence of an electrostatic field in the latter case. This effect can be explained by the essential intermolecular induction in the three-molecular nanocluster.

  4. A region in urokinase plasminogen receptor domain III controlling a functional association with alpha5beta1 integrin and tumor growth

    DEFF Research Database (Denmark)

    Chaurasia, Pratima; Aguirre-Ghiso, Julio; Liang, Olin D

    2006-01-01

    PAR(wt) or the uPAR(S245A) mutant. Transfecting uPAR(wt) into cells with low endogenous levels of uPAR, inactive integrin, low ERK activity, and a dormant phenotype in vivo restores these functions and reinstates growth in vivo. In contrast, transfection of the same cells with uPAR(S245A) elicits only very small...... and tumor growth implicates it as a possible specific target for cancer therapy....

  5. Signaling triggered by Thy-1 interaction with ß3 integrin on astrocytes is an essential step towards unraveling neuronal Thy-1 function

    Directory of Open Access Journals (Sweden)

    ANA MARIA AVALOS

    2002-01-01

    Full Text Available Thy-1 is an abundant neuronal glycoprotein in mammals. Despite such prevalence, Thy-1 function remains largely obscure in the absence of a defined ligand. Recently described evidence that Thy-1 interacts with ß3 integrin on astrocytes will be discussed. Thy-1 binding to ß3 integrin triggers tyrosine phosphorylation of focal adhesion proteins in astrocytes, thereby promoting focal adhesion formation, cell attachment and spreading. Thy-1 has been reported to modulate neurite outgrowth by triggering a cellular response in neurons. However, our data indicate that Thy-1 can also initiate signaling events that promote adhesion of adjacent astrocytes to the underlying surface. Preliminary results suggest that morphological changes observed in the actin cytoskeleton of astrocytes as a consequence of Thy-1 binding is mediated by small GTPases from the Rho family. Our findings argue that Thy-1 functions in a bimodal fashion, as a receptor on neuronal cells and as a ligand for ß3 integrin receptor on astrocytes. Since Thy-1 is implicated in the inhibition of neurite outgrowth, signaling events in astrocytes are likely to play an important role in this process

  6. Size-dependent structure of CdSe nanoclusters formed after ion implantation in MgO

    NARCIS (Netherlands)

    van Huis, MA; van Veen, A; Schut, H; Eijt, SWH; Kooi, BJ; De Hosson, JTM

    The band gap as well as the optical and structural properties of semiconductor CdSe nanoclusters change as a function of the nanocluster size. Embedded CdSe nanoclusters in MgO were created by means of sequential Cd and Se ion implantation followed by thermal annealing. Changes during annealing were

  7. A dual amplified electrochemical immunosensor for ofloxacin: Polypyrrole film-Au nanocluster as the matrix and multi-enzyme-antibody functionalized gold nanorod as the label

    International Nuclear Information System (INIS)

    Zang, Shuai; Liu, Yingju; Lin, Mouhong; Kang, Jianli; Sun, Yuanming; Lei, Hongtao

    2013-01-01

    Graphical abstract: Schematic representation of the OFL electrochemical immunosensor using Au nanoclusters/PPy/GCE as the substrate and multi-HRP-GNR-Ab2 bioconjugates as the label. Highlights: ► Gold nanorod was used to load HRP and Ab 2 to form multi-HRP-GNR-Ab 2 . ► A sensitive immunosensor for ofloxacin was constructed using the homemade antibody. ► A dual signal amplified strategy was based on the PPy-Au and multi-HRP-GNR-Ab 2 . -- Abstract: In this work, an electrochemical immunosensor, basing on a dual signal amplified strategy by employing a biocompatible polypyrrole film-Au nanocluster matrix as a sensor platform and multi-enzyme-antibody functionalized gold nanorod as an electrochemical detection label, is established for sensitive detection of ofloxacin (OFL). Firstly, polypyrrole film and Au nanoclusters were progressively fabricated onto the surface of a glassy carbon electrode via electropolymerization and electrochemical deposition, respectively. Such PPy-Au nanocomposite modified electrode was used to immobilize OFL-OVA, blocked with the blocking reagent, and then associated with the corresponding antibody. Secondly, gold nanorod (GNR) was synthesized to load horseradish peroxidase (HRP) and horseradish peroxidase-secondary antibody (HRP-Ab 2 ), and the resulting nanostructure (multi-HRP-GNR-Ab 2 ) was applied as the detection label. The fabrication process of the ordered multilayer structure and immunosensor were characterized by scanning electron microscopy (SEM) and electrochemical measurements, respectively. Finally, based on a competitive immunoassay, i.e., the association ability with the corresponding antibody between the captured antigen and free OFL in the solution, the fabricated immunosensor exhibited a sensitive response to OFL in the range from 0.08 to 410 ng/mL with a detection limit of 0.03 ng/mL. The current immunosensor exhibited good sensitivity, selectivity and long-term stability. This amplification strategy shows excellent

  8. The newcomer in the integrin family: Integrin α9 in biology and cancer

    DEFF Research Database (Denmark)

    Høye, Anette Melissa; Couchman, John Robert; Wewer, Ulla M.

    2012-01-01

    Integrins are heterodimeric transmembrane receptors regulating cell-cell and cell-extracellular matrix interactions. Of the 24 integrin heterodimers identified in humans, a9ß1 integrin is one of the least studied. a9, together with a4, comprise a more recent evolutionary sub-family of integrins...... of cell types, interacts with many ligands for example fibronectin, tenascin-C and ADAM12, and has been shown to have important functions in processes such as cell adhesion and migration, lung development, lymphatic and venous valve development, and in wound healing. This has sparked an interest...

  9. Characterization of Laminin Binding Integrin Internalization in Prostate Cancer Cells†

    Science.gov (United States)

    Das, Lipsa; Anderson, Todd A.; Gard, Jaime M.C.; Sroka, Isis C.; Strautman, Stephanie R.; Nagle, Raymond B.; Morrissey, Colm; Knudsen, Beatrice S.; Cress, Anne E.

    2017-01-01

    Laminin binding integrins α6 (CD49f) and α3 (CD49c) are persistently but differentially expressed in prostate cancer (PCa). Integrin internalization is an important determinant of their cell surface expression and function. Using flow cytometry, and first order kinetic modelling, we quantitated the intrinsic internalization rates of integrin subunits in a single cycle of internalization. In PCa cell line DU145, α6 integrin internalized with a rate constant (kactual) of 3.25min−1, 3-fold faster than α3 integrin (1.0 min−1), 1.5-fold faster than the vitronectin binding αv integrin (CD51) (2.2 min−1), and significantly slower than the unrelated transferrin receptor (CD71) (15 min−1). Silencing of α3 integrin protein expression in DU145, PC3 and PC3B1 cells resulted in up to a 1.71-fold increase in kactual for α6 integrin. The internalized α6 integrin was targeted to early endosomes but not to lamp1 vesicles. Depletion of α3 integrin expression resulted in redistribution of α6β4 integrin to an observed cell-cell staining pattern that is consistent with a suprabasal distribution observed in epidermis and early PIN lesions in PCa. Depletion of α3 integrin increased cell migration by 1.8 fold, which was dependent on α6β1 integrin. Silencing of α6 integrin expression however, had no significant effect on the kactual of α3 integrin or its distribution in early endosomes. These results indicate that α3 and α6 integrins have significantly different internalization kinetics and that coordination exists between them for internalization. This article is protected by copyright. All rights reserved PMID:27509031

  10. Characterization of Laminin Binding Integrin Internalization in Prostate Cancer Cells.

    Science.gov (United States)

    Das, Lipsa; Anderson, Todd A; Gard, Jaime M C; Sroka, Isis C; Strautman, Stephanie R; Nagle, Raymond B; Morrissey, Colm; Knudsen, Beatrice S; Cress, Anne E

    2017-05-01

    Laminin binding integrins α6 (CD49f) and α3 (CD49c) are persistently but differentially expressed in prostate cancer (PCa). Integrin internalization is an important determinant of their cell surface expression and function. Using flow cytometry, and first order kinetic modeling, we quantitated the intrinsic internalization rates of integrin subunits in a single cycle of internalization. In PCa cell line DU145, α6 integrin internalized with a rate constant (k actual ) of 3.25 min -1 , threefold faster than α3 integrin (1.0 min -1 ), 1.5-fold faster than the vitronectin binding αv integrin (CD51) (2.2 min -1 ), and significantly slower than the unrelated transferrin receptor (CD71) (15 min -1 ). Silencing of α3 integrin protein expression in DU145, PC3, and PC3B1 cells resulted in up to a 1.71-fold increase in k actual for α6 integrin. The internalized α6 integrin was targeted to early endosomes but not to lamp1 vesicles. Depletion of α3 integrin expression resulted in redistribution of α6β4 integrin to an observed cell-cell staining pattern that is consistent with a suprabasal distribution observed in epidermis and early PIN lesions in PCa. Depletion of α3 integrin increased cell migration by 1.8-fold, which was dependent on α6β1 integrin. Silencing of α6 integrin expression however, had no significant effect on the k actual of α3 integrin or its distribution in early endosomes. These results indicate that α3 and α6 integrins have significantly different internalization kinetics and that coordination exists between them for internalization. J. Cell. Biochem. 118: 1038-1049, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. The functional interactions between CD98, beta 1-integrins, and CD147 in the induction of U937 homotypic aggregation

    Czech Academy of Sciences Publication Activity Database

    Cho, J. Y.; Fox, D. A.; Hořejší, Václav; Sagawa, K.; Skubitz, K. M.; Katz, D. R.; Chain, B.

    2001-01-01

    Roč. 98, č. 2 (2001), s. 374-382 ISSN 0006-4971 R&D Projects: GA ČR GA310/99/0349 Institutional research plan: CEZ:AV0Z5052915 Keywords : integrin * CD98 * CD147 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.273, year: 2001

  12. Atomic structure of embedded Fe nanoclusters as a function of host matrix material: a synchrotron radiation study

    International Nuclear Information System (INIS)

    Baker, S H; Roy, M; Gurman, S J; Louch, S; Bleloch, A; Binns, C

    2004-01-01

    The atomic structure of Fe nanoclusters embedded in a range of matrix materials has been studied using synchrotron radiation. In particular, the effect of embedding the clusters in Ag, amorphous carbon (a-C) and a porous C 60 matrix is investigated. The embedded cluster samples were prepared by co-deposition using a gas aggregation cluster source. Samples with both dilute and high-volume-filling fraction of clusters, at 4 and 40% respectively, were prepared. Fe K edge EXAFS measurements were used to probe the structure within the clusters. In a Ag matrix, the Fe clusters retain the b.c.c. structure of bulk Fe while in a-C there is evidence for both b.c.c. and f.c.c. structures in the clusters. These results are independent of cluster volume-filling fraction over the range investigated. When embedded in a porous C 60 matrix, the Fe clusters oxidize to Fe 2 O 3

  13. Fabrication of transferrin functionalized gold nanoclusters/graphene oxide nanocomposite for turn-on near-infrared fluorescent bioimaging of cancer cells and small animals.

    Science.gov (United States)

    Wang, Yong; Chen, Jia-Tong; Yan, Xiu-Ping

    2013-02-19

    Transferrin (Tf)-functionalized gold nanoclusters (Tf-AuNCs)/graphene oxide (GO) nanocomposite (Tf-AuNCs/GO) was fabricated as a turn-on near-infrared (NIR) fluorescent probe for bioimaging cancer cells and small animals. A one-step approach was developed to prepare Tf-AuNCs via a biomineralization process with Tf as the template. Tf acted not only as a stabilizer and a reducer but also as a functional ligand for targeting the transferrin receptor (TfR). The prepared Tf-AuNCs gave intense NIR fluorescence that can avoid interference from biological media such as tissue autofluorescence and scattering light. The assembly of Tf-AuNCs and GO gave the Tf-AuNCs/GO nanocomposite, a turn-on NIR fluorescent probe with negligible background fluorescence due to the super fluorescence quenching property of GO. The NIR fluorescence of the Tf-AuNCs/GO nanocomposite was effectively restored in the presence of TfR, due to the specific interaction between Tf and TfR and the competition of TfR with the GO for the Tf in Tf-AuNCs/GO composite. The developed turn-on NIR fluorescence probe offered excellent water solubility, stability, and biocompatibility, and exhibited high specificity to TfR with negligible cytotoxicity. The probe was successfully applied for turn-on fluorescent bioimaging of cancer cells and small animals.

  14. Density functional investigation of the adsorption effects of PH3 and SH2 on the structure stability of the Au55 and Pt55 nanoclusters

    Science.gov (United States)

    Guedes-Sobrinho, Diego; Chaves, Anderson S.; Piotrowski, Maurício J.; Da Silva, Juarez L. F.

    2017-04-01

    Although several studies have been reported for Pt55 and Au55 nanoclusters, our atomistic understanding of the interplay between the adsorbate-surface interactions and the mechanisms that lead to the formation of the distorted reduced core (DRC) structures, instead of the icosahedron (ICO) structure in gas phase, is still far from satisfactory. Here, we report a density functional theory (DFT) investigation of the role of the adsorption effects of PH3 (one lone pair of electrons) and SH2 (two lone pairs) on the relative stability of the Pt55 and Au55 nanoclusters. In gas phase, we found that the DRC structures with 7 and 9 atoms in the core region are about 5.34 eV (Pt55) and 2.20 eV (Au55) lower in energy than the ICO model with Ih symmetry and 13 atoms in the core region. However, the stability of the ICO structure increases by increasing the number of adsorbed molecules from 1 to 18, in which both DRC and ICO structures are nearly degenerate in energy at the limit of 18 ligands, which can be explained as follows. In gas phase, there is a strong compression of the cationic core region by the anionic surface atoms induced by the attractive Coulomb interactions (core+-surface-), and hence, the strain release is obtained by reducing the number of atoms in the cationic core region, which leads to the 55 atoms distorted reduced core structures. Thus, the Coulomb interactions between the core+ and surface- contribute to break the symmetry in the ICO55 structure. On the other hand, the addition of ligands on the anionic surface reduces the charge transfer between the core and surface, which contributes to decrease the Coulomb interactions and the strain on the core region of the ICO structure, and hence, it stabilizes a compact ICO structure. The same conclusion is obtained by adding van der Waals corrections to the plain DFT calculations. Similar results are obtained by the addition of steric effects, which are considered through the adsorption of triphenylphosphine

  15. Density functional investigation of the adsorption effects of PH3 and SH2 on the structure stability of the Au55 and Pt55 nanoclusters.

    Science.gov (United States)

    Guedes-Sobrinho, Diego; Chaves, Anderson S; Piotrowski, Maurício J; Da Silva, Juarez L F

    2017-04-28

    Although several studies have been reported for Pt 55 and Au 55 nanoclusters, our atomistic understanding of the interplay between the adsorbate-surface interactions and the mechanisms that lead to the formation of the distorted reduced core (DRC) structures, instead of the icosahedron (ICO) structure in gas phase, is still far from satisfactory. Here, we report a density functional theory (DFT) investigation of the role of the adsorption effects of PH 3 (one lone pair of electrons) and SH 2 (two lone pairs) on the relative stability of the Pt 55 and Au 55 nanoclusters. In gas phase, we found that the DRC structures with 7 and 9 atoms in the core region are about 5.34 eV (Pt 55 ) and 2.20 eV (Au 55 ) lower in energy than the ICO model with I h symmetry and 13 atoms in the core region. However, the stability of the ICO structure increases by increasing the number of adsorbed molecules from 1 to 18, in which both DRC and ICO structures are nearly degenerate in energy at the limit of 18 ligands, which can be explained as follows. In gas phase, there is a strong compression of the cationic core region by the anionic surface atoms induced by the attractive Coulomb interactions (core + -surface - ), and hence, the strain release is obtained by reducing the number of atoms in the cationic core region, which leads to the 55 atoms distorted reduced core structures. Thus, the Coulomb interactions between the core + and surface - contribute to break the symmetry in the ICO 55 structure. On the other hand, the addition of ligands on the anionic surface reduces the charge transfer between the core and surface, which contributes to decrease the Coulomb interactions and the strain on the core region of the ICO structure, and hence, it stabilizes a compact ICO structure. The same conclusion is obtained by adding van der Waals corrections to the plain DFT calculations. Similar results are obtained by the addition of steric effects, which are considered through the adsorption of

  16. Elucidating the role of select cytoplasmic proteins in altering diffusion of integrin receptors.

    Science.gov (United States)

    Sander, Suzanne; Arora, Neha; Smith, Emily A

    2012-06-01

    Cytoplasmic proteins that affect integrin diffusion in the cell membrane are identified using a combination of fluorescence recovery after photobleaching (FRAP) and RNA interference. Integrin receptors are essential for many cellular events, and alterations in lateral diffusion are one mechanism for modulating their function. In cells expressing native cytoplasmic protein concentrations and spread on a slide containing integrin extracellular ligand, 45 ± 2% of the integrin is mobile with a time-dependent 5.2 ± 0.9 × 10(-9) cm(2)/s diffusion coefficient at 1 s. The time exponent is 0.90 ± 0.07, indicating integrin diffusion moderately slows at longer times. The role of a specific cytoplasmic protein in altering integrin diffusion is revealed through changes in the FRAP curve after reducing the cytoplasmic protein's expression. Decreased expression of cytoplasmic proteins rhea, focal adhesion kinase (FAK), or steamer duck decreases the integrin mobile fraction. For rhea and FAK, there is a concomitant shift to Brownian (i.e., time-independent) diffusion at reduced concentrations of these proteins. In contrast, when the expression of actin 42A, dreadlocks, paxillin, integrin-linked kinase (ILK), or vinculin is reduced, integrin diffusion generally becomes more constrained with an increase in the integrin mobile fraction. This same change in integrin diffusion is measured in the absence of integrin extracellular ligand. The results indicate breaking the extracellular ligand-integrin-cytoskeletal linkage alters integrin diffusion properties, and, in most cases, there is no correlation between integrin and lipid diffusion properties.

  17. Structural insight into the function of myelin basic protein as a ligand for integrin αMβ2

    DEFF Research Database (Denmark)

    Stapulionis, Romualdas; Oliveira, Cristiano; Gjelstrup, Mikkel Carstensen

    2008-01-01

    protein (MBP), a major autoantigen in MS, is a potent and specific ligand for the integrin αMβ2 (Mac-1, CD11b/CD18) expressed mainly on phagocytic cells. MBP undergoes a dramatic conformational change when liberated from the lipid-rich environment of the myelin sheath. The MS drug glatiramer acetate......Multiple sclerosis (MS) is an inflammatory disease where phagocytic cells infiltrate the nerve tissue and act as terminal agents in destruction of the myelin sheath. However, the mechanism that triggers the ability of these cells to recognize myelin remains obscure. We show that myelin basic...

  18. Large gradient high magnetic fields affect osteoblast ultrastructure and function by disrupting collagen I or fibronectin/αβ1 integrin.

    Directory of Open Access Journals (Sweden)

    Ai-Rong Qian

    Full Text Available The superconducting magnet generates a field and field gradient product that can levitate diamagnetic materials. In this study a specially designed superconducting magnet with a large gradient high magnetic field (LG-HMF, which can provide three apparent gravity levels (μ-g, 1-g, and 2-g, was used to simulate a space-like gravity environment. The effects of LG-HMF on the ultrastructure and function of osteoblast-like cells (MG-63 and MC3T3-E1 and the underlying mechanism were investigated by transmission electromicroscopy (TEM, MTT, and cell western (ICW assays. Under LG-HMF significant morphologic changes in osteoblast-like cells occurred, including expansion of endoplasmic reticulum and mitochondria, an increased number of lysosomes, distorted microvilli, and aggregates of actin filaments. Compared to controls, cell viability and alkaline phosphatase (ALP secretion were significantly increased, and collagen I (col I, fibronectin (FN, vinculin, integrin α3, αv, and β1 expression were changed under LG-HMF conditions. In conclusion, LG-HMF affects osteoblast ultrastructure, cell viability, and ALP secretion, and the changes caused by LG-HMF may be related to disrupting col I or FN/αβ1 integrin.

  19. Novel dual ligand co-functionalized fluorescent gold nanoclusters as a versatile probe for sensitive analysis of Hg(2+) and oxytetracycline.

    Science.gov (United States)

    Xu, Shenghao; Li, Xiaolin; Mao, Yaning; Gao, Teng; Feng, Xiuying; Luo, Xiliang

    2016-04-01

    In this work, we present a direct one-step strategy for rapidly preparing dual ligand co-functionalized fluorescent Au nanoclusters (NCs) by using threonine (Thr) and 11-mercaptoundecanoic acid (MUA) as assorted reductants and capping agents in aqueous solution at room temperature. Fluorescence spectra, high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and infrared (IR) spectroscopy were performed to demonstrate the optical properties and chemical composition of the as-prepared AuNCs. They possess many attractive features such as near-infrared emission (λem = 606 nm), a large Stoke's shift (>300 nm), high colloidal stability (pH, temperature, salt, and time stability), and water dispersibility. Subsequently, the as-prepared AuNCs were used as a versatile probe for "turn off" sensing of Hg(2+) based on aggregation-induced fluorescence quenching and for "turn-on" sensing of oxytetracycline (OTC). This assay provided good linearity ranging from 37.5 to 3750 nM for Hg(2+) and from 0.375 to 12.5 μM for OTC, with detection limits of 8.6 nM and 0.15 μM, respectively. Moreover, the practical application of this assay was further validated by detecting OTC in human serum samples.

  20. Ab initio Investigation of Helium in Vanadium Oxide Nanoclusters

    Science.gov (United States)

    Danielson, Thomas; Tea, Eric; Hin, Celine

    Nanostructured ferritic alloys (NFAs) are strong candidate materials for the next generation of fission reactors and future fusion reactors. They are characterized by a large number density of oxide nanoclusters dispersed throughout a BCC iron matrix, where current oxide nanoclusters are primarily comprised of Y-Ti-O compounds. The oxide nanoclusters provide the alloy with high resistance to neutron irradiation, high yield strength and high creep strength at the elevated temperatures of a reactor environment. In addition, the oxide nanoclusters serve as trapping sites for transmutation product helium providing substantially increased resistance to catastrophic cracking and embrittlement. Although the mechanical properties and radiation resistance of the existing NFAs is promising, the problem of forming large scale reactor components continues to present a formidable challenge due to the high hardness and unpredictable fracture behavior of the alloys. An alternative alloy has been previously proposed and fabricated where vanadium is added in order to form vanadium oxide nanoclusters that serve as deflection sites for crack propagation. Although experiments have shown evidence that the fracture behavior of the alloys is improved, it is unknown whether or not the vanadium oxide nanoclusters are effective trapping sites for helium. We present results obtained using density functional theory investigating the thermodynamic stability of helium with the vanadium oxide matrix to make a comparison of trapping effectiveness to traditional Y-Ti-O compounds.

  1. Cardiac integrins the ties that bind.

    Science.gov (United States)

    Simpson, D G; Reaves, T A; Shih, D T; Burgess, W; Borg, T K; Terracio, L

    1998-01-01

    An elaborate series of morphogenetic events must be precisely coordinated during development to promote the formation of the elaborate three-dimensional structure of the normal heart. In this study we focus on discussing how interconnections between the cardiac myocyte and its surrounding environment regulate cardiac form and function. In vitro experiments from our laboratories provide direct evidence that cardiac cell shape is regulated by a dynamic interaction between constituents of the extracellular matrix (ECM) and by specific members of the integrin family of matrix receptors. Our data indicates that phenotypic information is stored in the tertiary structure and chemical identity of the ECM. This information appears to be actively communicated and transduced by the α1β1 integrin molecule into an intracellular signal that regulates cardiac cell shape and myofibrillar organization. In this study we have assessed the phenotypic consequences of suppressing the expression and accumulation of the α1 integrin molecule in aligned cultures of cardiac myocytes. In related experiments we have examined how the overexpression of α2 and α5 integrin, integrins normally not present or present at very low copy number on the cell surface of neonatal cardiac myocytes, affect cardiac protein metabolism. We also consider how biochemical signals and the mechanical signals mediated by the integrins may converge on common intracellular signaling pathways in the heart. Experiments with the whole embryo culture system indicate that angiotensin II, a peptide that carries information concerning cardiac load, plays a role in controling cardiac looping and the proliferation of myofibrils during development.

  2. Synthesis and characterization of colloidal fluorescent silver nanoclusters.

    Science.gov (United States)

    Huang, Sherry; Pfeiffer, Christian; Hollmann, Jana; Friede, Sebastian; Chen, Justin Jin-Ching; Beyer, Andreas; Haas, Benedikt; Volz, Kerstin; Heimbrodt, Wolfram; Montenegro Martos, Jose Maria; Chang, Walter; Parak, Wolfgang J

    2012-06-19

    Ultrasmall water-soluble silver nanoclusters are synthesized, and their properties are investigated. The silver nanoclusters have high colloidal stability and show fluorescence in the red. This demonstrates that like gold nanoclusters also silver nanoclusters can be fluorescent.

  3. Generating Palladium Nanoclusters Inside Very Lipophilic Gel-Type Functional Resins: Preliminary Catalytic Tests in the Hydrogenation of 2-Ethyl-Anthraquinone to 2-Ethylanthrahydroquinone

    Czech Academy of Sciences Publication Activity Database

    Bombi, G.; Lora, S.; Zancato, M.; D'Archivio, A. A.; Jeřábek, Karel; Corain, B.

    2003-01-01

    Roč. 194, 1-2 (2003), s. 273-281 ISSN 1381-1169 Institutional research plan: CEZ:AV0Z4072921 Keywords : palladium nanoclusters * gel-type resins * catalyst Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 2.264, year: 2003

  4. Size effect on the adsorption and dissociation of CO{sub 2} on Co nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Haiyan; Cao, Dapeng; Fisher, Adrian [International Research Center for Soft Matter, State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Johnston, Roy L. [School of Chemistry, University of Birmingham, Edgbaston, Birmingham, B15 2TT (United Kingdom); Cheng, Daojian, E-mail: chengdj@mail.buct.edu.cn [International Research Center for Soft Matter, State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China)

    2017-02-28

    Highlights: • Co{sub 13}, Co{sub 38} and Co{sub 55} nanoclusters were predicted as the high-symmetry structures. • CO{sub 2} dissociation on the size-selected Co{sub 13}, Co{sub 38} and Co{sub 55} nanoclusters was studied. • Co{sub 55} nanocluster possesses the highest activity relevant to CO{sub 2} dissociation. • A non-monotonous behavior of the dissociation barrier of CO{sub 2} with the size was found. - Abstract: Spin-polarized density functional theory calculations were carried out to study the adsorption and dissociation properties of CO{sub 2} on size-selected Co{sub 13}, Co{sub 38} and Co{sub 55} nanoclusters. Based on genetic algorithm method, Co{sub 13}, Co{sub 38} and Co{sub 55} nanoclusters were predicted as the most stable high-symmetry structures among these Co{sub n} (n = 2–58) nanoclusters from the Gupta potential. For the adsorption of CO{sub 2}, CO and O on size-selected Co{sub 13}, Co{sub 38} and Co{sub 55} nanoclusters, the lowest adsorption strength is found for all the different adsorbates on Co{sub 55} nanocluster. For the dissociation of CO{sub 2} on these size-selected Co nanoclusters, the largest Co{sub 55} nanocluster possesses the greatest catalytic activity for the dissociation of CO{sub 2}, with the smallest reaction barrier of 0.38 eV. Our results reveal a non-monotonous behavior of the catalytic activities of Co nanoclusters on size, which is of fundamental interest for the design of new Co catalysts for the conversion of CO{sub 2}.

  5. Density functional theory study of neutral and singly-charged (NaBH{sub 4}){sub n} (n = 1–6) nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yongpeng [State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Wu, Xiangming [Ping Xiang Sports School, Jiangxi 337000 (China); Liu, Chuan [State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Huang, Shiping, E-mail: huangsp@mail.buct.edu.cn [State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China)

    2014-10-31

    Highlights: • Structures of (NaBH{sub 4}){sub n} (n = 1–6) clusters are optimized by DFT calculation. • The Kubas interaction is observed in each cationic cluster. • Hydrogen molecule interacts with attached boron atom by Kubas interaction. • Cationic NaBH{sub 4} nanoclusters exhibit more easily H{sub 2} desorption. - Abstract: We report the global minimum structures of (NaBH{sub 4}){sub n} (n = 1–6) clusters by combining the particle swarm optimization algorithm with density functional theory. A newly formed hydrogen molecule is observed in each cationic structure, and the H{sub 2} interacts with adjacent boron atom by Kubas interaction. The results of localized orbital locator and natural bond orbital analysis reveal that the hydrogen molecule interacts with attached boron atom by the σ-bond and σ{sup ∗}-antibond of H{sub 2} in [NaBH{sub 4}]{sub n}{sup +} (n = 1, 2, 3 and 5), and the σ{sup ∗}-antibond dominates this interaction in [NaBH{sub 4}]{sub 4}{sup +} and [NaBH{sub 4}]{sub 6}{sup +}. The desorption energy of the hydrogen molecule is relatively small for [NaBH{sub 4}]{sup +} (1.05 eV), [NaBH{sub 4}]{sub 2}{sup +} (0.99 eV) and [NaBH{sub 4}]{sub 3}{sup +} (0.97 eV). It is also found that the negative desorption energy of the [NaBH{sub 4}]{sub 4}{sup +} (−0.26 eV), [NaBH{sub 4}]{sub 5}{sup +} (−0.26 eV) and [NaBH{sub 4}]{sub 6}{sup +} (−0.54 eV) shows that the hydrogen molecule can be released easily.

  6. Expression of FLNa in human melanoma cells regulates the function of integrin α1β1 and phosphorylation and localisation of PKB/AKT/ERK1/2 kinases.

    Science.gov (United States)

    Krebs, Kristi; Ruusmann, Anu; Simonlatser, Grethel; Velling, Teet

    2015-12-01

    FLNa is a ubiquitous cytoskeletal protein that links transmembrane receptors, including integrins, to F-actin and functions as a signalling intermediate. We investigated FLNa's role in the function of integrin-type collagen receptors, EGF-EGFR signalling and regulation of PKB/Akt and ERK1/2. Using FLNa-deficient M2 human melanoma cells, and same cells expressing EGFP-FLNa (M2F) or its Ig-like repeats 1-8+24, 8-15+24 and 16-24, we found that in M2F and M2 8-15+24 cells, EGF induced the increased phosphorylation of PKB/Akt and ERK1/2. In M2F cells EGF induced the localisation of these kinases to cell nucleus and lamellipodia, respectively, and the ERK1/2 phosphorylation-dependent co-immunoprecipitation of FLNa with ERK1/2. Only M2F and M2 8-15+24 cells adhered to and spread on type I collagen whereas on fibronectin all cells behaved similarly. α1β1 and α2β1 were the integrin-type collagen receptors expressed on these cells with primarily α1β1 localising to focal contacts and affecting cell adhesion and migration in a manner dependent on FLNa or its Ig-like repeats 8-15. Our results suggest a role for FLNa repeats 8-15 in the α1-subunit-dependent regulation of integrin α1β1 function, EGF-EGFR signalling to PKB/Akt and ERK1/2, identify ERK1/2 in EGF-induced FLNa-associated protein complexes, and show that the function of different integrins is subjected to differential regulation by FLNa. Copyright © 2015. Published by Elsevier GmbH.

  7. Genetic analysis of beta1 integrin "activation motifs" in mice

    DEFF Research Database (Denmark)

    Czuchra, Aleksandra; Meyer, Hannelore; Legate, Kyle R

    2006-01-01

    -null phenotype in vivo. Surprisingly, neither the substitution of the tyrosines with phenylalanine nor the aspartic acid with alanine resulted in an obvious defect. These data suggest that the NPXY motifs of the beta1 integrin tail are essential for beta1 integrin function, whereas tyrosine phosphorylation...

  8. Integrin-directed modulation of macrophage responses to biomaterials.

    Science.gov (United States)

    Zaveri, Toral D; Lewis, Jamal S; Dolgova, Natalia V; Clare-Salzler, Michael J; Keselowsky, Benjamin G

    2014-04-01

    Macrophages are the primary mediator of chronic inflammatory responses to implanted biomaterials, in cases when the material is either in particulate or bulk form. Chronic inflammation limits the performance and functional life of numerous implanted medical devices, and modulating macrophage interactions with biomaterials to mitigate this response would be beneficial. The integrin family of cell surface receptors mediates cell adhesion through binding to adhesive proteins nonspecifically adsorbed onto biomaterial surfaces. In this work, the roles of integrin Mac-1 (αMβ2) and RGD-binding integrins were investigated using model systems for both particulate and bulk biomaterials. Specifically, the macrophage functions of phagocytosis and inflammatory cytokine secretion in response to a model particulate material, polystyrene microparticles were investigated. Opsonizing proteins modulated microparticle uptake, and integrin Mac-1 and RGD-binding integrins were found to control microparticle uptake in an opsonin-dependent manner. The presence of adsorbed endotoxin did not affect microparticle uptake levels, but was required for the production of inflammatory cytokines in response to microparticles. Furthermore, it was demonstrated that integrin Mac-1 and RGD-binding integrins influence the in vivo foreign body response to a bulk biomaterial, subcutaneously implanted polyethylene terephthalate. A thinner foreign body capsule was formed when integrin Mac-1 was absent (~30% thinner) or when RGD-binding integrins were blocked by controlled release of a blocking peptide (~45% thinner). These findings indicate integrin Mac-1 and RGD-binding integrins are involved and may serve as therapeutic targets to mitigate macrophage inflammatory responses to both particulate and bulk biomaterials. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells

    Science.gov (United States)

    Antonow, Michelli B.; Franco, Camila; Prado, Willian; Beckenkamp, Aline; Silveira, Gustavo P.; Buffon, Andréia; Guterres, Sílvia S.

    2017-01-01

    Doxorubicin (Dox) clinical use is limited by dose-related cardiomyopathy, becoming more prevalent with increasing cumulative doses. Previously, we developed Dox-loaded lipid-core nanocapsules (Dox-LNC) and, in this study, we hypothesized that self-assembling and interfacial reactions could be used to obtain arginylglycylaspartic acid (RGD)-surface-functionalized-Dox-LNC, which could target tumoral cells overexpressing αvβ3 integrin. Human breast adenocarcinoma cell line (MCF-7) and human glioblastoma astrocytoma (U87MG) expressing different levels of αvβ3 integrin were studied. RGD-functionalized Dox-LNC were prepared with Dox at 100 and 500 mg·mL−1 (RGD-MCMN (Dox100) and RGD-MCMN (Dox500)). Blank formulation (RGD-MCMN) had z-average diameter of 162 ± 6 nm, polydispersity index of 0.11 ± 0.04, zeta potential of +13.2 ± 1.9 mV and (6.2 ± 1.1) × 1011 particles mL−1, while RGD-MCMN (Dox100) and RGD-MCMN (Dox500) showed respectively 146 ± 20 and 215 ± 25 nm, 0.10 ± 0.01 and 0.09 ± 0.03, +13.8 ± 2.3 and +16.4 ± 1.5 mV and (6.9 ± 0.6) × 1011 and (6.1 ± 1.0) × 1011 particles mL−1. RGD complexation was 7.73 × 104 molecules per nanocapsule and Dox loading were 1.51 × 104 and 7.64 × 104 molecules per nanocapsule, respectively. RGD-functionalized nanocapsules had an improved uptake capacity by U87MG cells. Pareto chart showed that the cell viability was mainly affected by the Dox concentration and the period of treatment in both MCF-7 and U87MG. The influence of RGD-functionalization on cell viability was a determinant factor exclusively to U87MG. PMID:29271920

  10. Atomically Precise Nanocluster Assemblies Encapsulating Plasmonic Gold Nanorods.

    Science.gov (United States)

    Chakraborty, Amrita; Fernandez, Ann Candice; Som, Anirban; Mondal, Biswajit; Natarajan, Ganapati; Paramasivam, Ganesan; Lahtinen, Tanja; Häkkinen, Hannu; Nonappa, Nonappa; Pradeep, Thalappil

    2018-04-01

    We present the self-assembled structures of atomically precise, ligand-protected noble metal nanoclusters leading to encapsulation of plasmonic gold nanorods (GNRs). Unlike highly sophisticated DNA nanotechnology, our approach demonstrates a strategically simple hydrogen bonding-directed self-assembly of nanoclusters leading to octahedral nanocrystals encapsulating GNRs. Specifically, we use the p-mercaptobenzoic acid (pMBA) protected atomically precise nanocluster, Na4[Ag44(pMBA)30] and pMBA functionalized GNRs. High resolution transmission and scanning transmission electron tomographic reconstructions suggest that the geometry of the GNR surface is responsible for directing the assembly of silver nanoclusters via H-bonding leading to octahedral symmetry. Further, use of water dispersible gold nanoclusters, Au~250(pMBA)n and Au102(pMBA)44 also formed layered shells encapsulating GNRs. Such cluster assemblies on colloidal particles present a new category of precision hybrids with diverse possibilities. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Laminin-binding integrins and their tetraspanin partners as potential antimetastatic targets

    Science.gov (United States)

    Stipp, Christopher S.

    2010-01-01

    Within the integrin family of cell adhesion receptors, integrins α3β1, α6β1, α6β4 and α7β1 make up a laminin-binding subfamily. The literature is divided on the role of these laminin-binding integrins in metastasis, with different studies indicating either pro- or antimetastatic functions. The opposing roles of the laminin-binding integrins in different settings might derive in part from their unusually robust associations with tetraspanin proteins. Tetraspanins organise integrins into multiprotein complexes within discrete plasma membrane domains termed tetraspanin-enriched microdomains (TEMs). TEM association is crucial to the strikingly rapid cell migration mediated by some of the laminin-binding integrins. However, emerging data suggest that laminin-binding integrins also promote the stability of E-cadherin-based cell–cell junctions, and that tetraspanins are essential for this function as well. Thus, TEM association endows the laminin-binding integrins with both pro-invasive functions (rapid migration) and anti-invasive functions (stable cell junctions), and the composition of TEMs in different cell types might help determine the balance between these opposing activities. Unravelling the tetraspanin control mechanisms that regulate laminin-binding integrins will help to define the settings where inhibiting the function of these integrins would be helpful rather than harmful, and may create opportunities to modulate integrin activity in more sophisticated ways than simple functional blockade. PMID:20078909

  12. Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets

    Directory of Open Access Journals (Sweden)

    Marcinkiewicz C

    2017-05-01

    Full Text Available Cezary Marcinkiewicz,1,2 Jonathan A Gerstenhaber,1 Mark Sternberg,2 Peter I Lelkes,1 Giora Feuerstein1,2 1Department of Bioengineering, College of Engineering, Temple University, Philadelphia, 2Debina Diagnostic, Inc., Newton Square, PA, USA Abstract: Thromboembolic events (TEE underwrite key causes of death in developed countries. While advanced imaging technologies such as computed tomography scans serve to diagnose blood clots during acute cardiovascular events, no such technology is available in routine primary care for TEE risk assessment. Here, we describe an imaging platform technology based on bioengineered fluorescent nanodiamond particles (F-NDPs functionalized with bitistatin (Bit, a disintegrin that specifically binds to the αIIbβ3 integrin, platelet fibrinogen receptor (PFR on activated platelets. Covalent linkage of purified Bit to F-NDP was concentration-dependent and saturable, as validated by enzyme-linked immunosorbent assay using specific anti-Bit antibodies. F-NDP–Bit interacted with purified PFR, either in immobilized or soluble form. Lotrafiban, a nonpeptide, αIIbβ3 receptor antagonist, specifically blocked F-NDP–Bit–PFR complex formation. Moreover, F-NDP–Bit specifically binds to activated platelets incorporated into a clot generated by thrombin-activated rat platelet-rich plasma (PRP. Our results suggest that engineered F-NDP–Bit particles could serve as noninvasive, “real-time” optical diagnostics for clots present in blood vessels. Keywords: carbon nanoparticles, blood clots, imaging, platelet fibrinogen receptor, fluorescence, disintegrin, thromboembolic complications, thrombosis

  13. Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets.

    Science.gov (United States)

    Marcinkiewicz, Cezary; Gerstenhaber, Jonathan A; Sternberg, Mark; Lelkes, Peter I; Feuerstein, Giora

    2017-01-01

    Thromboembolic events (TEE) underwrite key causes of death in developed countries. While advanced imaging technologies such as computed tomography scans serve to diagnose blood clots during acute cardiovascular events, no such technology is available in routine primary care for TEE risk assessment. Here, we describe an imaging platform technology based on bioengineered fluorescent nanodiamond particles (F-NDPs) functionalized with bitistatin (Bit), a disintegrin that specifically binds to the α IIb β 3 integrin, platelet fibrinogen receptor (PFR) on activated platelets. Covalent linkage of purified Bit to F-NDP was concentration-dependent and saturable, as validated by enzyme-linked immunosorbent assay using specific anti-Bit antibodies. F-NDP-Bit interacted with purified PFR, either in immobilized or soluble form. Lotrafiban, a nonpeptide, α IIb β 3 receptor antagonist, specifically blocked F-NDP-Bit-PFR complex formation. Moreover, F-NDP-Bit specifically binds to activated platelets incorporated into a clot generated by thrombin-activated rat platelet-rich plasma (PRP). Our results suggest that engineered F-NDP-Bit particles could serve as noninvasive, "real-time" optical diagnostics for clots present in blood vessels.

  14. "light-on" sensing of antioxidants using gold nanoclusters

    KAUST Repository

    Hu, Lianzhe; Deng, Lin; Alsaiari, Shahad K.; Zhang, Dingyuan; Khashab, Niveen M.

    2014-01-01

    preservatives, and cosmetics has proved to be very vital. Gold nanoclusters (Au-NCs) have a core size below 2 nm and contain several metal atoms. They have interesting photophysical properties, are readily functionalized, and are safe to use in various

  15. Enhanced electrochemical water oxidation: the impact of nanoclusters and nanocavities

    NARCIS (Netherlands)

    Zhang, X.; Cao, C.; Bieberle, A.

    2017-01-01

    The structures of transition metal surfaces and metal oxides are commonly believed to have a significant effect on the catalytic reactions. Density functional theory calculations are therefore used in this study to investigate the oxygen evolution reaction (OER) over nanostructured, i.e. nanocluster

  16. Integrins and extracellular matrix in mechanotransduction

    Directory of Open Access Journals (Sweden)

    Ramage L

    2011-12-01

    Full Text Available Lindsay RamageQueen’s Medical Research Institute, University of Edinburgh, Edinburgh, UKAbstract: Integrins are a family of cell surface receptors which mediate cell–matrix and cell–cell adhesions. Among other functions they provide an important mechanical link between the cells external and intracellular environments while the adhesions that they form also have critical roles in cellular signal-transduction. Cell–matrix contacts occur at zones in the cell surface where adhesion receptors cluster and when activated the receptors bind to ligands in the extracellular matrix. The extracellular matrix surrounds the cells of tissues and forms the structural support of tissue which is particularly important in connective tissues. Cells attach to the extracellular matrix through specific cell-surface receptors and molecules including integrins and transmembrane proteoglycans. Integrins work alongside other proteins such as cadherins, immunoglobulin superfamily cell adhesion molecules, selectins, and syndecans to mediate cell–cell and cell–matrix interactions and communication. Activation of adhesion receptors triggers the formation of matrix contacts in which bound matrix components, adhesion receptors, and associated intracellular cytoskeletal and signaling molecules form large functional, localized multiprotein complexes. Cell–matrix contacts are important in a variety of different cell and tissue properties including embryonic development, inflammatory responses, wound healing, and adult tissue homeostasis. This review summarizes the roles and functions of integrins and extracellular matrix proteins in mechanotransduction.Keywords: ligand binding, α subunit, ß subunit, focal adhesion, cell differentiation, mechanical loading, cell–matrix interaction

  17. Protein mediated synthesis of fluorescent Au-nanoclusters for metal sensory coatings

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, Manja; Raff, Johannes [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Biogeochemistry

    2017-06-01

    Fluorescent Au-nanocluster were successfully synthesized and used for the selective detection of Cu{sup 2} {sup +}. The synthesized Au-BSA-nanoclusters remain functional also after immobilization and show high thermal stability. Additionally, the transfer of the protein mediated Au-nanocluster synthesis route to S-layer proteins was achieved. (The presented work is part of the project BIONEWS dealing with long-term stable cells for the set-up and regeneration of sensor and actor materials for strategic relevant metals, in particular rare earth elements).

  18. Interstitial cell migration: integrin-dependent and alternative adhesion mechanisms.

    NARCIS (Netherlands)

    Schmidt, S.; Friedl, P.H.A.

    2010-01-01

    Adhesion and migration are integrated cell functions that build, maintain and remodel the multicellular organism. In migrating cells, integrins are the main transmembrane receptors that provide dynamic interactions between extracellular ligands and actin cytoskeleton and signalling machineries. In

  19. Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking.

    Science.gov (United States)

    Lee, Hee Doo; Kim, Yeon Hyang; Kim, Doo-Sik

    2014-04-01

    Integrin trafficking, including internalization, recycling, and lysosomal degradation, is crucial for the regulation of cellular functions. Exosomes, nano-sized extracellular vesicles, are believed to play important roles in intercellular communications. This study demonstrates that exosomes released from human macrophages negatively regulate endothelial cell migration through control of integrin trafficking. Macrophage-derived exosomes promote internalization of integrin β1 in primary HUVECs. The internalized integrin β1 persistently accumulates in the perinuclear region and is not recycled back to the plasma membrane. Experimental results indicate that macrophage-derived exosomes stimulate trafficking of internalized integrin β1 to lysosomal compartments with a corresponding decrease in the integrin destined for recycling endosomes, resulting in proteolytic degradation of the integrin. Moreover, ubiquitination of HUVEC integrin β1 is enhanced by the exosomes, and exosome-mediated integrin degradation is blocked by bafilomycin A, a lysosomal degradation inhibitor. Macrophage-derived exosomes were also shown to effectively suppress collagen-induced activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway and HUVEC migration, which are both dependent on integrin β1. These observations provide new insight into the functional significance of exosomes in the regulation of integrin trafficking. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Epitopes in α8β1 and other RGD-binding integrins delineate classes of integrin-blocking antibodies and major binding loops in α subunits

    OpenAIRE

    Norihisa Nishimichi; Nagako Kawashima; Yasuyuki Yokosaki

    2015-01-01

    Identification of epitopes for integrin-blocking monoclonal antibodies (mAbs) has aided our understanding of structure-function relationship of integrins. We mapped epitopes of chicken anti-integrin-α8-subunit-blocking mAbs by mutational analyses, examining regions that harboured all mapped epitopes recognized by mAbs against other α-subunits in the RGD-binding-integrin subfamily. Six mAbs exhibited blocking function, and these mAbs recognized residues on the same W2:41-loop on the top-face o...

  1. Beyond the Matrix: The Many Non-ECM Ligands for Integrins

    Directory of Open Access Journals (Sweden)

    Bryce LaFoya

    2018-02-01

    Full Text Available The traditional view of integrins portrays these highly conserved cell surface receptors as mediators of cellular attachment to the extracellular matrix (ECM, and to a lesser degree, as coordinators of leukocyte adhesion to the endothelium. These canonical activities are indispensable; however, there is also a wide variety of integrin functions mediated by non-ECM ligands that transcend the traditional roles of integrins. Some of these unorthodox roles involve cell-cell interactions and are engaged to support immune functions such as leukocyte transmigration, recognition of opsonization factors, and stimulation of neutrophil extracellular traps. Other cell-cell interactions mediated by integrins include hematopoietic stem cell and tumor cell homing to target tissues. Integrins also serve as cell-surface receptors for various growth factors, hormones, and small molecules. Interestingly, integrins have also been exploited by a wide variety of organisms including viruses and bacteria to support infectious activities such as cellular adhesion and/or cellular internalization. Additionally, the disruption of integrin function through the use of soluble integrin ligands is a common strategy adopted by several parasites in order to inhibit blood clotting during hematophagy, or by venomous snakes to kill prey. In this review, we strive to go beyond the matrix and summarize non-ECM ligands that interact with integrins in order to highlight these non-traditional functions of integrins.

  2. Convulxin, a C-type lectin-like protein, inhibits HCASMCs functions via WAD-motif/integrin-αv interaction and NF-κB-independent gene suppression of GRO and IL-8

    Energy Technology Data Exchange (ETDEWEB)

    Shih, Chun-Ho; Chiang, Tin-Bin [Chang Gung University of Science and Technology, Guishan Dist., Taoyuan City, Taiwan (China); Wang, Wen-Jeng, E-mail: wjwang@mail.cgust.edu.tw [Chang Gung University of Science and Technology, Guishan Dist., Taoyuan City, Taiwan (China); Department of Neurological Surgery, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan City, Taiwan (China)

    2017-03-15

    Convulxin (CVX), a C-type lectin-like protein (CLPs), is a potent platelet aggregation inducer. To evaluate its potential applications in angiogenic diseases, the multimeric CVX were further explored on its mode of actions toward human coronary artery smooth muscle cells (HCASMCs). The N-terminus of β-chain of CVX (CVX-β) contains a putative disintegrin-like domain with a conserved motif upon the sequence comparison with other CLPs. Importantly, native CVX had no cytotoxic activity as examined by electrophoretic pattern. A Trp-Ala–Asp (WAD)-containing octapeptide, MTWADAEK, was thereafter synthesized and analyzed in functional assays. In the case of specific integrin antagonists as positive controls, the anti-angiogenic effects of CVX on HCASMCs were investigated by series of functional analyses. CVX showed to exhibit multiple inhibitory activities toward HCASMCs proliferation, adhesion and invasion with a dose- and integrin αvβ3-dependent fashion. However, the WAD-octapeptide exerting a minor potency could also work as an active peptidomimetic. In addition, flow cytometric analysis demonstrated both the intact CVX and synthetic peptide can specifically interact with integrin-αv on HCASMCs and CVX was shown to have a down-regulatory effect on the gene expression of CXC-chemokines, such as growth-related oncogene and interleukin-8. According to nuclear factor-κB (NF-κB) p65 translocation assay and Western blotting analysis, the NF-κB activation was not involved in the signaling events of CVX-induced gene expression. In conclusion, CVX may act as a disintegrin-like protein via the interactions of WAD-motif in CVX-β with integrin-αv on HCASMCs and it also is a gene suppressor with the ability to diminish the expression of two CXC-chemokines in a NF-κB-independent manner. Indeed, more extensive investigations are needed and might create a new avenue for the development of a novel angiostatic agent. - Highlights: • The tetrameric convulxin (CVX) with WAD

  3. Convulxin, a C-type lectin-like protein, inhibits HCASMCs functions via WAD-motif/integrin-αv interaction and NF-κB-independent gene suppression of GRO and IL-8

    International Nuclear Information System (INIS)

    Shih, Chun-Ho; Chiang, Tin-Bin; Wang, Wen-Jeng

    2017-01-01

    Convulxin (CVX), a C-type lectin-like protein (CLPs), is a potent platelet aggregation inducer. To evaluate its potential applications in angiogenic diseases, the multimeric CVX were further explored on its mode of actions toward human coronary artery smooth muscle cells (HCASMCs). The N-terminus of β-chain of CVX (CVX-β) contains a putative disintegrin-like domain with a conserved motif upon the sequence comparison with other CLPs. Importantly, native CVX had no cytotoxic activity as examined by electrophoretic pattern. A Trp-Ala–Asp (WAD)-containing octapeptide, MTWADAEK, was thereafter synthesized and analyzed in functional assays. In the case of specific integrin antagonists as positive controls, the anti-angiogenic effects of CVX on HCASMCs were investigated by series of functional analyses. CVX showed to exhibit multiple inhibitory activities toward HCASMCs proliferation, adhesion and invasion with a dose- and integrin αvβ3-dependent fashion. However, the WAD-octapeptide exerting a minor potency could also work as an active peptidomimetic. In addition, flow cytometric analysis demonstrated both the intact CVX and synthetic peptide can specifically interact with integrin-αv on HCASMCs and CVX was shown to have a down-regulatory effect on the gene expression of CXC-chemokines, such as growth-related oncogene and interleukin-8. According to nuclear factor-κB (NF-κB) p65 translocation assay and Western blotting analysis, the NF-κB activation was not involved in the signaling events of CVX-induced gene expression. In conclusion, CVX may act as a disintegrin-like protein via the interactions of WAD-motif in CVX-β with integrin-αv on HCASMCs and it also is a gene suppressor with the ability to diminish the expression of two CXC-chemokines in a NF-κB-independent manner. Indeed, more extensive investigations are needed and might create a new avenue for the development of a novel angiostatic agent. - Highlights: • The tetrameric convulxin (CVX) with WAD

  4. Cross-talk between integrins α1β1 and α2β1 in renal epithelial cells

    International Nuclear Information System (INIS)

    Abair, Tristin D.; Sundaramoorthy, Munirathinam; Chen, Dong; Heino, Jyrki; Ivaska, Johanna; Hudson, Billy G.; Sanders, Charles R.; Pozzi, Ambra; Zent, Roy

    2008-01-01

    The collagen-binding integrins α1β1 and α2β1 have profoundly different functions, yet they are often co-expressed in epithelial cells. When both integrins are expressed in the same cell, it has been suggested that α1β1 negatively regulates integrin α2β1-dependent functions. In this study we utilized murine ureteric bud (UB) epithelial cells, which express no functionally detectable levels of endogenous integrins α1β1 and α2β1, to determine the mechanism whereby this regulation occurs. We demonstrate that UB cells expressing integrin α2β1, but not α1β1 adhere, migrate and proliferate on collagen I as well as form cellular cords in 3D collagen I gels. Substitution of the transmembrane domain of the integrin α2 subunit with that of α1 results in decreased cell adhesion, migration and cord formation. In contrast, substitution of the integrin α2 cytoplasmic tail with that of α1, decreases cell migration and cord formation, but increases proliferation. When integrin α1 and α2 subunits are co-expressed in UB cells, the α1 subunit negatively regulates integrin α2β1-dependent cord formation, adhesion and migration and this inhibition requires expression of both α1 and α2 tails. Thus, we provide evidence that the transmembrane and cytoplasmic domains of the α2 integrin subunit, as well as the α1 integrin subunit, regulate integrin α2β1 cell function

  5. Experimental measurements of U24Py nanocluster behavior in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Flynn, Shannon L.; Szymanowski, Jennifer E.S.; Fein, Jeremy B. [Univ. of Notre Dame, IN (United States). Department of Civil and Environmental Engineering and Earth Sciences; Dembowski, Mateusz [Univ. of Notre Dame, IN (United States). Department of Chemistry and Biochemistry; Burns, Peter C. [Univ. of Notre Dame, IN (United States). Department of Civil and Environmental Engineering and Earth Sciences; Univ. of Notre Dame, IN (United States). Department of Chemistry and Biochemistry

    2016-07-01

    Uranyl peroxide nanoclusters may impact the mobility and partitioning of uranium at contaminated sites and could be used in the isolation of uranium during the reprocessing of nuclear waste. Their behavior in aqueous systems must be better understood to predict the environmental fate of uranyl peroxide nanoclusters and for their use in engineered systems. The aqueous stability of only one uranyl peroxide nanocluster, U60 (K{sub 16}Li{sub 44}[UO{sub 2}(O{sub 2})OH]{sub 60}), has been studied to date [Flynn, S. L., Szymanowski, J. E. S., Gao, Y., Liu, T., Burns, P. C., Fein, J. B.: Experimental measurements of U60 nanocluster stability in aqueous solution. Geochemica et Cosmochimica Acta 156, 94-105 (2015)]. In this study, we measured the aqueous stability of a second uranyl peroxide nanocluster, U24Py (Na{sub 30}[(UO{sub 2}){sub 24}(O{sub 2}){sub 24}(HP{sub 2}O{sub 7}){sub 6}(H{sub 2}P{sub 2}O{sub 7}){sub 6}]), in batch systems as a function of time, pH, and nanocluster concentration, and then compared the aqueous behavior of U24Py to U60 to determine whether the size and morphology differences result in differences in their aqueous behaviors. Systems containing U24Py nanoclusters took over 30 days to achieve steady-state concentrations of monomeric U, Na, and P, illustrating slower reaction kinetics than parallel U60 systems. Furthermore, U24Py exhibited lower stability in solution than U60, with an average of 72% of the total mass in each nanocluster suspension being associated with the U24Py nanocluster, whereas 97% was associated with the U60 nanocluster in parallel experiments [Flynn, S. L., Szymanowski, J. E. S., Gao, Y., Liu, T., Burns, P. C., Fein, J. B.: Experimental measurements of U60 nanocluster stability in aqueous solution. Geochemica et Cosmochimica Acta 156, 94-105 (2015)]. The measurements from the batch experiments were used to calculate ion activity product (IAP) values for the reaction between the U24Py nanocluster and its constituent monomeric

  6. Building machine learning force fields for nanoclusters

    Science.gov (United States)

    Zeni, Claudio; Rossi, Kevin; Glielmo, Aldo; Fekete, Ádám; Gaston, Nicola; Baletto, Francesca; De Vita, Alessandro

    2018-06-01

    We assess Gaussian process (GP) regression as a technique to model interatomic forces in metal nanoclusters by analyzing the performance of 2-body, 3-body, and many-body kernel functions on a set of 19-atom Ni cluster structures. We find that 2-body GP kernels fail to provide faithful force estimates, despite succeeding in bulk Ni systems. However, both 3- and many-body kernels predict forces within an ˜0.1 eV/Å average error even for small training datasets and achieve high accuracy even on out-of-sample, high temperature structures. While training and testing on the same structure always provide satisfactory accuracy, cross-testing on dissimilar structures leads to higher prediction errors, posing an extrapolation problem. This can be cured using heterogeneous training on databases that contain more than one structure, which results in a good trade-off between versatility and overall accuracy. Starting from a 3-body kernel trained this way, we build an efficient non-parametric 3-body force field that allows accurate prediction of structural properties at finite temperatures, following a newly developed scheme [A. Glielmo et al., Phys. Rev. B 95, 214302 (2017)]. We use this to assess the thermal stability of Ni19 nanoclusters at a fractional cost of full ab initio calculations.

  7. Evolution of embedded lithium nanoclusters in lithium implanted alumina

    International Nuclear Information System (INIS)

    Gaikwad, P.V.; Sharma, S.K.; Mukherjee, S.; Sudarshan, K.; Kshirsagar, A.; Pujari, P.K.

    2016-01-01

    High dose of ion implantation followed by annealing is considered a feasible way to generate thermally stable nanoclusters inside a transparent host matrix. Low energy (50 keV) Li ions have been implanted into single crystals of alumina with different fluence (1 × 10"1"5–1 × 10"1"7 ions/cm"2). The samples have been annealed at temperatures ranging from 500 to 1100 °C in air in step of 100 °C. Depth dependent Doppler broadening measurements have been carried out using high purity germanium detector coupled to a variable energy slow positron beam. Fractional area in the central and wing regions of Doppler broadened annihilation radiation spectrum, namely, S- and W- parameters, were evaluated from each spectrum. Any variation in positron annihilation probability with valence and core electrons which occurs on trapping of positrons at a defect site is reflected in these parameters. The effect of ion fluence and annealing temperature on evolution of defects and formation of embedded Li nanoclusters have been studied by indexing the variation in line shape S- (W-) parameter as a function of positron implantation depth. These studies supplemented by theoretical calculations confirm that with annealing up to 700 °C, vacancy clusters are created due to the aggregation of vacancies wherein Li nanoclusters are formed. On annealing at higher temperature, there is evidence for the breakdown of these Li clusters leaving behind vacancy clusters in the samples. - Highlights: • Embedded Li nanoclusters are efficiently created by annealing Li implanted Al_2O_3 crystal. • Depth dependent DBAR is a suitable method to characterize embedded nanoclusters. • The formation of Li nanoclusters is assisted by vacancy migration to form clusters. • At very high annealing temperature (>1000 °C), Li nanoclusters undergo breakdown. • e"+ annihilation at V_A_l site shows a unique observation i.e. a reduction in S-parameter.

  8. Phenomenological model of nanocluster in polymer matrix

    International Nuclear Information System (INIS)

    Oksengendler, B.L.; Turaeva, N.N.; Azimov, J.; Rashidova, S.Sh.

    2010-01-01

    The phenomenological model of matrix nanoclusters is presented based on the Wood-Saxon potential used in nuclear physics. In frame of this model the following problems have been considered: calculation of width of diffusive layer between nanocluster and matrix, definition of Tamm surface electronic state taking into account the diffusive layer width, receiving the expression for specific magnetic moment of nanoclusters taking into account the interface width. (authors)

  9. Nanocluster production for solar cell applications

    International Nuclear Information System (INIS)

    Al Dosari, Haila M.; Ayesh, Ahmad I.

    2013-01-01

    This research focuses on the fabrication and characterization of silver (Ag) and silicon (Si) nanoclusters that might be used for solar cell applications. Silver and silicon nanoclusters have been synthesized by means of dc magnetron sputtering and inert gas condensation inside an ultra-high vacuum compatible system. We have found that nanocluster size distributions can be tuned by various source parameters, such as the sputtering discharge power, flow rate of argon inert gas, and aggregation length. Quadrupole mass filter and transmission electron microscopy were used to evaluate the size distribution of Ag and Si nanoclusters. Ag nanoclusters with average size in the range of 3.6–8.3 nm were synthesized (herein size refers to the nanocluster diameter), whereas Si nanoclusters' average size was controlled to range between 2.9 and 7.4 nm by controlling the source parameters. This work illustrates the ability of controlling the Si and Ag nanoclusters' sizes by proper optimization of the operation conditions. By controlling nanoclusters' sizes, one can alter their surface properties to suit the need to enhance solar cell efficiency. Herein, Ag nanoclusters were deposited on commercial polycrystalline solar cells. Short circuit current (I SC ), open circuit voltage (V OC ), fill factor, and efficiency (η) were obtained under light source with an intensity of 30 mW/cm 2 . A 22.7% enhancement in solar cell efficiency could be measured after deposition of Ag nanoclusters, which demonstrates that Ag nanoclusters generated in this work are useful to enhance solar cell efficiency

  10. Possibility of superradiance by magnetic nanoclusters

    International Nuclear Information System (INIS)

    Yukalov, V I; Yukalova, E P

    2011-01-01

    The possibility of realizing spin superradiance by an assembly of magnetic nanoclusters is analyzed. The known obstacles for realizing such a coherent radiation by magnetic nanoclusters are their large magnetic anisotropy, strong dephasing dipole interactions, and an essential nonuniformity of their sizes. In order to give a persuasive conclusion, a microscopic theory is developed, providing an accurate description of nanocluster spin dynamics. It is shown that, despite the obstacles, it is feasible to organize such a setup that magnetic nanoclusters would produce strong superradiant emission

  11. Mechanisms of integrin-vascular endothelial growth factor receptor cross-activation in angiogenesis.

    Science.gov (United States)

    Mahabeleshwar, Ganapati H; Feng, Weiyi; Reddy, Kumar; Plow, Edward F; Byzova, Tatiana V

    2007-09-14

    The functional responses of endothelial cells are dependent on signaling from peptide growth factors and the cellular adhesion receptors, integrins. These include cell adhesion, migration, and proliferation, which, in turn, are essential for more complex processes such as formation of the endothelial tube network during angiogenesis. This study identifies the molecular requirements for the cross-activation between beta3 integrin and tyrosine kinase receptor 2 for vascular endothelial growth factor (VEGF) receptor (VEGFR-2) on endothelium. The relationship between VEGFR-2 and beta3 integrin appears to be synergistic, because VEGFR-2 activation induces beta3 integrin tyrosine phosphorylation, which, in turn, is crucial for VEGF-induced tyrosine phosphorylation of VEGFR-2. We demonstrate here that adhesion- and growth factor-induced beta3 integrin tyrosine phosphorylation are directly mediated by c-Src. VEGF-stimulated recruitment and activation of c-Src and subsequent beta3 integrin tyrosine phosphorylation are critical for interaction between VEGFR-2 and beta3 integrin. Moreover, c-Src mediates growth factor-induced beta3 integrin activation, ligand binding, beta3 integrin-dependent cell adhesion, directional migration of endothelial cells, and initiation of angiogenic programming in endothelial cells. Thus, the present study determines the molecular mechanisms and consequences of the synergism between 2 cell surface receptor systems, growth factor receptor and integrins, and opens new avenues for the development of pro- and antiangiogenic strategies.

  12. Vesicle-associated membrane protein 2 mediates trafficking of α5β1 integrin to the plasma membrane

    International Nuclear Information System (INIS)

    Hasan, Nazarul; Hu, Chuan

    2010-01-01

    Integrins are major receptors for cell adhesion to the extracellular matrix (ECM). As transmembrane proteins, the levels of integrins at the plasma membrane or the cell surface are ultimately determined by the balance between two vesicle trafficking events: endocytosis of integrins at the plasma membrane and exocytosis of the vesicles that transport integrins. Here, we report that vesicle-associated membrane protein 2 (VAMP2), a SNARE protein that mediates vesicle fusion with the plasma membrane, is involved in the trafficking of α5β1 integrin. VAMP2 was present on vesicles containing endocytosed β1 integrin. Small interfering RNA (siRNA) silencing of VAMP2 markedly reduced cell surface α5β1 and inhibited cell adhesion and chemotactic migration to fibronectin, the ECM ligand of α5β1, without altering cell surface expression of α2β1 integrin or α3β1 integrin. By contrast, silencing of VAMP8, another SNARE protein, had no effect on cell surface expression of the integrins or cell adhesion to fibronectin. In addition, VAMP2-mediated trafficking is involved in cell adhesion to collagen but not to laminin. Consistent with disruption of integrin functions in cell proliferation and survival, VAMP2 silencing diminished proliferation and triggered apoptosis. Collectively, these data indicate that VAMP2 mediates the trafficking of α5β1 integrin to the plasma membrane and VAMP2-dependent integrin trafficking is critical in cell adhesion, migration and survival.

  13. LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin

    Energy Technology Data Exchange (ETDEWEB)

    Kawamoto, Eiji [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507 (Japan); Okamoto, Takayuki, E-mail: okamotot@doc.medic.mie-u.ac.jp [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Takagi, Yoshimi [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Honda, Goichi [Medical Affairs Department, Asahi Kasei Pharma Corporation, 1-105 Kanda Jinbo-cho, Chiyoda-ku, Tokyo 101-8101 (Japan); Suzuki, Koji [Faculty of Pharmaceutical Science, Suzuka University of Medical Science, 3500-3, Minamitamagaki-cho, Suzuka, Mie 513-8679 (Japan); Imai, Hiroshi [Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507 (Japan); Shimaoka, Motomu, E-mail: shimaoka@doc.medic.mie-u.ac.jp [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan)

    2016-05-13

    LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins regulate leukocyte trafficking in health and disease by binding primarily to IgSF ligand ICAM-1 and ICAM-2 on endothelial cells. Here we have shown that the anti-coagulant molecule thrombomodulin (TM), found on the surface of endothelial cells, functions as a potentially new ligand for leukocyte integrins. We generated a recombinant extracellular domain of human TM and Fc fusion protein (TM-domains 123-Fc), and showed that pheripheral blood mononuclear cells (PBMCs) bind to TM-domains 123-Fc dependent upon integrin activation. We then demonstrated that αL integrin-blocking mAb, αM integrin-blocking mAb, and β2 integrin-blocking mAb inhibited the binding of PBMCs to TM-domains 123-Fc. Furthermore, we show that the serine/threonine-rich domain (domain 3) of TM is required for the interaction with the LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins to occur on PBMCs. These results demonstrate that the LFA-1 and Mac-1 integrins on leukocytes bind to TM, thereby establishing the molecular and structural basis underlying LFA-1 and Mac-1 integrin interaction with TM on endothelial cells. In fact, integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells. - Highlights: • LFA-1 and Mac-1 integrins bind to the anti-coagulant molecule thrombomodulin. • The serine/threonine-rich domain of thrombomodulin is essential to interact with the LFA-1 and Mac-1 integrins on PBMCs. • Integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells.

  14. Loss of ADAM9 expression impairs β1 integrin endocytosis, focal adhesion formation and cancer cell migration

    DEFF Research Database (Denmark)

    Mygind, Kasper J; Schwarz, Jeanette; Sahgal, Pranshu

    2018-01-01

    knockdown increases β1 integrin levels through mechanisms that are independent of its protease activity. In ADAM9-silenced cells, adhesion to collagen and fibronectin is reduced, suggesting an altered function of the accumulated integrins. Mechanistically, ADAM9 co-immunoprecipitates with β1 integrin......, and both internalization and subsequent degradation of β1 integrin are significantly decreased in ADAM9-silenced cells, with no effect on β1 integrin recycling. Accordingly, the formation of focal adhesions and actin stress fibres in ADAM9-silenced cells is altered, possibly explaining the reduction...

  15. Convulxin, a C-type lectin-like protein, inhibits HCASMCs functions via WAD-motif/integrin-αv interaction and NF-κB-independent gene suppression of GRO and IL-8.

    Science.gov (United States)

    Shih, Chun-Ho; Chiang, Tin-Bin; Wang, Wen-Jeng

    2017-03-15

    Convulxin (CVX), a C-type lectin-like protein (CLPs), is a potent platelet aggregation inducer. To evaluate its potential applications in angiogenic diseases, the multimeric CVX were further explored on its mode of actions toward human coronary artery smooth muscle cells (HCASMCs). The N-terminus of β-chain of CVX (CVX-β) contains a putative disintegrin-like domain with a conserved motif upon the sequence comparison with other CLPs. Importantly, native CVX had no cytotoxic activity as examined by electrophoretic pattern. A Trp-Ala-Asp (WAD)-containing octapeptide, MTWADAEK, was thereafter synthesized and analyzed in functional assays. In the case of specific integrin antagonists as positive controls, the anti-angiogenic effects of CVX on HCASMCs were investigated by series of functional analyses. CVX showed to exhibit multiple inhibitory activities toward HCASMCs proliferation, adhesion and invasion with a dose- and integrin αvβ3-dependent fashion. However, the WAD-octapeptide exerting a minor potency could also work as an active peptidomimetic. In addition, flow cytometric analysis demonstrated both the intact CVX and synthetic peptide can specifically interact with integrin-αv on HCASMCs and CVX was shown to have a down-regulatory effect on the gene expression of CXC-chemokines, such as growth-related oncogene and interleukin-8. According to nuclear factor-κB (NF-κB) p65 translocation assay and Western blotting analysis, the NF-κB activation was not involved in the signaling events of CVX-induced gene expression. In conclusion, CVX may act as a disintegrin-like protein via the interactions of WAD-motif in CVX-β with integrin-αv on HCASMCs and it also is a gene suppressor with the ability to diminish the expression of two CXC-chemokines in a NF-κB-independent manner. Indeed, more extensive investigations are needed and might create a new avenue for the development of a novel angiostatic agent. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Size-dependent structure of CdSe nanoclusters formed after ion implantation in MgO

    OpenAIRE

    van Huis, MA; van Veen, A; Schut, H; Eijt, SWH; Kooi, BJ; De Hosson, JTM

    2005-01-01

    The band gap as well as the optical and structural properties of semiconductor CdSe nanoclusters change as a function of the nanocluster size. Embedded CdSe nanoclusters in MgO were created by means of sequential Cd and Se ion implantation followed by thermal annealing. Changes during annealing were monitored using optical absorption and positron annihilation spectroscopy. High-resolution TEM on cross-sections after annealing at a temperature of 1300 K showed that clusters with a size below 5...

  17. The expanding universe of thiolated gold nanoclusters and beyond.

    Science.gov (United States)

    Jiang, De-en

    2013-08-21

    Thiolated gold nanoclusters form a universe of their own. Researchers in this field are constantly pushing the boundary of this universe by identifying new compositions and in a few "lucky" cases, solving their structures. Such solved structures, even if there are only few, provide important hints for predicting the many identified compositions that are yet to be crystallized or structure determined. Structure prediction is the most pressing issue for a computational chemist in this field. The success of the density functional theory method in gauging the energetic ordering of isomers for thiolated gold clusters has been truly remarkable, but to predict the most stable structure for a given composition remains a great challenge. In this feature article from a computational chemist's point of view, the author shows how one understands and predicts structures for thiolated gold nanoclusters based on his old and new results. To further entertain the reader, the author also offers several "imaginative" structures, claims, and challenges for this field.

  18. Diverse roles of integrin receptors in articular cartilage.

    Science.gov (United States)

    Shakibaei, M; Csaki, C; Mobasheri, A

    2008-01-01

    Integrins are heterodimeric integral membrane proteins made up of alpha and beta subunits. At least eighteen alpha and eight beta subunit genes have been described in mammals. Integrin family members are plasma membrane receptors involved in cell adhesion and active as intra- and extracellular signalling molecules in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic spread of tumour cells. Integrin beta 1 (beta1-integrin), the protein encoded by the ITGB1 gene (also known as CD29 and VLAB), is a multi-functional protein involved in cell-matrix adhesion, cell signalling, cellular defense, cell adhesion, protein binding, protein heterodimerisation and receptor-mediated activity. It is highly expressed in the human body (17.4 times higher than the average gene in the last updated revision of the human genome). The extracellular matrix (ECM) of articular cartilage is a unique environment. Interactions between chondrocytes and the ECM regulate many biological processes important to homeostasis and repair of articular cartilage, including cell attachment, growth, differentiation and survival. The beta1-integrin family of cell surface receptors appears to play a major role in mediating cell-matrix interactions that are important in regulating these fundamental processes. Chondrocyte mechanoreceptors have been proposed to incorporate beta1-integrins and mechanosensitive ion channels which link with key ECM, cytoskeletal and signalling proteins to maintain the chondrocyte phenotype, prevent chondrocyte apoptosis and regulate chondrocyte-specific gene expression. This review focuses on the expression and function of beta1-integrins in articular chondrocytes, its role in the unique biology of these cells and its distribution in cartilage.

  19. Effects of CD49d-targeted antisense-oligonucleotide on α4 integrin expression and function of acute lymphoblastic leukemia cells: Results of in vitro and in vivo studies.

    Directory of Open Access Journals (Sweden)

    Yann Duchartre

    Full Text Available We recently demonstrated the effectiveness of blocking CD49d with anti-functional antibodies or small molecule inhibitors as a rational targeted approach to the treatment of acute leukemia in combination with chemotherapy. Antisense oligonucleotide promises to be no less specific than antibodies and inhibitors, but more interesting for pharmacokinetics and pharmacodynamics. We addressed this using the published CD49d antisense drug ATL1102. In vitro, we incubated/nucleofected the ALL cell line Kasumi-2 with ATL1102. In vivo, immunodeficient hosts were engrafted with primary ALL cells and treated with ATL1102. Changes in expression of CD49d mRNA and CD49d protein, and of cooperating gene products, including ß1 integrin and CXCR4, as well as survival in the mouse experiments were quantified. We observed dose-dependent down-regulation of CD49d mRNA and protein levels and its partner integrin ß1 cell surface protein level and, up-regulation of CXCR4 surface expression. The suppression was more pronounced after nucleofection than after incubation, where down-regulation was significant only at the higher doses. In vivo effects of ATL1102 were not sufficient to translate into "clinical" benefit in the leukemia model. In summary, antisense oligonucleotides are successful tools for specifically modulating gene expression but sufficient delivery to down-regulate CD49d in vivo may be difficult to achieve.

  20. Sensitive and selective turn off-on fluorescence detection of heparin based on the energy transfer platform using the BSA-stabilized Au nanoclusters/amino-functionalized graphene oxide hybrids.

    Science.gov (United States)

    Lan, Jing; Zou, Hong Yan; Wang, Qiang; Zeng, Ping; Li, Yuan Fang; Huang, Cheng Zhi

    2016-12-01

    An ultra-sensitive and selective turn off-on fluorescence detection of heparin based on the energy transfer in the BSA-stabilized gold nanoclusters/amino-functionalized graphene oxide (BSA-AuNCs/NH 2 -GO) hybrids was successfully realized. The BSA-AuNCs containing amounts of carboxyl groups could be absorbed on the surface of NH 2 -GO through the electrostatic interaction, which resulted in the fluorescence quenching of BSA-AuNCs with high efficiency. However, heparin, possessing high density of negative charge, could compete with BSA-AuNCs to bind NH 2 -GO and block the energy transfer from BSA-AuNCs to NH 2 -GO. The fluorescence recovery of BSA-AuNCs was closely related to the amount of heparin and there was a good linear relationship between fluorescence recovery of BSA-AuNCs and heparin over the range of 100ng/mL to 30μg/mL with a detection limit of 40ng/mL. What's more, the fluorescence assay was successfully applied for heparin sensing in human serums and intracellular imaging. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Nanoclusters a bridge across disciplines

    CERN Document Server

    Jena, Purusottam

    2010-01-01

    This comprehensive book on Nanoclusters comprises sixteen authoritative chapters written by leading researchers in the field. It provides insight into topics that are currently at the cutting edge of cluster science, with the main focus on metal and metal compound systems that are of particular interest in materials science, and also on aspects related to biology and medicine. While there are numerous books on clusters, the focus on clusters as a bridge across disciplines sets this book apart from others. Delivers cutting edge coverage of cluster science Covers a broad range of topics in

  2. The role of minor alloying elements on the stability and dispersion of yttria nanoclusters in nanostructured ferritic alloys: An ab initio study

    International Nuclear Information System (INIS)

    Murali, D.; Panigrahi, B.K.; Valsakumar, M.C.; Chandra, Sharat; Sundar, C.S.; Raj, Baldev

    2010-01-01

    Nanostructured ferritic alloys derive their strength from the dispersion of oxide nanoclusters in the ferritic matrix. We have explored the relative role of minor alloying elements like Ti and Zr on the stability of nanoclusters of vacancy-Y-Ti-O by density functional theory calculations and shown that the binding energy of these clusters increases when we replace Ti with Zr. This could imply faster nucleation of the nanoclusters which, in turn, may lead to finer dispersion of nanoclusters resulting in improved performance of ferritic alloys. Further, we show a core/shell structure for these nanoclusters in which the core is enriched in Y, O, Ti while the shell is enriched in Cr.

  3. Stabilizing and Organizing Bi3 Cu4 and Bi7 Cu12 Nanoclusters in Two-Dimensional Metal-Organic Networks.

    Science.gov (United States)

    Yan, Linghao; Xia, Bowen; Zhang, Qiushi; Kuang, Guowen; Xu, Hu; Liu, Jun; Liu, Pei Nian; Lin, Nian

    2018-04-16

    Multinuclear heterometallic nanoclusters with controllable stoichiometry and structure are anticipated to possess promising catalytic, magnetic, and optical properties. Heterometallic nanoclusters with precise stoichiometry of Bi 3 Cu 4 and Bi 7 Cu 12 can be stabilized in the scaffold of two-dimensional metal-organic networks on a Cu(111) surface through on-surface metallosupramolecular self-assembly processes. The atomic structures of the nanoclusters were resolved using scanning tunneling microscopy and density functional theory calculations. The nanoclusters feature highly symmetric planar hexagonal shapes and core-shell charge modulation. The clusters are arranged as triangular lattices with a periodicity that can be tuned by choosing molecules of different size. This work shows that on-surface metallosupramolecular self-assembly creates unique possibilities for the design and synthesis of multinuclear heterometallic nanoclusters. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Absorption Spectra of CuGaSe2 and CuInSe2 Semiconducting Nanoclusters

    KAUST Repository

    Mokkath, Junais Habeeb

    2015-10-01

    The structural and optical properties of the chalcopyrite CunGanSe2n and CunInnSe2n nanoclusters (n = 2, 4, 6, and 8) are investigated as a function of the size using a combination of basin-hopping global optimization and time-dependent density functional theory. Although the lowest energy structures are found to show almost random geometries, the band gaps and absorption spectra still are subject to systematic blue shifts for decreasing cluster size in the case of CunGanSe2n, indicating strong electron confinement. The applicability of the nanoclusters in photovoltaics is discussed. © 2015 American Chemical Society.

  5. Shell model for REO{sub x} nanoclusters in amorphous SiO{sub 2}: charge trapping and electroluminescence quenching

    Energy Technology Data Exchange (ETDEWEB)

    Tiagulskyi, S.; Nazarov, A.; Tyagulskii, I.; Lysenko, V. [Lashkaryov Institute of Semiconductor Physics, National Academy of Sciences of Ukraine, Prospekt Nauki 41, 03028 Kiev (Ukraine); Rebohle, L.; Lehmann, J.; Skorupa, W. [Institute of Ion Beam Physics and Materials Research, Helmholtz-Zentrum Dresden Rossendorf e.V., POB 510119, 01314 Dresden (Germany)

    2012-06-15

    In this work charge trapping and electroluminescence (EL) quenching in rare-earth (RE) implanted SiO{sub 2} on Si as a function of injected charge into the dielectric were studied. The blocking of the luminescent REO{sub X} nanoclusters from the hot exciting electrons by negative charge trapping in a defect region (shell) located in the vicinity of the REO{sub X} nanocluster/SiO{sub 2} interface is considered as the main mechanism of EL quenching for small size (up to 10 nm) REO{sub X} nanoclusters. It is suggested that the increase of the nanoclusters size results in disordering of the SiO{sub 2} matrix but in a decrease of local blocking for excitation of the luminescent centers. (copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  6. Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and β4 integrin function in MDA-MB-231 breast cancer cells

    International Nuclear Information System (INIS)

    Lee, W.-J.; Chen, W.-K.; Wang, C.-J.; Lin, W.-L.; Tseng, T.-H.

    2008-01-01

    Hepatocyte growth factor (HGF) and its receptor, Met, known to control invasive growth program have recently been shown to play crucial roles in the survival of breast cancer patients. The diet-derived flavonoids have been reported to possess anti-invasion properties; however, knowledge on the pharmacological and molecular mechanisms in suppressing HGF/Met-mediated tumor invasion and metastasis is poorly understood. In our preliminary study, we use HGF as an invasive inducer to investigate the effect of flavonoids including apigenin, naringenin, genistein and kaempferol on HGF-dependent invasive growth of MDA-MB-231 human breast cancer cells. Results show that apigenin presents the most potent anti-migration and anti-invasion properties by Boyden chamber assay. Furthermore, apigenin represses the HGF-induced cell motility and scattering and inhibits the HGF-promoted cell migration and invasion in a dose-dependent manner. The effect of apigenin on HGF-induced signaling activation involving invasive growth was evaluated by immunoblotting analysis, it shows that apigenin blocks the HGF-induced Akt phosphorylation but not Met, ERK, and JNK phosphorylation. In addition to MDA-MB-231 cells, apigenin exhibits inhibitory effect on HGF-induced Akt phosphorylation in hepatoma SK-Hep1 cells and lung carcinoma A549 cells. By indirect immunofluorescence microscopy assay, apigenin inhibits the HGF-induced clustering of β4 integrin at actin-rich adhesive site and lamellipodia through PI3K-dependent manner. Treatment of apigenin inhibited HGF-stimulated integrin β4 function including cell-matrix adhesion and cell-endothelial cells adhesion in MDA-MB-231 cells. By Akt-siRNA transfection analysis, it confirmed that apigenin inhibited HGF-promoted invasive growth involving blocking PI3K/Akt pathway. Finally, we evaluated the effect of apigenin on HGF-promoted metastasis by lung colonization of tumor cells in nude mice and organ metastasis of tumor cells in chick embryo. By

  7. Conservation of the human integrin-type beta-propeller domain in bacteria.

    Directory of Open Access Journals (Sweden)

    Bhanupratap Chouhan

    Full Text Available Integrins are heterodimeric cell-surface receptors with key functions in cell-cell and cell-matrix adhesion. Integrin α and β subunits are present throughout the metazoans, but it is unclear whether the subunits predate the origin of multicellular organisms. Several component domains have been detected in bacteria, one of which, a specific 7-bladed β-propeller domain, is a unique feature of the integrin α subunits. Here, we describe a structure-derived motif, which incorporates key features of each blade from the X-ray structures of human αIIbβ3 and αVβ3, includes elements of the FG-GAP/Cage and Ca(2+-binding motifs, and is specific only for the metazoan integrin domains. Separately, we searched for the metazoan integrin type β-propeller domains among all available sequences from bacteria and unicellular eukaryotic organisms, which must incorporate seven repeats, corresponding to the seven blades of the β-propeller domain, and so that the newly found structure-derived motif would exist in every repeat. As the result, among 47 available genomes of unicellular eukaryotes we could not find a single instance of seven repeats with the motif. Several sequences contained three repeats, a predicted transmembrane segment, and a short cytoplasmic motif associated with some integrins, but otherwise differ from the metazoan integrin α subunits. Among the available bacterial sequences, we found five examples containing seven sequential metazoan integrin-specific motifs within the seven repeats. The motifs differ in having one Ca(2+-binding site per repeat, whereas metazoan integrins have three or four sites. The bacterial sequences are more conserved in terms of motif conservation and loop length, suggesting that the structure is more regular and compact than those example structures from human integrins. Although the bacterial examples are not full-length integrins, the full-length metazoan-type 7-bladed β-propeller domains are present, and

  8. The integrin-actin connection, an eternal love affair

    DEFF Research Database (Denmark)

    Brakebusch, Cord; Fässler, Reinhard

    2003-01-01

    Integrin receptors connect the extracellular matrix to the actin cytoskeleton. This interaction can be viewed as a cyclical liaison, which develops again and again at new adhesion sites only to cease at sites of de-adhesion. Recent work has demonstrated that multidomain proteins play crucial roles...... in the integrin-actin connection by providing a high degree of regulation adjusted to the needs of the cell. In this review we present several examples of this paradigm and with special emphasis on the ILK-PINCH-parvin complex, which amply demonstrates how structural and signalling functions are linked together....

  9. Positron confinement in embedded lithium nanoclusters

    Science.gov (United States)

    van Huis, M. A.; van Veen, A.; Schut, H.; Falub, C. V.; Eijt, S. W.; Mijnarends, P. E.; Kuriplach, J.

    2002-02-01

    Quantum confinement of positrons in nanoclusters offers the opportunity to obtain detailed information on the electronic structure of nanoclusters by application of positron annihilation spectroscopy techniques. In this work, positron confinement is investigated in lithium nanoclusters embedded in monocrystalline MgO. These nanoclusters were created by means of ion implantation and subsequent annealing. It was found from the results of Doppler broadening positron beam analysis that approximately 92% of the implanted positrons annihilate in lithium nanoclusters rather than in the embedding MgO, while the local fraction of lithium at the implantation depth is only 1.3 at. %. The results of two-dimensional angular correlation of annihilation radiation confirm the presence of crystalline bulk lithium. The confinement of positrons is ascribed to the difference in positron affinity between lithium and MgO. The nanocluster acts as a potential well for positrons, where the depth of the potential well is equal to the difference in the positron affinities of lithium and MgO. These affinities were calculated using the linear muffin-tin orbital atomic sphere approximation method. This yields a positronic potential step at the MgO||Li interface of 1.8 eV using the generalized gradient approximation and 2.8 eV using the insulator model.

  10. Direct Thy-1/alphaVbeta3 integrin interaction mediates neuron to astrocyte communication.

    Science.gov (United States)

    Hermosilla, Tamara; Muñoz, Daniel; Herrera-Molina, Rodrigo; Valdivia, Alejandra; Muñoz, Nicolás; Nham, Sang-Uk; Schneider, Pascal; Burridge, Keith; Quest, Andrew F G; Leyton, Lisette

    2008-06-01

    Thy-1 is an abundant neuronal glycoprotein of poorly defined function. We recently provided evidence indicating that Thy-1 clusters a beta3-containing integrin in astrocytes to induce tyrosine phosphorylation, RhoA activation and the formation of focal adhesions and stress fibers. To date, the alpha subunit partner of beta3 integrin in DI TNC1 astrocytes is unknown. Similarly, the ability of neuronal, membrane-bound Thy-1 to trigger astrocyte signaling via integrin engagement remains speculation. Here, evidence that alphav forms an alphavbeta3 heterodimer in DI TNC1 astrocytes was obtained. In neuron-astrocyte association assays, the presence of either anti-alphav or anti-beta3 integrin antibodies reduced cell-cell interaction demonstrating the requirement of both integrin subunits for this association. Moreover, anti-Thy-1 antibodies blocked stimulation of astrocytes by neurons but not the binding of these two cell types. Thus, neuron-astrocyte association involved binding between molecular components in addition to the Thy-1-integrin; however, the signaling events leading to focal adhesion formation in astrocytes depended exclusively on the latter interaction. Additionally, wild-type (RLD) but not mutated (RLE) Thy-1 was shown to directly interact with alphavbeta3 integrin by Surface Plasmon Resonance analysis. This interaction was promoted by divalent cations and was species-independent. Together, these results demonstrate that the alphavbeta3 integrin heterodimer interacts directly with Thy-1 present on neuronal cells to stimulate astrocytes.

  11. Formation and growth of embedded indium nanoclusters by In2+ implantation in silica

    International Nuclear Information System (INIS)

    Santhana Raman, P.; Nair, K.G.M.; Kesavamoorthy, R.; Panigrahi, B.K.; Dhara, S.; Ravichandran, V.

    2007-01-01

    Indium nanoclusters are synthesized in an amorphous silica matrix using an ion-implantation technique. Indium ions (In 2+ ) with energy of 890 keV are implanted on silica to fluences in the range of 3 x 10 16 -3 x 10 17 cm -2 . The formation of indium nanoclusters is confirmed by optical absorption spectrometry and glancing incidence X-ray diffraction studies. A low frequency Raman scattering technique is used to study the growth of embedded indium nanoclusters in the silica matrix as a function of fluence and post-implantation annealing duration. Rutherford backscattering spectrometry studies show the surface segregation of implanted indium. Photoluminescence studies indicate the formation of a small quantity of indium oxide phase in the ion-implanted samples. (orig.)

  12. Angiotensin converting enzyme (ACE and ACE2 bind integrins and ACE2 regulates integrin signalling.

    Directory of Open Access Journals (Sweden)

    Nicola E Clarke

    Full Text Available The angiotensin converting enzymes (ACEs are the key catalytic components of the renin-angiotensin system, mediating precise regulation of blood pressure by counterbalancing the effects of each other. Inhibition of ACE has been shown to improve pathology in cardiovascular disease, whilst ACE2 is cardioprotective in the failing heart. However, the mechanisms by which ACE2 mediates its cardioprotective functions have yet to be fully elucidated. Here we demonstrate that both ACE and ACE2 bind integrin subunits, in an RGD-independent manner, and that they can act as cell adhesion substrates. We show that cellular expression of ACE2 enhanced cell adhesion. Furthermore, we present evidence that soluble ACE2 (sACE2 is capable of suppressing integrin signalling mediated by FAK. In addition, sACE2 increases the expression of Akt, thereby lowering the proportion of the signalling molecule phosphorylated Akt. These results suggest that ACE2 plays a role in cell-cell interactions, possibly acting to fine-tune integrin signalling. Hence the expression and cleavage of ACE2 at the plasma membrane may influence cell-extracellular matrix interactions and the signalling that mediates cell survival and proliferation. As such, ectodomain shedding of ACE2 may play a role in the process of pathological cardiac remodelling.

  13. The Integrin Receptor in Biologically Relevant Bilayers

    DEFF Research Database (Denmark)

    Kalli, Antreas C.; Róg, Tomasz; Vattulainen, Ilpo

    2017-01-01

    /talin complex was inserted in biologically relevant bilayers that resemble the cell plasma membrane containing zwitterionic and charged phospholipids, cholesterol and sphingolipids to study the dynamics of the integrin receptor and its effect on bilayer structure and dynamics. The results of this study...... demonstrate the dynamic nature of the integrin receptor and suggest that the presence of the integrin receptor alters the lipid organization between the two leaflets of the bilayer. In particular, our results suggest elevated density of cholesterol and of phosphatidylserine lipids around the integrin....../talin complex and a slowing down of lipids in an annulus of ~30 Å around the protein due to interactions between the lipids and the integrin/talin F2–F3 complex. This may in part regulate the interactions of integrins with other related proteins or integrin clustering thus facilitating signal transduction...

  14. Atomically Precise Metal Nanoclusters for Catalytic Application

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Rongchao [Carnegie Mellon Univ., Pittsburgh, PA (United States)

    2016-11-18

    The central goal of this project is to explore the catalytic application of atomically precise gold nanoclusters. By solving the total structures of ligand-protected nanoclusters, we aim to correlate the catalytic properties of metal nanoclusters with their atomic/electronic structures. Such correlation unravel some fundamental aspects of nanocatalysis, such as the nature of particle size effect, origin of catalytic selectivity, particle-support interactions, the identification of catalytically active centers, etc. The well-defined nanocluster catalysts mediate the knowledge gap between single crystal model catalysts and real-world conventional nanocatalysts. These nanoclusters also hold great promise in catalyzing certain types of reactions with extraordinarily high selectivity. These aims are in line with the overall goals of the catalytic science and technology of DOE and advance the BES mission “to support fundamental research to understand, predict, and ultimately control matter and energy at the level of electrons, atoms, and molecules”. Our group has successfully prepared different sized, robust gold nanoclusters protected by thiolates, such as Au25(SR)18, Au28(SR)20, Au38(SR)24, Au99(SR)42, Au144(SR)60, etc. Some of these nanoclusters have been crystallographically characterized through X-ray crystallography. These ultrasmall nanoclusters (< 2 nm diameter) exhibit discrete electronic structures due to quantum size effect, as opposed to quasicontinuous band structure of conventional metal nanoparticles or bulk metals. The available atomic structures (metal core plus surface ligands) of nanoclusters serve as the basis for structure-property correlations. We have investigated the unique catalytic properties of nanoclusters (i.e. not observed in conventional nanogold catalysts) and revealed the structure-selectivity relationships. Highlights of our

  15. Zebrafish integrin-linked kinase is required in skeletal muscles for strengthening the integrin-ECM adhesion complex.

    NARCIS (Netherlands)

    Postel, R.; Vakeel, P.; Topczewski, J.; Knoll, R.; Bakkers, J.

    2008-01-01

    Mechanical instability of skeletal muscle cells is the major cause of congenital muscular dystrophy. Here we show that the zebrafish lost-contact mutant, that lacks a functional integrin-linked kinase (ilk) gene, suffers from mechanical instability of skeletal muscle fibres. With genetic and

  16. Absorption Spectra of CuGaSe2 and CuInSe2 Semiconducting Nanoclusters

    KAUST Repository

    Mokkath, Junais Habeeb; Singh, Nirpendra; Schwingenschlö gl, Udo

    2015-01-01

    The structural and optical properties of the chalcopyrite CunGanSe2n and CunInnSe2n nanoclusters (n = 2, 4, 6, and 8) are investigated as a function of the size using a combination of basin-hopping global optimization and time-dependent density

  17. Visualization of integrin Mac-1 in vivo.

    Science.gov (United States)

    Lim, Kihong; Hyun, Young-Min; Lambert-Emo, Kris; Topham, David J; Kim, Minsoo

    2015-11-01

    β2 integrins play critical roles in migration of immune cells and in the interaction with other cells, pathogens, and the extracellular matrix. Among the β2 integrins, Mac-1 (Macrophage antigen-1), composed of CD11b and CD18, is mainly expressed in innate immune cells and plays a major role in cell migration and trafficking. In order to image Mac-1-expressing cells both in live cells and mouse, we generated a knock-in (KI) mouse strain expressing CD11b conjugated with monomeric yellow fluorescent protein (mYFP). Expression of CD11b-mYFP protein was confirmed by Western blot and silver staining of CD11b-immunoprecipitates and total cell lysates from the mouse splenocytes. Mac-1-mediated functions of the KI neutrophils were comparable with those in WT cells. The fluorescence intensity of CD11b-mYFP was sufficient to image CD11b expressing cells in live mice using intravital two-photon microscopy. In vitro, dynamic changes in the intracellular localization of CD11b molecules could be measured by epifluorescent microscopy. Finally, CD11b-expressing immune cells from tissue were easily detected by flow cytometry without anti-CD11b antibody staining. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

    Energy Technology Data Exchange (ETDEWEB)

    Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J

    1998-06-29

    Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

  19. Epitopes in α8β1 and other RGD-binding integrins delineate classes of integrin-blocking antibodies and major binding loops in α subunits.

    Science.gov (United States)

    Nishimichi, Norihisa; Kawashima, Nagako; Yokosaki, Yasuyuki

    2015-09-09

    Identification of epitopes for integrin-blocking monoclonal antibodies (mAbs) has aided our understanding of structure-function relationship of integrins. We mapped epitopes of chicken anti-integrin-α8-subunit-blocking mAbs by mutational analyses, examining regions that harboured all mapped epitopes recognized by mAbs against other α-subunits in the RGD-binding-integrin subfamily. Six mAbs exhibited blocking function, and these mAbs recognized residues on the same W2:41-loop on the top-face of the β-propeller. Loop-tips sufficiently close to W2:41 (face was identified as an additional component of the epitope of one antibody, clone YZ5. Binding sequences on the two loops were conserved in virtually all mammals, and that on W3:34 was also conserved in chickens. These indicate 1) YZ5 binds both top and bottom loops, and the binding to W3:34 is by interactions to conserved residues between immunogen and host species, 2) five other blocking mAbs solely bind to W2:41 and 3) the α8 mAbs would cross-react with most mammals. Comparing with the mAbs against the other α-subunits of RGD-integrins, two classes were delineated; those binding to "W3:34 and an top-loop", and "solely W2:41", accounting for 82% of published RGD-integrin-mAbs.

  20. The loss of alpha2beta1 integrin suppresses joint inflammation and cartilage destruction in mouse models of rheumatoid arthritis.

    NARCIS (Netherlands)

    Peters, M.E.W.J.; Wendholt, D.; Strietholt, S.; Frank, S.; Pundt, N.; Korb-Pap, A.; Joosten, L.A.B.; Berg, W.B. van den; Kollias, G.; Eckes, B.; Pap, T.

    2012-01-01

    OBJECTIVE: Integrin alpha2beta1 functions as a major receptor for type I collagen on different cell types, including fibroblasts and inflammatory cells. Although in vitro data suggest a role for alpha2beta1 integrin in regulating both cell attachment and expression of matrix-degrading enzymes such

  1. Tumor suppressor KAI1 affects integrin αvβ3-mediated ovarian cancer cell adhesion, motility, and proliferation

    International Nuclear Information System (INIS)

    Ruseva, Zlatna; Geiger, Pamina Xenia Charlotte; Hutzler, Peter; Kotzsch, Matthias; Luber, Birgit; Schmitt, Manfred; Gross, Eva; Reuning, Ute

    2009-01-01

    The tetraspanin KAI1 had been described as a metastasis suppressor in many different cancer types, a function for which associations of KAI1 with adhesion and signaling receptors of the integrin superfamily likely play a role. In ovarian cancer, integrin αvβ3 correlates with tumor progression and its elevation in vitro provoked enhanced cell adhesion accompanied by significant increases in cell motility and proliferation in the presence of its major ligand vitronectin. In the present study, we characterized integrin αvβ3-mediated tumor biological effects as a function of cellular KAI1 restoration and proved for the first time that KAI1, besides its already known physical crosstalk with β1-integrins, also colocalizes with integrin αvβ3. Functionally, elevated KAI1 levels drastically increased integrin αvβ3/vitronectin-dependent ovarian cancer cell adhesion. Since an intermediate level of cell adhesive strength is required for optimal cell migration, we next studied ovarian cancer cell motility as a function of KAI1 restoration. By time lapse video microscopy, we found impaired integrin αvβ3/vitronectin-mediated cell migration most probably due to strongly enhanced cellular immobilization onto the adhesion-supporting matrix. Moreover, KAI1 reexpression significantly diminished cell proliferation. These data strongly indicate that KAI1 may suppress ovarian cancer progression by inhibiting integrin αvβ3/vitronectin-provoked tumor cell motility and proliferation as important hallmarks of the oncogenic process.

  2. Lumican alleviates hypertrophic scarring by suppressing integrin-FAK signaling

    International Nuclear Information System (INIS)

    Zhao, Yuqian; Li, Xueyong; Xu, Xiaoli; He, Zhi; Cui, Lei; Lv, Xiaoxing

    2016-01-01

    Hypertrophic scarring (HS) is an overcompensation of wound healing that increases the risk of cosmetic disfigurement and functional impairment. No gold standard has been established for the treatment or prevention of HS. Our study aims to elucidate the expression and function of lumican in the pathogenesis of HS as well as the underlying mechanism involved in this procedure. An animal model of HS (rabbit ear) was established, and the Ad-lumican vectors were locally injected. Primary fibroblasts isolated from patients with hypertrophic burn scars were used in vitro. Histological and molecular changes in HS pathogenesis were evaluated. The results showed that lumican is significantly reduced in HS tissues and fibroblasts from HS patients as compared to normal skin or cells. Lumican levels were further suppressed in response to TGF-β stimulation. However, lumican upregulation effectively thinned the scar area and inhibited fibroblast proliferation and the cell cycle. Meanwhile, Ad-lumican administration suppressed the deposition of extracellular matrix, such as collagen and CTGF. Ad-lumican injected animals or fibroblasts presented comparable integrin α 2 β 1 expression while greatly reduced phosphorylation of FAK compared to the negative control. Moreover, Ad-lumican administration largely enhanced the binding of lumican to integrin α 2 β 1 and may thus inhibit the signaling propagation of collagen-integrin α 2 β 1 . Overall, the restoration of lumican levels contributed to suppressing the HS progression by inhibiting collagen-integrin α 2 β 1 -FAK signaling. - Highlights: • Lumican is downregulated during hypertrophic scar formation. • Lumican inhibits fibroblast proliferation. • Lumican inhibits extracellular matrix deposition. • Lumican suppresses collagen-integrin-FAK signaling.

  3. The involvement of Gab1 and PI 3-kinase in β1 integrin signaling in keratinocytes

    International Nuclear Information System (INIS)

    Kuwano, Yoshihiro; Fujimoto, Manabu; Watanabe, Rei; Ishiura, Nobuko; Nakashima, Hiroko; Komine, Mayumi; Hamazaki, Tatsuo S.; Tamaki, Kunihiko; Okochi, Hitoshi

    2007-01-01

    The control of the stem cell compartment in epidermis is closely linked to the regulation of keratinocyte proliferation and differentiation. β1 integrins are expressed 2-fold higher by stem cells than transit-amplifying cells. Signaling from these β1 integrins is critical for the regulation of the epidermal stem cell compartment. To clarify the functional relevance of this differential expression of β1 integrins, we established HaCaT cells with high β1integrin expression by repeated flow cytometric sorting of this population from the parental cell line. In these obtained cells expressing β1 integrins by 5-fold, MAPK activation was markedly increased. Regarding the upstream of MAPK, Gab1 phosphorylation was also higher with high β1 integrin expression, while Shc phosphorylation was not altered. In addition, enhanced phosphatidylinositol 3-kinase activation was also observed. These observations suggest that Gab1 and phosphatidylinositol 3-kinase play pivotal roles in the β1 integrin-mediated regulation of the epidermal stem cell compartment

  4. Applications of snake venom components to modulate integrin activities in cell-matrix interactions

    Science.gov (United States)

    Marcinkiewicz, Cezary

    2013-01-01

    Snake venom proteins are broadly investigated in the different areas of life science. Direct interaction of these compounds with cells may involve a variety of mechanisms that result in diverse cellular responses leading to the activation or blocking of physiological functions of the cell. In this review, the snake venom components interacting with integrins will be characterized in context of their effect on cellular response. Currently, two major families of snake venom proteins are considered as integrin-binding molecules. The most attention has been devoted to the disintegrin family, which binds certain types of integrins through specific motifs recognized as a tri-peptide structurally localized on an integrin-binding loop. Other snake venom integrin-binding proteins belong to the C-type lectin family. Snake venom molecules bind to the cellular integrins resulting in a modulation of cell signaling and in consequence, the regulation of cell proliferation, migration and apoptosis. Therefore, snake venom research on the integrin-binding molecules may have significance in biomedicine and basic cell biology. PMID:23811033

  5. Plasmon tsunamis on metallic nanoclusters.

    Science.gov (United States)

    Lucas, A A; Sunjic, M

    2012-03-14

    A model is constructed to describe inelastic scattering events accompanying electron capture by a highly charged ion flying by a metallic nanosphere. The electronic energy liberated by an electron leaving the Fermi level of the metal and dropping into a deep Rydberg state of the ion is used to increase the ion kinetic energy and, simultaneously, to excite multiple surface plasmons around the positively charged hole left behind on the metal sphere. This tsunami-like phenomenon manifests itself as periodic oscillations in the kinetic energy gain spectrum of the ion. The theory developed here extends our previous treatment (Lucas et al 2011 New J. Phys. 13 013034) of the Ar(q+)/C(60) charge exchange system. We provide an analysis of how the individual multipolar surface plasmons of the metallic sphere contribute to the formation of the oscillatory gain spectrum. Gain spectra showing characteristic, tsunami-like oscillations are simulated for Ar(15+) ions capturing one electron in distant collisions with Al and Na nanoclusters.

  6. Enantioselective silver nanoclusters: Preparation, characterization and photoluminescence spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Farrag, Mostafa, E-mail: mostafafarrag@aun.edu.eg

    2016-09-01

    Herein, we report a new wet-synthesis method to separate some water-soluble chiral silver nanoclusters with high yield. The cluster material was obtained by the reduction of silver nitrate with NaBH{sub 4} in the presence of three ligands L-penicillamine (L-pen), D-penicillamine (D-pen) and racemic mixture of penicillamine (rac-pen), functioning as capping ligand. For characterizing all silver cluster samples, the particle size was assessed by transmission electron microscopy (TEM) and powder X-ray diffraction (XRD) and their average chemical formula was determined from thermogravimetric analysis (TGA) and elemental analysis (EA). The particles sizes of all three clusters are 2.1 ± 0.2 nm. The optical properties of the samples were studied by four different methods: UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), photoluminescence spectroscopy (PL) and circular dichroism (CD) spectroscopy. The spectra are dominated by the typical and intense plasmon peak at 486 nm accompanied by a small shoulder at 540 nm. Infrared spectroscopy was measured for the free ligand and protected silver nanoclusters, where the disappearance of the S-H vibrational band (2535–2570 cm{sup −1}) in the silver nanoclusters confirmed anchoring of ligand to the cluster surface through the sulfur atom. PL studies yielded the fluorescent properties of the samples. The main focus of this work, however, lies in the chirality of the particles. For all silver clusters CD spectra were recorded. While for clusters capped with one of the two enantiomers (D- or L-form) typical CD spectra were observed, no significant signals were detected for a racemic ligand mixture. Furthermore, silver clusters show quite large asymmetry factors (up to 3 × 10{sup −4}) in comparison to most other ligand protected clusters. These large factors and bands in the visible range of the spectrum suggest a strong chiral induction from the ligand to the metal core. Textural features of the

  7. Integrin α4 Enhances Metastasis and May Be Associated with Poor Prognosis in MYCN-low Neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Shanique A Young

    Full Text Available High-risk neuroblastoma is associated with an overall survival rate of 30-50%. Neuroblastoma-expressed cell adhesion receptors of the integrin family impact cell adhesion, migration, proliferation and survival. Integrin α4 is essential for neural crest cell motility during development, is highly expressed on leukocytes, and is critical for transendothelial migration. Thus, cancer cells that express this receptor may exhibit increased metastatic potential. We show that α4 expression in human and murine neuroblastoma cell lines selectively enhances in vitro interaction with the alternatively spliced connecting segment 1 of fibronectin, as well as vascular cell adhesion molecule-1 and increases migration. Integrin α4 expression enhanced experimental metastasis in a syngeneic tumor model, reconstituting a pattern of organ involvement similar to that seen in patients. Accordingly, antagonism of integrin α4 blocked metastasis, suggesting adhesive function of the integrin is required. However, adhesive function was not sufficient, as mutants of integrin α4 that conserved the matrix-adhesive and promigratory function in vitro were compromised in their metastatic capacity in vivo. Clinically, integrin α4 is more frequently expressed in non-MYNC amplified tumors, and is selectively associated with poor prognosis in this subset of disease. These results reveal an unexpected role for integrin α4 in neuroblastoma dissemination and identify α4 as a potential prognostic indicator and therapeutic target.

  8. The role of oxygen and water on molybdenum nanoclusters for electro catalytic ammonia production

    Directory of Open Access Journals (Sweden)

    Jakob G. Howalt

    2014-01-01

    Full Text Available The presence of water often gives rise to oxygen adsorption on catalyst surfaces through decomposition of water and the adsorbed oxygen or hydroxide species often occupy important surfaces sites, resulting in a decrease or a total hindrance of other chemical reactions taking place at that site. In this study, we present theoretical investigations of the influence of oxygen adsorption and reduction on pure and nitrogen covered molybdenum nanocluster electro catalysts for electrochemical reduction of N2 to NH3 with the purpose of understanding oxygen and water poisoning of the catalyst. Density functional theory calculations are used in combination with the computational hydrogen electrode approach to calculate the free energy profile for electrochemical protonation of O and N2 species on cuboctahedral Mo13 nanoclusters. The calculations show that the molybdenum nanocluster will preferentially bind oxygen over nitrogen and hydrogen at neutral bias, but under electrochemical reaction conditions needed for nitrogen reduction, oxygen adsorption is severely weakened and the adsorption energy is comparable to hydrogen and nitrogen adsorption. The potentials required to reduce oxygen off the surface are −0.72 V or lower for all oxygen coverages studied, and it is thus possible to (reactivate (partially oxidized nanoclusters for electrochemical ammonia production, e.g., using a dry proton conductor or an aqueous electrolyte. At lower oxygen coverages, nitrogen molecules can adsorb to the surface and electrochemical ammonia production via the associative mechanism is possible at potentials as low as −0.45 V to −0.7 V.

  9. Theoretical Studies of Nanoclusters (Briefing Charts)

    Science.gov (United States)

    2015-07-23

    nanoclusters. However, scanning transmission electron microscopy ( STEM ) measures show cluster inversion occurred to produce MgyCux(!) a) copper atoms b...methane (née CLL -1) as a potential explosive ingredient: a theoretical study”, Propellants, Explosives, Pyrotechnics 38, 9-13 (2013). Jesus Paulo L

  10. Peptide-stabilized, fluorescent silver nanoclusters

    DEFF Research Database (Denmark)

    Gregersen, Simon; Vosch, Tom André Jos; Jensen, Knud Jørgen

    2016-01-01

    Few-atom silver nanoclusters (AgNCs) can exhibit strong fluorescence; however, they require ligands to prevent aggregation into larger nanoparticles. Fluorescent AgNCs in biopolymer scaffolds have so far mainly been synthesized in solution, and peptides have only found limited use compared to DNA...

  11. Magnetic behavior of Si-Ge bond in SixGe4-x nano-clusters

    Science.gov (United States)

    Nahali, Masoud; Mehri, Ali

    2018-06-01

    The structure of SixGe4-x nano-clusters were optimized by MPW1B95 level of theory using MG3S and SDB-aug-cc-PVTZ basis set. The agreement of the calculated ionization and dissociation energies with experimental values validates the reported structures of nano-clusters and justifies the use of hybrid meta density functional method. Since the Si-Si bond is stronger than Si-Ge and Ge-Ge bonds, the Si-Si, Si-Ge, and Ge-Ge diagonal bonds determine the precedence of the stability in these nano-clusters. The hybrid meta density functional calculations were carried out to investigate the adsorption of CO on all possible SixGe4-x nano-clusters. It was found that the silicon atom generally makes a stronger bond with CO than germanium and thereby preferentially affects the shape of structures having higher multiplicity. In Si-Ge structures with higher spin more than 95% of spins accumulate on positions with less bonds to other atoms of the cluster. Through CO adsorption on these clusters bridge structures are made that behave as spin bridge which conduct the spin from the nano-cluster surface to the adsorbate atoms. A better understanding of bridged structures was achieved upon introducing the 'spin bridge' concept. Based on exhaustive spin density analysis, it was found that the reason for the extra negative charge on oxygen in the bridged structures is the relocation of spin from the surface through the bridge.

  12. Lipid raft regulates the initial spreading of melanoma A375 cells by modulating β1 integrin clustering.

    Science.gov (United States)

    Wang, Ruifei; Bi, Jiajia; Ampah, Khamal Kwesi; Zhang, Chunmei; Li, Ziyi; Jiao, Yang; Wang, Xiaoru; Ba, Xueqing; Zeng, Xianlu

    2013-08-01

    Cell adhesion and spreading require integrins-mediated cell-extracellular matrix interaction. Integrins function through binding to extracellular matrix and subsequent clustering to initiate focal adhesion formation and actin cytoskeleton rearrangement. Lipid raft, a liquid ordered plasma membrane microdomain, has been reported to play major roles in membrane motility by regulating cell surface receptor function. Here, we identified that lipid raft integrity was required for β1 integrin-mediated initial spreading of melanoma A375 cells on fibronectin. We found that lipid raft disruption with methyl-β-cyclodextrin led to the inability of focal adhesion formation and actin cytoskeleton rearrangement by preventing β1 integrin clustering. Furthermore, we explored the possible mechanism by which lipid raft regulates β1 integrin clustering and demonstrated that intact lipid raft could recruit and modify some adaptor proteins, such as talin, α-actinin, vinculin, paxillin and FAK. Lipid raft could regulate the location of these proteins in lipid raft fractions and facilitate their binding to β1 integrin, which may be crucial for β1 integrin clustering. We also showed that lipid raft disruption impaired A375 cell migration in both transwell and wound healing models. Together, these findings provide a new insight for the relationship between lipid raft and the regulation of integrins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Inhibition of Focal Adhesion Kinase Signaling by Integrin α6β1 Supports Human Pluripotent Stem Cell Self-Renewal.

    Science.gov (United States)

    Villa-Diaz, Luis G; Kim, Jin Koo; Laperle, Alex; Palecek, Sean P; Krebsbach, Paul H

    2016-07-01

    Self-renewal of human embryonic stem cells and human induced pluripotent stem cells (hiPSCs)-known as pluripotent stem cells (PSC)-is influenced by culture conditions, including the substrate on which they are grown. However, details of the molecular mechanisms interconnecting the substrate and self-renewal of these cells remain unclear. We describe a signaling pathway in hPSCs linking self-renewal and expression of pluripotency transcription factors to integrin α6β1 and inactivation of focal adhesion kinase (FAK). Disruption of this pathway results in hPSC differentiation. In hPSCs, α6β1 is the dominant integrin and FAK is not phosphorylated at Y397, and thus, it is inactive. During differentiation, integrin α6 levels diminish and Y397 FAK is phosphorylated and activated. During reprogramming of fibroblasts into iPSCs, integrin α6 is upregulated and FAK is inactivated. Knockdown of integrin α6 and activation of β1 integrin lead to FAK phosphorylation and reduction of Nanog, Oct4, and Sox2, suggesting that integrin α6 functions in inactivation of integrin β1 and FAK signaling and prevention of hPSC differentiation. The N-terminal domain of FAK, where Y397 is localized, is in the nuclei of hPSCs interacting with Oct4 and Sox2, and this immunolocalization is regulated by Oct4. hPSCs remodel the extracellular microenvironment and deposit laminin α5, the primary ligand of integrin α6β1. Knockdown of laminin α5 resulted in reduction of integrin α6 expression, phosphorylation of FAK and decreased Oct4. In conclusion, hPSCs promote the expression of integrin α6β1, and nuclear localization and inactivation of FAK to supports stem cell self-renewal. Stem Cells 2016;34:1753-1764. © 2016 AlphaMed Press.

  14. Radiation-sustained nanocluster metastability in oxide dispersion strengthened materials

    Science.gov (United States)

    Ribis, J.; Bordas, E.; Trocellier, P.; Serruys, Y.; de Carlan, Y.; Legris, A.

    2015-12-01

    ODS materials constitute a new promising class of structural materials for advanced fission and fusion energy application. These Fe-Cr based ferritic steels contain ultra-high density of dispersion-strengthening nanoclusters conferring excellent mechanical properties to the alloy. Hence, guarantee the nanocluster stability under irradiation remain a critical issue. Nanoclusters are non-equilibrium multicomponent compounds (YTiCrO) forming through a complex nucleation pathway during the elaboration process. In this paper, it is proposed to observe the response of these nanoclusters when the system is placed far from equilibrium by means of ion beam. The results indicate that the Y, Ti, O and Cr atoms self-organized so that nanoclusters coarsened but maintain their non-equilibrium chemical composition. It is discussed that the radiation-sustained nanocluster metastability emerges from cooperative effects: radiation-induced Ostwald ripening, permanent creation of vacancies in the clusters, and fast Cr diffusion mediated by interstitials.

  15. Radiation-sustained nanocluster metastability in oxide dispersion strengthened materials

    International Nuclear Information System (INIS)

    Ribis, J.; Bordas, E.; Trocellier, P.; Serruys, Y.; Carlan, Y. de; Legris, A.

    2015-01-01

    ODS materials constitute a new promising class of structural materials for advanced fission and fusion energy application. These Fe–Cr based ferritic steels contain ultra-high density of dispersion-strengthening nanoclusters conferring excellent mechanical properties to the alloy. Hence, guarantee the nanocluster stability under irradiation remain a critical issue. Nanoclusters are non-equilibrium multicomponent compounds (YTiCrO) forming through a complex nucleation pathway during the elaboration process. In this paper, it is proposed to observe the response of these nanoclusters when the system is placed far from equilibrium by means of ion beam. The results indicate that the Y, Ti, O and Cr atoms self-organized so that nanoclusters coarsened but maintain their non-equilibrium chemical composition. It is discussed that the radiation-sustained nanocluster metastability emerges from cooperative effects: radiation-induced Ostwald ripening, permanent creation of vacancies in the clusters, and fast Cr diffusion mediated by interstitials.

  16. CCM proteins control endothelial β1 integrin dependent response to shear stress

    Directory of Open Access Journals (Sweden)

    Zuzana Macek Jilkova

    2014-11-01

    Full Text Available Hemodynamic shear stress from blood flow on the endothelium critically regulates vascular function in many physiological and pathological situations. Endothelial cells adapt to shear stress by remodeling their cytoskeletal components and subsequently by changing their shape and orientation. We demonstrate that β1 integrin activation is critically controlled during the mechanoresponse of endothelial cells to shear stress. Indeed, we show that overexpression of the CCM complex, an inhibitor of β1 integrin activation, blocks endothelial actin rearrangement and cell reorientation in response to shear stress similarly to β1 integrin silencing. Conversely, depletion of CCM2 protein leads to an elongated “shear-stress-like” phenotype even in the absence of flow. Taken together, our findings reveal the existence of a balance between positive extracellular and negative intracellular signals, i.e. shear stress and CCM complex, for the control of β1 integrin activation and subsequent adaptation of vascular endothelial cells to mechanostimulation by fluid shear stress.

  17. Oncofetal chondroitin sulfate glycosaminoglycans are key players in integrin signaling and tumor cell motility

    DEFF Research Database (Denmark)

    Clausen, Thomas Mandel; Bento Ayres Pereira, Marina Maria; Al Nakouzi, Nader

    2016-01-01

    Many tumors express proteoglycans modified with oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS), which are normally restricted to the placenta. However, the role of ofCS in cancer is largely unknown. The function of ofCS in cancer was analyzed using the recombinant ofCS-binding VAR2...... revealed an overrepresentation of proteins involved in cell motility and integrin signaling, such as integrin-β1 (ITGB1) and integrin-α4 (ITGA4). Saturating concentrations of rVAR2 inhibited downstream integrin signaling, which was mimicked by knockdown of the core chondroitin sulfate synthesis enzymes β-1......,3-glucuronyltransferase 1 (B3GAT1) and chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1). The ofCS modification was highly expressed in both human and murine metastatic lesions in situ and preincubation or early intravenous treatment of tumor cells with rVAR2 inhibited seeding and spreading of tumor...

  18. Fluorescent Pressure Response of Protein-Nanocluster Polymer Composites

    Science.gov (United States)

    2016-05-01

    composites as pressure sensitive indicators of brain damage. The PNC composites are made up of protein coated gold nanoclusters and a styrene-ethylene...enhancement of the BSA- protected gold nanoclusters and the corresponding conformational changes of protein, J Phys Chem C. 2013;117:639–647...public release; distribution is unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT This research focuses on the uses of polymer gold nanocluster (PNC

  19. Modeling the photosensitizing properties of thiolate-protected gold nanoclusters.

    Science.gov (United States)

    Azarias, Cloé; Adamo, Carlo; Perrier, Aurélie

    2016-03-21

    An accurate computational strategy for studying the structural, redox and optical properties of thiolated gold nanoclusters (GNCs) using (Time-Dependent) Density Functional Theory is proposed. The influence of the pseudopotential/basis set, solvent description and the choice of the functional has been investigated to model the structural and electronic properties of the Au25(SR)18(-) system, with R being an organic ligand. This study aims to describe with a comparable precision both the GNC and the organic ligands and rationalize the effect of coating on different GNC properties. Two differently coated GNCs have been considered: the system with R = CH2CH2Ph and the GNC coated with 17 alkyl chains (C6H13) and functionalized by one fluorophore pyrene derivative (CH2CH2(NH)(CO)Py). The computational protocol we propose should then be used to design more efficient metal cluster-sensitized solar cells.

  20. Integrin-like proteins are localized to plasma membrane fractions, not plastids, in Arabidopsis

    Science.gov (United States)

    Swatzell, L. J.; Edelmann, R. E.; Makaroff, C. A.; Kiss, J. Z.

    1999-01-01

    Integrins are a large family of integral membrane proteins that function in signal transduction in animal systems. These proteins are conserved in vertebrates, invertebrates, and fungi. Evidence from previous research suggests that integrin-like proteins may be present in plants as well, and that these proteins may function in signal transduction during gravitropism. In past studies, researchers have used monoclonal and polyclonal antibodies to localize beta 1 integrin-like proteins in plants. However, there is a disparity between data collected from these studies, especially since molecular weights obtained from these investigations range from 55-120 kDa for integrin-like proteins. To date, a complete investigation which employs all three basic immunolabeling procedures, immunoblotting, immunofluorescence microscopy, and immunogold labeling, in addition to extensive fractionation and exhaustive controls, has been lacking. In this paper, we demonstrate that use of a polyclonal antibody against the cytoplasmic domain of avian beta 1-integrin can produce potential artifacts in immunolocalization studies. However, these problems can be eliminated through use of starchless mutants or proper specimen preparation prior to electrophoresis. We also show that this antibody, when applied within the described parameters and with careful controls, identifies a large (100 kDa) integrin-like protein that is localized to plasma membrane fractions in Arabidopsis.

  1. α6-Integrin alternative splicing: distinct cytoplasmic variants in stem cell fate specification and niche interaction.

    Science.gov (United States)

    Zhou, Zijing; Qu, Jing; He, Li; Peng, Hong; Chen, Ping; Zhou, Yong

    2018-05-02

    α6-Integrin subunit (also known as CD49f) is a stemness signature that has been found on the plasma membrane of more than 30 stem cell populations. A growing body of studies have focused on the critical role of α6-containing integrins (α6β1 and α6β4) in the regulation of stem cell properties, lineage-specific differentiation, and niche interaction. α6-Integrin subunit can be alternatively spliced at the post-transcriptional level, giving rise to divergent isoforms which differ in the cytoplasmic and/or extracellular domains. The cytoplasmic domain of integrins is an important functional part of integrin-mediated signals. Structural changes in the cytoplasmic domain of α6 provide an efficient means for the regulation of stem cell responses to biochemical stimuli and/or biophysical cues in the stem cell niche, thus impacting stem cell fate determination. In this review, we summarize the current knowledge on the structural variants of the α6-integrin subunit and spatiotemporal expression of α6 cytoplasmic variants in embryonic and adult stem/progenitor cells. We highlight the roles of α6 cytoplasmic variants in stem cell fate decision and niche interaction, and discuss the potential mechanisms involved. Understanding of the distinct functions of α6 splicing variants in stem cell biology may inform the rational design of novel stem cell-based therapies for a range of human diseases.

  2. Cre-loxP–mediated Inactivation of the α6A Integrin Splice Variant In Vivo: Evidence for a Specific Functional Role of α6A in Lymphocyte Migration but Not in Heart Development

    Science.gov (United States)

    Gimond, Clotilde; Baudoin, Christian; van der Neut, Ronald; Kramer, Duco; Calafat, Jero; Sonnenberg, Arnoud

    1998-01-01

    Two splice variants of the α6 integrin subunit, α6A and α6B, with different cytoplasmic domains, have previously been described. While α6B is expressed throughout the development of the mouse, the expression of α6A begins at 8.5 days post coitum and is initially restricted to the myocardium. Later in ontogeny, α6A is found in various epithelia and in certain cells of the immune system. In this study, we have investigated the function of α6A in vivo by generating knockout mice deficient for this splice variant. The Cre- loxP system of the bacteriophage P1 was used to specifically remove the exon encoding the cytoplasmic domain of α6A in embryonic stem cells, and the deletion resulted in the expression of α6B in all tissues that normally express α6A. We show that α6A−/− mice develop normally and are fertile. The substitution of α6A by α6B does not impair the development and function of the heart, hemidesmosome formation in the epidermis, or keratinocyte migration. Furthermore, T cells differentiated normally in α6A−/− mice. However, the substitution of α6A by α6B leads to a decrease in the migration of lymphocytes through laminin-coated Transwell filters and to a reduction of the number of T cells isolated from the peripheral and mesenteric lymph nodes. Lymphocyte homing to the lymph nodes, which involves various types of integrin–ligand interactions, was not affected in the α6A knockout mice, indicating that the reduced number of lymph node cells could not be directly attributed to defects in lymphocyte trafficking. Nevertheless, the expression of α6A might be necessary for optimal lymphocyte migration on laminin in certain pathological conditions. PMID:9763436

  3. Size-dependent structure of CdSe nanoclusters formed after ion implantation in MgO

    International Nuclear Information System (INIS)

    Huis, M.A. van; Veen, A. van; Schut, H.; Eijt, S.W.H.; Kooi, B.J.; Hosson, J.Th.M. de

    2005-01-01

    The band gap as well as the optical and structural properties of semiconductor CdSe nanoclusters change as a function of the nanocluster size. Embedded CdSe nanoclusters in MgO were created by means of sequential Cd and Se ion implantation followed by thermal annealing. Changes during annealing were monitored using optical absorption and positron annihilation spectroscopy. High-resolution TEM on cross-sections after annealing at a temperature of 1300 K showed that clusters with a size below 5 nm have the high-pressure rock-salt structure and are in a cube-on-cube orientation relation with MgO, whereas clusters larger than 5 nm adopt the stable wurtzite crystal structure and were observed in two different orientation relations with MgO

  4. A model for the ethylene and acetylene adsorption on the surface of Cu{sub n}(n = 10–15) nanoclusters: A theoretical study

    Energy Technology Data Exchange (ETDEWEB)

    Farmanzadeh, Davood, E-mail: d.farmanzad@umz.ac.ir; Abdollahi, Tahereh

    2016-11-01

    Highlights: • The most stable structures of Cu{sub n} (n = 10–15) were structures with C{sub S} symmetry. • It is expected that even clusters are better electron donors than the odd clusters. • Acetylene and ethylene adsorb molecularly on the Cu nanoclusters surface. • Acetylene never orient toward di-σ mode for Cu−Cu bond in odd copper nanoclusters. • For di- σ-Cu{sub n}C{sub 2}H{sub 4}, no stable structure is identified. - Abstract: In this work, we report the results of density functional theory calculations of ethylene and acetylene adsorption on the most stable Cu{sub n} (n = 10–15) nanoclusters, in two π and di- σ adsorption modes. Both the hydrocarbons molecularly adsorbed on the surface. Our results show that the quality of interaction of ethylene and acetylene with odd copper nanoclusters (n = 11, 13, 15) is different from what is found on even copper nanoclusters (n = 10, 12, 14). One of the interesting features of this adsorption is that acetylene never orient toward di-σ mode for Cu−Cu bond in odd copper nanoclusters. Also, for di- σ-Cu{sub n}C{sub 2}H{sub 4}, no stable structure is identified. The highest interaction and deformation energies are seen for the adsorption of acetylene and ethylene on Cu{sub 11} in π-mode.

  5. Long-lived, high-strength states of ICAM-1 bonds to beta2 integrin, I

    DEFF Research Database (Denmark)

    Evans, Evan; Kinoshita, Koji; Simon, Scott

    2010-01-01

    Using single-molecule force spectroscopy to probe ICAM-1 interactions with recombinant alphaLbeta2 immobilized on microspheres and beta2 integrin on neutrophils, we quantified an impressive hierarchy of long-lived, high-strength states of the integrin bond, which start from basal levels with inte......Using single-molecule force spectroscopy to probe ICAM-1 interactions with recombinant alphaLbeta2 immobilized on microspheres and beta2 integrin on neutrophils, we quantified an impressive hierarchy of long-lived, high-strength states of the integrin bond, which start from basal levels...... with integrin activation in solutions of divalent cations and shift dramatically upward to hyperactivated states with cell signaling in leukocytes. Taking advantage of very rare events, we used repeated measurements of bond lifetimes under steady ramps of force to achieve a direct assay for the off......-based assays of soluble ICAM-1 dissociation from immobilized LFA-1, i.e., approximately 10(-2)/s in Mg2+ or Mn2+ and approximately 1/s in Ca2+. At the same time, as expected for adhesive function, we find that the beta2 integrin bonds activated in Mn2+ or Mg2+ possess significant and persistent mechanical...

  6. β1-integrin controls cell fate specification in early lens development

    Science.gov (United States)

    Pathania, Mallika; Wang, Yan; Simirskii, Vladimir N.; Duncan, Melinda K.

    2016-01-01

    Integrins are heterodimeric cell surface molecules that mediate cell-extracellular matrix (ECM) adhesion, ECM assembly, and regulation of both ECM and growth factor induced signaling. However, the developmental context of these diverse functions is not clear. Loss of β1-integrin from the lens vesicle (mouse E10.5) results in abnormal exit of anterior lens epithelial cells (LECs) from the cell cycle and their aberrant elongation toward the presumptive cornea by E12.5. These cells lose expression of LEC markers and initiate expression of the Maf (also known as c-Maf) and Prox1 transcription factors as well as other lens fiber cell markers, β1-integrin null LECs also upregulate the ERK, AKT and Smad1/5/8 phosphorylation indicative of BMP and FGF signaling. By E14.5, β1-integrin null lenses have undergone a complete conversion of all lens epithelial cells into fiber cells. These data suggest that shortly after lens vesicle closure, β1-integrin blocks inappropriate differentiation of the lens epithelium into fibers, potentially by inhibiting BMP and/or FGF receptor activation. Thus, β1-integrin has an important role in fine-tuning the response of the early lens to the gradient of growth factors that regulate lens fiber cell differentiation. PMID:27596755

  7. Transmission of integrin β7 transmembrane domain topology enables gut lymphoid tissue development.

    Science.gov (United States)

    Sun, Hao; Lagarrigue, Frederic; Gingras, Alexandre R; Fan, Zhichao; Ley, Klaus; Ginsberg, Mark H

    2018-04-02

    Integrin activation regulates adhesion, extracellular matrix assembly, and cell migration, thereby playing an indispensable role in development and in many pathological processes. A proline mutation in the central integrin β3 transmembrane domain (TMD) creates a flexible kink that uncouples the topology of the inner half of the TMD from the outer half. In this study, using leukocyte integrin α4β7, which enables development of gut-associated lymphoid tissue (GALT), we examined the biological effect of such a proline mutation and report that it impairs agonist-induced talin-mediated activation of integrin α4β7, thereby inhibiting rolling lymphocyte arrest, a key step in transmigration. Furthermore, the α4β7(L721P) mutation blocks lymphocyte homing to and development of the GALT. These studies show that impairing the ability of an integrin β TMD to transmit talin-induced TMD topology inhibits agonist-induced physiological integrin activation and biological function in development. © 2018 Sun et al.

  8. Peripheral myelin protein-22 (PMP22 modulates alpha 6 integrin expression in the human endometrium

    Directory of Open Access Journals (Sweden)

    Braun Jonathan

    2011-04-01

    Full Text Available Abstract Background PMP22, a member of the GAS3 family of tetraspan proteins, is associated with a variety of neurological diseases. Previous studies have shown that PMP22 is expressed in proliferative endometrium, but its function within this tissue is poorly understood. In this study, we first characterized the expression of PMP22 in the human menstrual cycle and began to characterize its function in the endometrium. Methods Using a combination of immunohistochemistry and quantitative PCR, we characterized the expression of PMP22 in both proliferative and secretory endometrium. Differences in PMP22 expression between proliferative and secretory endometrium were determined using a Mann-Whitney U test. In order to investigate the influence of PMP22 on α6 integrin expression, cells were created that ectopically overexpressed PMP22 or expressed a siRNA to inhibit its expression. These cells were analyzed for changes in integrins and binding to extracellular matrices. Results In this study, we show that PMP22 expression is higher in proliferative phase than secretory phase. Functionally, we have begun to characterize the functional significance of this expression. Previous studies have suggested a link between PMP22 and α6 integrin, and therefore we asked whether PMP22 could associate or potentially modulate the expression of α6 integrin. Expression of both PMP22 and α6 integrin were detectable in endometrial epithelial and stromal cells, and we show that both proteins can associate and colocalize with each other. To understand if PMP22 directly altered the expression of a6 integrin, we examined cell lines with modulated levels of the protein. Overexpression of PMP22 was sufficient to increase α6 integrin surface expression with a concominant increase in binding to the extracellular matrix laminin, while a reduction in PMP22 suppressed α6 integrin surface expression. Conclusion These findings suggest a physiologic role for PMP22 on the

  9. Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium.

    Science.gov (United States)

    Rao, Rajiv G; Sudhakar, Deepthi; Hogue, Claire P; Amici, Stephanie; Gordon, Lynn K; Braun, Jonathan; Notterpek, Lucia; Goodglick, Lee; Wadehra, Madhuri

    2011-04-25

    PMP22, a member of the GAS3 family of tetraspan proteins, is associated with a variety of neurological diseases. Previous studies have shown that PMP22 is expressed in proliferative endometrium, but its function within this tissue is poorly understood. In this study, we first characterized the expression of PMP22 in the human menstrual cycle and began to characterize its function in the endometrium. Using a combination of immunohistochemistry and quantitative PCR, we characterized the expression of PMP22 in both proliferative and secretory endometrium. Differences in PMP22 expression between proliferative and secretory endometrium were determined using a Mann-Whitney U test. In order to investigate the influence of PMP22 on α6 integrin expression, cells were created that ectopically overexpressed PMP22 or expressed a siRNA to inhibit its expression. These cells were analyzed for changes in integrins and binding to extracellular matrices. In this study, we show that PMP22 expression is higher in proliferative phase than secretory phase. Functionally, we have begun to characterize the functional significance of this expression. Previous studies have suggested a link between PMP22 and α6 integrin, and therefore we asked whether PMP22 could associate or potentially modulate the expression of α6 integrin. Expression of both PMP22 and α6 integrin were detectable in endometrial epithelial and stromal cells, and we show that both proteins can associate and colocalize with each other. To understand if PMP22 directly altered the expression of a6 integrin, we examined cell lines with modulated levels of the protein. Overexpression of PMP22 was sufficient to increase α6 integrin surface expression with a concominant increase in binding to the extracellular matrix laminin, while a reduction in PMP22 suppressed α6 integrin surface expression. These findings suggest a physiologic role for PMP22 on the expression of α6 integrin. We predict that this may be important for the

  10. Functional inhibition of NF-kappa B signal transduction in alpha v alpha beta 3 integrin expressing endothelial cells by using RGD-PEG-modified adenovirus with a mutant I kappa B gene

    NARCIS (Netherlands)

    Ogawara, K; Kuldo, JM; Oosterhuis, K; Kroesen, BJ; Rots, MG; Trautwein, C; Kimura, T; Haisma, HJ; Molema, G

    2006-01-01

    In order to selectively block nuclear factor kappa B (NF-kappa B)-dependent signal transduction in angiogenic endothelial cells, we constructed an alpha v beta 3 integrin specific adenovirus encoding dominant negative I kappa B (dnI kappa B) as a therapeutic gene. By virtue of RGD modification of

  11. Astrocyte-to-neuron communication through integrin-engaged Thy-1/CBP/Csk/Src complex triggers neurite retraction via the RhoA/ROCK pathway.

    Science.gov (United States)

    Maldonado, H; Calderon, C; Burgos-Bravo, F; Kobler, O; Zuschratter, W; Ramirez, O; Härtel, S; Schneider, P; Quest, A F G; Herrera-Molina, R; Leyton, L

    2017-02-01

    Two key proteins for cellular communication between astrocytes and neurons are αvβ3 integrin and the receptor Thy-1. Binding of these molecules in the same (cis) or on adjacent (trans) cellular membranes induces Thy-1 clustering, triggering actin cytoskeleton remodeling. Molecular events that could explain how the Thy-1-αvβ3 integrin interaction signals have only been studied separately in different cell types, and the detailed transcellular communication and signal transduction pathways involved in neuronal cytoskeleton remodeling remain unresolved. Using biochemical and genetic approaches, single-molecule tracking, and high-resolution nanoscopy, we provide evidence that upon binding to αvβ3 integrin, Thy-1 mobility decreased while Thy-1 nanocluster size increased. This occurred concomitantly with inactivation and exclusion of the non-receptor tyrosine kinase Src from the Thy-1/C-terminal Src kinase (Csk)-binding protein (CBP)/Csk complex. The Src inactivation decreased the p190Rho GTPase activating protein phosphorylation, promoting RhoA activation, cofilin, and myosin light chain II phosphorylation and, consequently, neurite shortening. Finally, silencing the adaptor CBP demonstrated that this protein was a key transducer in the Thy-1 signaling cascade. In conclusion, these data support the hypothesis that the Thy-1-CBP-Csk-Src-RhoA-ROCK axis transmitted signals from astrocytic integrin-engaged Thy-1 (trans) to the neuronal actin cytoskeleton. Importantly, the β3 integrin in neurons (cis) was not found to be crucial for neurite shortening. This is the first study to detail the signaling pathway triggered by αvβ3, the endogenous Thy-1 ligand, highlighting the role of membrane-bound integrins as trans acting ligands in astrocyte-neuron communication. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Interfacial electron transfer dynamics of photosensitized zinc oxide nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Murakoshi, Kei; Yanagida, Shozo [Osaka Univ. (Japan). Graduate School of Engineering; Capel, M. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1997-06-01

    The authors have prepared and characterized photosensitized zinc oxide (ZnO) nanoclusters, dispersed in methanol, using carboxylated coumarin dyes for surface adsorption. Femtosecond time-resolved emission spectroscopy allows the authors to measure the photo-induced charge carrier injection rate constant from the adsorbed photosensitizer to the n-type semiconductor nanocluster. These results are compared with other photosensitized semiconductors.

  13. Synthesis and characterization of mixed ligand chiral nanoclusters

    KAUST Repository

    Guven, Zekiye P.

    2016-06-22

    Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

  14. Synthesis and characterization of mixed ligand chiral nanoclusters

    KAUST Repository

    Guven, Zekiye P.; Ustbas, Burcin; Harkness, Kellen M.; Coskun, Hikmet; Joshi, Chakra Prasad; Besong, Tabot M.D.; Stellacci, Francesco; Bakr, Osman; Akbulut, Ozge

    2016-01-01

    Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

  15. Exploring Low Internal Reorganization Energies for Silicene Nanoclusters

    Science.gov (United States)

    Pablo-Pedro, Ricardo; Lopez-Rios, Hector; Mendoza-Cortes, Jose-L.; Kong, Jing; Fomine, Serguei; Van Voorhis, Troy; Dresselhaus, Mildred S.

    2018-05-01

    This paper is a contribution to the Physical Review Applied collection in memory of Mildred S. Dresselhaus. High-performance materials rely on small reorganization energies to facilitate both charge separation and charge transport. Here, we perform density-functional-theory calculations to predict small reorganization energies of rectangular silicene nanoclusters with hydrogen-passivated edges denoted by H-SiNC. We observe that across all geometries, H-SiNCs feature large electron affinities and highly stabilized anionic states, indicating their potential as n -type materials. Our findings suggest that fine-tuning the size of H-SiNCs along the "zigzag" and "armchair" directions may permit the design of novel n -type electronic materials and spintronics devices that incorporate both high electron affinities and very low internal reorganization energies.

  16. Small molecule antagonists of integrin receptors.

    Science.gov (United States)

    Perdih, A; Dolenc, M Sollner

    2010-01-01

    The complex and widespread family of integrin receptors is involved in numerous physiological processes, such as tissue remodeling, angiogenesis, development of the immune response and homeostasis. In addition, their key role has been elucidated in important pathological disorders such as cancer, cardiovascular diseases, osteoporosis, autoimmune and inflammatory diseases and in the pathogenesis of infectious diseases, making them highly important targets for modern drug design campaigns. In this review we seek to present a concise overview of the small molecule antagonists of this diverse and highly complex receptor family. Integrin antagonists are classified according to the targeted integrin receptor and are discussed in four sections. First we present the fibrinogen alpha(IIb)beta3 and the vitronectin alpha (V)beta(3) receptor antagonists. The remaining selective integrin antagonists are examined in the third section. The final section is dedicated to molecules with dual or multiple integrin activity. In addition, the use of antibodies and peptidomimetic approaches to modulate the integrin receptors are discussed, as well providing the reader with an overall appreciation of the field.

  17. Tumour exosome integrins determine organotropic metastasis.

    Science.gov (United States)

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-11-19

    Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  18. Ab initio structural and electronic properties of hydrogenated silicon nanoclusters in the ground and excited state

    International Nuclear Information System (INIS)

    Degoli, Elena; Bisi, O.; Ossicini, Stefano; Cantele, G.; Ninno, D.; Luppi, Eleonora; Magri, Rita

    2004-01-01

    Electronic and structural properties of small hydrogenated silicon nanoclusters as a function of dimension are calculated from ab initio technique. The effects induced by the creation of an electron-hole pair are discussed in detail, showing the strong interplay between the structural and optical properties of the system. The distortion induced on the structure after an electronic excitation of the cluster is analyzed together with the role of the symmetry constraint during the relaxation. We point out how the overall effect is that of significantly changing the electronic spectrum if no symmetry constraint is imposed to the system. Such distortion can account for the Stokes shift and provides a possible structural model to be linked to the four-level scheme invoked in the literature to explain recent results for the optical gain in silicon nanoclusters. Finally, formation energies for clusters with increasing dimension are calculated and their relative stability discussed

  19. First-principles investigation of strain effects on the energy gaps in silicon nanoclusters

    International Nuclear Information System (INIS)

    Peng, X-H; Alizadeh, A; Bhate, N; Varanasi, K K; Kumar, S K; Nayak, S K

    2007-01-01

    First-principles density functional calculations were performed to study strain effects on the energy gaps in silicon nanoclusters with diameter ranging from 0.6 to 2 nm. Hydrostatic and non-hydrostatic strains have been found to affect the energy gaps differently. For the same strain energy density, non-hydrostatic strain leads to a significantly larger change in the energy gap of silicon clusters compared to that of the hydrostatic strain case. In contrast, hydrostatic and non-hydrostatic strain effects on the energy gaps of bulk Si or larger size Si quantum dots are comparable. Non-hydrostatic strains break the tetrahedral bonding symmetry in silicon, resulting in significant variation in the energy gaps due to the splitting of the degenerate orbitals in the clusters. Our results suggest that the combination of energy gaps and strains permits the engineering of photoluminescence in silicon nanoclusters and offers the possibility of designing novel optical devices and chemical sensors

  20. Iron Oxide Colloidal Nanoclusters as Theranostic Vehicles and Their Interactions at the Cellular Level

    Directory of Open Access Journals (Sweden)

    Athanasia Kostopoulou

    2018-05-01

    Full Text Available Advances in surfactant-assisted chemical approaches have led the way for the exploitation of nanoscale inorganic particles in medical diagnosis and treatment. In this field, magnetically-driven multimodal nanotools that perform both detection and therapy, well-designed in size, shape and composition, are highly advantageous. Such a theranostic material—which entails the controlled assembly of smaller (maghemite nanocrystals in a secondary motif that is highly dispersible in aqueous media—is discussed here. These surface functionalized, pomegranate-like ferrimagnetic nanoclusters (40–85 nm are made of nanocrystal subunits that show a remarkable magnetic resonance imaging contrast efficiency, which is better than that of the superparamagnetic contrast agent Endorem©. Going beyond this attribute and with their demonstrated low cytotoxicity in hand, we examine the critical interaction of such nanoprobes with cells at different physiological environments. The time-dependent in vivo scintigraphic imaging of mice experimental models, combined with a biodistribution study, revealed the accumulation of nanoclusters in the spleen and liver. Moreover, the in vitro proliferation of spleen cells and cytokine production witnessed a size-selective regulation of immune system cells, inferring that smaller clusters induce mainly inflammatory activities, while larger ones induce anti-inflammatory actions. The preliminary findings corroborate that the modular chemistry of magnetic iron oxide nanoclusters stimulates unexplored pathways that could be driven to alter their function in favor of healthcare.

  1. Iron Oxide Colloidal Nanoclusters as Theranostic Vehicles and Their Interactions at the Cellular Level.

    Science.gov (United States)

    Kostopoulou, Athanasia; Brintakis, Konstantinos; Fragogeorgi, Eirini; Anthousi, Amalia; Manna, Liberato; Begin-Colin, Sylvie; Billotey, Claire; Ranella, Anthi; Loudos, George; Athanassakis, Irene; Lappas, Alexandros

    2018-05-09

    Advances in surfactant-assisted chemical approaches have led the way for the exploitation of nanoscale inorganic particles in medical diagnosis and treatment. In this field, magnetically-driven multimodal nanotools that perform both detection and therapy, well-designed in size, shape and composition, are highly advantageous. Such a theranostic material—which entails the controlled assembly of smaller (maghemite) nanocrystals in a secondary motif that is highly dispersible in aqueous media—is discussed here. These surface functionalized, pomegranate-like ferrimagnetic nanoclusters (40⁻85 nm) are made of nanocrystal subunits that show a remarkable magnetic resonance imaging contrast efficiency, which is better than that of the superparamagnetic contrast agent Endorem © . Going beyond this attribute and with their demonstrated low cytotoxicity in hand, we examine the critical interaction of such nanoprobes with cells at different physiological environments. The time-dependent in vivo scintigraphic imaging of mice experimental models, combined with a biodistribution study, revealed the accumulation of nanoclusters in the spleen and liver. Moreover, the in vitro proliferation of spleen cells and cytokine production witnessed a size-selective regulation of immune system cells, inferring that smaller clusters induce mainly inflammatory activities, while larger ones induce anti-inflammatory actions. The preliminary findings corroborate that the modular chemistry of magnetic iron oxide nanoclusters stimulates unexplored pathways that could be driven to alter their function in favor of healthcare.

  2. The effect of conditional inactivation of beta 1 integrins using twist 2 Cre, Osterix Cre and osteocalcin Cre lines on skeletal phenotype.

    Science.gov (United States)

    Shekaran, Asha; Shoemaker, James T; Kavanaugh, Taylor E; Lin, Angela S; LaPlaca, Michelle C; Fan, Yuhong; Guldberg, Robert E; García, Andrés J

    2014-11-01

    Skeletal development and growth are complex processes regulated by multiple microenvironmental cues, including integrin-ECM interactions. The β1 sub-family of integrins is the largest integrin sub-family and constitutes the main integrin binding partners of collagen I, the major ECM component of bone. As complete β1 integrin knockout results in embryonic lethality, studies of β1 integrin function in vivo rely on tissue-specific gene deletions. While multiple in vitro studies indicate that β1 integrins are crucial regulators of osteogenesis and mineralization, in vivo osteoblast-specific perturbations of β1 integrins have resulted in mild and sometimes contradictory skeletal phenotypes. To further investigate the role of β1 integrins on skeletal phenotype, we used the Twist2-Cre, Osterix-Cre and osteocalcin-Cre lines to generate conditional β1 integrin deletions, where Cre is expressed primarily in mesenchymal condensation, pre-osteoblast, and mature osteoblast lineage cells respectively within these lines. Mice with Twist2-specific β1 integrin disruption were smaller, had impaired skeletal development, especially in the craniofacial and vertebral tissues at E19.5, and did not survive beyond birth. Osterix-specific β1 integrin deficiency resulted in viable mice which were normal at birth but displayed early defects in calvarial ossification, incisor eruption and growth as well as femoral bone mineral density, structure, and mechanical properties. Although these defects persisted into adulthood, they became milder with age. Finally, a lack of β1 integrins in mature osteoblasts and osteocytes resulted in minor alterations to femur structure but had no effect on mineral density, biomechanics or fracture healing. Taken together, our data indicate that β1 integrin expression in early mesenchymal condensations play an important role in skeletal ossification, while β1 integrin-ECM interactions in pre-osteoblast, odontoblast- and hypertrophic chondryocyte

  3. Relaxation path of metastable nanoclusters in oxide dispersion strengthened materials

    Energy Technology Data Exchange (ETDEWEB)

    Ribis, J., E-mail: joel.ribis@cea.fr [DEN-Service de Recherches Métallurgiques Appliquées, CEA, Université Paris-Saclay, F-91191, Gif-sur-Yvette (France); Thual, M.A. [LLB, CEA, CNRS, Université Paris-Saclay, CEA Saclay, 91191, Gif-sur-Yvette (France); Guilbert, T.; Carlan, Y. de [DEN-Service de Recherches Métallurgiques Appliquées, CEA, Université Paris-Saclay, F-91191, Gif-sur-Yvette (France); Legris, A. [UMET, CNRS/UMR 8207, Bât. C6, Univ. Lille 1, 59655 Villeneuve d’Ascq (France)

    2017-02-15

    ODS steels are a promising class of structural materials for sodium cooled fast reactor application. The ultra-high density of the strengthening nanoclusters dispersed within the ferritic matrix is responsible of the excellent creep properties of the alloy. Fine characterization of the nanoclusters has been conducted on a Fe-14Cr-0.3Ti-0.3Y{sub 2}O{sub 3} ODS material using High Resolution and Energy Filtered Transmission Electron Microscopy. The nanoclusters exhibit a cubic symmetry possibly identified as f.c.c and display a non-equilibrium YTiCrO chemical composition thought to be stabilized by a vacancy supersaturation. These nanoclusters undergo relaxation towards the Y{sub 2}Ti{sub 2}O{sub 7}-like state as they grow. A Cr shell is observed around the relaxed nano-oxides, this size-dependent shell may form after the release of Cr by the particles. The relaxation energy barrier appears to be higher for the smaller particles probably owing to a volume/surface ratio effect in reason to the full coherency of the nanoclusters. - Highlights: • The nanoclusters display a f.c.c. cubic symmetry and a non-equilibrium YTiCrO chemical composition. • During thermal annealing the coherent nanocluster transform into semi-coherent pyrochlore particles. • A Cr ring is observed around the relaxed pyrochlore type particles.

  4. Laminin isoforms differentially regulate adhesion, spreading, proliferation, and ERK activation of β1 integrin-null cells

    International Nuclear Information System (INIS)

    Kikkawa, Yamato; Yu, Hao; Genersch, Elke; Sanzen, Noriko; Sekiguchi, Kiyotoshi; Faessler, Reinhard; Campbell, Kevin P.; Talts, Jan F.; Ekblom, Peter

    2004-01-01

    The presence of many laminin receptors of the β1 integrin family on most cells makes it difficult to define the biological functions of other major laminin receptors such as integrin α6β4 and dystroglycan. We therefore tested the binding of a β1 integrin-null cell line GD25 to four different laminin variants. The cells were shown to produce dystroglycan, which based on affinity chromatography bound to laminin-1, -2/4, and -10/11, but not to laminin-5. The cells also expressed the integrin α6Aβ4A variant. GD25 β1 integrin-null cells are known to bind poorly to laminin-1, but we demonstrate here that these cells bind avidly to laminin-2/4, -5, and -10/11. The initial binding at 20 min to each of these laminins could be inhibited by an integrin α6 antibody, but not by a dystroglycan antibody. Hence, integrin α6Aβ4A of GD25 cells was identified as a major receptor for initial GD25 cell adhesion to three out of four tested laminin isoforms. Remarkably, cell adhesion to laminin-5 failed to promote cell spreading, proliferation, and extracellular signal-regulated kinase (ERK) activation, whereas all these responses occurred in response to adhesion to laminin-2/4 or -10/11. The data establish GD25 cells as useful tools to define the role integrin α6Aβ4A and suggest that laminin isoforms have distinctly different capacities to promote cell adhesion and signaling via integrin α6Aβ4A

  5. Endocytosis of Integrin-Binding Human Picornaviruses

    Directory of Open Access Journals (Sweden)

    Pirjo Merilahti

    2012-01-01

    Full Text Available Picornaviruses that infect humans form one of the largest virus groups with almost three hundred virus types. They include significant enteroviral pathogens such as rhino-, polio-, echo-, and coxsackieviruses and human parechoviruses that cause wide range of disease symptoms. Despite the economic importance of picornaviruses, there are no antivirals. More than ten cellular receptors are known to participate in picornavirus infection, but experimental evidence of their role in cellular infection has been shown for only about twenty picornavirus types. Three enterovirus types and one parechovirus have experimentally been shown to bind and use integrin receptors in cellular infection. These include coxsackievirus A9 (CV-A9, echovirus 9, and human parechovirus 1 that are among the most common and epidemic human picornaviruses and bind to αV-integrins via RGD motif that resides on virus capsid. In contrast, echovirus 1 (E-1 has no RGD and uses integrin α2β1 as cellular receptor. Endocytosis of CV-A9 has recently been shown to occur via a novel Arf6- and dynamin-dependent pathways, while, contrary to collagen binding, E-1 binds inactive β1 integrin and enters via macropinocytosis. In this paper, we review what is known about receptors and endocytosis of integrin-binding human picornaviruses.

  6. Nanoclusters and Microparticles in Gases and Vapors

    CERN Document Server

    Smirnov, Boris M

    2012-01-01

    Research of processes involving Nanoclusters and Microparticleshas been developing fastin many fields of rescent research, in particular in materials science. To stay at the cutting edge of this development, a sound understanding of the processes is needed. In this work, several processes involving small particles are described, such as transport processes in gases, charging of small particles in gases, chemical processes, atom attachment and quenching of excited atomic particles on surfaces, nucleation, coagulation, coalescence and growth processes for particles and aggregates. This work pres

  7. Rapid fluorescence assay for Sudan dyes using polyethyleneimine-coated copper nanoclusters

    International Nuclear Information System (INIS)

    Ling, Yu; Li, Jia Xing; Li, Nian Bing; Luo, Hong Qun; Qu, Fei

    2014-01-01

    We report that the intensity of the blue fluorescence of copper nanoclusters coated with polyethyleneimine (PEI) is strongly reduced in the presence of the food dyestuffs Sudan I-IV. This finding was exploited in a label-free fluorescence assay for these Sudan dyes both in ethanol and aqueous solutions. The PEI-capped nanoclusters have an average diameter of 1.8 nm and are displaying, under 355 nm excitation, a blue emission at 480 nm that matches the absorption bands of the Sudan dyes. The clusters are stable in solution for at least 1 month. Under optimum conditions, this assay can be applied to the quantification of the dyes Sudan I, II, III, and IV, respectively, in the 0.1−30, 0.1–30, 0.1–25, and 0.1–25 μM concentration ranges, and the detection limits (3σ/slope) are 65, 70, 45, and 50 nM, respectively. The capability of reducing the fluorescence of the PEI-capped copper nanoclusters is directly related to the number of the functional groups in that Sudan III and IV give lower detection limits. This analytical scheme exhibits a remarkably high selectivity for the Sudan dyes over potentially interfering substances. The method was successfully applied to determine Sudan I, II, III, and IV in hot chilli powder. (author)

  8. First-principles calculated decomposition pathways for LiBH4 nanoclusters

    Science.gov (United States)

    Huang, Zhi-Quan; Chen, Wei-Chih; Chuang, Feng-Chuan; Majzoub, Eric H.; Ozoliņš, Vidvuds

    2016-05-01

    We analyze thermodynamic stability and decomposition pathways of LiBH4 nanoclusters using grand-canonical free-energy minimization based on total energies and vibrational frequencies obtained from density-functional theory (DFT) calculations. We consider (LiBH4)n nanoclusters with n = 2 to 12 as reactants, while the possible products include (Li)n, (B)n, (LiB)n, (LiH)n, and Li2BnHn; off-stoichiometric LinBnHm (m ≤ 4n) clusters were considered for n = 2, 3, and 6. Cluster ground-state configurations have been predicted using prototype electrostatic ground-state (PEGS) and genetic algorithm (GA) based structural optimizations. Free-energy calculations show hydrogen release pathways markedly differ from those in bulk LiBH4. While experiments have found that the bulk material decomposes into LiH and B, with Li2B12H12 as a kinetically inhibited intermediate phase, (LiBH4)n nanoclusters with n ≤ 12 are predicted to decompose into mixed LinBn clusters via a series of intermediate clusters of LinBnHm (m ≤ 4n). The calculated pressure-composition isotherms and temperature-pressure isobars exhibit sloping plateaus due to finite size effects on reaction thermodynamics. Generally, decomposition temperatures of free-standing clusters are found to increase with decreasing cluster size due to thermodynamic destabilization of reaction products.

  9. Highly selective GaN-nanowire/TiO2-nanocluster hybrid sensors for detection of benzene and related environment pollutants

    International Nuclear Information System (INIS)

    Aluri, Geetha S; Motayed, Abhishek; Davydov, Albert V; Oleshko, Vladimir P; Bertness, Kris A; Sanford, Norman A; Rao, Mulpuri V

    2011-01-01

    Nanowire-nanocluster hybrid chemical sensors were realized by functionalizing gallium nitride (GaN) nanowires (NWs) with titanium dioxide (TiO 2 ) nanoclusters for selectively sensing benzene and other related aromatic compounds. Hybrid sensor devices were developed by fabricating two-terminal devices using individual GaN NWs followed by the deposition of TiO 2 nanoclusters using RF magnetron sputtering. The sensor fabrication process employed standard microfabrication techniques. X-ray diffraction and high-resolution analytical transmission electron microscopy using energy-dispersive x-ray and electron energy-loss spectroscopies confirmed the presence of the anatase phase in TiO 2 clusters after post-deposition anneal at 700 deg. C. A change of current was observed for these hybrid sensors when exposed to the vapors of aromatic compounds (benzene, toluene, ethylbenzene, xylene and chlorobenzene mixed with air) under UV excitation, while they had no response to non-aromatic organic compounds such as methanol, ethanol, isopropanol, chloroform, acetone and 1,3-hexadiene. The sensitivity range for the noted aromatic compounds except chlorobenzene were from 1% down to 50 parts per billion (ppb) at room temperature. By combining the enhanced catalytic properties of the TiO 2 nanoclusters with the sensitive transduction capability of the nanowires, an ultra-sensitive and selective chemical sensing architecture is demonstrated. We have proposed a mechanism that could qualitatively explain the observed sensing behavior.

  10. ADAM2 interactions with mouse eggs and cell lines expressing α4/α9 (ITGA4/ITGA9 integrins: implications for integrin-based adhesion and fertilization.

    Directory of Open Access Journals (Sweden)

    Ulyana V Desiderio

    2010-10-01

    Full Text Available Integrins are heterodimeric cell adhesion molecules, with 18 α (ITGA and eight β (ITGB subunits forming 24 heterodimers classified into five families. Certain integrins, especially the α(4/α(9 (ITGA4/ITGA9 family, interact with members of the ADAM (a disintegrin and metalloprotease family. ADAM2 is among the better characterized and also of interest because of its role in sperm function. Having shown that ITGA9 on mouse eggs participates in mouse sperm-egg interactions, we sought to characterize ITGA4/ITGA9-ADAM2 interactions.An anti-β(1/ITGB1 function-blocking antibody that reduces sperm-egg binding significantly inhibited ADAM2 binding to mouse eggs. Analysis of integrin subunit expression indicates that mouse eggs could express at least ten different integrins, five in the RGD-binding family, two in the laminin-binding family, two in the collagen-binding family, and ITGA9-ITGB1. Adhesion assays to characterize ADAM2 interactions with ITGA4/ITGA9 family members produced the surprising result that RPMI 8866 cell adhesion to ADAM2 was inhibited by an anti-ITGA9 antibody, noteworthy because ITGA9 has only been reported to dimerize with ITGB1, and RPMI 8866 cells lack detectable ITGB1. Antibody and siRNA studies demonstrate that ITGB7 is the β subunit contributing to RPMI 8866 adhesion to ADAM2.These data indicate that a novel integrin α-β combination, ITGA9-ITGB7 (α(9β(7, in RPMI 8866 cells functions as a binding partner for ADAM2. ITGA9 had previously only been reported to dimerize with ITGB1. Although ITGA9-ITGB7 is unlikely to be a widely expressed integrin and appears to be the result of "compensatory dimerization" occurring in the context of little/no ITGB1 expression, the data indicate that ITGA9-ITGB7 functions as an ADAM binding partner in certain cellular contexts, with implications for mammalian fertilization and integrin function.

  11. Integrins as Therapeutic Targets: Successes and Cancers

    Directory of Open Access Journals (Sweden)

    Sabine Raab-Westphal

    2017-08-01

    Full Text Available Integrins are transmembrane receptors that are central to the biology of many human pathologies. Classically mediating cell-extracellular matrix and cell-cell interaction, and with an emerging role as local activators of TGFβ, they influence cancer, fibrosis, thrombosis and inflammation. Their ligand binding and some regulatory sites are extracellular and sensitive to pharmacological intervention, as proven by the clinical success of seven drugs targeting them. The six drugs on the market in 2016 generated revenues of some US$3.5 billion, mainly from inhibitors of α4-series integrins. In this review we examine the current developments in integrin therapeutics, especially in cancer, and comment on the health economic implications of these developments.

  12. Controllable growth and magnetic properties of nickel nanoclusters electrodeposited on the ZnO nanorod template

    International Nuclear Information System (INIS)

    Tang Yang; Zhao Dongxu; Shen Dezhen; Zhang Jiying; Wang Xiaohua

    2009-01-01

    The ZnO nanorods were used as a template to fabricate nickel nanoclusters by electrodeposition. The ZnO nanorod arrays act as a nano-semiconductor electrode for depositing metallic and magnetic nickel nanoclusters. The growth sites of Ni nanoclusters could be controlled by adjusting the applied potential. Under -1.15 V the Ni nanoclusters could be grown on the tips of ZnO nanorods. On increasing the potential to be more negative the ZnO nanorods were covered by Ni nanoclusters. The magnetic properties of the electrodeposited Ni nanoclusters also evolved with the applied potentials.

  13. Controllable growth and magnetic properties of nickel nanoclusters electrodeposited on the ZnO nanorod template

    Energy Technology Data Exchange (ETDEWEB)

    Tang Yang; Zhao Dongxu; Shen Dezhen; Zhang Jiying [Key Laboratory of Excited State Processes, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, 16 East Nan-Hu Road, Open Economic Zone, Changchun 130033 (China); Wang Xiaohua, E-mail: dxzhao2000@yahoo.com.c [National Key Laboratory of High Power Semiconductor Laser, Changchun University of Science and Technology, 7089 WeiXing Road, ChangChun 130022 (China)

    2009-12-09

    The ZnO nanorods were used as a template to fabricate nickel nanoclusters by electrodeposition. The ZnO nanorod arrays act as a nano-semiconductor electrode for depositing metallic and magnetic nickel nanoclusters. The growth sites of Ni nanoclusters could be controlled by adjusting the applied potential. Under -1.15 V the Ni nanoclusters could be grown on the tips of ZnO nanorods. On increasing the potential to be more negative the ZnO nanorods were covered by Ni nanoclusters. The magnetic properties of the electrodeposited Ni nanoclusters also evolved with the applied potentials.

  14. Gfi1b controls integrin signaling-dependent cytoskeleton dynamics and organization in megakaryocytes.

    Science.gov (United States)

    Beauchemin, Hugues; Shooshtarizadeh, Peiman; Vadnais, Charles; Vassen, Lothar; Pastore, Yves D; Möröy, Tarik

    2017-03-01

    Mutations in GFI1B are associated with inherited bleeding disorders called GFI1B -related thrombocytopenias. We show here that mice with a megakaryocyte-specific Gfi1b deletion exhibit a macrothrombocytopenic phenotype along a megakaryocytic dysplasia reminiscent of GFI1B -related thrombocytopenia. GFI1B deficiency increases megakaryocyte proliferation and affects their ploidy, but also abrogates their responsiveness towards integrin signaling and their ability to spread and reorganize their cytoskeleton. Gfi1b -null megakaryocytes are also unable to form proplatelets, a process independent of integrin signaling. GFI1B-deficient megakaryocytes exhibit aberrant expression of several components of both the actin and microtubule cytoskeleton, with a dramatic reduction of α-tubulin. Inhibition of FAK or ROCK, both important for actin cytoskeleton organization and integrin signaling, only partially restored their response to integrin ligands, but the inhibition of PAK, a regulator of the actin cytoskeleton, completely rescued the responsiveness of Gfi1b -null megakaryocytes to ligands, but not their ability to form proplatelets. We conclude that Gfi1b controls major functions of megakaryocytes such as integrin-dependent cytoskeleton organization, spreading and migration through the regulation of PAK activity whereas the proplatelet formation defect in GFI1B-deficient megakaryocytes is due, at least partially, to an insufficient α-tubulin content. Copyright© Ferrata Storti Foundation.

  15. beta1 integrins are not required for the maintenance of lymphocytes within intestinal epithelia

    DEFF Research Database (Denmark)

    Marsal, Jan; Brakebusch, Cord; Bungartz, Gerd

    2005-01-01

    beta(1) integrins are thought to play a central role in maintaining lymphocytes within mucosal epithelia via their interactions with extracellular matrix proteins and subepithelial cellular components within and underlying the basement membrane. In the current study type a (CD8alphabetaTCRalphabe......beta(1) integrins are thought to play a central role in maintaining lymphocytes within mucosal epithelia via their interactions with extracellular matrix proteins and subepithelial cellular components within and underlying the basement membrane. In the current study type a (CD8alphabeta......TCRalphabeta) and type b (CD8alphaalphaTCRgammadelta and CD8alphaalphaTCRalphabeta) intraepithelial lymphocyte (IEL) subsets within the mouse small intestine were found to express functional beta(1) integrin and the beta(1) integrin alpha chain partners alpha(1), alpha(2), and alpha(4). Using inducible beta(1) integrin......-knockout bone marrow-chimeric mice we demonstrate that IEL expression of alpha(1) and alpha(2) but not alpha(4) is dependent on expression of the beta(1) chain. Importantly, deletion of the beta(1) chain in IEL did not alter the number or composition of lymphocytes within the intestinal epithelium. Thus, while...

  16. Theoretical Investigation of the Structural Stabilities of Ceria Surfaces and Supported Metal Nanocluster in Vapor and Aqueous Phases

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Zhibo [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Institute for Integrated Catalysis, Pacific Northwest National Laboratory, Richland, Washington 99352, United States; Liu, Ning [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Institute for Integrated Catalysis, Pacific Northwest National Laboratory, Richland, Washington 99352, United States; Chen, Biaohua [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Li, Jianwei [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Mei, Donghai [Institute for Integrated Catalysis, Pacific Northwest National Laboratory, Richland, Washington 99352, United States

    2018-01-25

    Understanding the structural stability and dynamics at the interface between the solid metal oxide and aqueous phase is significant in a variety of industrial applications including heterogeneous catalysis and environmental remediation. In the present work, the stabilities of three low-index ceria (CeO2) surfaces, i.e., (111), (110) and (100) in vapor and aqueous phases were studied using ab initio molecular dynamics simulations and density functional theory (DFT) calculations. Gibbs surface free energies as a function of temperature, water partial pressure, and water coverages were calculated using DFT based atomistic thermodynamic approach. On the basis of surface free energies, the morphology and exposed surface structures of the CeO2 nanoparticle were predicted using Wulff construction principle. It is found that the partially hydroxylated (111) and (100) are two major surface structures of CeO2 nanoparticles in vapor phase at ambient temperature (300 K). As the temperature increases, the fully dehydrated (111) surface gradually becomes the most dominant surface structure. While in aqueous phase, the exposed surface of the CeO2 nanoparticle is dominated by the hydroxylated (110) structure at 393 K. Finally, the morphology and stability of a cuboctahedron Pt13 nanocluster supported on CeO2 surfaces in both gas and aqueous phases were investigated. In gas phase, the supported Pt13 nanocluster has the tendency to wetting the CeO2 surface due to the strong metal-support interaction. The calculated interaction energies suggest the CeO2(110) surface provides the best stability for the Pt13 nanocluster. The CeO2 supported Pt13 nanoclusters are oxidized. Compared to the gas phase, the morphology of the CeO2 supported Pt13 nanocluster is less distorted due to the solvation effect provided by surrounding water molecules in aqueous phase. More electrons are transferred from the Pt13 nanocluster to the CeO2 support, implying the supported Pt13 nanocluster is further

  17. IGF-IR promotes prostate cancer growth by stabilizing α5β1 integrin protein levels.

    Directory of Open Access Journals (Sweden)

    Aejaz Sayeed

    Full Text Available Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. They also mediate signal transduction to regulate cell proliferation and survival. The type 1 insulin-like growth factor receptor (IGF-IR mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. We have previously demonstrated that β1 integrins regulate anchorage-independent growth of prostate cancer (PrCa cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. Furthermore, we have recently reported that IGF-IR regulates the expression of β1 integrins in PrCa cells. We have dissected the mechanism through which IGF-IR regulates β1 integrin expression in PrCa. Here we report that IGF-IR is crucial for PrCa cell growth and that β1 integrins contribute to the regulation of proliferation by IGF-IR. We demonstrate that β1 integrin regulation by IGF-IR does not occur at the mRNA level. Exogenous expression of a CD4 - β1 integrin cytoplasmic domain chimera does not interfere with such regulation and fails to stabilize β1 integrin expression in the absence of IGF-IR. This appears to be due to the lack of interaction between the β1 cytoplasmic domain and IGF-IR. We demonstrate that IGF-IR stabilizes the β1 subunit by protecting it from proteasomal degradation. The α5 subunit, one of the binding partners of β1, is also downregulated along with β1 upon IGF-IR knockdown while no change is observed in the expression of the α2, α3, α4, α6 and α7 subunits. Our results reveal a crucial mechanistic role for the α5β1 integrin, downstream of IGF-IR, in regulating cancer growth.

  18. Stable coordination of the inhibitory Ca2+ ion at MIDAS in integrin CD11b/CD18 by an antibody-derived ligand aspartate: Implications for integrin regulation and structure-based drug design

    Science.gov (United States)

    Mahalingam, Bhuvaneshwari; Ajroud, Kaouther; Alonso, Jose Luis; Anand, Saurabh; Adair, Brian; Horenstein, Alberto L; Malavasi, Fabio; Xiong, Jian-Ping; Arnaout, M. Amin

    2011-01-01

    A central feature of integrin interaction with physiologic ligands is the monodentate binding of a ligand carboxylate to a Mg2+ ion hexacoordinated at the metal-ion-dependent-adhesion site (MIDAS) in the integrin A-domain. This interaction stabilizes the A-domain in the high-affinity state, which is distinguished from the default low-affinity state by tertiary changes in the domain that culminate in cell adhesion. Small molecule ligand-mimetic integrin antagonists act as partial agonists, eliciting similar activating conformational changes in the A-domain, which has contributed to paradoxical adhesion and increased patient mortality in large clinical trials. As with other ligand-mimetic integrin antagonists, the function-blocking monoclonal antibody (mAb) 107 binds MIDAS of integrin CD11b/CD18 A-domain (CD11bA), but in contrast, it favors the inhibitory Ca2+ ion over Mg2+ at MIDAS. We determined the crystal structures of the Fab fragment of mAb 107 complexed to the low- and high-affinity states of CD11bA. Favored binding of Ca2+ at MIDAS is caused by the unusual symmetric bidentate ligation of a Fab-derived ligand Asp to a heptacoordinated MIDAS Ca2+. Binding of Fab 107 to CD11bA did not trigger the activating tertiary changes in the domain or in the full-length integrin. These data show that denticity of the ligand Asp/Glu can modify divalent cation selectivity at MIDAS and hence integrin function. Stabilizing the Ca2+ ion at MIDAS by bidentate ligation to a ligand Asp/Glu may provide one approach for designing pure integrin antagonists. PMID:22095715

  19. Electric Signals Regulate the Directional Migration of Oligodendrocyte Progenitor Cells (OPCs via β1 Integrin

    Directory of Open Access Journals (Sweden)

    Bangfu Zhu

    2016-11-01

    Full Text Available The guided migration of neural cells is essential for repair in the central nervous system (CNS. Oligodendrocyte progenitor cells (OPCs will normally migrate towards an injury site to re-sheath demyelinated axons; however the mechanisms underlying this process are not well understood. Endogenous electric fields (EFs are known to influence cell migration in vivo, and have been utilised in this study to direct the migration of OPCs isolated from neonatal Sprague-Dawley rats. The OPCs were exposed to physiological levels of electrical stimulation, and displayed a marked electrotactic response that was dependent on β1 integrin, one of the key subunits of integrin receptors. We also observed that F-actin, an important component of the cytoskeleton, was re-distributed towards the leading edge of the migrating cells, and that this asymmetric rearrangement was associated with β1 integrin function.

  20. Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

    DEFF Research Database (Denmark)

    Aszodi, Attila; Hunziker, Ernst B; Brakebusch, Cord

    2003-01-01

    Beta1 integrins are highly expressed on chondrocytes, where they mediate adhesion to cartilage matrix proteins. To assess the functions of beta1 integrin during skeletogenesis, we inactivated the beta1 integrin gene in chondrocytes. We show here that these mutant mice develop a chondrodysplasia...... of various severity. beta1-deficient chondrocytes had an abnormal shape and failed to arrange into columns in the growth plate. This is caused by a lack of motility, which is in turn caused by a loss of adhesion to collagen type II, reduced binding to and impaired spreading on fibronectin, and an abnormal F......-actin organization. In addition, mutant chondrocytes show decreased proliferation caused by a defect in G1/S transition and cytokinesis. The G1/S defect is, at least partially, caused by overexpression of Fgfr3, nuclear translocation of Stat1/Stat5a, and up-regulation of the cell cycle inhibitors p16 and p21...

  1. Passivation of cobalt nanocluster assembled thin films with hydrogen

    DEFF Research Database (Denmark)

    Romero, C.P.; Volodin, A.; Di Vece, M.

    2012-01-01

    The effect of hydrogen passivation on bare and Pd capped cobalt nanocluster assembled thin films was studied with Rutherford backscattering spectrometry (RBS) and magnetic force microscopy (MFM) after exposure to ambient conditions. The nanoclusters are produced in a laser vaporization cluster...... source in which the helium carrier gas was mixed with hydrogen. RBS revealed that oxidation of the Co nanoclusters is considerably reduced by the presence of hydrogen during cluster formation. The capping did not modify the influence of the passivation. The hydrogen passivation method is especially...... effective in cases when capping of the films is not desirable, for example for magnetic studies. Clear differences in the magnetic domain structures between hydrogen passivated and non-passivated Co nanocluster films were demonstrated by MFM and are attributed to a difference in inter-cluster magnetic...

  2. Adsorption of small gas molecules on B36 nanocluster

    Indian Academy of Sciences (India)

    Supplementary Information. Journal of Chemical Sciences. Adsorption of small gas molecules on B36 nanocluster. YOUNES VALADBEIGI. *. , HOSSEIN FARROKHPOUR and MAHMOUD TABRIZCHI. Department of chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Iran. *. Corresponding Author: Younes ...

  3. Tunneling-Electron-Induced Light Emission from Single Gold Nanoclusters.

    Science.gov (United States)

    Yu, Arthur; Li, Shaowei; Czap, Gregory; Ho, W

    2016-09-14

    The coupling of tunneling electrons with the tip-nanocluster-substrate junction plasmon was investigated by monitoring light emission in a scanning tunneling microscope (STM). Gold atoms were evaporated onto the ∼5 Å thick Al2O3 thin film grown on the NiAl (110) surface where they formed nanoclusters 3-7 nm wide. Scanning tunneling spectroscopy (STS) of these nanoclusters revealed quantum-confined electronic states. Spatially resolved photon imaging showed localized emission hot spots. Size dependent study and light emission from nanocluster dimers further support the viewpoint that coupling of tunneling electrons to the junction plasmon is the main radiative mechanism. These results showed the potential of the STM to reveal the electronic and optical properties of nanoscale metallic systems in the confined geometry of the tunnel junction.

  4. Switching a Nanocluster Core from Hollow to Non-hollow

    KAUST Repository

    Bootharaju, Megalamane Siddaramappa; Joshi, Chakra Prasad; Alhilaly, Mohammad J.; Bakr, Osman

    2016-01-01

    Modulating the structure-property relationship in atomically precise nanoclusters (NCs) is vital for developing novel NC materials and advancing their applications. While promising biphasic ligand-exchange (LE) strategies have been developed

  5. Silver Nanoclusters: From Design Principles to Practical Applications

    KAUST Repository

    Abdulhalim, Lina G.

    2015-12-08

    A strategy based on reticulating metal ions and organic ligands into atomically precise gold and silver nanoclusters (NCs) with high monodispersity has been advanced to a point that allows the design of NCs with strict stoichiometries, functionalities and valence. Of the Ag NCs discovered, Ag44 is the most studied, not only due to its high absorption that transcends the visible spectrum suitable for photovoltaics but also because of its long excited state lifetime, as revealed by nanosecond transient absorption spectroscopy. A major principle discovered in this dissertation is the ability to produce Ag44 in scalable amounts and with high stability in addition to modulation of the functional groups of the organic ligands via a fast and complete ligand exchange process. This new discovery has led to the development of synthetic designs in which new sizes were obtained by varying the reaction parameters (e.g., ligands functionality, reaction temperature and time), namely, Ag29 using dithiols and phosphines. The synthesized NCs possess tetravalent functionalities that facilitate their crystallization and characterization. Furthermore, Ag29 glows red and is therefore a possible candidate for sensing and imaging applications.

  6. Tailoring the magnetic properties of cobalt-ferrite nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Vega, A. Estrada de la; Garza-Navarro, M. A., E-mail: marco.garzanr@uanl.edu.mx; Durán-Guerrero, J. G.; Moreno Cortez, I. E.; Lucio-Porto, R.; González-González, V. [Universidad Autónoma de Nuevo León, Facultad de Ingeniería Mecánica y Eléctrica (Mexico)

    2016-01-15

    In this contribution, we report on the tuning of magnetic properties of cobalt-ferrite nanoclusters. The cobalt-ferrite nanoclusters were synthesized from a two-step approach that consists of the synthesis of cobalt-ferrite nanoparticles in organic media, followed by their dispersion into aqueous dissolution to form an oil-in-water emulsion. These emulsions were prepared at three different concentrations of the cationic surfactant cetyltrimethylammonium bromide (CTAB), in order to control the size and clustering density of the nanoparticles in the nanoclusters. The synthesized samples were characterized by transmission electron microscopy and their related techniques, such as bright-field and Z-contrast imaging, electron diffraction and energy-dispersive X-ray spectrometry; as well as static magnetic measures. The experimental evidence indicates that the size, morphology, and nanoparticles clustering density in the nanoclusters is highly dependent of the cobalt-ferrite:CTAB molar ratio that is used in their synthesis. In addition, due to the clustering of the nanoparticles into the nanoclusters, their magnetic moments are blocked to relax cooperatively. Hence, the magnetic response of the nanoclusters can be tailored by controlling the size and nanoparticles clustering density.

  7. Alterated integrin expression in lichen planopilaris

    Directory of Open Access Journals (Sweden)

    Erriquez Roberta

    2007-02-01

    Full Text Available Abstract Background Lichen planopilaris (LPP is an inflammatory disease characterized by a lymphomononuclear infiltrate surrounding the isthmus and infundibulum of the hair follicle of the scalp, that evolves into atrophic/scarring alopecia. In the active phase of the disease hairs are easily plucked with anagen-like hair-roots. In this study we focused on the expression of integrins and basement membrane components of the hair follicle in active LPP lesions. Methods Scalp biopsies were taken in 10 patients with LPP and in 5 normal controls. Using monoclonal antibodies against α3β1 and α6β4 integrins we showed the expression of these integrins and of the basement membrane components of the hair follicle in active LPP lesions and in healthy scalp skin. Results In the LPP involved areas, α3β1 was distributed in a pericellular pattern, the α6 subunit was present with a basolateral distribution while the β4 subunit showed discontinuous expression at the basal pole and occasionally, basolateral staining of the hair follicle. Conclusion: An altered distribution of the integrins in active LPP lesions can explain the phenomenon of easy pulling-out of the hair with a "gelatinous" root-sheath.

  8. Endothelial adhesion molecules and leukocyte integrins in preeclamptic patients.

    Science.gov (United States)

    Haller, H; Ziegler, E M; Homuth, V; Drab, M; Eichhorn, J; Nagy, Z; Busjahn, A; Vetter, K; Luft, F C

    1997-01-01

    Endothelial cell activation is important in the pathogenesis of preeclampsia; however, the nature of the activation is unknown. We investigated 22 patients with preeclampsia. 29 normotensive pregnancies, and 18 nonpregnant women to test the hypothesis that serum from preeclamptic patients induces expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) and stimulates intracellular free calcium concentrations [Ca2+]i in cultured endothelial cells. We then asked whether the corresponding integrin adhesive counter receptors lymphocyte function-associated antigen-1 (CD11a/CD18), macrophage-1 antigen (CD11b/CD18), p150,95 (CD11c/CD18), and very late activation antigen-4 (CD49/CD29) are increased in patients with preeclampsia. In the pregnant women, the measurements were conducted both before and after delivery. Integrin expression was measured by fluorescent antibody cell sorting analysis using monoclonal antibodies. ICAM-1 and VCAM-1 were analyzed on endothelial cells by enzyme-linked immunosorbent assay. [Ca2+]i was measured with fura 2. Serum from preeclamptic patients increased endothelial cell ICAM-1 expression but not VCAM-1 expression. Preeclamptic patients' serum also increased [Ca2+]i in endothelial cells compared with serum from normal nonpregnant or normal pregnant women. Endothelial cell [Ca2+]i concentrations were correlated with the ICAM-1 expression in preeclamptic patients (r = .80, P preclampsia and normal pregnancy compared with the nonpregnant state. The expression decreased significantly after delivery in both groups. Our results demonstrate that serum from preeclamptic women induces increased ICAM-1 surface expression on endothelial cells, while the expression of the integrin counterreceptors was not different. The effect on endothelial cells may be related to an increase in [Ca2+]i. The effect on cultured endothelial cells and the rapid decrease after delivery suggests the presence of a circulating serum

  9. The small GTPase, Rap1, mediates CD31-induced integrin adhesion

    NARCIS (Netherlands)

    Reedquist, K. A.; Ross, E.; Koop, E. A.; Wolthuis, R. M.; Zwartkruis, F. J.; van Kooyk, Y.; Salmon, M.; Buckley, C. D.; Bos, J. L.

    2000-01-01

    Integrin-mediated leukocyte adhesion is a critical aspect of leukocyte function that is tightly regulated by diverse stimuli, including chemokines, antigen receptors, and adhesion receptors. How cellular signals from CD31 and other adhesion amplifiers are integrated with those from classical

  10. EMMPRIN reduction via scFv-M6-1B9 intrabody affects α3β1-integrin and MCT1 functions and results in suppression of progressive phenotype in the colorectal cancer cell line Caco-2.

    Science.gov (United States)

    Sangboonruang, S; Thammasit, P; Intasai, N; Kasinrerk, W; Tayapiwatana, C; Tragoolpua, K

    2014-06-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) exhibits overexpression in various cancers and promotes cancer progression and metastasis via the interaction with its associated molecules. The scFv-M6-1B9 intrabody has a potential ability to reduce EMMPRIN cell surface expression. However, the subsequent effect of scFv-M6-1B9 intrabody-mediated EMMPRIN abatement on its related molecules, α3β1-integrin, MCT1, MMP-2 and MMP-9, is undefined. Our results demonstrated that the scFv-M6-1B9 intrabody efficiently decreased α3β1-integrin cell surface expression levels. In addition, intracellular accumulation of MCT1 and lactate were increased. These results lead to suppression of features characteristic for tumor progression, including cell migration, proliferation and invasion, in a colorectal cancer cell line (Caco-2) although there was no difference in MMP expression. Thus, EMMPRIN represents an attractive target molecule for the disruption of cancer proliferation and metastasis. An scFv-M6-1B9 intrabody-based approach could be relevant for cancer gene therapy.

  11. Integrins, muscle agrin and sarcoglycans during muscular inactivity conditions: an immunohistochemical study

    Directory of Open Access Journals (Sweden)

    G Anastasi

    2009-06-01

    Full Text Available Sarcoglycans are transmembrane proteins that seem to be functionally and pathologically as important as dystrophin. Sarcoglycans cluster together to form a complex, which is localized in the cell membrane of skeletal, cardiac, and smooth muscle. It has been proposed that the dystrophin-glycoprotein complex (DGC links the actin cytoskeleton with the extracellular matrix and the proper maintenance of this connection is thought to be crucial to the mechanical stability of the sarcolemma. The integrins are a family of heterodimeric cell surface receptors which play a crucial role in cell adhesion including cell-matrix and intracellular interactions and therefore are involved in various biological phenomena, including cell migration, and differentiation tissue repair. Sarcoglycans and integrins play a mechanical and signaling role stabilizing the systems during cycles of contraction and relaxation.Several studies suggested the possibility that integrins might play a role in muscle agrin signalling. On these basis, we performed an immunohistochemical analyzing sarcoglycans, integrins and agrin, on human skeletal muscle affected by sensitive-motor polyneuropathy, in order to better define the correlation between these proteins and neurogenic atrophy due to peripheral neuropathy. Our results showed the existence of a cascade mechanism which provoke a loss of regulatory effects of muscle activity on costameres, due to loss of muscle and neural agrin.This cascade mechanism could determine a quantitative modification of transmembrane receptors and loss of ?7B could be replaced and reinforced by enhanced expression of the ?7A integrin to restore muscle fiber viability. Second, it is possible that the reduced cycles of contraction and relaxation of muscle fibers, during muscular atrophy, provoke a loss of mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix. Consequently, these mechanical

  12. Kindlins, integrin activation and the regulation of talin recruitment to αIIbβ3.

    Directory of Open Access Journals (Sweden)

    Bryan N Kahner

    Full Text Available Talins and kindlins bind to the integrin β3 cytoplasmic tail and both are required for effective activation of integrin αIIbβ3 and resulting high-affinity ligand binding in platelets. However, binding of the talin head domain alone to β3 is sufficient to activate purified integrin αIIbβ3 in vitro. Since talin is localized to the cytoplasm of unstimulated platelets, its re-localization to the plasma membrane and to the integrin is required for activation. Here we explored the mechanism whereby kindlins function as integrin co-activators. To test whether kindlins regulate talin recruitment to plasma membranes and to αIIbβ3, full-length talin and kindlin recruitment to β3 was studied using a reconstructed CHO cell model system that recapitulates agonist-induced αIIbβ3 activation. Over-expression of kindlin-2, the endogenous kindlin isoform in CHO cells, promoted PAR1-mediated and talin-dependent ligand binding. In contrast, shRNA knockdown of kindlin-2 inhibited ligand binding. However, depletion of kindlin-2 by shRNA did not affect talin recruitment to the plasma membrane, as assessed by sub-cellular fractionation, and neither over-expression of kindlins nor depletion of kindlin-2 affected talin interaction with αIIbβ3 in living cells, as monitored by bimolecular fluorescence complementation. Furthermore, talin failed to promote kindlin-2 association with αIIbβ3 in CHO cells. In addition, purified talin and kindlin-3, the kindlin isoform expressed in platelets, failed to promote each other's binding to the β3 cytoplasmic tail in vitro. Thus, kindlins do not promote initial talin recruitment to αIIbβ3, suggesting that they co-activate integrin through a mechanism independent of recruitment.

  13. Targeted inhibition of αvβ3 integrin with an RNA aptamer impairs endothelial cell growth and survival

    International Nuclear Information System (INIS)

    Mi Jing; Zhang Xiuwu; Giangrande, Paloma H.; McNamara, James O.; Nimjee, Shahid M.; Sarraf-Yazdi, Shiva; Sullenger, Bruce A.; Clary, Bryan M.

    2005-01-01

    αvβ3 integrin is a crucial factor involved in a variety of physiological processes, such as cell growth and migration, tumor invasion and metastasis, angiogenesis, and wound healing. αvβ3 integrin exerts its effect by regulating endothelial cell (EC) migration, proliferation, and survival. Inhibiting the function of αvβ3 integrin, therefore, represents a potential anti-cancer, anti-thrombotic, and anti-inflammatory strategy. In this study, we tested an RNA aptamer, Apt-αvβ3 that binds recombinant αvβ3 integrin, for its ability to bind endogenous αvβ3 integrin on the surface of cells in culture and to subsequently affect cellular response. Our data illustrate that Apt-αvβ3 binds αvβ3 integrin expressed on the surface of live HUVECs. This interaction significantly decreases both basal and PDGF-induced cell proliferation as well as inhibition of cell adhesion. Apt-αvβ3 can also reduce PDGF-stimulated tube formation and increase HUVEC apoptosis through inhibition of FAK phosphorylation pathway. Our results demonstrate that by binding to its target, Apt-αvβ3 can efficiently inhibit human EC proliferation and survival, resulting in reduced angiogenesis. It predicts that Apt-αvβ3 could become useful in both tumor imaging and the treatment of tumor growth, atherosclerosis, thrombosis, and inflammation

  14. Down-regulation of integrin β1 and focal adhesion kinase in renal glomeruli under various hemodynamic conditions.

    Directory of Open Access Journals (Sweden)

    Xiaoli Yuan

    Full Text Available Given that integrin β1 is an important component of the connection to maintain glomerular structural integrity, by binding with multiple extracellular matrix proteins and mediating intracellular signaling. Focal adhesion kinase (FAK is the most essential intracellular integrator in the integrin β1-FAK signalling pathway. Here, we investigated the changes of the two molecules and visualized the possible interaction between them under various hemodynamic conditions in podocytes. Mice kidney tissues were prepared using in vivo cryotechnique (IVCT and then were stained and observed using light microscopy, confocal laser scanning microscopy and immunoelectron microscopy. The expression of these molecules were examined by western blot. Under the normal condition, integrin β1 stained continually and evenly at the membrane, and FAK was located in the cytoplasm and nuclei of the podocytes. There were significant colocalized plaques of two molecules. But under acute hypertensive and cardiac arrest conditions, integrin β1 decreased and stained intermittently. Similarly, FAK decreased and appeared uneven. Additionally, FAK translocated to the nuclei of the podocytes. As a result, the colocalization of integrin β1 and FAK reduced obviously under these conditions. Western blot assay showed a consistent result with the immunostaining. Collectively, the abnormal redistribution and decreased expressions of integrin β1 and FAK are important molecular events in regulating the functions of podocytes under abnormal hemodynamic conditions. IVCT could offer considerable advantages for morphological analysis when researching renal diseases.

  15. Synthesis of crystalline Ge nanoclusters in PE-CVD-deposited SiO2 films

    DEFF Research Database (Denmark)

    Leervad Pedersen, T.P.; Skov Jensen, J.; Chevallier, J.

    2005-01-01

    The synthesis of evenly distributed Ge nanoclusters in plasma-enhanced chemical-vapour-deposited (PE-CVD) SiO2 thin films containing 8 at. % Ge is reported. This is of importance for the application of nanoclusters in semiconductor technology. The average diameter of the Ge nanoclusters can...

  16. Silver Nanocluster Reparative Effect in Hernioplasty

    Directory of Open Access Journals (Sweden)

    Nikolay M. Anichkov

    2014-06-01

    Full Text Available Background: The acceleration of re-epithelialization and fibroblast differentiation were noted during the experiments with silver nanoclusters (SNs by interrupting the negative development of inflammation at the level of cytokines and promoting a positive course of reparative processes. The aim of this work was to elaborate the experimental model of prosthesis hernioplasty in subcutaneous and intraperitoneal locations of hernioprostheses with SNs, which allowed us to study the course of reparative reactions in all layers of the anterior abdominal wall. Material and Methods: We used a modified hernioprosthesis made from polyester fibers coated with a metal-polymer composition, including the stabilized SN in a concentration of 6.8 and 11.3 mg per 1 g of the hernioprosthesis mesh. During this research we used guinea pigs to study the in vivo tissue reactions. The clinical part of the study included the group of 212 patients who underwent removal of an inguinal hernia. We have identified various factors associated with infectious and toxic effects on the body by determining the level of the serum glutamate-pyruvate-transaminase (SGPT. Results: In implantation of the hernioprostheses, including the high concentration of SN in the laparotomy wound, the exudative component of the inflammation was weakly expressed. It was mostly the proliferative changes that took place. We did not find either CD8-positive type T lymphocytes or PAX5-positive type B activated cells in the exudate. Conclusion: Our research has shown that the use of hernioprostheses that include silver nanoclusters leads to the reduction of inflammation in the exudative phase and to a more favorable course of reparative processes.

  17. Controllable 5-sulfosalicylic acid assisted solvothermal synthesis of monodispersed superparamagnetic Fe{sub 3}O{sub 4} nanoclusters with tunable size

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wentao [State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Tang, Bingtao, E-mail: tangbt@dlut.edu.cn [State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Wu, Suli; Gao, Zhanming; Ju, Benzhi [State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Teng, Xiaoxu [School of Chemistry and Chemical Engineering, Yangtze Normal University, Chongqing 408100 (China); Zhang, Shufen [State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China)

    2017-02-01

    Monodispersed Fe{sub 3}O{sub 4} nanoclusters were synthesized in a one-pot solvothermal route with 5-sulfosalicylic acid (SSA) as the functional ligand in a mixed-solvent system of diethylene glycol/ethylene glycol (DEG/EG). Nucleation and aggregation growth model was responsible for the formation of secondary structure of the clusters. In the process, the size of the clusters can be effectively controlled by varying the amounts of SSA and the volume ratio of DEG/EG. The nanoclusters exhibited superparamagnetic properties with high saturation magnetization value of about 68.7 emu g{sup −1} at room temperature. The water-soluble small-molecule SSA grafted on the surface of Fe{sub 3}O{sub 4} nanocrystals rendered the superparamagnetic clusters dispersible in water, which is crucial for potential applications in biomedical fields. - Graphical abstract: 5-sulfosalicylic acid assisted solvothermal synthesis of monodispersed superparamagnetic Fe{sub 3}O{sub 4} nanoclusters with tunable size by a mixed-solvent system of DEG/EG. - Highlights: • Monodispersed Fe{sub 3}O{sub 4} nanoclusters were synthesized in a one-pot 5-sulfosalicylic acid assisted solvothermal route. • The size of the clusters are tunable by varying the amounts of 5-sulfosalicylic acid and the volume ratio of DEG/EG. • The nanoclusters exhibited superparamagnetic properties with high saturation magnetization value. • The 5-sulfosalicylic acid grafted Fe{sub 3}O{sub 4} nanoclusters can be dispersed in water.

  18. Resonant surface-enhanced Raman scattering by optical phonons in a monolayer of CdSe nanocrystals on Au nanocluster arrays

    Energy Technology Data Exchange (ETDEWEB)

    Milekhin, Alexander G., E-mail: milekhin@isp.nsc.ru [A.V. Rzhanov Institute of Semiconductor Physics, pr. Lavrentjeva, 13, 630090 Novosibirsk (Russian Federation); Novosibirsk State University, Pirogov str. 2, 630090 Novosibirsk (Russian Federation); Sveshnikova, Larisa L.; Duda, Tatyana A. [A.V. Rzhanov Institute of Semiconductor Physics, pr. Lavrentjeva, 13, 630090 Novosibirsk (Russian Federation); Rodyakina, Ekaterina E. [A.V. Rzhanov Institute of Semiconductor Physics, pr. Lavrentjeva, 13, 630090 Novosibirsk (Russian Federation); Novosibirsk State University, Pirogov str. 2, 630090 Novosibirsk (Russian Federation); Dzhagan, Volodymyr M. [Semiconductor Physics, Technische Universität Chemnitz, D-09107 Chemnitz (Germany); Sheremet, Evgeniya [Solid Surfaces Analysis, Technische Universität Chemnitz, D-09107 Chemnitz (Germany); Gordan, Ovidiu D. [Semiconductor Physics, Technische Universität Chemnitz, D-09107 Chemnitz (Germany); Himcinschi, Cameliu [Institut für Theoretische Physik, TU Bergakademie Freiberg, 09596 Freiberg (Germany); Latyshev, Alexander V. [A.V. Rzhanov Institute of Semiconductor Physics, pr. Lavrentjeva, 13, 630090 Novosibirsk (Russian Federation); Novosibirsk State University, Pirogov str. 2, 630090 Novosibirsk (Russian Federation); Zahn, Dietrich R.T. [Semiconductor Physics, Technische Universität Chemnitz, D-09107 Chemnitz (Germany)

    2016-05-01

    Highlights: • Regular Au nanocluster and dimer arrays as well as single Au dimers are fabricated. • Resonant SERS by monolayers of CdSe nanocrystals deposited on the Au nanostructures is observed. • LO energy change for CdSe NCs on different single Au dimers indicates SERS by single or a few NCs. - Abstract: Here we present the results on an investigation of resonant Stokes and anti- Stokes surface-enhanced Raman scattering (SERS) by optical phonons in colloidal CdSe nanocrystals (NCs) homogeneously deposited on arrays of Au nanoclusters using the Langmuir–Blodgett technology. The thickness of deposited NCs, determined by transmission and scanning electron microscopy, amounts to approximately 1 monolayer. Special attention is paid to the determination of the localized surface plasmon resonance (LSPR) energy in the arrays of Au nanoclusters as a function of the nanocluster size by means of micro-ellipsometry. SERS by optical phonons in CdSe NCs shows a significant enhancement factor with a maximal value of 2 × 10{sup 3} which depends resonantly on the Au nanocluster size and thus on the LSPR energy. The deposition of CdSe NCs on the arrays of Au nanocluster dimers enabled us to study the polarization dependence of SERS. It was found that a maximal SERS signal is observed for the light polarization along the dimer axis. Finally, SERS by optical phonons was observed for CdSe NCs deposited on the structures with a single Au dimer. A difference of the LO phonon energy is observed for CdSe NCs on different single dimers. This effect is explained as the confinement-induced shift which depends on the CdSe nanocrystal size and indicates quasi-single NC Raman spectra being obtained.

  19. Polarization of the epithelial layer and apical localization of integrins are required for engulfment of apoptotic cells in the Drosophila ovary

    Directory of Open Access Journals (Sweden)

    Tracy L. Meehan

    2015-12-01

    Full Text Available Inefficient clearance of dead cells or debris by epithelial cells can lead to or exacerbate debilitating conditions such as retinitis pigmentosa, macular degeneration, chronic obstructive pulmonary disease and asthma. Despite the importance of engulfment by epithelial cells, little is known about the molecular changes that are required within these cells. The misregulation of integrins has previously been associated with disease states, suggesting that a better understanding of the regulation of receptor trafficking could be key to treating diseases caused by defects in phagocytosis. Here, we demonstrate that the integrin heterodimer αPS3/βPS becomes apically enriched and is required for engulfment by the epithelial follicle cells of the Drosophila ovary. We found that integrin heterodimer localization and function is largely directed by the α-subunit. Moreover, proper cell polarity promotes asymmetric integrin enrichment, suggesting that αPS3/βPS trafficking occurs in a polarized fashion. We show that several genes previously known for their roles in trafficking and cell migration are also required for engulfment. Moreover, as in mammals, the same α-integrin subunit is required by professional and non-professional phagocytes and migrating cells in Drosophila. Our findings suggest that migrating and engulfing cells use common machinery, and demonstrate a crucial role for integrin function and polarized trafficking of integrin subunits during engulfment. This study also establishes the epithelial follicle cells of the Drosophila ovary as a powerful model for understanding the molecular changes required for engulfment by a polarized epithelium.

  20. NanoClusters Enhance Drug Delivery in Mechanical Ventilation

    Science.gov (United States)

    Pornputtapitak, Warangkana

    The overall goal of this thesis was to develop a dry powder delivery system for patients on mechanical ventilation. The studies were divided into two parts: the formulation development and the device design. The pulmonary system is an attractive route for drug delivery since the lungs have a large accessible surface area for treatment or drug absorption. For ventilated patients, inhaled drugs have to successfully navigate ventilator tubing and an endotracheal tube. Agglomerates of drug nanoparticles (also known as 'NanoClusters') are fine dry powder aerosols that were hypothesized to enable drug delivery through ventilator circuits. This Thesis systematically investigated formulations of NanoClusters and their aerosol performance in a conventional inhaler and a device designed for use during mechanical ventilation. These engineered powders of budesonide (NC-Bud) were delivered via a MonodoseRTM inhaler or a novel device through commercial endotracheal tubes, and analyzed by cascade impaction. NC-Bud had a higher efficiency of aerosol delivery compared to micronized stock budesonide. The delivery efficiency was independent of ventilator parameters such as inspiration patterns, inspiration volumes, and inspiration flow rates. A novel device designed to fit directly to the ventilator and endotracheal tubing connections and the MonodoseRTM inhaler showed the same efficiency of drug delivery. The new device combined with NanoCluster formulation technology, therefore, allowed convenient and efficient drug delivery through endotracheal tubes. Furthermore, itraconazole (ITZ), a triazole antifungal agent, was formulated as a NanoCluster powder via milling (top-down process) or precipitation (bottom-up process) without using any excipients. ITZ NanoClusters prepared by wet milling showed better aerosol performance compared to micronized stock ITZ and ITZ NanoClusters prepared by precipitation. ITZ NanoClusters prepared by precipitation methods also showed an amorphous state

  1. Study of nanocluster-assembled ZnO thin films by nanocluster-beam deposition

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Zhiwei; Lei, Wei; Zhang, Xiaobing [School of Electronic Science and Engieering, Southeast University, Nanjing (China); Tay, Beng Kang [School of Electronical and Electronic Engineering, Nanyang Technological University, Nanyang (Singapore)

    2012-01-15

    Nanocluster-assembled ZnO thin films were obtained by nanocluster-beam deposition, in which nanoclusters were produced by a magnetron sputtering gas aggregation source. Two kinds of ZnO thin films were obtained using this method with the one grown under the on-line heating temperature of 700 C, and the other grown without on-line heating. Film microstructure and optical properties are investigated by various diagnostic techniques. It was found that both of film microstructure of ZnO thin films keep wurtzite structure as that of ZnO bulk materials. The averaged particle size for the film grown without on-line heating is around 6 nm, which is a little lower than that grown with the on-line heating. It was also found that as increasing the wavelength, both of the absorbance spectra for the films decrease sharply near ultra-visible to extend slowly to the visible and infrared wavelength range. For the film grown without on-line heating, the bandgap energy was estimated to 3.77 eV, while for the film grown with on-line heating, the bandgap energy was redshift to 3.71 eV. Similar behavior was also found for PL spectra analysis, where PL spectrum exhibited a peak centered at 3.31 eV without on-line heating, while it redshift to 3.20 eV with on-line heating. The mechanisms behind these behaviors were presented in this article. (copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  2. Ultrafast, 2 min synthesis of monolayer-protected gold nanoclusters (d < 2 nm)

    Science.gov (United States)

    Martin, Matthew N.; Li, Dawei; Dass, Amala; Eah, Sang-Kee

    2012-06-01

    An ultrafast synthesis method is presented for hexanethiolate-coated gold nanoclusters (d gold nanoclusters are separated from the reaction byproducts fast and easily without any need for post-synthesis cleaning.An ultrafast synthesis method is presented for hexanethiolate-coated gold nanoclusters (d gold nanoclusters are separated from the reaction byproducts fast and easily without any need for post-synthesis cleaning. Electronic supplementary information (ESI) available: Experimental details of gold nanocluster synthesis and mass-spectrometry. See DOI: 10.1039/c2nr30890h

  3. Ag29(BDT)12(TPP)4: A Tetravalent Nanocluster

    KAUST Repository

    AbdulHalim, Lina G.

    2015-06-24

    The bottom-up assembly of nanoparticles into diverse ordered solids is a challenge because it requires nanoparticles, which are often quasi-spherical, to have interaction anisotropy akin to atoms and molecules. Typically, anisotropy has been introduced by changing the shape of the inorganic nanoparticle core. Here, we present the design, self-assembly, optical properties and total structural determination of Ag29(BDT)12(TPP)4, an atomically precise tetravalent nanocluster (NC) (BDT: 1,3-benzenedithiols; TPP: triphenylphosphine). It features four unique tetrahedrally symmetrical binding surface sites facilitated by the supramolecular assembly of 12 BDT—wide footprint bidentate thiols—in the ligand shell. When each of these sites was selectively functionalized by a single phosphine ligand, particle stability, synthetic yield and the propensity to self-assemble into macroscopic crystals increased. The solid crystallized NCs have a substantially narrowed optical bandgap compared to that of the solution state, suggesting strong inter-particle electronic coupling occurs in the solid state.

  4. Exotic high activity surface patterns in PtAu nanoclusters

    KAUST Repository

    Mokkath, Junais Habeeb

    2013-05-09

    The structure and chemical ordering of PtAu nanoclusters of 79, 135, and 201 atoms are studied via a combination of a basin hopping atom-exchange technique (to locate the lowest energy homotops at fixed composition), a symmetry orbit technique (to find the high symmetry isomers), and density functional theory local reoptimization (for determining the most stable homotop). The interatomic interactions between Pt and Au are derived from the empirical Gupta potential. The lowest energy structures show a marked tendency toward PtcoreAushell chemical ordering by enrichment of the more cohesive Pt in the core region and of Au in the shell region. We observe a preferential segregation of Pt atoms to (111) facets and Au atoms to (100) facets of the truncated octahedron cluster motif. Exotic surface patterns are obtained particularly for Pt-rich compositions, where Pt atoms are being surrounded by Au atoms. These surface arrangements boost the catalytic activity by creating a large number of active sites. © 2013 American Chemical Society.

  5. A strategy to find minimal energy nanocluster structures.

    Science.gov (United States)

    Rogan, José; Varas, Alejandro; Valdivia, Juan Alejandro; Kiwi, Miguel

    2013-11-05

    An unbiased strategy to search for the global and local minimal energy structures of free standing nanoclusters is presented. Our objectives are twofold: to find a diverse set of low lying local minima, as well as the global minimum. To do so, we use massively the fast inertial relaxation engine algorithm as an efficient local minimizer. This procedure turns out to be quite efficient to reach the global minimum, and also most of the local minima. We test the method with the Lennard-Jones (LJ) potential, for which an abundant literature does exist, and obtain novel results, which include a new local minimum for LJ13 , 10 new local minima for LJ14 , and thousands of new local minima for 15≤N≤65. Insights on how to choose the initial configurations, analyzing the effectiveness of the method in reaching low-energy structures, including the global minimum, are developed as a function of the number of atoms of the cluster. Also, a novel characterization of the potential energy surface, analyzing properties of the local minima basins, is provided. The procedure constitutes a promising tool to generate a diverse set of cluster conformations, both two- and three-dimensional, that can be used as an input for refinement by means of ab initio methods. Copyright © 2013 Wiley Periodicals, Inc.

  6. Ag29(BDT)12(TPP)4: A Tetravalent Nanocluster

    KAUST Repository

    AbdulHalim, Lina G.; Bootharaju, Megalamane Siddaramappa; Tang, Qing; Del Gobbo, Silvano; AbdulHalim, Rasha; Eddaoudi, Mohamed; Jiang, De-en; Bakr, Osman

    2015-01-01

    The bottom-up assembly of nanoparticles into diverse ordered solids is a challenge because it requires nanoparticles, which are often quasi-spherical, to have interaction anisotropy akin to atoms and molecules. Typically, anisotropy has been introduced by changing the shape of the inorganic nanoparticle core. Here, we present the design, self-assembly, optical properties and total structural determination of Ag29(BDT)12(TPP)4, an atomically precise tetravalent nanocluster (NC) (BDT: 1,3-benzenedithiols; TPP: triphenylphosphine). It features four unique tetrahedrally symmetrical binding surface sites facilitated by the supramolecular assembly of 12 BDT—wide footprint bidentate thiols—in the ligand shell. When each of these sites was selectively functionalized by a single phosphine ligand, particle stability, synthetic yield and the propensity to self-assemble into macroscopic crystals increased. The solid crystallized NCs have a substantially narrowed optical bandgap compared to that of the solution state, suggesting strong inter-particle electronic coupling occurs in the solid state.

  7. "light-on" sensing of antioxidants using gold nanoclusters

    KAUST Repository

    Hu, Lianzhe

    2014-05-20

    Depletion of intracellular antioxidants is linked to major cytotoxic events and cellular disorders, such as oxidative stress and multiple sclerosis. In addition to medical diagnosis, determining the concentration of antioxidants in foodstuffs, food preservatives, and cosmetics has proved to be very vital. Gold nanoclusters (Au-NCs) have a core size below 2 nm and contain several metal atoms. They have interesting photophysical properties, are readily functionalized, and are safe to use in various biomedical applications. Herein, a simple and quantitative spectroscopic method based on Au-NCs is developed to detect and image antioxidants such as ascorbic acid. The sensing mechanism is based on the fact that antioxidants can protect the fluorescence of Au-NCs against quenching by highly reactive oxygen species. Our method shows great accuracy when employed to detect the total antioxidant capacity in commercial fruit juice. Moreover, confocal fluorescence microscopy images of HeLa cells show that this approach can be successfully used to image antioxidant levels in living cells. Finally, the potential application of this "light-on" detection method in multiple logic gate fabrication was discussed using the fluorescence intensity of Au-NCs as output. © 2014 American Chemical Society.

  8. Integrin beta3 Leu33Pro polymorphism and risk of hip fracture: 25 years follow-up of 9233 adults from the general population

    DEFF Research Database (Denmark)

    Tofteng, Charlotte L; Bach-Mortensen, Pernille; Bojesen, Stig E

    2007-01-01

    OBJECTIVE: Integrin alphavbeta3 is essential for mature osteoclast function and therefore important for the development of osteoporosis and osteoporotic fractures. Integrin alphavbeta3 antagonists have antiresorptive effects in bone. We tested the hypothesis that the Leu33Pro polymorphism...... in the integrin beta3-subunit associates with risk of hip fracture. METHODS: We included 9233 men and women selected at random to represent the Danish general population as participants in the Copenhagen City Heart Study. First-ever hip fractures (n=267) were registered during 25 years follow-up. Log...

  9. Beta1 integrin is not essential for hematopoiesis but is necessary for the T cell-dependent IgM antibody response

    DEFF Research Database (Denmark)

    Brakebusch, Cord; Fillatreau, Simon; Potocnik, Alexandre J

    2002-01-01

    Several experimental evidences suggested that beta1 integrin-mediated adhesion of hematopoietic stem cells (HSC) is important for their function in the bone marrow (BM). Using induced deletion of the beta1 integrin gene restricted to the hematopoietic system, we show that beta1 integrin...... is not essential for HSC retention in the BM, hematopoiesis, and trafficking of lymphocytes. However, immunization with a T cell-dependent antigen resulted in virtually no IgM production and an increased secretion of IgG in mutant mice, while the response to a T cell-independent type 2 antigen showed decreases...

  10. The role of alpha3beta1 integrin in determining the supramolecular organization of laminin-5 in the extracellular matrix of keratinocytes.

    Science.gov (United States)

    deHart, Gregory W; Healy, Kevin E; Jones, Jonathan C R

    2003-02-01

    Analyses of mice with targeted deletions in the genes for alpha3 and beta1 integrin suggest that the alpha3beta1 integrin heterodimer likely determines the organization of the extracellular matrix within the basement membrane of skin. Here we tested this hypothesis using keratinocytes derived from alpha3 integrin-null mice. We have compared the organizational state of laminin-5, a ligand of alpha3beta1 integrin, in the matrix of wild-type keratinocytes with that of laminin-5 in the matrix of alpha3 integrin-null cells. Laminin-5 distributes diffusely in arc structures in the matrix of wild-type mouse keratinocytes, whereas laminin-5 is organized into linear, spike-like arrays by the alpha3 integrin-null cells. The fact that alpha3 integrin-null cells are deficient in their ability to assemble a proper laminin-5 matrix is also shown by their failure to remodel laminin-5 when plated onto surfaces coated with purified laminin-5 protein. In sharp contrast, wild-type keratinocytes organize exogenously added laminin-5 into discrete ring-like organizations. These findings led us next to assess whether differences in laminin-5 organization in the matrix of the wild-type and alpha3 integrin-null cells impact cell behavior. Our results indicate that alpha3 integrin-null cells are more motile than their wild-type counterparts and leave extensive trails of laminin-5 over the surface on which they move. Moreover, HEK 293 cells migrate significantly more on the laminin-5-rich matrix derived from the alpha3 integrin-null cells than on the wild-type keratinocyte laminin-5 matrix. In addition, alpha3 integrin-null cells show low strength of adhesion to surfaces coated with purified laminin-5 compared to wild-type cells although both the wild type and the alpha3 integrin-null keratinocytes adhere equally strongly to laminin-5 that has been organized into arrays by other epithelial cells. These data suggest: (1) that alpha3beta1 integrin plays an important role in determining the

  11. Nanocluster irradiation evolution in Fe-9%Cr ODS and ferritic-martensitic alloys

    Science.gov (United States)

    Swenson, M. J.; Wharry, J. P.

    2017-12-01

    The objective of this study is to evaluate the influence of dose rate and cascade morphology on nanocluster evolution in a model Fe-9%Cr oxide dispersion strengthened steel and the commercial ferritic/martensitic (F/M) alloys HCM12A and HT9. We present a large, systematic data set spanning the three alloys, three irradiating particle types, four orders of magnitude in dose rate, and doses ranging 1-100 displacements per atom over 400-500 °C. Nanoclusters are characterized using atom probe tomography. ODS oxide nanoclusters experience partial dissolution after irradiation due to inverse Ostwald ripening, while F/M nanoclusters undergo Ostwald ripening. Damage cascade morphology is indicative of nanocluster number density evolution. Finally, the effects of dose rate on nanocluster morphology provide evidence for a temperature dilation theory, which purports that a negative temperature shift is necessary for higher dose rate irradiations to emulate nanocluster evolution in lower dose rate irradiations.

  12. Anti-IL-5 attenuates activation and surface density of β2-integrins on circulating eosinophils after segmental antigen challenge

    Science.gov (United States)

    Johansson, Mats W.; Gunderson, Kristin A.; Kelly, Elizabeth A. B.; Denlinger, Loren C.; Jarjour, Nizar N.; Mosher, Deane F.

    2013-01-01

    minimal effects on properties of eosinophils in BAL. Dampening of β2-integrin function of eosinophils in transit to inflamed airway may contribute to the decrease in lung inflammation caused by anti-IL-5. PMID:23414537

  13. Cellular Interaction of Integrin α3β1 with Laminin 5 Promotes Gap Junctional Communication

    Science.gov (United States)

    Lampe, Paul D.; Nguyen, Beth P.; Gil, Susana; Usui, Marcia; Olerud, John; Takada, Yoshikazu; Carter, William G.

    1998-01-01

    Wounding of skin activates epidermal cell migration over exposed dermal collagen and fibronectin and over laminin 5 secreted into the provisional basement membrane. Gap junctional intercellular communication (GJIC) has been proposed to integrate the individual motile cells into a synchronized colony. We found that outgrowths of human keratinocytes in wounds or epibole cultures display parallel changes in the expression of laminin 5, integrin α3β1, E-cadherin, and the gap junctional protein connexin 43. Adhesion of keratinocytes on laminin 5, collagen, and fibronectin was found to differentially regulate GJIC. When keratinocytes were adhered on laminin 5, both structural (assembly of connexin 43 in gap junctions) and functional (dye transfer) assays showed a two- to threefold increase compared with collagen and five- to eightfold over fibronectin. Based on studies with immobilized integrin antibody and integrin-transfected Chinese hamster ovary cells, the interaction of integrin α3β1 with laminin 5 was sufficient to promote GJIC. Mapping of intermediate steps in the pathway linking α3β1–laminin 5 interactions to GJIC indicated that protein trafficking and Rho signaling were both required. We suggest that adhesion of epithelial cells to laminin 5 in the basement membrane via α3β1 promotes GJIC that integrates individual cells into synchronized epiboles. PMID:9852164

  14. SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity.

    Science.gov (United States)

    Barker, Thomas H; Baneyx, Gretchen; Cardó-Vila, Marina; Workman, Gail A; Weaver, Matt; Menon, Priya M; Dedhar, Shoukat; Rempel, Sandra A; Arap, Wadih; Pasqualini, Renata; Vogel, Viola; Sage, E Helene

    2005-10-28

    SPARC, a 32-kDa matricellular glycoprotein, mediates interactions between cells and their extracellular matrix, and targeted deletion of Sparc results in compromised extracellular matrix in mice. Fibronectin matrix provides provisional tissue scaffolding during development and wound healing and is essential for the stabilization of mature extracellular matrix. Herein, we report that SPARC expression does not significantly affect fibronectin-induced cell spreading but enhances fibronectin-induced stress fiber formation and cell-mediated partial unfolding of fibronectin molecules, an essential process in fibronectin matrix assembly. By phage display, we identify integrin-linked kinase as a potential binding partner of SPARC and verify the interaction by co-immunoprecipitation and colocalization in vitro. Cells lacking SPARC exhibit diminished fibronectin-induced integrin-linked kinase activation and integrin-linked kinase-dependent cell-contractile signaling. Furthermore, induced expression of SPARC in SPARC-null fibroblasts restores fibronectin-induced integrin-linked kinase activation, downstream signaling, and fibronectin unfolding. These data further confirm the function of SPARC in extracellular matrix organization and identify a novel mechanism by which SPARC regulates extracellular matrix assembly.

  15. Integrin and glycocalyx mediated contributions to cell adhesion identified by single cell force spectroscopy

    International Nuclear Information System (INIS)

    Boettiger, D; Wehrle-Haller, B

    2010-01-01

    The measurement of cell adhesion using single cell force spectroscopy methods was compared with earlier methods for measuring cell adhesion. This comparison provided a means and rationale for separating components of the measurement retract curve that were due to interactions between the substrate and the glycocalyx, and interactions that were due to cell surface integrins binding to a substrate-bound ligand. The glycocalyx adhesion was characterized by multiple jumps with dispersed jump sizes that extended from 5 to 30 μm from the origin. The integrin mediated adhesion was represented by the F max (maximum detachment force), was generally within the first 5 μm and commonly detached with a single rupture cascade. The integrin peak (F max ) increases with time and the rate of increase shows large cell to cell variability with a peak ∼ 50 nN s -1 and an average rate of increase of 75 pN s -1 . This is a measure of the rate of increase in the number of adhesive integrin-ligand bonds/cell as a function of contact time.

  16. Thermodynamics, kinetics, and catalytic effect of dehydrogenation from MgH2 stepped surfaces and nanocluster: a DFT study

    Science.gov (United States)

    Reich, Jason; Wang, Linlin; Johnson, Duane

    2013-03-01

    We detail the results of a Density Functional Theory (DFT) based study of hydrogen desorption, including thermodynamics and kinetics with(out) catalytic dopants, on stepped (110) rutile and nanocluster MgH2. We investigate competing configurations (optimal surface and nanoparticle configurations) using simulated annealing with additional converged results at 0 K, necessary for finding the low-energy, doped MgH2 nanostructures. Thermodynamics of hydrogen desorption from unique dopant sites will be shown, as well as activation energies using the Nudged Elastic Band algorithm. To compare to experiment, both stepped structures and nanoclusters are required to understanding and predict the effects of ball milling. We demonstrate how these model systems relate to the intermediary sized structures typically seen in ball milling experiments.

  17. Oncofetal Chondroitin Sulfate Glycosaminoglycans are Key Players in Integrin Signaling and Tumor Cell Motility

    Science.gov (United States)

    Clausen, Thomas Mandel; Pereira, Marina Ayres; Al Nakouzi, Nader; Oo, Htoo Zarni; Agerbæk, Mette Ø; Lee, Sherry; Ørum-Madsen, Maj Sofie; Christensen, Anders Riis; El-Naggar, Amal; Grandgenett, Paul M.; Grem, Jean L.; Hollingsworth, Michael A.; Holst, Peter J.; Theander, Thor; Sorensen, Poul H.; Daugaard, Mads; Salanti, Ali

    2016-01-01

    Many tumors express proteoglycans modified with oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS), which are normally restricted to the placenta. However, the role of ofCS in cancer is largely unknown. The function of ofCS in cancer was analyzed using the recombinant ofCS-binding VAR2CSA protein (rVAR2) derived from the malaria parasite, Plasmodium falciparum. We demonstrate that ofCS plays a key role in tumor cell motility by affecting canonical integrin signaling pathways. Binding of rVAR2 to tumor cells inhibited the interaction of cells with extracellular matrix (ECM) components, which correlated with decreased phosphorylation of Src kinase. Moreover, rVAR2 binding decreased migration, invasion and anchorage-independent growth of tumor cells in vitro. Mass spectrometry of ofCS-modified proteoglycan complexes affinity purified from tumor cell lines on rVAR2 columns, revealed an overrepresentation of proteins involved in cell motility and integrin signaling, such as integrin β1 (ITGB1) and integrin α4 (ITGA4). Saturating concentrations of rVAR2 inhibited downstream integrin signaling, which was mimicked by knockdown of the core CS synthesis enzymes Beta-1,3-Glucuronyltransferase 1 (B3GAT1) and Chondroitin Sulfate N-Acetylgalactosaminyltransferase 1 (CSGALNACT1). The ofCS modification was highly expressed in both human and murine metastatic lesions in situ and pre-incubation or early intravenous treatment of tumor cells with rVAR2 inhibited seeding and spreading of tumor cells in mice. This was associated with a significant increase in survival of the animals. These data functionally link ofCS modifications with cancer cell motility and further highlights ofCS as a novel therapeutic cancer target. Implications The cancer specific expression of oncofetal chondroitin sulfate aids in metastatic phenotypes and is a candidate target for therapy. PMID:27655130

  18. Enhanced pulsed magneto-motive ultrasound imaging using superparamagnetic nanoclusters

    International Nuclear Information System (INIS)

    Mehrmohammadi, M; Qu, M; Emelianov, S Y; Yoon, K Y; Johnston, K P

    2011-01-01

    Recently, pulsed magneto-motive ultrasound (pMMUS) imaging augmented with ultra-small magnetic nanoparticles has been introduced as a tool capable of imaging events at molecular and cellular levels. The sensitivity of a pMMUS system depends on several parameters, including the size, geometry and magnetic properties of the nanoparticles. Under the same magnetic field, larger magnetic nanostructures experience a stronger magnetic force and produce larger displacement, thus improving the sensitivity and signal-to-noise ratio (SNR) of pMMUS imaging. Unfortunately, large magnetic iron-oxide nanoparticles are typically ferromagnetic and thus are very difficult to stabilize against colloidal aggregation. In the current study we demonstrate improvement of pMMUS image quality by using large size superparamagnetic nanoclusters characterized by strong magnetization per particle. Water-soluble magnetic nanoclusters of two sizes (15 and 55 nm average size) were synthesized from 3 nm iron precursors in the presence of citrate capping ligand. The size distribution of synthesized nanoclusters and individual nanoparticles was characterized using dynamic light scattering (DLS) analysis and transmission electron microscopy (TEM). Tissue mimicking phantoms containing single nanoparticles and two sizes of nanoclusters were imaged using a custom-built pMMUS imaging system. While the magnetic properties of citrate-coated nanoclusters are identical to those of superparamagnetic nanoparticles, the magneto-motive signal detected from nanoclusters is larger, i.e. the same magnetic field produced larger magnetically induced displacement. Therefore, our study demonstrates that clusters of superparamagnetic nanoparticles result in pMMUS images with higher contrast and SNR.

  19. Can alterations in integrin and laminin-5 expression be used as markers of malignancy?

    DEFF Research Database (Denmark)

    Thorup, Alis Karabulut; Reibel, J.; Schjødt, Morten

    1998-01-01

    Integrins, laminin-5, cell adhesion molecules, oral, leukoplakia, premalignant, squamous cell carcinomas......Integrins, laminin-5, cell adhesion molecules, oral, leukoplakia, premalignant, squamous cell carcinomas...

  20. Cell adhesion in Drosophila: versatility of cadherin and integrin complexes during development

    OpenAIRE

    Bulgakova, Natalia A.; Klapholz, Benjamin; Brown, Nicholas H.

    2012-01-01

    We highlight recent progress in understanding cadherin and integrin function in the model organism Drosophila. New functions for these adhesion receptors continue to be discovered in this system, emphasising the importance of cell adhesion within the developing organism and showing that the requirement for cell adhesion changes between cell types. New ways to control adhesion have been discovered, including controlling the expression and recruitment of adhesion components, their posttranslati...

  1. How Does Amino Acid Ligand Modulate Au Core Structure and Characteristics in Peptide Coated Au Nanocluster?

    Science.gov (United States)

    Li, Nan; Li, Xu; Zhao, Hongkang; Zhao, Lina

    2018-03-01

    The atomic structures and the corresponding physicochemical properties of peptide coated Au nanoclusters determine their distinctive biological targeting applications. To learn the modulation of amino acid ligand on the atomic structure and electronic characteristics of coated Au core is the fundamental knowledge for peptide coated Au nanocluster design and construction. Based on our recent coated Au nanocluster configuration study (Nanoscale, 2016, 8, 11454), we built the typically simplified Au13(Cys-Au-Cys) system to more clearly learn the basic modulation information of amino acid ligand on Au core by the density functional theory (DFT) calculations. There are two isomers as ligand adjacent bonding (Iso1) and diagonal bonding (Iso2) to Au13 cores. The geometry optimizations indicate the adjacent bonding Iso1 is more stable than Iso2. More important, the Au13 core of Iso1 distorts much more significantly than that of Iso2 by Cys-Au-Cys bonding through the root-mean-square deviation (RMSD) analysis, which modulate their electronic characteristics in different ways. In addition, the frontier molecular orbital results of Au13(Cys-Au-Cys) isomers confirm that the Au cores mainly determine the blue shifts of Au13(Cys-Au-Cys) systems versus the original Au13 core in their UV-visible absorption spectrum studies. The configuration of Au13 core performs deformation under Cys-Au-Cys ligand modulation to reach new stability with distinct atomic structure and electronic properties, which could be the theory basis for peptide coated AuNCs design and construction.

  2. ADAM disintegrin-like domain recognition by the lymphocyte integrins α4β1 and α4β7

    Science.gov (United States)

    Bridges, Lance C.; Sheppard, Dean; Bowditch, Ron D.

    2004-01-01

    The ADAM (a disintegrin and metalloprotease) family of proteins possess both proteolytic and adhesive domains. We have established previously that the disintegrin domain of ADAM28, an ADAM expressed by human lymphocytes, is recognized by the integrin α4β1. The present study characterizes the integrin binding properties of the disintegrin-like domains of human ADAM7, ADAM28 and ADAM33 with the integrins α4β1, α4β7 and α9β1. Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 disintegrin domain supported α4β1-dependent Jurkat cell adhesion, whereas the ADAM33 disintegrin domain did not. The lymphocyte integrin α4β7 was also found to recognize both disintegrin domains of ADAM7 and ADAM28, but not of ADAM33. This is the first demonstration that mammalian disintegrins are capable of interacting with α4β7. All three disintegrin domains supported α9β1-dependent cell adhesion. Recognition by both α4β1 and α4β7 of ADAM7 and ADAM28 was activation-dependent, requiring either the presence of Mn2+ or an activating monoclonal antibody for cell attachment. Charge-to-alanine mutagenesis experiments revealed that the same residues within an individual ADAM disintegrin domain function in recognizing multiple integrins. However, the residues within a specific region of each ADAM disintegrin-like domain required for integrin binding were distinct. These results establish that ADAM7 and ADAM28 are recognized by the leucocyte integrins α4β1, α4β7 and α9β1. ADAM33 exclusively supported only α9β1-dependent adhesion. PMID:15504110

  3. Tumor cell adhesion to endothelial cells is increased by endotoxin via an upregulation of beta-1 integrin expression.

    LENUS (Irish Health Repository)

    Andrews, E J

    2012-02-03

    BACKGROUND: Recent studies have demonstrated that metastatic disease develops from tumor cells that adhere to endothelial cells and proliferate intravascularly. The beta-1 integrin family and its ligand laminin have been shown to be important in tumor-to-endothelial cell adhesion. Lipopolysaccharide (LPS) has been implicated in the increased metastatic tumor growth that is seen postoperatively. We postulated that LPS increases tumor cell expression of beta-1 integrins and that this leads to increased adhesion. METHODS: The human metastatic colon cancer cell line LS174T was labeled with an enhanced green fluorescent protein (eGFP) using retroviral transfection. Cell cultures were treated with LPS for 1, 2, and 4 h (n = 6 each) and were subsequently cocultured for 30 or 120 min with confluent human umbilical vein endothelial cells (HUVECs), to allow adherence. Adherent tumor cells were counted using fluorescence microscopy. These experiments were carried out in the presence or absence of a functional blocking beta-1 integrin monoclonal antibody (4B4). Expression of beta-1 integrin and laminin on tumor and HUVECs was assessed using flow cytometric analysis. Tumor cell NF-kappaB activation after incubation with LPS was measured. RESULTS: Tumor cell and HUVEC beta-1 integrin expression and HUVEC expression of laminin were significantly (P < 0.05) enhanced after incubation with LPS. Tumor cell adhesion to HUVECs was significantly increased. Addition of the beta-1 integrin blocking antibody reduced tumor cell adhesion to control levels. LPS increased tumor cell NF-kappaB activation. CONCLUSIONS: Exposure to LPS increases tumor cell adhesion to the endothelium through a beta-1 integrin-mediated pathway that is NF-kappaB dependent. This may provide a target for immunotherapy directed at reducing postoperative metastatic tumor growth.

  4. Luminescent Metal Nanoclusters for Potential Chemosensor Applications

    Directory of Open Access Journals (Sweden)

    Muthaiah Shellaiah

    2017-12-01

    Full Text Available Studies of metal nanocluster (M-NCs-based sensors for specific analyte detection have achieved significant progress in recent decades. Ultra-small-size (<2 nm M-NCs consist of several to a few hundred metal atoms and exhibit extraordinary physical and chemical properties. Similar to organic molecules, M-NCs display absorption and emission properties via electronic transitions between energy levels upon interaction with light. As such, researchers tend to apply M-NCs in diverse fields, such as in chemosensors, biological imaging, catalysis, and environmental and electronic devices. Chemo- and bio-sensory uses have been extensively explored with luminescent NCs of Au, Ag, Cu, and Pt as potential sensory materials. Luminescent bi-metallic NCs, such as Au-Ag, Au-Cu, Au-Pd, and Au-Pt have also been used as probes in chemosensory investigations. Both metallic and bi-metallic NCs have been utilized to detect various analytes, such as metal ions, anions, biomolecules, proteins, acidity or alkalinity of a solution (pH, and nucleic acids, at diverse detection ranges and limits. In this review, we have summarized the chemosensory applications of luminescent M-NCs and bi-metallic NCs.

  5. Catalytic photooxidation of pentachlorophenol using semiconductor nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    WILCOXON,JESS P.

    2000-04-17

    Pentachlorophenol (PCP) is a toxic chlorinated aromatic molecule widely used as fungicide, a bactericide and a wood preservation, and thus ubiquitous in the environment. The authors report photo-oxidation of PCP using a variety of nanosize semiconductor metal oxides and sulfides in both aqueous and polar organic solvents and compare the photo-oxidation kinetics of these nanoclusters to widely studied bulk powders like Degussa P-25 TiO{sub 2} and CdS. They study both the light intensity dependence of PCP photooxidation for nanosize SnO{sub 2} and the size dependence of PCP photooxidation for both nanosize SnO{sub 2} and MoS{sub 2}. They find an extremely strong size dependence for the latter which they attribute to its size-dependent band gap and the associated change in redox potentials due to quantum confinement of the hole-electron pair. The authors show that nanosize MoS{sub 2} with a diameter of d=3.0 nm and an absorbance edge of {approximately}450 nm is a very effective photooxidation catalyst for complete PCP mineralization, even when using only visible light irradiation.

  6. Integrin α6Bβ4 inhibits colon cancer cell proliferation and c-Myc activity

    International Nuclear Information System (INIS)

    Dydensborg, Anders Bondo; Teller, Inga C; Groulx, Jean-François; Basora, Nuria; Paré, Fréderic; Herring, Elizabeth; Gauthier, Rémy; Jean, Dominique; Beaulieu, Jean-François

    2009-01-01

    Integrins are known to be important contributors to cancer progression. We have previously shown that the integrin β4 subunit is up-regulated in primary colon cancer. Its partner, the integrin α6 subunit, exists as two different mRNA splice variants, α6A and α6B, that differ in their cytoplasmic domains but evidence for distinct biological functions of these α6 splice variants is still lacking. In this work, we first analyzed the expression of integrin α6A and α6B at the protein and transcript levels in normal human colonic cells as well as colorectal adenocarcinoma cells from both primary tumors and established cell lines. Then, using forced expression experiments, we investigated the effect of α6A and α6B on the regulation of cell proliferation in a colon cancer cell line. Using variant-specific antibodies, we observed that α6A and α6B are differentially expressed both within the normal adult colonic epithelium and between normal and diseased colonic tissues. Proliferative cells located in the lower half of the glands were found to predominantly express α6A, while the differentiated and quiescent colonocytes in the upper half of the glands and surface epithelium expressed α6B. A relative decrease of α6B expression was also identified in primary colon tumors and adenocarcinoma cell lines suggesting that the α6A/α6B ratios may be linked to the proliferative status of colonic cells. Additional studies in colon cancer cells showed that experimentally restoring the α6A/α6B balance in favor of α6B caused a decrease in cellular S-phase entry and repressed the activity of c-Myc. The findings that the α6Bβ4 integrin is expressed in quiescent normal colonic cells and is significantly down-regulated in colon cancer cells relative to its α6Aβ4 counterpart are consistent with the anti-proliferative influence and inhibitory effect on c-Myc activity identified for this α6Bβ4 integrin. Taken together, these findings point out the importance of integrin

  7. Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface laminin organization

    DEFF Research Database (Denmark)

    Henry, M D; Satz, J S; Brakebusch, C

    2001-01-01

    Dystroglycan (DG) is a cell surface receptor for several extracellular matrix (ECM) molecules including laminins, agrin and perlecan. Recent data indicate that DG function is required for the formation of basement membranes in early development and the organization of laminin on the cell surface...... integrin-deficient ES cells, laminin-1 binds to the cell surface, but fails to organize into more morphologically complex structures. This result indicates that beta1 integrin function is required after DG function in the cell surface-mediated laminin assembly process. In perlecan-deficient ES cells......, the formation of complex laminin-1 structures is defective, implicating perlecan in the laminin matrix assembly process. Moreover, laminin and perlecan reciprocally modulate the organization of the other on the cell surface. Taken together, the data support a model whereby DG serves as a receptor essential...

  8. The CD157-integrin partnership controls transendothelial migration and adhesion of human monocytes.

    Science.gov (United States)

    Lo Buono, Nicola; Parrotta, Rossella; Morone, Simona; Bovino, Paola; Nacci, Giulia; Ortolan, Erika; Horenstein, Alberto L; Inzhutova, Alona; Ferrero, Enza; Funaro, Ada

    2011-05-27

    CD157, a member of the CD38 gene family, is an NAD-metabolizing ectoenzyme and a signaling molecule whose role in polarization, migration, and diapedesis of human granulocytes has been documented; however, the molecular events underpinning this role remain to be elucidated. This study focused on the role exerted by CD157 in monocyte migration across the endothelial lining and adhesion to extracellular matrix proteins. The results demonstrated that anti-CD157 antibodies block monocyte transmigration and adhesion to fibronectin and fibrinogen but that CD157 cross-linking is sufficient to overcome the block, suggesting an active signaling role for the molecule. Consistent with this is the observation that CD157 is prevalently located within the detergent-resistant membrane microdomains to which, upon clustering, it promotes the recruitment of β(1) and β(2) integrin, which, in turn, leads to the formation of a multimolecular complex favoring signal transduction. This functional cross-talk with integrins allows CD157 to act as a receptor despite its intrinsic structural inability to do so on its own. Intracellular signals mediated by CD157 rely on the integrin/Src/FAK (focal adhesion kinase) pathway, resulting in increased activity of the MAPK/ERK1/2 and the PI3K/Akt downstream signaling pathways, which are crucial in the control of monocyte transendothelial migration. Collectively, these findings indicate that CD157 acts as a molecular organizer of signaling-competent membrane microdomains and that it forms part of a larger molecular machine ruled by integrins. The CD157-integrin partnership provides optimal adhesion and transmigration of human monocytes.

  9. The CD157-Integrin Partnership Controls Transendothelial Migration and Adhesion of Human Monocytes*

    Science.gov (United States)

    Lo Buono, Nicola; Parrotta, Rossella; Morone, Simona; Bovino, Paola; Nacci, Giulia; Ortolan, Erika; Horenstein, Alberto L.; Inzhutova, Alona; Ferrero, Enza; Funaro, Ada

    2011-01-01

    CD157, a member of the CD38 gene family, is an NAD-metabolizing ectoenzyme and a signaling molecule whose role in polarization, migration, and diapedesis of human granulocytes has been documented; however, the molecular events underpinning this role remain to be elucidated. This study focused on the role exerted by CD157 in monocyte migration across the endothelial lining and adhesion to extracellular matrix proteins. The results demonstrated that anti-CD157 antibodies block monocyte transmigration and adhesion to fibronectin and fibrinogen but that CD157 cross-linking is sufficient to overcome the block, suggesting an active signaling role for the molecule. Consistent with this is the observation that CD157 is prevalently located within the detergent-resistant membrane microdomains to which, upon clustering, it promotes the recruitment of β1 and β2 integrin, which, in turn, leads to the formation of a multimolecular complex favoring signal transduction. This functional cross-talk with integrins allows CD157 to act as a receptor despite its intrinsic structural inability to do so on its own. Intracellular signals mediated by CD157 rely on the integrin/Src/FAK (focal adhesion kinase) pathway, resulting in increased activity of the MAPK/ERK1/2 and the PI3K/Akt downstream signaling pathways, which are crucial in the control of monocyte transendothelial migration. Collectively, these findings indicate that CD157 acts as a molecular organizer of signaling-competent membrane microdomains and that it forms part of a larger molecular machine ruled by integrins. The CD157-integrin partnership provides optimal adhesion and transmigration of human monocytes. PMID:21478153

  10. Chondrocyte heterogeneity: immunohistologically defined variation of integrin expression at different sites in human fetal knees.

    Science.gov (United States)

    Salter, D M; Godolphin, J L; Gourlay, M S

    1995-04-01

    During development and at maturity different forms of cartilage vary in morphology and macromolecular content. This reflects heterogeneity of chondrocyte activity, in part involving differential interactions with the adjacent extracellular matrix via specialized cell surface receptors such as integrins. We undertook an immunohistological study on a series of human fetal knee joints to assess variation in the expression of integrins by chondrocytes and potential matrix ligands in articular, epiphyseal, growth plate, and meniscal cartilage. The results show that articular chondrocytes (beta 1+, beta 5 alpha V+, alpha 1+, alpha 2+/-, alpha 5+, weakly alpha 6+, alpha V+) differed from epiphyseal (beta 1+, beta 5 alpha V+, alpha 1+/-, alpha 2+/-, alpha 5+, alpha 6+, alpha V+) growth plate (beta 1+, beta 5 alpha V+, alpha 1-, alpha 2-, alpha 5+, alpha 6+, alpha V+), and meniscal cells (beta 1+, beta 5 alpha V+, alpha 1+, strongly alpha 2+, alpha 5+, alpha 6+, alpha V+ in expression of integrin subunits. There was no expression of beta 3, beta 4, beta 6, or alpha 3 by chondrocytes. These results differ from previous reports on the expression of integrins by adult articular cartilage, where alpha 2 and alpha 6 are not seen. Variation in distribution of matrix ligands was also seen. Fibronectin, laminin and Type VI collagen were expressed in all cartilages but there was restricted expression of tenascin, ED-A and ED-B fibronectin isoforms (articular cartilage and meniscus), and vitronectin (absent from growth plate cartilage). Regulated expression of integrins by chondrocytes, associated with changes in the pericellular matrix composition, is of potential importance in control of cartilage differentiation and function in health and disease.

  11. Deposition and characterization of Pt nanocluster films by means of gas aggregation cluster source

    Energy Technology Data Exchange (ETDEWEB)

    Kylián, Ondřej, E-mail: ondrej.kylian@gmail.com; Prokeš, Jan; Polonskyi, Oleksandr; Čechvala, Juraj; Kousal, Jaroslav; Pešička, Josef; Hanuš, Jan; Biederman, Hynek

    2014-11-28

    In this study we report on the deposition of Pt nanocluster films prepared by gas aggregation source that was operated with argon as working gas. The aim of this study was optimization of deposition process as well as determination of properties of deposited nanocluster films and their temporal stability. It was found that the production of Pt nanoclusters reached maximum value for pressure of 100 Pa and increases monotonously with magnetron current. The deposition rate at optimized deposition conditions was 0.7 nm of the Pt nanocluster film per second. Deposited films were porous and composed of 4 nm Pt nanoclusters. The nanoclusters were metallic and no sights of their oxidation were observed after 1 year on open air as witnessed by X-ray photoelectron spectroscopy. Regarding the electrical properties, a dramatic decrease of the resistivity was observed with increasing amount of deposited nanoclusters. This decrease saturated for the films approximately 50 nm thick. Such behavior indicates transition between different mechanisms of electrical conductivity: charge hopping for thin discontinuous films and current conduction through conducting path formed when higher amount of nanoclusters is deposited. Different mechanisms of electrical conduction for thin and thick layers of Pt were confirmed by subsequent investigation of temperature dependence of resistivity. In addition, no changes in resistivity were observed after one year on open air that confirms stability of produced Pt nanocluster films. - Highlights: • Pt nanocluster films were deposited by gas aggregation nanocluster source. • Conditions leading to effective deposition of Pt nanocluster films were found. • Deposited nanocluster films have good temporal stability. • Electrical properties of Pt films were found to depend on their thickness.

  12. The impact of quercetin on wound healing relates to changes in αV and β1 integrin expression.

    Science.gov (United States)

    Doersch, Karen M; Newell-Rogers, M Karen

    2017-08-01

    Overly fibrotic wound healing can lead to excess scar formation, causing functional impairment and undesirable cosmetic results. However, there are few successful treatments available to prevent or remediate scars. This study sought to explore the molecular mechanisms by which quercetin, a naturally-occurring antifibrotic agent, diminishes scar formation. Using both mice and fibroblast cells, we examined quercetin's impact on fibrosis and the wound healing rate, and potential molecular mechanisms underlying the quercetin-mediated reduction of fibrosis. While cultured fibroblasts demonstrated normal growth in response to quercetin, quercetin increased surface αV integrin and decreased β1 integrin. These changes in surface integrin expression may impact factors that contribute to fibrosis including cell migration, proliferation, and extracellular matrix production. In both quercetin-treated and control mice, wounds healed in about 14 days. Masson's trichrome stain revealed diminished fibrosis at the wound site in quercetin-treated animals despite the normal healing rate, indicating the potential for better cosmetic results without delaying healing. An in vitro scratch wound model using cells plated on an artificial extracellular matrix demonstrated delayed closure following quercetin treatment. The extracellular matrix also ameliorated quercetin's effect on αV integrin. Thus, αV integrin recruitment in response to quercetin treatment may promote the quercetin-mediated decrease extracellular matrix because cells require less extracellular matrix to migrate into a wound. With added extracellular matrix, β1 integrin remained diminished in response to quercetin, indicating that quercetin's effect on β1 integrin expression is independent of extracellular matrix -mediated signaling and is likely driven by inhibition of the intracellular mechanisms driving β1 expression. These findings suggest that quercetin could alter the cells' interactions with the extracellular

  13. The Size of Activating and Inhibitory Killer Ig-like Receptor Nanoclusters Is Controlled by the Transmembrane Sequence and Affects Signaling

    Directory of Open Access Journals (Sweden)

    Anna Oszmiana

    2016-05-01

    Full Text Available Super-resolution microscopy has revealed that immune cell receptors are organized in nanoscale clusters at cell surfaces and immune synapses. However, mechanisms and functions for this nanoscale organization remain unclear. Here, we used super-resolution microscopy to compare the surface organization of paired killer Ig-like receptors (KIR, KIR2DL1 and KIR2DS1, on human primary natural killer cells and cell lines. Activating KIR2DS1 assembled in clusters two-fold larger than its inhibitory counterpart KIR2DL1. Site-directed mutagenesis established that the size of nanoclusters is controlled by transmembrane amino acid 233, a lysine in KIR2DS1. Super-resolution microscopy also revealed two ways in which the nanoscale clustering of KIR affects signaling. First, KIR2DS1 and DAP12 nanoclusters are juxtaposed in the resting cell state but coalesce upon receptor ligation. Second, quantitative super-resolution microscopy revealed that phosphorylation of the kinase ZAP-70 or phosphatase SHP-1 is favored in larger KIR nanoclusters. Thus, the size of KIR nanoclusters depends on the transmembrane sequence and affects downstream signaling.

  14. Distinct metal-exchange pathways of doped Ag25 nanoclusters

    KAUST Repository

    Bootharaju, Megalamane Siddaramappa; Sinatra, Lutfan; Bakr, Osman

    2016-01-01

    Atomically precise metal nanoclusters (NCs) containing more than one type of metal atom (i.e., doped or alloyed), due to synergistic effects, open new avenues for engineering the catalytic and optical properties of NCs in a manner that homometal NCs

  15. In-vitro Synthesis of Gold Nanoclusters in Neurons

    Science.gov (United States)

    2016-04-01

    ARL-TN-0753 ● APR 2016 US Army Research Laboratory In-vitro Synthesis of Gold Nanoclusters in Neurons by Maggie Gillan and...longer needed. Do not return it to the originator. ARL-TN-0753 ● APR 2016 US Army Research Laboratory In-vitro Synthesis of...

  16. Organization of copper nanoclusters in Langmuir–Blodgett films

    Indian Academy of Sciences (India)

    Stable nanoclusters of Cu were synthesized using Langmuir–Blodgett films of octadecylsuccinic acid (ODSA) as template. The Langmuir–Blodgett films of ODSA formed from subphase containing copper ions were first subjected to sulphidation (S) using sodium sulphide and then hydrogenated (H) using hydrogen gas.

  17. Nanoclustering as a dominant feature of plasma membrane organization

    NARCIS (Netherlands)

    Garcia-Parajo, M.F.; Cambi, A.; Torreno-Pina, J.A.; Thompson, N.; Jacobson, K.

    2014-01-01

    Early studies have revealed that some mammalian plasma membrane proteins exist in small nanoclusters. The advent of super-resolution microscopy has corroborated and extended this picture, and led to the suggestion that many, if not most, membrane proteins are clustered at the plasma membrane at

  18. Integrin β1 regulates leiomyoma cytoskeletal integrity and growth

    Science.gov (United States)

    Malik, Minnie; Segars, James; Catherino, William H.

    2014-01-01

    Uterine leiomyomas are characterized by an excessive extracellular matrix, increased mechanical stress, and increased active RhoA. Previously, we observed that mechanical signaling was attenuated in leiomyoma, but the mechanisms responsible remain unclear. Integrins, especially integrin β1, are transmembrane adhesion receptors that couple extracellular matrix stresses to the intracellular cytoskeleton to influence cell proliferation and differentiation. Here we characterized integrin and laminin to signaling in leiomyoma cells. We observed a 2.25 ± 0.32 fold increased expression of integrin β1 in leiomyoma cells, compared to myometrial cells. Antibody-mediated inhibition of integrin β1 led to significant growth inhibition in leiomyoma cells and a loss of cytoskeletal integrity. Specifically, polymerization of actin filaments and formation of focal adhesions were reduced by inhibition of integrin p1. Inhibition of integrin β1 in leiomyoma cells led to 0.81 ± 0.02 fold decrease in active RhoA, and resembled levels found in serum-starved cells. Likewise, inhibition of integrin β1 was accompanied by a decrease in phospho-ERK. Compared to myometrial cells, leiomyoma cells demonstrated increased expression of integrin α6 subunit to laminin receptor (1.91 ± 0.11 fold), and increased expression of laminin 5α (1.52±0.02), laminin 5β (3.06±0.92), and laminin 5γ (1.66 ± 0.06). Of note, leiomyoma cells grown on laminin matrix appear to realign themselves. Taken together, the findings reveal that the attenuated mechanical signaling in leiomyoma cells is accompanied by an increased expression and a dependence on integrin β1 signaling in leiomyoma cells, compared to myometrial cells. PMID:23023061

  19. Multifaced Roles of the αvβ3 Integrin in Ehlers–Danlos and Arterial Tortuosity Syndromes’ Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Nicoletta Zoppi

    2018-03-01

    Full Text Available The αvβ3 integrin, an endothelial cells’ receptor-binding fibronectin (FN in the extracellular matrix (ECM of blood vessels, regulates ECM remodeling during migration, invasion, angiogenesis, wound healing and inflammation, and is also involved in the epithelial mesenchymal transition. In vitro-grown human control fibroblasts organize a fibrillar network of FN, which is preferentially bound on the entire cell surface to its canonical α5β1 integrin receptor, whereas the αvβ3 integrin is present only in rare patches in focal contacts. We report on the preferential recruitment of the αvβ3 integrin, due to the lack of FN–ECM and its canonical integrin receptor, in dermal fibroblasts from Ehlers–Danlos syndromes (EDS and arterial tortuosity syndrome (ATS, which are rare multisystem connective tissue disorders. We review our previous findings that unraveled different biological mechanisms elicited by the αvβ3 integrin in fibroblasts derived from patients affected with classical (cEDS, vascular (vEDS, hypermobile EDS (hEDS, hypermobility spectrum disorders (HSD, and ATS. In cEDS and vEDS, respectively, due to defective type V and type III collagens, αvβ3 rescues patients’ fibroblasts from anoikis through a paxillin-p60Src-mediated cross-talk with the EGF receptor. In hEDS and HSD, without a defined molecular basis, the αvβ3 integrin transduces to the ILK-Snail1-axis inducing a fibroblast-to-myofibroblast-transition. In ATS cells, the deficiency of the dehydroascorbic acid transporter GLUT10 leads to redox imbalance, ECM disarray together with the activation of a non-canonical αvβ3 integrin-TGFBRII signaling, involving p125FAK/p60Src/p38MAPK. The characterization of these different biological functions triggered by αvβ3 provides insights into the multifaced nature of this integrin, at least in cultured dermal fibroblasts, offering future perspectives for research in this field.

  20. The journey of integrins and partners in a complex interactions landscape studied by super-resolution microscopy and single protein tracking

    International Nuclear Information System (INIS)

    Rossier, Olivier; Giannone, Grégory

    2016-01-01

    Cells adjust their adhesive and cytoskeletal organizations according to changes in the biochemical and physical nature of their surroundings. In return, by adhering and generating forces on the extracellular matrix (ECM) cells organize their microenvironment. Integrin-dependent focal adhesions (FAs) are the converging zones integrating biochemical and biomechanical signals arising from the ECM and the actin cytoskeleton. Thus, integrin-mediated adhesion and mechanotransduction, the conversion of mechanical forces into biochemical signals, are involved in critical cellular functions such as migration, proliferation and differentiation, and their deregulation contributes to pathologies including cancer. A challenging problem is to decipher how stochastic protein movements and interactions lead to formation of dynamic architecture such as integrin-dependent adhesive structures. In this review, we will describe recent advances made possible by super-resolution microscopies and single molecule tracking approaches that provided new understanding on the organization and the dynamics of integrins and intracellular regulators at the nanoscale in living cells.

  1. The journey of integrins and partners in a complex interactions landscape studied by super-resolution microscopy and single protein tracking

    Energy Technology Data Exchange (ETDEWEB)

    Rossier, Olivier; Giannone, Grégory [Univ. Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux (France); CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux (France)

    2016-04-10

    Cells adjust their adhesive and cytoskeletal organizations according to changes in the biochemical and physical nature of their surroundings. In return, by adhering and generating forces on the extracellular matrix (ECM) cells organize their microenvironment. Integrin-dependent focal adhesions (FAs) are the converging zones integrating biochemical and biomechanical signals arising from the ECM and the actin cytoskeleton. Thus, integrin-mediated adhesion and mechanotransduction, the conversion of mechanical forces into biochemical signals, are involved in critical cellular functions such as migration, proliferation and differentiation, and their deregulation contributes to pathologies including cancer. A challenging problem is to decipher how stochastic protein movements and interactions lead to formation of dynamic architecture such as integrin-dependent adhesive structures. In this review, we will describe recent advances made possible by super-resolution microscopies and single molecule tracking approaches that provided new understanding on the organization and the dynamics of integrins and intracellular regulators at the nanoscale in living cells.

  2. RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages

    DEFF Research Database (Denmark)

    von Wichert, Gotz; Jiang, Guoying; Kostic, Ana

    2003-01-01

    Cell motility on ECM critically depends on the cellular response to force from the matrix. We find that force-dependent reinforcement of alphav/beta3-integrin-mediated cell-matrix connections requires the receptor-like tyrosine phosphatase alpha (RPTPalpha). RPTPalpha colocalizes with alphav...... of alphav/beta3-integrin-cytoskeleton connections during the initial phase of ECM contact. These observations indicate that Src family kinases have distinct functions during adhesion site assembly, and that RPTPalpha is an early component in force-dependent signal transduction pathways leading...

  3. Photoconductivity, photoluminescence and optical Kerr nonlinear effects in zinc oxide films containing chromium nanoclusters

    International Nuclear Information System (INIS)

    Torres-Torres, C.; García-Cruz, M.L.; Castañeda, L.; Rangel Rojo, R.; Tamayo-Rivera, L.; Maldonado, A.; Avendaño-Alejo, M.

    2012-01-01

    Chromium doped zinc oxide thin solid films were deposited on soda–lime glass substrates. The photoconductivity of the material and its influence on the optical behavior was evaluated. A non-alkoxide sol–gel synthesis approach was used for the preparation of the samples. An enhancement of the photoluminescence response exhibited by the resulting photoconductive films with embedded chromium nanoclusters is presented. The modification in the photoconduction induced by a 445 nm wavelength was measured and then associated with the participation of the optical absorptive response. In order to investigate the third order optical nonlinearities of the samples, a standard time-resolved Optical Kerr Gate configuration with 80 fs pulses at 830 nm was used and a quasi-instantaneous pure electronic nonlinearity without the contribution of nonlinear optical absorption was observed. We estimate that from the inclusion of Cr nanoclusters into the sample results a strong optical Kerr effect originated by quantum confinement. The large photoluminescence response and the important refractive nonlinearity of the photoconductive samples seem to promise potential applications for the development of multifunctional all-optical nanodevices. - Highlights: ► Enhancement in photoluminescence for chromium doped zinc oxide films is presented. ► A strong and ultrafast optical Kerr effect seems to result from quantum confinement. ► Photoconductive properties for optical and optoelectronic functions were observed.

  4. Photoconductivity, photoluminescence and optical Kerr nonlinear effects in zinc oxide films containing chromium nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Torres-Torres, C., E-mail: crstorres@yahoo.com.mx [Seccion de Estudios de Posgrado e Investigacion, ESIME-Z, Instituto Politecnico Nacional, Mexico, DF 07738 (Mexico); Garcia-Cruz, M.L. [Centro de Investigacion en Dispositivos Semiconductores, Benemerita Universidad Autonoma de Puebla, A. P. J-48, Puebla 72570, Mexico (Mexico); Castaneda, L., E-mail: luisca@sirio.ifuap.buap.mx [Instituto de Fisica, Benemerita Universidad Autonoma de Puebla, A. P. J-48, Puebla 72570, Mexico (Mexico); Rangel Rojo, R. [CICESE/Depto. de Optica, A. P. 360, Ensenada, BC 22860 (Mexico); Tamayo-Rivera, L. [Instituto de Fisica, Universidad Nacional Autonoma de Mexico, Mexico, DF 01000 (Mexico); Maldonado, A. [Depto. de Ing. Electrica, CINVESTAV IPN-SEES, A. P. 14740, Mexico DF 07000 (Mexico); Avendano-Alejo, M., E-mail: imax_aa@yahoo.com.mx [Centro de Ciencias Aplicadas y Desarrollo Tecnologico, Universidad Nacional Autonoma de Mexico, A. P. 70-186, 04510, DF (Mexico); and others

    2012-04-15

    Chromium doped zinc oxide thin solid films were deposited on soda-lime glass substrates. The photoconductivity of the material and its influence on the optical behavior was evaluated. A non-alkoxide sol-gel synthesis approach was used for the preparation of the samples. An enhancement of the photoluminescence response exhibited by the resulting photoconductive films with embedded chromium nanoclusters is presented. The modification in the photoconduction induced by a 445 nm wavelength was measured and then associated with the participation of the optical absorptive response. In order to investigate the third order optical nonlinearities of the samples, a standard time-resolved Optical Kerr Gate configuration with 80 fs pulses at 830 nm was used and a quasi-instantaneous pure electronic nonlinearity without the contribution of nonlinear optical absorption was observed. We estimate that from the inclusion of Cr nanoclusters into the sample results a strong optical Kerr effect originated by quantum confinement. The large photoluminescence response and the important refractive nonlinearity of the photoconductive samples seem to promise potential applications for the development of multifunctional all-optical nanodevices. - Highlights: Black-Right-Pointing-Pointer Enhancement in photoluminescence for chromium doped zinc oxide films is presented. Black-Right-Pointing-Pointer A strong and ultrafast optical Kerr effect seems to result from quantum confinement. Black-Right-Pointing-Pointer Photoconductive properties for optical and optoelectronic functions were observed.

  5. Hydrophilic magnetic nanoclusters with thermo-responsive properties and their drug controlled release

    International Nuclear Information System (INIS)

    Meerod, Siraprapa; Rutnakornpituk, Boonjira; Wichai, Uthai; Rutnakornpituk, Metha

    2015-01-01

    Synthesis and drug controlled release properties of thermo-responsive magnetic nanoclusters grafted with poly(N-isopropylacrylamide) (poly(NIPAAm)) and poly(NIPAAm-co-poly(ethylene glycol) methyl ether methacrylate) (PEGMA) copolymers were described. These magnetic nanoclusters were synthesized via an in situ radical polymerization in the presence of acrylamide-grafted magnetic nanoparticles (MNPs). Poly(NIPAAm) provided thermo-responsive properties, while PEGMA played a role in good water dispersibility to the nanoclusters. The ratios of PEGMA to NIPAAm in the (co)polymerization in the presence of the MNPs were fine-tuned such that the nanoclusters with good water dispersibility, good magnetic sensitivity and thermo responsiveness were obtained. The size of the nanoclusters was in the range of 50–100 nm in diameter with about 100–200 particles/cluster. The nanoclusters were well dispersible in water at room temperature and can be suddenly agglomerated when temperature was increased beyond the lower critical solution temperature (LCST) (32 °C). The release behavior of an indomethacin model drug from the nanoclusters was also investigated. These novel magnetic nanoclusters with good dispersibility in water and reversible thermo-responsive properties might be good candidates for the targeting drug controlled release applications. - Highlights: • Nanoclusters with good water dispersibility and magnetic response were prepared. • They were grafted with thermo-responsive poly(NIPAAm) and/or poly(PEGMA). • Poly(NIPAAm) provided thermo-responsive properties to the nanoclusters. • Poly(PEGMA) provided good water dispersibilityto the nanoclusters. • Accelerated and controllable releases of a drug from the nanoclusters were shown

  6. Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

    OpenAIRE

    Marija Matulionyte; Dominyka Dapkute; Laima Budenaite; Greta Jarockyte; Ricardas Rotomskis

    2017-01-01

    In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. The...

  7. Epitope mapping for monoclonal antibody reveals the activation mechanism for αVβ3 integrin.

    Directory of Open Access Journals (Sweden)

    Tetsuji Kamata

    Full Text Available Epitopes for a panel of anti-αVβ3 monoclonal antibodies (mAbs were investigated to explore the activation mechanism of αVβ3 integrin. Experiments utilizing αV/αIIb domain-swapping chimeras revealed that among the nine mAbs tested, five recognized the ligand-binding β-propeller domain and four recognized the thigh domain, which is the upper leg of the αV chain. Interestingly, the four mAbs included function-blocking as well as non-functional mAbs, although they bound at a distance from the ligand-binding site. The epitopes for these four mAbs were further determined using human-to-mouse αV chimeras. Among the four, P3G8 recognized an amino acid residue, Ser-528, located on the side of the thigh domain, while AMF-7, M9, and P2W7 all recognized a common epitope, Ser-462, that was located close to the α-genu, where integrin makes a sharp bend in the crystal structure. Fibrinogen binding studies for cells expressing wild-type αVβ3 confirmed that AMF-7, M9, and P2W7 were inhibitory, while P3G8 was non-functional. However, these mAbs were all unable to block binding when αVβ3 was constrained in its extended conformation. These results suggest that AMF-7, M9, and P2W7 block ligand binding allosterically by stabilizing the angle of the bend in the bent conformation. Thus, a switchblade-like movement of the integrin leg is indispensable for the affinity regulation of αVβ3 integrin.

  8. Mass spectrometric identification of Au68(SR)34 molecular gold nanoclusters with 34-electron shell closing.

    Science.gov (United States)

    Dass, Amala

    2009-08-26

    The molecular formula Au(68)(SCH(2)CH(2)Ph)(34) has been assigned to the 14 kDa nanocluster using MALDI-TOF mass spectrometry. The 34-electron shell closing in a macroscopically obtained thiolated gold nanocluster is demonstrated. The Au(68) nanocluster is predicted to have a 49 atom Marks decahedral core with 19 inner core atoms and 30 outer atoms chelating with the staple motifs. The nanoclusters' predicted formulation is [Au](19+30) [Au(SR)(2)](11) [Au(2)(SR)(3)](4).

  9. Electrostatic Interactions Positively Regulate K-Ras Nanocluster Formation and Function▿

    Science.gov (United States)

    Plowman, Sarah J.; Ariotti, Nicholas; Goodall, Andrew; Parton, Robert G.; Hancock, John F.

    2008-01-01

    The organization of Ras proteins into plasma membrane nanoclusters is essential for high-fidelity signal transmission, but whether the nanoscale enviroments of different Ras nanoclusters regulate effector interactions is unknown. We show using high-resolution spatial mapping that Raf-1 is recruited to and retained in K-Ras-GTP nanoclusters. In contrast, Raf-1 recruited to the plasma membrane by H-Ras is not retained in H-Ras-GTP nanoclusters. Similarly, upon epidermal growth factor receptor activation, Raf-1 is preferentially recruited to K-Ras-GTP and not H-Ras-GTP nanoclusters. The formation of K-Ras-GTP nanoclusters is inhibited by phosphorylation of S181 in the C-terminal polybasic domain or enhanced by blocking S181 phosphorylation, with a concomitant reduction or increase in Raf-1 plasma membrane recruitment, respectively. Phosphorylation of S181 does not, however, regulate in vivo interactions with the nanocluster scaffold galectin-3 (Gal3), indicating separate roles for the polybasic domain and Gal3 in driving K-Ras nanocluster formation. Together, these data illustrate that Ras nanocluster composition regulates effector recruitment and highlight the importance of lipid/protein nanoscale environments to the activation of signaling cascades. PMID:18458061

  10. The role of integrin αv in proliferation and differentiation of human dental pulp cell response to calcium silicate cement.

    Science.gov (United States)

    Hung, Chi-Jr; Hsu, Hsin-I; Lin, Chi-Chang; Huang, Tsui-Hsien; Wu, Buor-Chang; Kao, Chia-Tze; Shie, Ming-You

    2014-11-01

    It has been proved that integrin αv activity is related to cell proliferation, differentiation, migration, and organ development. However, the biological functions of integrin αv in human dental pulp cells (hDPCs) cultured on silicate-based materials have not been explored. The aim of this study was to investigate the role of integrin αv in the proliferation and odontogenic differentiation of hDPCs cultured with the effect of calcium silicate (CS) cement and β-tricalcium phosphate (TCP) cement. In this study, hDPCs were cultured on CS and TCP materials, and we evaluated fibronectin (FN) secretion and integrin αv expression during the cell attachment stage. After small interfering RNA transfection targeting integrin αv, the proliferation and odontogenesis differentiation behavior of hDPCs were analyzed. The results indicate that CS releases Si ion-increased FN secretion and adsorption, which promote cell attachment more effectively than TCP. The CS cement facilitates FN and αv subintegrin expression. However, the FN adsorption and integrin expression of TCP are similar to that observed in the control dish. Integrin αv small interfering RNA inhibited odontogenic differentiation of hDPCs with the decreased formation of mineralized nodules on CS. It also down-regulated the protein expression of multiple markers of odontogenesis and the expression of dentin sialophosphoprotein protein. These results establish composition-dependent differences in integrin binding and its effectiveness as a mechanism regulating cellular responses to biomaterial surface. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  11. Simulated Microgravity Alters Actin Cytoskeleton and Integrin-Mediated Focal Adhesions of Cultured Human Mesenchymal Stromal Cells

    Science.gov (United States)

    Gershovich, P. M.; Gershovic, J. G.; Buravkova, L. B.

    2008-06-01

    Cytoskeletal alterations occur in several cell types including lymphocytes, glial cells, and osteoblasts, during spaceflight and under simulated microgravity (SMG) (3, 4). One potential mechanism for cytoskeletal gravisensitivity is disruption of extracellular matrix (ECM) and integrin interactions. Focal adhesions are specialized sites of cell-matrix interaction composed of integrins and the diversity of focal adhesion-associated cytoplasmic proteins including vinculin, talin, α-actinin, and actin filaments (4, 5). Integrins produce signals essential for proper cellular function, survival and differentiation. Therefore, we investigated the effects of SMG on F-actin cytoskeleton structure, vinculin focal adhesions, expression of some integrin subtypes and cellular adhesion molecules (CAMs) in mesenchymal stem cells derived from human bone marrow (hMSCs). Simulated microgravity was produced by 3D-clinostat (Dutch Space, Netherlands). Staining of actin fibers with TRITC-phalloidin showed reorganization even after 30 minutes of simulated microgravity. The increasing of cells number with abnormal F-actin was observed after subsequent terms of 3D-clinorotation (6, 24, 48, 120 hours). Randomization of gravity vector altered dimensional structure of stress fibers and resulted in remodeling of actin fibers inside the cells. In addition, we observed vinculin redistribution inside the cells after 6 hours and prolonged terms of clinorotation. Tubulin fibers in a contrast with F-actin and vinculin didn't show any reorganization even after long 3Dclinorotation (120 hours). The expression of integrin α2 increased 1,5-6-fold in clinorotated hMSCs. Also we observed decrease in number of VCAM-1-positive cells and changes in expression of ICAM-1. Taken together, our findings indicate that SMG leads to microfilament and adhesion alterations of hMSCs most probably associated with involvement of some integrin subtypes.

  12. Absence of integrin alpha 7 causes a novel form of muscular dystrophy.

    Science.gov (United States)

    Mayer, U; Saher, G; Fässler, R; Bornemann, A; Echtermeyer, F; von der Mark, H; Miosge, N; Pöschl, E; von der Mark, K

    1997-11-01

    Integrin alpha 7 beta 1 is a specific cellular receptor for the basement membrane protein laminin-1 (refs 1,2), as well as for the laminin isoforms -2 and -4 (ref. 3). The alpha 7 subunit is expressed mainly in skeletal and cardiac muscle and has been suggested to be involved in differentiation and migration processes during myogenesis. Three cytoplasmic and two extracellular splice variants that have been described are developmentally regulated and expressed in different sites in the muscle. In adult muscle, the alpha 7A and alpha 7B subunits are concentrated in myotendinous junctions but can also be detected in neuromuscular junctions and along the sarcolemmal membrane. To study the potential involvement of alpha 7 integrin, during myogenesis and its role in muscle integrity and function, we generated a null allele of the alpha 7 gene (Itga7) in the germline of mice by homologous recombination in embryonic stem (ES) cells. Surprisingly, mice homozygous for the mutation are viable and fertile, indicating that the alpha 7 beta 1 integrin is not essential for myogenesis. However, histological analysis of skeletal muscle revealed typical symptoms of a progressive muscular dystrophy starting soon after birth, but with a distinct variability in different muscle types. The observed histopathological changes strongly indicate an impairment of function of the myotendinous junctions. These findings demonstrate that alpha 7 beta 1 integrin represents an indispensable linkage between the muscle fibre and the extracellular matrix that is independent of the dystrophin-dystroglycan complex-mediated interaction of the cytoskeleton with the muscle basement membrane.

  13. Advancement in integrin facilitated drug delivery.

    Science.gov (United States)

    Arosio, Daniela; Casagrande, Cesare

    2016-02-01

    The research of integrin-targeted anticancer agents has recorded important advancements in ingenious design of delivery systems, based either on the prodrug approach, or on nanoparticle carriers, but for now, none of these has reached a clinical stage of development. Past work in this area has been extensively reviewed by us and others. Thus, the purpose and scope of the present review is to survey the advancement reported in the last 3years, with focus on innovative delivery systems that appear to afford openings for future developments. These systems exploit the labelling with conventional and novel integrin ligands for targeting the interface of cancer cells and of endothelial cells involved in cancer angiogenesis, with the proteins of the extracellular matrix, in the circulation, in tissues, and in tumour stroma, as the site of progression and metastatic evolution of the disease. Furthermore, these systems implement the expertise in the development of nanomedicines to the purpose of achieving preferential biodistribution and uptake in cancer tissues, internalisation in cancer cells, and release of the transported drugs at intracellular sites. The assessment of the value of controlling these factors, and their combination, for future developments requires support of biological testing in appropriate mechanistic models, but also imperatively demand confirmation in therapeutically relevant in vivo models for biodistribution, efficacy, and lack of off-target effects. Thus, among many studies, we have tried to point out the results supported by relevant in vivo studies, and we have emphasised in specific sections those addressing the medical needs of drug delivery to brain tumours, as well as the delivery of oligonucleotides modulating gene-dependent pathological mechanism. The latter could constitute the basis of a promising third branch in the therapeutic armamentarium against cancer, in addition to antibody-based agents and to cytotoxic agents. Copyright © 2015

  14. Algorithm based on the Thomson problem for determination of equilibrium structures of metal nanoclusters

    Science.gov (United States)

    Arias, E.; Florez, E.; Pérez-Torres, J. F.

    2017-06-01

    A new algorithm for the determination of equilibrium structures suitable for metal nanoclusters is proposed. The algorithm performs a stochastic search of the minima associated with the nuclear potential energy function restricted to a sphere (similar to the Thomson problem), in order to guess configurations of the nuclear positions. Subsequently, the guessed configurations are further optimized driven by the total energy function using the conventional gradient descent method. This methodology is equivalent to using the valence shell electron pair repulsion model in guessing initial configurations in the traditional molecular quantum chemistry. The framework is illustrated in several clusters of increasing complexity: Cu7, Cu9, and Cu11 as benchmark systems, and Cu38 and Ni9 as novel systems. New equilibrium structures for Cu9, Cu11, Cu38, and Ni9 are reported.

  15. A nanocluster-based fluorescent sensor for sensitive hemoglobin detection.

    Science.gov (United States)

    Yang, Dongqin; Meng, Huijie; Tu, Yifeng; Yan, Jilin

    2017-08-01

    In this report, a fluorescence sensor for sensitive detection of hemoglobin was developed. Gold nanoclusters were first synthesized with bovine serum albumin. It was found that both hydrogen peroxide and hemoglobin could weakly quench the fluorescence from the gold nanoclusters, but when these two were applied onto the nanolcusters simultaneously, a much improved quenching was resulted. This enhancing effect was proved to come from the catalytic generation of hydroxyl radical by hemoglobin. Under an optimized condition, the quenching linearly related to the concentration of hemoglobin in the range of 1-250nM, and a limit of detection as low as 0.36nM could be obtained. This provided a sensitive means for the quantification of Hb. The sensor was then successfully applied for blood analyses with simple sample pretreatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Integrins in cell migration – the actin connection

    OpenAIRE

    Vicente-Manzanares, Miguel; Choi, Colin Kiwon; Horwitz, Alan Rick

    2008-01-01

    The connection between integrins and actin is driving the field of cell migration in new directions. Integrins and actin are coupled through a physical linkage, which provides traction for migration. Recent studies show the importance of this linkage in regulating adhesion organization and development. Actin polymerization orchestrates adhesion assembly near the leading edge of a migrating cell, and the dynamic cross-linking of actin filaments promotes adhesion maturat...

  17. Theory of Nanocluster Size Distributions from Ion Beam Synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, C.W.; Yi, D.O.; Sharp, I.D.; Shin, S.J.; Liao, C.Y.; Guzman, J.; Ager III, J.W.; Haller, E.E.; Chrzan, D.C.

    2008-06-13

    Ion beam synthesis of nanoclusters is studied via both kinetic Monte Carlo simulations and the self-consistent mean-field solution to a set of coupled rate equations. Both approaches predict the existence of a steady state shape for the cluster size distribution that depends only on a characteristic length determined by the ratio of the effective diffusion coefficient to the ion flux. The average cluster size in the steady state regime is determined by the implanted species/matrix interface energy.

  18. Chemical- or radiation-assisted selective dealloying in bimetallic nanoclusters

    International Nuclear Information System (INIS)

    Mattei, G.; De Marchi, G.; Maurizio, C.; Mazzoldi, P.; Sada, C.; Bello, V.; Battaglin, G.

    2003-01-01

    A selective dealloying in bimetallic nanoclusters prepared by ion implantation has been found upon thermal annealing in oxidizing atmosphere or irradiation with light ions. In the first process, the incoming oxygen interacts preferentially with copper promoting Cu 2 O formation, therefore extracting copper from the alloy. In the second process the irradiation with Ne ions promotes a preferential extraction of Au from the alloy, resulting in the formation of Au-enriched 'satellite' nanoparticles around the original Au x Cu 1-x cluster

  19. Activated integrin VLA-4 localizes to the lamellipodia and mediates T cell migration on VCAM-11

    Science.gov (United States)

    Hyun, Young-Min; Chung, Hung-Li; McGrath, James L.; Waugh, Richard E.; Kim, Minsoo

    2009-01-01

    Lymphocyte migration from blood into lymphoid tissues or to sites of inflammation occurs through interactions between cell surface integrins and their ligands expressed on the vascular endothelium and the extracellular matrix. Very Late Antigen-4 (VLA-4, α4β1) is a key integrin in the effective trafficking of lymphocytes. Although it has been well established that integrins undergo functionally significant conformational changes to mediate cell adhesion, there is no mechanistic information that explains how these are dynamically and spatially regulated during lymphocyte polarization and migration. Using dynamic fluorescence resonance energy transfer (FRET) analysis of a novel VLA-4 FRET sensor under total internal reflection fluorescence (TIRF) microscopy, we show that VLA-4 activation localizes to the lamellipodium in living cells. During T cell migration on VCAM-1, VLA-4 activation concurs with spatial redistribution of chemokine receptor and active Rap1 at the leading edge. Selective inhibition of the activated VLA-4 at leading edge with a small molecule inhibitor is sufficient to block T cell migration. These data suggest that a subpopulation of activated VLA-4 is mainly localized to the leading edge of polarized human T cells, and is critical for T cell migration on VCAM-1. PMID:19542447

  20. PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility

    Directory of Open Access Journals (Sweden)

    Ana E. González Wusener

    2016-01-01

    Full Text Available Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoA-myosin-dependent contractility. Using PTP1B null (KO cells and PTP1B reconstituted (WT cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype. We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration.

  1. PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility

    Science.gov (United States)

    González Wusener, Ana E.; González, Ángela; Nakamura, Fumihiko; Arregui, Carlos O.

    2016-01-01

    ABSTRACT Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoA-myosin-dependent contractility. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype. We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration. PMID:26700725

  2. Lamellipodia nucleation by filopodia depends on integrin occupancy and downstream Rac1 signaling

    International Nuclear Information System (INIS)

    Guillou, Herve; Depraz-Depland, Adeline; Planus, Emmanuelle; Vianay, Benoit; Chaussy, Jacques; Grichine, Alexei; Albiges-Rizo, Corinne; Block, Marc R.

    2008-01-01

    Time-lapse video-microscopy unambiguously shows that fibroblast filopodia are the scaffold of lamellipodia nucleation that allows anisotropic cell spreading. This process was dissected into elementary stages by monitoring cell adhesion on micropatterned extracellular matrix arrays of various pitches. Adhesion structures are stabilized by contact with the adhesive plots and subsequently converted into lamellipodia-like extensions starting at the filopodia tips. This mechanism progressively leads to full cell spreading. Stable expression of the dominant-negative Rac1 N17 impairs this change in membrane extension mode and stops cell spreading on matrix arrays. Similar expression of the dominant-negative Cdc42 N17 impairs cell spreading on homogenous and structured substrate, suggesting that filopodia extension is a prerequisite for cell spreading in this model. The differential polarity of the nucleation of lamellipodial structures by filopodia on homogenous and structured surfaces starting from the cell body and of filopodia tip, respectively, suggested that this process is triggered by areas that are in contact with extracellular matrix proteins for longer times. Consistent with this view, wild-type cells cannot spread on microarrays made of function blocking or neutral anti-β 1 integrin antibodies. However, stable expression of a constitutively active Rac1 mutant rescues the cell ability to spread on these integrin microarrays. Thereby, lamellipodia nucleation by filopodia requires integrin occupancy by matrix substrate and downstream Rac1 signaling

  3. Adenylate cyclase toxin promotes internalisation of integrins and raft components and decreases macrophage adhesion capacity.

    Directory of Open Access Journals (Sweden)

    César Martín

    Full Text Available Bordetella pertussis, the bacterium that causes whooping cough, secretes an adenylate cyclase toxin (ACT that must be post-translationally palmitoylated in the bacterium cytosol to be active. The toxin targets phagocytes expressing the CD11b/CD18 integrin receptor. It delivers a catalytic adenylate cyclase domain into the target cell cytosol producing a rapid increase of intracellular cAMP concentration that suppresses bactericidal functions of the phagocyte. ACT also induces calcium fluxes into target cells. Biochemical, biophysical and cell biology approaches have been applied here to show evidence that ACT and integrin molecules, along with other raft components, are rapidly internalized by the macrophages in a toxin-induced calcium rise-dependent process. The toxin-triggered internalisation events occur through two different routes of entry, chlorpromazine-sensitive receptor-mediated endocytosis and clathrin-independent internalisation, maybe acting in parallel. ACT locates into raft-like domains, and is internalised, also in cells devoid of receptor. Altogether our results suggest that adenylate cyclase toxin, and maybe other homologous pathogenic toxins from the RTX (Repeats in Toxin family to which ACT belongs, may be endowed with an intrinsic capacity to, directly and efficiently, insert into raft-like domains, promoting there its multiple activities. One direct consequence of the integrin removal from the cell surface of the macrophages is the hampering of their adhesion ability, a fundamental property in the immune response of the leukocytes that could be instrumental in the pathogenesis of Bordetella pertussis.

  4. Adenylate cyclase toxin promotes internalisation of integrins and raft components and decreases macrophage adhesion capacity.

    Science.gov (United States)

    Martín, César; Uribe, Kepa B; Gómez-Bilbao, Geraxane; Ostolaza, Helena

    2011-02-23

    Bordetella pertussis, the bacterium that causes whooping cough, secretes an adenylate cyclase toxin (ACT) that must be post-translationally palmitoylated in the bacterium cytosol to be active. The toxin targets phagocytes expressing the CD11b/CD18 integrin receptor. It delivers a catalytic adenylate cyclase domain into the target cell cytosol producing a rapid increase of intracellular cAMP concentration that suppresses bactericidal functions of the phagocyte. ACT also induces calcium fluxes into target cells. Biochemical, biophysical and cell biology approaches have been applied here to show evidence that ACT and integrin molecules, along with other raft components, are rapidly internalized by the macrophages in a toxin-induced calcium rise-dependent process. The toxin-triggered internalisation events occur through two different routes of entry, chlorpromazine-sensitive receptor-mediated endocytosis and clathrin-independent internalisation, maybe acting in parallel. ACT locates into raft-like domains, and is internalised, also in cells devoid of receptor. Altogether our results suggest that adenylate cyclase toxin, and maybe other homologous pathogenic toxins from the RTX (Repeats in Toxin) family to which ACT belongs, may be endowed with an intrinsic capacity to, directly and efficiently, insert into raft-like domains, promoting there its multiple activities. One direct consequence of the integrin removal from the cell surface of the macrophages is the hampering of their adhesion ability, a fundamental property in the immune response of the leukocytes that could be instrumental in the pathogenesis of Bordetella pertussis.

  5. Essential role of integrin-linked kinase in regulation of phagocytosis in keratinocytes.

    Science.gov (United States)

    Sayedyahossein, Samar; Nini, Lylia; Irvine, Timothy S; Dagnino, Lina

    2012-10-01

    Phagocytic melanosome uptake by epidermal keratinocytes is a central protective mechanism against damage induced by ultraviolet radiation. Phagocytosis requires formation of pseudopodia via actin cytoskeleton rearrangements. Integrin-linked kinase (ILK) is an important modulator of actin cytoskeletal dynamics. We have examined the role of ILK in regulation of phagocytosis, using epidermal keratinocytes isolated from mice with epidermis-restricted Ilk gene inactivation. ILK-deficient cells exhibited severely impaired capacity to engulf fluorescent microspheres in response to stimulation of the keratinocyte growth factor (KGF) receptor or the protease-activated receptor-2. KGF induced ERK phosphorylation in ILK-expressing and ILK-deficient cells, suggesting that ILK is not essential for KGF receptor signaling. In contrast, KGF promoted activation of Rac1 and formation of pseudopodia in ILK-expressing, but not in ILK-deficient cells. Rac1-deficient keratinocytes also showed substantially impaired phagocytic ability, underlining the importance of ILK-dependent Rac1 function for particle engulfment. Finally, cross-modulation of KGF receptors by integrins may be another important element, as integrin β1-deficient keratinocytes also fail to show significant phagocytosis in response to KGF. Thus, we have identified a novel signaling pathway essential for phagocytosis in keratinocytes, which involves ILK-dependent activation of Rac1 in response to KGF, resulting in the formation of pseudopodia and particle uptake.

  6. Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10.

    Directory of Open Access Journals (Sweden)

    Kaisa Kyöstilä

    Full Text Available The skeletal dysplasias are disorders of the bone and cartilage tissues. Similarly to humans, several dog breeds have been reported to suffer from different types of genetic skeletal disorders. We have studied the molecular genetic background of an autosomal recessive chondrodysplasia that affects the Norwegian Elkhound and Karelian Bear Dog breeds. The affected dogs suffer from disproportionate short stature dwarfism of varying severity. Through a genome-wide approach, we mapped the chondrodysplasia locus to a 2-Mb region on canine chromosome 17 in nine affected and nine healthy Elkhounds (praw = 7.42×10(-6, pgenome-wide = 0.013. The associated locus contained a promising candidate gene, cartilage specific integrin alpha 10 (ITGA10, and mutation screening of its 30 exons revealed a nonsense mutation in exon 16 (c.2083C>T; p.Arg695* that segregated fully with the disease in both breeds (p = 2.5×10(-23. A 24% mutation carrier frequency was indicated in NEs and an 8% frequency in KBDs. The ITGA10 gene product, integrin receptor α10-subunit combines into a collagen-binding α10β1 integrin receptor, which is expressed in cartilage chondrocytes and mediates chondrocyte-matrix interactions during endochondral ossification. As a consequence of the nonsense mutation, the α10-protein was not detected in the affected cartilage tissue. The canine phenotype highlights the importance of the α10β1 integrin in bone growth, and the large animal model could be utilized to further delineate its specific functions. Finally, this study revealed a candidate gene for human chondrodysplasias and enabled the development of a genetic test for breeding purposes to eradicate the disease from the two dog breeds.

  7. α5β1-Integrin inhibitor (CLT-28643) effective in rabbit trabeculectomy model.

    Science.gov (United States)

    Schultheiss, Maximilian; Schnichels, Sven; Konrad, Eva-Maria; Bartz-Schmidt, Karl U; Zahn, Grit; Caldirola, Patrizia; Fsadni, Mario G; Caram-Lelham, Ninus; Spitzer, Martin S

    2017-02-01

    Glaucoma filtration surgery (GFS) fails due to fibrosis. The α5β1-integrin plays a pivotal role in fibrosis, angiogenesis and inflammation. This is the first experiment evaluating the prevention of fibrosis after GFS by a specific small molecule α5β1-integrin inhibitor (CLT-28643). Twenty-four rabbits received trabeculectomy on their right eyes. The rabbits were randomized into three groups of eight eyes each. CLT-28643 was given as a single subconjunctival injection intraoperatively to two of the right eye groups followed by postoperative vehicle eye drops (CLT+ group) or CLT-28643 eye drops 4 times daily (CLT++ group). A third group received mitomycin-C (MMC) intraoperatively (sponge application, 0.04%, 2 min) followed by vehicle eye drops postoperatively. The control-surgery group consisted of 12 left eyes having trabeculectomy with no adjunctive therapy. The remaining 12 left eyes formed the untreated group. Clinical assessment included intraocular pressure (IOP) measurement, slit-lamp examination (including bleb survival and morphology) and bleb photography. The rabbits were killed after four weeks for histology. Both CLT-28643-treated groups showed significantly prolonged bleb survival, and better bleb score compared to the control-surgery group. At end of the study, most functioning blebs were found in the MMC group (MMC group 75%; CLT+ group 12.5%, CLT++ group 25%; CLT+ group 12.5%, control-surgery group 0%). CLT-28643 was non-toxic and well tolerated. This rabbit GFS study indicates that inhibition of α5β1-integrin by the novel α5β1-integrin antagonist CLT-28643 significantly improved the outcome. The effect of a single intro-operative application of CLT-28643 seems to be inferior to 0.04% MMC. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  8. First-principles study of the electronic transport properties in (GaAs)n (n=2–4) nanocluster-based molecular junctions

    International Nuclear Information System (INIS)

    Zhang, Daoli; Xu, Yuanlan; Zhang, Jianbing; Miao, Xiangshui

    2012-01-01

    In this program the geometric structures and electronic transport properties of a series of (GaAs) n (n=2,3,4) clusters are comparatively studied using non-equilibrium Green's function (NEGF) combined with density functional theory (DFT). It is find that all the GaAs nanocluster-based molecular junctions show metallic behavior at low biases ([−2 V,2 V]) while negative differential resistance (NDR) appears at a certain high bias range. Our calculation shows that the current of (GaAs) 3 nanocluster-based molecular junction is almost the smallest at any bias. The mechanisms of the current–voltage characteristics of all the three molecular junctions are proposed.

  9. Chiral Gold Nanoclusters: Atomic Level Origins of Chirality.

    Science.gov (United States)

    Zeng, Chenjie; Jin, Rongchao

    2017-08-04

    Chiral nanomaterials have received wide interest in many areas, but the exact origin of chirality at the atomic level remains elusive in many cases. With recent significant progress in atomically precise gold nanoclusters (e.g., thiolate-protected Au n (SR) m ), several origins of chirality have been unveiled based upon atomic structures determined by using single-crystal X-ray crystallography. The reported chiral Au n (SR) m structures explicitly reveal a predominant origin of chirality that arises from the Au-S chiral patterns at the metal-ligand interface, as opposed to the chiral arrangement of metal atoms in the inner core (i.e. kernel). In addition, chirality can also be introduced by a chiral ligand, manifested in the circular dichroism response from metal-based electronic transitions other than the ligand's own transition(s). Lastly, the chiral arrangement of carbon tails of the ligands has also been discovered in a very recent work on chiral Au 133 (SR) 52 and Au 246 (SR) 80 nanoclusters. Overall, the origins of chirality discovered in Au n (SR) m nanoclusters may provide models for the understanding of chirality origins in other types of nanomaterials and also constitute the basis for the development of various applications of chiral nanoparticles. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. UV luminescence of dendrimer-encapsulated gold nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Hyeong Seop; Kim, Jun Myung; Sohn, So Hyeong; Han, Noh Soo; Park, Seung Min [Dept. of Chemistry, Kyung Hee University, Seoul (Korea, Republic of)

    2016-10-15

    Size-dependent luminescence color is one of the interesting properties of metal nanocrystals, whose sizes are in the dimension of the Fermi wavelength of an electron. Despite the short Fermi wavelength of electrons in gold (-0.7 nm), luminescence of gold nanoclusters has been reported to range from the near-infrared to near-ultraviolet, depending on the number of atoms in the nanoclusters. The photoluminescence of G4-OH (Au) obtained by the excitation of 266 nm showed UV emission in addition to the well-known blue emission. The higher intensity and red-shifted emission of the gold nanoclusters was distinguished from the emission of dendrimers. The UV emission at 352 nm matched the emission energy of Au{sub 4} in the spherical jellium model, rather than the planar Au{sub 8}, which supported the emission of Au{sub 4} formed in G4-OH. Despite the change of [HAuCl{sub 4} ]/[G4-OH], the relative population between Au{sub 4} and Au{sub 8} was similar in G4-OH(Au), which indicated that the closed electronic and geometric structures stabilized the magic number of Au{sub 4}.

  11. Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium

    Science.gov (United States)

    Chen, Jichao; Krasnow, Mark A.

    2012-01-01

    Epithelia are classified as either simple, a single cell layer thick, or stratified (multilayered). Stratified epithelia arise from simple epithelia during development, and transcription factor p63 functions as a key positive regulator of epidermal stratification. Here we show that deletion of integrin beta 1 (Itgb1) in the developing mouse airway epithelium abrogates airway branching and converts this monolayer epithelium into a multilayer epithelium with more than 10 extra layers. Mutant lung epithelial cells change mitotic spindle orientation to seed outer layers, and cells in different layers become molecularly and functionally distinct, hallmarks of normal stratification. However, mutant lung epithelial cells do not activate p63 and do not switch to the stratified keratin profile of epidermal cells. These data, together with previous data implicating Itgb1 in regulation of epidermal stratification, suggest that the simple-versus-stratified developmental decision may involve not only stratification inducers like p63 but suppressors like Itgb1 that prevent simple epithelia from inappropriately activating key steps in the stratification program. PMID:23285215

  12. Protein coated gold nanoparticles as template for the directed synthesis of highly fluorescent gold nanoclusters

    Science.gov (United States)

    Zhang, Lingyan; Han, Fei

    2018-04-01

    Bovine serum albumin (BSA) modified gold nanoparticles (AuNPs) was selected as template for the synthesis of AuNPs@gold nanoclusters (AuNCs) core/shell nanoparticles, in which BSA not only acted as dual functions agent for both anchoring and reducing Au3+ ions, but also was employed as a bridge between the AuNPs and AuNCs. Optical properties of AuNPs@AuNCs core/shell nanoparticles were studied using UV-visible and fluorescence spectroscopy. The prepared AuNPs@AuNCs core/shell nanoparticles exhibited sphere size uniformity with improved monodispersity, excellent fluorescence and fluorescent stability. Compared with AuNCs, AuNPs@AuNCs core/shell nanoparticles possessed large size and strong fluorescence intensity due to the effect of AuNPs as core. Moreover, the mechanism of the AuNPs induced fluorescence changes of the core/shell nanoparticles was first explored.

  13. Investigating the adsorption of H2O on ZnO nanoclusters by first principle calculations

    KAUST Repository

    Al-Sunaidi, Abdullah A.

    2011-04-01

    The interaction of a single H2O molecule on selected ZnO nanoclusters is investigated by carrying out calculations based on the density-functional theory at the hybrid-GGA (B97-2) level. These clusters have ring, drum, tube and bubble shapes and their physical properties like the binding energy and the band gap energy depend strongly on the shape and size of the cluster. Depending on the stability of the cluster, H2O show both chemisorption and dissociation on the surfaces of the clusters. We analyzed the effect of H2O adsorption on the properties of clusters of size n = 12 via the density of state, HOMO-LUMO orbitals and the changes in the IR frequencies. © 2011 Elsevier B.V. All rights reserved.

  14. Highly fluorescent silver nanoclusters in alumina-silica composite optical fiber

    Energy Technology Data Exchange (ETDEWEB)

    Halder, A.; Chattopadhyay, R.; Majumder, S.; Paul, M. C.; Das, S.; Bhadra, S. K., E-mail: skbhadra@cgcri.res.in [Fiber Optics and Photonics Division, CSIR-Central Glass and Ceramic Research Institute, 196, Raja S. C. Mullick Road, Kolkata 700032 (India); Bysakh, S.; Unnikrishnan, M. [Material Characterization Division, CSIR-Central Glass and Ceramic Research Institute, 196, Raja S. C. Mullick Road, Kolkata 700032 (India)

    2015-01-05

    An efficient visible fluorescent optical fiber embedded with silver nanoclusters (Ag-NCs) having size ∼1 nm, uniformly distributed in alumina-silica composite core glass, is reported. Fibers are fabricated in a repetitive controlled way through modified chemical vapour deposition process associated with solution doping technique. Fibers are drawn from the transparent preforms by conventional fiber drawing process. Structural characteristics of the doped fibers are studied using transmission electron microscopy and electron probe micro analysis. The oxidation state of Ag within Ag-NCs is investigated by X-ray photo electron spectroscopy. The observed significant fluorescence of the metal clusters in fabricated fibers is correlated with electronic model. The experimentally observed size dependent absorption of the metal clusters in fabricated fibers is explained with the help of reported results calculated by ab-initio density functional theory. These optical fibers may open up an opportunity of realizing tunable wavelength fiber laser without the help of rare earth elements.

  15. Dual emission fluorescent silver nanoclusters for sensitive detection of the biological coenzyme NAD+/NADH.

    Science.gov (United States)

    Yuan, Yufeng; Huang, Kehan; Chang, Mengfang; Qin, Cuifang; Zhang, Sanjun; Pan, Haifeng; Chen, Yan; Xu, Jianhua

    2016-02-01

    Fluorescent silver nanoclusters (Ag NCs) displaying dual-excitation and dual-emission properties have been developed for the specific detection of NAD(+) (nicotinamide adenine dinucleotide, oxidized form). With the increase of NAD(+) concentrations, the longer wavelength emission (with the peak at 550 nm) was gradually quenched due to the strong interactions between the NAD(+) and Ag NCs, whereas the shorter wavelength emission (peaking at 395 nm) was linearly enhanced. More important, the dual-emission intensity ratio (I395/I550), fitting by a single-exponential decay function, can efficiently detect various NAD(+) levels from 100 to 4000 μM, as well as label NAD(+)/NADH (reduced form of NAD) ratios in the range of 1-50. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. A New Class of Atomically Precise, Hydride-Rich Silver Nanoclusters Co-Protected by Phosphines

    KAUST Repository

    Bootharaju, Megalamane Siddaramappa

    2016-10-10

    Thiols and phosphines are the most widely used organic ligands to attain atomically precise metal nanoclusters (NCs). Here, we used simple hydrides (e.g., H–) as ligands along with phosphines, such as triphenylphosphine (TPP), 1,2-bis(diphenylphosphino)ethane [DPPE], and tris(4-fluorophenyl)phosphine [TFPP] to design and synthesize a new class of hydride-rich silver NCs. This class includes [Ag18H16(TPP)10]2+, [Ag25H22(DPPE)8]3+, and [Ag26H22(TFPP)13]2+. Our work reveals a new family of atomically precise NCs protected by H– ligands and labile phosphines, with potentially more accessible active metal sites for functionalization and provides a new set of stable NC sizes with simpler ligand–metal bonding for researchers to explore both experimentally and computationally.

  17. The changing integrin expression and a role for integrin β8 in the chondrogenic differentiation of mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Vanessa L S LaPointe

    Full Text Available Many cartilage tissue engineering approaches aim to differentiate human mesenchymal stem cells (hMSCs into chondrocytes and develop cartilage in vitro by targeting cell-matrix interactions. We sought to better inform the design of cartilage tissue engineering scaffolds by understanding how integrin expression changes during chondrogenic differentiation. In three models of in vitro chondrogenesis, we studied the temporal change of cartilage phenotype markers and integrin subunits during the differentiation of hMSCs. We found that transcript expression of most subunits was conserved across the chondrogenesis models, but was significantly affected by the time-course of differentiation. In particular, ITGB8 was up-regulated and its importance in chondrogenesis was further established by a knockdown of integrin β8, which resulted in a non-hyaline cartilage phenotype, with no COL2A1 expression detected. In conclusion, we performed a systematic study of the temporal changes of integrin expression during chondrogenic differentiation in multiple chondrogenesis models, and revealed a role for integrin β8 in chondrogenesis. This work enhances our understanding of the changing adhesion requirements of hMSCs during chondrogenic differentiation and underlines the importance of integrins in establishing a cartilage phenotype.

  18. The Changing Integrin Expression and a Role for Integrin β8 in the Chondrogenic Differentiation of Mesenchymal Stem Cells

    Science.gov (United States)

    LaPointe, Vanessa L. S.; Verpoorte, Amanda; Stevens, Molly M.

    2013-01-01

    Many cartilage tissue engineering approaches aim to differentiate human mesenchymal stem cells (hMSCs) into chondrocytes and develop cartilage in vitro by targeting cell-matrix interactions. We sought to better inform the design of cartilage tissue engineering scaffolds by understanding how integrin expression changes during chondrogenic differentiation. In three models of in vitro chondrogenesis, we studied the temporal change of cartilage phenotype markers and integrin subunits during the differentiation of hMSCs. We found that transcript expression of most subunits was conserved across the chondrogenesis models, but was significantly affected by the time-course of differentiation. In particular, ITGB8 was up-regulated and its importance in chondrogenesis was further established by a knockdown of integrin β8, which resulted in a non-hyaline cartilage phenotype, with no COL2A1 expression detected. In conclusion, we performed a systematic study of the temporal changes of integrin expression during chondrogenic differentiation in multiple chondrogenesis models, and revealed a role for integrin β8 in chondrogenesis. This work enhances our understanding of the changing adhesion requirements of hMSCs during chondrogenic differentiation and underlines the importance of integrins in establishing a cartilage phenotype. PMID:24312400

  19. Integrin αβ1, αvβ, α6β effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

    International Nuclear Information System (INIS)

    Sansing, Hope A.; Sarkeshik, Ali; Yates, John R.; Patel, Vyomesh; Gutkind, J. Silvio; Yamada, Kenneth M.; Berrier, Allison L.

    2011-01-01

    Research highlights: → Proteomics of clustered integrin αβ1, α v β, α 6 β receptors in oral carcinoma. → p130Cas, Dek, Src and talin regulate oral carcinoma invasion. → p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomics screen of proteins recruited to clustered integrin αβ1, α v β or α 6 β receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.

  20. Integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

    Energy Technology Data Exchange (ETDEWEB)

    Sansing, Hope A. [Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center-New Orleans, School of Dentistry, New Orleans, LA (United States); Sarkeshik, Ali; Yates, John R. [Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA (United States); Patel, Vyomesh; Gutkind, J. Silvio [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Yamada, Kenneth M. [Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Berrier, Allison L., E-mail: allison.berrier@gmail.com [Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center-New Orleans, School of Dentistry, New Orleans, LA (United States)

    2011-03-11

    Research highlights: {yields} Proteomics of clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} receptors in oral carcinoma. {yields} p130Cas, Dek, Src and talin regulate oral carcinoma invasion. {yields} p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomics screen of proteins recruited to clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta} or {alpha}{sub 6}{beta} receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.

  1. Pt, Co–Pt and Fe–Pt alloy nanoclusters encapsulated in virus capsids

    International Nuclear Information System (INIS)

    Okuda, M; Eloi, J-C; Jones, S E Ward; Schwarzacher, W; Verwegen, M; Cornelissen, J J L M

    2016-01-01

    Nanostructured Pt-based alloys show great promise, not only for catalysis but also in medical and magnetic applications. To extend the properties of this class of materials, we have developed a means of synthesizing Pt and Pt-based alloy nanoclusters in the capsid of a virus. Pure Pt and Pt-alloy nanoclusters are formed through the chemical reduction of [PtCl 4 ] − by NaBH 4 with/without additional metal ions (Co or Fe). The opening and closing of the ion channels in the virus capsid were controlled by changing the pH and ionic strength of the solution. The size of the nanoclusters is limited to 18 nm by the internal diameter of the capsid. Their magnetic properties suggest potential applications in hyperthermia for the Co–Pt and Fe–Pt magnetic alloy nanoclusters. This study introduces a new way to fabricate size-restricted nanoclusters using virus capsid. (paper)

  2. A Comparative XAFS Study of Gold-thiolate Nanoparticles and Nanoclusters

    International Nuclear Information System (INIS)

    Chevrier, D M; Chatt, A; Zhang, P; Sham, T K

    2013-01-01

    Tiopronin-capped gold nanoparticles and gold nanoclusters of sizes 3.0 and 1.5 nm, respectively, were investigated with XAFS at the gold L 3 -edge. The specific EXAFS fitting procedure is discussed for obtaining reliable fit parameters for each system. The difficulties and challenges faced when analysing EXAFS data for gold nanoparticles and nanoclusters are also mentioned. Fitting results for gold nanoparticles reveal a small amount of surface Au-thiolate interactions with a large Au-Au metal core. For gold nanoclusters, only a one-shell fit was obtainable. Instead of Au-Au metal core, long-range interactions are expected for gold nanoclusters. Tiopronin-capped gold nanoclusters are proposed to be polymeric in nature, which helps explain the observed red luminescence.

  3. pH-Induced transformation of ligated Au25 to brighter Au23 nanoclusters.

    Science.gov (United States)

    Waszkielewicz, Magdalena; Olesiak-Banska, Joanna; Comby-Zerbino, Clothilde; Bertorelle, Franck; Dagany, Xavier; Bansal, Ashu K; Sajjad, Muhammad T; Samuel, Ifor D W; Sanader, Zeljka; Rozycka, Miroslawa; Wojtas, Magdalena; Matczyszyn, Katarzyna; Bonacic-Koutecky, Vlasta; Antoine, Rodolphe; Ozyhar, Andrzej; Samoc, Marek

    2018-05-01

    Thiolate-protected gold nanoclusters have recently attracted considerable attention due to their size-dependent luminescence characterized by a long lifetime and large Stokes shift. However, the optimization of nanocluster properties such as the luminescence quantum yield is still a challenge. We report here the transformation of Au25Capt18 (Capt labels captopril) nanoclusters occurring at low pH and yielding a product with a much increased luminescence quantum yield which we have identified as Au23Capt17. We applied a simple method of treatment with HCl to accomplish this transformation and we characterized the absorption and emission of the newly created ligated nanoclusters as well as their morphology. Based on DFT calculations we show which Au nanocluster size transformations can lead to highly luminescent species such as Au23Capt17.

  4. The formation of Cr2O3 nanoclusters over graphene sheet and carbon nanotubes

    Science.gov (United States)

    Dabaghmanesh, Samira; Neek-Amal, Mehdi; Partoens, Bart; Neyts, Erik C.

    2017-11-01

    Carbon supported metal oxide nanoparticles hold promise for various future applications in diverse areas including spintronics, catalysis and biomedicine. These applications, however, typically depend on the structure and morphology of the nanoparticles. In this contribution, we employ classical molecular dynamic simulations based on a recently developed force field to study the structural properties of Cr2O3 nanoclusters over graphene and carbon nanotubes. We observe that Cr2O3 nanoclusters tend to aggregate over both freestanding graphene and carbon nanotubes and form larger nanoclusters. These large nanoclusters are characterized by their worm-like shape with a lattice constant similar to that of bulk Cr2O3. We also investigate the structural deformation induced in graphene due to the presence of Cr2O3 nanoclusters.

  5. Synthesis and Doping of Ligand-Protected Atomically-Precise Metal Nanoclusters

    KAUST Repository

    Aljuhani, Maha A.

    2016-05-01

    Rapidly expanding research in nanotechnology has led to exciting progress in a versatile array of applications from medical diagnostics to catalysis. This success resulted from the manipulation of the desired properties of nanomaterials by controlling their size, shape, and composition. Among the most thriving areas of research about nanoparticle is the synthesis and doping of the ligand-protected atomically-precise metal nanoclusters. In this thesis, we developed three different novel metal nanoclusters, such as doped Ag29 with five gold (Au) atoms leading to enhance its quantum yield with remarkable stability. We also developed half-doped (alloyed) cluster of Ni6 nanocluster with molybdenum (Mo). This enabled enhanced stability and better catalytic activity. The third metal nanocluster that we synthesized was Au28 nanocluster by using di-thiolate as the ligand stabilizer instead of mono-thiolate. The new metal clusters obtained have been characterized by spectroscopic, electrochemical and crystallographic methods.

  6. Generalized rate-equation analysis of excitation exchange between silicon nanoclusters and erbium ions

    International Nuclear Information System (INIS)

    Kenyon, A. J.; Wojdak, M.; Ahmad, I.; Loh, W. H.; Oton, C. J.

    2008-01-01

    We discuss the use of rate equations to analyze the sensitization of erbium luminescence by silicon nanoclusters. In applying the general form of second-order coupled rate-equations to the Si nanocluster-erbium system, we find that the photoluminescence dynamics cannot be described using a simple rate equation model. Both rise and fall times exhibit a stretched exponential behavior, which we propose arises from a combination of a strongly distance-dependent nanocluster-erbium interaction, along with the finite size distribution and indirect band gap of the silicon nanoclusters. Furthermore, the low fraction of erbium ions that can be excited nonresonantly is a result of the small number of ions coupled to nanoclusters

  7. Coalition of Oct4A and β1 integrins in facilitating metastasis in ovarian cancer

    International Nuclear Information System (INIS)

    Samardzija, Chantel; Luwor, Rodney B.; Quinn, Michael A.; Kannourakis, George; Findlay, Jock K.; Ahmed, Nuzhat

    2016-01-01

    Ovarian cancer is a metastatic disease and one of the leading causes of gynaecology malignancy-related deaths in women. Cancer stem cells (CSCs) are key contributors of cancer metastasis and relapse. Integrins are a family of cell surface receptors which allow interactions between cells and their surrounding microenvironment and play a fundamental role in promoting metastasis. This study investigates the molecular mechanism which associates CSCs and integrins in ovarian cancer metastasis. The expression of Oct4A in high-grade serous ovarian tumors and normal ovaries was determined by immunofluorescence analysis. The functional role of Oct4A was evaluated by generating stable knockdown (KD) of Oct4A clones in an established ovarian cancer cell line HEY using shRNA-mediated silencing. The expression of integrins in cell lines was evaluated by flow cytometry. Spheroid forming ability, adhesion and the activities of matrix metalloproteinases 9/2 (MMP-9/2) was measured by in vitro functional assays and gelatin zymography. These observations were further validated in in vivo mouse models using Balb/c nu/nu mice. We report significantly elevated expression of Oct4A in high-grade serous ovarian tumors compared to normal ovarian tissues. The expression of Oct4A in ovarian cancer cell lines correlated with their CSC-related sphere forming abilities. The suppression of Oct4A in HEY cells resulted in a significant diminution of integrin β1 expression and associated α5 and α2 subunits compared to vector control cells. This was associated with a reduced adhesive ability on collagen and fibronectin and decreased secretion of pro-MMP2 in Oct4A KD cells compared to vector control cells. In vivo, Oct4A knock down (KD) cells produced tumors which were significantly smaller in size and weight compared to tumors derived from vector control cells. Immunohistochemical analyses of Oct4A KD tumor xenografts demonstrated a significant loss of cytokeratin 7 (CK7), Glut-1 as well as CD34

  8. Oncofetal Chondroitin Sulfate Glycosaminoglycans Are Key Players in Integrin Signaling and Tumor Cell Motility.

    Science.gov (United States)

    Clausen, Thomas Mandel; Pereira, Marina Ayres; Al Nakouzi, Nader; Oo, Htoo Zarni; Agerbæk, Mette Ø; Lee, Sherry; Ørum-Madsen, Maj Sofie; Kristensen, Anders Riis; El-Naggar, Amal; Grandgenett, Paul M; Grem, Jean L; Hollingsworth, Michael A; Holst, Peter J; Theander, Thor; Sorensen, Poul H; Daugaard, Mads; Salanti, Ali

    2016-12-01

    Many tumors express proteoglycans modified with oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS), which are normally restricted to the placenta. However, the role of ofCS in cancer is largely unknown. The function of ofCS in cancer was analyzed using the recombinant ofCS-binding VAR2CSA protein (rVAR2) derived from the malaria parasite, Plasmodium falciparum We demonstrate that ofCS plays a key role in tumor cell motility by affecting canonical integrin signaling pathways. Binding of rVAR2 to tumor cells inhibited the interaction of cells with extracellular matrix (ECM) components, which correlated with decreased phosphorylation of Src kinase. Moreover, rVAR2 binding decreased migration, invasion, and anchorage-independent growth of tumor cells in vitro Mass spectrometry of ofCS-modified proteoglycan complexes affinity purified from tumor cell lines on rVAR2 columns revealed an overrepresentation of proteins involved in cell motility and integrin signaling, such as integrin-β1 (ITGB1) and integrin-α4 (ITGA4). Saturating concentrations of rVAR2 inhibited downstream integrin signaling, which was mimicked by knockdown of the core chondroitin sulfate synthesis enzymes β-1,3-glucuronyltransferase 1 (B3GAT1) and chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1). The ofCS modification was highly expressed in both human and murine metastatic lesions in situ and preincubation or early intravenous treatment of tumor cells with rVAR2 inhibited seeding and spreading of tumor cells in mice. This was associated with a significant increase in survival of the animals. These data functionally link ofCS modifications with cancer cell motility and further highlights ofCS as a novel therapeutic cancer target. The cancer-specific expression of ofCS aids in metastatic phenotypes and is a candidate target for therapy. Mol Cancer Res; 14(12); 1288-99. ©2016 AACR. ©2016 American Association for Cancer Research.

  9. Fabrication of highly catalytic silver nanoclusters/graphene oxide nanocomposite as nanotag for sensitive electrochemical immunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiamian; Wang, Xiuyun; Wu, Shuo, E-mail: wushuo@dlut.edu.cn; Song, Jie; Zhao, Yanqiu; Ge, Yanqiu; Meng, Changgong

    2016-02-04

    Silver nanoclusters and graphene oxide nanocomposite (AgNCs/GRO) is synthesized and functionalized with detection antibody for highly sensitive electrochemical sensing of carcinoembryonic antigen (CEA), a model tumor marker involved in many cancers. AgNCs with large surface area and abundant amount of low-coordinated sites are synthesized with DNA as template and exhibit high catalytic activity towards the electrochemical reduction of H{sub 2}O{sub 2}. GRO is employed to assemble with AgNCs because it has large specific surface area, super electronic conductivity and strong π-π stacking interaction with the hydrophobic bases of DNA, which can further improve the catalytic ability of the AgNCs. Using AgNCs/GRO as signal amplification tag, an enzyme-free electrochemical immunosensing protocol is designed for the highly sensitive detection of CEA on the capture antibody functionalized immunosensing interface. Under optimal conditions, the designed immunosensor exhibits a wide linear range from 0.1 pg mL{sup −1} to 100 ng mL{sup −1} and a low limit of detection of 0.037 pg mL{sup −1}. Practical sample analysis reveals the sensor has good accuracy and reproducibility, indicating the great application prospective of the AgNCs/GRO in fabricating highly sensitive immunosensors, which can be extended to the detection of various kinds of low abundance disease related proteins. - Highlights: • An enzyme-free electrochemical immunosensor is reported for detecting proteins. • A silver nanocluster/graphene oxide composite is synthesized as nanotag. • The nanotags exhibit highly catalytic activity to the electro-reduction of H{sub 2}O{sub 2}. • The as-fabricated immunosensor could detect protein in serum samples.

  10. A single disulfide bond disruption in the β3 integrin subunit promotes thiol/disulfide exchange, a molecular dynamics study.

    Directory of Open Access Journals (Sweden)

    Lihie Levin

    Full Text Available The integrins are a family of membrane receptors that attach a cell to its surrounding and play a crucial function in cell signaling. The combination of internal and external stimuli alters a folded non-active state of these proteins to an extended active configuration. The β3 subunit of the platelet αIIbβ3 integrin is made of well-structured domains rich in disulfide bonds. During the activation process some of the disulfides are re-shuffled by a mechanism requiring partial reduction of some of these bonds; any disruption in this mechanism can lead to inherent blood clotting diseases. In the present study we employed Molecular Dynamics simulations for tracing the sequence of structural fluctuations initiated by a single cysteine mutation in the β3 subunit of the receptor. These simulations showed that in-silico protein mutants exhibit major conformational deformations leading to possible disulfide exchange reactions. We suggest that any mutation that prevents Cys560 from reacting with one of the Cys(567-Cys(581 bonded pair, thus disrupting its ability to participate in a disulfide exchange reaction, will damage the activation mechanism of the integrin. This suggestion is in full agreement with previously published experiments. Furthermore, we suggest that rearrangement of disulfide bonds could be a part of a natural cascade of thiol/disulfide exchange reactions in the αIIbβ3 integrin, which are essential for the native activation process.

  11. VANGL2 interacts with integrin αv to regulate matrix metalloproteinase activity and cell adhesion to the extracellular matrix.

    Science.gov (United States)

    Jessen, Tammy N; Jessen, Jason R

    2017-12-15

    Planar cell polarity (PCP) proteins are implicated in a variety of morphogenetic processes including embryonic cell migration and potentially cancer progression. During zebrafish gastrulation, the transmembrane protein Vang-like 2 (VANGL2) is required for PCP and directed cell migration. These cell behaviors occur in the context of a fibrillar extracellular matrix (ECM). While it is thought that interactions with the ECM regulate cell migration, it is unclear how PCP proteins such as VANGL2 influence these events. Using an in vitro cell culture model system, we previously showed that human VANGL2 negatively regulates membrane type-1 matrix metalloproteinase (MMP14) and activation of secreted matrix metalloproteinase 2 (MMP2). Here, we investigated the functional relationship between VANGL2, integrin αvβ3, and MMP2 activation. We provide evidence that VANGL2 regulates cell surface integrin αvβ3 expression and adhesion to fibronectin, laminin, and vitronectin. Inhibition of MMP14/MMP2 activity suppressed the cell adhesion defect in VANGL2 knockdown cells. Furthermore, our data show that MMP14 and integrin αv are required for increased proteolysis by VANGL2 knockdown cells. Lastly, we have identified integrin αvβ3 as a novel VANGL2 binding partner. Together, these findings begin to dissect the molecular underpinnings of how VANGL2 regulates MMP activity and cell adhesion to the ECM. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Multiple advanced logic gates made of DNA-Ag nanocluster and the application for intelligent detection of pathogenic bacterial genes.

    Science.gov (United States)

    Lin, Xiaodong; Liu, Yaqing; Deng, Jiankang; Lyu, Yanlong; Qian, Pengcheng; Li, Yunfei; Wang, Shuo

    2018-02-21

    The integration of multiple DNA logic gates on a universal platform to implement advance logic functions is a critical challenge for DNA computing. Herein, a straightforward and powerful strategy in which a guanine-rich DNA sequence lighting up a silver nanocluster and fluorophore was developed to construct a library of logic gates on a simple DNA-templated silver nanoclusters (DNA-AgNCs) platform. This library included basic logic gates, YES, AND, OR, INHIBIT, and XOR, which were further integrated into complex logic circuits to implement diverse advanced arithmetic/non-arithmetic functions including half-adder, half-subtractor, multiplexer, and demultiplexer. Under UV irradiation, all the logic functions could be instantly visualized, confirming an excellent repeatability. The logic operations were entirely based on DNA hybridization in an enzyme-free and label-free condition, avoiding waste accumulation and reducing cost consumption. Interestingly, a DNA-AgNCs-based multiplexer was, for the first time, used as an intelligent biosensor to identify pathogenic genes, E. coli and S. aureus genes, with a high sensitivity. The investigation provides a prototype for the wireless integration of multiple devices on even the simplest single-strand DNA platform to perform diverse complex functions in a straightforward and cost-effective way.

  13. The role of carbon solubility in Fe-C nano-clusters on the growth of small single-walled carbon nanotubes

    Science.gov (United States)

    Curtarolo, Stefano; Awasthy, Neha; Setyawan, Wahyu; Mora, Elena; Tokune, Toshio; Bolton, Kim; Harutyunyan, Avetik

    2008-03-01

    Various diameters of alumina-supported Fe catalysts are used to grow single-walled carbon nanotubes (SWCNTs) with chemical vapor decomposition. We find that the reduction of the catalyst size requires an increase of the minimum temperature necessary for the growth. We address this phenomenon in terms of solubility of C in Fe nanoclusters and, by using first principles calculations, we devise a simple model to predict the behavior of the phases competing for stability in Fe-C nanoclusters at low temperature. We show that, as a function particles size, there are three scenarios compatible with steady state-, limited- and no-growth of SWCNTs, corresponding to unaffected, reduced and no solubility of C in the particles. The result raises previously unknown concerns about the growth feasibility of small and very-long SWCNTs within the current Fe CVD technology, and suggests new strategies in the search of better catalysts. Research supported by Honda R.I. and NSF.

  14. Calreticulin overexpression correlates with integrin-α5 and transforming growth factor-β1 expression in the atria of patients with rheumatic valvular disease and atrial fibrillation.

    Science.gov (United States)

    Zhao, Fei; Zhang, Shijiang; Shao, Yongfeng; Wu, Yanhu; Qin, Jianwei; Chen, Yijiang; Chen, Liang; Gu, Haitao; Wang, Xiaowei; Huang, Chenjun; Zhang, Wei

    2013-10-03

    The aim of this study was to determine whether altered calreticulin expression and distribution contribute to the pathogenesis of atrial fibrillation (AF) associated with valvular heart disease (VHD). AF affects electrophysiological and structural changes that exacerbate AF. Atrial remodeling reportedly underlies AF generation, but the precise mechanism of atrial remodeling in AF remains unclear. Right and left atrial specimens were obtained from 68 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (SR; n=25), paroxysmal AF (PaAF; n=11), and persistent AF (PeAF; AF lasting >6 months; n=32) groups. Calreticulin, integrin-α5, and transforming growth factor-β1 (TGF-β1) mRNA and protein expression were measured. We also performed immunoprecipitation for calreticulin with either calcineurin B or integrin-α5. Calreticulin, integrin-α5, and TGF-β1 mRNA and protein expression were increased in the AF groups, especially in the left atrium in patients with mitral valve disease. Calreticulin interacted with both calcineurin B and integrin-α5. Integrin-α5 expression correlated with TGF-β1 expression, while calreticulin expression correlated with integrin-α5 and TGF-β1 expression. Despite similar cardiac function classifications, calreticulin expression was greater in the PeAF group than in the SR group. Calreticulin, integrin-α5, and TGF-β1 expression was increased in atrial tissue in patients with AF and was related to AF type, suggesting that calreticulin is involved in the pathogenesis of AF in VHD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. α6β1- and αV-integrins are required for long-term self-renewal of murine embryonic stem cells in the absence of LIF.

    Science.gov (United States)

    Cattavarayane, Sandhanakrishnan; Palovuori, Riitta; Tanjore Ramanathan, Jayendrakishore; Manninen, Aki

    2015-02-27

    The growth properties and self-renewal capacity of embryonic stem (ES) cells are regulated by their immediate microenvironment such as the extracellular matrix (ECM). Integrins, a central family of cellular ECM receptors, have been implicated in these processes but their specific role in ES cell self-renewal remains unclear. Here we have studied the effects of different ECM substrates and integrins in mouse ES cells in the absence of Leukemia Inhibitory Factor (LIF) using short-term assays as well as long-term cultures. Removal of LIF from ES cell culture medium induced morphological differentiation of ES cells into polarized epistem cell-like cells. These cells maintained epithelial morphology and expression of key stemness markers for at least 10 passages in the absence of LIF when cultured on laminin, fibronectin or collagen IV substrates. The specific functional roles of α6-, αV- and β1-integrin subunits were dissected using stable lentivirus-mediated RNAi methodology. β1-integrins were required for ES cell survival in long-term cultures and for the maintenance of stem cell marker expression. Inhibition of α6-integrin expression compromised self-renewal on collagen while αV-integrins were required for robust ES cell adhesion on laminin. Analysis of the stemness marker expression revealed subtle differences between α6- and αV-depleted ES cells but the expression of both was required for optimal self-renewal in long-term ES cell cultures. In the absence of LIF, long-term ES cell cultures adapt an epistem cell-like epithelial phenotype and retain the expression of multiple stem cell markers. Long-term maintenance of such self-renewing cultures depends on the expression of β1-, α6- and αV-integrins.

  16. Factors responsible for the stability and the existence of a clean energy gap of a silicon nanocluster

    International Nuclear Information System (INIS)

    Liu, Lei; Jayanthi, C. S.; Wu, Shi-Yu

    2001-01-01

    We present a critical theoretical study of electronic properties of silicon nanoclusters, in particular the roles played by symmetry, relaxation, and hydrogen passivation on the stability, the gap states and the energy gap of the system using the order N [O(N)] nonorthogonal tight-binding molecular dynamics and the local analysis of electronic structure. We find that for an unrelaxed cluster with its atoms occupying the regular tetrahedral network, the presence of undistorted local bonding configuration is sufficient for the appearance of a small clean energy gap. However, the energy gap of the unrelaxed cluster does not start at the highest occupied molecular orbital (HOMO). In fact, between the HOMO and the lower edge of the energy gap, localized dangling bond states are found. With hydrogen passivation, the localized dangling bond states are eliminated, resulting in a wider and clean energy gap. Relaxation of these hydrogen passivated clusters does not alter either the structure or the energy gap appreciably. However, if the silicon clusters are allowed to relax first, the majority of the dangling bonds are eliminated but additional defect states due to bond distortion appear, making the energy gap dirty. Hydrogen passivation of these relaxed clusters will further eliminate most of the remnant dangling bonds but no appreciable effect on the defect states associated with bond distortions will take place, thus still resulting in a dirty gap. For the hydrogen-passivated Si N nanoclusters with no bond distortion and no overall symmetry, we have studied the variation of the energy gap as a function of size of the cluster for N in the range of 80< N<6000. The dependence of the energy gap on the size shows similar behavior to that for silicon nanoclusters with no bond distortion but possessing overall symmetry

  17. Secondary reduction of alpha7B integrin in laminin alpha2 deficient congenital muscular dystrophy supports an additional transmembrane link in skeletal muscle.

    Science.gov (United States)

    Cohn, R D; Mayer, U; Saher, G; Herrmann, R; van der Flier, A; Sonnenberg, A; Sorokin, L; Voit, T

    1999-03-01

    in young boys (age <2 years). The expression of the beta1D integrin subunit was not altered in any of our patients with different types of muscular dystrophy. In contrast, sarcolemmal expression of beta1D integrin was significantly reduced in the alpha7 integrin knock-out mice, whereas the expression of the components of the DGC was not altered. The secondary loss of alpha7B in laminin alpha2 chain deficiency defines a biochemical change in the composition of the plasma membrane resulting from a primary protein deficiency in the basal lamina. These findings, in addition to the occurrence of a muscular dystrophy in alpha7 deficient mice, implies that the alpha7B integrin is an important laminin receptor within the plasma membrane which plays a significant role in skeletal muscle function and stability.

  18. Alterations in integrin expression modulates invasion of pancreatic cancer cells.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2009-01-01

    BACKGROUND: Factors mediating the invasion of pancreatic cancer cells through the extracellular matrix (ECM) are not fully understood. METHODS: In this study, sub-populations of the human pancreatic cancer cell line, MiaPaCa-2 were established which displayed differences in invasion, adhesion, anoikis, anchorage-independent growth and integrin expression. RESULTS: Clone #3 displayed higher invasion with less adhesion, while Clone #8 was less invasive with increased adhesion to ECM proteins compared to MiaPaCa-2. Clone #8 was more sensitive to anoikis than Clone #3 and MiaPaCa-2, and displayed low colony-forming efficiency in an anchorage-independent growth assay. Integrins beta 1, alpha 5 and alpha 6 were over-expressed in Clone #8. Using small interfering RNA (siRNA), integrin beta1 knockdown in Clone #8 cells increased invasion through matrigel and fibronectin, increased motility, decreased adhesion and anoikis. Integrin alpha 5 and alpha 6 knockdown also resulted in increased motility, invasion through matrigel and decreased adhesion. CONCLUSION: Our results suggest that altered expression of integrins interacting with different extracellular matrixes may play a significant role in suppressing the aggressive invasive phenotype. Analysis of these clonal populations of MiaPaCa-2 provides a model for investigations into the invasive properties of pancreatic carcinoma.

  19. Alpha5beta1 integrin-fibronectin interactions specify liquid to solid phase transition of 3D cellular aggregates.

    Directory of Open Access Journals (Sweden)

    Carlos E Caicedo-Carvajal

    2010-07-01

    of control between integrins and the ECM that can influence tissue cohesion and other mechanical properties, which may translate to the specification of tissue structure and function. These studies provide insights into important biological processes such as embryonic development, wound healing, and for tissue engineering applications.

  20. Expression of integrin α3β1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer

    International Nuclear Information System (INIS)

    Aggarwal, Anshu; Al-Rohil, Rami N; Batra, Anupam; Feustel, Paul J; Jones, David M; DiPersio, C Michael

    2014-01-01

    Expression of integrin α3β1 is associated with tumor progression, metastasis, and poor prognosis in several cancers, including breast cancer. Moreover, preclinical studies have revealed important pro-tumorigenic and pro-metastatic functions for this integrin, including tumor growth, survival, invasion, and paracrine induction of angiogenesis. Our previously published work in a preclinical breast cancer model showed that integrin α3β1 promotes expression of cyclooxygenase-2 (COX2/PTGS2), a known driver of breast cancer progression. However, the clinical significance of this regulation was unknown. The objective of the current study was to assess the clinical relevance of the relationship between integrin α3β1 and COX2 by testing for their correlated expression among various forms of human breast cancer. Immunohistochemistry was performed to assess co-expression of α3 and COX2 in specimens of human invasive ductal carcinoma (IDC), either on a commercial tissue microarray (n = 59 samples) or obtained from Albany Medical Center archives (n = 68 samples). Immunostaining intensity for the integrin α3 subunit or COX2 was scored, and Spearman’s rank correlation coefficient analysis was performed to assess their co-expression across and within different tumor subtypes or clinicopathologic criteria. Although expression of integrin α3 or COX2 varied among clinical IDC samples, a statistically significant, positive correlation was detected between α3 and COX2 in both tissue microarrays (r s = 0.49, p < 0.001, n = 59) and archived samples (r s = 0.59, p < 0.0001, n = 68). In both sample sets, this correlation was independent of hormone receptor status, histological grade, or disease stage. COX2 and α3 are correlated in IDC independently of hormone receptor status or other clinicopathologic features, supporting the hypothesis that integrin α3β1 is a determinant of COX2 expression in human breast cancer. These results support the clinical relevance of α3β1

  1. The β3-Integrin Binding Protein β3-Endonexin Is a Novel Negative Regulator of Hypoxia-Inducible Factor-1

    Science.gov (United States)

    Kračun, Damir; Rieß, Florian; Kanchev, Ivan; Gawaz, Meinrad

    2014-01-01

    Abstract Aims: Integrins are multifunctional heterodimeric adhesion receptors that mediate the attachment between a cell and the extracellular matrix or other surrounding cells. In endothelial cells, integrins can modulate cell migration and motility. In particular, β3-integrin is expressed in angiogenic vessels. Signal transduction by β3-integrins requires the recruitment of intracellular signaling molecules. β3-endonexin is a highly spliced molecule that has been identified as a β3-integrin binding protein. β3-endonexin isoforms are expressed in endothelial cells and have been suggested to act as shuttle proteins between the membrane and the nucleus. However, their functional role in angiogenesis is unclear. In this study, we investigated whether β3-endonexin isoforms are involved in endothelial angiogenic processes under hypoxia. Results: The overexpression of β3-endonexin isoforms decreased endothelial proliferation and tube formation under hypoxia, while the depletion of β3-endonexin by RNAi promoted angiogenic responses in vitro and in vivo. In hypoxia, β3-endonexin accumulated in the nucleus, and prevention of this response by depletion of β3-endonexin increased hypoxic activation and induction of the hypoxia-inducible factor (HIF)-1 and its target genes VEGF and PAI-1. β3-endonexin diminished nuclear factor kappa B (NFκB) activation and decreased NFκB binding to the HIF-1α promoter under hypoxia, subsequently diminishing NFκB-dependent transcription of HIF-1α under hypoxia. Innovation: Our results indicate for the first time that the overexpression of β3-endonexin can decrease hypoxic induction and activation of HIF-1α and can prevent hypoxic endothelial proliferation and angiogenic responses. Conclusion: β3-endonexin can act as a novel anti-angiogenic factor specifically in the response to hypoxia due to its negative impact on the activation of HIF-1. Antioxid. Redox Signal. 20, 1964–1976. PMID:24386901

  2. Force via integrins but not E-cadherin decreases Oct3/4 expression in embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Uda, Yuhei [Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Department of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, 6-6-01, Aramaki-aoba, Aoba-ward, Sendai City (Japan); Poh, Yeh-Chuin; Chowdhury, Farhan; Wu, Douglas C. [Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Tanaka, Tetsuya S. [Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Sato, Masaaki [Department of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, 6-6-01, Aramaki-aoba, Aoba-ward, Sendai City (Japan); Wang, Ning, E-mail: nwangrw@illinois.edu [Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Force via integrins or cadherins induces similar cell stiffening responses. Black-Right-Pointing-Pointer Force via integrins but not cadherins induces cell spreading. Black-Right-Pointing-Pointer Force via integrins but not cadherins induces differentiation of embryonic stem cells. -- Abstract: Increasing evidence suggests that mechanical factors play a critical role in fate decisions of stem cells. Recently we have demonstrated that a local force applied via Arg-Gly-Asp (RGD) peptides coated magnetic beads to mouse embryonic stem (ES) cells increases cell spreading and cell stiffness and decreases Oct3/4 (Pou5f1) gene expression. However, it is not clear whether the effects of the applied stress on these functions of ES cells can be extended to natural extracellular matrix proteins or cell-cell adhesion molecules. Here we show that a local cyclic shear force applied via fibronectin or laminin to integrin receptors increased cell spreading and stiffness, downregulated Oct3/4 gene expression, and decreased cell proliferation rate. In contrast, the same cyclic force applied via cell-cell adhesion molecule E-cadherin (Cdh1) had no effects on cell spreading, Oct3/4 gene expression, and the self-renewal of mouse ES cells, but induced significant cell stiffening. Our findings demonstrate that biological responses of ES cells to force applied via integrins are different from those to force via E-cadherin, suggesting that mechanical forces might play different roles in different force transduction pathways to shape early embryogenesis.

  3. Modeling of metal nanocluster growth on patterned substrates and surface pattern formation under ion bombardment

    Energy Technology Data Exchange (ETDEWEB)

    Numazawa, Satoshi

    2012-11-01

    This work addresses the metal nanocluster growth process on prepatterned substrates, the development of atomistic simulation method with respect to an acceleration of the atomistic transition states, and the continuum model of the ion-beam inducing semiconductor surface pattern formation mechanism. Experimentally, highly ordered Ag nanocluster structures have been grown on pre-patterned amorphous SiO{sub 2} surfaces by oblique angle physical vapor deposition at room temperature. Despite the small undulation of the rippled surface, the stripe-like Ag nanoclusters are very pronounced, reproducible and well-separated. The first topic is the investigation of this growth process with a continuum theoretical approach to the surface gas condensation as well as an atomistic cluster growth model. The atomistic simulation model is a lattice-based kinetic Monte-Carlo (KMC) method using a combination of a simplified inter-atomic potential and experimental transition barriers taken from the literature. An effective transition event classification method is introduced which allows a boost factor of several thousand compared to a traditional KMC approach, thus allowing experimental time scales to be modeled. The simulation predicts a low sticking probability for the arriving atoms, millisecond order lifetimes for single Ag monomers and {approx}1 nm square surface migration ranges of Ag monomers. The simulations give excellent reproduction of the experimentally observed nanocluster growth patterns. The second topic specifies the acceleration scheme utilized in the metallic cluster growth model. Concerning the atomistic movements, a classical harmonic transition state theory is considered and applied in discrete lattice cells with hierarchical transition levels. The model results in an effective reduction of KMC simulation steps by utilizing a classification scheme of transition levels for thermally activated atomistic diffusion processes. Thermally activated atomistic movements

  4. Modeling of metal nanocluster growth on patterned substrates and surface pattern formation under ion bombardment

    Energy Technology Data Exchange (ETDEWEB)

    Numazawa, Satoshi

    2012-11-01

    This work addresses the metal nanocluster growth process on prepatterned substrates, the development of atomistic simulation method with respect to an acceleration of the atomistic transition states, and the continuum model of the ion-beam inducing semiconductor surface pattern formation mechanism. Experimentally, highly ordered Ag nanocluster structures have been grown on pre-patterned amorphous SiO{sub 2} surfaces by oblique angle physical vapor deposition at room temperature. Despite the small undulation of the rippled surface, the stripe-like Ag nanoclusters are very pronounced, reproducible and well-separated. The first topic is the investigation of this growth process with a continuum theoretical approach to the surface gas condensation as well as an atomistic cluster growth model. The atomistic simulation model is a lattice-based kinetic Monte-Carlo (KMC) method using a combination of a simplified inter-atomic potential and experimental transition barriers taken from the literature. An effective transition event classification method is introduced which allows a boost factor of several thousand compared to a traditional KMC approach, thus allowing experimental time scales to be modeled. The simulation predicts a low sticking probability for the arriving atoms, millisecond order lifetimes for single Ag monomers and {approx}1 nm square surface migration ranges of Ag monomers. The simulations give excellent reproduction of the experimentally observed nanocluster growth patterns. The second topic specifies the acceleration scheme utilized in the metallic cluster growth model. Concerning the atomistic movements, a classical harmonic transition state theory is considered and applied in discrete lattice cells with hierarchical transition levels. The model results in an effective reduction of KMC simulation steps by utilizing a classification scheme of transition levels for thermally activated atomistic diffusion processes. Thermally activated atomistic movements

  5. Polymer stabilized Ni-Ag and Ni-Fe alloy nanoclusters: Structural and magnetic properties

    Energy Technology Data Exchange (ETDEWEB)

    Kabir, L.; Mandal, A.R. [Department of Physics, Visva-Bharati, Santiniketan-731 235 (India); Mandal, S.K., E-mail: sk_mandal@hotmail.co [Department of Physics, Visva-Bharati, Santiniketan-731 235 (India)

    2010-04-15

    We report here the structural and magnetic behaviors of nickel-silver (Ni-Ag) and nickel-iron (Ni-Fe) nanoclusters stabilized with polymer (polypyrrole). High resolution transmission electron microscopy (HRTEM) indicates Ni-Ag nanoclusters to stabilize in core-shell configuration while that of Ni-Fe nanoclusters in a mixed type of geometry. Structural characterizations by X-ray diffraction (XRD) reveal the possibility of alloying in such bimetallic nanoclusters to some extent even at temperatures much lower than that of bulk alloying. Electron paramagnetic resonance (EPR) spectra clearly reveal two different absorption behaviors: one is ascribed to non-isolated Ni{sup 2+} clusters surrounded by either silver or iron giving rise to a broad signal, other (very narrow signal) being due to the isolated superparamagnetic Ni{sup 2+} clusters or bimetallic alloy nanoclusters. Results obtained for Ni-Ag and Ni-Fe nanoclusters have been further compared with the behavior exhibited by pure Ni nanoclusters in polypyrrole host. Temperature dependent studies (at 300 and 77 K) of EPR parameters, e.g. linewidth, g-value, line shape and signal intensity indicating the significant influence of surrounding paramagnetic silver or ferromagnetic iron within polymer host on the EPR spectra have been presented.

  6. Polymer stabilized Ni-Ag and Ni-Fe alloy nanoclusters: Structural and magnetic properties

    Science.gov (United States)

    Kabir, L.; Mandal, A. R.; Mandal, S. K.

    2010-04-01

    We report here the structural and magnetic behaviors of nickel-silver (Ni-Ag) and nickel-iron (Ni-Fe) nanoclusters stabilized with polymer (polypyrrole). High resolution transmission electron microscopy (HRTEM) indicates Ni-Ag nanoclusters to stabilize in core-shell configuration while that of Ni-Fe nanoclusters in a mixed type of geometry. Structural characterizations by X-ray diffraction (XRD) reveal the possibility of alloying in such bimetallic nanoclusters to some extent even at temperatures much lower than that of bulk alloying. Electron paramagnetic resonance (EPR) spectra clearly reveal two different absorption behaviors: one is ascribed to non-isolated Ni 2+ clusters surrounded by either silver or iron giving rise to a broad signal, other (very narrow signal) being due to the isolated superparamagnetic Ni 2+ clusters or bimetallic alloy nanoclusters. Results obtained for Ni-Ag and Ni-Fe nanoclusters have been further compared with the behavior exhibited by pure Ni nanoclusters in polypyrrole host. Temperature dependent studies (at 300 and 77 K) of EPR parameters, e.g. linewidth, g-value, line shape and signal intensity indicating the significant influence of surrounding paramagnetic silver or ferromagnetic iron within polymer host on the EPR spectra have been presented.

  7. Polymer stabilized Ni-Ag and Ni-Fe alloy nanoclusters: Structural and magnetic properties

    International Nuclear Information System (INIS)

    Kabir, L.; Mandal, A.R.; Mandal, S.K.

    2010-01-01

    We report here the structural and magnetic behaviors of nickel-silver (Ni-Ag) and nickel-iron (Ni-Fe) nanoclusters stabilized with polymer (polypyrrole). High resolution transmission electron microscopy (HRTEM) indicates Ni-Ag nanoclusters to stabilize in core-shell configuration while that of Ni-Fe nanoclusters in a mixed type of geometry. Structural characterizations by X-ray diffraction (XRD) reveal the possibility of alloying in such bimetallic nanoclusters to some extent even at temperatures much lower than that of bulk alloying. Electron paramagnetic resonance (EPR) spectra clearly reveal two different absorption behaviors: one is ascribed to non-isolated Ni 2+ clusters surrounded by either silver or iron giving rise to a broad signal, other (very narrow signal) being due to the isolated superparamagnetic Ni 2+ clusters or bimetallic alloy nanoclusters. Results obtained for Ni-Ag and Ni-Fe nanoclusters have been further compared with the behavior exhibited by pure Ni nanoclusters in polypyrrole host. Temperature dependent studies (at 300 and 77 K) of EPR parameters, e.g. linewidth, g-value, line shape and signal intensity indicating the significant influence of surrounding paramagnetic silver or ferromagnetic iron within polymer host on the EPR spectra have been presented.

  8. Microwave-heating synthesis and sensing applications of bright gold nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    He, Ding-Fei; Xiang, Yang; Wang, Xu [Department of Physics, Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Yu, Xue-Feng, E-mail: yxf@whu.edu.cn [Department of Physics, Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education and School of Physics and Technology, Wuhan University, Wuhan 430072 (China)

    2011-12-15

    Highlights: Black-Right-Pointing-Pointer We establish a microwave-heating method to synthesize protein-stabilized Au nanoclusters. Black-Right-Pointing-Pointer The obtained Au nanoclusters show bright red fluorescence. Black-Right-Pointing-Pointer The Au nanoclusters can be used as efficient fluorescence probe for Cu{sup 2+} ion sensing. -- Abstract: A rapid microwave-heating method has been developed for the synthesis of bright Au nanoclusters by using bull serum albumin as the template in an aqueous environment. The reaction time needed is only 7.0 min, and the weight of the products at one batch can reach 15 g. The Au nanoclusters exhibit bright fluorescence at {approx}613 nm with quantum yield of {approx}6.0%. By adjusting the pH value, the products can be controlled to precipitate or re-disperse in aqueous solution. Furthermore, the Au nanoclusters have exhibited high sensitivity and selectivity in the determination of Cu{sup 2+} ions in water. These results suggest an efficient method for obtaining metal nanoclusters for the detection and sensing applications.

  9. A DFT study for the structural and electronic properties of Zn m Se n nanoclusters

    Science.gov (United States)

    Yadav, Phool Singh; Pandey, Dheeraj Kumar

    2012-09-01

    An ab initio study has been performed for the stability, structural and electronic properties of 19 small zinc selenide Zn m Se n ( m + n = 2-4) nanoclusters. Out of these nanoclusters, one nanocluster is found to be unstable due to its imaginary vibrational frequency. A B3LYP-DFT/6-311G(3df) method is used in the optimization of the geometries of the nanoclusters. We have calculated the zero point energy (ZPE), which is ignored by the other workers. The binding energies (BE), HOMO-LUMO gaps and bond lengths have been obtained for all the optimized nanoclusters. For the same value of ` m' and ` n', we designate the most stable structure the one, which has maximum final binding energy (FBE) per atom. The adiabatic and vertical ionization potentials (IP) and electron affinities (EA), dipole moments and charge on atoms have been investigated for the most stable nanoclusters. For the same value of ` m' and ` n', the nanocluster containing maximum number of Se atoms is found to be most stable.

  10. The membrane-cytoplasm interface of integrin alpha subunits is critical for receptor latency.

    OpenAIRE

    Briesewitz, R; Kern, A; Smilenov, L B; David, F S; Marcantonio, E E

    1996-01-01

    Localization of integrin receptors to focal contact sites occurs upon ligand binding. This activity is latent, since unoccupied integrin receptors do not localize to focal contacts. Deletion analysis has revealed that the alpha cytoplasmic domains is required for the maintenance of integrin receptor latency. Our current hypothesis for the mechanism of integrin post-ligand binding events is that there is a change in relationship of alpha and beta cytoplasmic domains, which overcomes receptor l...

  11. The therapeutic potential of I-domain integrins.

    Science.gov (United States)

    Brennan, Marian; Cox, Dermot

    2014-01-01

    Due to their role in processes central to cancer and autoimmune disease I-domain integrins are an attractive drug target. Both antibodies and small molecule antagonists have been discovered and tested in the clinic. Much of the effort has focused on αLβ2 antagonists. Maybe the most successful was the monoclonal antibody efalizumab, which was approved for the treatment of psoriasis but subsequently withdrawn from the market due to the occurrence of a serious adverse effect (progressive multifocal leukoencephalopathy). Other monoclonal antibodies were tested for the treatment of reperfusion injury, post-myocardial infarction, but failed to progress due to lack of efficacy. New potent small molecule inhibitors of αv integrins are promising reagents for treating fibrotic disease. Small molecule inhibitors targeting collagen-binding integrins have been discovered and future work will focus on identifying molecules selectively targeting each of the collagen receptors and identifying appropriate target diseases for future clinical studies.

  12. Integrins and small GTPases as modulators of phagocytosis.

    Science.gov (United States)

    Sayedyahossein, Samar; Dagnino, Lina

    2013-01-01

    Phagocytosis is the mechanism whereby cells engulf large particles. This process has long been recognized as a critical component of the innate immune response, which constitutes the organism's defense against microorganisms. In addition, phagocytic internalization of apoptotic cells or cell fragments plays important roles in tissue homeostasis and remodeling. Phagocytosis requires target interactions with receptors on the plasma membrane of the phagocytic cell. Integrins have been identified as important mediators of particle clearance, in addition to their well-established roles in cell adhesion, migration and mechanotransduction. Indeed, these ubiquitously expressed proteins impart phagocytic capacity to epithelial, endothelial and mesenchymal cell types. The importance of integrins in particle internalization is emphasized by the ability of microbial and viral pathogens to exploit their signaling pathways to invade host cells, and by the wide variety of disorders that arise from abnormalities in integrin-dependent phagocytic uptake. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Direct immobilization of antibodies on Zn-doped Fe_3O_4 nanoclusters for detection of pathogenic bacteria

    International Nuclear Information System (INIS)

    Pal, Monalisa; Lee, Sanghee; Kwon, Donghoon; Hwang, Jeongin; Lee, Hyeonjeong; Hwang, Seokyung; Jeon, Sangmin

    2017-01-01

    Zinc-doped magnetic nanoclusters (Zn-MNCs) were synthesized and used to detect pathogenic bacteria in milk. Hydrothermally synthesized Zn-MNCs exhibited stronger magnetic properties than pure MNCs, which facilitated the magnetic separation from the sample using a permanent magnet. The presence of accessible Zn sites allows the direct immobilization of half-fragmented antibodies over Zn-MNCs through strong Zn−S bonds and prevents the tedious multiple steps of molecular functionalization or coating with costly noble metals prior to conjugation with an antibody. After the capture and magnetic separation of Salmonella in milk using the antibody-functionalized Zn-MNCs, the concentration of bacteria was determined with a portable ATP luminometer and the detection limit was found to be 10 CFU/mL. - Highlights: • Zn-doped Fe_3O_4 nanoclusters (Zn-MNCs) were synthesized by hydrothermal method. • Antibodies were directly immobilized over Zn-MNCs through strong Zn–S_t_h_i_o_l bonds. • Higher magnetization of Zn-MNCs than pure MNCs facilitates the magnetic separation. • Detection limit of pathogenic bacteria in milk was found to be 10 cfu/mL. • Cost effective, sensitive and selective detection of bacteria.

  14. Integrin β1, osmosensing, and chemoresistance in mouse ehrlich carcinoma cells

    DEFF Research Database (Denmark)

    Sørensen, Belinda Halling; Rasmussen, Line Jee Hartmann; Broberg, Bjørn Sindballe

    2015-01-01

    BACKGROUND/AIMS: Altered expression of the integrin family of cell adhesion receptors has been associated with initiation, progression, and metastasis of solid tumors as well as in the development of chemoresistance. Here, we investigated the role of integrins, in particular integrin β1, in cell ...

  15. Targeting of beta 1 integrins impairs DNA repair for radiosensitization of head and neck cancer cells

    NARCIS (Netherlands)

    Dickreuter, E.; Eke, I.; Krause, M.; Borgmann, K.; van Vugt, M. A.; Cordes, N.

    2016-01-01

    beta 1 Integrin-mediated cell-extracellular matrix interactions allow cancer cell survival and confer therapy resistance. It was shown that inhibition of beta 1 integrins sensitizes cells to radiotherapy. Here, we examined the impact of beta 1 integrin targeting on the repair of radiation-induced

  16. Synthesis and biological evaluation of potent alphavbeta3-integrin receptor antagonists.

    NARCIS (Netherlands)

    Dijkgraaf, I.; Kruijtzer, J.A.; Frielink, C.; Soede, A.C.; Hilbers, H.W.; Oyen, W.J.G.; Corstens, F.H.M.; Liskamp, R.M.; Boerman, O.C.

    2006-01-01

    INTRODUCTION: alpha(v)beta(3) Integrin is expressed in sprouting endothelial cells in growing tumors, whereas it is absent in quiescent blood vessels. In addition, various tumor cell types express alpha(v)beta(3) integrin. alpha(v)beta(3) Integrin, a transmembrane heterodimeric protein, binds to the

  17. Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection.

    Science.gov (United States)

    Yun, Bing-Ling; Guan, Xiao-Lu; Liu, Yong-Zhen; Zhang, Yao; Wang, Yong-Qiang; Qi, Xiao-Le; Cui, Hong-Yu; Liu, Chang-Jun; Zhang, Yan-Ping; Gao, Hong-Lei; Gao, Li; Li, Kai; Gao, Yu-Long; Wang, Xiao-Mei

    2016-07-08

    Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or β1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and β1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection*

    Science.gov (United States)

    Yun, Bing-Ling; Guan, Xiao-Lu; Liu, Yong-Zhen; Zhang, Yao; Wang, Yong-Qiang; Qi, Xiao-Le; Cui, Hong-Yu; Liu, Chang-Jun; Zhang, Yan-Ping; Gao, Hong-Lei; Gao, Li; Li, Kai; Gao, Yu-Long; Wang, Xiao-Mei

    2016-01-01

    Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or β1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and β1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. PMID:27226547

  19. Morphological and magnetic properties of cobalt nanoclusters electrodeposited onto HOPG

    International Nuclear Information System (INIS)

    Rivera, M.; Rios-Reyes, C.H.; Mendoza-Huizar, L.H.

    2008-01-01

    In this work, the morphological and magnetic properties of cobalt nanoclusters obtained from two different sulphate electrolyte solutions were studied. The aggregates were electrodeposited onto highly oriented pyrolytic graphite electrodes in overpotential conditions, in order to investigate the cationic influence on the final properties of the aggregates. In both cases, scanning electron microscopy and atomic force microscopy showed random isolated clusters on the electrode surface, where size variations were determined by the electrolyte solution. By using magnetic force microscopy, the distribution of the electrodeposited magnetic material was more clearly observed which gave some insights on the growth mechanism of these aggregates.

  20. Ion implantation induced conducting nano-cluster formation in PPO

    International Nuclear Information System (INIS)

    Das, A.; Patnaik, A.; Ghosh, G.; Dhara, S.

    1997-01-01

    Conversion of polymers and non-polymeric organic molecules from insulating to semiconducting materials as an effect of energetic ion implantation is an established fact. Formation of nano-clusters enriched with carbonaceous materials are made responsible for the insulator-semiconductor transition. Conduction in these implanted materials is observed to follow variable range hopping (VRH) mechanism. Poly(2,6-dimethyl phenylene oxide) [PPO] compatible in various proportion with polystyrene is used as a high thermal resistant insulating polymer. PPO has been used for the first time in the ion implantation study

  1. Ultrafast coherence transfer in DNA-templated silver nanoclusters

    DEFF Research Database (Denmark)

    Thyrhaug, Erling; Bogh, Sidsel Ammitzbøll; Carro, Miguel

    2017-01-01

    DNA-templated silver nanoclusters of a few tens of atoms or less have come into prominence over the last several years due to very strong absorption and efficient emission. Applications in microscopy and sensing have already been realized, however little is known about the excited-state structure...... and dynamics in these clusters. Here we report on a multidimensional spectroscopy investigation of the energy-level structure and the early-time relaxation cascade, which eventually results in the population of an emitting state. We find that the ultrafast intramolecular relaxation is strongly coupled...

  2. Effect of quencher, denaturants, temperature and pH on the fluorescent properties of BSA protected gold nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Chib, Rahul, E-mail: Rahul.chib@live.unthsc.edu [Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States); Butler, Susan [Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States); Raut, Sangram [Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States); Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX 76129 (United States); Shah, Sunil; Borejdo, Julian [Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States); Gryczynski, Zygmunt [Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States); Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX 76129 (United States); Gryczynski, Ignacy, E-mail: ignacy.gryczynski@unthsc.edu [Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

    2015-12-15

    In this paper, we have synthesized BSA protected gold nanoclusters (BSA Au nanocluster) and studied the effect of quencher, protein denaturant, pH and temperature on the fluorescence properties of the tryptophan molecule of the BSA Au nanocluster and native BSA. We have also studied their effect on the peak emission of BSA Au nanoclusters (650 nm). The photophysical characterization of a newly developed fluorophore in different environments is absolutely necessary to futher develop their biomedical and analytical applications. It was observed from our experiments that the tryptophan in BSA Au nanoclusters is better shielded from the polar environment. Tryptophan in native BSA showed a red shift in its peak emission wavelength position. Tryptophan is a highly polarity sensitive dye and a minimal change in its microenvironment can be easily observed in its photophysical properties. - Highlights: • Tryptophan is easily accessible in native BSA compared to BSA Au nanoclusters. • Guanidine HCL denatures native BSA more compared to BSA Au nanoclusters. • High temperature decreases the quantum yield of tryptophan and BSA Au nanocluster. • Emission wavelength of BSA Au nanoclusters remains constant with increasing pH. • BSA Au nanoclusters are robust to the changes in their environments.

  3. Effect of quencher, denaturants, temperature and pH on the fluorescent properties of BSA protected gold nanoclusters

    International Nuclear Information System (INIS)

    Chib, Rahul; Butler, Susan; Raut, Sangram; Shah, Sunil; Borejdo, Julian; Gryczynski, Zygmunt; Gryczynski, Ignacy

    2015-01-01

    In this paper, we have synthesized BSA protected gold nanoclusters (BSA Au nanocluster) and studied the effect of quencher, protein denaturant, pH and temperature on the fluorescence properties of the tryptophan molecule of the BSA Au nanocluster and native BSA. We have also studied their effect on the peak emission of BSA Au nanoclusters (650 nm). The photophysical characterization of a newly developed fluorophore in different environments is absolutely necessary to futher develop their biomedical and analytical applications. It was observed from our experiments that the tryptophan in BSA Au nanoclusters is better shielded from the polar environment. Tryptophan in native BSA showed a red shift in its peak emission wavelength position. Tryptophan is a highly polarity sensitive dye and a minimal change in its microenvironment can be easily observed in its photophysical properties. - Highlights: • Tryptophan is easily accessible in native BSA compared to BSA Au nanoclusters. • Guanidine HCL denatures native BSA more compared to BSA Au nanoclusters. • High temperature decreases the quantum yield of tryptophan and BSA Au nanocluster. • Emission wavelength of BSA Au nanoclusters remains constant with increasing pH. • BSA Au nanoclusters are robust to the changes in their environments.

  4. Size-Dependent Specific Surface Area of Nanoporous Film Assembled by Core-Shell Iron Nanoclusters

    Directory of Open Access Journals (Sweden)

    Jiji Antony

    2006-01-01

    Full Text Available Nanoporous films of core-shell iron nanoclusters have improved possibilities for remediation, chemical reactivity rate, and environmentally favorable reaction pathways. Conventional methods often have difficulties to yield stable monodispersed core-shell nanoparticles. We produced core-shell nanoclusters by a cluster source that utilizes combination of Fe target sputtering along with gas aggregations in an inert atmosphere at 7∘C. Sizes of core-shell iron-iron oxide nanoclusters are observed with transmission electron microscopy (TEM. The specific surface areas of the porous films obtained from Brunauer-Emmett-Teller (BET process are size-dependent and compared with the calculated data.

  5. Ge nanoclusters in PECVD-deposited glass caused only by heat treatment

    DEFF Research Database (Denmark)

    Ou, Haiyan; Rørdam, Troels Peter; Rottwitt, Karsten

    2008-01-01

    This paper reports the formation of Ge nanoclusters in a multi-layer structure consisting of alternating thin films of Ge-doped silica glass and SiGe, deposited by plasma-enhanced chemical vapor deposition (PECVD) and post annealed at 1100 °C in N2 atmosphere. We studied the annealed samples...... embedded with Ge nanoclusters after annealing. These nanoclusters are crystalline and varied in size. There were no clusters in the Ge-doped glass layer. Raman spectra verified the existence of crystalline Ge clusters. The positional shift of the Ge vibrational peak with the change of the focus depth...

  6. Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists.

    Science.gov (United States)

    Kollmann, Christopher S; Bai, Xiaopeng; Tsai, Ching-Hsuan; Yang, Hongfang; Lind, Kenneth E; Skinner, Steven R; Zhu, Zhengrong; Israel, David I; Cuozzo, John W; Morgan, Barry A; Yuki, Koichi; Xie, Can; Springer, Timothy A; Shimaoka, Motomu; Evindar, Ghotas

    2014-04-01

    The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.1 billion compounds was exposed to the I-domain of the target protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the lymphocyte function-associated antigen 1/intercellular adhesion molecule-1 interaction with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the target protein. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Hierarchical self-assembly of magnetic nanoclusters for theranostics: Tunable size, enhanced magnetic resonance imagability, and controlled and targeted drug delivery.

    Science.gov (United States)

    Nguyen, Dai Hai; Lee, Jung Seok; Choi, Jong Hoon; Park, Kyung Min; Lee, Yunki; Park, Ki Dong

    2016-04-15

    Nanoparticle-based imaging and therapy are of interest for theranostic nanomedicine. In particular, superparamagnetic iron oxide (SPIO) nanoparticles (NPs) have attracted much attention in cancer imaging, diagnostics, and treatment because of their superior imagability and biocompatibility (approved by the Food and Drug Administration). Here, we developed SPIO nanoparticles (NPs) that self-assembled into magnetic nanoclusters (SAMNs) in aqueous environments as a theranostic nano-system. To generate multi-functional SPIO NPs, we covalently conjugated β-cyclodextrin (β-CD) to SPIO NPs using metal-adhesive dopamine groups. Polyethylene glycol (PEG) and paclitaxel (PTX) were hosted in the β-CD cavity through high affinity complexation. The core-shell structure of the magnetic nanoclusters was elucidated based on the condensed SPIO core and a PEG shell using electron microscopy and the composition was analyzed by thermogravimetric analysis (TGA). Our results indicate that nanocluster size could be readily controlled by changing the SPIO/PEG ratio in the assemblies. Interestingly, we observed a significant enhancement in magnetic resonance contrast due to the large cluster size and dense iron oxide core. In addition, tethering a tumor-targeting peptide to the SAMNs enhanced their uptake into tumor cells. PTX was efficiently loaded into β-CDs and released in a controlled manner when exposed to competitive guest molecules. These results strongly indicate that the SAMNs developed in this study possess great potential for application in image-guided cancer chemotherapy. In this study, we developed multi-functional SPIO NPs that self-assembled into magnetic nanoclusters (SAMNs) in aqueous conditions as a theranostic nano-system. The beta-cyclodextrin (β-CD) was immobilized on the surfaces of SPIO NPs and RGD-conjugated polyethylene glycol (PEG) and paclitaxel (PTX) were hosted in the β-CD cavity through high affinity complexation. We found that nanocluster size could be

  8. The cysteine-rich domain of human ADAM 12 supports cell adhesion through syndecans and triggers signaling events that lead to beta1 integrin-dependent cell spreading

    DEFF Research Database (Denmark)

    Iba, K; Albrechtsen, R; Gilpin, B

    2000-01-01

    The ADAMs (a disintegrin and metalloprotease) family of proteins is involved in a variety of cellular interactions, including cell adhesion and ecto- domain shedding. Here we show that ADAM 12 binds to cell surface syndecans. Three forms of recombinant ADAM 12 were used in these experiments......-dependent manner attach to ADAM 12 via members of the syndecan family. After binding to syndecans, mesenchymal cells spread and form focal adhesions and actin stress fibers. Integrin beta1 was responsible for cell spreading because function-blocking monoclonal antibodies completely inhibited cell spreading......, and chondroblasts lacking beta1 integrin attached but did not spread. These data suggest that mesenchymal cells use syndecans as the initial receptor for the ADAM 12 cysteine-rich domain-mediated cell adhesion, and then the beta1 integrin to induce cell spreading. Interestingly, carcinoma cells attached but did...

  9. Coherent radiation by quantum dots and magnetic nanoclusters

    International Nuclear Information System (INIS)

    Yukalov, V. I.; Yukalova, E. P.

    2014-01-01

    The assemblies of either quantum dots or magnetic nanoclusters are studied. It is shown that such assemblies can produce coherent radiation. A method is developed for solving the systems of nonlinear equations describing the dynamics of such assemblies. The method is shown to be general and applicable to systems of different physical nature. Despite mathematical similarities of dynamical equations, the physics of the processes for quantum dots and magnetic nanoclusters is rather different. In a quantum dot assembly, coherence develops due to the Dicke effect of dot interactions through the common radiation field. For a system of magnetic clusters, coherence in the spin motion appears due to the Purcell effect caused by the feedback action of a resonator. Self-organized coherent spin radiation cannot arise without a resonator. This principal difference is connected with the different physical nature of dipole forces between the objects. Effective dipole interactions between the radiating quantum dots, appearing due to photon exchange, collectivize the dot radiation. While the dipolar spin interactions exist from the beginning, yet before radiation, and on the contrary, they dephase spin motion, thus destroying the coherence of moving spins. In addition, quantum dot radiation exhibits turbulent photon filamentation that is absent for radiating spins

  10. Formation of nanoclusters of gadolinium atoms in silicon

    International Nuclear Information System (INIS)

    Iliev, Kh.M.; Saparniyazova, Z.M.; Ismajlov, K.A.; Madzhitov, M.Kh.

    2011-01-01

    A technology of stage wise low temperature diffusion of gadolinium into silicon that makes it possible to form nanoclusters of impurity atoms with a significant magnetic moment distributed throughout the volume of the material has been developed. It is shown that, unlike the samples obtained by high temperature diffusion doping, the samples prepared by the new technology do not have surface erosion, and alloys and silicides are not formed in the near surface region. Nanoclusters of impurity atoms of gadolinium in the volume of the crystal lattice of the silicon are studied using an MIK-5 infrared microscope. It is found that, in the stage wise low temperature diffusion, the temperature and time of the diffusion have an effect not only on the depth of penetration of the impurities but also on the sizes of the resulting clusters; these factors can also prevent the formation of clusters. The study of the effect of low temperature treatments on the size and distribution of clusters shows that, upon annealing in the temperature range of 500-700 degrees Celsius, the ordering of the clusters of gadolinium impurity atoms is observed. A further increase in the annealing temperature leads to the destruction of gadolinium clusters in the silicon bulk. (authors)

  11. Fluorescence enhancement of DNA-silver nanoclusters from guanine proximity

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Hsin-chih [Los Alamos National Laboratory; Sharma, Jaswinder [Los Alamos National Laboratory; Yoo, Hyojong [Los Alamos National Laboratory; Martinez, Jennifer S [Los Alamos National Laboratory

    2010-01-01

    Oligonucleotide-templated, silver nanoclusters (DNA/Ag NCs) are a versatile set of fluorophores and have already been used for live cell imaging, detection of specific metal ions, and single-nucleotide variation identification. Compared to commonly used organic dyes, these fluorescent nanoclusters have much better photostability and are often a few times brighter. Owing to their small size, simple preparation, and biocompatibility (i.e. made of nontoxic metals), DNA/Ag NCs should find more applications in biological imaging and chemical detection in the years to come. While clearly promising as new fluorophores, DNA/Ag NCs possess a unique and poorly understood dynamic process not shared by organic dyes or photoluminescent nanocrystals - the conversion among different NC species due to silver oxidation/reduction or NC regrouping. While this environmental sensitivity can be viewed as a drawback, in the appropriate context, it can be used as a sensor or reporter. Often reversible, conversions among different NC species have been found to depend upon a number of factors, including time, temperature, oxygen and salt content. In this communication, we report significant fluorescence enhancement of DNA/Ag NCs via interactions with guanine-rich DNA sequences. Moreover, we demonstrated this property can be used for sensitive detection of specific target DNA from a human oncogene (i.e. Braf gene).

  12. Betal-integrins in the primary cilium of MDCK cells potentiate fibronectin-induced Ca2+ signalling

    DEFF Research Database (Denmark)

    Prætorius, Helle; Prætorius, Jeppe; Nielsen, Søren

    2004-01-01

    observed that β1-integrin, α3-integrin, and perhaps α5-integrin were localized to the primary cilium of MDCK cells by combining lectin and immunofluorescence confocal microscopy. β1-Integrin was also colocalized with tubulin to the primary cilia of the rat renal collecting ducts, as well as to the cilia...

  13. Colloidal Gold Nanoclusters Spiked Silica Fillers in Mixed Matrix Coatings: Simultaneous Detection and Inhibition of Healthcare-Associated Infections

    KAUST Repository

    Alsaiari, Shahad K.; Hammami, Mohamed Amen; Croissant, Jonas G.; Omar, Haneen; Neelakanda, Pradeep; Yapici, Tahir; Peinemann, Klaus-Viktor; Khashab, Niveen M.

    2017-01-01

    Healthcare-associated infections (HAIs) are the infections that patients get while receiving medical treatment in a medical facility with bacterial HAIs being the most common. Silver and gold nanoparticles (NPs) have been successfully employed as antibacterial motifs; however, NPs leaching in addition to poor dispersion and overall reproducibility are major hurdles to further product development. In this study, the authors design and fabricate a smart antibacterial mixed-matrix membrane coating comprising colloidal lysozyme-templated gold nanoclusters as nanofillers in poly(ethylene oxide)/poly(butylene terephthalate) amphiphilic polymer matrix. Mesoporous silica nanoparticles-lysozyme functionalized gold nanoclusters disperse homogenously within the polymer matrix with no phase separation and zero NPs leaching. This mixed-matrix coating can successfully sense and inhibit bacterial contamination via a controlled release mechanism that is only triggered by bacteria. The system is coated on a common radiographic dental imaging device (photostimulable phosphor plate) that is prone to oral bacteria contamination. Variation and eventually disappearance of the red fluorescence surface under UV light signals bacterial infection. Kanamycin, an antimicrobial agent, is controllably released to instantly inhibit bacterial growth. Interestingly, the quality of the images obtained with these coated surfaces is the same as uncoated surfaces and thus the safe application of such smart coatings can be expanded to include other medical devices without compromising their utility.

  14. Colloidal Gold Nanoclusters Spiked Silica Fillers in Mixed Matrix Coatings: Simultaneous Detection and Inhibition of Healthcare-Associated Infections.

    Science.gov (United States)

    Alsaiari, Shahad K; Hammami, Mohammed A; Croissant, Jonas G; Omar, Haneen W; Neelakanda, Pradeep; Yapici, Tahir; Peinemann, Klaus-Viktor; Khashab, Niveen M

    2017-03-01

    Healthcare-associated infections (HAIs) are the infections that patients get while receiving medical treatment in a medical facility with bacterial HAIs being the most common. Silver and gold nanoparticles (NPs) have been successfully employed as antibacterial motifs; however, NPs leaching in addition to poor dispersion and overall reproducibility are major hurdles to further product development. In this study, the authors design and fabricate a smart antibacterial mixed-matrix membrane coating comprising colloidal lysozyme-templated gold nanoclusters as nanofillers in poly(ethylene oxide)/poly(butylene terephthalate) amphiphilic polymer matrix. Mesoporous silica nanoparticles-lysozyme functionalized gold nanoclusters disperse homogenously within the polymer matrix with no phase separation and zero NPs leaching. This mixed-matrix coating can successfully sense and inhibit bacterial contamination via a controlled release mechanism that is only triggered by bacteria. The system is coated on a common radiographic dental imaging device (photostimulable phosphor plate) that is prone to oral bacteria contamination. Variation and eventually disappearance of the red fluorescence surface under UV light signals bacterial infection. Kanamycin, an antimicrobial agent, is controllably released to instantly inhibit bacterial growth. Interestingly, the quality of the images obtained with these coated surfaces is the same as uncoated surfaces and thus the safe application of such smart coatings can be expanded to include other medical devices without compromising their utility. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Tuning Ag29 nanocluster light emission from red to blue with one and two-photon excitation.

    Science.gov (United States)

    Russier-Antoine, Isabelle; Bertorelle, Franck; Hamouda, Ramzi; Rayane, Driss; Dugourd, Philippe; Sanader, Željka; Bonačić-Koutecký, Vlasta; Brevet, Pierre-François; Antoine, Rodolphe

    2016-02-07

    We demonstrate that the tuning of the light emission from red to blue in dihydrolipoic acid (DHLA) capped Ag29 nanoclusters can be trigged with one and two photon excitations. The cluster stoichiometry was determined with mass spectrometry and found to be Ag29(DHLA)12. In a detailed optical investigation, we show that these silver nanoclusters exhibit a strong red photoluminescence visible to the naked eye and characterized by a quantum yield of nearly ∼2% upon one-photon excitation. In the nonlinear optical (NLO) study of the properties of the clusters, the two-photon excited fluorescence spectra were recorded and their first hyperpolarizability obtained. The two-photon absorption cross-section at ∼800 nm for Ag29(DHLA)12 is higher than 10(4) GM and the hyperpolarizability is 106 × 10(-30) esu at the same excitation wavelength. The two-photon excited fluorescence spectrum appears strongly blue-shifted as compared to the one-photon excited spectrum, displaying a broad band between 400 and 700 nm. The density functional theory (DFT) provides insight into the structural and electronic properties of Ag29(DHLA)12 as well as into interplay between metallic subunit or core and ligands which is responsible for unique optical properties.

  16. Non-covalent attachment of silver nanoclusters onto single-walled carbon nanotubes with human serum albumin as linking molecule

    Energy Technology Data Exchange (ETDEWEB)

    Rodríguez-Galván, Andrés, E-mail: andres.rodriguez@nucleares.unam.mx [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico); Instituto de Física, Dpto. Física Experimental, Universidad Nacional Autónoma de México, Coyoacán, México, DF 04510 (Mexico); Unidad de Investigación Biomédica en Cáncer INCan-UNAM, Instituto Nacional de Cancerología, México, DF 14080 (Mexico); Heredia, Alejandro [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico); Amelines-Sarria, Oscar; Rivera, Margarita [Instituto de Física, Dpto. Materia Condensada, Universidad Nacional Autónoma de México, Coyoacán, 04510 México D.F. (Mexico); and others

    2015-03-15

    The attachment of silver nanoclusters (AgNCs) onto single-walled carbon nanotubes (SWNTs) for the formation of integrated fluorescence sites has attracted much attention due their potential applications as biological probes and nanovectors in theragnosis. Here, we report the preparation through assembly of fluorescent quasi 1-D nanomaterial based on SWNTs and silver nanoclusters (AgNCs) non-covalently attached to human serum albumin as biological linker. The fluorescent SWNT–AgNCs–HSA conjugates were characterized by atomic force microscopy, high-resolution transmission electron microscopy (HRTEM), high angle annular dark field scanning TEM (HAADF-STEM), fluorescent and UV–vis spectroscopy. The above techniques confirmed that AgNCs were non-covalently attached onto the external surface of SWNTs. In addition, it was observed that the modification did not affect the optical properties of the synthesized AgNCs since the absorption spectra and fluorescence under UV irradiation (λ = 365 nm) remain the same. The effect of the functionalized systems was tested on mammal red blood cells (RBCs) and it was found that their structural integrity was compromised by the conjugates, limiting their biological and medical applications.

  17. Non-covalent attachment of silver nanoclusters onto single-walled carbon nanotubes with human serum albumin as linking molecule

    International Nuclear Information System (INIS)

    Rodríguez-Galván, Andrés; Heredia, Alejandro; Amelines-Sarria, Oscar; Rivera, Margarita

    2015-01-01

    The attachment of silver nanoclusters (AgNCs) onto single-walled carbon nanotubes (SWNTs) for the formation of integrated fluorescence sites has attracted much attention due their potential applications as biological probes and nanovectors in theragnosis. Here, we report the preparation through assembly of fluorescent quasi 1-D nanomaterial based on SWNTs and silver nanoclusters (AgNCs) non-covalently attached to human serum albumin as biological linker. The fluorescent SWNT–AgNCs–HSA conjugates were characterized by atomic force microscopy, high-resolution transmission electron microscopy (HRTEM), high angle annular dark field scanning TEM (HAADF-STEM), fluorescent and UV–vis spectroscopy. The above techniques confirmed that AgNCs were non-covalently attached onto the external surface of SWNTs. In addition, it was observed that the modification did not affect the optical properties of the synthesized AgNCs since the absorption spectra and fluorescence under UV irradiation (λ = 365 nm) remain the same. The effect of the functionalized systems was tested on mammal red blood cells (RBCs) and it was found that their structural integrity was compromised by the conjugates, limiting their biological and medical applications

  18. Colloidal Gold Nanoclusters Spiked Silica Fillers in Mixed Matrix Coatings: Simultaneous Detection and Inhibition of Healthcare-Associated Infections

    KAUST Repository

    Alsaiari, Shahad K.

    2017-01-25

    Healthcare-associated infections (HAIs) are the infections that patients get while receiving medical treatment in a medical facility with bacterial HAIs being the most common. Silver and gold nanoparticles (NPs) have been successfully employed as antibacterial motifs; however, NPs leaching in addition to poor dispersion and overall reproducibility are major hurdles to further product development. In this study, the authors design and fabricate a smart antibacterial mixed-matrix membrane coating comprising colloidal lysozyme-templated gold nanoclusters as nanofillers in poly(ethylene oxide)/poly(butylene terephthalate) amphiphilic polymer matrix. Mesoporous silica nanoparticles-lysozyme functionalized gold nanoclusters disperse homogenously within the polymer matrix with no phase separation and zero NPs leaching. This mixed-matrix coating can successfully sense and inhibit bacterial contamination via a controlled release mechanism that is only triggered by bacteria. The system is coated on a common radiographic dental imaging device (photostimulable phosphor plate) that is prone to oral bacteria contamination. Variation and eventually disappearance of the red fluorescence surface under UV light signals bacterial infection. Kanamycin, an antimicrobial agent, is controllably released to instantly inhibit bacterial growth. Interestingly, the quality of the images obtained with these coated surfaces is the same as uncoated surfaces and thus the safe application of such smart coatings can be expanded to include other medical devices without compromising their utility.

  19. Determination of the activity of telomerase in cancer cells by using BSA-protected gold nanoclusters as a fluorescent probe.

    Science.gov (United States)

    Xu, Yujuan; Zhang, Peng; Wang, Zhen; Lv, Shaoping; Ding, Caifeng

    2018-02-27

    Gold nanoclusters (AuNCs) protected with a bovine serum albumin (BSA) coating are known to emit red fluorescence (peaking at 650 nm) on photoexcitation with ultraviolet light (365 nm). On addition of Cu(II) ions, fluorescence is quenched because Cu(II) complexes certain amino acid units in the BSA chain. Fluorescence is, however, restored if pyrophosphate (PPi) is added because it will chelate Cu(II) and remove it from the BSA coating on the AuNCs. Because PPi is involved in the function of telomerase, the BSA@AuNCs loaded with Cu(II) can act as a fluorescent probe for determination of the activity of telomerase. A fluorescent assay was worked out for telomerase that is highly sensitive and has a wide linear range (10 nU to 10 fM per mL). The fluorescent probe was applied to the determination of telomerase activity in cervix carcinoma cells via imaging. It is shown that tumor cells can be well distinguished from normal cells by monitoring the differences in intracellular telomerase activity. Graphical abstract Gold nanoclusters (AuNCs) protected by bovine serum albumin (BSA) and displaying red photoluminescence were prepared as fluorescent probe for the determination of telomerase activity and used for imaging of cervix carcinoma (HeLa) cells.

  20. SNARE-mediated trafficking of α5β1 integrin is required for spreading in CHO cells

    International Nuclear Information System (INIS)

    Skalski, Michael; Coppolino, Marc G.

    2005-01-01

    In this study, the role of SNARE-mediated membrane traffic in regulating integrin localization was examined and the requirement for SNARE function in cellular spreading was quantitatively assessed. Membrane traffic was inhibited with the VAMP-specific catalytic light chain from tetanus toxin (TeTx-LC), a dominant-negative form (E329Q) of N-ethylmaleimide-sensitive fusion protein (NSF), and brefeldin A (BfA). Inhibition of membrane traffic with either E329Q-NSF or TeTx-LC, but not BfA, significantly inhibited spreading of CHO cells on fibronectin. Spreading was rescued in TeTx-LC-expressing cells by co-transfection with a TeTx-resistant cellubrevin/VAMP3. E329Q-NSF, a general inhibitor of SNARE function, was a more potent inhibitor of cell spreading than TeTx-LC, suggesting that tetanus toxin-insensitive SNAREs contribute to adhesion. It was found that E329Q-NSF prevented trafficking of α 5 β 1 integrins from a central Rab11-containing compartment to sites of protrusion during cell adhesion, while TeTx-LC delayed this trafficking. These results are consistent with a model of cellular adhesion that implicates SNARE function as an important component of integrin trafficking during the process of cell spreading

  1. Hydrothermal Synthesis of Nanoclusters of ZnS Comprised on Nanowires

    Directory of Open Access Journals (Sweden)

    Magnus Willander

    2013-09-01

    Full Text Available Cetyltrimethyl ammonium bromide cationic (CTAB surfactant was used as template for the synthesis of nanoclusters of ZnS composed of nanowires, by hydrothermal method. The structural and morphological studies were performed by using X-ray diffraction (XRD, scanning electron microscopy (SEM and high resolution transmission electron microscopy (HRTEM techniques. The synthesized ZnS nanoclusters are composed of nanowires and high yield on the substrate was observed. The ZnS nanocrystalline consists of hexagonal phase and polycrystalline in nature. The chemical composition of ZnS nanoclusters composed of nanowires was studied by X-ray photo electron microscopy (XPS. This investigation has shown that the ZnS nanoclusters are composed of Zn and S atoms.

  2. Hydrothermal Synthesis of Nanoclusters of ZnS Comprised on Nanowires.

    Science.gov (United States)

    Ibupoto, Zafar Hussain; Khun, Kimleang; Liu, Xianjie; Willander, Magnus

    2013-09-09

    Cetyltrimethyl ammonium bromide cationic (CTAB) surfactant was used as template for the synthesis of nanoclusters of ZnS composed of nanowires, by hydrothermal method. The structural and morphological studies were performed by using X-ray diffraction (XRD), scanning electron microscopy (SEM) and high resolution transmission electron microscopy (HRTEM) techniques. The synthesized ZnS nanoclusters are composed of nanowires and high yield on the substrate was observed. The ZnS nanocrystalline consists of hexagonal phase and polycrystalline in nature. The chemical composition of ZnS nanoclusters composed of nanowires was studied by X-ray photo electron microscopy (XPS). This investigation has shown that the ZnS nanoclusters are composed of Zn and S atoms.

  3. Multilayered nanoclusters of platinum and gold: insights on electrodeposition pathways, electrocatalysis, surface and bulk compositional properties

    CSIR Research Space (South Africa)

    Mkwizu, TS

    2013-06-01

    Full Text Available Electrochemical, surface and bulk compositional properties of multilayered nanoclusters of Pt and Au, electrochemically deposited on glassy carbon under conditions involving sequential surface–limited redox–replacement reactions (performed at open...

  4. Mechanical stability of titanium and plasma polymer nanoclusters in nanocomposite coatings

    Energy Technology Data Exchange (ETDEWEB)

    Palesch, E. [Institute of Materials Chemistry, Brno University of Technology, Brno (Czech Republic); Marek, A. [HVM Plasma, spol. s r.o., Prague (Czech Republic); Solar, P.; Kylian, O. [Faculty of Mathematics and Physics, Charles University, Prague (Czech Republic); Vyskocil, J. [HVM Plasma, spol. s r.o., Prague (Czech Republic); Biederman, H. [Faculty of Mathematics and Physics, Charles University, Prague (Czech Republic); Cech, V., E-mail: cech@fch.vutbr.cz [Institute of Materials Chemistry, Brno University of Technology, Brno (Czech Republic)

    2013-10-01

    The mechanical stability of nanoclusters embedded in nanocomposite coatings was investigated by scratch and wear tests supported by atomic force microscopy using surface topography mode. Titanium and plasma polymer nanoclusters were deposited on planar substrates (glass, titanium) using a magnetron-based gas aggregation cluster source. The deposited clusters were overcoated with a thin titanium film of different thicknesses to stabilize the position of the clusters in the nanocomposite coating. Nanotribological measurements were carried out to optimize the thickness of the overcoating film for sufficient interfacial adhesion of the cluster/film system. - Highlights: ► Titanium and plasma polymer nanoclusters were overcoated with thin titanium film. ► The mechanical stability of nanoclusters was characterized by nanotribological tests. ► The film thickness was optimized to stabilize the position of the clusters in coating.

  5. A colloidal assembly approach to synthesize magnetic porous composite nanoclusters for efficient protein adsorption

    Science.gov (United States)

    Yang, Qi; Lan, Fang; Yi, Qiangying; Wu, Yao; Gu, Zhongwei

    2015-10-01

    A combination strategy of the inverse emulsion crosslinking approach and the colloidal assembly technique is first proposed to synthesize Fe3O4/histidine composite nanoclusters as new-type magnetic porous nanomaterials. The nanoclusters possess uniform morphology, high magnetic content and excellent protein adsorption capacity, exhibiting their great potential for bio-separation.A combination strategy of the inverse emulsion crosslinking approach and the colloidal assembly technique is first proposed to synthesize Fe3O4/histidine composite nanoclusters as new-type magnetic porous nanomaterials. The nanoclusters possess uniform morphology, high magnetic content and excellent protein adsorption capacity, exhibiting their great potential for bio-separation. Electronic supplementary information (ESI) available: Experimental details. See DOI: 10.1039/c5nr05800g

  6. Ge nanoclusters in PECVD-deposited glass after heat treating and electron irradiation

    DEFF Research Database (Denmark)

    Ou, Haiyan; Rørdam, Troels Peter; Rottwitt, Karsten

    2007-01-01

    This paper reports the formation of Ge nanoclusters in silica glass thin films deposited by plasma-enhanced chemical vapor deposition (PECVD). We studied the samples by transmission electron microscopy (TEM) and Raman spectroscopy after annealing. TEM investigation shows that the Ge nanoclusters...... at two areaswere formed by different mechanisms. The Ge nanoclusters formed in a single row along the interface of a silicon substrate and the silica glass film by annealing during high-temperature heat treatment. Ge nanoclusters did not initially form in the bulk of the film but could be subsequently...... formed by the electron-beam irradiation. The interface between the silicon substrate and the silica glass film was investigated by Raman spectroscopy. The shift of the Raman peaks around 286.8 cm−1 and 495 cm−1 suggests that the interface is a Si1−xGex alloy film and that the composition x varies along...

  7. Pure white-light emitting ultrasmall organic-inorganic hybrid perovskite nanoclusters.

    Science.gov (United States)

    Teunis, Meghan B; Lawrence, Katie N; Dutta, Poulami; Siegel, Amanda P; Sardar, Rajesh

    2016-10-14

    Organic-inorganic hybrid perovskites, direct band-gap semiconductors, have shown tremendous promise for optoelectronic device fabrication. We report the first colloidal synthetic approach to prepare ultrasmall (∼1.5 nm diameter), white-light emitting, organic-inorganic hybrid perovskite nanoclusters. The nearly pure white-light emitting ultrasmall nanoclusters were obtained by selectively manipulating the surface chemistry (passivating ligands and surface trap-states) and controlled substitution of halide ions. The nanoclusters displayed a combination of band-edge and broadband photoluminescence properties, covering a major part of the visible region of the solar spectrum with unprecedentedly large quantum yields of ∼12% and photoluminescence lifetime of ∼20 ns. The intrinsic white-light emission of perovskite nanoclusters makes them ideal and low cost hybrid nanomaterials for solid-state lighting applications.

  8. Encapsulation of nanoclusters in dried gel materials via an inverse micelle/sol gel synthesis

    Science.gov (United States)

    Martino, Anthony; Yamanaka, Stacey A.; Kawola, Jeffrey S.; Showalter, Steven K.; Loy, Douglas A.

    1998-01-01

    A dried gel material sterically entrapping nanoclusters of a catalytically active material and a process to make the material via an inverse micelle/sol-gel synthesis. A surfactant is mixed with an apolar solvent to form an inverse micelle solution. A salt of a catalytically active material, such as gold chloride, is added along with a silica gel precursor to the solution to form a mixture. To the mixture are then added a reducing agent for the purpose of reducing the gold in the gold chloride to atomic gold to form the nanoclusters and a condensing agent to form the gel which sterically entraps the nanoclusters. The nanoclusters are normally in the average size range of from 5-10 nm in diameter with a monodisperse size distribution.

  9. Synthesis and Optical Properties of a Dithiolate/Phosphine-Protected Au28 Nanocluster

    KAUST Repository

    Aljuhani, Maha A.; Bootharaju, Megalamane Siddaramappa; Sinatra, Lutfan; Basset, Jean-Marie; Mohammed, Omar F.; Bakr, Osman

    2016-01-01

    While monothiols and simple phosphines are commonly exploited for size-controlled synthesis of atomically precise gold nanoclusters (NCs), dithiols or dithiol-phosphine combinations are seldom applied. Herein, we used a dithiol (benzene-1,3-dithiol

  10. Synthesis of Co–Al layered double hydroxide nanoclusters as reduction nanocatalyst in aqueous media

    Directory of Open Access Journals (Sweden)

    Daisuke Kino

    2017-12-01

    Full Text Available Layered double hydroxides (LDHs have attracted attention as green materials due to their catalytic ability in benign aqueous solvents. We here demonstrate the synthesis of colloidal Co–Al LDH nanoclusters with an average size of <10 nm via a facile liquid-phase reaction for the enhancement of the catalytic activity. To the best of our knowledge, the present LDH is the smallest Co–Al LDH with an extremely large surface area and stability in an aqueous solvent, forming a stable and concentrated colloidal solution as high as 40 g/L. We investigated the formation mechanism, and the catalytic activity of Co–Al LDH nanoclusters. The Co–Al LDH nanoclusters showed 47 times higher rate of the reduction of dye molecules in the aqueous media than standard Co–Al LDH particles with a micrometer size. LDH nanoclusters demonstrated here are promising green nanocatalysts for the aqueous reaction processes.

  11. Magnetic properties of MnAs nanoclusters embedded in a GaAs semiconductor matrix

    International Nuclear Information System (INIS)

    Hai, Pham Nam; Takahashi, Keisuke; Yokoyama, Masafumi; Ohya, Shinobu; Tanaka, Masaaki

    2007-01-01

    We have clarified fundamental magnetic properties of MnAs nanoclusters (10 nm in diameter) embedded in a thin GaAs matrix (referred to as GaAs:MnAs) through tunneling magnetoresistance (TMR) characteristics of magnetic tunnel junctions (MTJs) consisting of a GaAs:MnAs thin film and a MnAs metal thin film as ferromagnetic electrodes. Although MnAs nanoclusters have coercive forces as small as 150 Oe at 7 K, they show unusually high blocking temperature, which is as large as 300 K. The remanent magnetization of the MnAs nanocluster system linearly decreases with increasing temperature. Those magnetic behaviors cannot be explained by the non-interacting particle model, revealing the important existence of dipolar interactions in MnAs nanocluster system

  12. Synthesis and Doping of Ligand-Protected Atomically-Precise Metal Nanoclusters

    KAUST Repository

    Aljuhani, Maha A.

    2016-01-01

    by controlling their size, shape, and composition. Among the most thriving areas of research about nanoparticle is the synthesis and doping of the ligand-protected atomically-precise metal nanoclusters. In this thesis, we developed three different novel metal

  13. Developmental control of integrin expression regulates Th2 effector homing

    Science.gov (United States)

    Integrin CD18, a component of the LFA-1 complex that also includes CD11a, is essential for Th2, but not Th1, cell homing, but the explanation for this phenomenon remains obscure. In this study, we investigate the mechanism by which Th2 effector responses require the LFA-1 complex. CD11a-deficient T ...

  14. Hierarchy of ADAM12 binding to integrins in tumor cells

    DEFF Research Database (Denmark)

    Thodeti, Charles Kumar; Fröhlich, Camilla; Nielsen, Christian Kamp

    2005-01-01

    ADAMs (a disintegrin and metalloprotease) comprise a family of cell surface proteins with protease and cell-binding activities. Using different forms and fragments of ADAM12 as substrates in cell adhesion and spreading assays, we demonstrated that alpha9beta1 integrin is the main receptor for ADA...

  15. Role of α and β Transmembrane Domains in Integrin Clustering

    Directory of Open Access Journals (Sweden)

    Amir Shamloo

    2015-11-01

    Full Text Available Integrins are transmembrane proteins playing a crucial role in the mechanical signal transduction from the outside to the inside of a cell, and vice versa. Nevertheless, this signal transduction could not be implemented by a single protein. Rather, in order for integrins to be able to participate in signal transduction, they need to be activated and produce clusters first. As integrins consist of α- and β-subunits that are separate in the active state, studying both subunits separately is of a great importance, for, in the active state, the distance between α- and β-subunits is long enough that they do not influence one another significantly. Thus, this study aims to investigate the tendency of transmembrane domains of integrins to form homodimers. We used both Steered and MARTINI Coarse-grained molecular dynamics method to perform our simulations, mainly because of a better resolution and computational feasibility that each of these methods could provide to us. Using the Steered molecular dynamics method for α- and β-subunits, we found that the localized lipid packing prevented them from clustering. Nonetheless, the lipid packing phenomenon was found to be an artifact after investigating this process using a coarse grained (CG model. Exploiting the coarse-grained molecular dynamics simulations, we found that α- and β-subunits tend to form a stable homo-dimer.

  16. Integrins promote axonal regeneration after injury of the nervous system

    NARCIS (Netherlands)

    Nieuwenhuis, Bart; Haenzi, B.; Andrews, M.R.; Verhaagen, J.; Fawcett, J.W.

    2018-01-01

    Integrins are cell surface receptors that form the link between extracellular matrix molecules of the cell environment and internal cell signalling and the cytoskeleton. They are involved in several processes, e.g. adhesion and migration during development and repair. This review focuses on the role

  17. Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling

    Science.gov (United States)

    Morgan, Mark R.; Hamidi, Hellyeh; Bass, Mark D.; Warwood, Stacey; Ballestrem, Christoph; Humphries, Martin J.

    2013-01-01

    Summary Precise spatiotemporal coordination of integrin adhesion complex dynamics is essential for efficient cell migration. For cells adherent to fibronectin, differential engagement of α5β1 and αVβ3 integrins is used to elicit changes in adhesion complex stability, mechanosensation, matrix assembly, and migration, but the mechanisms responsible for receptor regulation have remained largely obscure. We identify phosphorylation of the membrane-intercalated proteoglycan syndecan-4 as an essential switch controlling integrin recycling. Src phosphorylates syndecan-4 and, by driving syntenin binding, leads to suppression of Arf6 activity and recycling of αVβ3 to the plasma membrane at the expense of α5β1. The resultant elevation in αVβ3 engagement promotes stabilization of focal adhesions. Conversely, abrogation of syndecan-4 phosphorylation drives surface expression of α5β1, destabilizes adhesion complexes, and disrupts cell migration. These data identify the dynamic spatiotemporal regulation of Src-mediated syndecan-4 phosphorylation as an essential switch controlling integrin trafficking and adhesion dynamics to promote efficient cell migration. PMID:23453597

  18. Beta 1 integrin is essential for teratoma growth and angiogenesis

    DEFF Research Database (Denmark)

    Bloch, W; Forsberg, E; Lentini, S

    1997-01-01

    Teratomas are benign tumors that form after ectopic injection of embryonic stem (ES) cells into mice and contain derivatives of all primitive germ layers. To study the role of beta 1 integrin during teratoma formation, we compared teratomas induced by normal and beta1-null ES cells. Injection of ...

  19. The strength of integrin binding between neutrophils and endothelial cells

    Czech Academy of Sciences Publication Activity Database

    Labrador, V.; Říha, Pavel; Muller, S.; Dumas, D.; Wang, X.; Stoltz, J. F.

    2003-01-01

    Roč. 32, č. 8 (2003), s. 684-688 ISSN 0175-7571 R&D Projects: GA ČR GA305/01/1605 Institutional research plan: CEZ:AV0Z2060917 Keywords : endothelium * integrins * neutrophil adhesion * scanning microscopy Subject RIV: BO - Biophysics Impact factor: 1.769, year: 2003

  20. Integrin α5β1, the Fibronectin Receptor, as a Pertinent Therapeutic Target in Solid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schaffner, Florence; Ray, Anne Marie; Dontenwill, Monique, E-mail: monique.dontenwill@unistra.fr [UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Tumoral signaling and therapeutic targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch (France)

    2013-01-15

    Integrins are transmembrane heterodimeric proteins sensing the cell microenvironment and modulating numerous signalling pathways. Changes in integrin expression between normal and tumoral cells support involvement of specific integrins in tumor progression and aggressiveness. This review highlights the current knowledge about α5β1 integrin, also called the fibronectin receptor, in solid tumors. We summarize data showing that α5β1 integrin is a pertinent therapeutic target expressed by tumoral neovessels and tumoral cells. Although mainly evaluated in preclinical models, α5β1 integrin merits interest in particular in colon, breast, ovarian, lung and brain tumors where its overexpression is associated with a poor prognosis for patients. Specific α5β1 integrin antagonists will be listed that may represent new potential therapeutic agents to fight defined subpopulations of particularly aggressive tumors.

  1. Salt bridge interactions within the β2 integrin α7 helix mediate force-induced binding and shear resistance ability.

    Science.gov (United States)

    Zhang, Xiao; Li, Linda; Li, Ning; Shu, Xinyu; Zhou, Lüwen; Lü, Shouqin; Chen, Shenbao; Mao, Debin; Long, Mian

    2018-01-01

    The functional performance of the αI domain α 7 helix in β 2 integrin activation depends on the allostery of the α 7 helix, which axially slides down; therefore, it is critical to elucidate what factors regulate the allostery. In this study, we determined that there were two conservative salt bridge interaction pairs that constrain both the upper and bottom ends of the α 7 helix. Molecular dynamics (MD) simulations for three β 2 integrin members, lymphocyte function-associated antigen-1 (LFA-1; α L β 2 ), macrophage-1 antigen (Mac-1; α M β 2 ) and α x β 2 , indicated that the magnitude of the salt bridge interaction is related to the stability of the αI domain and the strength of the corresponding force-induced allostery. The disruption of the salt bridge interaction, especially with double mutations in both salt bridges, significantly reduced the force-induced allostery time for all three members. The effects of salt bridge interactions of the αI domain α 7 helix on β 2 integrin conformational stability and allostery were experimentally validated using Mac-1 constructs. The results demonstrated that salt bridge mutations did not alter the conformational state of Mac-1, but they did increase the force-induced ligand binding and shear resistance ability, which was consistent with MD simulations. This study offers new insight into the importance of salt bridge interaction constraints of the αI domain α 7 helix and external force for β 2 integrin function. © 2017 Federation of European Biochemical Societies.

  2. Stable silver nanoclusters electrochemically deposited on nitrogen-doped graphene as efficient electrocatalyst for oxygen reduction reaction

    Science.gov (United States)

    Jin, Shi; Chen, Man; Dong, Haifeng; He, Bingyu; Lu, Huiting; Su, Lei; Dai, Wenhao; Zhang, Qiaochu; Zhang, Xueji

    2015-01-01

    Metal nanoclusters exhibit unusually high catalytic activity toward oxygen reduction reaction (ORR) due to their small size and unique electronic structures. However, controllable synthesis of stable metal nanoclusters is a challenge, and the durability of metal clusters suffers from the deficiency of dissolution, aggregation, and sintering during catalysis reactions. Herein, silver nanoclusters (AgNCs) (diameter , which is vital in high performance fuel cells, batteries and nanodevices.

  3. Stabilizing Protein Effects on the Pressure Sensitivity of Fluorescent Gold Nanoclusters

    Science.gov (United States)

    2016-01-13

    affected by the environment of the stabilizing protein, allowing these hybrid systems to act as sensors in many applications.2,9,14–19 This has led...Biosens Bioelectron. 2012;32:297–299. 8. Joseph D, Geckeler KE. Synthesis of highly fluorescent gold nanoclusters using egg white proteins. Colloids Surf...Chang HW, Chien YC, Hsiao JK, Cheng JT, Chou PT. Insulin -directed synthesis of fluorescent gold nanoclusters: preservation of insulin bioactivity and

  4. Kernel Tuning and Nonuniform Influence on Optical and Electrochemical Gaps of Bimetal Nanoclusters.

    Science.gov (United States)

    He, Lizhong; Yuan, Jinyun; Xia, Nan; Liao, Lingwen; Liu, Xu; Gan, Zibao; Wang, Chengming; Yang, Jinlong; Wu, Zhikun

    2018-03-14

    Fine tuning nanoparticles with atomic precision is exciting and challenging and is critical for tuning the properties, understanding the structure-property correlation and determining the practical applications of nanoparticles. Some ultrasmall thiolated metal nanoparticles (metal nanoclusters) have been shown to be precisely doped, and even the protecting staple metal atom could be precisely reduced. However, the precise addition or reduction of the kernel atom while the other metal atoms in the nanocluster remain the same has not been successful until now, to the best of our knowledge. Here, by carefully selecting the protecting ligand with adequate steric hindrance, we synthesized a novel nanocluster in which the kernel can be regarded as that formed by the addition of two silver atoms to both ends of the Pt@Ag 12 icosohedral kernel of the Ag 24 Pt(SR) 18 (SR: thiolate) nanocluster, as revealed by single crystal X-ray crystallography. Interestingly, compared with the previously reported Ag 24 Pt(SR) 18 nanocluster, the as-obtained novel bimetal nanocluster exhibits a similar absorption but a different electrochemical gap. One possible explanation for this result is that the kernel tuning does not essentially change the electronic structure, but obviously influences the charge on the Pt@Ag 12 kernel, as demonstrated by natural population analysis, thus possibly resulting in the large electrochemical gap difference between the two nanoclusters. This work not only provides a novel strategy to tune metal nanoclusters but also reveals that the kernel change does not necessarily alter the optical and electrochemical gaps in a uniform manner, which has important implications for the structure-property correlation of nanoparticles.

  5. Lymphocyte integrin expression differences between SIRS and sepsis patients.

    Science.gov (United States)

    Heffernan, D S; Monaghan, S F; Ayala, Alfred

    2017-11-01

    Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically β1 (CD29) and β2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories. T-Lymphocytes were isolated from whole blood collected from ICU patients exhibiting SIRS or sepsis. Samples were analyzed for CD18 (β2) and CD29 (β1) on CD3 + T cells through flow cytometry. Septic patients were stratified into either exclusively abdominal or non-abdominal sources of sepsis. CD18 was almost ubiquitously expressed on CD3 + T cells irrespective of clinical condition. However, CD29 (β1 integrin) was lowest in SIRS patients (20.4% of CD3 + T cells) when compared with either septic patients (35.5%) or healthy volunteers (54.1%). Furthermore, there was evidence of compartmentalization in septic patients, where abdominal sources had a greater percentage of CD3 + CD29 + T cells (41.7%) when compared with those with non-abdominal sources (29.5%). Distinct differences in T-cell integrin expression exists between patients in SIRS versus sepsis, as well as relative to the source of sepsis. Further work is needed to understand cause and effect relative to the progression from SIRS into sepsis.

  6. Iron/iron oxide core-shell nanoclusters for biomedical applications

    International Nuclear Information System (INIS)

    Qiang You; Antony, Jiji; Sharma, Amit; Nutting, Joseph; Sikes, Daniel; Meyer, Daniel

    2006-01-01

    Biocompatible magnetic nanoparticles have been found promising in several biomedical applications for tagging, imaging, sensing and separation in recent years. Most magnetic particles or beads currently used in biomedical applications are based on ferromagnetic iron oxides with very low specific magnetic moments of about 20-30 emu/g. Here we report a new approach to synthesize monodispersed core-shell nanostructured clusters with high specific magnetic moments above 200 emu/g. Iron nanoclusters with monodispersive size of diameters from 2 nm to 100 nm are produced by our newly developed nanocluster source and go to a deposition chamber, where a chemical reaction starts, and the nanoclusters are coated with iron oxides. HRTEM Images show the coatings are very uniform and stable. The core-shell nanoclusters are superparamagnetic at room temperature for sizes less than 15 nm, and then become ferromagnetic when the cluster size increases. The specific magnetic moment of core-shell nanoclusters is size dependent, and increases rapidly from about 80 emu/g at the cluster size of around 3 nm to over 200 emu/g up to the size of 100 nm. The use of high magnetic moment nanoclusters for biomedical applications could dramatically enhance the contrast for MRI, reduce the concentration of magnetic particle needs for cell separation, or make drug delivery possible with much lower magnetic field gradients

  7. Optical properties of multicomponent antimony-silver nanoclusters formed in silica by sequential ion implantation

    International Nuclear Information System (INIS)

    Zuhr, R.A.

    1995-11-01

    The linear and nonlinear optical properties of nanometer dimension metal colloids embedded in a dielectric depend explicitly on the electronic structure of the metal nanoclusters. The ability to control the electronic structure of the nanoclusters may make it possible to tailor the optical properties for enhanced performance. By sequential implantation of different metal ion species multi-component nanoclusters can be formed with significantly different optical properties than single element metal nanoclusters. The authors report the formation of multi-component Sb/Ag nanoclusters in silica by sequential implantation of Sb and Ag. Samples were implanted with relative ratios of Sb to Ag of 1:1 and 3:1. A second set of samples was made by single element implantations of Ag and Sb at the same energies and doses used to make the sequentially implanted samples. All samples were characterized using RBS and both linear and nonlinear optical measurements. The presence of both ions significantly modifies the optical properties of the composites compared to the single element nanocluster glass composites. In the sequentially implanted samples the optical density is lower, and the strong surface plasmon resonance absorption observed in the Ag implanted samples is not present. At the same time the nonlinear response of the these samples is larger than for the samples implanted with Sb alone, suggesting that the addition of Ag can increase the nonlinear response of the Sb particles formed. The results are consistent with the formation of multi-component Sb/Ag colloids

  8. Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species.

    Science.gov (United States)

    Matulionyte, Marija; Dapkute, Dominyka; Budenaite, Laima; Jarockyte, Greta; Rotomskis, Ricardas

    2017-02-10

    In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS) of bovine serum albumin-encapsulated (BSA-Au NCs) and 2-(N-morpholino) ethanesulfonic acid (MES)capped photoluminescent gold nanoclusters (Au-MES NCs) were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters.

  9. Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Marija Matulionyte

    2017-02-01

    Full Text Available In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS of bovine serum albumin-encapsulated (BSA-Au NCs and 2-(N-morpholino ethanesulfonic acid (MEScapped photoluminescent gold nanoclusters (Au-MES NCs were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters.

  10. PRL-3 promotes the motility, invasion, and metastasis of LoVo colon cancer cells through PRL-3-integrin β1-ERK1/2 and-MMP2 signaling

    Directory of Open Access Journals (Sweden)

    Wu Jian

    2009-11-01

    Full Text Available Abstract Background Phosphatase of regenerating liver-3 (PRL-3 plays a causative role in tumor metastasis, but the underlying mechanisms are not well understood. In our previous study, we observed that PRL-3 could decrease tyrosine phosphorylation of integrin β1 and enhance activation of ERK1/2 in HEK293 cells. Herein we aim to explore the association of PRL-3 with integrin β1 signaling and its functional implications in motility, invasion, and metastasis of colon cancer cell LoVo. Methods Transwell chamber assay and nude mouse model were used to study motility and invasion, and metastsis of LoVo colon cancer cells, respectively. Knockdown of integrin β1 by siRNA or lentivirus were detected with Western blot and RT-PCR. The effect of PRL-3 on integrin β1, ERK1/2, and MMPs that mediate motility, invasion, and metastasis were measured by Western blot, immunofluorencence, co-immunoprecipitation and zymographic assays. Results We demonstrated that PRL-3 associated with integrin β1 and its expression was positively correlated with ERK1/2 phosphorylation in colon cancer tissues. Depletion of integrin β1 with siRNA, not only abrogated the activation of ERK1/2 stimulated by PRL-3, but also abolished PRL-3-induced motility and invasion of LoVo cells in vitro. Similarly, inhibition of ERK1/2 phosphorylation with U0126 or MMP activity with GM6001 also impaired PRL-3-induced invasion. In addition, PRL-3 promoted gelatinolytic activity of MMP2, and this stimulation correlated with decreased TIMP2 expression. Moreover, PRL-3-stimulated lung metastasis of LoVo cells in a nude mouse model was inhibited when integrin β1 expression was interfered with shRNA. Conclusion Our results suggest that PRL-3's roles in motility, invasion, and metastasis in colon cancer are critically controlled by the integrin β1-ERK1/2-MMP2 signaling.

  11. Astrocytic αVβ3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1.

    Directory of Open Access Journals (Sweden)

    Rodrigo Herrera-Molina

    Full Text Available Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to α(Vβ(3 integrin in trans eliciting responses in astrocytes. Nonetheless, whether α(Vβ(3 integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of α(Vβ(3 integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous α(Vβ(3 integrin restricted neurite outgrowth. Likewise, α(Vβ(3-Fc was sufficient to suppress neurite extension in Thy-1(+, but not in Thy-1(- CAD cells. In differentiating primary neurons exposed to α(Vβ(3-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC. Moreover, α(Vβ(3-Fc also induced retraction of already extended Thy-1(+-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by α(Vβ(3 integrin. Binding of α(Vβ(3-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, α(Vβ(3-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that α(Vβ(3 integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage.

  12. SU9516 Increases α7β1 Integrin and Ameliorates Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Sarathy, Apurva; Wuebbles, Ryan D; Fontelonga, Tatiana M; Tarchione, Ashley R; Mathews Griner, Lesley A; Heredia, Dante J; Nunes, Andreia M; Duan, Suzann; Brewer, Paul D; Van Ry, Tyler; Hennig, Grant W; Gould, Thomas W; Dulcey, Andrés E; Wang, Amy; Xu, Xin; Chen, Catherine Z; Hu, Xin; Zheng, Wei; Southall, Noel; Ferrer, Marc; Marugan, Juan; Burkin, Dean J

    2017-06-07

    Duchenne muscular dystrophy (DMD) is a fatal muscle disease caused by mutations in the dystrophin gene, resulting in a complete loss of the dystrophin protein. Dystrophin is a critical component of the dystrophin glycoprotein complex (DGC), which links laminin in the extracellular matrix to the actin cytoskeleton within myofibers and provides resistance to shear stresses during muscle activity. Loss of dystrophin in DMD patients results in a fragile sarcolemma prone to contraction-induced muscle damage. The α7β1 integrin is a laminin receptor protein complex in skeletal and cardiac muscle and a major modifier of disease progression in DMD. In a muscle cell-based screen for α7 integrin transcriptional enhancers, we identified a small molecule, SU9516, that promoted increased α7β1 integrin expression. Here we show that SU9516 leads to increased α7B integrin in murine C2C12 and human DMD patient myogenic cell lines. Oral administration of SU9516 in the mdx mouse model of DMD increased α7β1 integrin in skeletal muscle, ameliorated pathology, and improved muscle function. We show that these improvements are mediated through SU9516 inhibitory actions on the p65-NF-κB pro-inflammatory and Ste20-related proline alanine rich kinase (SPAK)/OSR1 signaling pathways. This study identifies a first in-class α7 integrin-enhancing small-molecule compound with potential for the treatment of DMD. Copyright © 2017 The American Society of Gene and Cell Therapy. All rights reserved.

  13. Medium-chain, triglyceride-containing lipid emulsions increase human neutrophil beta2 integrin expression, adhesion, and degranulation.

    Science.gov (United States)

    Wanten, G J; Geijtenbeek, T B; Raymakers, R A; van Kooyk, Y; Roos, D; Jansen, J B; Naber, A H

    2000-01-01

    To test the hypothesis that lipid emulsions with different triglyceride structures have distinct immunomodulatory properties, we analyzed human neutrophil adhesion and degranulation after lipid incubation. Neutrophils, isolated from the blood of 10 healthy volunteers, were incubated in medium or physiologic (2.5 mmol/L) emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, or structured (SL) triglycerides. Expression of adhesion molecules and degranulation markers was evaluated by flow cytometry. Also, functional adhesion was investigated by means of a flow cytometric assay using fluorescent beads coated with the integrin ligand intercellular adhesion molecule (ICAM)-1. Although LCT and SL had no effect, LCT/MCT significantly increased expression of the beta2 integrins lymphocyte-function-associated antigen 1 (+18%), macrophage antigen 1 (+387%), p150,95 (+82%), and (alphaDbeta2 (+230%). Degranulation marker expression for azurophilic (CD63, +210%) and specific granules (CD66b, +370%) also significantly increased, whereas L-selectin (CD62L, -70%) decreased. The effects of LCT/MCT were mimicked by the MCT emulsion. ICAM-1 adhesion (% beads bound) was increased by LCT/MCT (34% +/- 4%), whereas LCT (19% +/-3%) and SL (20% +/- 2%) had no effect compared with medium (17% +/- 3%). LCT/MCT and MCT, contrary to LCT and SL emulsions, increased neutrophil beta2 integrin expression, adhesion, and degranulation. Apart from other emulsion constituents, triglyceride chain length might therefore be a key feature in the interaction of lipid emulsions and the phagocyte immune system.

  14. Role of ligand-ligand vs. core-core interactions in gold nanoclusters.

    Science.gov (United States)

    Milowska, Karolina Z; Stolarczyk, Jacek K

    2016-05-14

    The controlled assembly of ligand-coated gold nanoclusters (NCs) into larger structures paves the way for new applications ranging from electronics to nanomedicine. Here, we demonstrate through rigorous density functional theory (DFT) calculations employing novel functionals accounting for van der Waals forces that the ligand-ligand interactions determine whether stable assemblies can be formed. The study of NCs with different core sizes, symmetry forms, ligand lengths, mutual crystal orientations, and in the presence of a solvent suggests that core-to-core van der Waals interactions play a lesser role in the assembly. The dominant interactions originate from combination of steric effects, augmented by ligand bundling on NC facets, and related to them changes in electronic properties induced by neighbouring NCs. We also show that, in contrast to standard colloidal theory approach, DFT correctly reproduces the surprising experimental trends in the strength of the inter-particle interaction observed when varying the length of the ligands. The results underpin the importance of understanding NC interactions in designing gold NCs for a specific function.

  15. Bio-NCs--the marriage of ultrasmall metal nanoclusters with biomolecules.

    Science.gov (United States)

    Goswami, Nirmal; Zheng, Kaiyuan; Xie, Jianping

    2014-11-21

    Ultrasmall metal nanoclusters (NCs) have attracted increasing attention due to their fascinating physicochemical properties. Today, functional metal NCs are finding growing acceptance in biomedical applications. To achieve a better performance in biomedical applications, metal NCs can be interfaced with biomolecules, such as proteins, peptides, and DNA, to form a new class of biomolecule-NC composites (or bio-NCs in short), which typically show synergistic or novel physicochemical and physiological properties. This feature article focuses on the recent studies emerging at the interface of metal NCs and biomolecules, where the interactions could impart unique physicochemical properties to the metal NCs, as well as mutually regulate biological functions of the bio-NCs. In this article, we first provide a broad overview of key concepts and developments in the novel biomolecule-directed synthesis of metal NCs. A special focus is placed on the key roles of biomolecules in metal NC synthesis. In the second part, we describe how the encapsulated metal NCs affect the structure and function of biomolecules. Followed by that, we discuss several unique synergistic effects observed in the bio-NCs, and illustrate them with examples highlighting their potential biomedical applications. Continued interdisciplinary efforts are required to build up in-depth knowledge about the interfacial chemistry and biology of bio-NCs, which could further pave their ways toward biomedical applications.

  16. Bio-NCs - the marriage of ultrasmall metal nanoclusters with biomolecules

    Science.gov (United States)

    Goswami, Nirmal; Zheng, Kaiyuan; Xie, Jianping

    2014-10-01

    Ultrasmall metal nanoclusters (NCs) have attracted increasing attention due to their fascinating physicochemical properties. Today, functional metal NCs are finding growing acceptance in biomedical applications. To achieve a better performance in biomedical applications, metal NCs can be interfaced with biomolecules, such as proteins, peptides, and DNA, to form a new class of biomolecule-NC composites (or bio-NCs in short), which typically show synergistic or novel physicochemical and physiological properties. This feature article focuses on the recent studies emerging at the interface of metal NCs and biomolecules, where the interactions could impart unique physicochemical properties to the metal NCs, as well as mutually regulate biological functions of the bio-NCs. In this article, we first provide a broad overview of key concepts and developments in the novel biomolecule-directed synthesis of metal NCs. A special focus is placed on the key roles of biomolecules in metal NC synthesis. In the second part, we describe how the encapsulated metal NCs affect the structure and function of biomolecules. Followed by that, we discuss several unique synergistic effects observed in the bio-NCs, and illustrate them with examples highlighting their potential biomedical applications. Continued interdisciplinary efforts are required to build up in-depth knowledge about the interfacial chemistry and biology of bio-NCs, which could further pave their ways toward biomedical applications.

  17. N-cadherin and integrin blockade inhibit arteriolar myogenic reactivity but not pressure-induced increases in intracellular Ca2+

    Directory of Open Access Journals (Sweden)

    Teresa Y. Jackson

    2010-12-01

    Full Text Available The vascular myogenic response is characterized by arterial constriction in response to an increase in intraluminal pressure and dilatation to a decrease in pressure. This mechanism is important for the regulation of blood flow, capillary pressure and arterial pressure. The identity of the mechanosensory mechanism(s for this response is incompletely understood but has been shown to include the integrins as cell-extracellular matrix receptors. The possibility that a cell-cell adhesion receptor is involved has not been studied. Thus, we tested the hypothesis that N-cadherin, a cell-cell adhesion molecule in vascular smooth muscle cells (VSMCs, was important for myogenic responsiveness. The purpose of this study was to investigate:
    1. whether cadherin inhibition blocks myogenic responses to increases in intraluminal pressure and 2. the effect of the cadherin or integrin blockade on pressure-induced changes in [Ca2+]i. Cadherin blockade was tested in isolated rat cremaster arterioles on myogenic responses to acute pressure steps from 60 – 100 mmHg and changes in VSMC Ca2+ were measured using fura-2. In the presence of a synthetic cadherin inhibitory peptide or a function blocking antibody, myogenic responses were inhibited. In contrast, during N-cadherin blockade, pressure-induced changes in [Ca2+]i were not altered. Similarly, vessels treated with function-blocking β1- or β3-integrin antibodies maintained pressure-induced [Ca2+]i responses despite inhibition of myogenic constriction. Collectively, these data suggest that both cadherins and integrins play a fundamental role in mediating myogenic constriction but argue against their direct involvement in mediating pressure-induced [Ca2+]i increases.

  18. Integrin specificity and enhanced cellular activities associated with surfaces presenting a recombinant fibronectin fragment compared to RGD supports.

    Science.gov (United States)

    Petrie, Timothy A; Capadona, Jeffrey R; Reyes, Catherine D; García, Andrés J

    2006-11-01

    Biomimetic strategies focusing on presenting short bioadhesive oligopeptides, including the arginine-glycine-aspartic acid (RGD) motif present in numerous adhesive proteins, on a non-fouling support have emerged as promising approaches to improve cellular activities and healing responses. Nevertheless, these bio-inspired strategies are limited by low activity of the oligopeptides compared to the native ligand due to the absence of complementary or modulatory domains. In the present analysis, we generated well-defined biointerfaces presenting RGD-based ligands of increasing complexity to directly compare their biological activities in terms of cell adhesion strength, integrin binding and signaling. Mixed self-assembled monolayers of alkanethiols on gold were optimized to engineer robust supports that present anchoring groups for ligand tethering within a non-fouling, protein adsorption-resistant background. Controlled bioadhesive interfaces were generated by tethering adhesive ligands via standard peptide chemistry. On a molar basis, biointerfaces functionalized with the FNIII7-10 recombinant fragment presenting the RGD and PHSRN adhesive motifs in the correct structural context exhibited significantly higher adhesion strength, FAK activation, and cell proliferation rate than supports presenting RGD ligand or RGD-PHSRN, an oligopeptide presenting these two sites separated by a polyglycine linker. Moreover, FNIII7-10-functionalized surfaces displayed specificity for alpha5beta1 integrin, while cell adhesion to supports presenting RGD or RGD-PHSRN was primarily mediated by alphavbeta3 integrin. These results are significant to the rational engineering of bioactive materials that convey integrin binding specificity for directed cellular and tissue responses in biomedical and biotechnological applications.

  19. Electrochemical ammonia production on molybdenum nitride nanoclusters

    DEFF Research Database (Denmark)

    Howalt, Jakob Geelmuyden; Vegge, Tejs

    2013-01-01

    Theoretical investigations of electrochemical production of ammonia at ambient temperature and pressure on nitrogen covered molybdenum nanoparticles are presented. Density functional theory calculations are used in combination with the computational hydrogen electrode approach to calculate the free...... energy profile for electrochemical protonation of N2 and N adatoms on cuboctahedral Mo13 nanoparticles. Pathways for electrochemical ammonia production via direct protonation of N adatoms and N2 admolecules with an onset potential as low as -0.5 V and generally lower than -0.8 V on both a nitrogen...

  20. Synthesis of immunotargeted magneto-plasmonic nanoclusters.

    Science.gov (United States)

    Wu, Chun-Hsien; Sokolov, Konstantin

    2014-08-22

    Magnetic and plasmonic properties combined in a single nanoparticle provide a synergy that is advantageous in a number of biomedical applications including contrast enhancement in novel magnetomotive imaging modalities, simultaneous capture and detection of circulating tumor cells (CTCs), and multimodal molecular imaging combined with photothermal therapy of cancer cells. These applications have stimulated significant interest in development of protocols for synthesis of magneto-plasmonic nanoparticles with optical absorbance in the near-infrared (NIR) region and a strong magnetic moment. Here, we present a novel protocol for synthesis of such hybrid nanoparticles that is based on an oil-in-water microemulsion method. The unique feature of the protocol described herein is synthesis of magneto-plasmonic nanoparticles of various sizes from primary blocks which also have magneto-plasmonic characteristics. This approach yields nanoparticles with a high density of magnetic and plasmonic functionalities which are uniformly distributed throughout the nanoparticle volume. The hybrid nanoparticles can be easily functionalized by attaching antibodies through the Fc moiety leaving the Fab portion that is responsible for antigen binding available for targeting.

  1. Chemokine Receptors and Integrin Function in Prostate Cancer

    National Research Council Canada - National Science Library

    McCarthy, James

    2000-01-01

    Preliminary data demonstrated that the addition of specific alpha-chemokines, IL-8 and Gro-alpha, to prostate carcinoma cell cultures, leads to an increase in the motility and invasion of these cells in vitro...

  2. Size distribution of silver nanoclusters induced by ion, electron, laser beams and thermal treatments of an organometallic precursor

    International Nuclear Information System (INIS)

    D'Urso, L.; Nicolosi, V.; Compagnini, G.; Puglisi, O.

    2004-01-01

    Recently, a huge variety of physical and chemical synthetic processes have been reported to prepare nanostructured materials made of very small (diameter<50 nm) metallic clusters. Depending on the nature of clusters, this new kind of materials posses interesting properties (electronic, optical, magnetic, catalytic) that can be tailored as a function of the particles size and shape. Silver nanoparticles have been obtained by direct thermal treatment or by beam-enhanced decomposition (ion, electron and laser) of a silver organometallic compound (precursor) spinned onto suitable substrates. In this paper, we present the results of a study on the size distribution of such nanoparticles as a function of the different synthesis methods. It was found that the methods employed strongly affect the silver nanoparticles formation. Smaller silver nanoclusters were obtained after reduction by ion beam irradiation and thermal treatment, as observed by using different techniques (AFM, XRD and UV-Vis)

  3. An Investigation of Electronic Structure and Aromaticity in Medium-Sized Nanoclusters of Gold-Doped Germanium

    Directory of Open Access Journals (Sweden)

    Xiao-Jun Li

    2012-01-01

    Full Text Available The electronic property and aromaticity of endohedrally doped and clusters are investigated using the density-functional theory (DFT within the hybrid B3LYP method. The calculated results reveal that the two clusters have high thermodynamic stability reflected by reaction energy. At the same time, it could be hoped that their high stability may arise from the closed-shell spherical aromaticity with eight -electrons satisfying the counting rule with . A popular nucleus-independent chemical shifts (NICSs calculation on basis of magnetic shieldings is also performed to confirm the aromaticity of the three-dimensional nanoclusters with largely negative NICS values. In addition, the electronic features and chemical bonding of the two clusters are analyzed with the help of the density of states (DOS and electron localization function (ELF, and the majority of Ge–Ge bonds on the cage show more covalent characters.

  4. Shellwise Mackay transformation in iron nanoclusters.

    Science.gov (United States)

    Rollmann, Georg; Gruner, Markus E; Hucht, Alfred; Meyer, Ralf; Entel, Peter; Tiago, Murilo L; Chelikowsky, James R

    2007-08-24

    Structure and magnetism of iron clusters with up to 641 atoms have been investigated by means of density functional theory calculations including full geometric optimizations. Body-centered cubic (bcc) isomers are found to be lowest in energy when the clusters contain more than about 100 atoms. In addition, another stable conformation has been identified for magic-number clusters, which lies well within the range of thermal energies as compared to the bcc isomers. Its structure is characterized by a close-packed particle core and an icosahedral surface, while intermediate shells are partially transformed along the Mackay path between icosahedral and cuboctahedral geometry. The gradual transformation results in a favorable bcc environment for the subsurface atoms. For Fe55, the shellwise Mackay-transformed morphology is a promising candidate for the ground state.

  5. Assessing activation of hepatic stellate cells by 99mTc-3PRGD2 scintigraphy targeting integrin αvβ3: a feasibility study

    International Nuclear Information System (INIS)

    Zhang, Xin; Xin, Jun; Shi, Yu; Xu, Weina; Yu, Shupeng; Yang, Zhiguang; Liu, Changping; Cao, Li; Guo, Qiyong

    2015-01-01

    Objective: Hepatic stellate cell (HSC) activation, which is accompanied by increased expression of integrin αvβ3, is an important factor in liver fibrogenesis. Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on the activated HSCs (aHSCs) in the injured liver, and then provide important prognostic information. 99m Tc-3PRGD2 is such a radiotracer specific for integrin αvβ3. In this study, we aimed to compare the differences in liver uptake and retention of the 99m Tc-3PRGD2 between normal liver and injured liver to evaluate the feasibility of 99m Tc-3PRGD2 scintigraphy for this purpose. Methods: We used planar scintigraphy to assess changes in integrin αvβ3 binding of intravenously-administered 99m Tc-3PRGD2 in the livers of rats with thioacetamide (TAA)-induced liver fibrosis compared with the controls. We co-injected cold c(RGDyK) with 99m Tc-3PRGD2 to assess the specific binding of the radiotracer. We performed Sirius red staining to assess liver fibrosis, immunofluorescent colocalization to identify the location of integrin αvβ3 expressed in the fibrotic liver, and we measured protein and messenger RNA expression of integrin αvβ3 and alpha smooth muscle actin (α-SMA) in the control and fibrotic livers. Results: The fibrotic livers showed enhanced 99m Tc-3PRGD2 uptake and retention. The radiotracer was demonstrated to bind specifically with the integrin αvβ3 mainly expressed on the aHSCs. The liver-to-heart ratio at 30 min post-injection was higher in the fibrotic livers than in the control livers (TAA, 1.98 ± 0.08 vs. control, 1.50 ± 0.12, p < 0.01). The liver t 1/2 was longer than in the controls (TAA, 27.07 ± 10.69 min vs. control, 12.67 ± 4.10 min, p < 0.01). The difference of heart t 1/2 between the two groups was not statistically significant (TAA, 3.13 ± 0.63 min vs. control, 3.41 ± 0.77 min, p = 0.94). Conclusions: 99m Tc-3PRGD2

  6. Eco-friendly (green) synthesis of magnetically active gold nanoclusters

    Science.gov (United States)

    Kadasala, Naveen Reddy; Lin, Lu; Gilpin, Christopher; Wei, Alexander

    2017-12-01

    Au-FexOy composite nanoparticles (NPs) are of great technological interest due to their combined optical and magnetic properties. However, typical syntheses are neither simple nor ecologically friendly, creating a challenging situation for process scale-up. Here we describe conditions for preparing Au-FexOy NPs in aqueous solutions and at ambient temperatures, without resorting to solvents or amphiphilic surfactants with poor sustainability profiles. These magnetic gold nanoclusters (MGNCs) are prepared in practical yields with average sizes slightly below 100 nm, and surface plasmon resonances that extend to near-infrared wavelengths, and sufficient magnetic moment (up to 6 emu g-1) to permit collection within minutes by handheld magnets. The MGNCs also produce significant photoluminescence when excited at 488 nm. Energy dispersive X-ray (EDX) analysis indicates a relatively even distribution of Fe within the MGNCs, as opposed to a central magnetic core.

  7. Gold Nanocluster-Mediated Cellular Death under Electromagnetic Radiation.

    Science.gov (United States)

    Cifuentes-Rius, Anna; Ivask, Angela; Das, Shreya; Penya-Auladell, Nuria; Fabregas, Laura; Fletcher, Nicholas L; Houston, Zachary H; Thurecht, Kristofer J; Voelcker, Nicolas H

    2017-11-29

    Gold nanoclusters (Au NCs) have become a promising nanomaterial for cancer therapy because of their biocompatibility and fluorescent properties. In this study, the effect of ultrasmall protein-stabilized 2 nm Au NCs on six types of mammalian cells (fibroblasts, B-lymphocytes, glioblastoma, neuroblastoma, and two types of prostate cancer cells) under electromagnetic radiation is investigated. Cellular association of Au NCs in vitro is concentration-dependent, and Au NCs have low intrinsic toxicity. However, when Au NC-incubated cells are exposed to a 1 GHz electromagnetic field (microwave radiation), cell viability significantly decreases, thus demonstrating that Au NCs exhibit specific microwave-dependent cytotoxicity, likely resulting from localized heating. Upon i.v. injection in mice, Au NCs are still present at 24 h post administration. Considering the specific microwave-dependent cytotoxicity and low intrinsic toxicity, our work suggests the potential of Au NCs as effective and safe nanomedicines for cancer therapy.

  8. A comparison of interatomic potentials for modeling tungsten nanocluster structures

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Jiannan; Shu, Xiaolin, E-mail: shuxlin@buaa.edu.cn; Jin, Shuo; Zhang, Xuesong; Zhang, Ying; Lu, Guang-Hong

    2017-02-15

    Molecular dynamic simulation is utilized to study the nanocluster and the fuzz structure on the PFM surface of tungsten. The polyhedral and linear cluster structures based on the icosahedron, cuboctahedron and rhombic dodecahedron are built up. Three interatomic potentials are used in calculating the relationship between the cluster energy and the number of atoms. The results are compared with first-principles calculation to show each potential’s best application scale. Furthermore, the transition between the icosahedral and the cuboctahedral clusters is observed in molecular dynamic simulation at different temperatures, which follows a critical curve for different numbers of atoms. The linear structures are proved to be stable at experimental temperatures by thermodynamics. The work presents a selection of interatomic potentials in simulating tungsten cluster systems and helps researchers understand the growth and evolution laws of clusters and the fuzz-like structure formation process in fusion devices.

  9. Electrically driven light emission from an array of Si nanoclusters

    International Nuclear Information System (INIS)

    Mazzitello, K I; Martin, H O; Aldao, C M; Roman, H E

    2004-01-01

    Charge transport and light emission properties of an array of silicon nanoclusters (NCs), sandwiched between a p-type and an n-type doped silicon crystal, are studied theoretically by assuming that electrons and holes enter from the opposite sides of the array in response to an applied electric field. The size of the NCs considered ranges from 16 nm down to 3.6 nm and their spatial distribution is optimized so that light emission, resulting from radiative recombinations, is peaked in the visible red around 1.8 eV. The light emission efficiency is limited by the carrier hopping times and is found to be in the range 2-0.5%, for fields ranging from 100 kV cm -1 to 500 kV cm -1 , respectively

  10. Melting of Cu nanoclusters by molecular dynamics simulation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Li; Zhang, Yanning; Bian, Xiufang; Chen, Ying

    2003-04-14

    We present a detailed molecular dynamics study of the melting of copper nanoclusters with up to 8628 atoms within the framework of the embedded-atom method. The finding indicates that there exists an intermediate nanocrystal regime above 456 atoms. The linear relation between the cluster size and its thermodynamics properties is obeyed in this regime. Melting first occurs at the surface of the clusters, leading to T{sub m,N}=T{sub m,Bulk}-{alpha}N{sup -1/3}, dropping from T{sub m,Bulk}=1360 K to T{sub m,456}=990 K. In addition, the size, surface energy as well as the root mean square displacement (RMSD) of the clusters in the intermediate regime have been investigated.

  11. Exploring Low Internal Reorganization Energies for Silicene Nanoclusters

    KAUST Repository

    Pablo-Pedro, Ricardo

    2017-08-17

    High-performance materials rely on small reorganization energies to facilitate both charge separation and charge transport. Here, we performed DFT calculations to predict small reorganization energies of rectangular silicene nanoclusters with hydrogen-passivated edges denoted by H-SiNC. We observe that across all geometries, H-SiNCs feature large electron affinities and highly stabilized anionic states, indicating their potential as n-type materials. Our findings suggest that fine-tuning the size of H-SiNCs along the zigzag and armchair directions may permit the design of novel n-type electronic materials and spinctronics devices that incorporate both high electron affinities and very low internal reorganization energies.

  12. A comparison of interatomic potentials for modeling tungsten nanocluster structures

    International Nuclear Information System (INIS)

    Hao, Jiannan; Shu, Xiaolin; Jin, Shuo; Zhang, Xuesong; Zhang, Ying; Lu, Guang-Hong

    2017-01-01

    Molecular dynamic simulation is utilized to study the nanocluster and the fuzz structure on the PFM surface of tungsten. The polyhedral and linear cluster structures based on the icosahedron, cuboctahedron and rhombic dodecahedron are built up. Three interatomic potentials are used in calculating the relationship between the cluster energy and the number of atoms. The results are compared with first-principles calculation to show each potential’s best application scale. Furthermore, the transition between the icosahedral and the cuboctahedral clusters is observed in molecular dynamic simulation at different temperatures, which follows a critical curve for different numbers of atoms. The linear structures are proved to be stable at experimental temperatures by thermodynamics. The work presents a selection of interatomic potentials in simulating tungsten cluster systems and helps researchers understand the growth and evolution laws of clusters and the fuzz-like structure formation process in fusion devices.

  13. Connections Between Theory and Experiment for Gold and Silver Nanoclusters

    Science.gov (United States)

    Weerawardene, K. L. Dimuthu M.; Häkkinen, Hannu; Aikens, Christine M.

    2018-04-01

    Ligand-stabilized gold and silver nanoparticles are of tremendous current interest in sensing, catalysis, and energy applications. Experimental and theoretical studies have closely interacted to elucidate properties such as the geometric and electronic structures of these fascinating systems. In this review, the interplay between theory and experiment is described; areas such as optical absorption and doping, where the theory-experiment connections are well established, are discussed in detail; and the current status of these connections in newer fields of study, such as luminescence, transient absorption, and the effects of solvent and the surrounding environment, are highlighted. Close communication between theory and experiment has been extremely valuable for developing an understanding of these nanocluster systems in the past decade and will undoubtedly continue to play a major role in future years.

  14. Critical sizes and critical characteristics of nanoclusters, nanostructures and nanomaterials

    International Nuclear Information System (INIS)

    Suzdalev, I.P.

    2005-01-01

    Full text: Critical sizes and characteristics of nanoclusters and nanostructures are introduced as the parameters of nanosystems and nanomaterials. The next critical characteristics are considered: atomic and electronic 'magic number', critical size of cluster nucleation, critical size of melting-freezing of cluster, critical size of quantum (laser) radiation, critical sizes for the single electron conductivity, critical energy and magnetic field for the magnetic tunneling, critical cluster sizes for the giant magnetic resistance, critical size of the first order magnetic phase transition. The critical characteristics are estimated by thermodynamic approaches, by Moessbauer spectroscopy, AFM, heat capacity, SQUID magnetometry and other technique, The influence of cluster-cluster interactions, cluster-matrix interactions and cluster defects on cluster atomic dynamics, cluster melting, cluster critical sizes, Curie or Neel points and the character of magnetic phase transitions were investigated. The applications of critical size and critical characteristic parameters for the nanomaterial characterization are considered

  15. Osteopontin binding to the alpha 4 integrin requires highest affinity integrin conformation, but is independent of post-translational modifications of osteopontin

    DEFF Research Database (Denmark)

    Hui, Tommy; Sørensen, Esben Skipper; Rittling, Susan R.

    2015-01-01

    Osteopontin (OPN) is a ligand for the α4 integrin, but the physiological importance of this binding is not well understood. Here, we have assessed the effect of posttranslational modifications on OPN binding to the α4 integrin on cultured human leukocyte cell lines, and compared OPN interaction...

  16. Electrical transport properties in Co nanocluster-assembled granular film

    Science.gov (United States)

    Zhang, Qin-Fu; Wang, Lai-Sen; Wang, Xiong-Zhi; Zheng, Hong-Fei; Liu, Xiang; Xie, Jia; Qiu, Yu-Long; Chen, Yuanzhi; Peng, Dong-Liang

    2017-03-01

    A Co nanocluster-assembled granular film with three-dimensional cross-connection paralleled conductive paths was fabricated by using the plasma-gas-condensation method in a vacuum environment. The temperature-dependent longitudinal resistivity and anomalous Hall effect of this new type granular film were systematically studied. The longitudinal resistivity of the Co nanocluster-assembled granular film first decreased and then increased with increasing measuring temperature, revealing a minimum value at certain temperature, T min . In a low temperature region ( T governed the electrical transport process, and the temperature coefficient of resistance (TCR) showed an insulator-type behavior. The thermal fluctuation-induced tunneling conduction progressively increased with increasing temperature, which led to a decrease in the longitudinal resistivity. In a high temperature region, the TCR showed a metallic-type behavior, which was primarily attributed to the temperature-dependent scattering. Different from the longitudinal resistivity behavior, the saturated anomalous Hall resistivity increased monotonically with increasing measuring temperature. The value of the anomalous Hall coefficient ( R S ) reached 2.3 × 10-9 (Ω cm)/G at 300 K, which was about three orders of magnitude larger than previously reported in blocky single-crystal Co [E. N. Kondorskii, Sov. Phys. JETP 38, 977 (1974)]. Interestingly, the scaling relation ( ρx y A ∝ ρx x γ ) between saturated anomalous Hall resistivity ( ρx y A ) and longitudinal resistivity ( ρ x x ) was divided into two regions by T min . However, after excluding the contribution of tunneling, the scaling relation followed the same rule. The corresponding physical mechanism was also proposed to explain these phenomena.

  17. Iron-oxide colloidal nanoclusters: from fundamental physical properties to diagnosis and therapy

    Science.gov (United States)

    Kostopoulou, Athanasia; Brintakis, Konstantinos; Lascialfari, Alessandro; Angelakeris, Mavroeidis; Vasilakaki, Marianna; Trohidou, Kalliopi; Douvalis, Alexios P.; Psycharakis, Stylianos; Ranella, Anthi; Manna, Liberato; Lappas, Alexandros

    2014-03-01

    Research on magnetic nanocrystals attracts wide-spread interest because of their challenging fundamental properties, but it is also driven by problems of practical importance to the society, ranging from electronics (e.g. magnetic recording) to biomedicine. In that respect, iron oxides are model functional materials as they adopt a variety of oxidation states and coordinations that facilitate their use. We show that a promising way to engineer further their technological potential in diagnosis and therapy is the assembly of primary nanocrystals into larger colloidal entities, possibly with increased structural complexity. In this context, elevated-temperature nanochemistry (c.f. based on a polyol approach) permitted us to develop size-tunable, low-cytotoxicity iron-oxide nanoclusters, entailing iso-oriented nanocrystals, with enhanced magnetization. Experimental (magnetometry, electron microscopy, Mössbauer and NMR spectroscopies) results supported by Monte Carlo simulations are reviewed to show that such assemblies of surface-functionalized iron oxide nanocrystals have a strong potential for innovation. The clusters' optimized magnetic anisotropy (including microscopic surface spin disorder) and weak ferrimagnetism at room temperature, while they do not undermine colloidal stability, endow them a profound advantage as efficient MRI contrast agents and hyperthermic mediators with important biomedical potential.

  18. Cloning and characterization of the human integrin β6 gene promoter.

    Directory of Open Access Journals (Sweden)

    Mingyan Xu

    Full Text Available The integrin β6 (ITGB6 gene, which encodes the limiting subunit of the integrin αvβ6 heterodimer, plays an important role in wound healing and carcinogenesis. The mechanism underlying ITGB6 regulation, including the identification of DNA elements and cognate transcription factors responsible for basic transcription of human ITGB6 gene, remains unknown. This report describes the cloning and characterization of the human ITGB6 promoter. Using 5'-RACE (rapid amplification of cDNA ends analysis, the transcriptional initiation site was identified. Promoter deletion analysis identified and functionally validated a TATA box located in the region -24 to -18 base pairs upstream of the ITGB6 promoter. The regulatory elements for transcription of the ITGB6 gene were predominantly located -289 to -150 from the ITGB6 promoter and contained putative binding sites for transcription factors such as STAT3 and C/EBPα. Using chromatin immunoprecipitation assays, this study has demonstrated, for the first time, that transcription factors STAT3 and C/EBPα are involved in the positive regulation of ITGB6 transcription in oral squamous cell carcinoma cells. These findings have important implications for unraveling the mechanism of abnormal ITGB6 activation in tissue remodeling and tumorigenesis.

  19. Modulation of type II TGF-β receptor degradation by integrin-linked kinase.

    Science.gov (United States)

    Vi, Linda; Boo, Stellar; Sayedyahossein, Samar; Singh, Randeep K; McLean, Sarah; Di Guglielmo, Gianni M; Dagnino, Lina

    2015-03-01

    Cutaneous responses to injury, infection, and tumor formation involve the activation of resident dermal fibroblasts and subsequent transition to myofibroblasts. The key for induction of myofibroblast differentiation is the activation of transforming growth factor-β (TGF-β) receptors and stimulation of integrins and their associated proteins, including integrin-linked kinase (ILK). Cross-talk processes between TGF-β and ILK are crucial for myofibroblast formation, as ILK-deficient dermal fibroblasts exhibit impaired responses to TGF-β receptor stimulation. We now show that ILK associates with type II TGF-β receptors (TβRII) in ligand- and receptor kinase activity-independent manners. In cells with targeted Ilk gene inactivation, cellular levels of TβRII are decreased, through mechanisms that involve enhanced ubiquitination and proteasomal degradation. Partitioning of TGF-β receptors into membrane has been linked to proteasome-dependent receptor degradation. We found that interfering with membrane raft formation in ILK-deficient cells restored TβRII levels and signaling. These observations support a model whereby ILK functions in fibroblasts to direct TβRII away from degradative pathways during their differentiation into myofibroblasts.

  20. Isthmin exerts pro-survival and death-promoting effect on endothelial cells through alphavbeta5 integrin depending on its physical state.

    Science.gov (United States)

    Zhang, Y; Chen, M; Venugopal, S; Zhou, Y; Xiang, W; Li, Y-H; Lin, Q; Kini, R M; Chong, Y-S; Ge, R

    2011-05-05

    Isthmin (ISM) is a 60 kDa secreted-angiogenesis inhibitor that suppresses tumor growth in mouse and disrupts vessel patterning in zebrafish embryos. It selectively binds to alphavbeta5 (αvβ5) integrin on the surface of endothelial cells (ECs), but the mechanism of its antiangiogenic action remains unknown. In this work, we establish that soluble ISM suppresses in vitro angiogenesis and induces EC apoptosis by interacting with its cell surface receptor αvβ5 integrin through a novel 'RKD' motif localized within its adhesion-associated domain in MUC4 and other proteins domain. ISM induces EC apoptosis through integrin-mediated death (IMD) by direct recruitment and activation of caspase-8 without causing anoikis. On the other hand, immobilized ISM loses its antiangiogenic function and instead promotes EC adhesion, survival and migration through αvβ5 integrin by activating focal adhesion kinase (FAK). ISM unexpectedly has both a pro-survival and death-promoting effect on ECs depending on its physical state. This dual function of a single antiangiogenic protein may impact its antiangiogenic efficacy in vivo.

  1. Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

    Science.gov (United States)

    Lonsdorf, Anke S.; Krämer, Björn F.; Fahrleitner, Manuela; Schönberger, Tanja; Gnerlich, Stephan; Ring, Sabine; Gehring, Sarah; Schneider, Stefan W.; Kruhlak, Michael J.; Meuth, Sven G.; Nieswandt, Bernhard; Gawaz, Meinrad; Enk, Alexander H.; Langer, Harald F.

    2012-01-01

    A mutual relationship exists between metastasizing tumor cells and components of the coagulation cascade. The exact mechanisms as to how platelets influence blood-borne metastasis, however, remain poorly understood. Here, we used murine B16 melanoma cells to observe functional aspects of how platelets contribute to the process of hematogenous metastasis. We found that platelets interfere with a distinct step of the metastasis cascade, as they promote adhesion of melanoma cells to the endothelium in vitro under shear conditions. Constitutively active platelet receptor GPIIb/IIIa (integrin αIIbβ3) expressed on Chinese hamster ovary cells promoted melanoma cell adhesion in the presence of fibrinogen, whereas blocking antibodies to aνβ3 integrin on melanoma cells or to GPIIb/IIIa significantly reduced melanoma cell adhesion to platelets. Furthermore, using intravital microscopy, we observed functional platelet-melanoma cell interactions, as platelet depletion resulted in significantly reduced melanoma cell adhesion to the injured vascular wall in vivo. Using a mouse model of hematogenous metastasis to the lung, we observed decreased metastasis of B16 melanoma cells to the lung by treatment with a mAb blocking the aν subunit of aνβ3 integrin. This effect was significantly reduced when platelets were depleted in vivo. Thus, the engagement of GPIIb/IIIa with aνβ3 integrin interaction mediates tumor cell-platelet interactions and highlights how this interaction is involved in hematogenous tumor metastasis. PMID:22102277

  2. Hydrogen Sulfide Recruits Macrophage Migration by Integrin β1-Src-FAK/Pyk2-Rac Pathway in Myocardial Infarction

    Science.gov (United States)

    Miao, Lei; Xin, Xiaoming; Xin, Hong; Shen, Xiaoyan; Zhu, Yi-Zhun

    2016-03-01

    Myocardial infarction (MI) triggers an inflammatory reaction, in which macrophages are of key importance for tissue repairing. Infiltration and/or migration of macrophages into the infarct area early after MI is critical for infarct healing, vascularization, and cardiac function. Hydrogen sulfide (H2S) has been demonstrated to possess cardioprotective effects post MI and during the progress of cardiac remodeling. However, the specific molecular and cellular mechanisms involved in macrophage recruitment by H2S remain to be identified. In this study, the NaHS (exogenous sources of H2S) treatment exerted an increased infiltration of macrophages into the infarcted myocardium at early stage of MI cardiac tissues in both wild type (WT) and cystathionine-γ-lyase-knockout (CSE-KO) mice. And NaHS accelerated the migration of macrophage cells in vitro. While, the inhibitors not only significantly diminished the migratory ability in response to NaHS, but also blocked the activation of phospho-Src, -Pyk2, -FAK397, and -FAK925. Furthermore, NaHS induced the internalization of integrin β1 on macrophage surface, but, integrin β1 silencing inhibited macrophage migration and Src signaling activation. These results indicate that H2S may have the potential as an anti-infarct of MI by governing macrophage migration, which was achieved by accelerating internalization of integrin β1 and activating downstream Src-FAK/Pyk2-Rac pathway.

  3. Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo

    DEFF Research Database (Denmark)

    Grüner, Sabine; Prostredna, Miroslava; Schulte, Valerie

    2003-01-01

    by intravital fluorescence microscopy that platelet adhesion and thrombus growth on the exposed ECM of the injured carotid artery is not significantly altered in alpha2-null mice and even in mice with a Cre/loxP-mediated loss of all beta1 integrins on their platelets. In contrast, inhibition of alphaIIbbeta3...... integrin on platelets in wild-type mice blocked aggregate formation and reduced platelet adhesion by 60.0%. Strikingly, alphaIIbbeta3 inhibition had a comparable effect in alpha2-null mice, demonstrating that other receptors mediate shear-resistant adhesion in the absence of functional alpha2beta1...... and alphaIIbbeta3. These were identified to be alpha5beta1 and/or alpha6beta1 as alphaIIbbeta3 inhibition abrogated platelet adhesion in beta1-null mice. We conclude that shear-resistant platelet adhesion on the injured vessel wall in vivo is a highly integrated process involving multiple integrin...

  4. The Role of Integrin α6 (CD49f) in Stem Cells: More than a Conserved Biomarker.

    Science.gov (United States)

    Krebsbach, Paul H; Villa-Diaz, Luis G

    2017-08-01

    Stem cells have the capacity for self-renewal and differentiation into specialized cells that form and repopulated all tissues and organs, from conception to adult life. Depending on their capacity for differentiation, stem cells are classified as totipotent (ie, zygote), pluripotent (ie, embryonic stem cells), multipotent (ie, neuronal stem cells, hematopoietic stem cells, epithelial stem cells, etc.), and unipotent (ie, spermatogonial stem cells). Adult or tissue-specific stem cells reside in specific niches located in, or nearby, their organ or tissue of origin. There, they have microenvironmental support to remain quiescent, to proliferate as undifferentiated cells (self-renewal), and to differentiate into progenitors or terminally differentiated cells that migrate from the niche to perform specialized functions. The presence of proteins at the cell surface is often used to identify, classify, and isolate stem cells. Among the diverse groups of cell surface proteins used for these purposes, integrin α6, also known as CD49f, may be the only biomarker commonly found in more than 30 different populations of stem cells, including some cancer stem cells. This broad expression among stem cell populations indicates that integrin α6 may play an important and conserved role in stem cell biology, which is reaffirmed by recent demonstrations of its role maintaining self-renewal of pluripotent stem cells and breast and glioblastoma cancer stem cells. Therefore, this review intends to highlight and synthesize new findings on the importance of integrin α6 in stem cell biology.

  5. Alteration of Pituitary Tumor Transforming Gene-1 Regulates Trophoblast Invasion via the Integrin/Rho-Family Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Seung Mook Lim

    Full Text Available Trophoblast invasion ability is an important factor in early implantation and placental development. Recently, pituitary tumor transforming gene 1 (PTTG1 was shown to be involved in invasion and proliferation of cancer. However, the role of PTTG1 in trophoblast invasion remains unknown. Thus, in this study we analyzed PTTG1 expression in trophoblasts and its effect on trophoblast invasion activity and determined the mechanism through which PTTG1 regulates trophoblast invasion. Trophoblast proliferation and invasion abilities, regardless of PTTG1 expression, were analyzed by quantitative real-time polymerase chain reaction, fluorescence-activated cell sorting analysis, invasion assay, western blot, and zymography after treatment with small interfering RNA against PTTG1 (siPTTG1. Additionally, integrin/Rho-family signaling in trophoblasts by PTTG1 alteration was analyzed. Furthermore, the effect of PTTG1 on trophoblast invasion was evaluated by microRNA (miRNA mimic and inhibitor treatment. Trophoblast invasion was significantly reduced through decreased matrix metalloproteinase (MMP-2 and MMP-9 expression when PTTG1 expression was inhibited by siPTTG1 (p < 0.05. Furthermore, knockdown of PTTG1 increased expression of integrin alpha 4 (ITGA4, ITGA5, and integrin beta 1 (ITGB1; otherwise, RhoA expression was significantly decreased (p < 0.05. Treatment of miRNA-186-5p mimic and inhibitor controlled trophoblast invasion ability by altering PTTG1 and MMP expression. PTTG1 can control trophoblast invasion ability via regulation of MMP expression through integrin/Rho-family signaling. In addition, PTTG1 expression and its function were regulated by miRNA-186-5p. These results help in understanding the mechanism through which PTTG1 regulates trophoblast invasion and thereby implantation and placental development.

  6. 9-cis-retinoic Acid and troglitazone impacts cellular adhesion, proliferation, and integrin expression in K562 cells.

    Science.gov (United States)

    Hanson, Amanda M; Gambill, Jessica; Phomakay, Venusa; Staten, C Tyler; Kelley, Melissa D

    2014-01-01

    Retinoids are established pleiotropic regulators of both adaptive and innate immune responses. Recently, troglitazone, a PPAR gamma agonist, has been demonstrated to have anti-inflammatory effects. Separately, retinoids and troglitazone are implicated in immune related processes; however, their combinatory role in cellular adhesion and proliferation has not been well established. In this study, the effect of 9-cis-retinoic acid (9-cis-RA) and troglitazone on K562 cellular adhesion and proliferation was investigated. Troglitazone exposure decreased K562 cellular adhesion to RGD containing extracellular matrix proteins fibronectin, FN-120, and vitronectin in a concentration and time-dependent manner. In the presence of troglitazone, 9-cis-retinoic acid restores cellular adhesion to levels comparable to vehicle treatment alone on fibronectin, FN-120, and vitronectin substrates within 72 hours. Due to the prominent role of integrins in attachment to extracellular matrix proteins, we evaluated the level of integrin α5 subunit expression. Troglitazone treatment results in decrease in α5 subunit expression on the cell surface. In the presence of both agonists, cell surface α5 subunit expression was restored to levels comparable to vehicle treatment alone. Additionally, troglitazone and 9-cis-RA mediated cell adhesion was decreased in the presence of a function blocking integrin alpha 5 inhibitor. Further, through retinoid metabolic profiling and HPLC analysis, our study demonstrates that troglitazone augments retinoid availability in K562 cells. Finally, we demonstrate that troglitazone and 9-cis-retinoic acid synergistically dampen cellular proliferation in K562 cells. Our study is the first to report that the combination of troglitazone and 9-cis-retinoic acid restores cellular adhesion, alters retinoid availability, impacts integrin expression, and dampens cellular proliferation in K562 cells.

  7. Electrical transport properties in Fe-Cr nanocluster-assembled granular films

    Science.gov (United States)

    Wang, Xiong-Zhi; Wang, Lai-Sen; Zhang, Qin-Fu; Liu, Xiang; Xie, Jia; Su, A.-Mei; Zheng, Hong-Fei; Peng, Dong-Liang

    2017-09-01

    The Fe100-xCrx nanocluster-assembled granular films with Cr atomic fraction (x) ranging from 0 to 100 were fabricated by using a plasma-gas-condensation cluster deposition system. The TEM characterization revealed that the uniform Fe clusters were coated with a Cr layer to form a Fe-Cr core-shell structure. Then, the as-prepared Fe100-xCrx nanoclusters were randomly assembled into a granular film in vacuum environments with increasing the deposition time. Because of the competition between interfacial resistance and shunting effect of Cr layer, the room temperature resistivity of the Fe100-xCrx nanocluster-assembled granular films first increased and then decreased with increasing the Cr atomic fraction (x), and revealed a maximum of 2 × 104 μΩ cm at x = 26 at.%. The temperature-dependent longitudinal resistivity (ρxx), magnetoresistance (MR) effect and anomalous Hall effect (AHE) of these Fe100-xCrx nanocluster-assembled granular films were also studied systematically. As the x increased from 0 to 100, the ρxx of all samples firstly decreased and then increased with increasing the measuring temperature. The dependence of ρxx on temperature could be well addressed by a mechanism incorporated for the fluctuation-induced-tunneling (FIT) conduction process and temperature-dependent scattering effect. It was found that the anomalous Hall effect (AHE) had no legible scaling relation in Fe100-xCrx nanocluster-assembled granular films. However, after deducting the contribution of tunneling effect, the scaling relation was unambiguous. Additionally, the Fe100-xCrx nanocluster-assembled granular films revealed a small negative magnetoresistance (MR), which decreased with the increase of x. The detailed physical mechanism of the electrical transport properties in these Fe100-xCrx nanocluster-assembled granular films was also studied.

  8. A scalable synthesis of highly stable and water dispersible Ag 44(SR)30 nanoclusters

    KAUST Repository

    AbdulHalim, Lina G.; Ashraf, Sumaira; Katsiev, Khabiboulakh; Kirmani, Ahmad R.; Kothalawala, Nuwan; Anjum, Dalaver H.; Abbas, Sikandar Zameer; Amassian, Aram; Stellacci, Francesco; Dass, Amala; Hussain, Irshad; Bakr, Osman

    2013-01-01

    We report the synthesis of atomically monodisperse thiol-protected silver nanoclusters [Ag44(SR)30] m, (SR = 5-mercapto-2-nitrobenzoic acid) in which the product nanocluster is highly stable in contrast to previous preparation methods. The method is one-pot, scalable, and produces nanoclusters that are stable in aqueous solution for at least 9 months at room temperature under ambient conditions, with very little degradation to their unique UV-Vis optical absorption spectrum. The composition, size, and monodispersity were determined by electrospray ionization mass spectrometry and analytical ultracentrifugation. The produced nanoclusters are likely to be in a superatom charge-state of m = 4-, due to the fact that their optical absorption spectrum shares most of the unique features of the intense and broadly absorbing nanoparticles identified as [Ag44(SR) 30]4- by Harkness et al. (Nanoscale, 2012, 4, 4269). A protocol to transfer the nanoclusters to organic solvents is also described. Using the disperse nanoclusters in organic media, we fabricated solid-state films of [Ag44(SR)30]m that retained all the distinct features of the optical absorption spectrum of the nanoclusters in solution. The films were studied by X-ray diffraction and photoelectron spectroscopy in order to investigate their crystallinity, atomic composition and valence band structure. The stability, scalability, and the film fabrication method demonstrated in this work pave the way towards the crystallization of [Ag44(SR)30]m and its full structural determination by single crystal X-ray diffraction. Moreover, due to their unique and attractive optical properties with multiple optical transitions, we anticipate these clusters to find practical applications in light-harvesting, such as photovoltaics and photocatalysis, which have been hindered so far by the instability of previous generations of the cluster. © 2013 The Royal Society of Chemistry.

  9. Role of Integrin-Beta1 in Polycystic Kidney Disease

    Science.gov (United States)

    2012-04-01

    interactions affect proliferation and cell differentiation2. We previously showed an increase of integrin-!2ŕ expression in polycystin-1 (PC1) deficient...that since the Cre activity in TgAqp2-Cre transgenic mouse was observed also in testes, our breeding scheme was devised to ensure maternal ...inheritance of the transgene, as paternal transmission would lead to gene recombination not only in the kidneys, but also in sperm and the resulting

  10. Synthesis of biocompatible AuAgS/Ag2S nanoclusters and their applications in photocatalysis and mercury detection

    International Nuclear Information System (INIS)

    Zhao, Qian; Chen, Shenna; Zhang, Lingyang; Huang, Haowen; Liu, Fengping; Liu, Xuanyong

    2014-01-01

    In this paper, a facile approach for preparation of AuAgS/Ag 2 S nanoclusters was developed. The unique AuAgS/Ag 2 S nanoclusters capped with biomolecules exhibit interesting excellent optical and catalytic properties. The fluorescent AuAgS/Ag 2 S nanoclusters show tunable luminescence depending on the nanocluster size. The apoptosis assay demonstrated that the AuAgS/Ag 2 S nanoclusters showed low cytotoxicity and good biocompatibility. Therefore, the nanoclusters can be used not only as a probe for labeling cells but also for their photocatalytic activity for photodegradation of organic dye. Moreover, a highly selective and sensitive assay for detection of mercury including Hg 2+ and undissociated mercury complexes was developed based on the quenching fluorescent AuAgS/Ag 2 S nanoclusters, which provides a promising approach for determining various forms of Hg in the mercury-based compounds in environment. These unique nanoclusters may have potential applications in biological labeling, sensing mercury, and photodegradation of various organic pollutants in waste water.Graphical Abstract

  11. Integrin αβ3-Targeted Imaging of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoyuan Chen

    2005-03-01

    Full Text Available A series of radiolabeled cyclic arginine-glycineaspartic acid (RGD peptide ligands for cell adhesion molecule integrin αβ3-targeted tumor angiogenesis targeting are being developed in our laboratory. In this study, this effort continues by applying a positron emitter 64Cu-labeled PEGylated dimeric RGD peptide radiotracer 64Cu-DOTA-PEG-E[c(RGDyK]2 for lung cancer imaging. The PEGylated RGD peptide indicated integrin αβ3 avidity, but the PEGylation reduced the receptor binding affinity of this ligand compared to the unmodified RGD dimer. The radiotracer revealed rapid blood clearance and predominant renal clearance route. The minimum nonspecific activity accumulation in normal lung tissue and heart rendered high-quality orthotopic lung cancer tumor images, enabling clear demarcation of both the primary tumor at the upper lobe of the left lung, as well as metastases in the mediastinum, contralateral lung, diaphragm. As a comparison, fluorodeoxyglucose (FDG scans on the same mice were only able to identify the primary tumor, with the metastatic lesions masked by intense cardiac uptake and high lung background. 64Cu-DOTA-PEGE[c(RGDyK]2 is an excellent positron emission tomography (PET tracer for integrin-positive tumor imaging. Further studies to improve the receptor binding affinity of the tracer and subsequently to increase the magnitude of tumor uptake without comprising the favorable in vivo kinetics are currently in progress.

  12. Sensitive detection of alkaline phosphatase by switching on gold nanoclusters fluorescence quenched by pyridoxal phosphate.

    Science.gov (United States)

    Halawa, Mohamed Ibrahim; Gao, Wenyue; Saqib, Muhammad; Kitte, Shimeles Addisu; Wu, Fengxia; Xu, Guobao

    2017-09-15

    In this work, we designed highly sensitive and selective luminescent detection method for alkaline phosphatase using bovine serum albumin functionalized gold nanoclusters (BSA-AuNCs) as the nanosensor probe and pyridoxal phosphate as the substrate of alkaline phosphatase. We found that pyridoxal phosphate can quench the fluorescence of BSA-AuNCs and pyridoxal has little effect on the fluorescence of BSA-AuNCs. The proposed mechanism of fluorescence quenching by PLP was explored on the basis of data obtained from high-resolution transmission electron microscopy (HRTEM), dynamic light scattering (DLS), UV-vis spectrophotometry, fluorescence spectroscopy, fluorescence decay time measurements and circular dichroism (CD) spectroscopy. Alkaline phosphatase catalyzes the hydrolysis of pyridoxal phosphate to generate pyridoxal, restoring the fluorescence of BSA-AuNCs. Therefore, a recovery type approach has been developed for the sensitive detection of alkaline phosphatase in the range of 1.0-200.0U/L (R 2 =0.995) with a detection limit of 0.05U/L. The proposed sensor exhibit excellent selectivity among various enzymes, such as glucose oxidase, lysozyme, trypsin, papain, and pepsin. The present switch-on fluorescence sensing strategy for alkaline phosphatase was successfully applied in human serum plasma with good recoveries (100.60-104.46%), revealing that this nanosensor probe is a promising tool for ALP detection. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Preparation and Characterization of Chitosan/Soy Protein Isolate Nanocomposite Film Reinforced by Cu Nanoclusters

    Directory of Open Access Journals (Sweden)

    Kuang Li

    2017-06-01

    Full Text Available Soy protein isolate (SPI based films have received considerable attention for use in packaging materials. However, SPI-based films exhibit relatively poor mechanical properties and water resistance ability. To tackle these challenges, chitosan (CS and endogenous Cu nanoclusters (NCs capped with protein were proposed and designed to modify SPI-based films. Attenuated total reflectance-Fourier transform infrared spectroscopy and X-ray diffraction patterns of composite films demonstrated that interactions, such as hydrogen bonds in the film forming process, promoted the cross-linking of composite films. The surface microstructure of CS/SPI films modified with Cu NCs was more uniform and transmission electron microscopy (TEM showed that uniform and discrete clusters were formed. Compared with untreated SPI films, the tensile strength and elongation at break of composite films were simultaneously improved by 118.78% and 74.93%, respectively. Moreover, these composite films also exhibited higher water contact angle and degradation temperature than that of pure SPI film. The water vapor permeation of the modified film also decreased. These improved properties of functional bio-polymers show great potential as food packaging materials.

  14. Na-ion batteries based on the inorganic BN nanocluster anodes: DFT studies.

    Science.gov (United States)

    Nejati, K; Hosseinian, A; Bekhradnia, A; Vessally, E; Edjlali, L

    2017-06-01

    It has been recently indicated that the Li-ion batteries may be replaced by Na-ion batteries because of their low safety, high cost, and low-temperature performance, and lack of the Li mineral reserves. Here, using density functional theory calculations, we studied the potential application of B 12 N 12 nanoclusters as anode in Na-ion batteries. Our calculations indicate that the adsorption energy of Na + and Na are about -23.4 and -1.4kcal/mol, respectively, and the pristine BN cage to improve suffers from a low cell voltage (∼0.92V) as an anode in Na-ion batteries. We presented a strategy to increase the cell voltage and performance of Na-ion batteries. We showed that encapsulation of different halides (X=F - , Cl - , or Br - ) into BN cage significantly increases the cell voltage. By increasing the atomic number of X, the Gibbs free energy change of cell becomes more negative and the cell voltage is increased up to 3.93V. The results are discussed based on the structural, energetic, frontier molecular orbital, charge transfer and electronic properties and compared with the performance of other nanostructured anodes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Search Directions for Direct H2O2 Synthesis Catalysts Starting from Au-12 Nanoclusters

    DEFF Research Database (Denmark)

    Grabow, Lars; Larsen, Britt Hvolbæk; Falsig, Hanne

    2012-01-01

    that the rate of H2O2 and H2O formation can be determined from a single descriptor, namely, the binding energy of oxygen (E-O). Our model predicts the search direction starting from an Au-12 nanocluster for an optimal catalyst in terms of activity and selectivity for direct H2O2 synthesis. Taking also stability......We present density functional theory calculations on the direct synthesis of H2O2 from H-2 and O-2 over an Au-12 corner model of a gold nanoparticle. We first show a simple route for the direct formation of H2O2 over a gold nanocatalyst, by studying the energetics of 20 possible elementary...... reactions involved in the oxidation of H-2 by O-2. The unwanted side reaction to H2O is also considered. Next we evaluate the degree of catalyst control and address the factors controlling the activity and the selectivity. By combining well-known energy scaling relations with microkinetic modeling, we show...

  16. Experimental determination of the energy difference between competing isomers of deposited, size-selected gold nanoclusters.

    Science.gov (United States)

    Foster, D M; Ferrando, R; Palmer, R E

    2018-04-03

    The equilibrium structures and dynamics of a nanoscale system are regulated by a complex potential energy surface (PES). This is a key target of theoretical calculations but experimentally elusive. We report the measurement of a key PES parameter for a model nanosystem: size-selected Au nanoclusters, soft-landed on amorphous silicon nitride supports. We obtain the energy difference between the most abundant structural isomers of magic number Au 561 clusters, the decahedron and face-centred-cubic (fcc) structures, from the equilibrium proportions of the isomers. These are measured by atomic-resolution scanning transmission electron microscopy, with an ultra-stable heating stage, as a function of temperature (125-500 °C). At lower temperatures (20-125 °C) the behaviour is kinetic, exhibiting down conversion of metastable decahedra into fcc structures; the higher state is repopulated at higher temperatures in equilibrium. We find the decahedron is 0.040 ± 0.020 eV higher in energy than the fcc isomer, providing a benchmark for the theoretical treatment of nanoparticles.

  17. An Atomically Precise Au10 Ag2 Nanocluster with Red-Near-IR Dual Emission.

    Science.gov (United States)

    Lei, Zhen; Guan, Zong-Jie; Pei, Xiao-Li; Yuan, Shang-Fu; Wan, Xian-Kai; Zhang, Jin-Yuan; Wang, Quan-Ming

    2016-08-01

    A red-near-IR dual-emissive nanocluster with the composition [Au10 Ag2 (2-py-C≡C)3 (dppy)6 ](BF4 )5 (1; 2-py-C≡C is 2-pyridylethynyl, dppy=2-pyridyldiphenylphosphine) has been synthesized. Single-crystal X-ray structural analysis reveals that 1 has a trigonal bipyramidal Au10 Ag2 core that contains a planar Au4 (2-py-C≡C)3 unit sandwiched by two Au3 Ag(dppy)3 motifs. Cluster 1 shows intense red-NIR dual emission in solution. The visible emission originates from metal-to-ligand charge transfer (MLCT) from silver atoms to phosphine ligands in the Au3 Ag(dppy)3 motifs, and the intense NIR emission is associated with the participation of 2-pyridylethynyl in the frontier orbitals of the cluster, which is confirmed by a time-dependent density functional theory (TD-DFT) calculation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Engineering ultrasmall water-soluble gold and silver nanoclusters for biomedical applications.

    Science.gov (United States)

    Luo, Zhentao; Zheng, Kaiyuan; Xie, Jianping

    2014-05-25

    Gold and silver nanoclusters or Au/Ag NCs with core sizes smaller than 2 nm have been an attractive frontier of nanoparticle research because of their unique physicochemical properties such as well-defined molecular structure, discrete electronic transitions, quantized charging, and strong luminescence. As a result of these unique properties, ultrasmall size, and good biocompatibility, Au/Ag NCs have great potential for a variety of biomedical applications, such as bioimaging, biosensing, antimicrobial agents, and cancer therapy. In this feature article, we will first discuss some critical biological considerations, such as biocompatibility and renal clearance, of Au/Ag NCs that are applied for biomedical applications, leading to some design criteria for functional Au/Ag NCs in the biological settings. According to these biological considerations, we will then survey some efficient synthetic strategies for the preparation of protein- and peptide-protected Au/Ag NCs with an emphasis on our recent contributions in this fast-growing field. In the last part, we will highlight some potential biomedical applications of these protein- and peptide-protected Au/Ag NCs. It is believed that with continued efforts to understand the interactions of biomolecule-protected Au/Ag NCs with the biological systems, scientists can largely realize the great potential of Au/Ag NCs for biomedical applications, which could finally pave their way towards clinical use.

  19. Comparative Analysis of Particle Swarm and Differential Evolution via Tuning on Ultrasmall Titanium Oxide Nanoclusters

    Science.gov (United States)

    Inclan, Eric; Lassester, Jack; Geohegan, David; Yoon, Mina

    Optimization algorithms (OA) coupled with numerical methods enable researchers to identify and study (meta) stable nanoclusters without the control restrictions of empirical methods. An algorithm's performance is governed by two factors: (1) its compatibility with an objective function, (2) the dimension of a design space, which increases with cluster size. Although researchers often tune an algorithm's user-defined parameters (UDP), tuning is not guaranteed to improve performance. In this research, Particle Swarm (PSO) and Differential Evolution (DE), are compared by tuning their UDP in a multi-objective optimization environment (MOE). Combined with a Kolmogorov Smirnov test for statistical significance, the MOE enables the study of the Pareto Front (PF), made of the UDP settings that trade-off between best performance in energy minimization (``effectiveness'') based on force-field potential energy, and best convergence rate (``efficiency''). By studying the PF, this research finds that UDP values frequently suggested in the literature do not provide best effectiveness for these methods. Additionally, monotonic convergence is found to significantly improve efficiency without sacrificing effectiveness for very small systems, suggesting better compatibility. Work is supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Materials Sciences and Engineering Division.

  20. Spherical harmonics based descriptor for neural network potentials: Structure and dynamics of Au147 nanocluster.

    Science.gov (United States)

    Jindal, Shweta; Chiriki, Siva; Bulusu, Satya S

    2017-05-28

    We propose a highly efficient method for fitting the potential energy surface of a nanocluster using a spherical harmonics based descriptor integrated with an artificial neural network. Our method achieves the accuracy of quantum mechanics and speed of empirical potentials. For large sized gold clusters (Au 147 ), the computational time for accurate calculation of energy and forces is about 1.7 s, which is faster by several orders of magnitude compared to density functional theory (DFT). This method is used to perform the global minimum optimizations and molecular dynamics simulations for Au 147 , and it is found that its global minimum is not an icosahedron. The isomer that can be regarded as the global minimum is found to be 4 eV lower in energy than the icosahedron and is confirmed from DFT. The geometry of the obtained global minimum contains 105 atoms on the surface and 42 atoms in the core. A brief study on the fluxionality in Au 147 is performed, and it is concluded that Au 147 has a dynamic surface, thus opening a new window for studying its reaction dynamics.

  1. Biomimetic Mineralization of Gold Nanoclusters as Multifunctional Thin Films for Glass Nanopore Modification, Characterization, and Sensing.

    Science.gov (United States)

    Cao, Sumei; Ding, Shushu; Liu, Yingzi; Zhu, Anwei; Shi, Guoyue

    2017-08-01

    Hurdles of nanopore modification and characterization restrain the development of glass capillary-based nanopore sensing platforms. In this article, a simple but effective biomimetic mineralization method was developed to decorate glass nanopore with a thin film of bovine serum albumin-protected Au nanocluster (BSA-Au NC). The BSA-Au NC film emitted a strong red fluorescence whereby nondestructive characterization of Au film decorated at the inner surface of glass nanopore can be facilely achieved by a fluorescence microscopy. Besides, the BSA molecules played dual roles in the fabrication of functionalized Au thin film in glass nanopore: they not only directed the synthesis of fluorescent Au thin film but also provided binding sites for recognition, thus achieving synthesis-modification integration. This occurred due to the ionized carboxyl groups (-COO - ) of a BSA coating layer on Au NCs which can interacted with arginine (Arg) via guanidinium groups. The added Arg selectively led to the change in the charge and ionic current of BSA-Au NC film-decorated glass nanopore. Such ionic current responses can be used for quantifying Arg with a detection limit down to 1 fM, which was more sensitive than that of previous sensing systems. Together, the designed method exhibited great promise in providing a facile and controllable solution for glass nanopore modification, characterization, and sensing.

  2. Synthesis of indium nanoclusters and formation of thin film contacts on plastic substrates for organic and flexible electronics applications

    International Nuclear Information System (INIS)

    Shi, Frank F; Bulkowski, Michal; Hsieh, K C

    2007-01-01

    In this work, we described the processes of synthesizing free-standing indium nanoclusters using inverse micelles and microemulsions as well as synthesizing organic-encapsulated indium nanoclusters using alkanethiols as the organic encapsulants. The synthesized organic-encapsulated indium nanoclusters have demonstrated the feasibilities to be used as plastic compatible soft metal contacts for emerging organic devices. The homogeneously distributed indium nanoclusters with sizes of 10-30 nm have been fabricated on a few different plastic substrates. By changing the alkanethiol carbon chain length and the sizes of the indium nanoclusters, the annealing temperature required to form low-resistance indium thin film conductors has been reduced to 80-100 deg. C, which is acceptable for a variety of organic thin films

  3. The Integrin-Regulated Kinase PYK-2: A Therapeutic Target for Prostate Cancer

    National Research Council Canada - National Science Library

    Edlund, Magnus

    2001-01-01

    ...) . A number of promising therapeutic targets for androgen-independent and metastatic prostate cancers are contained within the signaling cascades downstream of the ECM-binding Integrin molecules...

  4. Selective Modulation of Integrin-mediated Cell Migration by Distinct ADAM Family MembersV⃞

    Science.gov (United States)

    Huang, Jing; Bridges, Lance C.; White, Judith M.

    2005-01-01

    A disintegrin and a metalloprotease (ADAM) family members have been implicated in many biological processes. Although it is recognized that recombinant ADAM disintegrin domains can interact with integrins, little is known about ADAM-integrin interactions in cellular context. Here, we tested whether ADAMs can selectively regulate integrin-mediated cell migration. ADAMs were expressed in Chinese hamster ovary cells that express defined integrins (α4β1, α5β1, or both), and cell migration on full-length fibronectin or on its α4β1 or α5β1 binding fragments was studied. We found that ADAMs inhibit integrin-mediated cell migration in patterns dictated by the integrin binding profiles of their isolated disintegrin domains. ADAM12 inhibited cell migration mediated by the α4β1 but not the α5β1 integrin. ADAM17 had the reciprocal effect; it inhibited α5β1- but not α4β1-mediated cell migration. ADAM19 and ADAM33 inhibited migration mediated by both α4β1 and α5β1 integrins. A point mutation in the ADAM12 disintegrin loop partially reduced the inhibitory effect of ADAM12 on cell migration on the α4β1 binding fragment of fibronectin, whereas mutations that block metalloprotease activity had no effect. Our results indicate that distinct ADAMs can modulate cell migration mediated by specific integrins in a pattern dictated, at least in part, by their disintegrin domains. PMID:16079176

  5. Real-time transmission electron microscope observation of gold nanoclusters diffusing into silicon at room temperature

    International Nuclear Information System (INIS)

    Ishida, Tadashi; Nakajima, Yuuki; Fujita, Hiroyuki; Endo, Junji; Collard, Dominique

    2009-01-01

    Gold diffusion into silicon at room temperature was observed in real time with atomic resolution. Gold nanoclusters were formed on a silicon surface by an electrical discharge between a silicon tip and a gold coated tip inside an ultrahigh-vacuum transmission electron microscope (TEM) specimen chamber. At the moment of the gold nanocluster deposition, the gold nanoclusters had a crystalline structure. The crystalline structure gradually disappeared due to the interdiffusion between silicon and gold as observed after the deposition of gold nanoclusters. The shape of the nanocluster gradually changed due to the gold diffusion into the damaged silicon. The diffusion front between silicon and gold moved toward the silicon side. From the observations of the diffusion front, the gold diffusivity at room temperature was extracted. The extracted activation energy, 0.21 eV, matched the activation energy in bulk diffusion between damaged silicon and gold. This information is useful for optimizing the hybridization between solid-state and biological nanodevices in which gold is used as an adhesive layer between the two devices.

  6. Self-trapping nature of Tl nanoclusters on the Si(111)-7x7 surface

    International Nuclear Information System (INIS)

    Hwang, C G; Kim, N D; Lee, G; Shin, S Y; Kim, J S; Chung, J W

    2008-01-01

    We have studied properties of thallium (Tl) nanoclusters formed on the Si(111)-7x7 surface at room temperature (RT) by utilizing photoemission spectroscopy (PES) and high-resolution electron-energy-loss spectroscopy (HREELS) combined with first principles calculations. Our PES data reveal that the surface states stemming from the Si substrate remain quite inert with Tl adsorption producing no Tl-induced state until saturation at Tl coverage θ=0.21 monolayers. Such a behavior, in sharp contrast with the extremely reactive surface states upon the formation of Na or Li nanoclusters, together with the presence of a unique Tl-induced loss peak in HREELS spectra suggests no strong Si-Tl bonding, and is well understood in terms of gradual filling of Si dangling bonds with increasing θ. Our calculation further indicates the presence of several metastable atomic structures of Tl nanoclusters at RT rapidly transforming from one to another faster than 10 10 flippings per second. We thus conclude that the highly mobile Tl atoms form self-trapped nanoclusters within the attractive basins of the Si substrate at RT with several metastable phases. The mobile and multi-phased nature of Tl nanoclusters not only accounts for all the existing experimental observations available at present, but also provides an example of self-trapping of atoms in a nanometre-scale region

  7. Synthesis and Optical Properties of Au-Ag Alloy Nanoclusters with Controlled Composition

    Directory of Open Access Journals (Sweden)

    J. F. Sánchez-Ramírez

    2008-01-01

    Full Text Available Colloidal solid-solution-like Au-Ag alloy nanoclusters of different compositions were synthesized through citrate reduction of mixed metal ions of low concentrations, without using any other protective or capping agents. Optical absorption of the alloy nanoclusters was studied both theoretically and experimentally. The position of the surface plasmon resonance (SPR absorption band of the nanoclusters could be tuned from 419 nm to 521 nm through the variation of their composition. Considering effective dielectric constant of the alloy, optical absorption spectra for the nanoclusters were calculated using Mie theory, and compared with the experimentally obtained spectra. Theoretically obtained optical spectra well resembled the experimental spectra when the true size distribution of the nanoparticles was considered. High-resolution transmission electron microscopy (HREM, high-angle annular dark field (HAADF imaging, and energy dispersive spectroscopy (EDS revealed the true alloy nature of the nanoparticles with nominal composition being preserved. The synthesis technique can be extended to other bimetallic alloy nanoclusters containing Ag.

  8. Caveolin 3-mediated integrin β1 signaling is required for the proliferation of folliculostellate cells in rat anterior pituitary gland under the influence of extracellular matrix.

    Science.gov (United States)

    Horiguchi, Kotaro; Fujiwara, Ken; Ilmiawati, Cimi; Kikuchi, Motoshi; Tsukada, Takehiro; Kouki, Tom; Yashiro, Takashi

    2011-07-01

    Folliculostellate (FS) cells in the anterior pituitary gland are believed to have multifunctional properties. Using transgenic rats that express green fluorescent protein (GFP) specifically in FS cells in the anterior pituitary gland (S100b-GFP rats), we recently revealed that FS cells in primary culture exhibited marked proliferation in the presence of laminin, an extracellular matrix (ECM) component of the basement membrane. In a process referred to as matricrine action, FS cells receive ECM as a signal through their receptors, which results in morphological and functional changes. In this study, we investigated matricrine signaling in FS cells and observed that the proliferation of FS cells is mediated by integrin β1, which is involved in various signaling pathways for cell migration and proliferation in response to ECM. Then, we analyzed downstream events of the integrin β1 signaling pathway in the proliferation of FS cells and identified caveolin 3 as a potential candidate molecule. Caveolin 3 is a membrane protein that binds cholesterol and a number of signaling molecules that interact with integrin β1. Using specific small interfering RNA of caveolin 3, the proliferation of FS cells was inhibited. Furthermore, caveolin 3 drove activation of the mitogen-activated protein kinase (MAPK) signaling cascades, which resulted in upregulation of cyclin D1 in FS cells. These findings suggest that matricrine signaling in the proliferation of FS cells was transduced by a caveolin 3-mediated integrin β1 signaling pathway and subsequent activation of the MAPK pathway. © 2011 Society for Endocrinology

  9. Human U87 astrocytoma cell invasion induced by interaction of βig-h3 with integrin α5β1 involves calpain-2.

    Directory of Open Access Journals (Sweden)

    Jie Ma

    Full Text Available It is known that βig-h3 is involved in the invasive process of many types of tumors, but its mechanism in glioma cells has not been fully clarified. Using immunofluorescent double-staining and confocal imaging analysis, and co-immunoprecipitation assays, we found that βig-h3 co-localized with integrin α5β1 in U87 cells. We sought to elucidate the function of this interaction by performing cell invasion assays and gelatin zymography experiments. We found that siRNA knockdowns of βig-h3 and calpain-2 impaired cell invasion and MMP secretion. Moreover, βig-h3, integrins and calpain-2 are known to be regulated by Ca(2+, and they are also involved in tumor cell invasion. Therefore, we further investigated if calpain-2 was relevant to βig-h3-integrin α5β1 interaction to affect U87 cell invasion. Our data showed that βig-h3 co-localized with integrin α5β1 to enhance the invasion of U87 cells, and that calpain-2, is involved in this process, acting as a downstream molecule.

  10. Dwarfism in Mice Lacking Collagen-binding Integrins α2β1 and α11β1 Is Caused by Severely Diminished IGF-1 Levels*

    Science.gov (United States)

    Blumbach, Katrin; Niehoff, Anja; Belgardt, Bengt F.; Ehlen, Harald W. A.; Schmitz, Markus; Hallinger, Ralf; Schulz, Jan-Niklas; Brüning, Jens C.; Krieg, Thomas; Schubert, Markus; Gullberg, Donald; Eckes, Beate

    2012-01-01

    Mice with a combined deficiency in the α2β1 and α11β1 integrins lack the major receptors for collagen I. These mutants are born with inconspicuous differences in size but develop dwarfism within the first 4 weeks of life. Dwarfism correlates with shorter, less mineralized and functionally weaker bones that do not result from growth plate abnormalities or osteoblast dysfunction. Besides skeletal dwarfism, internal organs are correspondingly smaller, indicating proportional dwarfism and suggesting a systemic cause for the overall size reduction. In accordance with a critical role of insulin-like growth factor (IGF)-1 in growth control and bone mineralization, circulating IGF-1 levels in the sera of mice lacking either α2β1 or α11β1 or both integrins were sharply reduced by 39%, 64%, or 81% of normal levels, respectively. Low hepatic IGF-1 production resulted from diminished growth hormone-releasing hormone expression in the hypothalamus and, subsequently, reduced growth hormone expression in the pituitary glands of these mice. These findings point out a novel role of collagen-binding integrin receptors in the control of growth hormone/IGF-1-dependent biological activities. Thus, coupling hormone secretion to extracellular matrix signaling via integrins represents a novel concept in the control of endocrine homeostasis. PMID:22210772

  11. Dwarfism in mice lacking collagen-binding integrins α2β1 and α11β1 is caused by severely diminished IGF-1 levels.

    Science.gov (United States)

    Blumbach, Katrin; Niehoff, Anja; Belgardt, Bengt F; Ehlen, Harald W A; Schmitz, Markus; Hallinger, Ralf; Schulz, Jan-Niklas; Brüning, Jens C; Krieg, Thomas; Schubert, Markus; Gullberg, Donald; Eckes, Beate

    2012-02-24

    Mice with a combined deficiency in the α2β1 and α11β1 integrins lack the major receptors for collagen I. These mutants are born with inconspicuous differences in size but develop dwarfism within the first 4 weeks of life. Dwarfism correlates with shorter, less mineralized and functionally weaker bones that do not result from growth plate abnormalities or osteoblast dysfunction. Besides skeletal dwarfism, internal organs are correspondingly smaller, indicating proportional dwarfism and suggesting a systemic cause for the overall size reduction. In accordance with a critical role of insulin-like growth factor (IGF)-1 in growth control and bone mineralization, circulating IGF-1 levels in the sera of mice lacking either α2β1 or α11β1 or both integrins were sharply reduced by 39%, 64%, or 81% of normal levels, respectively. Low hepatic IGF-1 production resulted from diminished growth hormone-releasing hormone expression in the hypothalamus and, subsequently, reduced growth hormone expression in the pituitary glands of these mice. These findings point out a novel role of collagen-binding integrin receptors in the control of growth hormone/IGF-1-dependent biological activities. Thus, coupling hormone secretion to extracellular matrix signaling via integrins represents a novel concept in the control of endocrine homeostasis.

  12. High Affinity vs. Native Fibronectin in the Modulation of αvβ3 Integrin Conformational Dynamics: Insights from Computational Analyses and Implications for Molecular Design.

    Directory of Open Access Journals (Sweden)

    Antonella Paladino

    2017-01-01

    Full Text Available Understanding how binding events modulate functional motions of multidomain proteins is a major issue in chemical biology. We address several aspects of this problem by analyzing the differential dynamics of αvβ3 integrin bound to wild type (wtFN10, agonist or high affinity (hFN10, antagonist mutants of fibronectin. We compare the dynamics of complexes from large-scale domain motions to inter-residue coordinated fluctuations to characterize the distinctive traits of conformational evolution and shed light on the determinants of differential αvβ3 activation induced by different FN sequences. We propose an allosteric model for ligand-based integrin modulation: the conserved integrin binding pocket anchors the ligand, while different residues on the two FN10's act as the drivers that reorganize relevant interaction networks, guiding the shift towards inactive (hFN10-bound or active states (wtFN10-bound. We discuss the implications of results for the design of integrin inhibitors.

  13. The journey of integrins and partners in a complex interactions landscape studied by super-resolution microscopy and single protein tracking.

    Science.gov (United States)

    Rossier, Olivier; Giannone, Grégory

    2016-04-10

    Cells adjust their adhesive and cytoskeletal organizations according to changes in the biochemical and physical nature of their surroundings. In return, by adhering and generating forces on the extracellular matrix (ECM) cells organize their microenvironment. Integrin-dependent focal adhesions (FAs) are the converging zones integrating biochemical and biomechanical signals arising from the ECM and the actin cytoskeleton. Thus, integrin-mediated adhesion and mechanotransduction, the conversion of mechanical forces into biochemical signals, are involved in critical cellular functions such as migration, proliferation and differentiation, and their deregulation contributes to pathologies including cancer. A challenging problem is to decipher how stochastic protein movements and interactions lead to formation of dynamic architecture such as integrin-dependent adhesive structures. In this review, we will describe recent advances made possible by super-resolution microscopies and single molecule tracking approaches that provided new understanding on the organization and the dynamics of integrins and intracellular regulators at the nanoscale in living cells. Copyright © 2015. Published by Elsevier Inc.

  14. Integrin inhibitor (Cilengitide) as radiosensitization strategy for malignant tumors

    International Nuclear Information System (INIS)

    Silva, Felipe Henrique de Souza

    2017-01-01

    Radiotherapy is effective in tumor control, but several tumors have molecular characteristics that lead to radioresistance and possible posttreatment recurrence. Many tumors have overexpression of integrin receptors. Integrins play a central role in growth, motility, regulation of adhesion and survival, leading to increased proliferation, invasion and metastasis of tumors, making these receptors excellent targets for the development of new therapies. Studies have shown that inhibiting the interaction of matrix proteins with integrin receptors may increase the cytotoxic effect of ionizing radiation by demonstrating the radiosensitizing potential of combination therapy in tumoral lines. Cilengitide an inhibitor of integrins receptors α Vβ3 and αVβ5 stands out for its great antitumor potential against gliomas. Thus, the combination of ionizing radiation with cilengitide is an alternative therapeutic strategy. However, the effect of this combination is little studied in Glioblastomas (U87 and T98) and not studied in melanoma (UACC). The objective of this study was to evaluate the radiosensitising potential of the RGD molecule cilengitida by means of the combined treatment with gamma radiation in different tumor lines, as well as to compare the effect of this combination therapy with cisplatin, a molecule already used in clinical practice. Our panel of tumor cell lines was composed of U87 (wild-type p53 malignant glioblastoma) T98 (malignant glioblastoma mutant p53), MCF7 (mammary carcinoma) and UACC (melanoma). The radiosensitizer effect of cilengitide was evaluated by the quantification of metabolic cell viability through the MTT assay. Inhibition of colony formation was investigated in clonogenicity assays. The flow cytometer was used to investigate cell cycle distribution and the type of cell death induced. We observed that in all cell lines examined, cilengitida promoted detachment, metabolic alterations and reduction of proliferation, as well as alteration of

  15. Nanocrystals and Nanoclusters as Cocatalysts for Photocatalytic Water Splitting

    KAUST Repository

    Sinatra, Lutfan

    2016-12-04

    studied for the photocatalytic H2 production in order to explore the synergistic effect of the plasmonic resonance from the Au nanoparticles and pn-junction between Cu2O and TiO2. Additionally, the plasmonic effect of the Au films was also studied and utilized in order to improve the PWS. Secondly, the nanoscaling of cocatalysts was studied in order to improve the efficiency thereof and to reduce the cost of the cocatalyst materials. Moreover, it is sought to explore the quantum size effect on the properties of the cocatalyst and their effect on the photocatalytic reaction. Atomically precise Au and Ni nanoclusters were employed in these studies. Au nanoclusters were studied in relation to the cocatalysts in the photocatalytic water splitting, and Ni nanoclusters were studied in relation to the cocatalysts in the electrocatalytic water oxidation. The results of these studies will provide new insights in relation to the strategy used in order to develop efficient cocatalysts for the purpose of photocatalytic water splitting.

  16. Charge Carrier Dynamics at Silver Nanocluster-Molecular Acceptor Interfaces

    KAUST Repository

    Almansaf, Abdulkhaleq

    2017-07-01

    A fundamental understanding of interfacial charge transfer at donor-acceptor interfaces is very crucial as it is considered among the most important dynamical processes for optimizing performance in many light harvesting systems, including photovoltaics and photo-catalysis. In general, the photo-generated singlet excitons in photoactive materials exhibit very short lifetimes because of their dipole-allowed spin radiative decay and short diffusion lengths. In contrast, the radiative decay of triplet excitons is dipole forbidden; therefore, their lifetimes are considerably longer. The discussion in this thesis primarily focuses on the relevant parameters that are involved in charge separation (CS), charge transfer (CT), intersystem crossing (ISC) rate, triplet state lifetime, and carrier recombination (CR) at silver nanocluster (NCs) molecular-acceptors interfaces. A combination of steady-state and femto- and nanosecond broadband transient absorption spectroscopies were used to investigate the charge carrier dynamics in various donor-acceptor systems. Additionally, this thesis was prolonged to investigate some important factors that influence the charge carrier dynamics in Ag29 silver NCs donor-acceptor systems, such as the metal doping and chemical structure of the nanocluster and molecular acceptors. Interestingly, clear correlations between the steady-state measurements and timeresolved spectroscopy results are found. In the first study, we have investigated the interfacial charge transfer dynamics in positively charged meso units of 5, 10, 15, 20-tetra (1- methyl-4-pyridino)-porphyrin tetra (p-toluene sulfonate) (TMPyP) and neutral charged 5, 10, 15, 20-tetra (4-pyridyl)-porphyrin (TPyP), with negatively charged undoped and gold (Au)- doped silver Ag29 NCs. Moreover, this study showed the impact of Au doping on the charge carrier dynamics of the system. In the second study, we have investigated the interfacial charge transfer dynamics in [Pt2 Ag23 Cl7 (PPh3

  17. Cluster-to-cluster transformation among Au6, Au8 and Au11 nanoclusters.

    Science.gov (United States)

    Ren, Xiuqing; Fu, Junhong; Lin, Xinzhang; Fu, Xuemei; Yan, Jinghui; Wu, Ren'an; Liu, Chao; Huang, Jiahui

    2018-05-22

    We present the cluster-to-cluster transformations among three gold nanoclusters, [Au6(dppp)4]2+ (Au6), [Au8(dppp)4Cl2]2+ (Au8) and [Au11(dppp)5]3+ (Au11). The conversion process follows a rule that states that the transformation of a small cluster to a large cluster is achieved through an oxidation process with an oxidizing agent (H2O2) or with heating, while the conversion of a large cluster to a small one occurs through a reduction process with a reducing agent (NaBH4). All the reactions were monitored using UV-Vis spectroscopy and ESI-MS. This work may provide an alternative approach to the synthesis of novel gold nanoclusters and a further understanding of the structural transformation relationship of gold nanoclusters.

  18. Fabrication and modification of metal nanocluster composites using ion and laser beams

    International Nuclear Information System (INIS)

    Haglund, R.F. Jr.; Osborne, D.H. Jr.; Magruder, R.H. III; White, C.W.; Zuhr, R.A.; Townsend, P.D.; Hole, D.E.; Leuchtner, R.E.

    1994-12-01

    Metal nanocluster composites have attractive properties for applications in nonlinear optics. However, traditional fabrication techniques -- using melt-glass substrates -- are severely constrained by equilibrium thermodynamics and kinetics. This paper describes the fabrication of metal nanoclusters in both crystalline and glassy hosts by ion implantation and pulsed laser deposition. The size and size distribution of the metal nanoclusters can be modified by controlling substrate temperature during implantation, by subsequent thermal annealing, or by laser irradiation. The authors have characterized the optical response of the composites by absorption and third-order nonlinear-optical spectroscopies; electron and scanning-probe microscopies have been used to benchmark the physical characteristics of the composites. The outlook for controlling the structure and nonlinear optical response properties of these nanophase materials appears increasingly promising

  19. Extension of the radiative lifetime of Wannier-Mott excitons in semiconductor nanoclusters

    International Nuclear Information System (INIS)

    Kukushkin, V. A.

    2015-01-01

    The purpose of the study is to calculate the radiative lifetime of Wannier-Mott excitons in three-dimensional potential wells formed of direct-gap narrow-gap semiconductor nanoclusters in wide-gap semiconductors and assumed to be large compared to the exciton radius. Calculations are carried out for the InAs/GaAs heterosystem. It is shown that, as the nanocluster dimensions are reduced to values on the order of the exciton radius, the exciton radiative lifetime becomes several times longer compared to that in a homogeneous semiconductor. The increase in the radiative lifetime is more pronounced at low temperatures. Thus, it is established that the placement of Wannier-Mott excitons into direct-gap semiconductor nanoclusters, whose dimensions are of the order of the exciton radius, can be used for considerable extension of the exciton radiative lifetime

  20. XAFS studies of monodisperse Au nanoclusters formation in the etching process

    International Nuclear Information System (INIS)

    Yang, Lina; Huang, Ting; Liu, Wei; Bao, Jie; Huang, Yuanyuan; Cao, Yuanjie; Yao, Tao; Sun, Zhihu; Wei, Shiqiang

    2016-01-01

    Understanding the formation mechanism of gold nanoclusters is essential to the development of their synthetic chemistry. Here, by using x-ray absorption fine-structure (XAFS) spectroscopy, UV-Vis and MS spectra, the formation process of monodisperse Au 13 nanoclusters is investigated. We find that a critical step involving the formation of smaller Au 8 -Au 11 metastable intermediate clusters induced by the HCl + HSR etching of the polydisperse Au n precursor clusters occurs firstly. Then these intermediate species undergo a size-growth to Au 13 cores, followed by a slow structure rearrangement to reach the final stable structure. This work enriches the understanding of cluster formation chemistry and may guide the way towards the design and the controllable synthesis of nanoclusters. (paper)

  1. Synthesis of hydrophobic gold nanoclusters: growth mechanism study, luminescence property and catalytic application

    International Nuclear Information System (INIS)

    Selvam, Tamil Selvi; Chi, Kai-Ming

    2011-01-01

    One-pot synthesis of well dispersed, size-controlled gold nanoparticles with the average size of 10–15 nm and luminescent gold nanoclusters with average size of 1.7–2.0 nm were successfully achieved by thermal decomposition of gold organometallic precursor CH 3 AuPPh 3 in the presence of thiol surfactants in o-xylene. Only difference between the preparations of two types of Au nanoparticles is the amount of thiol surfactant employed. The mechanistic study of formation of gold nanoparticles was carried out by analyzing the samples at different reaction time intervals and revealed that two-staged growth process was involved. The nanoclusters showed strong red emission with the maximum intensity at about 600 nm. The maximum room temperature photoluminescence quantum yield was measured as 1.2%. The catalytic ability of the Au nanoclusters to promote Suzuki–Miyaura coupling involving the C–C bond formation was also investigated.

  2. Nanocluster metal films as thermoelectric material for radioisotope mini battery unit

    International Nuclear Information System (INIS)

    Borisyuk, P.V.; Krasavin, A.V.; Tkalya, E.V.; Lebedinskii, Yu.Yu.; Vasiliev, O.S.; Yakovlev, V.P.; Kozlova, T.I.; Fetisov, V.V.

    2016-01-01

    The paper is devoted to studying the thermoelectric and structural properties of films based on metal nanoclusters (Au, Pd, Pt). The experimental results of the study of single nanoclusters’ tunneling conductance obtained with scanning tunneling spectroscopy are presented. The obtained data allowed us to evaluate the thermoelectric power of thin film consisting of densely packed individual nanoclusters. It is shown that such thin films can operate as highly efficient thermoelectric materials. A scheme of miniature thermoelectric radioisotope power source based on the thorium-228 isotope is proposed. The efficiency of the radioisotope battery using thermoelectric converters based on nanocluster metal films is shown to reach values up to 1.3%. The estimated characteristics of the device are comparable with the parameters of up-to-date radioisotope batteries based on nickel-63.

  3. Targeting ILK and β4 integrin abrogates the invasive potential of ovarian cancer

    International Nuclear Information System (INIS)

    Choi, Yoon Pyo; Kim, Baek Gil; Gao, Ming-Qing; Kang, Suki; Cho, Nam Hoon

    2012-01-01

    Highlights: ► The potential of targeting ILK and integrins for highly aggressive ovarian cancer. ► Unanticipated synergistic effect for the combination of ILK/β4 integrin. ► Combination of ILK/β4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. ► Targeting of β4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of β1 and β4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of β1 and β4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of β4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of β4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting β4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  4. Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Pyo; Kim, Baek Gil [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Gao, Ming-Qing; Kang, Suki [Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Nam Hoon, E-mail: cho1988@yuhs.ac [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  5. Phenotypic Screening Identifies Protein Synthesis Inhibitors as H-Ras-Nanocluster-Increasing Tumor Growth Inducers.

    Science.gov (United States)

    Najumudeen, Arafath K; Posada, Itziar M D; Lectez, Benoit; Zhou, Yong; Landor, Sebastian K-J; Fallarero, Adyary; Vuorela, Pia; Hancock, John; Abankwa, Daniel

    2015-12-15

    Ras isoforms H-, N-, and K-ras are each mutated in specific cancer types at varying frequencies and have different activities in cell fate control. On the plasma membrane, Ras proteins are laterally segregated into isoform-specific nanoscale signaling hubs, termed nanoclusters. As Ras nanoclusters are required for Ras signaling, chemical modulators of nanoclusters represent ideal candidates for the specific modulation of Ras activity in cancer drug development. We therefore conducted a chemical screen with commercial and in-house natural product libraries using a cell-based H-ras-nanoclustering FRET assay. Next to established Ras inhibitors, such as a statin and farnesyl-transferase inhibitor, we surprisingly identified five protein synthesis inhibitors as positive regulators. Using commonly employed cycloheximide as a representative compound, we show that protein synthesis inhibition increased nanoclustering and effector recruitment specifically of active H-ras but not of K-ras. Consistent with these data, cycloheximide treatment activated both Erk and Akt kinases and specifically promoted H-rasG12V-induced, but not K-rasG12V-induced, PC12 cell differentiation. Intriguingly, cycloheximide increased the number of mammospheres, which are enriched for cancer stem cells. Depletion of H-ras in combination with cycloheximide significantly reduced mammosphere formation, suggesting an exquisite synthetic lethality. The potential of cycloheximide to promote tumor cell growth was also reflected in its ability to increase breast cancer cell tumors grown in ovo. These results illustrate the possibility of identifying Ras-isoform-specific modulators using nanocluster-directed screening. They also suggest an unexpected feedback from protein synthesis inhibition to Ras signaling, which might present a vulnerability in certain tumor cell types.

  6. Fluorescent silver nanoclusters for ultrasensitive determination of chromium(VI) in aqueous solution

    International Nuclear Information System (INIS)

    Zhang, Jian Rong; Zeng, Ai Lian; Luo, Hong Qun; Li, Nian Bing

    2016-01-01

    Highlights: • Fluorescent Ag nanoclusters were first applied to Cr(VI) detection. • The proposed method is simple, rapid, and environmentally friendly. • The sensor shows a wide linear range, low detection limit, and good selectivity. • The system can also be used for the indirect assay of total chromium and Cr(III). • The analyses in real water samples are satisfactory. - Abstract: In this work, a simple and sensitive Cr(VI) sensor is proposed based on fluorescent polyethyleneimine-stabilized Ag nanoclusters, which allows the determination over a wide concentration range of 0.1 nM–3.0 μM and with a detection limit as low as 0.04 nΜ and a good selectivity. The quenching mechanism was discussed in terms of the absorption and fluorescence spectra, suggesting that Cr(VI) is connected to Ag nanoclusters by hydrogen bond between the oxygen atom at the vertex of tetrahedron structure of Cr(VI) and the amino nitrogen of polyethyleneimine that surrounded Ag nanoclusters and electron transfer from Ag nanoclusters to highly electron-deficient Cr(VI) results in fluorescence quenching. Despite the failure to quench the fluorescence efficiently, Cr(III) can also be measured using the proposed Ag nanoclusters by being oxidized to Cr(VI) in alkaline solution (pH ∼9) containing H 2 O 2 . Therefore, our approach could be used to detect Cr(VI), Cr(III) and the total chromium level in aqueous solution. In addition, Cr(VI) analysis in real water samples were satisfactory, indicating this method could be practically promising for chromium measurements.

  7. The Phosphorylation and Distribution of Cortactin Downstream of Integrin α9β1 Affects Cancer Cell Behaviour

    DEFF Research Database (Denmark)

    Høye, Anette M; Couchman, John R; Wewer, Ulla M

    2016-01-01

    Integrins, a family of heterodimeric adhesion receptors are implicated in cell migration, development and cancer progression. They can adopt conformations that reflect their activation states and thereby impact adhesion strength and migration. Integrins in an intermediate activation state may be ...

  8. One-pot synthesis of gold nanoclusters with bright red fluorescence and good biorecognition abilities for visualization fluorescence enhancement detection of E. coli.

    Science.gov (United States)

    Liu, Jiali; Lu, Lili; Xu, Suying; Wang, Leyu

    2015-03-01

    A facile one-pot strategy was developed for the synthesis of lysozyme functionalized fluorescence gold nanoclusters (AuNCs). The lysozymes added to reduce Au(3+) ions and stabilize the AuNCs during the synthesis were coated on the AuNCs surface and retained their specific recognition ability for bacteria such as Escherichia coli (E. coli). Based on such ability, these AuNCs were specifically attached onto the surface of E. coli, which resulted in great red fluorescence enhancement. Nevertheless, the bovine serum albumin (BSA) stabilized AuNCs could not recognize E. coli and no fluorescence enhancement was observed. Upon the addition of E. coli, the red fluorescence intensity of lysozyme-AuNCs was enhanced linearly over the range of 2.4×10(4) -6.0×10(6) CFU/mL of E. coli with high sensitivity (LOD=2.0×10(4) CFU/mL, S/N=3). The visualization fluorescence evolution may enable the rapid and real-time detection of bacteria. This study may be extended to other functional proteins such as antibody, enzyme, and peptide functionalized nanoclusters while retaining the bioactivity of coating proteins and find wide applications in the fields of biochemistry and biomedicine. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Integrin-linked kinase: a Scaffold protein unique among its ilk.

    Science.gov (United States)

    Dagnino, Lina

    2011-06-01

    Integrin-linked kinase (ILK) is a scaffolding protein with central roles in tissue development and homeostasis. Much debate has focused on whether ILK is a bona fide or a pseudo- kinase. This aspect of ILK function has been complicated by the large volumes of conflicting observations obtained from a wide variety of experimental approaches, from in vitro models, to analyses in invertebrates and in mammals. Key findings in support or against the notion that ILK is catalytically active are summarized. The importance of ILK as an adaptor protein is well established, and defining its role as a signaling hub will be the next key step to understand its distinct biological roles across tissues and species.

  10. Intriguing structures and magic sizes of heavy noble metal nanoclusters around size 55 governed by relativistic effect and covalent bonding

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, X. J.; Xue, X. L.; Jia, Yu [International Laboratory for Quantum Functional Materials of Henan and School of Physics and Engineering, Zhengzhou University, Zhengzhou 450001 (China); Guo, Z. X. [International Laboratory for Quantum Functional Materials of Henan and School of Physics and Engineering, Zhengzhou University, Zhengzhou 450001 (China); Department of Chemistry and London Centre for Nanotechnology, University College London, London WC1H (United Kingdom); Li, S. F., E-mail: sflizzu@zzu.edu.cn [International Laboratory for Quantum Functional Materials of Henan and School of Physics and Engineering, Zhengzhou University, Zhengzhou 450001 (China); ICQD, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zhang, Zhenyu, E-mail: zhangzy@ustc.edu.cn [ICQD, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230026 (China); Synergetic Innovation Center of Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Gao, Y. F., E-mail: ygao7@utk.edu [Department of Materials Science and Engineering, University of Tennessee, Knoxville, Tennessee 37996 (United States); Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States)

    2015-11-07

    Nanoclusters usually display exotic physical and chemical properties due to their intriguing geometric structures in contrast to their bulk counterparts. By means of first-principles calculations within density functional theory, we find that heavy noble metal Pt{sub N} nanoclusters around the size N = 55 begin to prefer an open configuration, rather than previously reported close-packed icosahedron or core-shell structures. Particularly, for Pt{sub N}, the widely supposed icosahedronal magic cluster is changed to a three-atomic-layered structure with D{sub 6h} symmetry, which can be well addressed by our recently established generalized Wulff construction principle (GWCP). However, the magic number of Pt{sub N} clusters around 55 is shifted to a new odd number of 57. The high symmetric three-layered Pt{sub 57} motif is mainly stabilized by the enhanced covalent bonding contributed by both spin-orbital coupling effect and the open d orbital (5d{sup 9}6s{sup 1}) of Pt, which result in a delicate balance between the enhanced Pt–Pt covalent bonding of the interlayers and negligible d dangling bonds on the cluster edges. These findings about Pt{sub N} clusters are also applicable to Ir{sub N} clusters, but qualitatively different from their earlier neighboring element Os and their later neighboring element Au. The magic numbers for Os and Au are even, being 56 and 58, respectively. The findings of the new odd magic number 57 are the important supplementary of the recently established GWCP.

  11. A highly efficient nano-cluster artificial peroxidase and its direct electrochemistry on a nano complex modified glassy carbon electrode.

    Science.gov (United States)

    Hong, Jun; Wang, Wei; Huang, Kun; Yang, Wei-Yun; Zhao, Ying-Xue; Xiao, Bao-Lin; Gao, Yun-Fei; Moosavi-Movahedi, Zainab; Ghourchian, Hedayatollah; Moosavi-Movahedi, Ali Akbar

    2012-01-01

    A nano-cluster with highly efficient peroxide activity was constructed based on nafion (NF) and cytochrome c (Cyt c). UV-Vis spectrometry and transmission electron microscopy (TEM) methods were utilized for characterization of the nano-structured enzyme or artificial peroxidase (AP). The nano-cluster was composed of a Chain-Ball structure, with an average ball size of about 40 nm. The Michaelis-Menten (K(m)) and catalytic rate (k(cat)) constants of the AP were determined to be 2.5 ± 0.4 µM and 0.069 ± 0.001 s(-1), respectively, in 50 mM PBS at pH 7.0. The catalytic efficiency of the AP was evaluated to be 0.028 ± 0.005 µM(-1) s(-1), which was 39 ± 5% as efficient as the native horseradish peroxidase (HRP). The AP was also immobilized on a functional multi-wall carbon nanotube (MWNCTs)-gold colloid nanoparticles (AuNPs) nano-complex modified glassy carbon (GC) electrode. The cyclic voltammetry of AP on the nano complex modified GC electrode showed a pair of well-defined redox peaks with a formal potential (E°') of -45 ± 2 mV (vs. Ag/AgCl) at a scan rate of 0.05 V/s. The heterogeneous electron transfer rate constant (k(s)) was evaluated to be 0.65 s(-1). The surface concentration of electroactive AP on GC electrode (Γ) was 7 × 10(-10) mol cm(-2). The apparent Michaelis-Menten constant (K(m)(app)) was 0.23 nM.

  12. Ouabain interactions with the α4 isoform of the sodium pump trigger non-classical steroid hormone signaling and integrin expression in spermatogenic cells.

    Science.gov (United States)

    Upmanyu, Neha; Dietze, Raimund; Kirch, Ulrike; Scheiner-Bobis, Georgios

    2016-11-01

    In addition to the ubiquitous α1 isoform of the sodium pump, sperm cells also express a male-specific α4 isoform whose function has been associated with sperm motility, fertility, and capacitation. Here we investigate in the murine spermatogenic cell line GC-2 interactions of the α4 isoform with the cardiotonic steroid ouabain in signaling cascades involved in the non-classical action of steroid hormones. Exposure of GC-2 cells to low concentrations of ouabain stimulates the phosphorylation of Erk1/2 and of the transcription factors CREB and ATF-1. As a consequence of this signaling cascade, ouabain stimulates on the mRNA level the expression of integrins αv, β3 and α5, whose expression is also modulated by the cAMP response element. Increased expression of integrins αv and β3 is also seen in cultures of seminiferous tubules exposed to 10nM ouabain. At the protein level we observed a significant stimulation of β3 integrin expression by ouabain. Abrogation of α4 isoform expression by siRNA leads to the complete suppression of all ouabain-induced signaling mentioned above, including its stimulatory effect on the expression of β3 integrin. The results presented here demonstrate for the first time the induction of signaling cascades through the interaction of ouabain with the α4 isoform in a germ-cell derived cell line. The novel finding that these interactions lead to increased expression of integrins in GC-2 cells and the confirmation of these results in the ex vivo experiments indicate that hormone/receptor-like interactions of ouabain with the α4 isoform might be of significance for male physiology. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Bulky Counterions: Enhancing the Two-Photon Excited Fluorescence of Gold Nanoclusters.

    Science.gov (United States)

    Bertorelle, Franck; Moulin, Christophe; Soleilhac, Antonin; Comby-Zerbino, Clothilde; Dugourd, Philippe; Russier-Antoine, Isabelle; Brevet, Pierre-François; Antoine, Rodolphe

    2018-01-19

    Increasing fluorescence quantum yields of ligand-protected gold nanoclusters has attracted wide research interest. The strategy consisting in using bulky counterions has been found to dramatically enhance the fluorescence. In this Communication, we push forward this concept to the nonlinear optical regime. We show that by an appropriate choice of bulky counterions and of solvent, a 30-fold increase in two-photon excited fluorescence (TPEF) signal at ≈600 nm for gold nanoclusters can be obtained. This would correspond to a TPEF cross-section in the range of 0.1 to 1 GM. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Polarization memory of white luminescence of Ag nanoclusters dispersed in glass host.

    Science.gov (United States)

    Kuznetsov, A S; Tikhomirov, V K; Moshchalkov, V V

    2012-09-10

    A mechanism for white luminescence of Ag nanoclusters dispersed in oxyfluoride glass host has been revealed by studying a temperature dependence of its polarization memory. The spectral dependence of the polarization memory indicates the presence of a variety of Ag nanoclusters, particularly emitting in the blue, green and red. Temperature activated intercluster energy transfer has been found responsible for white luminescence. The means for increasing luminescence quantum yield have been suggested. This efficient white luminescence may be used in highly demanded devices, such as luminescent lamps, displays, color phosphors for LEDs, photovoltaic devices based on down shifting of solar spectrum.

  15. Tetrahedral 1B4Sb nanoclusters in GaP:(B, Sb)

    Energy Technology Data Exchange (ETDEWEB)

    Elyukhin, V A, E-mail: elyukhin@cinvestav.m [Departamento de Ingenieria Electrica-SEES, CINVESTAV-IPN, Avenida IPN 2508, Col. San Pedro Zacatenco, C. P. 07360, Mexico, D. F. (Mexico)

    2009-05-01

    Self-assembling conditions of 1B4Sb tetrahedral nanoclusters in GaP doped with boron and Sb isoelectronic impurities are represented in the ultradilute and dilute limits of the boron and Sb contents, respectively. The fulfilled estimates demonstrated the preferential complete or almost complete allocation of boron atoms in 1B4Sb nanoclusters at temperatures of 500 {sup 0}C and 900 {sup 0}C, respectively. The significant decrease of the sum of the free energies of the constituent compounds is the main origin of self-assembling. The reduction of the strain energy is the additional cause of this phenomenon.

  16. Efficient Removal of Arsenic Using Magnetic Multi-Granule Nanoclusters

    International Nuclear Information System (INIS)

    Lee, Seungho; Cha, Jinmyung; Sim, Kyunjong; Lee, Jinkyu

    2014-01-01

    Magnetic multi-granule nanoclusters (MGNCs) were investigated as an inexpensive means to effectively remove arsenic from aqueous environment, particularly groundwater sources consumed by humans. Various size MGNCs were examined to determine both their capacity and efficiency for arsenic adsorption for different initial arsenic concentrations. The MGNCs showed highly efficient arsenic adsorption characteristics, thereby meeting the allowable safety limit of 10 μg/L (ppb), prescribed by the World Health Organization (WHO), and confirming that 0.4 g and 0.6 g of MGNCs were sufficient to remove 0.5 mg/L and 1.0 mg/L of arsenate (AsO 4 3- ) from water, respectively. Adsorption isotherm models for the MGNCs were used to estimate the adsorption parameters. They showed similar parameters for both the Langmuir and Sips models, confirming that the adsorption process in this work was active at a region of low arsenic concentration. The actual efficiency of arsenate removal was then tested against 1 L of artificial arsenic-contaminated groundwater with an arsenic concentration of 0.6 mg/L in the presence of competing ions. In this case, only 1.0 g of 100 nm MGNCs was sufficient to reduce the arsenic concentrations to below the WHO permissible safety limit for drinking water, without adjusting the pH or temperature, which is highly advantageous for practical field applications

  17. Peculiar features of heat capacity for Cu and Ni nanoclusters

    International Nuclear Information System (INIS)

    Gafner, S. L.; Redel, L. V.; Gafner, Yu. Ya.; Samsonov, V. M.

    2011-01-01

    The heat capacity of copper and nickel clusters (from 2 to 6 nm in diameter) was investigated in the temperature range 200–800 K using molecular dynamics method and a modified tight-binding potential. The simulation results demonstrate a very good agreement with the available experimental data at T = 200 K and a fairy good agreement at higher temperatures. A number of regular trends are revealed in computer experiments which agree with the corresponding theoretical predictions. A conclusion is made that in the case of single free clusters the heat capacity may exceed the capacity of the corresponding bulk material. It is found that at 200 K, the copper nanocluster (D = 6 nm) heat capacity is higher by 10% and for nickel cluster by 13%. The difference diminishes with increasing the nanoparticles size proportionally to the relative number of surface atoms. A conclusion is made that very high values of the nanostructure heat capacity observed in laboratory experiments should not be attributed to free clusters, i.e., the effect in question is caused by other reasons.

  18. Mercury speciation with fluorescent gold nanocluster as a probe.

    Science.gov (United States)

    Yang, Jian-Yu; Yang, Ting; Wang, Xiao-Yan; Chen, Ming-Li; Yu, Yong-Liang; Wang, Jian-Hua

    2018-05-11

    Fluorescent nanoparticles are widely used for sensing biologically significant species. However, it is rarely reported for the discrimination or speciation of metal species. In this work, we report for the first time the speciation of mercury (Hg 2+ ) and methylmercury (CH 3 Hg + ) by taking advantage of the fluorescence feature of folic acid-capped gold nanoclusters (FA-AuNCs). FA-Au NCs exhibit an average size of 2.08±0.15 nm and a maximum emission at λ ex /λ em = 280/440 nm with a quantum yield of 27.3%. It is interesting that Hg 2+ causes a significant quench on the fluorescence of FA-Au NCs, whereas CH 3 Hg + leads to a remarkable fluorescence enhancement. Based on this discriminative fluorescent response between Hg 2+ and CH 3 Hg + , a novel nanosensor for the speciation of CH 3 Hg + and Hg 2+ was developed, providing limits of detection (LOD) of 28 nM for Hg 2+ and 25 nM for CH 3 Hg + within 100-1000 nM. This sensing system is highly selective to mercury. Its practical applications were further demonstrated by the analysis of CH 3 Hg + and the speciation of mercury (CH 3 Hg + and Hg 2+ ) in environmental water and fish samples.

  19. Efficient Removal of Arsenic Using Magnetic Multi-Granule Nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seungho; Cha, Jinmyung; Sim, Kyunjong; Lee, Jinkyu [Seoul National Univ., Seoul (Korea, Republic of)

    2014-02-15

    Magnetic multi-granule nanoclusters (MGNCs) were investigated as an inexpensive means to effectively remove arsenic from aqueous environment, particularly groundwater sources consumed by humans. Various size MGNCs were examined to determine both their capacity and efficiency for arsenic adsorption for different initial arsenic concentrations. The MGNCs showed highly efficient arsenic adsorption characteristics, thereby meeting the allowable safety limit of 10 μg/L (ppb), prescribed by the World Health Organization (WHO), and confirming that 0.4 g and 0.6 g of MGNCs were sufficient to remove 0.5 mg/L and 1.0 mg/L of arsenate (AsO{sub 4}{sup 3-}) from water, respectively. Adsorption isotherm models for the MGNCs were used to estimate the adsorption parameters. They showed similar parameters for both the Langmuir and Sips models, confirming that the adsorption process in this work was active at a region of low arsenic concentration. The actual efficiency of arsenate removal was then tested against 1 L of artificial arsenic-contaminated groundwater with an arsenic concentration of 0.6 mg/L in the presence of competing ions. In this case, only 1.0 g of 100 nm MGNCs was sufficient to reduce the arsenic concentrations to below the WHO permissible safety limit for drinking water, without adjusting the pH or temperature, which is highly advantageous for practical field applications.

  20. Towards understanding of poly-guanine activated fluorescent silver nanoclusters

    International Nuclear Information System (INIS)

    Walczak, Sylwia; Morishita, Kiyoshi; Ahmed, Moin; Liu, Juewen

    2014-01-01

    It has been recently reported that the fluorescence of some DNA-templated silver nanoclusters (AgNCs) can be significantly enhanced upon by hybridizing with a partially complementary DNA containing a G-rich overhang near the AgNCs. This discovery has found a number of analytical applications but many fundamental questions remain to be answered. In this work, the photostability of these activated AgNCs is reported. After adding the G-rich DNA activator, the fluorescence intensity peaks in ∼1 h and then starts to decay, where the decaying rate is much faster with light exposure. The lost fluorescence is recovered by adding NaBH 4 , suggesting that the bleaching is an oxidative process. Once activated, the G-rich activator can be removed while the AgNCs still maintain most of their fluorescence intensity. UV–vis spectroscopy suggests that new AgNC species are generated upon hybridization with the activator. The base sequence and length of the template DNA have also been varied, leading to different emission colors and color change after hybridization. G-rich aptamers can also serve as activators. Our results indicate that activation of the fluorescence by G-rich DNA could be a convenient method for biosensor development since the unstable NaBH 4 is not required for the activation step. (paper)

  1. Synthesis and characterization of human transferrin-stabilized gold nanoclusters

    International Nuclear Information System (INIS)

    Le Guevel, Xavier; Schneider, Marc; Daum, Nicole

    2011-01-01

    Human transferrin has been biolabelled with gold nanoclusters (Au NCs) using a simple, fast and non-toxic method. These nanocrystals ( em = 695 nm). Structural investigation and photophysical measurements show a high population of clusters formed of 22-33 gold atoms covalently bound to the transferrin. In solutions with pH ranging from 5 to 10 and in buffer solutions (PBS, HEPES), those biolabelled proteins exhibit a good stability. No significant quenching effect of the fluorescent transferrin has been detected after iron loading of iron-free transferrin (apoTf) and in the presence of a specific polyclonal antibody. Additionally, antibody-induced agglomeration demonstrates no alteration in the protein activity and the receptor target ability. MTT and Vialight Plus tests show no cytotoxicity of these labelled proteins in cells (1 μg ml -1 -1 mg ml -1 ). Cell line experiments (A549) indicate also an uptake of the iron loaded fluorescent proteins inside cells. These remarkable data highlight the potential of a new type of non-toxic fluorescent transferrin for imaging and targeting.

  2. Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

    Directory of Open Access Journals (Sweden)

    David Judah

    Full Text Available Integrin-linked kinase (ILK is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

  3. Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

    Science.gov (United States)

    Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

    2012-01-01

    Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

  4. Integrin αv in the mechanical response of osteoblast lineage cells

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Keiko [Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511 (Japan); Ito, Masako [Medical Work-Life-Balance Center, Nagasaki University Hospital, Nagasaki 852-8501 (Japan); Naoe, Yoshinori [Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511 (Japan); Lacy-Hulbert, Adam [Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114 (United States); Ikeda, Kyoji, E-mail: kikeda@ncgg.go.jp [Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511 (Japan)

    2014-05-02

    Highlights: • Deletion of integrin αv in osteoblast lineage results in an impaired SOST response to loading in vivo. • c-Src–p130Cas–JNK–YAP/TAZ is activated via integrin αv on osteoblasts in response to FSS. • Deletion of integrin αv in osteoblasts results in impaired responses to mechanical stimulation. • Integrin αv is a key component of the mechanosensing machinery in bone. - Abstract: Although osteoblast lineage cells, especially osteocytes, are thought to be a primary mechanosensory cell in bone, the identity of the mechano-receptor and downstream mechano-signaling pathways remain largely unknown. Here we show using osteoblastic cell model of mechanical stimulation with fluid shear stress that in the absence of integrin αv, phosphorylation of the Src substrate p130Cas and JNK was impaired, culminating in an inhibition of nuclear translocation of YAP/TAZ and subsequent transcriptional activation of target genes. Targeted deletion of the integrin αv in osteoblast lineage cells results in an attenuated response to mechanical loading in terms of Sost gene expression, indicative of a role for integrin αv in mechanoreception in vivo. Thus, integrin αv may be integral to a mechanosensing machinery in osteoblastic cells and involved in activation of a Src–JNK–YAP/TAZ pathway in response to mechanical stimulation.

  5. β1 integrins regulate chondrogenesis and rock signaling in adipose stem cells

    NARCIS (Netherlands)

    Lu, Z.F.; Doulabi, B.Z.; Huang, C.L.; Bank, R.A.; Helder, M.N.

    2008-01-01

    β1 integrins play a controversial role during chondrogenesis. Since the maturation of chondrocytes relies on a signaling switch from cell-cell to cell-matrix interactions, we hypothesized that β1 integrins play a different role at the earlier (mainly cell-cell interaction) from the later stage

  6. EMMPRIN regulates β1 integrin-mediated adhesion through Kindlin-3 in human melanoma cells.

    Science.gov (United States)

    Delyon, Julie; Khayati, Farah; Djaafri, Ibtissem; Podgorniak, Marie-Pierre; Sadoux, Aurélie; Setterblad, Niclas; Boutalbi, Zineb; Maouche, Kamel; Maskos, Uwe; Menashi, Suzanne; Lebbé, Céleste; Mourah, Samia

    2015-06-01

    EMMPRIN is known to promote tumor invasion through extracellular matrix (ECM) degradation. Here we report that EMMPRIN can regulate melanoma cell adhesion to the ECM through an interaction with β1 integrin involving kindlin-3. In this study, EMMPRIN knockdown in the human melanoma cell line M10 using siRNA decreased cell invasion and significantly increased cell adhesion and spreading. A morphological change from a round to a spread shape was observed associated with enhanced phalloidin-labelled actin staining. In situ proximity ligation assay and co-immunoprecipitation revealed that EMMPRIN silencing increased the interaction of β1 integrin with kindlin-3, a focal adhesion protein. This was associated with an increase in β1 integrin activation and a decrease in the phosphorylation of the downstream integrin kinase FAK. Moreover, the expression at both the transcript and protein level of kindlin-3 and of β1 integrin was inversely regulated by EMMPRIN. EMMPRIN did not regulate either talin expression or its interaction with β1 integrin. These results are consistent with our in vivo demonstration that EMMPRIN inhibition increased β1 integrin activation and its interaction with kindlin-3. To conclude, these findings reveal a new role of EMMPRIN in tumor cell migration through ß1 integrin/kindlin-3-mediated adhesion pathway. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Integrin αv in the mechanical response of osteoblast lineage cells

    International Nuclear Information System (INIS)

    Kaneko, Keiko; Ito, Masako; Naoe, Yoshinori; Lacy-Hulbert, Adam; Ikeda, Kyoji

    2014-01-01

    Highlights: • Deletion of integrin αv in osteoblast lineage results in an impaired SOST response to loading in vivo. • c-Src–p130Cas–JNK–YAP/TAZ is activated via integrin αv on osteoblasts in response to FSS. • Deletion of integrin αv in osteoblasts results in impaired responses to mechanical stimulation. • Integrin αv is a key component of the mechanosensing machinery in bone. - Abstract: Although osteoblast lineage cells, especially osteocytes, are thought to be a primary mechanosensory cell in bone, the identity of the mechano-receptor and downstream mechano-signaling pathways remain largely unknown. Here we show using osteoblastic cell model of mechanical stimulation with fluid shear stress that in the absence of integrin αv, phosphorylation of the Src substrate p130Cas and JNK was impaired, culminating in an inhibition of nuclear translocation of YAP/TAZ and subsequent transcriptional activation of target genes. Targeted deletion of the integrin αv in osteoblast lineage cells results in an attenuated response to mechanical loading in terms of Sost gene expression, indicative of a role for integrin αv in mechanoreception in vivo. Thus, integrin αv may be integral to a mechanosensing machinery in osteoblastic cells and involved in activation of a Src–JNK–YAP/TAZ pathway in response to mechanical stimulation

  8. Cellular and substrate adhesion molecules (integrins) and their ligands in cerebral amyloid plaques in Alzheimer's disease

    NARCIS (Netherlands)

    Eikelenboom, P.; Zhan, S. S.; Kamphorst, W.; van der Valk, P.; Rozemuller, J. M.

    1994-01-01

    Integrins belonging to different subfamilies can be identified immunohistochemically in cerebral amyloid plaques. Monoclonal antibodies against the VLA family beta 1-integrins show staining of the corona of classical amyloid plaques for beta 1, alpha 3 and alpha 6. Immunostaining reveal also the

  9. Ligand-Occupied Integrin Internalization Links Nutrient Signaling to Invasive Migration

    Directory of Open Access Journals (Sweden)

    Elena Rainero

    2015-01-01

    Full Text Available Integrin trafficking is key to cell migration, but little is known about the spatiotemporal organization of integrin endocytosis. Here, we show that α5β1 integrin undergoes tensin-dependent centripetal movement from the cell periphery to populate adhesions located under the nucleus. From here, ligand-engaged α5β1 integrins are internalized under control of the Arf subfamily GTPase, Arf4, and are trafficked to nearby late endosomes/lysosomes. Suppression of centripetal movement or Arf4-dependent endocytosis disrupts flow of ligand-bound integrins to late endosomes/lysosomes and their degradation within this compartment. Arf4-dependent integrin internalization is required for proper lysosome positioning and for recruitment and activation of mTOR at this cellular subcompartment. Furthermore, nutrient depletion promotes subnuclear accumulation and endocytosis of ligand-engaged α5β1 integrins via inhibition of mTORC1. This two-way regulatory interaction between mTORC1 and integrin trafficking in combination with data describing a role for tensin in invasive cell migration indicate interesting links between nutrient signaling and metastasis.

  10. The connection between metal ion affinity and ligand affinity in integrin I domains

    DEFF Research Database (Denmark)

    Vorup-Jensen, Thomas; Waldron, TT; Astrof, N

    2007-01-01

    Integrins are cell-surface heterodimeric proteins that mediate cell-cell, cell-matrix, and cell-pathogen interactions. Half of the known integrin alpha subunits contain inserted domains (I domains) that coordinate ligand through a metal ion. Although the importance of conformational changes withi...

  11. Albumin fibrillization induces apoptosis via integrin/FAK/Akt pathway

    Directory of Open Access Journals (Sweden)

    Liang Chi-Ming

    2009-01-01

    Full Text Available Abstract Background Numerous proteins can be converted to amyloid-like fibrils to increase cytotoxicity and induce apoptosis, but the methods generally require a high concentration of protein, vigorous shaking, or fibril seed. As well, the detailed mechanism of the cytotoxic effects is not well characterized. In this study, we have developed a novel process to convert native proteins into the fibrillar form. We used globular bovine serum albumin (BSA as a model protein to verify the properties of the fibrillar protein, investigated its cellular effects and studied the signaling cascade induced by the fibrillar protein. Results We induced BSA, a non-cytotoxic globular protein, to become fibril by a novel process involving Superdex-200 column chromatography in the presence of anionic or zwittergenic detergent(s. The column pore size was more important than column matrix composite in fibril formation. The fibrillar BSA induced apoptosis in BHK-21 cell as well as breast cancer cell line T47D. Pre-treating cells with anti-integrin antibodies blocked the apoptotic effect. Fibrillar BSA, but not globular BSA, bound to integrin, dephosphorylated focal adhesion kinase (FAK, Akt and glycogen synthase kinase-3β (GSK-3β. Conclusion We report on a novel process for converting globular proteins into fibrillar form to cause apoptosis by modulating the integrin/FAK/Akt/GSK-3β/caspase-3 signaling pathway. Our findings may be useful for understanding the pathogenesis of amyloid-like fibrils and applicable for the development of better therapeutic agents that target the underlying mechanism(s of the etiologic agents.

  12. Energy of the Isolated Metastable Iron-Nickel FCC Nanocluster with a Carbon Atom in the Tetragonal Interstice.

    Science.gov (United States)

    Bondarenko, Natalya V; Nedolya, Anatoliy V

    2017-12-01

    The energy of the isolated iron-nickel nanocluster was calculated by molecular mechanics method using Lennard-Jones potential. The cluster included a carbon atom that drifted from an inside octahedral interstice to a tetrahedral interstice in [Formula: see text] direction and after that in direction to the surface. In addition, one of 14 iron atoms was replaced by a nickel atom, the position of which was changing during simulation.The energy of the nanocluster was estimated at the different interatomic distances. As a result of simulation, the optimal interatomic distances of Fe-Ni-C nanocluster was chosen for the simulation, in which height of the potential barrier was maximal and face-centered cubic (FCC) nanocluster was the most stable.It is shown that there were three main positions of a nickel atom that significantly affected nanocluster's energy.The calculation results indicated that position of the carbon atom in the octahedral interstice was more energetically favorable than tetrahedral interstice in the case of FCC nanocluster. On the other side, the potential barrier was smaller in the direction [Formula: see text] than in the direction .This indicates that there are two ways for carbon atom to drift to the surface of the nanocluster.

  13. Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors

    DEFF Research Database (Denmark)

    Oxboel, Jytte; Binderup, Tina; Knigge, Ulrich

    2009-01-01

    , in neuroendocrine tumors. We used quantitative real-time PCR for measuring mRNA gene-expression of vascular endothelial growth factor (VEGF), integrin alphaV, and integrin beta3, and CD34 for a group of patients with neuroendocrine tumors (n=13). Tissue from patients with colorectal cancer liver metastases (n=14...... compared to both colorectal liver metastases (p=0.10) and normal liver tissue (p=0.06). In neuroendocrine tumors, gene-expression was highly variable of VEGF (530-fold), integrin alphaV (23-fold) and integrin beta3 (106-fold). Quantitative gene-expression levels of the key angiogenesis molecules VEGF......Anti-angiogenesis treatment is a promising new therapy for cancer that recently has also been suggested for patients with neuroendocrine tumors. The aim of the present study was therefore to investigate the level of tumor angiogenesis, and thereby the molecular basis for anti-angiogenesis treatment...

  14. DMPD: Immunoreceptor-like signaling by beta 2 and beta 3 integrins. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17913496 Immunoreceptor-like signaling by beta 2 and beta 3 integrins. Jakus Z, Fod...) Show Immunoreceptor-like signaling by beta 2 and beta 3 integrins. PubmedID 17913496 Title Immunoreceptor-...like signaling by beta 2 and beta 3 integrins. Authors Jakus Z, Fodor S, Abram CL

  15. Beta1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

    DEFF Research Database (Denmark)

    Brakebusch, C; Wennerberg, K; Krell, H W

    1999-01-01

    To investigate the role of beta1 integrin during tumor metastasis, we established a ras-myc transformed fibroblastoid cell line with a disrupted beta1 integrin gene on both alleles (GERM 11). Stable transfection of this cell line with an expression vector encoding beta1A integrin resulted in beta1A......, tumors induced by the high expressing clones 1A10 and 2F2 were markedly smaller, suggesting an inverse correlation of tumor growth and beta1 integrin expression. The metastasis potential of all three beta1 integrin-expressing GERM 11 sublines tested was significantly higher than that of the beta1......-deficient GERM 11 cells. GERM 116 tumors led in all animals to severe metastasis in lung and liver, while GERM 11 tumors induced only a few metastatic foci in the lung. Stroma of both tumors contained nidogen and high amounts of tenascin C, but only a few very low levels of fibronectin, laminin-1...

  16. Direct immobilization of antibodies on Zn-doped Fe{sub 3}O{sub 4} nanoclusters for detection of pathogenic bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Pal, Monalisa; Lee, Sanghee; Kwon, Donghoon; Hwang, Jeongin; Lee, Hyeonjeong; Hwang, Seokyung; Jeon, Sangmin, E-mail: jeons@postech.ac.kr

    2017-02-01

    Zinc-doped magnetic nanoclusters (Zn-MNCs) were synthesized and used to detect pathogenic bacteria in milk. Hydrothermally synthesized Zn-MNCs exhibited stronger magnetic properties than pure MNCs, which facilitated the magnetic separation from the sample using a permanent magnet. The presence of accessible Zn sites allows the direct immobilization of half-fragmented antibodies over Zn-MNCs through strong Zn−S bonds and prevents the tedious multiple steps of molecular functionalization or coating with costly noble metals prior to conjugation with an antibody. After the capture and magnetic separation of Salmonella in milk using the antibody-functionalized Zn-MNCs, the concentration of bacteria was determined with a portable ATP luminometer and the detection limit was found to be 10 CFU/mL. - Highlights: • Zn-doped Fe{sub 3}O{sub 4} nanoclusters (Zn-MNCs) were synthesized by hydrothermal method. • Antibodies were directly immobilized over Zn-MNCs through strong Zn–S{sub thiol} bonds. • Higher magnetization of Zn-MNCs than pure MNCs facilitates the magnetic separation. • Detection limit of pathogenic bacteria in milk was found to be 10 cfu/mL. • Cost effective, sensitive and selective detection of bacteria.

  17. Effect of cold rolling on the formation and distribution of nanoclusters during pre-aging in an Al–Mg–Si alloy

    International Nuclear Information System (INIS)

    Serizawa, A.; Sato, T.; Miller, M.K.

    2013-01-01

    The effect of high densities of dislocations on the formation behavior of two types of nano-scale clusters (nanoclusters), which are formed at room temperature or during pre-aging at ∼373 K in an Al–Mg–Si alloy, was investigated by atom probe tomography. Cold rolling was applied to modify the formation behavior and/or the characteristics of the nanoclusters and also the precipitation sequence, which involve both nanoclusters and a strengthening phase to improve the bake-hardening response. Nanoclusters formed during pre-aging tended to form along the dislocations. Cold rolling accelerated the preferential formation of the nanoclusters, whereas the number density of the nanoclusters decreased by cold rolling before pre-aging. However, the number density of the nanoclusters was considerably higher than that of the β″ phase. Cold rolling before pre-aging enhanced the age-hardenability the most compared with other processes such as the contemporary pre-aging process. It is considered that the nanoclusters along dislocations lead to the preferential transformation to the β″ phase and then the rapid growth of the β″ phase. The nanoclusters formed on dislocations are effective in improving the bake-hardening response for the duration of the bake-hardening process. The kinetics and the distribution of the nanoclusters were found to be affected by the dislocations which were induced by cold rolling.

  18. Quantum Chemical Studies of Actinides and Lanthanides: From Small Molecules to Nanoclusters

    Science.gov (United States)

    Vlaisavljevich, Bess

    Research into actinides is of high interest because of their potential applications as an energy source and for the environmental implications therein. Global concern has arisen since the development of the actinide concept in the 1940s led to the industrial scale use of the commercial nuclear energy cycle and nuclear weapons production. Large quantities of waste have been generated from these processes inspiring efforts to address fundamental questions in actinide science. In this regard, the objective of this work is to use theory to provide insight and predictions into actinide chemistry, where experimental work is extremely challenging because of the intrinsic difficulties of the experiments themselves and the safety issues associated with this type of chemistry. This thesis is a collection of theoretical studies of actinide chemistry falling into three categories: quantum chemical and matrix isolation studies of small molecules, the electronic structure of organoactinide systems, and uranyl peroxide nanoclusters and other solid state actinide compounds. The work herein not only spans a wide range of systems size but also investigates a range of chemical problems. Various quantum chemical approaches have been employed. Wave function-based methods have been used to study the electronic structure of actinide containing molecules of small to middle-size. Among these methods, the complete active space self consistent field (CASSCF) approach with corrections from second-order perturbation theory (CASPT2), the generalized active space SCF (GASSCF) approach, and Moller-Plesset second-order perturbation theory (MP2) have been employed. Likewise, density functional theory (DFT) has been used along with analysis tools like bond energy decomposition, bond orders, and Bader's Atoms in Molecules. From these quantum chemical results, comparison with experimentally obtained structures and spectra are made.

  19. Pressurized polyol synthesis of Al-doped ZnO nanoclusters with high electrical conductivity and low near-infrared transmittance

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ho-Nyun; Shin, Chi-Ho [Surface Technology R& BD Group, Korea Institute of Industrial Technology (KITECH), Incheon 406-840 (Korea, Republic of); Hwang, Duck Kun [Department of Corporate Diagnosis, Small and Medium Business Corporation, Seoul 150-718 (Korea, Republic of); Kim, Haekyoung [School of Materials Science and Engineering, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of); Oh, Kyeongseok [Department of Chemical and Environmental Technology, Inha Technical College, Incheon 402-752 (Korea, Republic of); Kim, Hyun-Jong, E-mail: hjkim23@kitech.re.kr [Surface Technology R& BD Group, Korea Institute of Industrial Technology (KITECH), Incheon 406-840 (Korea, Republic of)

    2015-09-25

    Highlights: • Low-temperature pressurized polyol method synthesized Al-doped ZnO nanoclusters. • Reaction time affected the doping efficiency, resistivity, and NIR transmittance. • The near-IR blocking efficiency of Al-doped ZnO (AZO) nanoclusters reached 85%. • AZO nanocluster coatings could be used for heat reflectors or artificial glasses. - Abstract: In this study, a novel pressurized polyol method is proposed to synthesize aluminum-doped ZnO (AZO) nanoclusters without utilizing additional thermal treatment to avoid the merging of nanoclusters. The size of the AZO nanoclusters range from 100 to 150 nm with a resistivity of 204 Ω cm. The AZO nanoclusters primarily consist of approximately 10-nm nanocrystals that form a spherically clustered morphology. A two-stage growth model has been proposed based on the results of scanning electron microscopy and transmission electron microscopy images, nanocluster sizes, and X-ray diffraction patterns. The primary AZO nanocrystals first nucleate under pressurized conditions and then spontaneously aggregate into larger nanoclusters. Optically, the AZO nanoclusters exhibit a significant decrease in the near-infrared (NIR) transmittance compared to pure ZnO nanoparticles. The NIR blocking efficiency of AZO nanoclusters reached 85%. Moreover, the doping efficiency, resistivity, and NIR transmittance of AZO nanoclusters are influenced by the reaction time in the pressurized polyol solution. On the other hand, the reaction time has no effect on the particle size and crystallinity. An optically transparent coating for the AZO nanoclusters, which consisted of iso-propanol solvent and ultraviolet-curable acrylic binder, was also demonstrated.

  20. Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

    Energy Technology Data Exchange (ETDEWEB)

    Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J. [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); Bridges, Lance C., E-mail: bridgesl@ecu.edu [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); East Carolina Diabetes and Obesity Institute, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States)

    2014-11-28

    Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH){sub 2}D{sub 3}, a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion.

  1. Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

    International Nuclear Information System (INIS)

    Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J.; Bridges, Lance C.

    2014-01-01

    Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH) 2 D 3 , a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion

  2. Dwarfism in mice lacking collagen-binding integrins alpha 2 beta 1 and alpha 11 beta 1 is caused by severely diminished IGF-1 levels

    OpenAIRE

    Blumbach, Katrin; Niehoff, Anja; Belgardt, Bengt F.; Ehlen, Harald W.A.; Schmitz, Markus; Hallinger, Ralf; Schulz, Jan-Niklas; Brüning, Jens C.; Krieg, Thomas; Schubert, Markus; Gullberg, Donald; Eckes, Beate

    2012-01-01

    Mice with a combined deficiency in the α2β1 and α11β1 integrins lack the major receptors for collagen I. These mutants are born with inconspicuous differences in size but develop dwarfism within the first 4 weeks of life. Dwarfism correlates with shorter, less mineralized and functionally weaker bones that do not result from growth plate abnormalities or osteoblast dysfunction. Besides skeletal dwarfism, internal organs are correspondingly smaller, indicating proportional dwarfism and suggest...

  3. Enzymatic reduction of U60 nanoclusters by Shewanella oneidensis MR-1

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Qiang; Fein, Jeremy B. [Notre Dame Univ., IN (United States). Dept. of Civil and Environmental Engineering and Earth Sciences

    2018-04-01

    In this study, a series of reduction experiments were conducted using a representative uranyl peroxide nanocluster, U60 (K{sub 16}Li{sub 44}[UO{sub 2}(O{sub 2})OH]{sub 60}) and a bacterial species, Shewanella oneidensis MR-1, that is capable of enzymatic U(VI) reduction. U60 was reduced by S. oneidensis in the absence of O{sub 2}, but the reduction kinetics for U60 were significantly slower than was observed in this study for aqueous uranyl acetate, and were faster than was reported in previous studies for solid phase U(VI). Our results indicate that U60 aggregates bigger than 0.2 μm formed immediately upon mixing with the bacterial growth medium, and that these aggregates were gradually broken down during the process of reduction. Neither reduction nor dissolution of U60 was observed during 72 h of control experiments open to the atmosphere, indicating that the breakdown and dissolution of U60 aggregates is caused by the reduction of U60, and that S. oneidensis is capable of direct reduction of the U(VI) within the U60 nanoclusters, likely due to the adsorption of U60 aggregates onto bacterial cells. This study is first to show the reduction capacity of bacteria for uranyl peroxide nanoclusters, and the results yield a better understanding of the long term fate of uranium in environmental systems in which uranyl peroxide nanoclusters are present.

  4. Pinning of size-selected gold and nickel nanoclusters on graphite

    NARCIS (Netherlands)

    Di Vece, M.|info:eu-repo/dai/nl/248753355; Paloma, S.; Palmer, R.E.

    2005-01-01

    Size-selected gold and nickel nanoclusters are of interest from an electronic, catalytic, and biological point of view. These applications require the deposition of the clusters on a surface, and a key challenge is to retain the cluster size. Here controlled energy impact is used to immobilize the

  5. Spectroscopy of metal "superatom" nanoclusters and high-Tc superconducting pairing

    Science.gov (United States)

    Halder, Avik; Kresin, Vitaly V.

    2015-12-01

    A unique property of metal nanoclusters is the "superatom" shell structure of their delocalized electrons. The electronic shell levels are highly degenerate and therefore represent sharp peaks in the density of states. This can enable exceptionally strong electron pairing in certain clusters composed of tens to hundreds of atoms. In a finite system, such as a free nanocluster or a nucleus, pairing is observed most clearly via its effect on the energy spectrum of the constituent fermions. Accordingly, we performed a photoionization spectroscopy study of size-resolved aluminum nanoclusters and observed a rapid rise in the near-threshold density of states of several clusters (A l37 ,44 ,66 ,68 ) with decreasing temperature. The characteristics of this behavior are consistent with compression of the density of states by a pairing transition into a high-temperature superconducting state with Tc≳100 K. This value exceeds that of bulk aluminum by two orders of magnitude. These results highlight the potential of novel pairing effects in size-quantized systems and the possibility to attain even higher critical temperatures by optimizing the particles' size and composition. As a new class of high-temperature superconductors, such metal nanocluster particles are promising building blocks for high-Tc materials, devices, and networks.

  6. Electron microscopy and positron annihilation study of CdSe nanoclusters embedded in MgO

    International Nuclear Information System (INIS)

    Huis, M.A. van; Veen, A. van; Schut, H.; Eijt, S.W.H.; Kooi, B.J.; Hosson, J.Th.M. de

    2004-01-01

    CdSe nanoclusters are created in MgO by means of co-implantation of 280 keV, 1 x 10 16 Cd ions cm -2 and 210 keV, 1 x 10 16 Se ions cm -2 in single crystals of MgO(0 0 1) and subsequent thermal annealing at a temperature of 1300 K. The structural properties and the orientation relationship between the CdSe and the MgO are investigated using cross-sectional transmission electron microscopy (XTEM). The crystal structure of the nanoclusters depends on their size. The smallest nanoclusters with a size below 5 nm have the cubic rocksalt crystal structure. The larger nanoclusters have a different (most likely the cubic sphalerite) crystal structure. The defect evolution in the sample after ion implantation and during thermal annealing is investigated using Doppler broadening positron beam analysis (PBA). The defect evolution in samples co-implanted with Cd and Se is compared to the defect evolution in samples implanted with only Cd or only Se ions

  7. Definition of the size of nanoclusters of silver and palladium in carbon fiber