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Sample records for focal adhesion complex

  1. TRIM15 is a focal adhesion protein that regulates focal adhesion disassembly

    Science.gov (United States)

    Uchil, Pradeep D.; Pawliczek, Tobias; Reynolds, Tracy D.; Ding, Siyuan; Hinz, Angelika; Munro, James B.; Huang, Fang; Floyd, Robert W.; Yang, Haitao; Hamilton, William L.; Bewersdorf, Joerg; Xiong, Yong; Calderwood, David A.; Mothes, Walther

    2014-01-01

    ABSTRACT Focal adhesions are macromolecular complexes that connect the actin cytoskeleton to the extracellular matrix. Dynamic turnover of focal adhesions is crucial for cell migration. Paxillin is a multi-adaptor protein that plays an important role in regulating focal adhesion dynamics. Here, we identify TRIM15, a member of the tripartite motif protein family, as a paxillin-interacting factor and a component of focal adhesions. TRIM15 localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. Unlike other focal adhesion proteins, TRIM15 is a stable focal adhesion component with restricted mobility due to its ability to form oligomers. TRIM15-depleted cells display impaired cell migration and reduced focal adhesion disassembly rates, in addition to enlarged focal adhesions. Thus, our studies demonstrate a cellular function for TRIM15 as a regulatory component of focal adhesion turnover and cell migration. PMID:25015296

  2. Heterogeneity of Focal Adhesions and Focal Contacts in Motile Fibroblasts.

    Science.gov (United States)

    Gladkikh, Aleena; Kovaleva, Anastasia; Tvorogova, Anna; Vorobjev, Ivan A

    2018-01-01

    Cell-extracellular matrix (ECM) adhesion is an important property of virtually all cells in multicellular organisms. Cell-ECM adhesion studies, therefore, are very significant both for biology and medicine. Over the last three decades, biomedical studies resulted in a tremendous advance in our understanding of the molecular basis and functions of cell-ECM adhesion. Based on morphological and molecular criteria, several different types of model cell-ECM adhesion structures including focal adhesions, focal complexes, fibrillar adhesions, podosomes, and three-dimensional matrix adhesions have been described. All the subcellular structures that mediate cell-ECM adhesion are quite heterogeneous, often varying in size, shape, distribution, dynamics, and, to a certain extent, molecular constituents. The morphological "plasticity" of cell-ECM adhesion perhaps reflects the needs of cells to sense, adapt, and respond to a variety of extracellular environments. In addition, cell type (e.g., differentiation status, oncogenic transformation, etc.) often exerts marked influence on the structure of cell-ECM adhesions. Although molecular, genetic, biochemical, and structural studies provide important maps or "snapshots" of cell-ECM adhesions, the area of research that is equally valuable is to study the heterogeneity of FA subpopulations within cells. Recently time-lapse observations on the FA dynamics become feasible, and behavior of individual FA gives additional information on cell-ECM interactions. Here we describe a robust method of labeling of FA using plasmids with fluorescent markers for paxillin and vinculin and quantifying the morphological and dynamical parameters of FA.

  3. A Discovery Strategy for Selective Inhibitors of c-Src in Complex with the Focal Adhesion Kinase SH3/SH2-binding Region.

    Science.gov (United States)

    Moroco, Jamie A; Baumgartner, Matthew P; Rust, Heather L; Choi, Hwan Geun; Hur, Wooyoung; Gray, Nathanael S; Camacho, Carlos J; Smithgall, Thomas E

    2015-08-01

    The c-Src tyrosine kinase co-operates with the focal adhesion kinase to regulate cell adhesion and motility. Focal adhesion kinase engages the regulatory SH3 and SH2 domains of c-Src, resulting in localized kinase activation that contributes to tumor cell metastasis. Using assay conditions where c-Src kinase activity required binding to a tyrosine phosphopeptide based on the focal adhesion kinase SH3-SH2 docking sequence, we screened a kinase-biased library for selective inhibitors of the Src/focal adhesion kinase peptide complex versus c-Src alone. This approach identified an aminopyrimidinyl carbamate compound, WH-4-124-2, with nanomolar inhibitory potency and fivefold selectivity for c-Src when bound to the phospho-focal adhesion kinase peptide. Molecular docking studies indicate that WH-4-124-2 may preferentially inhibit the 'DFG-out' conformation of the kinase active site. These findings suggest that interaction of c-Src with focal adhesion kinase induces a unique kinase domain conformation amenable to selective inhibition. © 2014 John Wiley & Sons A/S.

  4. Focal adhesions and cell-matrix interactions

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    1988-01-01

    Focal adhesions are areas of cell surfaces where specializations of cytoskeletal, membrane and extracellular components combine to produce stable cell-matrix interactions. The morphology of these adhesions and the components identified in them are discussed together with possible mechanisms...

  5. Focal adhesions, stress fibers and mechanical tension

    Energy Technology Data Exchange (ETDEWEB)

    Burridge, Keith, E-mail: Keith_Burridge@med.unc.edu [Department of Cell Biology and Physiology, and Lineberger Comprehensive Cancer Center, 12-016 Lineberger, CB#7295, University of North Carolina, Chapel Hill, NC (United States); Guilluy, Christophe, E-mail: christophe.guilluy@univ-nantes.fr [Inserm UMR-S1087, CNRS UMR-C6291, L' institut du Thorax, and Université de Nantes, Nantes (France)

    2016-04-10

    Stress fibers and focal adhesions are complex protein arrays that produce, transmit and sense mechanical tension. Evidence accumulated over many years led to the conclusion that mechanical tension generated within stress fibers contributes to the assembly of both stress fibers themselves and their associated focal adhesions. However, several lines of evidence have recently been presented against this model. Here we discuss the evidence for and against the role of mechanical tension in driving the assembly of these structures. We also consider how their assembly is influenced by the rigidity of the substratum to which cells are adhering. Finally, we discuss the recently identified connections between stress fibers and the nucleus, and the roles that these may play, both in cell migration and regulating nuclear function. - Highlights: • The different types of stress fiber and focal adhesion are described. • We discuss the controversy about tension and assembly of these structures. • We describe the different models used to investigate assembly of these structures. • The influence of substratum rigidity is discussed. • Stress fiber connections to the nucleus are reviewed.

  6. Syndecan-4 and focal adhesion function

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    2001-01-01

    Two groups have now reported the viability of mice that lack syndecan-4. These mice have wound healing/angiogenesis problems, and fibroblasts from these animals differ in adhesion and migration from normal. This is consistent with recent in vitro data indicating a need for signaling via syndecan-4...... for focal adhesion formation, and reports that overexpression of proteins that bind syndecan-4 can modify cell adhesion and migration....

  7. Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration.

    Science.gov (United States)

    Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

    2015-12-18

    Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration.

  8. A ZIP6-ZIP10 heteromer controls NCAM1 phosphorylation and integration into focal adhesion complexes during epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Brethour, Dylan; Mehrabian, Mohadeseh; Williams, Declan; Wang, Xinzhu; Ghodrati, Farinaz; Ehsani, Sepehr; Rubie, Elizabeth A; Woodgett, James R; Sevalle, Jean; Xi, Zhengrui; Rogaeva, Ekaterina; Schmitt-Ulms, Gerold

    2017-01-18

    The prion protein (PrP) evolved from the subbranch of ZIP metal ion transporters comprising ZIPs 5, 6 and 10, raising the prospect that the study of these ZIPs may reveal insights relevant for understanding the function of PrP. Building on data which suggested PrP and ZIP6 are critical during epithelial-to-mesenchymal transition (EMT), we investigated ZIP6 in an EMT paradigm using ZIP6 knockout cells, mass spectrometry and bioinformatic methods. Reminiscent of PrP, ZIP6 levels are five-fold upregulated during EMT and the protein forms a complex with NCAM1. ZIP6 also interacts with ZIP10 and the two ZIP transporters exhibit interdependency during their expression. ZIP6 contributes to the integration of NCAM1 in focal adhesion complexes but, unlike cells lacking PrP, ZIP6 deficiency does not abolish polysialylation of NCAM1. Instead, ZIP6 mediates phosphorylation of NCAM1 on a cluster of cytosolic acceptor sites. Substrate consensus motif features and in vitro phosphorylation data point toward GSK3 as the kinase responsible, and interface mapping experiments identified histidine-rich cytoplasmic loops within the ZIP6/ZIP10 heteromer as a novel scaffold for GSK3 binding. Our data suggests that PrP and ZIP6 inherited the ability to interact with NCAM1 from their common ZIP ancestors but have since diverged to control distinct posttranslational modifications of NCAM1.

  9. Focal adhesion kinase is required for actin polymerization and remodeling of the cytoskeleton during sperm capacitation

    Science.gov (United States)

    Roa-Espitia, Ana L.; Hernández-Rendón, Eva R.; Baltiérrez-Hoyos, Rafael; Muñoz-Gotera, Rafaela J.; Cote-Vélez, Antonieta; Jiménez, Irma; González-Márquez, Humberto

    2016-01-01

    ABSTRACT Several focal adhesion proteins are known to cooperate with integrins to link the extracellular matrix to the actin cytoskeleton; as a result, many intracellular signaling pathways are activated and several focal adhesion complexes are formed. However, how these proteins function in mammalian spermatozoa remains unknown. We confirm the presence of focal adhesion proteins in guinea pig spermatozoa, and we explore their role during capacitation and the acrosome reaction, and their relationship with the actin cytoskeleton. Our results suggest the presence of a focal adhesion complex formed by β1-integrin, focal adhesion kinase (FAK), paxillin, vinculin, talin, and α-actinin in the acrosomal region. Inhibition of FAK during capacitation affected the protein tyrosine phosphorylation associated with capacitation that occurs within the first few minutes of capacitation, which caused the acrosome reaction to become increasingly Ca2+ dependent and inhibited the polymerization of actin. The integration of vinculin and talin into the complex, and the activation of FAK and paxillin during capacitation, suggests that the complex assembles at this time. We identify that vinculin and α-actinin increase their interaction with F-actin while it remodels during capacitation, and that during capacitation focal adhesion complexes are structured. FAK contributes to acrosome integrity, likely by regulating the polymerization and the remodeling of the actin cytoskeleton. PMID:27402964

  10. PKCbeta-dependent activation of RhoA by syndecan-4 during focal adhesion formation

    DEFF Research Database (Denmark)

    Dovas, Athanassios; Yoneda, Atsuko; Couchman, John R

    2006-01-01

    Syndecan-4 is a ubiquitously expressed transmembrane heparan sulphate proteoglycan acting in concert with integrins in the formation of focal adhesions and stress fibres. Signalling events studied thus far suggest the formation of a ternary complex between syndecan-4, phosphatidylinositol 4...... necessary for the formation and maintenance of stress fibres in primary rat embryo fibroblasts. Inhibition of PKCalpha activity through the use of specific pharmacological inhibitors, a dominant-negative construct, or siRNA downregulation of protein levels, attenuated focal adhesion formation...

  11. The intermediate filament protein vimentin binds specifically to a recombinant integrin α2/β1 cytoplasmic tail complex and co-localizes with native α2/β1 in endothelial cell focal adhesions

    International Nuclear Information System (INIS)

    Kreis, Stephanie; Schoenfeld, Hans-Joachim; Melchior, Chantal; Steiner, Beat; Kieffer, Nelly

    2005-01-01

    Integrin receptors are crucial players in cell adhesion and migration. Identification and characterization of cellular proteins that interact with their short α and β cytoplasmic tails will help to elucidate the molecular mechanisms by which integrins mediate bi-directional signaling across the plasma membrane. Integrin α2β1 is a major collagen receptor but to date, only few proteins have been shown to interact with the α2 cytoplasmic tail or with the α2β1 complex. In order to identify novel binding partners of a α2β1cytoplasmic domain complex, we have generated recombinant GST-fusion proteins, incorporating the leucine zipper heterodimerization cassettes of Jun and Fos. To ascertain proper functionality of the recombinant proteins, interaction with natural binding partners was tested. GST-α2 and GST-Jun α2 bound His-tagged calreticulin while GST-β1 and GST-Fos β1 proteins bound talin. In screening assays for novel binding partners, the immobilized GST-Jun α2/GST-Fos β1 heterodimeric complex, but not the single subunits, interacted specifically with endothelial cell-derived vimentin. Vimentin, an abundant intermediate filament protein, has previously been shown to co-localize with αvβ3-positive focal contacts. Here, we provide evidence that this interaction also occurs with α2β1-enriched focal adhesions and we further show that this association is lost after prolonged adhesion of endothelial cells to collagen

  12. Theory of the mechanical response of focal adhesions to shear flow

    International Nuclear Information System (INIS)

    Biton, Y Y; Safran, S A

    2010-01-01

    The response of cells to shear flow is primarily determined by the asymmetry of the external forces and moments that are sensed by each member of a focal adhesion pair connected by a contractile stress fiber. In the theory presented here, we suggest a physical model in which each member of such a pair of focal adhesions is treated as an elastic body subject to both a myosin-activated contractile force and the shear stress induced by the external flow. The elastic response of a focal adhesion complex is much faster than the active cellular processes that determine the size of the associated focal adhesions and the direction of the complex relative to the imposed flow. Therefore, the complex attains its mechanical equilibrium configuration which may change because of the cellular activity. Our theory is based on the experimental observation that focal adhesions modulate their cross-sectional area in order to attain an optimal shear. Using this assumption, our elastic model shows that such a complex can passively change its orientation to align parallel to the direction of the flow.

  13. Flotillins Regulate Focal Adhesions by Interacting with α-Actinin and by Influencing the Activation of Focal Adhesion Kinase

    Directory of Open Access Journals (Sweden)

    Antje Banning

    2018-04-01

    Full Text Available Cell–matrix adhesion and cell migration are physiologically important processes that also play a major role in cancer spreading. In cultured cells, matrix adhesion depends on integrin-containing contacts such as focal adhesions. Flotillin-1 and flotillin-2 are frequently overexpressed in cancers and are associated with poor survival. Our previous studies have revealed a role for flotillin-2 in cell–matrix adhesion and in the regulation of the actin cytoskeleton. We here show that flotillins are important for cell migration in a wound healing assay and influence the morphology and dynamics of focal adhesions. Furthermore, anchorage-independent growth in soft agar is enhanced by flotillins. In the absence of flotillins, especially flotillin-2, phosphorylation of focal adhesion kinase and extracellularly regulated kinase is diminished. Flotillins interact with α-actinin, a major regulator of focal adhesion dynamics. These findings are important for understanding the molecular mechanisms of how flotillin overexpression in cancers may affect cell migration and, especially, enhance metastasis formation.

  14. Protein kinase C involvement in focal adhesion formation

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    1992-01-01

    Matrix molecules such as fibronectin can promote cell attachment, spreading and focal adhesion formation. Although some interactions of fibronectin with cell surface receptors have now been identified, the consequent activation of intracellular messenger systems by cell/matrix interactions have...... still to be elucidated. We show here that the kinase inhibitors H7 and HA1004 reduce focal adhesion and stress fiber formation in response to fibronectin in a dose-dependent manner, and that activators of protein kinase C can promote their formation under conditions where they do not normally form....... Fibroblasts spread within 1h on substrata composed of fibronectin and formed focal adhesions by 3h, as monitored by interference reflection microscopy (IRM) and by labeling for talin, vinculin and integrin beta 1 subunits. In addition, stress fibers were visible. When cells were allowed to spread for 1h...

  15. Focal adhesion interactions with topographical structures: a novel method for immuno-SEM labelling of focal adhesions in S-phase cells.

    Science.gov (United States)

    Biggs, M J P; Richards, R G; Wilkinson, C D W; Dalby, M J

    2008-07-01

    Current understanding of the mechanisms involved in osseointegration following implantation of a biomaterial has led to adhesion quantification being implemented as an assay of cytocompatibility. Such measurement can be hindered by intra-sample variation owing to morphological changes associated with the cell cycle. Here we report on a new scanning electron microscopical method for the simultaneous immunogold labelling of cellular focal adhesions and S-phase nuclei identified by BrdU incorporation. Prior to labelling, cellular membranes are removed by tritonization and antigens of non-interest blocked by serum incubation. Adhesion plaque-associated vinculin and S-phase nuclei were both separately labelled with a 1.4 nm gold colloid and visualized by subsequent colloid enhancement via silver deposition. This study is specifically concerned with the effects microgroove topographies have on adhesion formation in S-phase osteoblasts. By combining backscattered electron (BSE) imaging with secondary electron (SE) imaging it was possible to visualize S-phase nuclei and the immunogold-labelled adhesion sites in one energy 'plane' and the underlying nanotopography in another. Osteoblast adhesion to these nanotopographies was ascertained by quantification of adhesion complex formation.

  16. Focal adhesion kinase maintains, but not increases the adhesion of dental pulp cells.

    Science.gov (United States)

    Qian, Yuyan; Shao, Meiying; Zou, Wenlin; Wang, Linyan; Cheng, Ran; Hu, Tao

    2017-04-01

    Focal adhesion kinase (FAK) functions as a key enzyme in the integrin-mediated adhesion-signalling pathway. Here, we aimed to investigate the effects of FAK on adhesion of human dental pulp (HDP) cells. We transfected lentiviral vectors to silence or overexpress FAK in HDP cells ex vivo. Early cell adhesion, cell survival and focal contacts (FCs)-related proteins (FAK and paxillin) were examined. By using immunofluorescence, the formation of FCs and cytoskeleton was detected, respectively. We found that both adhesion and survival of HDP cells were suppressed by FAK inhibition. However, FAK overexpression slightly inhibited cell adhesion and exhibited no change in cell survival compared with the control. A thick rim of cytoskeleton accumulated and smaller dot-shaped FCs appeared in FAK knockdown cells. Phosphorylation of paxillin (p-paxillin) was inhibited in FAK knockdown cells, verifying that the adhesion was inhibited. Less cytoskeleton and elongated FCs were observed in FAK-overexpressed cells. However, p-paxillin had no significant difference compared with the control. In conclusion, the data suggest that FAK maintains cell adhesion, survival and cytoskeleton formation, but excessive FAK has no positive effects on these aspects.

  17. Comparing the mechanical influence of vinculin, focal adhesion kinase and p53 in mouse embryonic fibroblasts

    International Nuclear Information System (INIS)

    Klemm, Anna H.; Diez, Gerold; Alonso, Jose-Luis; Goldmann, Wolfgang H.

    2009-01-01

    Cytoskeletal reorganization is an ongoing process when cells adhere, move or invade extracellular substrates. The cellular force generation and transmission are determined by the intactness of the actomyosin-(focal adhesion complex)-integrin connection. We investigated the intracellular course of action in mouse embryonic fibroblasts deficient in the focal adhesion proteins vinculin and focal adhesion kinase (FAK) and the nuclear matrix protein p53 using magnetic tweezer and nanoparticle tracking techniques. Results show that the lack of these proteins decrease cellular stiffness and affect cell rheological behavior. The decrease in cellular binding strength was higher in FAK- to vinculin-deficient cells, whilst p53-deficient cells showed no effect compared to wildtype cells. The intracellular cytoskeletal activity was lowest in wildtype cells, but increased in the following order when cells lacked FAK+p53 > p53 > vinculin. In summary, cell mechanical processes are differently affected by the focal adhesion proteins vinculin and FAK than by the nuclear matrix protein, p53.

  18. Actin dynamics at focal adhesions: a common endpoint and putative therapeutic target for proteinuric kidney diseases.

    Science.gov (United States)

    Sever, Sanja; Schiffer, Mario

    2018-06-01

    Proteinuria encompasses diverse causes including both genetic diseases and acquired forms such as diabetic and hypertensive nephropathy. The basis of proteinuria is a disturbance in size selectivity of the glomerular filtration barrier, which largely depends on the podocyte: a terminally differentiated epithelial cell type covering the outer surface of the glomerulus. Compromised podocyte structure is one of the earliest signs of glomerular injury. The phenotype of diverse animal models and podocyte cell culture firmly established the essential role of the actin cytoskeleton in maintaining functional podocyte structure. Podocyte foot processes, actin-based membrane extensions, contain 2 molecularly distinct "hubs" that control actin dynamics: a slit diaphragm and focal adhesions. Although loss of foot processes encompasses disassembly of slit diaphragm multiprotein complexes, as long as cells are attached to the glomerular basement membrane, focal adhesions will be the sites in which stress due to filtration flow is counteracted by forces generated by the actin network in foot processes. Numerous studies within last 20 years have identified actin binding and regulatory proteins as well as integrins as essential components of signaling and actin dynamics at focal adhesions in podocytes, suggesting that some of them may become novel, druggable targets for proteinuric kidney diseases. Here we review evidence supporting the idea that current treatments for chronic kidney diseases beneficially and directly target the podocyte actin cytoskeleton associated with focal adhesions and suggest that therapeutic reagents that target the focal adhesion-regulated actin cytoskeleton in foot processes have potential to modernize treatments for chronic kidney diseases. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  19. Protein kinase C, focal adhesions and the regulation of cell migration

    DEFF Research Database (Denmark)

    Fogh, Betina S; Multhaupt, Hinke A B; Couchman, John Robert

    2014-01-01

    in their intracellular compartment. Among these are tyrosine kinases, which have received a great deal of attention, whereas the serine/threonine kinase protein kinase C has received much less. Here the status of protein kinase C in focal adhesions and cell migration is reviewed, together with discussion of its roles...... and adhesion turnover. Focal adhesions, or focal contacts, are widespread organelles at the cell-matrix interface. They arise as a result of receptor interactions with matrix ligands, together with clustering. Recent analysis shows that focal adhesions contain a very large number of protein components...

  20. Crystal Structure of the FERM Domain of Focal Adhesion Kinase

    International Nuclear Information System (INIS)

    Ceccarelli, D.; Song, H.; Poy, F.; Schaller, M.; Eck, M.

    2006-01-01

    Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. Through phosphorylation of proteins assembled at the cytoplasmic tails of integrins, FAK promotes signaling events that modulate cellular growth, survival, and migration. The amino-terminal region of FAK contains a region of sequence homology with band 4.1 and ezrin/radixin/moesin (ERM) proteins termed a FERM domain. FERM domains are found in a variety of signaling and cytoskeletal proteins and are thought to mediate intermolecular interactions with partner proteins and phospholipids at the plasma membrane and intramolecular regulatory interactions. Here we report two crystal structures of an NH2-terminal fragment of avian FAK containing the FERM domain and a portion of the regulatory linker that connects the FERM and kinase domains. The tertiary folds of the three subdomains (F1, F2, and F3) are similar to those of known FERM structures despite low sequence conservation. Differences in the sequence and relative orientation of the F3 subdomain alters the nature of the interdomain interface, and the phosphoinositide binding site found in ERM family FERM domains is not present in FAK. A putative protein interaction site on the F3 lobe is masked by the proximal region of the linker. Additionally, in one structure the adjacent Src SH3 and SH2 binding sites in the linker associate with the surfaces of the F3 and F1 lobes, respectively. These structural features suggest the possibility that protein interactions of the FAK FERM domain can be regulated by binding of Src kinases to the linker segment

  1. Super-resolution links vinculin localization to function in focal adhesions.

    Science.gov (United States)

    Giannone, Grégory

    2015-07-01

    Integrin-based focal adhesions integrate biochemical and biomechanical signals from the extracellular matrix and the actin cytoskeleton. The combination of three-dimensional super-resolution imaging and loss- or gain-of-function protein mutants now links the nanoscale dynamic localization of proteins to their activation and function within focal adhesions.

  2. ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation

    Directory of Open Access Journals (Sweden)

    Timothy J. Mead

    2018-04-01

    Full Text Available Summary: Focal adhesions anchor cells to extracellular matrix (ECM and direct assembly of a pre-stressed actin cytoskeleton. They act as a cellular sensor and regulator, linking ECM to the nucleus. Here, we identify proteolytic turnover of the anti-adhesive proteoglycan versican as a requirement for maintenance of smooth muscle cell (SMC focal adhesions. Using conditional deletion in mice, we show that ADAMTS9, a secreted metalloprotease, is required for myometrial activation during late gestation and for parturition. Through knockdown of ADAMTS9 in uterine SMC, and manipulation of pericellular versican via knockdown or proteolysis, we demonstrate that regulated pericellular matrix dynamics is essential for focal adhesion maintenance. By influencing focal adhesion formation, pericellular versican acts upstream of cytoskeletal assembly and SMC differentiation. Thus, pericellular versican proteolysis by ADAMTS9 balances pro- and anti-adhesive forces to maintain an SMC phenotype, providing a concrete example of the dynamic reciprocity of cells and their ECM. : Mead et al. identify a proteolytic mechanism that actively maintains a pericellular microenvironment conducive to uterine smooth muscle activation prior to parturition. They show that pericellular matrix proteolysis by the secreted metalloprotease ADAMTS9 is crucial for maintenance of focal adhesions in uterine smooth muscle cells, and its absence impairs parturition. Keywords: metalloprotease, extracellular matrix, smooth muscle, proteoglycan, myometrium, parturition, uterus, focal adhesion, proteolysis, interference reflection microscopy

  3. Conformational Dynamics of the Focal Adhesion Targeting Domain Control Specific Functions of Focal Adhesion Kinase in Cells

    KAUST Repository

    Kadaré, Gress

    2015-01-02

    Focal adhesion (FA) kinase (FAK) regulates cell survival and motility by transducing signals from membrane receptors. The C-terminal FA targeting (FAT) domain of FAK fulfils multiple functions, including recruitment to FAs through paxillin binding. Phosphorylation of FAT on Tyr925 facilitates FA disassembly and connects to the MAPK pathway through Grb2 association, but requires dissociation of the first helix (H1) of the four-helix bundle of FAT. We investigated the importance of H1 opening in cells by comparing the properties of FAK molecules containing wild-type or mutated FAT with impaired or facilitated H1 openings. These mutations did not alter the activation of FAK, but selectively affected its cellular functions, including self-association, Tyr925 phosphorylation, paxillin binding, and FA targeting and turnover. Phosphorylation of Tyr861, located between the kinase and FAT domains, was also enhanced by the mutation that opened the FAT bundle. Similarly phosphorylation of Ser910 by ERK in response to bombesin was increased by FAT opening. Although FAK molecules with the mutation favoring FAT opening were poorly recruited at FAs, they efficiently restored FA turnover and cell shape in FAK-deficient cells. In contrast, the mutation preventing H1 opening markedly impaired FAK function. Our data support the biological importance of conformational dynamics of the FAT domain and its functional interactions with other parts of the molecule.

  4. Cancer cell metastasis; perspectives from the focal adhesion

    Directory of Open Access Journals (Sweden)

    Lefteris C Zacharia

    2015-10-01

    Full Text Available In almost all cancers, most patients die from metastatic disease and not from the actual primary tumor. That is why addressing the problem of metastasis is of utmost importance for the successful treatment and improved survival of cancer patients. Metastasis is a complex process that ultimately leads to cancer cells spreading from the tumor to distant sites of the body. During this process, cancer cells tend to lose contact with the extracellular matrix (ECM and neighboring cells within the primary tumor, and are thus able to invade surrounding tissues. Hence, ECM, and the ECM-associated adhesion proteins play a critical role in the metastatic process. This review will focus on recent literature regarding interesting and novel molecules at the cell-ECM adhesion sites, namely migfilin, mitogen-inducible gene-2 (Mig-2 and Ras suppressor-1 (RSU-1, that are also critically involved in cancer cell metastasis, emphasizing on data from experiments performed in vitro in breast cancer and hepatocellular carcinoma cell lines as well as human breast cancer tissue samples.

  5. HAb18G/CD147 regulates vinculin-mediated focal adhesion and cytoskeleton organization in cultured human hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Qiang Liang

    Full Text Available Focal adhesions (FAs, integrin-mediated macromolecular complexes located at the cell membrane extracellular interface, have been shown to regulate cell adhesion and migration. Our previous studies have indicated that HAb18G/CD147 (CD147 is involved in cytoskeleton reorganization and FA formation in human hepatocellular carcinoma (HCC cells. However, the precise mechanisms underlying these processes remain unclear. In the current study, we determined that CD147 was involved in vinculin-mediated FA focal adhesion formation in HCC cells. We also found that deletion of CD147 led to reduced vinculin-mediated FA areas (P<0.0001, length/width ratios (P<0.0001, and mean intensities (P<0.0001. CD147 promoted lamellipodia formation by localizing Arp2/3 to the leading edge of the cell. Deletion of CD147 significantly reduced the fluorescence (t1/2 recovery times (22.7±3.3 s of vinculin-mediated focal adhesions (P<0.0001. In cell-spreading assays, CD147 was found to be essential for dynamic focal adhesion enlargement and disassembly. Furthermore, the current data showed that CD147 reduced tyrosine phosphorylation in vinculin-mediated focal adhesions, and enhanced the accumulation of the acidic phospholipid phosphatidylinositol-4, 5-bisphosphate (PIP2. Together, these results revealed that CD147 is involved in vinculin-mediated focal adhesion formation, which subsequently promotes cytoskeleton reorganization to facilitate invasion and migration of human HCC cells.

  6. Substrate, focal adhesions, and actin filaments: a mechanical unit with a weak spot for mechanosensitive proteins

    International Nuclear Information System (INIS)

    Kirchenbuechler, David; Born, Simone; Kirchgessner, Norbert; Houben, Sebastian; Hoffmann, Bernd; Merkel, Rudolf

    2010-01-01

    Mechanosensing is a vital prerequisite for dynamic remodeling of focal adhesions and cytoskeletal structures upon substrate deformation. For example, tissue formation, directed cell orientation or cell differentiation are regulated by such mechanosensing processes. Focal adhesions and the actin cytoskeleton are believed to be involved in these processes, but where mechanosensing molecules are located and how elastic substrate, focal adhesions and the cytoskeleton couple with each other upon substrate deformation still remains obscure. To approach these questions we have developed a sensitive method to apply defined spatially decaying deformation fields to cells cultivated on ultrasoft elastic substrates and to accurately quantify the resulting displacements of the actin cytoskeleton, focal adhesions, as well as the substrate. Displacement fields were recorded in live cell microscopy by tracking either signals from fluorescent proteins or marker particles in the substrate. As model cell type we used myofibroblasts. These cells are characterized by highly stable adhesion and force generating structures but are still able to detect mechanical signals with high sensitivity. We found a rigid connection between substrate and focal adhesions. Furthermore, stress fibers were found to be barely extendable almost over their whole lengths. Plastic deformation took place only at the very ends of actin filaments close to focal adhesions. As a result, this area became elongated without extension of existing actin filaments by polymerization. Both ends of the stress fibers were mechanically coupled with detectable plastic deformations on either site. Interestingly, traction force dependent substrate deformation fields remained mostly unaffected even when stress fiber elongations were released. These data argue for a location of mechanosensing proteins at the ends of actin stress fibers and describe, except for these domains, the whole system to be relatively rigid for tensile

  7. Fetuin-A associates with histones intracellularly and shuttles them to exosomes to promote focal adhesion assembly resulting in rapid adhesion and spreading in breast carcinoma cells.

    Science.gov (United States)

    Nangami, Gladys; Koumangoye, Rainelli; Shawn Goodwin, J; Sakwe, Amos M; Marshall, Dana; Higginbotham, James; Ochieng, Josiah

    2014-11-01

    The present analyses were undertaken to define the mechanisms by which fetuin-A modulates cellular adhesion. FLAG-tagged fetuin-A was expressed in breast carcinoma and HEK-293T cells. We demonstrated by confocal microscopy that fetuin-A co-localizes with histone H2A in the cell nucleus, forms stable complexes with histones such as H2A and H3 in solution, and shuttles histones to exosomes. The rate of cellular adhesion and spreading to either fibronectin or laminin coated wells was accelerated significantly in the presence of either endogenous fetuin-A or serum derived protein. More importantly, the formation of focal adhesion complexes on surfaces coated by laminin or fibronectin was accelerated in the presence of fetuin-A or histone coated exosomes. Cellular adhesion mediated by histone coated exosomes was abrogated by heparin and heparinase III. Heparinase III cleaves heparan sulfate from cell surface heparan sulfate proteoglycans. Lastly, the uptake of histone coated exosomes and subsequent cellular adhesion, was abrogated by heparin. Taken together, the data suggest a mechanism where fetuin-A, either endogenously synthesized or supplied extracellularly can extract histones from the nucleus or elsewhere in the cytosol/membrane and load them on cellular exosomes which then mediate adhesion by interacting with cell surface heparan sulfate proteoglycans via bound histones. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Inhibiting focal adhesion kinase (FAK) blocks IL-4 induced VCAM-1 expression and eosinophil recruitment in vitro and in vivo.

    Science.gov (United States)

    Aulakh, Gurpreet K; Petri, Björn; Wojcik, Katarzyna M; Colarusso, Pina; Lee, James J; Patel, Kamala D

    2018-04-06

    Leukocyte recruitment plays a critical role during both normal inflammation and chronic inflammatory diseases, and ongoing studies endeavor to better understand the complexities of this process. Focal adhesion kinase (FAK) is well known for its role in cancer, yet it also has been shown to regulate aspects of neutrophil and B16 melanoma cell recruitment by rapidly influencing endothelial cell focal adhesion dynamics and junctional opening. Recently, we found that FAK related non-kinase (FRNK), a protein that is often used as a FAK dominant negative, blocked eosinophil transmigration by preventing the transcription of vascular cell adhesion molecule-1 (VCAM-1) and eotaxin-3 (CCL26). Surprisingly, the blocking occurred even in the absence of endogenous FAK. To better understand the role of FAK in leukocyte recruitment, we used a FAK-specific inhibitor (PF-573228) and determined the effect on IL-4 induced eosinophil recruitment in vitro and in vivo. PF-573228 prevented the expression of VCAM-1 and CCL26 expression in IL-4-stimulated human endothelial cells in vitro. As a result, eosinophil adhesion and transmigration were blocked. PF-572338 also prevented IL-4-induced VCAM-1 expression in vivo. Using brightfield intravital microscopy, we found that PF-573228 decreased leukocyte rolling flux, adhesion, and emigration. We specifically examined eosinophil recruitment in vivo by using an eosinophil-GFP reporter mouse and found PF-573228 attenuated eosinophil emigration. This study reveals that a FAK inhibitor influences inflammation through its action on eosinophil recruitment. ©2018 Society for Leukocyte Biology.

  9. Focal adhesive arachnoiditis of the spinal cord: Imaging diagnosis and surgical resolution

    Directory of Open Access Journals (Sweden)

    Hiroki Morisako

    2010-01-01

    Full Text Available Background: Although adhesive arachnoiditis of the spinal cord can cause progressive symptoms associated with syringomyelia or myelomalacia, its surgical resolution based on the imaging diagnosis is not well characterized. This study aims to describe the use of imaging for the diagnosis of focal adhesive arachnoiditis of the spinal cord and its surgical resolution using microsurgical arachnoidolysis. Materials and Methods: Four consecutive patients with symptomatic syringomyelia or myelomalacia caused by focal adhesive arachnoiditis underwent microsurgical arachnoidolysis. Comprehensive imaging evaluation using constructive interference in steady-state (CISS magnetic resonance imaging (MRI or myelographic MR imaging using true fast imaging with steady-state precession (TrueFISP sequences was included before surgery to determine the surgical indication. Results: In all four patients a focal adhesion was identified at the cervical or thoracic level of the spinal cord, a consequence of infection or trauma. Three patients showed modest or minor improvement in neurological function, and one patient was unchanged after surgery. The syringomyelia or myelomalacia resolved after surgery and no recurrence was noted within the follow-up period, which ranged from 5 months to 30 months. Conclusions: MRI diagnosis of focal adhesive arachnoiditis is critical to determine the surgical indication. Microsurgical arachnoidolysis appears to be a straightforward method for stabilizing the progressive symptoms, though the procedure is technically demanding.

  10. Quantitative measurement of changes in adhesion force involving focal adhesion kinase during cell attachment, spread, and migration

    International Nuclear Information System (INIS)

    Wu, C.-C.; Su, H.-W.; Lee, C.-C.; Tang, M.-J.; Su, F.-C.

    2005-01-01

    Focal adhesion kinase (FAK) is a critical protein for the regulation of integrin-mediated cellular functions and it can enhance cell motility in Madin-Darby canine kidney (MDCK) cells by hepatocyte growth factor (HGF) induction. We utilized optical trapping and cytodetachment techniques to measure the adhesion force between pico-Newton and nano-Newton (nN) for quantitatively investigating the effects of FAK on adhesion force during initial binding (5 s), beginning of spreading (30 min), spreadout (12 h), and migration (induced by HGF) in MDCK cells with overexpressed FAK (FAK-WT), FAK-related non-kinase (FRNK), as well as normal control cells. Optical tweezers was used to measure the initial binding force between a trapped cell and glass coverslide or between a trapped bead and a seeded cell. In cytodetachment, the commercial atomic force microscope probe with an appropriate spring constant was used as a cyto-detacher to evaluate the change of adhesion force between different FAK expression levels of cells in spreading, spreadout, and migrating status. The results demonstrated that FAK-WT significantly increased the adhesion forces as compared to FRNK cells throughout all the different stages of cell adhesion. For cells in HGF-induced migration, the adhesion force decreased to almost the same level (∼600 nN) regardless of FAK levels indicating that FAK facilitates cells to undergo migration by reducing the adhesion force. Our results suggest FAK plays a role of enhancing cell adhesive ability in the binding and spreading, but an appropriate level of adhesion force is required for HGF-induced cell migration

  11. Combining PALM and SOFI for quantitative imaging of focal adhesions in living cells

    Science.gov (United States)

    Deschout, Hendrik; Lukes, Tomas; Sharipov, Azat; Feletti, Lely; Lasser, Theo; Radenovic, Aleksandra

    2017-02-01

    Focal adhesions are complicated assemblies of hundreds of proteins that allow cells to sense their extracellular matrix and adhere to it. Although most focal adhesion proteins have been identified, their spatial organization in living cells remains challenging to observe. Photo-activated localization microscopy (PALM) is an interesting technique for this purpose, especially since it allows estimation of molecular parameters such as the number of fluorophores. However, focal adhesions are dynamic entities, requiring a temporal resolution below one minute, which is difficult to achieve with PALM. In order to address this problem, we merged PALM with super-resolution optical fluctuation imaging (SOFI) by applying both techniques to the same data. Since SOFI tolerates an overlap of single molecule images, it can improve the temporal resolution compared to PALM. Moreover, an adaptation called balanced SOFI (bSOFI) allows estimation of molecular parameters, such as the fluorophore density. We therefore performed simulations in order to assess PALM and SOFI for quantitative imaging of dynamic structures. We demonstrated the potential of our PALM-SOFI concept as a quantitative imaging framework by investigating moving focal adhesions in living cells.

  12. A role for the juxtamembrane cytoplasm in the molecular dynamics of focal adhesions.

    Directory of Open Access Journals (Sweden)

    Haguy Wolfenson

    Full Text Available Focal adhesions (FAs are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. Considerable information is available on the complex molecular composition of these sites, yet the regulation of FA dynamics is largely unknown. Based on a combination of FRAP studies in live cells, with in silico simulations and mathematical modeling, we show that the FA plaque proteins paxillin and vinculin exist in four dynamic states: an immobile FA-bound fraction, an FA-associated fraction undergoing exchange, a juxtamembrane fraction experiencing attenuated diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane region surrounding FAs displays a gradient of FA plaque proteins with respect to both concentration and dynamics. Based on these findings, we propose a new model for the regulation of FA dynamics in which this juxtamembrane domain acts as an intermediary layer, enabling an efficient regulation of FA formation and reorganization.

  13. Targeted Molecular Dynamics to determine Focal Adhesion Targeting Domain Folding Intermediates

    Directory of Open Access Journals (Sweden)

    Pallavi Mohanty

    2017-10-01

    Full Text Available The Focal adhesion kinase (FAT domain of Focal Adhesion Kinase is a four helical bundle known for conformational plasticity. FAT adopts two distinctly different conformations i.e., close (cFAT and arm-exchanged (aeFAT states under native conditions [1]. The slow transition from cFAT to aeFAT is likely to proceed through an open intermediate state that allows YENV motif to attain β-turn conformation and phosphorylation of Y925 by Src kinases [2]. The two end states of FAT are known to interact with Paxillin and are responsible for maintaining steady state in Heart while intermediate conformation interacts with Grb2-SH2 leading to Pathological Cardiac Hypertrophy (PAH [2]. 10ns Targeted Molecular Dynamics (TMD was done between c- and aeFAT in order to explore the conformational transition and to capture pathologically relevant oFAT. Cluster and dynamic cross correlation analysis (DCCA of TMD generated trajectory was done and the selected FAT intermediate was docked with Grb2-SH2 using HADDOCK v2.2 docking followed by molecular dynamics. Conservation analysis of FAT-Grb2 binding site was done using CONSURF [3]. A Pharmacophore FAT-Grb2 complex was generated using SPARKv1.2 and submitted for Virtual screening using BLAZE v4. Drug likeliness and ADMET properties were calculated using MOLINSPIRATION tool. TMD reveals six clusters and DCCA showed positively and negatively correlated region along the transition pathway. Intermediates with competence for Grb2 interaction were docked with Grb2 and best binding complex was further refined. MMPBSA binding energy calculations revealed the best binding pose where the phosphorylated YENV motif of Human FAT interacted with a charged and hydrophobic pocket of Grb2. The conservation analysis showed that the charged pocket was more conserved in comparison with the hydrophobic pocket, hence providing useful insights on binding and specificity determining residues in Grb2. Virtual screening using the pharmacophore

  14. Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes

    DEFF Research Database (Denmark)

    Goñi, Guillermina M; Epifano, Carolina; Boskovic, Jasminka

    2014-01-01

    Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase (NRTK) with key roles in integrating growth and cell matrix adhesion signals, and FAK is a major driver of invasion and metastasis in cancer. Cell adhesion via integrin receptors is well known to trigger FAK signaling, and many of the p...

  15. FAK dimerization controls its kinase-dependent functions at focal adhesions

    KAUST Repository

    Brami-Cherrier, Karen; Gervasi, Nicolas; Arsenieva, Diana A.; Walkiewicz, Katarzyna; Boutterin, Marie Claude; Ortega, Á lvaro Darí o; Leonard, Paul G.; Seantier, Bastien; Gasmi, Laï la; Bouceba, Tahar; Kadaré , Gress; Girault -, Jean Antoine; Arold, Stefan T.

    2014-01-01

    Focal adhesion kinase (FAK) controls adhesion-dependent cell motility, survival, and proliferation. FAK has kinase-dependent and kinase-independent functions, both of which play major roles in embryogenesis and tumor invasiveness. The precise mechanisms of FAK activation are not known. Using x-ray crystallography, small angle x-ray scattering, and biochemical and functional analyses, we show that the key step for activation of FAK's kinase-dependent functions-autophosphorylation of tyrosine-397-requires site-specific dimerization of FAK. The dimers form via the association of the N-terminal FERM domain of FAK and are stabilized by an interaction between FERM and the C-terminal FAT domain. FAT binds to a basic motif on FERM that regulates co-activation and nuclear localization. FAK dimerization requires local enrichment, which occurs specifically at focal adhesions. Paxillin plays a dual role, by recruiting FAK to focal adhesions and by reinforcing the FAT:FERM interaction. Our results provide a structural and mechanistic framework to explain how FAK combines multiple stimuli into a site-specific function. The dimer interfaces we describe are promising targets for blocking FAK activation. © 2014 The Authors.

  16. FAK dimerization controls its kinase-dependent functions at focal adhesions

    KAUST Repository

    Brami-Cherrier, Karen

    2014-01-30

    Focal adhesion kinase (FAK) controls adhesion-dependent cell motility, survival, and proliferation. FAK has kinase-dependent and kinase-independent functions, both of which play major roles in embryogenesis and tumor invasiveness. The precise mechanisms of FAK activation are not known. Using x-ray crystallography, small angle x-ray scattering, and biochemical and functional analyses, we show that the key step for activation of FAK\\'s kinase-dependent functions-autophosphorylation of tyrosine-397-requires site-specific dimerization of FAK. The dimers form via the association of the N-terminal FERM domain of FAK and are stabilized by an interaction between FERM and the C-terminal FAT domain. FAT binds to a basic motif on FERM that regulates co-activation and nuclear localization. FAK dimerization requires local enrichment, which occurs specifically at focal adhesions. Paxillin plays a dual role, by recruiting FAK to focal adhesions and by reinforcing the FAT:FERM interaction. Our results provide a structural and mechanistic framework to explain how FAK combines multiple stimuli into a site-specific function. The dimer interfaces we describe are promising targets for blocking FAK activation. © 2014 The Authors.

  17. Human fibroblasts display a differential focal adhesion phenotype relative to chimpanzee.

    Science.gov (United States)

    Advani, Alexander S; Chen, Annie Y; Babbitt, Courtney C

    2016-01-01

    There are a number of documented differences between humans and our closest relatives in responses to wound healing and in disease susceptibilities, suggesting a differential cellular response to certain environmental factors. In this study, we sought to look at a specific cell type, fibroblasts, to examine differences in cellular adhesion between humans and chimpanzees in visualized cells and in gene expression. We have found significant differences in the number of focal adhesions between primary human and chimpanzee fibroblasts. Additionally, we see that adhesion related gene ontology categories are some of the most differentially expressed between human and chimpanzee in normal fibroblast cells. These results suggest that human and chimpanzee fibroblasts may have somewhat different adhesive properties, which could play a role in differential disease phenotypes and responses to external factors. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  18. How to awaken your nanomachines: Site-specific activation of focal adhesion kinases through ligand interactions

    KAUST Repository

    Walkiewicz, Katarzyna Wiktoria

    2015-06-17

    The focal adhesion kinase (FAK) and the related protein-tyrosine kinase 2-beta (Pyk2) are highly versatile multidomain scaffolds central to cell adhesion, migration, and survival. Due to their key role in cancer metastasis, understanding and inhibiting their functions are important for the development of targeted therapy. Because FAK and Pyk2 are involved in many different cellular functions, designing drugs with partial and function-specific inhibitory effects would be desirable. Here, we summarise recent progress in understanding the structural mechanism of how the tug-of-war between intramolecular and intermolecular interactions allows these protein ‘nanomachines’ to become activated in a site-specific manner.

  19. Stretch activates human myometrium via ERK, caldesmon and focal adhesion signaling.

    Directory of Open Access Journals (Sweden)

    Yunping Li

    2009-10-01

    Full Text Available An incomplete understanding of the molecular mechanisms responsible for myometrial activation from the quiescent pregnant state to the active contractile state during labor has hindered the development of effective therapies for preterm labor. Myometrial stretch has been implicated clinically in the initiation of labor and the etiology of preterm labor, but the molecular mechanisms involved in the human have not been determined. We investigated the mechanisms by which gestation-dependent stretch contributes to myometrial activation, by using human uterine samples from gynecologic hysterectomies and Cesarean sections. Here we demonstrate that the Ca requirement for activation of the contractile filaments in human myometrium increases with caldesmon protein content during gestation and that an increase in caldesmon phosphorylation can reverse this inhibitory effect during labor. By using phosphotyrosine screening and mass spectrometry of stretched human myometrial samples, we identify 3 stretch-activated focal adhesion proteins, FAK, p130Cas, and alpha actinin. FAK-Y397, which signals integrin engagement, is constitutively phosphorylated in term human myometrium whereas FAK-Y925, which signals downstream ERK activation, is phosphorylated during stretch. We have recently identified smooth muscle Archvillin (SmAV as an ERK regulator. A newly produced SmAV-specific antibody demonstrates gestation-specific increases in SmAV protein levels and stretch-specific increases in SmAV association with focal adhesion proteins. Thus, whereas increases in caldesmon levels suppress human myometrium contractility during pregnancy, stretch-dependent focal adhesion signaling, facilitated by the ERK activator SmAV, can contribute to myometrial activation. These results suggest that focal adhesion proteins may present new targets for drug discovery programs aimed at regulation of uterine contractility.

  20. Angiogenin enhances cell migration by regulating stress fiber assembly and focal adhesion dynamics.

    Directory of Open Access Journals (Sweden)

    Saisai Wei

    Full Text Available Angiogenin (ANG acts on both vascular endothelial cells and cancer cells, but the underlying mechanism remains elusive. In this study, we carried out a co-immunoprecipitation assay in HeLa cells and identified 14 potential ANG-interacting proteins. Among these proteins, β-actin, α-actinin 4, and non-muscle myosin heavy chain 9 are stress fiber components and involved in cytoskeleton organization and movement, which prompted us to investigate the mechanism of action of ANG in cell migration. Upon confirmation of the interactions between ANG and the three proteins, further studies revealed that ANG co-localized with β-actin and α-actinin 4 at the leading edge of migrating cells. Down-regulation of ANG resulted in fewer but thicker stress fibers with less dynamics, which was associated with the enlargements of focal adhesions. The focal adhesion kinase activity and cell migration capacity were significantly decreased in ANG-deficient cells. Taken together, our data demonstrated that the existence of ANG in the cytoplasm optimizes stress fiber assembly and focal adhesion formation to accommodate cell migration. The finding that ANG promoted cancer cell migration might provide new clues for tumor metastasis research.

  1. The Src SH2 domain interacts dynamically with the focal adhesion kinase binding site as demonstrated by paramagnetic NMR spectroscopy.

    Science.gov (United States)

    Lindfors, Hanna E; Drijfhout, Jan Wouter; Ubbink, Marcellus

    2012-06-01

    The interaction between the tyrosine kinases Src and focal adhesion kinase (FAK) is a key step in signaling processes from focal adhesions. The phosphorylated tyrosine residue 397 in FAK is able to bind the Src SH2 domain. To establish the extent of the FAK binding motif, the binding affinity of the SH2 domain for phosphorylated and unphosphorylated FAK-derived peptides of increasing length was determined and compared with that of the internal Src SH2 binding site. It is shown that the FAK peptides have higher affinity than the internal binding site and that seven negative residues adjacent to the core SH2 binding motif increase the binding constant 30-fold. A rigid spin-label incorporated in the FAK peptides was used to establish on the basis of paramagnetic relaxation enhancement whether the peptide-protein complex is well defined. A large spread of the paramagnetic effects on the surface of the SH2 domain suggests that the peptide-protein complex exhibits dynamics, despite the high affinity of the peptide. The strong electrostatic interaction between the positive side of the SH2 domain and the negative peptide results in a high affinity but may also favor a dynamic interaction. Copyright © 2012 Wiley Periodicals, Inc.

  2. Disrupting the Scaffold to Improve Focal Adhesion Kinase–Targeted Cancer Therapeutics

    Science.gov (United States)

    Cance, William G.; Kurenova, Elena; Marlowe, Timothy; Golubovskaya, Vita

    2013-01-01

    Focal adhesion kinase (FAK) is emerging as a promising cancer target because it is highly expressed at both the transcriptional and translational level in cancer and is involved in many aspects of tumor growth, invasion, and metastasis. Existing FAK-based therapeutics focus on inhibiting the kinase's catalytic function and not the large scaffold it creates that includes many oncogenic receptor tyrosine kinases and tumor suppressor proteins. Targeting the FAK scaffold is a feasible and promising approach for developing highly specific therapeutics that disrupt FAK signaling pathways in cancer. PMID:23532331

  3. Disrupting the scaffold to improve focal adhesion kinase-targeted cancer therapeutics.

    Science.gov (United States)

    Cance, William G; Kurenova, Elena; Marlowe, Timothy; Golubovskaya, Vita

    2013-03-26

    Focal adhesion kinase (FAK) is emerging as a promising cancer target because it is highly expressed at both the transcriptional and translational level in cancer and is involved in many aspects of tumor growth, invasion, and metastasis. Existing FAK-based therapeutics focus on inhibiting the kinase's catalytic function and not the large scaffold it creates that includes many oncogenic receptor tyrosine kinases and tumor suppressor proteins. Targeting the FAK scaffold is a feasible and promising approach for developing highly specific therapeutics that disrupt FAK signaling pathways in cancer.

  4. Visualizing the interior architecture of focal adhesions with high-resolution traction maps.

    Science.gov (United States)

    Morimatsu, Masatoshi; Mekhdjian, Armen H; Chang, Alice C; Tan, Steven J; Dunn, Alexander R

    2015-04-08

    Focal adhesions (FAs) are micron-sized protein assemblies that coordinate cell adhesion, migration, and mechanotransduction. How the many proteins within FAs are organized into force sensing and transmitting structures is poorly understood. We combined fluorescent molecular tension sensors with super-resolution light microscopy to visualize traction forces within FAs with <100 nm spatial resolution. We find that αvβ3 integrin selectively localizes to high force regions. Paxillin, which is not generally considered to play a direct role in force transmission, shows a higher degree of spatial correlation with force than vinculin, talin, or α-actinin, proteins with hypothesized roles as force transducers. These observations suggest that αvβ3 integrin and paxillin may play important roles in mechanotransduction.

  5. How to awaken your nanomachines: Site-specific activation of focal adhesion kinases through ligand interactions.

    Science.gov (United States)

    Walkiewicz, Katarzyna W; Girault, Jean-Antoine; Arold, Stefan T

    2015-10-01

    The focal adhesion kinase (FAK) and the related protein-tyrosine kinase 2-beta (Pyk2) are highly versatile multidomain scaffolds central to cell adhesion, migration, and survival. Due to their key role in cancer metastasis, understanding and inhibiting their functions are important for the development of targeted therapy. Because FAK and Pyk2 are involved in many different cellular functions, designing drugs with partial and function-specific inhibitory effects would be desirable. Here, we summarise recent progress in understanding the structural mechanism of how the tug-of-war between intramolecular and intermolecular interactions allows these protein 'nanomachines' to become activated in a site-specific manner. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase.

    Science.gov (United States)

    Schlaepfer, D D; Hanks, S K; Hunter, T; van der Geer, P

    The cytoplasmic focal adhesion protein-tyrosine kinase (FAK) localizes with surface integrin receptors at sites where cells attach to the extracellular matrix. Increased FAK tyrosine phosphorylation occurs upon integrin engagement with fibronectin. Here we show that adhesion of murine NIH3T3 fibroblasts to fibronectin promotes SH2-domain-mediated association of the GRB2 adaptor protein and the c-Src protein-tyrosine kinase (PTK) with FAK in vivo, and also results in activation of mitogen-activated protein kinase (MAPK). In v-Src-transformed NIH3T3, the association of v-Src, GRB2 and Sos with FAK is independent of cell adhesion to fibronectin. The GRB2 SH2 domain binds directly to tyrosine-phosphorylated FAK. Mutation of tyrosine residue 925 of FAK (YENV motif) to phenylalanine blocks GRB2 SH2-domain binding to FAK in vitro. Our results show that fibronectin binding to integrins on NIH3T3 fibroblasts promotes c-Src and FAK association and formation of an integrin-activated signalling complex. Phosphorylation of FAK at Tyr 925 upon fibronectin stimulation creates an SH2-binding site for GRB2 which may link integrin engagement to the activation of the Ras/MAPK signal transduction pathway.

  7. The role of focal adhesion kinase in the regulation of cellular mechanical properties

    International Nuclear Information System (INIS)

    Mierke, Claudia Tanja

    2013-01-01

    The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation. (paper)

  8. The role of focal adhesion kinase in the regulation of cellular mechanical properties

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation.

  9. Mechanical stimulation of C2C12 cells increases m-calpain expression, focal adhesion plaque protein degradation

    DEFF Research Database (Denmark)

    Grossi, Alberto; Karlsson, Anders H; Lawson, Moira Ann

    2008-01-01

    . Stimulation due to stretch- or load-induced signaling is now beginning to be understood as a factor which affects gene sequences, protein synthesis and an increase in Ca2+ influx in myocytes. Evidence of the involvement of Ca2+ -dependent activity in myoblast fusion, cell membrane and cytoskeleton component...... reorganization due to the activity of the ubiquitous proteolytic enzymes, calpains, has been reported. Whether there is a link between stretch- or load-induced signaling and calpain expression and activation is not known. Using a magnetic bead stimulation assay and C2C12 mouse myoblasts cell population, we have...... demonstrated that mechanical stimulation via laminin receptors leads to an increase in m-calpain expression, but no increase in the expression of other calpain isoforms. Our study revealed that after a short period of stimulation, m-calpain relocates into focal adhesion complexes and is followed by a breakdown...

  10. FAK/src-family dependent activation of the Ste20-like kinase SLK is required for microtubule-dependent focal adhesion turnover and cell migration.

    Directory of Open Access Journals (Sweden)

    Simona Wagner

    2008-04-01

    Full Text Available Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown and dominant negative approaches, we show that the microtubule-associated Ste20-like kinase SLK is required for focal adhesion turnover and cell migration downstream of the FAK/c-src complex. Our results show that SLK co-localizes with paxillin, Rac1 and the microtubules at the leading edge of migrating cells and is activated by scratch wounding. SLK activation is dependent on FAK/c-src/MAPK signaling, whereas SLK recruitment to the leading edge is src-dependent but FAK independent. Our results show that SLK represents a novel focal adhesion disassembly signal.

  11. Organization and post-transcriptional processing of focal adhesion kinase gene

    Directory of Open Access Journals (Sweden)

    Enslen Hervé

    2006-08-01

    Full Text Available Abstract Background Focal adhesion kinase (FAK is a non-receptor tyrosine kinase critical for processes ranging from embryo development to cancer progression. Although isoforms with specific molecular and functional properties have been characterized in rodents and chicken, the organization of FAK gene throughout phylogeny and its potential to generate multiple isoforms are not well understood. Here, we study the phylogeny of FAK, the organization of its gene, and its post-transcriptional processing in rodents and human. Results A single orthologue of FAK and the related PYK2 was found in non-vertebrate species. Gene duplication probably occurred in deuterostomes after the echinoderma embranchment, leading to the evolution of PYK2 with distinct properties. The amino acid sequence of FAK and PYK2 is conserved in their functional domains but not in their linker regions, with the absence of autophosphorylation site in C. elegans. Comparison of mouse and human FAK genes revealed the existence of multiple combinations of conserved and non-conserved 5'-untranslated exons in FAK transcripts suggesting a complex regulation of their expression. Four alternatively spliced coding exons (13, 14, 16, and 31, previously described in rodents, are highly conserved in vertebrates. Cis-regulatory elements known to regulate alternative splicing were found in conserved alternative exons of FAK or in the flanking introns. In contrast, other reported human variant exons were restricted to Homo sapiens, and, in some cases, other primates. Several of these non-conserved exons may correspond to transposable elements. The inclusion of conserved alternative exons was examined by RT-PCR in mouse and human brain during development. Inclusion of exons 14 and 16 peaked at the end of embryonic life, whereas inclusion of exon 13 increased steadily until adulthood. Study of various tissues showed that inclusion of these exons also occurred, independently from each other, in a

  12. Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation

    DEFF Research Database (Denmark)

    Steffen, Anika; Ladwein, Markus; Dimchev, Georgi A

    2013-01-01

    can be potently stimulated by Rho GTPases of the Rac subfamily, but also by RhoG or Cdc42. Here we describe viable fibroblast cell lines genetically deficient for Rac1 that lack detectable levels of Rac2 and Rac3. Rac-deficient cells were devoid of apparent lamellipodia, but these structures were...... filopodia and established focal adhesions. Spreading in these cells was achieved by the extension of filopodia followed by the advancement of cytoplasmic veils between them. The number and size of focal adhesions as well as their intensity were largely unaffected by genetic removal of Rac1. However, Rac...

  13. Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation

    DEFF Research Database (Denmark)

    Bax, Daniel V; Mahalingam, Yashithra; Cain, Stuart

    2007-01-01

    We have defined the molecular basis of cell adhesion to fibrillin-1, the major structural component of extracellular microfibrils that are associated with elastic fibres. Using human dermal fibroblasts, and recombinant domain swap fragments containing the Arg-Gly-Asp motif, we have demonstrated...... a requirement for upstream domains for integrin-alpha(5)beta(1)-mediated cell adhesion and migration. An adjacent heparin-binding site, which supports focal adhesion formation, was mapped to the fibrillin-1 TB5 motif. Site-directed mutagenesis revealed two arginine residues that are crucial for heparin binding...

  14. Constrained Adherable Area of Nanotopographic Surfaces Promotes Cell Migration through the Regulation of Focal Adhesion via Focal Adhesion Kinase/Rac1 Activation.

    Science.gov (United States)

    Lim, Jiwon; Choi, Andrew; Kim, Hyung Woo; Yoon, Hyungjun; Park, Sang Min; Tsai, Chia-Hung Dylan; Kaneko, Makoto; Kim, Dong Sung

    2018-05-02

    Cell migration is crucial in physiological and pathological processes such as embryonic development and wound healing; such migration is strongly guided by the surrounding nanostructured extracellular matrix. Previous studies have extensively studied the cell migration on anisotropic nanotopographic surfaces; however, only a few studies have reported cell migration on isotropic nanotopographic surfaces. We herein, for the first time, propose a novel concept of adherable area on cell migration using isotropic nanopore surfaces with sufficient nanopore depth by adopting a high aspect ratio. As the pore size of the nanopore surface was controlled to 200, 300, and 400 nm in a fixed center-to-center distance of 480 nm, it produced 86, 68, and 36% of adherable area, respectively, on the fabricated surface. A meticulous investigation of the cell migration in response to changes in the constrained adherable area of the nanotopographic surface showed 1.4-, 1.5-, and 1.6-fold increase in migration speeds and a 1.4-, 2-, and 2.5-fold decrease in the number of focal adhesions as the adherable area was decreased to 86, 68, and 36%, respectively. Furthermore, a strong activation of FAK/Rac1 signaling was observed to be involved in the promoted cell migration. These results suggest that the reduced adherable area promotes cell migration through decreasing the FA formation, which in turn upregulates FAK/Rac1 activation. The findings in this study can be utilized to control the cell migration behaviors, which is a powerful tool in the research fields involving cell migration such as promoting wound healing and tissue repair.

  15. Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation.

    Directory of Open Access Journals (Sweden)

    Tomas Garzon-Muvdi

    Full Text Available Glioblastoma (GB is a highly invasive and lethal brain tumor due to its universal recurrence. Although it has been suggested that the electroneutral Na(+-K(+-Cl(- cotransporter 1 (NKCC1 can play a role in glioma cell migration, the precise mechanism by which this ion transporter contributes to GB aggressiveness remains poorly understood. Here, we focused on the role of NKCC1 in the invasion of human primary glioma cells in vitro and in vivo. NKCC1 expression levels were significantly higher in GB and anaplastic astrocytoma tissues than in grade II glioma and normal cortex. Pharmacological inhibition and shRNA-mediated knockdown of NKCC1 expression led to decreased cell migration and invasion in vitro and in vivo. Surprisingly, knockdown of NKCC1 in glioma cells resulted in the formation of significantly larger focal adhesions and cell traction forces that were approximately 40% lower than control cells. Epidermal growth factor (EGF, which promotes migration of glioma cells, increased the phosphorylation of NKCC1 through a PI3K-dependant mechanism. This finding is potentially related to WNK kinases. Taken together, our findings suggest that NKCC1 modulates migration of glioma cells by two distinct mechanisms: (1 through the regulation of focal adhesion dynamics and cell contractility and (2 through regulation of cell volume through ion transport. Due to the ubiquitous expression of NKCC1 in mammalian tissues, its regulation by WNK kinases may serve as new therapeutic targets for GB aggressiveness and can be exploited by other highly invasive neoplasms.

  16. Resveratrol Regulates Colorectal Cancer Cell Invasion by Modulation of Focal Adhesion Molecules.

    Science.gov (United States)

    Buhrmann, Constanze; Shayan, Parviz; Goel, Ajay; Shakibaei, Mehdi

    2017-09-27

    Resveratrol, a safe and multi-targeted agent, has been associated with suppression of survival, proliferation and metastasis of cancer, however, the underlying mechanisms for its anti-cancer activity, particularly on cellular signaling during cancer cell migration still remain poorly understood. We investigated the invasion response of two human colorectal cancer (CRC) cells (HCT116 and SW480) to resveratrol and studied the effect of specific pharmacological inhibitors, cytochalasin D (CytD) and focal adhesion kinase-inhibitor (FAK-I) on FAK, cell viability and migration in CRC. We found that resveratrol altered cell phenotype of both CRC cells, reduced cell viability and the results were comparable to FAK-I and CytD. These effects of resveratrol were associated with marked Sirt1 up-regulation, FAK down-regulation, inhibition of focal adhesion and potentiation of effects by combinatorial treatment of resveratrol and inhibitors. Interestingly, inhibition of FAK with FAK-I or treatment with CytD suppressed resveratrol-induced Sirt1 up-regulation and markedly down-regulated FAK expression. Resveratrol or combination treatment with inhibitors significantly activated caspase-3 and potentiated apoptosis. Moreover, resveratrol suppressed invasion and colony forming capacity, cell proliferation, β1-Integrin expression and activation of FAK of cells in alginate tumor microenvironment, similar to FAK-I or CytD. Finally, we demonstrated that resveratrol, FAK-I or CytD inhibited activation of NF-κB, suppressed NF-κB-dependent gene end-products involved in invasion, metastasis, and apoptosis; and these effects of resveratrol were potentiated by combination treatment with FAK-I or CytD. Our data illustrated that the anti-invasion effect of resveratrol by inhibition of FAK activity has a potential beneficial role in disease prevention and therapeutic management of CRC.

  17. HIGH PERFORMANCE PIAA CORONAGRAPHY WITH COMPLEX AMPLITUDE FOCAL PLANE MASKS

    International Nuclear Information System (INIS)

    Guyon, Olivier; Martinache, Frantz; Belikov, Ruslan; Soummer, Remi

    2010-01-01

    We describe a coronagraph approach where the performance of a Phase-Induced Amplitude Apodization (PIAA) coronagraph is improved by using a partially transmissive phase-shifting focal plane mask and a Lyot stop. This approach combines the low inner working angle offered by phase mask coronagraphy, the full throughput and uncompromized angular resolution of the PIAA approach, and the design flexibility of Apodized Pupil Lyot Coronagraph. A PIAA complex mask coronagraph (PIAACMC) is fully described by the focal plane mask size, or, equivalently, its complex transmission which ranges from 0 (opaque) to -1 (phase shifting). For all values of the transmission, the PIAACMC theoretically offers full on-axis extinction and 100% throughput at large angular separations. With a pure phase focal plane mask (complex transmission = -1), the PIAACMC offers 50% throughput at 0.64 λ/D while providing total extinction of an on-axis point source. This performance is very close to the 'fundamental performance limit' of coronagraphy derived from first principles. For very high contrast level, imaging performance with PIAACMC is in practice limited by the angular size of the on-axis target (usually a star). We show that this fundamental limitation must be taken into account when choosing the optimal value of the focal plane mask size in the PIAACMC design. We show that the PIAACMC enables visible imaging of Jupiter-like planets at ∼1.2 λ/D from the host star, and can therefore offer almost three times more targets than a PIAA coronagraph optimized for this type of observation. We find that for visible imaging of Earth-like planets, the PIAACMC gain over a PIAA is probably much smaller, as coronagraphic performance is then strongly constrained by stellar angular size. For observations at 'low' contrast (below ∼ 10 8 ), the PIAACMC offers significant performance enhancement over PIAA. This is especially relevant for ground-based high contrast imaging systems in the near-IR, where

  18. Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling

    NARCIS (Netherlands)

    Ashton, Gabrielle H.; Morton, Jennifer P.; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.

    2010-01-01

    The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration

  19. A Site-Specific Phosphorylation of the Focal Adhesion Kinase Controls the Formation of Spheroid Cell Clusters

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Gosau, Martin; Kristensen, Lars Peter

    2014-01-01

    approach revealed regulated phosphorylated proteins in SCCs, which were derived from DFCs after 24 and 48 h in SFM. These regulated proteins were categorized using the Kyoto encyclopedia of genes and genomes program. Here, cellular processes and signaling pathway were identified such as the focal adhesion...

  20. PROLACTIN-INDUCED TYROSINE PHOSPHORYLATION, ACTIVATION AND RECEPTOR ASSOCIATION OF FOCAL ADHESION KINASE (FAK) IN MAMMARY EPITHELIAL CELLS

    Science.gov (United States)

    Prolactin-Induced Tyrosine Phosphorylation, Activation and ReceptorAssociation of Focal Adhesion Kinase (FAK) in Mammary Epithelial Cells. Suzanne E. Fenton1 and Lewis G. Sheffield2. 1U.S. Environmental ProtectionAgency, MD-72, Research Triangle Park, NC 27711, and

  1. MVL-PLA2, a snake venom phospholipase A2, inhibits angiogenesis through an increase in microtubule dynamics and disorganization of focal adhesions.

    Directory of Open Access Journals (Sweden)

    Amine Bazaa

    Full Text Available Integrins are essential protagonists of the complex multi-step process of angiogenesis that has now become a major target for the development of anticancer therapies. We recently reported and characterized that MVL-PLA2, a novel phospholipase A2 from Macrovipera lebetina venom, exhibited anti-integrin activity. In this study, we show that MVL-PLA2 also displays potent anti-angiogenic properties. This phospholipase A2 inhibited adhesion and migration of human microvascular-endothelial cells (HMEC-1 in a dose-dependent manner without being cytotoxic. Using Matrigel and chick chorioallantoic membrane assays, we demonstrated that MVL-PLA2, as well as its catalytically inactivated form, significantly inhibited angiogenesis both in vitro and in vivo. We have also found that the actin cytoskeleton and the distribution of alphav beta3 integrin, a critical regulator of angiogenesis and a major component of focal adhesions, were disturbed after MVL-PLA2 treatment. In order to further investigate the mechanism of action of this protein on endothelial cells, we analyzed the dynamic instability behavior of microtubules in living endothelial cells. Interestingly, we showed that MVL-PLA2 significantly increased microtubule dynamicity in HMEC-1 cells by 40%. We propose that the enhancement of microtubule dynamics may explain the alterations in the formation of focal adhesions, leading to inhibition of cell adhesion and migration.

  2. The small G-protein MglA connects to the MreB actin cytoskeleton at bacterial focal adhesions.

    Science.gov (United States)

    Treuner-Lange, Anke; Macia, Eric; Guzzo, Mathilde; Hot, Edina; Faure, Laura M; Jakobczak, Beata; Espinosa, Leon; Alcor, Damien; Ducret, Adrien; Keilberg, Daniela; Castaing, Jean Philippe; Lacas Gervais, Sandra; Franco, Michel; Søgaard-Andersen, Lotte; Mignot, Tâm

    2015-07-20

    In Myxococcus xanthus the gliding motility machinery is assembled at the leading cell pole to form focal adhesions, translocated rearward to propel the cell, and disassembled at the lagging pole. We show that MglA, a Ras-like small G-protein, is an integral part of this machinery. In this function, MglA stimulates the assembly of the motility complex by directly connecting it to the MreB actin cytoskeleton. Because the nucleotide state of MglA is regulated spatially and MglA only binds MreB in the guanosine triphosphate-bound form, the motility complexes are assembled at the leading pole and dispersed at the lagging pole where the guanosine triphosphatase activating protein MglB disrupts the MglA-MreB interaction. Thus, MglA acts as a nucleotide-dependent molecular switch to regulate the motility machinery spatially. The function of MreB in motility is independent of its function in peptidoglycan synthesis, representing a coopted function. Our findings highlight a new function for the MreB cytoskeleton and suggest that G-protein-cytoskeleton interactions are a universally conserved feature. © 2015 Treuner-Lange et al.

  3. High-performance mussel-inspired adhesives of reduced complexity.

    Science.gov (United States)

    Ahn, B Kollbe; Das, Saurabh; Linstadt, Roscoe; Kaufman, Yair; Martinez-Rodriguez, Nadine R; Mirshafian, Razieh; Kesselman, Ellina; Talmon, Yeshayahu; Lipshutz, Bruce H; Israelachvili, Jacob N; Waite, J Herbert

    2015-10-19

    Despite the recent progress in and demand for wet adhesives, practical underwater adhesion remains limited or non-existent for diverse applications. Translation of mussel-inspired wet adhesion typically entails catechol functionalization of polymers and/or polyelectrolytes, and solution processing of many complex components and steps that require optimization and stabilization. Here we reduced the complexity of a wet adhesive primer to synthetic low-molecular-weight catecholic zwitterionic surfactants that show very strong adhesion (∼50 mJ m(-2)) and retain the ability to coacervate. This catecholic zwitterion adheres to diverse surfaces and self-assembles into a molecularly smooth, thin (adhesive for nanofabrication. This study significantly simplifies bio-inspired themes for wet adhesion by combining catechol with hydrophobic and electrostatic functional groups in a small molecule.

  4. Focal Adhesion Kinase as a Potential Target in AML and MDS.

    Science.gov (United States)

    Carter, Bing Z; Mak, Po Yee; Wang, Xiangmeng; Yang, Hui; Garcia-Manero, Guillermo; Mak, Duncan H; Mu, Hong; Ruvolo, Vivian R; Qiu, Yihua; Coombes, Kevin; Zhang, Nianxiang; Ragon, Brittany; Weaver, David T; Pachter, Jonathan A; Kornblau, Steven; Andreeff, Michael

    2017-06-01

    Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics ( P = 2 × 10 -4 ) and relapse ( P = 0.02) in AML. FAK expression was significantly lower in patients with FLT3 -ITD ( P = 0.0024) or RAS ( P = 0.05) mutations and strongly correlated with p-SRC and integrinβ3 levels. FAK protein levels were significantly higher in CD34 + ( P = 5.42 × 10 -20 ) and CD34 + CD38 - MDS ( P = 7.62 × 10 -9 ) cells compared with normal CD34 + cells. MDS patients with higher FAK in CD34 + cells tended to have better overall survival ( P = 0.05). FAK expression was significantly higher in MDS patients who later transformed to compared with those who did not transform to AML and in AML patients who transformed from MDS compared with those with de novo AML. Coculture with mesenchymal stromal cells (MSC) increased FAK expression in AML cells. Inhibition of FAK decreased MSC-mediated adhesion/migration and viability of AML cells and prolonged survival in an AML xenograft murine model. Our results suggest that FAK regulates leukemia-stromal interactions and supports leukemia cell survival; hence, FAK is a potential therapeutic target in myeloid leukemia. Mol Cancer Ther; 16(6); 1133-44. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. Laminin α2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis.

    Directory of Open Access Journals (Sweden)

    Duane Delimont

    Full Text Available It has been known for some time that laminins containing α1 and α2 chains, which are normally restricted to the mesangial matrix, accumulate in the glomerular basement membranes (GBM of Alport mice, dogs, and humans. We show that laminins containing the α2 chain, but not those containing the α1 chain activates focal adhesion kinase (FAK on glomerular podocytes in vitro and in vivo. CD151-null mice, which have weakened podocyte adhesion to the GBM rendering these mice more susceptible to biomechanical strain in the glomerulus, also show progressive accumulation of α2 laminins in the GBM, and podocyte FAK activation. Analysis of glomerular mRNA from both models demonstrates significant induction of MMP-9, MMP-10, MMP-12, MMPs linked to GBM destruction in Alport disease models, as well as the pro-inflammatory cytokine IL-6. SiRNA knockdown of FAK in cultured podocytes significantly reduced expression of MMP-9, MMP-10 and IL-6, but not MMP-12. Treatment of Alport mice with TAE226, a small molecule inhibitor of FAK activation, ameliorated fibrosis and glomerulosclerosis, significantly reduced proteinuria and blood urea nitrogen levels, and partially restored GBM ultrastructure. Glomerular expression of MMP-9, MMP-10 and MMP-12 mRNAs was significantly reduced in TAE226 treated animals. Collectively, this work identifies laminin α2-mediated FAK activation in podocytes as an important early event in Alport glomerular pathogenesis and suggests that FAK inhibitors, if safe formulations can be developed, might be employed as a novel therapeutic approach for treating Alport renal disease in its early stages.

  6. The emerin-binding transcription factor Lmo7 is regulated by association with p130Cas at focal adhesions

    Directory of Open Access Journals (Sweden)

    Michele A. Wozniak

    2013-08-01

    Full Text Available Loss of function mutations in the nuclear inner membrane protein, emerin, cause X-linked Emery-Dreifuss muscular dystrophy (X-EDMD. X-EDMD is characterized by contractures of major tendons, skeletal muscle weakening and wasting, and cardiac conduction system defects. The transcription factor Lmo7 regulates muscle- and heart-relevant genes and is inhibited by binding to emerin, suggesting Lmo7 misregulation contributes to EDMD disease. Lmo7 associates with cell adhesions and shuttles between the plasma membrane and nucleus, but the regulation and biological consequences of this dual localization were unknown. We report endogenous Lmo7 also associates with focal adhesions in cells, and both co-localizes and co-immunoprecipitates with p130Cas, a key signaling component of focal adhesions. Lmo7 nuclear localization and transcriptional activity increased significantly in p130Cas-null MEFs, suggesting Lmo7 is negatively regulated by p130Cas-dependent association with focal adhesions. These results support EDMD models in which Lmo7 is a downstream mediator of integrin-dependent signaling that allows tendon cells and muscles to adapt to and withstand mechanical stress.

  7. Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas.

    Science.gov (United States)

    Polte, T R; Hanks, S K

    1995-11-07

    The focal adhesion kinase (FAK) has been implicated in integrin-mediated signaling events and in the mechanism of cell transformation by the v-Src and v-Crk oncoproteins. To gain further insight into FAK signaling pathways, we used a two-hybrid screen to identify proteins that interact with mouse FAK. The screen identified two proteins that interact with FAK via their Src homology 3 (SH3) domains: a v-Crk-associated tyrosine kinase substrate (Cas), p130Cas, and a still uncharacterized protein, FIPSH3-2, which contains an SH3 domain closely related to that of p130Cas. These SH3 domains bind to the same proline-rich region of FAK (APPKPSR) encompassing residues 711-717. The mouse p130Cas amino acid sequence was deduced from cDNA clones, revealing an overall high degree of similarity to the recently reported rat sequence. Coimmunoprecipitation experiments confirmed that p130Cas and FAK are associated in mouse fibroblasts. The stable interaction between p130Cas and FAK emerges as a likely key element in integrin-mediated signal transduction and further represents a direct molecular link between the v-Src and v-Crk oncoproteins. The Src family kinase Fyn, whose Src homology 2 (SH2) domain binds to the major FAK autophosphorylation site (tyrosine 397), was also identified in the two-hybrid screen.

  8. Copper deficiency induced emphysema is associated with focal adhesion kinase inactivation.

    Directory of Open Access Journals (Sweden)

    Shiro Mizuno

    Full Text Available Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1α dependent vascular endothelial growth factor (VEGF expression, and is also required for the activity of lysyl oxidase (LOX to effect matrix protein cross-linking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis via inactivation of focal adhesion kinase (FAK.To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the inhibitor of auto-phosphorylation of FAK, 1,2,4,5-benzenetetraamine tetrahydrochloride (1,2,4,5-BT or FAK small interfering RNA (siRNA.Copper depletion caused emphysematous changes, decreased HIF-1α activity, and downregulated VEGF expression in the rat lungs. Cleaved caspase-3, caspase-8 and Bcl-2 interacting mediator of cell death (Bim expression was increased, and the phosphorylation of FAK was decreased in copper depleted rat lungs. Administration of 1,2,4,5-BT and FAK siRNA caused emphysematous lung destruction associated with increased expression of cleaved capase-3, caspase-8 and Bim.These data indicate that copper-dependent mechanisms contribute to the pathogenesis of emphysema, which may be associated with decreased HIF-1α and FAK activity in the lung.

  9. Dual targeting of EGFR and focal adhesion kinase in 3D grown HNSCC cell cultures

    International Nuclear Information System (INIS)

    Eke, Iris; Cordes, Nils

    2011-01-01

    Purpose: Epidermal growth factor receptor (EGFR) and focal adhesion kinase (FAK) show frequent overexpression and hyperactivity in various human malignancies including head and neck squamous cell carcinomas (HNSCC). To examine effects of dual EGFR/FAK inhibition on cellular radiosensitivity of HNSCC cells in a more physiological environment, we employed a previously established laminin-rich extracellular matrix (lrECM) based three-dimensional (3D) cell culture model. Materials and methods: UTSCC15 and SAS HNSCC cell lines stably transfected with EGFR-CFP or CFP were used. Single or combined EGFR (Cetuximab, siRNA) and FAK (TAE226, siRNA) inhibition were accomplished prior to measuring clonogenic survival and protein expression and phosphorylation. Immunofluorescence enabled visualization of EGFR-CFP and FAK. Results: Cetuximab resulted in higher radiosensitization in EGFR-CFP overexpressing cell lines than CFP controls. Single EGFR or FAK inhibition mediated radiosensitization, while dual EGFR/FAK targeting further augmented this effect. Despite signaling alterations upon Cetuximab and siRNA knockdown, analysis of protein expression and phosphorylation indicates EGFR and FAK signaling coexistence without obvious overlap. Conclusions: Combined EGFR/FAK targeting yielded stronger radiosensitization than either approach alone, which might be based on non-overlapping downstream signaling. Whether dual targeting of EGFR and FAK can reasonably be combined with radiotherapy and chemotherapy needs clarification.

  10. Cytokine Release and Focal Adhesion Proteins in Normal Thyroid Cells Cultured on the Random Positioning Machine

    Directory of Open Access Journals (Sweden)

    Elisabeth Warnke

    2017-08-01

    Full Text Available Background/Aims: Spaceflight impacts on the function of the thyroid gland in vivo. In vitro normal and malignant thyrocytes assemble in part to multicellular spheroids (MCS after exposure to the random positioning machine (RPM, while a number of cells remain adherent (AD. We aim to elucidate possible differences between AD and MCS cells compared to 1g-controls of normal human thyroid cells. Methods: Cells of the human follicular epithelial thyroid cell line Nthy-ori 3-1 were incubated for up to 72 h on the RPM. Afterwards, they were investigated by phase-contrast microscopy, quantitative real-time PCR and by determination of cytokines released in their supernatants. Results: A significant up-regulation of IL6, IL8 and CCL2 gene expression was found after a 4h RPM-exposure, when the whole population was still growing adherently. MCS and AD cells were detected after 24 h on the RPM. At this time, a significantly reduced gene expression in MCS compared to 1g-controls was visible for IL6, IL8, FN1, ITGB1, LAMA1, CCL2, and TLN1. After a 72 h RPM-exposure, IL-6, IL-8, and TIMP-1 secretion rates were increased significantly. Conclusion: Normal thyrocytes form MCS within 24 h. Cytokines seem to be involved in the initiation of MCS formation via focal adhesion proteins.

  11. Focal adhesion kinase regulates neuronal growth, synaptic plasticity and hippocampus-dependent spatial learning and memory.

    Science.gov (United States)

    Monje, Francisco J; Kim, Eun-Jung; Pollak, Daniela D; Cabatic, Maureen; Li, Lin; Baston, Arthur; Lubec, Gert

    2012-01-01

    The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory. Copyright © 2011 S. Karger AG, Basel.

  12. 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...

  13. Changes in microfilament and focal adhesion distribution with loss of androgen responsiveness in cultured mammary tumor cells

    DEFF Research Database (Denmark)

    Couchman, J R; Yates, J; King, R J

    1981-01-01

    of the cells to grow in suspension culture. All these parameters were documented for androgen-responsive and -unresponsive cells grown in culture, as well as the transition of androgen-responsive to -unresponsive cells when deprived of androgen. The androgen-unresponsive cells had extensive and prominent...... microfilament bundles together with focal adhesions on the lower cell surface and also showed strict anchorage dependence for growth. In contrast, microfilament bundles and focal adhesions were absent from androgen-responsive cells, which furthermore had the ability to grow in suspension culture. Differences......, characteristics of both cell types were visible in the cell populations. However, at the stage where all androgen-responsive characteristics were lost, the cells were no longer androgen sensitive. The loss of androgen responsiveness in Shionogi 115 mouse mammary tumor cells is correlated with changes at the cell...

  14. Formation of multiple focal spots using a high NA lens with a complex spiral phase mask

    Science.gov (United States)

    Lalithambigai, K.; Anbarasan, P. M.; Rajesh, K. B.

    2014-07-01

    The formation of a transversally polarized beam by transmitting a tightly focused double-ring-shaped azimuthally polarized beam through a complex spiral phase mask and high numerical aperture lens is presented based on vector diffraction theory. The generation of transversally polarized focal spot segment splitting and multiple focal spots is illustrated numerically. Moreover, we found that a properly designed complex spiral phase mask can move the focal spots along the optical axis in the z direction. Therefore, one can achieve a focal segment of two, three or multiple completely transversely polarized focal spots, which finds applications in optical trapping and in material processing technologies.

  15. 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.

  16. CD147-targeting siRNA inhibits cell-matrix adhesion of human malignant melanoma cells by phosphorylating focal adhesion kinase.

    Science.gov (United States)

    Nishibaba, Rie; Higashi, Yuko; Su, Juan; Furukawa, Tatsuhiko; Kawai, Kazuhiro; Kanekura, Takuro

    2012-01-01

    CD147/basigin, highly expressed on the surface of malignant tumor cells including malignant melanoma (MM) cells, plays a critical role in the invasiveness and metastasis of MM. Metastasis is an orchestrated process comprised of multiple steps including adhesion and invasion. Integrin, a major adhesion molecule, co-localizes with CD147/basigin on the cell surface. Using the human MM cell line A375 that highly expresses CD147/basigin, we investigated whether CD147/basigin is involved in adhesion in association with integrin. CD147/basigin was knocked-down using siRNA targeting CD147 to elucidate the role of CD147/basigin. Cell adhesion was evaluated by adhesion assay on matrix-coated plates. The localization of integrin was inspected under a confocal microscope and the expression and phosphorylation of focal adhesion kinase (FAK), a downstream kinase of integrin, were examined by western blot analysis. Silencing of CD147/basigin in A375 cells by siRNA induced the phosphorylation of FAK at Y397. Integrin identified on the surface of parental cells was distributed in a speckled fashion in the cytoplasm of CD147 knockdown cells, resulting in morphological changes from a round to a polygonal shape with pseudopodial protrusions. Silencing of CD147/basigin in A375 cells clearly weakened their adhesiveness to collagen I and IV. Our results suggest that CD147/basigin regulates the adhesion of MM cells to extracellular matrices and of integrin β1 signaling via the phosphorylation of FAK. © 2011 Japanese Dermatological Association.

  17. Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma.

    Science.gov (United States)

    Kanteti, Rajani; Mirzapoiazova, Tamara; Riehm, Jacob J; Dhanasingh, Immanuel; Mambetsariev, Bolot; Wang, Jiale; Kulkarni, Prakash; Kaushik, Garima; Seshacharyulu, Parthasarathy; Ponnusamy, Moorthy P; Kindler, Hedy L; Nasser, Mohd W; Batra, Surinder K; Salgia, Ravi

    2018-04-03

    The non-receptor cytoplasmic tyrosine kinase, Focal Adhesion Kinase (FAK) is known to play a key role in a variety of normal and cancer cellular functions such as survival, proliferation, migration and invasion. It is highly active and overexpressed in various cancers including Pancreatic Ductal Adenocarcinoma (PDAC) and Malignant Pleural Mesothelioma (MPM). Here, initially, we demonstrate that FAK is overexpressed in both PDAC and MPM cell lines. Then we analyze effects of two small molecule inhibitors PF-573228, and PF-431396, which are dual specificity inhibitors of FAK and proline rich tyrosine kinase 2 (PYK2), as well as VS-6063, another small molecule inhibitor that specifically inhibits FAK but not PYK2 for cell growth, motility and invasion of PDAC and MPM cell lines. Treatment with PF-573228, PF-431396 and VS-6063 cells resulted in a dose-dependent inhibition of growth and anchorage-independent colony formation in both cancer cell lines. Furthermore, these compounds suppressed the phosphorylation of FAK at its active site, Y397, and functionally induced significant apoptosis and cell cycle arrest in both cell lines. Using the ECIS (Electric cell-substrate impedance sensing) system, we found that treatment of both PF compounds suppressed adherence and migration of PDAC cells on fibronectin. Interestingly, 3D-tumor organoids derived from autochthonous KC (Kras;PdxCre) mice treated with PF-573228 revealed a significant decrease in tumor organoid size and increase in organoid cell death. Taken together, our results show that FAK is an important target for mesothelioma and pancreatic cancer therapy that merit further translational studies.

  18. Reorganization of the actin cytoskeleton via transcriptional regulation of cytoskeletal/focal adhesion genes by myocardin-related transcription factors (MRTFs/MAL/MKLs)

    International Nuclear Information System (INIS)

    Morita, Tsuyoshi; Mayanagi, Taira; Sobue, Kenji

    2007-01-01

    RhoA is a crucial regulator of stress fiber and focal adhesion formation through the activation of actin nucleation and polymerization. It also regulates the nuclear translocation of myocardin-related transcription factor-A and -B (MRTF-A/B, MAL or MKL 1/2), which are co-activators of serum response factor (SRF). In dominant-negative MRTF-A (DN-MRTF-A)-expressing NIH 3T3 cell lines, the expressions of several cytoskeletal/focal adhesion genes were down-regulated, and the formation of stress fiber and focal adhesion was severely diminished. MRTF-A/B-knockdown cells also exhibited such cytoskeletal defects. In reporter assays, both RhoA and MRTF-A enhanced promoter activities of these genes in a CArG-box-dependent manner, and DN-MRTF-A inhibited the RhoA-mediated activation of these promoters. In dominant-negative RhoA (RhoA-N19)-expressing NIH 3T3 cell lines, the nuclear translocation of MRTF-A/B was predominantly prevented, resulting in the reduced expression of cytoskeletal/focal adhesion proteins. Further, constitutive-active MRTF-A/B increased the expression of endogenous cytoskeletal/focal adhesion proteins, and thereby rescued the defective phenotype of stress fibers and focal adhesions in RhoA-N19 expressing cells. These results indicate that MRTF-A/B act as pivotal mediators of stress fiber and focal adhesion formation via the transcriptional regulation of a subset of cytoskeletal/focal adhesion genes

  19. SYMPATHETIC ACTIVATION CAUSES FOCAL ADHESION SIGNALING ALTERATION IN EARLY COMPENSATED VOLUME OVERLOAD DUE TO ISOLATED MITRAL REGURGITATION IN THE DOG

    OpenAIRE

    Sabri, Abdelkarim; Rafiq, Khadija; Seqqat, Rachid; Kolpakov, Mikhail A; Dillon, Ray; Dell’italia, Louis J

    2008-01-01

    We reported that left ventricular (LV) dilatation after four weeks of isolated mitral regurgitation (MR) in the dogs is marked by extracellular matrix (ECM) loss and an increase in adrenergic drive. Given that ECM proteins and their receptors integrins influence β-adrenergic receptor (β-AR) responses in-vitro, we tested whether β1-AR activation modulates focal adhesion (FA) signaling and LV remodeling in these same dogs with isolated MR. Normal dogs (NL) were compared with dogs with MR of 4-w...

  20. Expression of MLN64 influences cellular matrix adhesion of breast cancer cells, the role for focal adhesion kinase.

    Science.gov (United States)

    Cai, Wei; Ye, Lin; Sun, Jiabang; Mansel, Robert E; Jiang, Wen G

    2010-04-01

    The metastatic lymph node 64 (MLN64) gene was initially identified as highly expressed in the metastatic lymph node from breast cancer. It is localized in q12-q21 of the human chromosome 17 and is often co-amplified with erbB-2. However, the role played by MLN64 in breast cancer remains unclear. In the present study, the expression of MLN64 was examined in a breast cancer cohort using quantitative real-time PCR and immunohistochemical staining. It demonstrated that MLN64 was highly expressed in breast tumours compared to corresponding background tissues at both transcript level and protein level. The elevated level of MLN64 transcripts was correlated with the poor prognosis and overall survival of the patients. A panel of breast cancer cell sublines was subsequently developed by knockdown of MLN64 expression. Loss of MLN64 expression in MCF-7 cells resulted in a significant reduction of cell growth (absorbance for MCF-7DeltaMLN64 being 0.87+/-0.07, Padhesion assay, MDA-MB-231DeltaMLN64 cells showed a significant increase in adhesion (86+/-14), padhesion kinase (FAK) in MDA-MB-231DeltaMLN64 cells using Western blot analysis and immunofluorescent staining of FAK. Moreover, addition of FAK inhibitor to these cells diminished the effect of MLN64 on cell-matrix adhesion, suggesting that FAK contributed to the increased adhesion in MDA-MB-231DeltaMLN64 cells. In conclusion, MLN64 is overexpressed in breast cancer, and its level correlates with poor prognosis and patient survival. MLN64 contributes to the development and progression of breast cancer through the regulation of cell proliferation and adhesive capacity.

  1. Interleukin 1β induces rapid phosphorylation and redistribution of talin: A possible mechanism for modulation of fibroblast focal adhesion

    International Nuclear Information System (INIS)

    Qwarnstroem, E.E.; MacFarlane, S.A.; Page, R.C.; Dower, S.K.

    1991-01-01

    The majority of interleukin 1 (IL-1) receptors in human fibroblasts has been shown to be localized at focal adhesions. This study describes rapid alterations caused by IL-1β/IL-1-receptor interaction at these sites. Fibroblast monolayers, incubated with IL-1β and prepared for electron microscopy, showed successive loss of cell-substratum contact and fewer and less-pronounced processes. Immunocytochemistry revealed loss and redistribution of the talin staining initially observed after 5-15 min of IL-1β incubation. Similarly, the cytoskeleton showed a decrease in staining and a disorganization starting from 15 to 30 min after IL-1 addition, whereas extracellular fibronectin appeared largely unaffected. Prelabeling with [ 32 P]phosphate showed a 2- to 3-fold increase in the level of talin phosphorylation, peaking at 15 min. Phospho amino acid analyses revealed a higher level of serine and threonine phosphorylation. The data suggest that the action of IL-1β on fibroblasts may be partially mediated by direct phosphorylation of talin via activation of a protein serine/threonine kinase, leading to changes in transmembrane linkage proteins and the cytoskeleton. Such alterations at focal adhesions may provide a mechanism by which IL-1 can rapidly modulate cell-matrix interactions during inflammation and wound healing

  2. Resveratrol and Estradiol Exert Disparate Effects on Cell Migration, Cell Surface Actin Structures, and Focal Adhesion Assembly in MDA-MB-231 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Nicolas G. Azios

    2005-02-01

    Full Text Available Resveratrol, a grape polyphenol, is thought to be a cancer preventive, yet its effects on metastatic breast cancer are relatively unknown. Since cancer cell invasion is dependent on cell migration, the chemotactic response of MDA-MB-231 metastatic human breast cancer cells to resveratrol, estradiol (E2, or epidermal growth factor (EGF was investigated. Resveratrol decreased while E2 and EGF increased directed cell migration. Resveratrol may inhibit cell migration by altering the cytoskeleton. Resveratrol induced a rapid global array of filopodia and decreased focal adhesions and focal adhesion kinase (FAK activity. E2 or EGF treatment did not affect filopodia extension but increased lamellipodia and associated focal adhesions that are integral for cell migration. Combined resveratrol and E2 treatment resulted in a filopodia and focal adhesion response similar to resveratrol alone. Combined resveratrol and EGF resulted in a lamellipodia and focal adhesion response similar to EGF alone. E2 and to a lesser extent resveratrol increased EGFR activity. The cytoskeletal changes and EGFR activity in response to E2 were blocked by EGFR1 inhibitor indicating that E2 may increase cell migration via crosstalk with EGFR signaling. These data suggest a promotional role for E2 in breast cancer cell migration but an antiestrogenic, preventative role for resveratrol.

  3. Mechanical stimulation of C2C12 cells increases m-calpain expression and activity, focal adhesion plaque degradation and cell fusion

    DEFF Research Database (Denmark)

    Grossi, Alberto; Karlsson, Anders Hans; Lawson, Moira A.

    2005-01-01

    Abstract Mechanical Stimulation of C2C12 Cells Increases m-calpain Expression and Activity, Focal Adhesion Plaque Degradation and Cell Fusion A. Grossi, A. H. Karlsson, M. A. Lawson; Department of Dairy and Food Science, Royal Veterinary and Agricultural University, Frederiksberg C, Denmark...... Myogenesis is a complex sequence of events, including the irreversible transition from the proliferation-competent myoblast stage into fused, multinucleated myotubes. During embryonic development, myogenic differentiation is regulated by positive and negative signals from surrounding tissues. Stimulation due...... to the activity of ubiquitous proteolytic enzymes known as calpains has been reported. Whether there is a link between stretch- or load induced signaling and calpain expression and activation is not known. Using a magnetic bead stimulation assay and C2C12 mouse myoblasts cell population, we have demonstrated...

  4. Cellular adhesome screen identifies critical modulators of focal adhesion dynamics, cellular traction forces and cell migration behaviour

    Science.gov (United States)

    Fokkelman, Michiel; Balcıoğlu, Hayri E.; Klip, Janna E.; Yan, Kuan; Verbeek, Fons J.; Danen, Erik H. J.; van de Water, Bob

    2016-01-01

    Cancer cells migrate from the primary tumour into surrounding tissue in order to form metastasis. Cell migration is a highly complex process, which requires continuous remodelling and re-organization of the cytoskeleton and cell-matrix adhesions. Here, we aimed to identify genes controlling aspects of tumour cell migration, including the dynamic organization of cell-matrix adhesions and cellular traction forces. In a siRNA screen targeting most cell adhesion-related genes we identified 200+ genes that regulate size and/or dynamics of cell-matrix adhesions in MCF7 breast cancer cells. In a subsequent secondary screen, the 64 most effective genes were evaluated for growth factor-induced cell migration and validated by tertiary RNAi pool deconvolution experiments. Four validated hits showed significantly enlarged adhesions accompanied by reduced cell migration upon siRNA-mediated knockdown. Furthermore, loss of PPP1R12B, HIPK3 or RAC2 caused cells to exert higher traction forces, as determined by traction force microscopy with elastomeric micropillar post arrays, and led to considerably reduced force turnover. Altogether, we identified genes that co-regulate cell-matrix adhesion dynamics and traction force turnover, thereby modulating overall motility behaviour. PMID:27531518

  5. A synthetic peptide from the COOH-terminal heparin-binding domain of fibronectin promotes focal adhesion formation

    DEFF Research Database (Denmark)

    Woods, A; McCarthy, J B; Furcht, L T

    1993-01-01

    Cell adhesion to extracellular matrix molecules such as fibronectin involves complex transmembrane signaling processes. Attachment and spreading of primary fibroblasts can be promoted by interactions of cell surface integrins with RGD-containing fragments of fibronectin, but the further process o...

  6. Stress relaxing hyaluronic acid-collagen hydrogels promote cell spreading, fiber remodeling, and focal adhesion formation in 3D cell culture.

    Science.gov (United States)

    Lou, Junzhe; Stowers, Ryan; Nam, Sungmin; Xia, Yan; Chaudhuri, Ovijit

    2018-02-01

    The physical and architectural cues of the extracellular matrix (ECM) play a critical role in regulating important cellular functions such as spreading, migration, proliferation, and differentiation. Natural ECM is a complex viscoelastic scaffold composed of various distinct components that are often organized into a fibrillar microstructure. Hydrogels are frequently used as synthetic ECMs for 3D cell culture, but are typically elastic, due to covalent crosslinking, and non-fibrillar. Recent work has revealed the importance of stress relaxation in viscoelastic hydrogels in regulating biological processes such as spreading and differentiation, but these studies all utilize synthetic ECM hydrogels that are non-fibrillar. Key mechanotransduction events, such as focal adhesion formation, have only been observed in fibrillar networks in 3D culture to date. Here we present an interpenetrating network (IPN) hydrogel system based on HA crosslinked with dynamic covalent bonds and collagen I that captures the viscoelasticity and fibrillarity of ECM in tissues. The IPN hydrogels exhibit two distinct processes in stress relaxation, one from collagen and the other from HA crosslinking dynamics. Stress relaxation in the IPN hydrogels can be tuned by modulating HA crosslinker affinity, molecular weight of the HA, or HA concentration. Faster relaxation in the IPN hydrogels promotes cell spreading, fiber remodeling, and focal adhesion (FA) formation - behaviors often inhibited in other hydrogel-based materials in 3D culture. This study presents a new, broadly adaptable materials platform for mimicking key ECM features of viscoelasticity and fibrillarity in hydrogels for 3D cell culture and sheds light on how these mechanical and structural cues regulate cell behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Focal adhesion kinase, a downstream mediator of Raf-1 signaling, suppresses cellular adhesion, migration, and neuroendocrine markers in BON carcinoid cells.

    Science.gov (United States)

    Ning, Li; Chen, Herbert; Kunnimalaiyaan, Muthusamy

    2010-05-01

    We have recently reported that activation of the Raf-1/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2)/ERK1/2 signaling cascade in gastrointestinal carcinoid cell line (BON) alters cellular morphology and neuroendocrine phenotype. The mechanisms by which Raf-1 mediates these changes in carcinoid cells are unclear. Here, we report that activation of the Raf-1 signaling cascade in BON cells induced the expression of focal adhesion kinase (FAK) protein, suppressed the production of neuroendocrine markers, and resulted in significant decreases in cellular adhesion and migration. Importantly, inactivation of MEK1/2 by 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene or abolition of FAK induction in Raf-1-activated BON cells by targeted siRNA led to reversal of the Raf-1-mediated reduction in neuroendocrine markers and cellular adhesion and migration. Phosphorylation site-specific antibodies detected the phosphorylated FAK(Tyr407), but not FAK(Tyr397), in these Raf-1-activated cells, indicating that FAK(Tyr407) may be associated with changes in the neuroendocrine phenotype. Overexpression of constitutively active FAK plasmids (wild-type FAK or FAK(Tyr397) mutant) into BON cells reduced neuroendocrine markers, whereas the FAK(Tyr407) mutant plasmid did not show any decrease in the levels of neuroendocrine markers, indicating that phosphorylation of FAK at the Tyr(407) residue may be important for these effects. Our results showed for the first time that FAK is an essential downstream effector of the Raf-1/MEK1/2/ERK1/2 signaling cascade and negatively regulated the neuroendocrine and metastatic phenotype in BON cells. (c)2010 AACR.

  8. Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling

    Science.gov (United States)

    Ashton, Gabrielle H.; Morton, Jennifer P.; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.

    2012-01-01

    SUMMARY The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein within the intestinal epithelium. Following Apc loss, FAK expression increased in a c-Myc-dependent manner. Codeletion of Apc and Fak strongly reduced proliferation normally induced following Apc loss, and this was associated with reduced levels of phospho-Akt and suppression of intestinal tumorigenesis in Apc heterozygous mice. Thus, FAK is required downstream of Wnt Signaling, for Akt/mTOR activation, intestinal regeneration, and tumorigenesis. Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer. PMID:20708588

  9. Linker length dependent binding of a focal adhesion kinase derived peptide to the Src SH3-SH2 domains.

    Science.gov (United States)

    Lindfors, Hanna E; Venkata, Bharat Somireddy; Drijfhout, Jan W; Ubbink, Marcellus

    2011-02-18

    The interaction between a peptide encompassing the SH3 and SH2 binding motifs of focal adhesion kinase (FAK) and the Src SH3-SH2 domains has been investigated with NMR spectroscopy and calorimetry. The binding to both motifs is anti-cooperative. Reduction of the long linker connecting the motifs does not lead to cooperativity. Short linkers that do not allow simultaneous intramolecular binding of the peptide to both motifs cause peptide-mediated dimerisation, even with a linker of only three amino acids. The role of the SH3 binding motif is discussed in view of the independent nature of the SH interactions. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. Expression and organization of basement membranes and focal adhesion proteins in pregnant myometrium is regulated by uterine stretch.

    Science.gov (United States)

    Shynlova, Oksana; Chow, Michelle; Lye, Stephen J

    2009-10-01

    The mechanisms underlying the preparation of the uterus for labor are not fully understood. We have previously found a significant increase in the expression of messenger RNA (mRNAs) encoding extracellular basement membrane (BM) proteins of the smooth muscle cells (SMCs) in late pregnant rat myometrium. At term, the myometrium is stretched by growing fetuses and these mechanical signals are transmitted from extracellular matrix into SMCs through focal adhesions (FA). The aim of this study was to investigate the effect of gravidity on the expression and spatiotemporal distribution of major BM proteins, laminin-gamma2 and collagen IV, as well as typical FA constituents, vinculin and paxillin, in the myometrium during gestation and parturition, using a unilaterally pregnant rat model. We found that the expression of laminin-gamma2 and collagen IV proteins increased significantly with gestational age (P proteins were not affected. Near term, BM proteins from gravid horn myometrium demonstrated increased extracellular immunostaining and major rearrangement from sporadic protein distribution to organized, continuous, and regular structures surrounding the plasma membrane of each myocyte. Examination of FA proteins revealed that paxillin was translocated from the cytoplasm to the cell periphery, while vinculin was sequestered specifically to FAs. At labor, BM and FA proteins, organized in similar bead-like structures, were localized on opposing sides of SMC plasma membrane into 2 different compartments. We suggest that these stretch-induced changes facilitate formation of stable cell-matrix adhesions and provide the molecular basis for optimal force transduction during labor contractions.

  11. Impaired Expression of Focal Adhesion Kinase in Mesenchymal Stromal Cells from Low-Risk Myelodysplastic Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Yuenv Wu

    2017-08-01

    Full Text Available The pathogenic role of mesenchymal stromal cells (MSCs in myelodysplastic syndromes (MDS development and progression has been investigated by numerous studies, yet, it remains controversial in some aspects (1, 2. In the present study, we found distinct features of MSCs from low-risk (LR-MDS stromal microenvironment as compared to those from healthy subjects. At the molecular level, focal adhesion kinase, a key tyrosine kinase in control of cell proliferation, survival, and adhesion process, was found profoundly suppressed in expression and activation in LR-MDS MSC. At a functional level, LR-MDS MSCs showed impaired growth and clonogenic capacity, which were independent of cellular senescence and apoptosis. The pro-adipogenic differentiation and attenuated osteogenic capacity along with reduced SDF-1 expression could be involved in creating an unfavorable microenvironment for hematopoiesis. In conclusion, our experiments support the theory that the stromal microenvironment is fundamentally altered in LR-MDS, and these preliminary data offer a new perspective on LR-MDS pathophysiology.

  12. Contribution of the LIM domain and nebulin-repeats to the interaction of Lasp-2 with actin filaments and focal adhesions.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Nakagawa

    Full Text Available Lasp-2 binds to actin filaments and concentrates in the actin bundles of filopodia and lamellipodia in neural cells and focal adhesions in fibroblastic cells. Lasp-2 has three structural regions: a LIM domain, a nebulin-repeat region, and an SH3 domain; however, the region(s responsible for its interactions with actin filaments and focal adhesions are still unclear. In this study, we revealed that the N-terminal fragment from the LIM domain to the first nebulin-repeat module (LIM-n1 retained actin-binding activity and showed a similar subcellular localization to full-length lasp-2 in neural cells. The LIM domain fragment did not interact with actin filaments or localize to actin filament bundles. In contrast, LIM-n1 showed a clear subcellular localization to filopodial actin bundles. Although truncation of the LIM domain caused the loss of F-actin binding activity and the accumulation of filopodial actin bundles, these truncated fragments localized to focal adhesions. These results suggest that lasp-2 interactions with actin filaments are mediated through the cooperation of the LIM domain and the first nebulin-repeat module in vitro and in vivo. Actin filament binding activity may be a major contributor to the subcellular localization of lasp-2 to filopodia but is not crucial for lasp-2 recruitment to focal adhesions.

  13. Structural and functional assessment of the interaction between focal adhesion kinase and sarcomeric myosin

    OpenAIRE

    Aline Mara dos Santos

    2011-01-01

    Resumo: A tirosino-quinase de adesão focal (FAK) tem papel crítico na mediação da migração, sobrevivência e proliferação celular. Estudos anteriores de nosso laboratório demonstraram que a FAK é ativada pelo estresse mecânico em miócitos cardíacos e que ela se coimunoprecipita com a miosina sarcomérica. No presente trabalho foi demonstrado que o domínio FERM da FAK medeia à interação com a miosina sarcomérica, sendo que esta interação leva a inibição da autofosforilação da FAK, enquanto que a...

  14. PRL-3 engages the focal adhesion pathway in triple-negative breast cancer cells to alter actin structure and substrate adhesion properties critical for cell migration and invasion.

    Science.gov (United States)

    Gari, Hamid H; DeGala, Gregory D; Ray, Rahul; Lucia, M Scott; Lambert, James R

    2016-10-01

    Triple-negative breast cancers (TNBCs) are among the most aggressive cancers characterized by a high propensity to invade, metastasize and relapse. We previously reported that the TNBC-specific inhibitor, AMPI-109, significantly impairs the ability of TNBC cells to migrate and invade by reducing levels of the metastasis-promoting phosphatase, PRL-3. Here, we examined the mechanisms by which AMPI-109 and loss of PRL-3 impede cell migration and invasion. AMPI-109 treatment or knock down of PRL-3 expression were associated with deactivation of Src and ERK signaling and concomitant downregulation of RhoA and Rac1/2/3 GTPase protein levels. These cellular changes led to rearranged filamentous actin networks necessary for cell migration and invasion. Conversely, overexpression of PRL-3 promoted TNBC cell invasion by upregulating matrix metalloproteinase 10, which resulted in increased TNBC cell adherence to, and degradation of, the major basement membrane component laminin. Our data demonstrate that PRL-3 engages the focal adhesion pathway in TNBC cells as a key mechanism for promoting TNBC cell migration and invasion. Collectively, these data suggest that blocking PRL-3 activity may be an effective method for reducing the metastatic potential of TNBC cells. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

  15. Mechanisms underlying the attachment and spreading of human osteoblasts: from transient interactions to focal adhesions on vitronectin-grafted bioactive surfaces.

    Science.gov (United States)

    Brun, Paola; Scorzeto, Michele; Vassanelli, Stefano; Castagliuolo, Ignazio; Palù, Giorgio; Ghezzo, Francesca; Messina, Grazia M L; Iucci, Giovanna; Battaglia, Valentina; Sivolella, Stefano; Bagno, Andrea; Polzonetti, Giovanni; Marletta, Giovanni; Dettin, Monica

    2013-04-01

    The features of implant devices and the reactions of bone-derived cells to foreign surfaces determine implant success during osseointegration. In an attempt to better understand the mechanisms underlying osteoblasts attachment and spreading, in this study adhesive peptides containing the fibronectin sequence motif for integrin binding (Arg-Gly-Asp, RGD) or mapping the human vitronectin protein (HVP) were grafted on glass and titanium surfaces with or without chemically induced controlled immobilization. As shown by total internal reflection fluorescence microscopy, human osteoblasts develop adhesion patches only on specifically immobilized peptides. Indeed, cells quickly develop focal adhesions on RGD-grafted surfaces, while HVP peptide promotes filopodia, structures involved in cellular spreading. As indicated by immunocytochemistry and quantitative polymerase chain reaction, focal adhesions kinase activation is delayed on HVP peptides with respect to RGD while an osteogenic phenotypic response appears within 24h on osteoblasts cultured on both peptides. Cellular pathways underlying osteoblasts attachment are, however, different. As demonstrated by adhesion blocking assays, integrins are mainly involved in osteoblast adhesion to RGD peptide, while HVP selects osteoblasts for attachment through proteoglycan-mediated interactions. Thus an interfacial layer of an endosseous device grafted with specifically immobilized HVP peptide not only selects the attachment and supports differentiation of osteoblasts but also promotes cellular migration. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. Manipulation of the response of human endothelial colony-forming cells by focal adhesion assembly using gradient nanopattern plates.

    Science.gov (United States)

    Cui, Long-Hui; Joo, Hyung Joon; Kim, Dae Hwan; Seo, Ha-Rim; Kim, Jung Suk; Choi, Seung-Cheol; Huang, Li-Hua; Na, Ji Eun; Lim, I-Rang; Kim, Jong-Ho; Rhyu, Im Joo; Hong, Soon Jun; Lee, Kyu Back; Lim, Do-Sun

    2018-01-01

    Nanotopography plays a pivotal role in the regulation of cellular responses. Nonetheless, little is known about how the gradient size of nanostructural stimuli alters the responses of endothelial progenitor cells without chemical factors. Herein, the fabrication of gradient nanopattern plates intended to mimic microenvironment nanotopography is described. The gradient nanopattern plates consist of nanopillars of increasing diameter ranges [120-200 nm (GP 120/200), 200-280 nm (GP 200/280), and 280-360 nm (GP 280/360)] that were used to screen the responses of human endothelial colony-forming cells (hECFCs). Nanopillars with a smaller nanopillar diameter caused the cell area and perimeter of hECFCs to decrease and their filopodial outgrowth to increase. The structure of vinculin (a focal adhesion marker in hECFCs) was also modulated by nanostructural stimuli of the gradient nanopattern plates. Moreover, Rho-associated protein kinase (ROCK) gene expression was significantly higher in hECFCs cultured on GP 120/200 than in those on flat plates (no nanopillars), and ROCK suppression impaired the nanostructural-stimuli-induced vinculin assembly. These results suggest that the gradient nanopattern plates generate size-specific nanostructural stimuli suitable for manipulation of the response of hECFCs, in a process dependent on ROCK signaling. This is the first evidence of size-specific nanostructure-sensing behavior of hECFCs. Nano feature surfaces are of growing interest as materials for a controlled response of various cells. In this study, we successfully fabricated gradient nanopattern plates to manipulate the response of blood-derived hECFCs without any chemical stimulation. Interestingly, we find that the sensitive nanopillar size for manipulation of hECFCs is range between 120 nm and 200 nm, which decreased the area and increased the filopodial outgrowth of hECFCs. Furthermore, we only modulate the nanopillar size to increase ROCK expression can be an

  17. Migration of periodontal ligament fibroblasts on nanometric topographical patterns: influence of filopodia and focal adhesions on contact guidance.

    Directory of Open Access Journals (Sweden)

    Douglas W Hamilton

    Full Text Available Considered to be the "holy grail" of dentistry, regeneration of the periodontal ligament in humans remains a major clinical problem. Removal of bacterial biofilms is commonly achieved using EDTA gels or lasers. One side effect of these treatment regimens is the etching of nanotopographies on the surface of the tooth. However, the response of periodontal ligament fibroblasts to such features has received very little attention. Using laser interference lithography, we fabricated precisely defined topographies with continuous or discontinuous nanogrooves to assess the adhesion, spreading and migration of PDL fibroblasts. PDL fibroblasts adhered to and spread on all tested surfaces, with initial spreading and focal adhesion formation slower on discontinuous nanogrooves. Cells had a significantly smaller planar area on both continuous and discontinuous nanogrooves in comparison with cells on non-patterned controls. At 24 h post seeding, cells on both types of nanogrooves were highly elongated parallel to the groove long axis. Time-lapse video microscopy revealed that PDL fibroblast movement was guided on both types of grooves, but migration velocity was not significantly different from cells cultured on non-patterned controls. Analysis of filopodia formation using time-lapse video microscopy and labeling of vinculin and F-actin revealed that on nanogrooves, filopodia were highly aligned at both ends of the cell, but with increasing time filopodia and membrane protrusions developed at the side of the cell perpendicular to the cell long axis. We conclude that periodontal ligament fibroblasts are sensitive to nanotopographical depths of 85-100 µm, which could be utilized in regeneration of the periodontal ligament.

  18. The extracellular matrix and focal adhesion kinase signaling regulate cancer stem cell function in pancreatic ductal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Asma Begum

    Full Text Available Cancer stem cells (CSCs play an important role in the clonogenic growth and metastasis of pancreatic ductal adenocarcinoma (PDAC. A hallmark of PDAC is the desmoplastic reaction, but the impact of the tumor microenvironment (TME on CSCs is unknown. In order to better understand the mechanisms, we examined the impact of extracellular matrix (ECM proteins on PDAC CSCs. We quantified the effect of ECM proteins, β1-integrin, and focal adhesion kinase (FAK on clonogenic PDAC growth and migration in vitro and tumor initiation, growth, and metastasis in vivo in nude mice using shRNA and overexpression constructs as well as small molecule FAK inhibitors. Type I collagen increased PDAC tumor initiating potential, self-renewal, and the frequency of CSCs through the activation of FAK. FAK overexpression increased tumor initiation, whereas a dominant negative FAK mutant or FAK kinase inhibitors reduced clonogenic PDAC growth in vitro and in vivo. Moreover, the FAK inhibitor VS-4718 extended the anti-tumor response to gemcitabine and nab-paclitaxel in patient-derived PDAC xenografts, and the loss of FAK expression limited metastatic dissemination of orthotopic xenografts. Type I collagen enhances PDAC CSCs, and both kinase-dependent and independent activities of FAK impact PDAC tumor initiation, self-renewal, and metastasis. The anti-tumor impact of FAK inhibitors in combination with standard chemotherapy support the clinical testing of this combination.

  19. Heat shock protein 90β stabilizes focal adhesion kinase and enhances cell migration and invasion in breast cancer cells

    International Nuclear Information System (INIS)

    Xiong, Xiangyang; Wang, Yao; Liu, Chengmei; Lu, Quqin; Liu, Tao; Chen, Guoan; Rao, Hai; Luo, Shiwen

    2014-01-01

    Focal adhesion kinase (FAK) acts as a regulator of cellular signaling and may promote cell spreading, motility, invasion and survival in malignancy. Elevated expression and activity of FAK frequently correlate with tumor cell metastasis and poor prognosis in breast cancer. However, the mechanisms by which the turnover of FAK is regulated remain elusive. Here we report that heat shock protein 90β (HSP90β) interacts with FAK and the middle domain (amino acids 233–620) of HSP90β is mainly responsible for this interaction. Furthermore, we found that HSP90β regulates FAK stability since HSP90β inhibitor 17-AAG triggers FAK ubiquitylation and subsequent proteasome-dependent degradation. Moreover, disrupted FAK-HSP90β interaction induced by 17-AAG contributes to attenuation of tumor cell growth, migration, and invasion. Together, our results reveal how HSP90β regulates FAK stability and identifies a potential therapeutic strategy to breast cancer. - Highlights: • HSP90β protects FAK from degradation by the ubiquitin-proteasome pathway. • Inhibition of HSP90β or FAK attenuates tumorigenesis of breast cancer cells. • Genetic repression of HSP90β or FAK inhibits tumor cell migration and proliferation. • Inhibition of HSP90β or FAK interferes cell invasion and cytoskeleton

  20. Down-regulation of procaspase-8 expression by focal adhesion kinase protects HL-60 cells from TRAIL-induced apoptosis

    International Nuclear Information System (INIS)

    Tamagiku, Yuji; Sonoda, Yoshiko; Kunisawa, Mari; Ichikawa, Daiju; Murakami, Yayoi; Aizu-Yokota, Eriko; Kasahara, Tadashi

    2004-01-01

    We have demonstrated that focal adhesion kinase (FAK)-overexpressed (HL-60/FAK) cells have marked resistance against various apoptotic stimuli such as hydrogen peroxide, etoposide, and ionizing radiation compared with the vector-transfected (HL-60/Vect) cells. HL-60/FAK cells are highly resistant to TRAIL-induced apoptosis, while original HL-60 or HL-60/Vect cells were sensitive. TRAIL at 500 ng/ml induced significant DNA fragmentation, activation of caspase-8 and 3, the processing of a proapoptotic BID, and mitochondrial release of cytochrome c in HL-60/Vect cells, whereas no such events were observed in the HL-60/FAK cells. In particular, the expression of procaspase-8 gene and subsequent cleavage of caspase-8 were markedly reduced in HL-60/FAK cells, while expression of TRAIL-receptor 2 and 3, TRADD, and FADD was equivalent in both types of cells. In HL-60/FAK cells, the phosphoinositide 3 (PI3)-kinase/Akt survival pathway was constitutively activated, accompanied by significant induction of inhibitor-of-apoptosis proteins, XIAP, RIP, and Bcl-XL. The introduction of FAK siRNA in HL-60/FAK cells sensitized them against TRAIL-induced apoptosis, confirming that overexpressed FAK downregulates procaspase-8 expression, which subsequently inhibits downstream apoptosis pathway in the HL-60/FAK cells

  1. Protective influence of hyaluronic acid on focal adhesion kinase activity in human skin fibroblasts exposed to ethanol.

    Science.gov (United States)

    Donejko, Magdalena; Rysiak, Edyta; Galicka, Elżbieta; Terlikowski, Robert; Głażewska, Edyta Katarzyna; Przylipiak, Andrzej

    2017-01-01

    The aim of this study was to evaluate the effect of ethanol and hyaluronic acid (HA) on cell survival and apoptosis in cultured human skin fibroblasts. Regarding the mechanism of ethanol action on human skin fibroblasts, we investigated cell viability and apoptosis, expression of focal adhesion kinase (FAK), and the influence of HA on those processes. Studies were conducted in confluent human skin fibroblast cultures that were treated with 25 mM, 50 mM, and 100 mM ethanol or with ethanol and 500 µg/mL HA. Cell viability was examined using methyl thiazolyl tetrazolium (MTT) assay and NC-300 Nucleo-Counter. Imaging of the cells using a fluorescence microscope Pathway 855 was performed to measure FAK expression. Depending on the dosage, ethanol decreased cell viability and activated the process of apoptosis in human skin fibroblasts. HA prevented the negative influence of ethanol on cell viability and prevented apoptosis. The analysis of fluorescence imaging using BD Pathway 855 High-Content Bioimager showed the inhibition of FAK migration to the cell nucleus, depending on the increasing concentration of ethanol. This study proves that downregulation of signaling pathway of FAK is involved in ethanol-induced apoptosis in human skin fibroblasts. The work also indicates a protective influence of HA on FAK activity in human skin fibroblasts exposed to ethanol.

  2. Heat shock protein 90β stabilizes focal adhesion kinase and enhances cell migration and invasion in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Xiangyang [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi 330006 (China); State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047 (China); Wang, Yao [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Liu, Chengmei [State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047 (China); Lu, Quqin [Department of Biostatistics and Epidemiology, School of Public Health, Nanchang University, Nanchang, Jiangxi 330006 (China); Liu, Tao [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Chen, Guoan [Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006 (China); Rao, Hai [Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Luo, Shiwen, E-mail: shiwenluo@ncu.edu.cn [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China)

    2014-08-01

    Focal adhesion kinase (FAK) acts as a regulator of cellular signaling and may promote cell spreading, motility, invasion and survival in malignancy. Elevated expression and activity of FAK frequently correlate with tumor cell metastasis and poor prognosis in breast cancer. However, the mechanisms by which the turnover of FAK is regulated remain elusive. Here we report that heat shock protein 90β (HSP90β) interacts with FAK and the middle domain (amino acids 233–620) of HSP90β is mainly responsible for this interaction. Furthermore, we found that HSP90β regulates FAK stability since HSP90β inhibitor 17-AAG triggers FAK ubiquitylation and subsequent proteasome-dependent degradation. Moreover, disrupted FAK-HSP90β interaction induced by 17-AAG contributes to attenuation of tumor cell growth, migration, and invasion. Together, our results reveal how HSP90β regulates FAK stability and identifies a potential therapeutic strategy to breast cancer. - Highlights: • HSP90β protects FAK from degradation by the ubiquitin-proteasome pathway. • Inhibition of HSP90β or FAK attenuates tumorigenesis of breast cancer cells. • Genetic repression of HSP90β or FAK inhibits tumor cell migration and proliferation. • Inhibition of HSP90β or FAK interferes cell invasion and cytoskeleton.

  3. Homozygous mutation of focal adhesion kinase in embryonic stem cell derived neurons: normal electrophysiological and morphological properties in vitro

    Directory of Open Access Journals (Sweden)

    Komiyama NH

    2006-06-01

    Full Text Available Abstract Background Genetically manipulated embryonic stem (ES cell derived neurons (ESNs provide a powerful system with which to study the consequences of gene manipulation in mature, synaptically connected neurons in vitro. Here we report a study of focal adhesion kinase (FAK, which has been implicated in synapse formation and regulation of ion channels, using the ESN system to circumvent the embryonic lethality of homozygous FAK mutant mice. Results Mouse ES cells carrying homozygous null mutations (FAK-/- were generated and differentiated in vitro into neurons. FAK-/- ESNs extended axons and dendrites and formed morphologically and electrophysiologically intact synapses. A detailed study of NMDA receptor gated currents and voltage sensitive calcium currents revealed no difference in their magnitude, or modulation by tyrosine kinases. Conclusion FAK does not have an obligatory role in neuronal differentiation, synapse formation or the expression of NMDA receptor or voltage-gated calcium currents under the conditions used in this study. The use of genetically modified ESNs has great potential for rapidly and effectively examining the consequences of neuronal gene manipulation and is complementary to mouse studies.

  4. Focal adhesion kinase (FAK1 regulates SHB phosphorylation and its binding with a range of signaling proteins

    Directory of Open Access Journals (Sweden)

    Dergai O. V.

    2016-02-01

    Full Text Available Aim. To investigate an effect of the Focal adhesion kinase 1 (FAK1 expression on the level of tyrosine phosphorylation of an adaptor protein SHB and to find functional consequences of this posttranslational modification. Methods. Recombinant DNA construction, protein expression and purification, human cell transfection, western blot. Results. The expression of FAK1 induces the massive tyrosine phosphorylation of SHB adaptor and enhances its interaction in vitro with SH2 domains of a range of the signaling proteins such as PI3K, ABL, CRK and PLCG1. Additionally we have found that Epstein-Barr virus protein LMP2A can partially mimic the FAK1-mediated effect strongly elevating the efficiency and SHB interaction with the mentioned above proteins. While the expression of individual proteins elevated SHB phosphorylation level, the co-expression of LMP2A and FAK1 did not display a synergetic effect. Conclusions. FAK1 as well as LMP2A induce the SHB tyrosine phosphorylation and enhance its interaction with a set of the signaling proteins.

  5. 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.

  6. Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation.

    Science.gov (United States)

    He, Kangmin; Sakai, Tsuyoshi; Tsukasaki, Yoshikazu; Watanabe, Tomonobu M; Ikebe, Mitsuo

    2017-10-20

    Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell's leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia. Arp2/3 and integrin-β then became localized at the tip of filopodia, from where myosin X initiated the second extension of filopodia with a change in extension direction, thus producing long filopodia. Elimination of integrin-β, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation. We propose the following mechanism. Myosin X accumulates at nascent focal adhesions at the cell's leading edge, where myosin X promotes actin convergence to create the base of filopodia. Then myosin X moves to the filopodia tip and attracts integrin-β and Arp2/3 for further actin nucleation. The tip-located myosin X then initiates the second cycle of filopodia elongation to produce the long filopodia.

  7. Cell nanomechanics and focal adhesions are regulated by retinol and conjugated linoleic acid in a dose-dependent manner

    International Nuclear Information System (INIS)

    Silberberg, Yaron R; Horton, Michael A; Pelling, Andrew E; Yakubov, Gleb E

    2009-01-01

    Retinol and conjugated linoleic acid (CLA) have previously been shown to have an important role in gene expression and various cellular processes, including differentiation, proliferation and cell death. In this study we have investigated the effect of retinol and CLA, both individually and in combination, on the intracellular cytoskeleton, focal adhesions (FAs) and the nanomechanical properties of 3T3 fibroblasts. We observed a dose-dependent decrease in the formation of FAs following treatment with either compound, which was directly correlated to an increase in cell height (>30%) and a decrease in the measured Young's modulus (∼28%). Furthermore, treatments with both compounds demonstrated an increased effect and led to a reduction of>70% in the average number of FAs per cell and a decrease of >50% in average cell stiffness. These data reveal that retinol and CLA disrupt FA formation, leading to an increase in cell height and a significant decrease in stiffness. These results may broaden our understanding of the interplay between cell nanomechanics and cellular contact with the external microenvironment, and help to shed light on the important role of retinoids and CLA in health and disease.

  8. Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions

    International Nuclear Information System (INIS)

    Sakwe, Amos M.; Koumangoye, Rainelli; Guillory, Bobby; Ochieng, Josiah

    2011-01-01

    The interaction of annexin A6 (AnxA6) with membrane phospholipids and either specific extracellular matrix (ECM) components or F-actin suggests that it may influence cellular processes associated with rapid plasma membrane reorganization such as cell adhesion and motility. Here, we examined the putative roles of AnxA6 in adhesion-related cellular processes that contribute to breast cancer progression. We show that breast cancer cells secrete annexins via the exosomal pathway and that the secreted annexins are predominantly cell surface-associated. Depletion of AnxA6 in the invasive BT-549 breast cancer cells is accompanied by enhanced anchorage-independent cell growth but cell-cell cohesion, cell adhesion/spreading onto collagen type IV or fetuin-A, cell motility and invasiveness were strongly inhibited. To explain the loss in adhesion/motility, we show that vinculin-based focal adhesions in the AnxA6-depleted BT-549 cells are elongated and randomly distributed. These focal contacts are also functionally defective because the activation of focal adhesion kinase and the phosphoinositide-3 kinase/Akt pathway were strongly inhibited while the MAP kinase pathway remained constitutively active. Compared with normal human breast tissues, reduced AnxA6 expression in breast carcinoma tissues correlates with enhanced cell proliferation. Together this suggests that reduced AnxA6 expression contributes to breast cancer progression by promoting the loss of functional cell-cell and/or cell-ECM contacts and anchorage-independent cell proliferation.

  9. Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions

    Energy Technology Data Exchange (ETDEWEB)

    Sakwe, Amos M., E-mail: asakwe@mmc.edu [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Koumangoye, Rainelli; Guillory, Bobby [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Ochieng, Josiah [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Center for Aids Health Disparity Research, Meharry Medical College, Nashville, TN 37208 (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States)

    2011-04-01

    The interaction of annexin A6 (AnxA6) with membrane phospholipids and either specific extracellular matrix (ECM) components or F-actin suggests that it may influence cellular processes associated with rapid plasma membrane reorganization such as cell adhesion and motility. Here, we examined the putative roles of AnxA6 in adhesion-related cellular processes that contribute to breast cancer progression. We show that breast cancer cells secrete annexins via the exosomal pathway and that the secreted annexins are predominantly cell surface-associated. Depletion of AnxA6 in the invasive BT-549 breast cancer cells is accompanied by enhanced anchorage-independent cell growth but cell-cell cohesion, cell adhesion/spreading onto collagen type IV or fetuin-A, cell motility and invasiveness were strongly inhibited. To explain the loss in adhesion/motility, we show that vinculin-based focal adhesions in the AnxA6-depleted BT-549 cells are elongated and randomly distributed. These focal contacts are also functionally defective because the activation of focal adhesion kinase and the phosphoinositide-3 kinase/Akt pathway were strongly inhibited while the MAP kinase pathway remained constitutively active. Compared with normal human breast tissues, reduced AnxA6 expression in breast carcinoma tissues correlates with enhanced cell proliferation. Together this suggests that reduced AnxA6 expression contributes to breast cancer progression by promoting the loss of functional cell-cell and/or cell-ECM contacts and anchorage-independent cell proliferation.

  10. [Functional connectivity and complex networks in focal epilepsy. Pathophysiology and therapeutic implications].

    Science.gov (United States)

    Pastor, Jesús; Sola, Rafael G; Vega-Zelaya, Lorena; Garnes, Óscar; Ortega, Guillermo J

    2014-05-01

    The traditional surgical approach to treat drug-resistant focal epileptic patients is in the resection or disconnection of the epileptic focus. However, a significant minority of patients continue to experience seizures after surgery, which shows the incomplete level of knowledge that currently we have of this pathology. This paper introduces some concepts of functional connectivity and complex networks methodology with its application to the study of neurophysiological recordings from patients suffering from drug-resistant focal epilepsy. In order to fully understand the new developments in the area of complex networks and its applications to the study of epilepsy, we will here review fundamental concepts in complex networks methodology, synchronization and functional connectivity. Some of the most recent published works dealing with focal epilepsy viewed under this new perspective will be revised and commented. We think that a wider perspective in the study of epilepsy, such as the one reviewed in this work, will allow epileptologists to consider surgical alternatives in the usual treatment of focal epilepsy at those currently performed in most medical centers around the world. Combining the traditional knowledge with new insights provided by network theory will certainly fill many of the gaps we have today in the fragmented understanding of epilepsy.

  11. Suppression of β3-integrin in mice triggers a neuropilin-1-dependent change in focal adhesion remodelling that can be targeted to block pathological angiogenesis

    Directory of Open Access Journals (Sweden)

    Tim S. Ellison

    2015-09-01

    Full Text Available Anti-angiogenic treatments against αvβ3-integrin fail to block tumour growth in the long term, which suggests that the tumour vasculature escapes from angiogenesis inhibition through αvβ3-integrin-independent mechanisms. Here, we show that suppression of β3-integrin in mice leads to the activation of a neuropilin-1 (NRP1-dependent cell migration pathway in endothelial cells via a mechanism that depends on NRP1's mobilisation away from mature focal adhesions following VEGF-stimulation. The simultaneous genetic targeting of both molecules significantly impairs paxillin-1 activation and focal adhesion remodelling in endothelial cells, and therefore inhibits tumour angiogenesis and the growth of already established tumours. These findings provide a firm foundation for testing drugs against these molecules in combination to treat patients with advanced cancers.

  12. The Src homology 2 protein Shb promotes cell cycle progression in murine hematopoietic stem cells by regulation of focal adhesion kinase activity

    Energy Technology Data Exchange (ETDEWEB)

    Gustafsson, Karin [Department of Medical Cell Biology, Uppsala University, Uppsala 751 23 (Sweden); Heffner, Garrett; Wenzel, Pamela L.; Curran, Matthew [HHMI, Children' s Hospital Boston, Harvard Medical School, Boston, 02115 MA (United States); Grawé, Jan [Department of Genetics and Pathology, Uppsala University, Uppsala 75185 (Sweden); McKinney-Freeman, Shannon L. [Department of Hematology, St. Jude Children' s Research Hospital, Memphis, TN 38105 (United States); Daley, George Q. [HHMI, Children' s Hospital Boston, Harvard Medical School, Boston, 02115 MA (United States); Welsh, Michael, E-mail: michael.welsh@mcb.uu.se [Department of Medical Cell Biology, Uppsala University, Uppsala 751 23 (Sweden)

    2013-07-15

    The widely expressed adaptor protein Shb has previously been reported to contribute to T cell function due to its association with the T cell receptor and furthermore, several of Shb's known interaction partners are established regulators of blood cell development and function. In addition, Shb deficient embryonic stem cells displayed reduced blood cell colony formation upon differentiation in vitro. The aim of the current study was therefore to explore hematopoietic stem and progenitor cell function in the Shb knockout mouse. Shb deficient bone marrow contained reduced relative numbers of long-term hematopoietic stem cells (LT-HSCs) that exhibited lower proliferation rates. Despite this, Shb knockout LT-HSCs responded promptly by entering the cell cycle in response to genotoxic stress by 5-fluorouracil treatment. In competitive LT-HSC transplantations, Shb null cells initially engrafted as well as the wild-type cells but provided less myeloid expansion over time. Moreover, Shb knockout bone marrow cells exhibited elevated basal activities of focal adhesion kinase/Rac1/p21-activated kinase signaling and reduced responsiveness to Stem Cell Factor stimulation. Consequently, treatment with a focal adhesion kinase inhibitor increased Shb knockout LT-HSC proliferation. The altered signaling characteristics thus provide a plausible mechanistic explanation for the changes in LT-HSC proliferation since these signaling intermediates have all been shown to participate in LT-HSC cell cycle control. In summary, the loss of Shb dependent signaling in bone marrow cells, resulting in elevated focal adhesion kinase activity and reduced proliferative responses in LT-HSCs under steady state hematopoiesis, confers a disadvantage to the maintenance of LT-HSCs over time. -- Highlights: • Shb is an adaptor protein operating downstream of tyrosine kinase receptors. • Shb deficiency reduces hematopoietic stem cell proliferation. • The proliferative effect of Shb occurs via

  13. The Src homology 2 protein Shb promotes cell cycle progression in murine hematopoietic stem cells by regulation of focal adhesion kinase activity

    International Nuclear Information System (INIS)

    Gustafsson, Karin; Heffner, Garrett; Wenzel, Pamela L.; Curran, Matthew; Grawé, Jan; McKinney-Freeman, Shannon L.; Daley, George Q.; Welsh, Michael

    2013-01-01

    The widely expressed adaptor protein Shb has previously been reported to contribute to T cell function due to its association with the T cell receptor and furthermore, several of Shb's known interaction partners are established regulators of blood cell development and function. In addition, Shb deficient embryonic stem cells displayed reduced blood cell colony formation upon differentiation in vitro. The aim of the current study was therefore to explore hematopoietic stem and progenitor cell function in the Shb knockout mouse. Shb deficient bone marrow contained reduced relative numbers of long-term hematopoietic stem cells (LT-HSCs) that exhibited lower proliferation rates. Despite this, Shb knockout LT-HSCs responded promptly by entering the cell cycle in response to genotoxic stress by 5-fluorouracil treatment. In competitive LT-HSC transplantations, Shb null cells initially engrafted as well as the wild-type cells but provided less myeloid expansion over time. Moreover, Shb knockout bone marrow cells exhibited elevated basal activities of focal adhesion kinase/Rac1/p21-activated kinase signaling and reduced responsiveness to Stem Cell Factor stimulation. Consequently, treatment with a focal adhesion kinase inhibitor increased Shb knockout LT-HSC proliferation. The altered signaling characteristics thus provide a plausible mechanistic explanation for the changes in LT-HSC proliferation since these signaling intermediates have all been shown to participate in LT-HSC cell cycle control. In summary, the loss of Shb dependent signaling in bone marrow cells, resulting in elevated focal adhesion kinase activity and reduced proliferative responses in LT-HSCs under steady state hematopoiesis, confers a disadvantage to the maintenance of LT-HSCs over time. -- Highlights: • Shb is an adaptor protein operating downstream of tyrosine kinase receptors. • Shb deficiency reduces hematopoietic stem cell proliferation. • The proliferative effect of Shb occurs via increased

  14. Recruitment of focal adhesion kinase and paxillin to β1 integrin promotes cancer cell migration via mitogen activated protein kinase activation

    International Nuclear Information System (INIS)

    Crowe, David L; Ohannessian, Arthur

    2004-01-01

    Integrin-extracellular matrix interactions activate signaling cascades such as mitogen activated protein kinases (MAPK). Integrin binding to extracellular matrix increases tyrosine phosphorylation of focal adhesion kinase (FAK). Inhibition of FAK activity by expression of its carboxyl terminus decreases cell motility, and cells from FAK deficient mice also show reduced migration. Paxillin is a focal adhesion protein which is also phosphorylated on tyrosine. FAK recruitment of paxillin to the cell membrane correlates with Shc phosphorylation and activation of MAPK. Decreased FAK expression inhibits papilloma formation in a mouse skin carcinogenesis model. We previously demonstrated that MAPK activation was required for growth factor induced in vitro migration and invasion by human squamous cell carcinoma (SCC) lines. Adapter protein recruitment to integrin subunits was examined by co-immunoprecipitation in SCC cells attached to type IV collagen or plastic. Stable clones overexpressing FAK or paxillin were created using the lipofection technique. Modified Boyden chambers were used for invasion assays. In the present study, we showed that FAK and paxillin but not Shc are recruited to the β1 integrin cytoplasmic domain following attachment of SCC cells to type IV collagen. Overexpression of either FAK or paxillin stimulated cancer cell migration on type IV collagen and invasion through reconstituted basement membrane which was dependent on MAPK activity. We concluded that recruitment of focal adhesion kinase and paxillin to β1 integrin promoted cancer cell migration via the mitogen activated protein kinase pathway

  15. Recruitment of focal adhesion kinase and paxillin to β1 integrin promotes cancer cell migration via mitogen activated protein kinase activation

    Directory of Open Access Journals (Sweden)

    Ohannessian Arthur

    2004-05-01

    Full Text Available Abstract Background Integrin-extracellular matrix interactions activate signaling cascades such as mitogen activated protein kinases (MAPK. Integrin binding to extracellular matrix increases tyrosine phosphorylation of focal adhesion kinase (FAK. Inhibition of FAK activity by expression of its carboxyl terminus decreases cell motility, and cells from FAK deficient mice also show reduced migration. Paxillin is a focal adhesion protein which is also phosphorylated on tyrosine. FAK recruitment of paxillin to the cell membrane correlates with Shc phosphorylation and activation of MAPK. Decreased FAK expression inhibits papilloma formation in a mouse skin carcinogenesis model. We previously demonstrated that MAPK activation was required for growth factor induced in vitro migration and invasion by human squamous cell carcinoma (SCC lines. Methods Adapter protein recruitment to integrin subunits was examined by co-immunoprecipitation in SCC cells attached to type IV collagen or plastic. Stable clones overexpressing FAK or paxillin were created using the lipofection technique. Modified Boyden chambers were used for invasion assays. Results In the present study, we showed that FAK and paxillin but not Shc are recruited to the β1 integrin cytoplasmic domain following attachment of SCC cells to type IV collagen. Overexpression of either FAK or paxillin stimulated cancer cell migration on type IV collagen and invasion through reconstituted basement membrane which was dependent on MAPK activity. Conclusions We concluded that recruitment of focal adhesion kinase and paxillin to β1 integrin promoted cancer cell migration via the mitogen activated protein kinase pathway.

  16. Akt1 binds focal adhesion kinase via the Akt1 kinase domain independently of the pleckstrin homology domain.

    Science.gov (United States)

    Basson, M D; Zeng, B; Wang, S

    2015-10-01

    Akt1 and focal adhesion kinase (FAK) are protein kinases that play key roles in normal cell signaling. Individually, aberrant expression of these kinases has been linked to a variety of cancers. Together, Akt1/FAK interactions facilitate cancer metastasis by increasing cell adhesion under conditions of increased extracellular pressure. Pathological and iatrogenic sources of pressure arise from tumor growth against constraining stroma or direct perioperative manipulation. We previously reported that 15 mmHg increased extracellular pressure causes Akt1 to both directly interact with FAK and to phosphorylate and activate it. We investigated the nature of the Akt1/FAK binding by creating truncations of recombinant FAK, conjugated to glutathione S-transferase (GST), to pull down full-length Akt1. Western blots probing for Akt1 showed that FAK/Akt1 binding persisted in FAK truncations consisting of only amino acids 1-126, FAK(NT1), which contains the F1 subdomain of its band 4.1, ezrin, radixin, and moesin (FERM) domain. Using FAK(NT1) as bait, we then pulled down truncated versions of recombinant Akt1 conjugated to HA (human influenza hemagglutinin). Probes for GST-FAK(NT1) showed Akt1-FAK binding to occur in the absence of the both the Akt1 (N)-terminal pleckstrin homology (PH) domain and its adjacent hinge region. The Akt1 (C)-terminal regulatory domain was equally unnecessary for Akt1/FAK co-immunoprecipitation. Truncations involving the Akt1 catalytic domain showed that the domain by itself was enough to pull down FAK. Additionally, a fragment spanning from the PH domain to half way through the catalytic domain demonstrated increased FAK binding compared to full length Akt1. These results begin to delineate the Akt1/FAK interaction and can be used to manipulate their force-activated signal interactions. Furthermore, the finding that the N-terminal half of the Akt1 catalytic domain binds so strongly to FAK when cleaved from the rest of the protein may suggest a means

  17. Adhesion

    Science.gov (United States)

    ... Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Adhesion URL of this page: //medlineplus.gov/ency/article/001493.htm Adhesion To use the sharing features on this page, please enable JavaScript. Adhesions are bands of scar-like tissue that form between two ...

  18. Oncogenic Receptor Tyrosine Kinases Directly Phosphorylate Focal Adhesion Kinase (FAK) as a Resistance Mechanism to FAK-Kinase Inhibitors.

    Science.gov (United States)

    Marlowe, Timothy A; Lenzo, Felicia L; Figel, Sheila A; Grapes, Abigail T; Cance, William G

    2016-12-01

    Focal adhesion kinase (FAK) is a major drug target in cancer and current inhibitors targeted to the ATP-binding pocket of the kinase domain have entered clinical trials. However, preliminary results have shown limited single-agent efficacy in patients. Despite these unfavorable data, the molecular mechanisms that drive intrinsic and acquired resistance to FAK-kinase inhibitors are largely unknown. We have demonstrated that receptor tyrosine kinases (RTK) can directly bypass FAK-kinase inhibition in cancer cells through phosphorylation of FAK's critical tyrosine 397 (Y397). We also showed that HER2 forms a direct protein-protein interaction with the FAK-FERM-F1 lobe, promoting direct phosphorylation of Y397. In addition, FAK-kinase inhibition induced two forms of compensatory RTK reprogramming: (i) the rapid phosphorylation and activation of RTK signaling pathways in RTK High cells and (ii) the long-term acquisition of RTKs novel to the parental cell line in RTK Low cells. Finally, HER2 +: cancer cells displayed resistance to FAK-kinase inhibition in 3D growth assays using a HER2 isogenic system and HER2 + cancer cell lines. Our data indicate a novel drug resistance mechanism to FAK-kinase inhibitors whereby HER2 and other RTKs can rescue and maintain FAK activation (pY397) even in the presence of FAK-kinase inhibition. These data may have important ramifications for existing clinical trials of FAK inhibitors and suggest that individual tumor stratification by RTK expression would be important to predict patient response to FAK-kinase inhibitors. Mol Cancer Ther; 15(12); 3028-39. ©2016 AACR. ©2016 American Association for Cancer Research.

  19. Expression of focal adhesion kinase in uveal melanoma and the effects of Hsp90 inhibition by 17-AAG.

    Science.gov (United States)

    Faingold, Dana; Filho, Vasco Bravo; Fernandes, Bruno; Jagan, Lisa; de Barros, Alexandre M; Orellana, Maria Eugenia; Antecka, Emilia; Burnier, Miguel N

    2014-11-01

    Focal adhesion kinase (FAK) is implicated in tumor progression and metastatic cascade, and has been shown to be overexpressed in a variety of human cancers. However, the role of FAK in human uveal melanoma (UM) is not well defined. The purpose of this study was to evaluate the expression of FAK in UM tumors and normal eyes, and to determine the effect of Hsp90 inhibition on FAK expression in UM cells. FAK expression was assessed in 39 UM specimens, FAK[pY397] expression was assessed in 51 UM specimens, and both FAK and FAK[pY397] expression were assessed in 20 normal eyes. The expression of FAK and FAK[pY397] was detected by Western blot in five UM cell lines after treatment with 10 μmol/L of 17-AAG. FAK was positive in 87.2% and FAK[pY397] in 90% of UM specimens. Low FAK expression was detected in non-tumor structures and in normal eyes. The cell lines with the most proliferative, invasive phenotype (92.1, SP6.5 and MKT-BR) displayed high expression of FAK[pY397], and the levels of FAK and FAK[pY397] were decreased in the presence of 17-AAG starting with 24 h of exposure. FAK and FAK[pY397] were overexpressed in human UM tumors compared to normal ocular tissue and high levels of FAK[pY397] were seen in the most aggressive UM cell lines. Hsp90 inhibition led to downregulation of FAK expression. We propose a role for FAK in the pathogenesis of UM. Future studies are needed to explore the use of Hsp90 inhibitors as a feasible approach for modulating FAK in UM. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. 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.

  1. SH2 domain-containing protein tyrosine phosphatase 2 and focal adhesion kinase protein interactions regulate pulmonary endothelium barrier function.

    Science.gov (United States)

    Chichger, Havovi; Braza, Julie; Duong, Huetran; Harrington, Elizabeth O

    2015-06-01

    Enhanced protein tyrosine phosphorylation is associated with changes in vascular permeability through formation and dissolution of adherens junctions and regulation of stress fiber formation. Inhibition of the protein tyrosine phosphorylase SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) increases tyrosine phosphorylation of vascular endothelial cadherin and β-catenin, resulting in disruption of the endothelial monolayer and edema formation in the pulmonary endothelium. Vascular permeability is a hallmark of acute lung injury (ALI); thus, enhanced SHP2 activity offers potential therapeutic value for the pulmonary vasculature in diseases such as ALI, but this has not been characterized. To assess whether SHP2 activity mediates protection against edema in the endothelium, we assessed the effect of molecular activation of SHP2 on lung endothelial barrier function in response to the edemagenic agents LPS and thrombin. Both LPS and thrombin reduced SHP2 activity, correlated with decreased focal adhesion kinase (FAK) phosphorylation (Y(397) and Y(925)) and diminished SHP2 protein-protein associations with FAK. Overexpression of constitutively active SHP2 (SHP2(D61A)) enhanced baseline endothelial monolayer resistance and completely blocked LPS- and thrombin-induced permeability in vitro and significantly blunted pulmonary edema formation induced by either endotoxin (LPS) or Pseudomonas aeruginosa exposure in vivo. Chemical inhibition of FAK decreased SHP2 protein-protein interactions with FAK concomitant with increased permeability; however, overexpression of SHP2(D61A) rescued the endothelium and maintained FAK activity and FAK-SHP2 protein interactions. Our data suggest that SHP2 activation offers the pulmonary endothelium protection against barrier permeability mediators downstream of the FAK signaling pathway. We postulate that further studies into the promotion of SHP2 activation in the pulmonary endothelium may offer a therapeutic approach for patients

  2. Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth

    International Nuclear Information System (INIS)

    Golubovskaya, Vita M; Ho, Baotran; Zheng, Min; Magis, Andrew; Ostrov, David; Morrison, Carl; Cance, William G

    2013-01-01

    Focal Adhesion Kinase (FAK) is a 125 kDa non-receptor kinase that plays a major role in cancer cell survival and metastasis. We performed computer modeling of the p53 peptide containing the site of interaction with FAK, predicted the peptide structure and docked it into the three-dimensional structure of the N-terminal domain of FAK involved in the complex with p53. We screened small molecule compounds that targeted the site of the FAK-p53 interaction and identified compounds (called Roslins, or R compounds) docked in silico to this site. By different assays in isogenic HCT116p53 + / + and HCT116 p53 - / - cells we identified a small molecule compound called Roslin 2 (R2) that bound FAK, disrupted the binding of FAK and p53 and decreased cancer cell viability and clonogenicity in a p53-dependent manner. In addition, dual-luciferase assays demonstrated that the R2 compound increased p53 transcriptional activity that was inhibited by FAK using p21, Mdm-2, and Bax-promoter targets. R2 also caused increased expression of p53 targets: p21, Mdm-2 and Bax proteins. Furthermore, R2 significantly decreased tumor growth, disrupted the complex of FAK and p53, and up-regulated p21 in HCT116 p53 + / + but not in HCT116 p53 - / - xenografts in vivo. In addition, R2 sensitized HCT116p53 + / + cells to doxorubicin and 5-fluorouracil. Thus, disruption of the FAK and p53 interaction with a novel small molecule reactivated p53 in cancer cells in vitro and in vivo and can be effectively used for development of FAK-p53 targeted cancer therapy approaches

  3. Focal glomerular immune complex deposition: possible role of periglomerular fibrosis/atubular glomeruli.

    Science.gov (United States)

    Satoskar, Anjali A; Calomeni, Edward; Bott, Cherri; Nadasdy, Gyongyi M; Nadasdy, Tibor

    2009-02-01

    Consensus exists among renal pathologists that, in biopsies with immune complex glomerulonephritis, even a single glomerulus with open capillary loops may be sufficient for immunofluorescence and/or electron microscopy evaluation because immune complex deposition is a diffuse phenomenon. However, we have encountered renal biopsies with focal absence of immune complexes in glomeruli on either immunofluorescence or electron microscopy examination despite presence of open glomerular capillary loops. To evaluate renal biopsies with focal immune complex deposition and look for any subtle or unusual morphologic changes in the glomeruli (and in the biopsy in general). Native and transplant renal biopsies were reviewed. All biopsies had been triaged and processed according to our routine protocol for light microscopy, immunofluorescence, and electron microscopy examination. Of 2018 renal biopsies from December 2005 to December 2007, we found 10 such biopsies; 5 native and 5 transplant kidney biopsies. We found that the glomeruli with absent immune complex deposits had periglomerular fibrosis with open, albeit, wrinkled appearing capillary loops but no glomerular sclerosis. We hypothesize that these histologic features are indicative of nonfunctional glomeruli and may be associated with disconnection between the Bowman capsule and proximal tubule (atubular glomeruli). These glomeruli may not have effective filtration, despite some degree of circulation through the open capillary loops, and therefore are unable to accumulate immune complex deposits. If biopsies are small and only such glomeruli are available for immunofluorescence or electron microscopy examination, the absence of immune complex deposition in them should be evaluated carefully.

  4. Inhibition of cell migration by focal adhesion kinase: Time-dependent difference in integrin-induced signaling between endothelial and hepatoblastoma cells.

    Science.gov (United States)

    Yu, Hongchi; Gao, Min; Ma, Yunlong; Wang, Lijuan; Shen, Yang; Liu, Xiaoheng

    2018-05-01

    angiogenesis plays an important role in the development and progression of tumors, and it involves a series of signaling pathways contributing to the migration of endothelial cells for vascularization and to the invasion of cancer cells for secondary tumor formation. Among these pathways, the focal adhesion kinase (FAK) signaling cascade has been implicated in a variety of human cancers in connection with cell adhesion and migration events leading to tumor angiogenesis, metastasis and invasion. Therefore, the inhibition of FAK in endothelial and/or cancer cells is a potential target for anti‑angiogenic therapy. In the present study, a small‑molecule FAK inhibitor, 1,2,4,5-benzenetetramine tetrahydrochloride (Y15), was used to study the effects of FAK inhibition on the adhesion and migration behaviors of vascular endothelial cells (VECs) and human hepatoblastoma cells. Furthermore, the time-dependent differences in proteins associated with the integrin-mediated FAK/Rho GTPases signaling pathway within 2 h were examined. The results indicated that the inhibition of FAK significantly decreased the migration ability of VECs and human hepatoblastoma cells in a dose-dependent manner. Inhibition of FAK promoted cell detachment by decreasing the expression of focal adhesion components, and blocked cell motility by reducing the level of Rho GTPases. However, the expression of crucial proteins involved in integrin-induced signaling in two cell lines exhibited a time-dependent difference with increased duration of FAK inhibitor treatment, suggesting different mechanisms of FAK-mediated cell migration behavior. These results suggest that the mechanism underlying FAK-mediated adhesion and migration behavior differs among various cells, which is expected to provide evidence for future FAK therapy targeted against tumor angiogenesis.

  5. Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases.

    OpenAIRE

    Schlaepfer, D D; Hunter, T

    1996-01-01

    Focal adhesion kinase (FAK) is a nonreceptor protein-tyrosine kinase (PTK) that associates with integrin receptors and participates in extracellular matrix-mediated signal transduction events. We showed previously that the c-Src nonreceptor PTK and the Grb2 SH2/SH3 adaptor protein bound directly to FAK after fibronectin stimulation (D. D. Schlaepfer, S.K. Hanks, T. Hunter, and P. van der Geer, Nature [London] 372:786-791, 1994). Here, we present evidence that c-Src association with FAK is req...

  6. Friction and solid-solid adhesion on complex metallic alloys

    Science.gov (United States)

    Dubois, Jean-Marie; Belin-Ferré, Esther

    2014-01-01

    The discovery in 1987 of stable quasicrystals in the Al–Cu–Fe system was soon exploited to patent specific coatings that showed reduced friction in ambient air against hard antagonists. Henceforth, it was possible to develop a number of applications, potential or commercially exploited to date, that will be alluded to in this topical review. A deeper understanding of the characteristics of complex metallic alloys (CMAs) may explain why material made of metals like Al, Cu and Fe offers reduced friction; low solid–solid adhesion came later. It is linked to the surface energy being significantly lower on those materials, in which translational symmetry has become a weak property, that is determined by the depth of the pseudo-gap at the Fermi energy. As a result, friction is anisotropic in CMAs that builds up according to the translation symmetry along one direction, but is aperiodic along the other two directions. A review is given in this article of the most salient data found along these lines during the past two decades or so. PMID:27877675

  7. RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T lymphocytes.

    Science.gov (United States)

    Ganju, R K; Hatch, W C; Avraham, H; Ona, M A; Druker, B; Avraham, S; Groopman, J E

    1997-03-17

    The related adhesion focal tyrosine kinase (RAFTK), a recently discovered member of the focal adhesion kinase family, has previously been reported to participate in signal transduction in neuronal cells, megakaryocytes, and B lymphocytes. We have found that RAFTK is constitutively expressed in human T cells and is rapidly phosphorylated upon the activation of the T cell receptor (TCR). This activation also results in an increase in the autophosphorylation and kinase activity of RAFTK. After its stimulation, there was an increase in the association of the src cytoplasmic tyrosine kinase Fyn and the adapter protein Grb2. This association was mediated through the SH2 domains of Fyn and Grb2. RAFTK also co-immunoprecipitates with the SH2 domain of Lck and with the cytoskeletal protein paxillin through its COOH-terminal proline-rich domain. The tyrosine phosphorylation of RAFTK after T cell receptor-mediated stimulation was reduced by the pretreatment of cells with cytochalasin D, suggesting the role of the cytoskeleton in this process. These observations indicate that RAFTK participates in T cell receptor signaling and may act to link signals from the cell surface to the cytoskeleton and thereby affect the host immune response.

  8. Molecular architecture of a complex between an adhesion protein from the malaria parasite and intracellular adhesion molecule 1

    DEFF Research Database (Denmark)

    Brown, Alan; Turner, Louise; Christoffersen, Stig

    2013-01-01

    The adhesion of Plasmodium falciparum-infected erythrocytes to human tissues or endothelium is central to the pathology caused by the parasite during malaria. It contributes to the avoidance of parasite clearance by the spleen and to the specific pathologies of cerebral and placental malaria....... The PfEMP1 family of adhesive proteins is responsible for this sequestration by mediating interactions with diverse human ligands. In addition, as the primary targets of acquired, protective immunity, the PfEMP1s are potential vaccine candidates. PfEMP1s contain large extracellular ectodomains made from......, intercellular adhesion molecule-1 (ICAM-1). We show through small angle x-ray scattering that IT4VAR13 is rigid, elongated, and monomeric. We also show that it interacts with ICAM-1 through the DBLß domain alone, forming a 1:1 complex. These studies provide a first low resolution structural view of a PfEMP1...

  9. Cell adhesion to textured silicone surfaces : The influence of time of adhesion and texture on focal contact and fibronectin fibril formation

    NARCIS (Netherlands)

    van Kooten, TG; von Recum, AF

    Cell adhesion and spreading on biomaterials is a key issue in the study of cell-biomaterial interactions. With the development of new disciplines within biomaterials research such as tissue engineering and cellular therapy, information at molecular and structural levels is needed in order to

  10. Complex of radionuclide methods in diagnosis of diffuse and focal hepatic lesions

    International Nuclear Information System (INIS)

    Yakovleva, L.A.

    1984-01-01

    For demonstrating focal affections of the liver a complex of dynamic and static examinations may be recommended with the application of hepatotropic and tumorotropic radiopharmaceuticals. The result indicates that patients with abscesses echinococcus or a cystic affection of the liver are affected by a several-fold decrease of blood flow in the ''cold'' foci or no flow. In the primary or secondary tumorous process there is no blood flow in the foci; there is, however, a prolonged half-life of accumulation of the preparation and a 50% decrease in the velocity of the uptake of the preparation in the liver. The changes of quantitative indices, characterizing an increase of blood flow to 150 to 200% of normal values, with a prevailing arterial component of the blood flow through the liver in all segments may be the sign of a cirrhotic process. (author)

  11. Complex of radionuclide methods in diagnosis of diffuse and focal hepatic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Yakovleva, L.A. (Centralni Vedeckovyzkumny Rentgenradiologicky Institut MZ SSSR, Leningrad (USSR))

    1984-03-01

    For demonstrating focal affections of the liver a complex of dynamic and static examinations may be recommended with the application of hepatotropic and tumorotropic radiopharmaceuticals. The result indicates that patients with abscesses echinococcus or a cystic affection of the liver are affected by a several-fold decrease of blood flow in the ''cold'' foci or no flow. In the primary or secondary tumorous process there is no blood flow in the foci; there is, however, a prolonged half-life of accumulation of the preparation and a 50% decrease in the velocity of the uptake of the preparation in the liver. The changes of quantitative indices, characterizing an increase of blood flow to 150 to 200% of normal values, with a prevailing arterial component of the blood flow through the liver in all segments may be the sign of a cirrhotic process.

  12. Cellular prion protein is required for neuritogenesis: fine-tuning of multiple signaling pathways involved in focal adhesions and actin cytoskeleton dynamics

    Directory of Open Access Journals (Sweden)

    Alleaume-Butaux A

    2013-07-01

    Full Text Available Aurélie Alleaume-Butaux,1,2 Caroline Dakowski,1,2 Mathéa Pietri,1,2 Sophie Mouillet-Richard,1,2 Jean-Marie Launay,3,4 Odile Kellermann,1,2 Benoit Schneider1,2 1INSERM, UMR-S 747, 2Paris Descartes University, Sorbonne Paris Cité, UMR-S 747, 3Public Hospital of Paris, Department of Biochemistry, INSERM UMR-S 942, Lariboisière Hospital, Paris, France; 4Pharma Research Department, Hoffmann La Roche Ltd, Basel, Switzerland Abstract: Neuritogenesis is a dynamic phenomenon associated with neuronal differentiation that allows a rather spherical neuronal stem cell to develop dendrites and axon, a prerequisite for the integration and transmission of signals. The acquisition of neuronal polarity occurs in three steps: (1 neurite sprouting, which consists of the formation of buds emerging from the postmitotic neuronal soma; (2 neurite outgrowth, which represents the conversion of buds into neurites, their elongation and evolution into axon or dendrites; and (3 the stability and plasticity of neuronal polarity. In neuronal stem cells, remodeling and activation of focal adhesions (FAs associated with deep modifications of the actin cytoskeleton is a prerequisite for neurite sprouting and subsequent neurite outgrowth. A multiple set of growth factors and interactors located in the extracellular matrix and the plasma membrane orchestrate neuritogenesis by acting on intracellular signaling effectors, notably small G proteins such as RhoA, Rac, and Cdc42, which are involved in actin turnover and the dynamics of FAs. The cellular prion protein (PrPC, a glycosylphosphatidylinositol (GPI-anchored membrane protein mainly known for its role in a group of fatal neurodegenerative diseases, has emerged as a central player in neuritogenesis. Here, we review the contribution of PrPC to neuronal polarization and detail the current knowledge on the signaling pathways fine-tuned by PrPC to promote neurite sprouting, outgrowth, and maintenance. We emphasize that Pr

  13. LEFTY2 Controls Migration of Human Endometrial Cancer Cells via Focal Adhesion Kinase Activity (FAK) and miRNA-200a.

    Science.gov (United States)

    Alowayed, Nour; Salker, Madhuri S; Zeng, Ni; Singh, Yogesh; Lang, Florian

    2016-01-01

    LEFTY2, a suppressor of cell proliferation, tumor growth, regulator of stemness and embryonic differentiation, is a negative regulator of cancer cell reprogramming. Malignant transformation may lead to migration requiring loss of adhesion and gain of migratory activity. Signaling involved in the orchestration of migration, proliferation and spreading of cells include focal adhesion kinase (FAK) and adhesion molecule E-cadherin. The present study explored whether LEFTY2 influences the proliferation marker MKi67, FAK activity, E-cadherin abundance and migration of Ishikawa human endometrial carcinoma cells. Moreover, the study explored the involvement of microRNA-200a (miR-200a), which is known to regulate cellular adhesion by targeting E-Cadherin. FAK activity was estimated from FAK phosphorylation quantified by Western blotting, migration utilizing a wound healing assay, miR-200a and MKi67 expression levels utilizing qRT-PCR, cell proliferation and apoptosis using BrdU and Annexin V staining, respectively, and E-Cadherin (E-Cad) abundance, using confocal microscopy. LEFTY2 (25 ng/ml, 48 hours) treatment was followed by decrease of MKi67 expression, FAK activity and migration. LEFTY2 upregulated miRNA-200a and E-Cad protein level in Ishikawa cells. The effect of LEFTY2 on migration was mimicked by FAK inhibitor PF 573228 (50 µM). Addition of LEFTY2 in the presence of PF-573228 did not result in a further significant decline of migration. In conclusion, LEFTY2 down-regulates MKi67 expression and FAK activity, up-regulates miR-200a and E-cadherin, and is thus a powerful negative regulator of endometrial cell proliferation and migration. © 2016 The Author(s) Published by S. Karger AG, Basel.

  14. Osthole Suppresses the Migratory Ability of Human Glioblastoma Multiforme Cells via Inhibition of Focal Adhesion Kinase-Mediated Matrix Metalloproteinase-13 Expression

    Directory of Open Access Journals (Sweden)

    Cheng-Fang Tsai

    2014-03-01

    Full Text Available Glioblastoma multiforme (GBM is the most common type of primary and malignant tumor occurring in the adult central nervous system. GBM often invades surrounding regions of the brain during its early stages, making successful treatment difficult. Osthole, an active constituent isolated from the dried C. monnieri fruit, has been shown to suppress tumor migration and invasion. However, the effects of osthole in human GBM are largely unknown. Focal adhesion kinase (FAK is important for the metastasis of cancer cells. Results from this study show that osthole can not only induce cell death but also inhibit phosphorylation of FAK in human GBM cells. Results from this study show that incubating GBM cells with osthole reduces matrix metalloproteinase (MMP-13 expression and cell motility, as assessed by cell transwell and wound healing assays. This study also provides evidence supporting the potential of osthole in reducing FAK activation, MMP-13 expression, and cell motility in human GBM cells.

  15. Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases.

    Science.gov (United States)

    Schlaepfer, D D; Hunter, T

    1996-10-01

    Focal adhesion kinase (FAK) is a nonreceptor protein-tyrosine kinase (PTK) that associates with integrin receptors and participates in extracellular matrix-mediated signal transduction events. We showed previously that the c-Src nonreceptor PTK and the Grb2 SH2/SH3 adaptor protein bound directly to FAK after fibronectin stimulation (D. D. Schlaepfer, S.K. Hanks, T. Hunter, and P. van der Geer, Nature [London] 372:786-791, 1994). Here, we present evidence that c-Src association with FAK is required for Grb2 binding to FAK. Using a tryptic phosphopeptide mapping approach, the in vivo phosphorylation of the Grb2 binding site on FAK (Tyr-925) was detected after fibronectin stimulation of NIH 3T3 cells and was constitutively phosphorylated in v-Src-transformed NIH 3T3 cells. In vitro, c-Src phosphorylated FAK Tyr-925 in a glutathione S-transferase-FAK C-terminal domain fusion protein, whereas FAK did not. Using epitope-tagged FAK constructs, transiently expressed in human 293 cells, we determined the effect of site-directed mutations on c-Src and Grb2 binding to FAK. Mutation of FAK Tyr-925 disrupted Grb2 binding, whereas mutation of the c-Src binding site on FAK (Tyr-397) disrupted both c-Src and Grb2 binding to FAK in vivo. These results support a model whereby Src-family PTKs are recruited to FAK and focal adhesions following integrin-induced autophosphorylation and exposure of FAK Tyr-397. Src-family binding and phosphorylation of FAK at Tyr-925 creates a Grb2 SH2-domain binding site and provides a link to the activation of the Ras signal transduction pathway. In Src-transformed cells, this pathway may be constitutively activated as a result of FAK Tyr-925 phosphorylation in the absence of integrin stimulation.

  16. Focal uptake at the rotator interval or inferior capsule of shoulder on "1"8F-FDG PET/CT is associated with adhesive capsulitis

    International Nuclear Information System (INIS)

    Sridharan, Radhika; Engle, Mitchell Philip; Garg, Naveen; Wei, Wei; Amini, Behrang

    2017-01-01

    To determine if focal increased uptake at the rotator interval (RI) and/or inferior capsule (IC) on"1"8F-FDG PET/CT (''positive PET'') predicts the presence of adhesive capsulitis (AC). Three populations were retrospectively examined. Group 1 included 1,137 consecutive "1"8F-FDG PET/CT studies and was used to determine the prevalence of focal uptake at the RI or IC. Group 2 included 361 cases from a 10-year period with "1"8F-FDG PET/CT and MRI of shoulder performed within 45 days of each other and was used to enrich the study group. Group 3 included 109 randomly selected patients from the same time frame as groups 1 and 2 and was used to generate the control group. The study group consisted of 15 cases from the three groups, which had positive PET findings. PET/CT images were assessed in consensus by two musculoskeletal radiologists. The reference standard for a diagnosis of AC was clinical and was made by review of the medical record by a pain medicine physician. The prevalence of focal activity at either the RI or IC (''positive PET'') was 0.53%. Nine patients had a clinical diagnosis of AC and 15 patients had a positive PET. The sensitivity and specificity of PET for detection of AC was 56% and 87%, respectively. PET/CT had a positive likelihood ratio for AC of 6.3 (95% CI: 2.8-14.6). Increased uptake at the RI or IC on PET/CT confers a moderate increase in the likelihood of AC. (orig.)

  17. Focal uptake at the rotator interval or inferior capsule of shoulder on {sup 18}F-FDG PET/CT is associated with adhesive capsulitis

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Radhika [Universiti Kebangsaan Malaysia Medical Centre, Department of Diagnostic Imaging, Kuala Lumpur (Malaysia); Engle, Mitchell Philip [The University of Texas M.D. Anderson Cancer Center, Department of Pain Medicine, Houston, TX (United States); Garg, Naveen [The University of Texas M.D. Anderson Cancer Center, Department of Diagnostic Imaging, Houston, TX (United States); Wei, Wei; Amini, Behrang [The University of Texas M.D. Anderson Cancer Center, Department of Biostatistics, Houston, TX (United States)

    2017-04-15

    To determine if focal increased uptake at the rotator interval (RI) and/or inferior capsule (IC) on{sup 18}F-FDG PET/CT (''positive PET'') predicts the presence of adhesive capsulitis (AC). Three populations were retrospectively examined. Group 1 included 1,137 consecutive {sup 18}F-FDG PET/CT studies and was used to determine the prevalence of focal uptake at the RI or IC. Group 2 included 361 cases from a 10-year period with {sup 18}F-FDG PET/CT and MRI of shoulder performed within 45 days of each other and was used to enrich the study group. Group 3 included 109 randomly selected patients from the same time frame as groups 1 and 2 and was used to generate the control group. The study group consisted of 15 cases from the three groups, which had positive PET findings. PET/CT images were assessed in consensus by two musculoskeletal radiologists. The reference standard for a diagnosis of AC was clinical and was made by review of the medical record by a pain medicine physician. The prevalence of focal activity at either the RI or IC (''positive PET'') was 0.53%. Nine patients had a clinical diagnosis of AC and 15 patients had a positive PET. The sensitivity and specificity of PET for detection of AC was 56% and 87%, respectively. PET/CT had a positive likelihood ratio for AC of 6.3 (95% CI: 2.8-14.6). Increased uptake at the RI or IC on PET/CT confers a moderate increase in the likelihood of AC. (orig.)

  18. Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis.

    Science.gov (United States)

    Miller, Thomas D; Chong, Trevor T-J; Aimola Davies, Anne M; Ng, Tammy W C; Johnson, Michael R; Irani, Sarosh R; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A; Rosenthal, Clive R

    2017-05-01

    Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P 3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  19. Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice

    Directory of Open Access Journals (Sweden)

    Nietfeld Wilfried

    2010-03-01

    Full Text Available Abstract Background The complement system is a crucial mediator of inflammation and cell lysis after cerebral ischemia. However, there is little information about the exact contribution of the membrane attack complex (MAC and its inhibitor-protein CD59. Methods Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO in young male and female CD59a knockout and wild-type mice. Two models of MCAO were applied: 60 min MCAO and 48 h reperfusion, as well as 30 min MCAO and 72 h reperfusion. CD59a knockout animals were compared to wild-type animals in terms of infarct size, edema, neurological deficit, and cell death. Results and Discussion CD59a-deficiency in male mice caused significantly increased infarct volumes and brain swelling when compared to wild-type mice at 72 h after 30 min-occlusion time, whereas no significant difference was observed after 1 h-MCAO. Moreover, CD59a-deficient mice had impaired neurological function when compared to wild-type mice after 30 min MCAO. Conclusion We conclude that CD59a protects against ischemic brain damage, but depending on the gender and the stroke model used.

  20. The focal adhesion-associated proteins DOCK5 and GIT2 comprise a rheostat in control of epithelial invasion

    DEFF Research Database (Denmark)

    Frank, Scott R; Köllmann, C P; van Lidth de Jeude, J F

    2017-01-01

    DOCK proteins are guanine nucleotide exchange factors for Rac and Cdc42 GTPases. DOCK1 is the founding member of the family and acts downstream of integrins via the canonical Crk-p130Cas complex to activate Rac GTPases in numerous contexts. In contrast, DOCK5, which possesses the greatest similar......:10.1038/onc.2016.345....

  1. Low intensity shear stress increases endothelial ELR+ CXC chemokine production via a focal adhesion kinase-p38{beta} MAPK-NF-{kappa}B pathway.

    Science.gov (United States)

    Shaik, Sadiq S; Soltau, Thomas D; Chaturvedi, Gaurav; Totapally, Balagangadhar; Hagood, James S; Andrews, William W; Athar, Mohammad; Voitenok, Nikolai N; Killingsworth, Cheryl R; Patel, Rakesh P; Fallon, Michael B; Maheshwari, Akhil

    2009-02-27

    CXC chemokines with a glutamate-leucine-arginine (ELR) tripeptide motif (ELR(+) CXC chemokines) play an important role in leukocyte trafficking into the tissues. For reasons that are not well elucidated, circulating leukocytes are recruited into the tissues mainly in small vessels such as capillaries and venules. Because ELR(+) CXC chemokines are important mediators of endothelial-leukocyte interaction, we compared chemokine expression by microvascular and aortic endothelium to investigate whether differences in chemokine expression by various endothelial types could, at least partially, explain the microvascular localization of endothelial-leukocyte interaction. Both in vitro and in vivo models indicate that ELR(+) CXC chemokine expression is higher in microvascular endothelium than in aortic endothelial cells. These differences can be explained on the basis of the preferential activation of endothelial chemokine production by low intensity shear stress. Low shear activated endothelial ELR(+) CXC chemokine production via cell surface heparan sulfates, beta(3)-integrins, focal adhesion kinase, the mitogen-activated protein kinase p38beta, mitogen- and stress-associated protein kinase-1, and the transcription factor.

  2. START-GAP3/DLC3 is a GAP for RhoA and Cdc42 and is localized in focal adhesions regulating cell morphology

    International Nuclear Information System (INIS)

    Kawai, Katsuhisa; Kiyota, Minoru; Seike, Junichi; Deki, Yuko; Yagisawa, Hitoshi

    2007-01-01

    In the human genome there are three genes encoding RhoGAPs that contain the START (steroidogenic acute regulatory protein (StAR)-related lipid transfer)-domain. START-GAP3/DLC3 is a tumor suppressor gene similar to two other human START-GAPs known as DLC1 or DLC2. Although expression of START-GAP3/DLC3 inhibits the proliferation of cancer cells, its molecular function is not well understood. In this study we carried out biochemical characterization of START-GAP3/DLC3, and explored the effects of its expression on cell morphology and intracellular localization. We found that START-GAP3/DLC3 serves as a stimulator of PLCδ1 and as a GAP for both RhoA and Cdc42 in vitro. Moreover, we found that the GAP activity is responsible for morphological changes. The intracellular localization of endogenous START-GAP3/DLC3 was explored by immunocytochemistry and was revealed in focal adhesions. These results indicate that START-GAP3/DLC3 has characteristics similar to other START-GAPs and the START-GAP family seems to share common characteristics

  3. Mycosporine-Like Amino Acids Promote Wound Healing through Focal Adhesion Kinase (FAK and Mitogen-Activated Protein Kinases (MAP Kinases Signaling Pathway in Keratinocytes

    Directory of Open Access Journals (Sweden)

    Yun-Hee Choi

    2015-11-01

    Full Text Available Mycosporine-like amino acids (MAAs are secondary metabolites found in diverse marine, freshwater, and terrestrial organisms. Evidence suggests that MAAs have several beneficial effects on skin homeostasis such as protection against UV radiation and reactive oxygen species (ROS. In addition, MAAs are also involved in the modulation of skin fibroblasts proliferation. However, the regulatory function of MAAs on wound repair in human skin is not yet clearly elucidated. To investigate the roles of MAAs on the wound healing process in human keratinocytes, three MAAs, Shinorine (SH, Mycosporine-glycine (M-Gly, and Porphyra (P334 were purified from Chlamydomonas hedlyei and Porphyra yezoensis. We found that SH, M-Gly, and P334 have significant effects on the wound healing process in human keratinocytes and these effects were mediated by activation of focal adhesion kinases (FAK, extracellular signal-regulated kinases (ERK, and c-Jun N-terminal kinases (JNK. These results suggest that MAAs accelerate wound repair by activating the FAK-MAPK signaling pathways. This study also indicates that MAAs can act as a new wound healing agent and further suggests that MAAs might be a novel biomaterial for wound healing therapies.

  4. Mycosporine-Like Amino Acids Promote Wound Healing through Focal Adhesion Kinase (FAK) and Mitogen-Activated Protein Kinases (MAP Kinases) Signaling Pathway in Keratinocytes

    Science.gov (United States)

    Choi, Yun-Hee; Yang, Dong Joo; Kulkarni, Atul; Moh, Sang Hyun; Kim, Ki Woo

    2015-01-01

    Mycosporine-like amino acids (MAAs) are secondary metabolites found in diverse marine, freshwater, and terrestrial organisms. Evidence suggests that MAAs have several beneficial effects on skin homeostasis such as protection against UV radiation and reactive oxygen species (ROS). In addition, MAAs are also involved in the modulation of skin fibroblasts proliferation. However, the regulatory function of MAAs on wound repair in human skin is not yet clearly elucidated. To investigate the roles of MAAs on the wound healing process in human keratinocytes, three MAAs, Shinorine (SH), Mycosporine-glycine (M-Gly), and Porphyra (P334) were purified from Chlamydomonas hedlyei and Porphyra yezoensis. We found that SH, M-Gly, and P334 have significant effects on the wound healing process in human keratinocytes and these effects were mediated by activation of focal adhesion kinases (FAK), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinases (JNK). These results suggest that MAAs accelerate wound repair by activating the FAK-MAPK signaling pathways. This study also indicates that MAAs can act as a new wound healing agent and further suggests that MAAs might be a novel biomaterial for wound healing therapies. PMID:26703626

  5. 3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226

    International Nuclear Information System (INIS)

    Hehlgans, Stephanie; Lange, Inga; Eke, Iris; Cordes, Nils

    2009-01-01

    Background and purpose: Focal adhesion kinase (FAK), a main player in integrin signaling and survival, is frequently overexpressed in human cancers and therefore postulated as potential target in cancer therapy. The aim of this study was to evaluate the radiosensitizing potential of the FAK inhibitor TAE226 in three-dimensional (3D) tumor cell cultures. Materials and methods: Head and neck squamous cell carcinoma (HNSCC) cells (FaDu, UT-SCC15, UT-SCC45), lung cancer cells (A549), colorectal carcinoma cells (DLD-1, HCT-116) and pancreatic tumor cells (MiaPaCa2, Panc1) were treated with different concentrations of TAE226 (0-1 μm; 1 or 24 h) without or in combination with irradiation (0-6 Gy, X-ray, single dose). Subsequently, 3D clonogenic survival assays (laminin-rich extracellular matrix) and Western blotting (expression/phosphorylation, e.g. FAK, Akt, ERK1/2) were performed. Results: All investigated 3D cell cultures showed a dose-dependent reduction in clonogenic survival by TAE226. Intriguingly, TAE226 only significantly radiosensitized 3D HNSCC cell cultures accompanied by a pronounced dephosphorylation of FAK, Akt and ERK1/2. Conclusions: Our data demonstrate TAE226 as potent FAK inhibitor that enhances the cellular radiosensitivity particularly of HNSCC cells grown in a 3D cell culture model. Future in vitro and in vivo investigations will clarify, to which extent this approach might be clinically relevant for radiotherapy of HNSCC.

  6. Ultrastable cellulosome-adhesion complex tightens under load.

    Science.gov (United States)

    Schoeler, Constantin; Malinowska, Klara H; Bernardi, Rafael C; Milles, Lukas F; Jobst, Markus A; Durner, Ellis; Ott, Wolfgang; Fried, Daniel B; Bayer, Edward A; Schulten, Klaus; Gaub, Hermann E; Nash, Michael A

    2014-12-08

    Challenging environments have guided nature in the development of ultrastable protein complexes. Specialized bacteria produce discrete multi-component protein networks called cellulosomes to effectively digest lignocellulosic biomass. While network assembly is enabled by protein interactions with commonplace affinities, we show that certain cellulosomal ligand-receptor interactions exhibit extreme resistance to applied force. Here, we characterize the ligand-receptor complex responsible for substrate anchoring in the Ruminococcus flavefaciens cellulosome using single-molecule force spectroscopy and steered molecular dynamics simulations. The complex withstands forces of 600-750 pN, making it one of the strongest bimolecular interactions reported, equivalent to half the mechanical strength of a covalent bond. Our findings demonstrate force activation and inter-domain stabilization of the complex, and suggest that certain network components serve as mechanical effectors for maintaining network integrity. This detailed understanding of cellulosomal network components may help in the development of biocatalysts for production of fuels and chemicals from renewable plant-derived biomass.

  7. A protocadherin-cadherin-FLRT3 complex controls cell adhesion and morphogenesis.

    Directory of Open Access Journals (Sweden)

    Xuejun Chen

    2009-12-01

    Full Text Available Paraxial protocadherin (PAPC and fibronectin leucine-rich domain transmembrane protein-3 (FLRT3 are induced by TGFbeta signaling in Xenopus embryos and both regulate morphogenesis by inhibiting C-cadherin mediated cell adhesion.We have investigated the functional and physical relationships between PAPC, FLRT3, and C-cadherin. Although neither PAPC nor FLRT3 are required for each other to regulate C-cadherin adhesion, they do interact functionally and physically, and they form a complex with cadherins. By itself PAPC reduces cell adhesion physiologically to induce cell sorting, while FLRT3 disrupts adhesion excessively to cause cell dissociation. However, when expressed together PAPC limits the cell dissociating and tissue disrupting activity of FLRT3 to make it effective in physiological cell sorting. PAPC counteracts FLRT3 function by inhibiting the recruitment of the GTPase RND1 to the FLRT3 cytoplasmic domain.PAPC and FLRT3 form a functional complex with cadherins and PAPC functions as a molecular "governor" to maintain FLRT3 activity at the optimal level for physiological regulation of C-cadherin adhesion, cell sorting, and morphogenesis.

  8. Cell surface clustering of Cadherin adhesion complex induced by antibody coated beads

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Cadherin receptors mediate cell-cell adhesion, signal transduction and assembly of cytoskeletons. How a single transmembrane molecule Cadherin can be involved in multiple functions through modulating its binding activities with many membrane adhesion molecules and cytoskeletal components is an unanswered question which can be elucidated by clues from bead experiments. Human lung cells expressing N-Cadherin were examined. After co-incubation with anti-N-Cadherin monoclonal antibody coated beads, cell surface clustering of N-Cadherin was induced. Immunofluorescent detection demonstrated that in addition to Cadherin, β-Catenin, α-Catenin, α-Actinin and Actin fluorescence also aggregated respectively at the membrane site of bead attachment. Myosin heavy chain (MHC), another major component of Actin cytoskeleton, did not aggregate at the membrane site of bead attachment. Adhesion unrelated protein Con A and polylysine conjugated beads did not induce the clustering of adhesion molecules. It is indicated that the Cadherin/Catenins/α-Actinin/Actin complex is formed at Cadherin mediated cell adherens junction; occupancy and cell surface clustering of Cadherin is crucial for the formation of Cadherin adhesion protein complexes.

  9. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy

    Science.gov (United States)

    Marshall, Jamie L.; Kwok, Yukwah; McMorran, Brian; Baum, Linda G.; Crosbie-Watson, Rachelle H.

    2013-01-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important therapeutic target. Here, we review current protein replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. PMID:23601082

  10. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy.

    Science.gov (United States)

    Marshall, Jamie L; Kwok, Yukwah; McMorran, Brian J; Baum, Linda G; Crosbie-Watson, Rachelle H

    2013-09-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. © 2013 FEBS.

  11. Mechanical stimuli on C2C12 myoblasts affect myoblast differentiation, focal adhesion kinase phosphorylation and galectin-1 expression

    DEFF Research Database (Denmark)

    Grossi, Alberto Blak; Lametsch, Rene; Karlsson, Anders H

    2011-01-01

    Mechanical forces are crucial in the regulation of cell morphology and function. At the cellular level, these forces influence myoblast differentiation and fusion. In this study we applied mechanical stimuli to embryonic muscle cells using magnetic microbeads, a method shown to apply stress...... by mechanical stimulation including Galectin-1, Annexin III, and RhoGDI. In this study we demonstrate how the combination of this method of mechanical stimuli and proteomic analysis can be a powerful tool to detect proteins that are potentially interacting in biochemical pathways or complex cellular mechanisms...... during the process of myoblast differentiation. We determined an increase in expression and changes in cellular localization of Galectin-1, in mechanically stimulated myoblasts. A potential involvement of Galectin-1 in myoblast differentiation is presented....

  12. Role of focal adhesion tyrosine kinases in GPVI-dependent platelet activation and reactive oxygen species formation.

    Directory of Open Access Journals (Sweden)

    Naadiya Carrim

    Full Text Available We have previously shown the presence of a TRAF4/p47phox/Hic5/Pyk2 complex associated with the platelet collagen receptor, GPVI, consistent with a potential role of this complex in GPVI-dependent ROS formation. In other cell systems, NOX-dependent ROS formation is facilitated by Pyk2, which along with its closely related homologue FAK are known to be activated and phosphorylated downstream of ligand binding to GPVI.To evaluate the relative roles of Pyk2 and FAK in GPVI-dependent ROS formation and to determine their location within the GPVI signaling pathway.Human and mouse washed platelets (from WT or Pyk2 KO mice were pre-treated with pharmacological inhibitors targeting FAK or Pyk2 (PF-228 and Tyrphostin A9, respectively and stimulated with the GPVI-specific agonist, CRP. FAK, but not Pyk2, was found to be essential for GPVI-dependent ROS production and aggregation. Subsequent human platelet studies with PF-228 confirmed FAK is essential for GPVI-mediated phosphatidylserine exposure, α-granule secretion (P-selectin (CD62P surface expression and integrin αIIbβ3 activation. To determine the precise location of FAK within the GPVI pathway, we analyzed the effect of PF-228 inhibition in CRP-stimulated platelets in conjunction with immunoprecipitation and pulldown analysis to show that FAK is downstream of Lyn, Spleen tyrosine kinase (Syk, PI3-K and Bruton's tyrosine kinase (Btk and upstream of Rac1, PLCγ2, Ca2+ release, PKC, Hic-5, NOX1 and αIIbβ3 activation.Overall, these data suggest a novel role for FAK in GPVI-dependent ROS formation and platelet activation and elucidate a proximal signaling role for FAK within the GPVI pathway.

  13. Matriptase is required for the active form of hepatocyte growth factor induced Met, focal adhesion kinase and protein kinase B activation on neural stem/progenitor cell motility.

    Science.gov (United States)

    Fang, Jung-Da; Lee, Sheau-Ling

    2014-07-01

    Hepatocyte growth factor (HGF) is a chemoattractant and inducer for neural stem/progenitor (NS/P) cell migration. Although the type II transmembrane serine protease, matriptase (MTP) is an activator of the latent HGF, MTP is indispensable on NS/P cell motility induced by the active form of HGF. This suggests that MTP's action on NS/P cell motility involves mechanisms other than proteolytic activation of HGF. In the present study, we investigate the role of MTP in HGF-stimulated signaling events. Using specific inhibitors of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) or focal adhesion kinase (FAK), we demonstrated that in NS/P cells HGF-activated c-Met induces PI3k-Akt signaling which then leads to FAK activation. This signaling pathway ultimately induces MMP2 expression and NS/P cell motility. Knocking down of MTP in NS/P cells with specific siRNA impaired HGF-stimulation of c-Met, Akt and FAK activation, blocked HGF-induced production of MMP2 and inhibited HGF-stimulated NS/P cell motility. MTP-knockdown NS/P cells cultured in the presence of recombinant protein of MTP protease domain or transfected with the full-length wild-type but not the protease-defected MTP restored HGF-responsive events in NS/P cells. In addition to functioning as HGF activator, our data revealed novel function of MTP on HGF-stimulated c-Met signaling activation. Copyright © 2014. Published by Elsevier B.V.

  14. Focal adhesion kinase-mediated activation of glycogen synthase kinase 3β regulates IL-33 receptor internalization and IL-33 signaling.

    Science.gov (United States)

    Zhao, Jing; Wei, Jianxin; Bowser, Rachel K; Traister, Russell S; Fan, Ming-Hui; Zhao, Yutong

    2015-01-15

    IL-33, a relatively new member of the IL-1 cytokine family, plays a crucial role in allergic inflammation and acute lung injury. Long form ST2 (ST2L), the receptor for IL-33, is expressed on immune effector cells and lung epithelia and plays a critical role in triggering inflammation. We have previously shown that ST2L stability is regulated by the ubiquitin-proteasome system; however, its upstream internalization has not been studied. In this study, we demonstrate that glycogen synthase kinase 3β (GSK3β) regulates ST2L internalization and IL-33 signaling. IL-33 treatment induced ST2L internalization, and an effect was attenuated by inhibition or downregulation of GSK3β. GSK3β was found to interact with ST2L on serine residue 446 in response to IL-33 treatment. GSK3β binding site mutant (ST2L(S446A)) and phosphorylation site mutant (ST2L(S442A)) are resistant to IL-33-induced ST2L internalization. We also found that IL-33 activated focal adhesion kinase (FAK). Inhibition of FAK impaired IL-33-induced GSK3β activation and ST2L internalization. Furthermore, inhibition of ST2L internalization enhanced IL-33-induced cytokine release in lung epithelial cells. These results suggest that modulation of the ST2L internalization by FAK/GSK3β might serve as a unique strategy to lessen pulmonary inflammation. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. Focal Adhesion Kinase Inhibitors in Combination with Erlotinib Demonstrate Enhanced Anti-Tumor Activity in Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Grant A Howe

    Full Text Available Blockade of epidermal growth factor receptor (EGFR activity has been a primary therapeutic target for non-small cell lung cancers (NSCLC. As patients with wild-type EGFR have demonstrated only modest benefit from EGFR tyrosine kinase inhibitors (TKIs, there is a need for additional therapeutic approaches in patients with wild-type EGFR. As a key component of downstream integrin signalling and known receptor cross-talk with EGFR, we hypothesized that targeting focal adhesion kinase (FAK activity, which has also been shown to correlate with aggressive stage in NSCLC, would lead to enhanced activity of EGFR TKIs. As such, EGFR TKI-resistant NSCLC cells (A549, H1299, H1975 were treated with the EGFR TKI erlotinib and FAK inhibitors (PF-573,228 or PF-562,271 both as single agents and in combination. We determined cell viability, apoptosis and 3-dimensional growth in vitro and assessed tumor growth in vivo. Treatment of EGFR TKI-resistant NSCLC cells with FAK inhibitor alone effectively inhibited cell viability in all cell lines tested; however, its use in combination with the EGFR TKI erlotinib was more effective at reducing cell viability than either treatment alone when tested in both 2- and 3-dimensional assays in vitro, with enhanced benefit seen in A549 cells. This increased efficacy may be due in part to the observed inhibition of Akt phosphorylation when the drugs were used in combination, where again A549 cells demonstrated the most inhibition following treatment with the drug combination. Combining erlotinib with FAK inhibitor was also potent in vivo as evidenced by reduced tumor growth in the A549 mouse xenograft model. We further ascertained that the enhanced sensitivity was irrespective of the LKB1 mutational status. In summary, we demonstrate the effectiveness of combining erlotinib and FAK inhibitors for use in known EGFR wild-type, EGFR TKI resistant cells, with the potential that a subset of cell types, which includes A549, could be

  16. Adhesive F-actin Waves: A Novel Integrin-Mediated Adhesion Complex Coupled to Ventral Actin Polymerization

    OpenAIRE

    Case, Lindsay B.; Waterman, Clare M.

    2011-01-01

    At the leading lamellipodium of migrating cells, protrusion of an Arp2/3-nucleated actin network is coupled to formation of integrin-based adhesions, suggesting that Arp2/3-mediated actin polymerization and integrin-dependent adhesion may be mechanistically linked. Arp2/3 also mediates actin polymerization in structures distinct from the lamellipodium, in "ventral F-actin waves" that propagate as spots and wavefronts along the ventral plasma membrane. Here we show that integrins engage the ex...

  17. Protein adhesives

    Science.gov (United States)

    Charles R. Frihart; Linda F. Lorenz

    2018-01-01

    Nature uses a wide variety of chemicals for providing adhesion internally (e.g., cell to cell) and externally (e.g., mussels to ships and piers). This adhesive bonding is chemically and mechanically complex, involving a variety of proteins, carbohydrates, and other compounds.Consequently,the effect of protein structures on adhesive properties is only partially...

  18. Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

    OpenAIRE

    Miller, T; Chong, T; Aimola Davies, A; Ng, T; Johnson, M; Irani, S; Vincent, A; Husain, M; Jacob, S; Maddison, P; Kennard, C; Gowland, P; Rosenthal, C

    2017-01-01

    Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0....

  19. Cell adhesion controlled by adhesion G protein-coupled receptor GPR124/ADGRA2 is mediated by a protein complex comprising intersectins and Elmo-Dock.

    Science.gov (United States)

    Hernández-Vásquez, Magda Nohemí; Adame-García, Sendi Rafael; Hamoud, Noumeira; Chidiac, Rony; Reyes-Cruz, Guadalupe; Gratton, Jean Philippe; Côté, Jean-François; Vázquez-Prado, José

    2017-07-21

    Developmental angiogenesis and the maintenance of the blood-brain barrier involve endothelial cell adhesion, which is linked to cytoskeletal dynamics. GPR124 (also known as TEM5/ADGRA2) is an adhesion G protein-coupled receptor family member that plays a pivotal role in brain angiogenesis and in ensuring a tight blood-brain barrier. However, the signaling properties of GPR124 remain poorly defined. Here, we show that ectopic expression of GPR124 promotes cell adhesion, additive to extracellular matrix-dependent effect, coupled with filopodia and lamellipodia formation and an enrichment of a pool of the G protein-coupled receptor at actin-rich cellular protrusions containing VASP, a filopodial marker. Accordingly, GPR124-expressing cells also displayed increased activation of both Rac and Cdc42 GTPases. Mechanistically, we uncover novel direct interactions between endogenous GPR124 and the Rho guanine nucleotide exchange factors Elmo/Dock and intersectin (ITSN). Small fragments of either Elmo or ITSN1 that bind GPR124 blocked GPR124-induced cell adhesion. In addition, Gβγ interacts with the C-terminal tail of GPR124 and promotes the formation of a GPR124-Elmo complex. Furthermore, GPR124 also promotes the activation of the Elmo-Dock complex, as measured by Elmo phosphorylation on a conserved C-terminal tyrosine residue. Interestingly, Elmo and ITSN1 also interact with each other independently of their GPR124-recognition regions. Moreover, endogenous phospho-Elmo and ITSN1 co-localize with GPR124 at lamellipodia of adhering endothelial cells, where GPR124 expression contributes to polarity acquisition during wound healing. Collectively, our results indicate that GPR124 promotes cell adhesion via Elmo-Dock and ITSN. This constitutes a previously unrecognized complex formed of atypical and conventional Rho guanine nucleotide exchange factors for Rac and Cdc42 that is putatively involved in GPR124-dependent angiogenic responses. © 2017 by The American Society for

  20. Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Groothuis, D.R.; Mikhael, M.A.

    1986-06-01

    In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system.

  1. Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

    International Nuclear Information System (INIS)

    Groothuis, D.R.; Mikhael, M.A.

    1986-01-01

    In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system

  2. 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...

  3. Forced-rupture of cell-adhesion complexes reveals abrupt switch between two brittle states

    Science.gov (United States)

    Toan, Ngo Minh; Thirumalai, D.

    2018-03-01

    Cell adhesion complexes (CACs), which are activated by ligand binding, play key roles in many cellular functions ranging from cell cycle regulation to mediation of cell extracellular matrix adhesion. Inspired by single molecule pulling experiments using atomic force spectroscopy on leukocyte function-associated antigen-1 (LFA-1), expressed in T-cells, bound to intercellular adhesion molecules (ICAM), we performed constant loading rate (rf) and constant force (F) simulations using the self-organized polymer model to describe the mechanism of ligand rupture from CACs. The simulations reproduce the major experimental finding on the kinetics of the rupture process, namely, the dependence of the most probable rupture forces (f*s) on ln rf (rf is the loading rate) exhibits two distinct linear regimes. The first, at low rf, has a shallow slope, whereas the slope at high rf is much larger, especially for a LFA-1/ICAM-1 complex with the transition between the two occurring over a narrow rf range. Locations of the two transition states (TSs) extracted from the simulations show an abrupt change from a high value at low rf or constant force, F, to a low value at high rf or F. This unusual behavior in which the CACs switch from one brittle (TS position is a constant over a range of forces) state to another brittle state is not found in forced-rupture in other protein complexes. We explain this novel behavior by constructing the free energy profiles, F(Λ)s, as a function of a collective reaction coordinate (Λ), involving many key charged residues and a critical metal ion (Mg2+). The TS positions in F(Λ), which quantitatively agree with the parameters extracted using the Bell-Evans model, change abruptly at a critical force, demonstrating that it, rather than the molecular extension, is a good reaction coordinate. Our combined analyses using simulations performed in both the pulling modes (constant rf and F) reveal a new mechanism for the two loading regimes observed in the

  4. Interleukin-2 induces beta2-integrin-dependent signal transduction involving the focal adhesion kinase-related protein B (fakB)

    DEFF Research Database (Denmark)

    Brockdorff, J; Kanner, S B; Nielsen, M

    1998-01-01

    beta2 integrin molecules are involved in a multitude of cellular events, including adhesion, migration, and cellular activation. Here, we studied the influence of beta2 integrins on interleukin-2 (IL-2)-mediated signal transduction in human CD4(+) T cell lines obtained from healthy donors...

  5. RACK1 Targets the Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathway To Link Integrin Engagement with Focal Adhesion Disassembly and Cell Motility

    Czech Academy of Sciences Publication Activity Database

    Vomastek, Tomáš; Iwanicki, M. P.; Schaeffer, J.; J.; Tarcsafalvi, A.; Parsons, J. T.; Weber, M. J.

    2007-01-01

    Roč. 27, č. 23 (2007), s. 8296-8305 ISSN 0270-7306 R&D Projects: GA AV ČR IAA500200716 Institutional research plan: CEZ:AV0Z50200510 Keywords : protein kinase * adhesion * cell Subject RIV: EE - Microbiology, Virology Impact factor: 6.420, year: 2007

  6. Focal myositis

    International Nuclear Information System (INIS)

    Kransdorf, M.J.; Temple, H.T.; Sweet, D.E.

    1998-01-01

    Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep soft tissue of the extremities, and is a relatively rare lesion. There is a wide clinical spectrum, with approximately one-third of patients with focal myositis subsequently developing polymyositis, and clinical symptoms of generalized weakness, fever, myalgia, and weight loss, with elevation of creatine phosphokinase. We report the case of a patient with focal myositis who subsequently developed myositis ossificans-like features. (orig.)

  7. Focal myositis

    International Nuclear Information System (INIS)

    Galloway, H.R.; Dahlstrom, J.E.; Bennett, G.M.

    2001-01-01

    Focal myositis is a rare, benign focal inflammation of muscle. The lesion often presents as a mass that may be mistaken for a soft tissue sarcoma. This report describes the MRI and histopathological features of a case and illustrates how the diagnosis may be suspected on the basis of the MR findings. Copyright (2001) Blackwell Science Pty Ltd

  8. Human-derived physiological heat shock protein 27 complex protects brain after focal cerebral ischemia in mice.

    Directory of Open Access Journals (Sweden)

    Shinichiro Teramoto

    Full Text Available Although challenging, neuroprotective therapies for ischemic stroke remain an interesting strategy for countering ischemic injury and suppressing brain tissue damage. Among potential neuroprotective molecules, heat shock protein 27 (HSP27 is a strong cell death suppressor. To assess the neuroprotective effects of HSP27 in a mouse model of transient middle cerebral artery occlusion, we purified a "physiological" HSP27 (hHSP27 from normal human lymphocytes. hHSP27 differed from recombinant HSP27 in that it formed dimeric, tetrameric, and multimeric complexes, was phosphorylated, and contained small amounts of αβ-crystallin and HSP20. Mice received intravenous injections of hHSP27 following focal cerebral ischemia. Infarct volume, neurological deficit scores, physiological parameters, and immunohistochemical analyses were evaluated 24 h after reperfusion. Intravenous injections of hHSP27 1 h after reperfusion significantly reduced infarct size and improved neurological deficits. Injected hHSP27 was localized in neurons on the ischemic side of the brain. hHSP27 suppressed neuronal cell death resulting from cytochrome c-mediated caspase activation, oxidative stress, and inflammatory responses. Recombinant HSP27 (rHSP27, which was artificially expressed and purified from Escherichia coli, and dephosphorylated hHSP27 did not have brain protective effects, suggesting that the phosphorylation of hHSP27 may be important for neuroprotection after ischemic insults. The present study suggests that hHSP27 with posttranslational modifications provided neuroprotection against ischemia/reperfusion injury and that the protection was mediated through the inhibition of apoptosis, oxidative stress, and inflammation. Intravenously injected human HSP27 should be explored for the treatment of acute ischemic strokes.

  9. Pathogenesis of Focal Segmental Glomerulosclerosis

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    Beom Jin Lim

    2016-11-01

    Full Text Available Focal segmental glomerulosclerosis (FSGS is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice.

  10. 25 Years of Tension over Actin Binding to the Cadherin Cell Adhesion Complex: The Devil is in the Details.

    Science.gov (United States)

    Nelson, W James; Weis, William I

    2016-07-01

    Over the past 25 years, there has been a conceptual (re)evolution in understanding how the cadherin cell adhesion complex, which contains F-actin-binding proteins, binds to the actin cytoskeleton. There is now good synergy between structural, biochemical, and cell biological results that the cadherin-catenin complex binds to F-actin under force. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Implications for complex cognition from the hafting of tools with compound adhesives in the Middle Stone Age, South Africa

    Science.gov (United States)

    Wadley, Lyn; Hodgskiss, Tamaryn; Grant, Michael

    2009-01-01

    Compound adhesives made from red ochre mixed with plant gum were used in the Middle Stone Age (MSA), South Africa. Replications reported here suggest that early artisans did not merely color their glues red; they deliberately effected physical transformations involving chemical changes from acidic to less acidic pH, dehydration of the adhesive near wood fires, and changes to mechanical workability and electrostatic forces. Some of the steps required for making compound adhesive seem impossible without multitasking and abstract thought. This ability suggests overlap between the cognitive abilities of modern people and people in the MSA. Our multidisciplinary analysis provides a new way to recognize complex cognition in the MSA without necessarily invoking the concept of symbolism. PMID:19433786

  12. Focal myositis

    Energy Technology Data Exchange (ETDEWEB)

    Kransdorf, M.J. [Saint Mary`s Hospital, Richmond, VA (United States). Dept. of Radiol.]|[Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Temple, H.T. [Department of Orthopedic Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia (United States)]|[Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Sweet, D.E. [Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States)

    1998-05-01

    Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep soft tissue of the extremities, and is a relatively rare lesion. There is a wide clinical spectrum, with approximately one-third of patients with focal myositis subsequently developing polymyositis, and clinical symptoms of generalized weakness, fever, myalgia, and weight loss, with elevation of creatine phosphokinase. We report the case of a patient with focal myositis who subsequently developed myositis ossificans-like features. (orig.) With 3 figs., 25 refs.

  13. The direct effect of Focal Adhesion Kinase (FAK, dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis

    Directory of Open Access Journals (Sweden)

    Zhang Li

    2009-08-01

    Full Text Available Abstract Background Focal adhesion kinase (FAK is a non-receptor tyrosine kinase that plays an important role in survival signaling. FAK has been shown to be overexpressed in breast cancer tumors at early stages of tumorigenesis. Methods To study the direct effect of FAK on breast tumorigenesis, we developed Tet-ON (tetracycline-inducible system of MCF-7 breast cancer cells stably transfected with FAK or dominant-negative, C-terminal domain of FAK (FAK-CD, and also FAKsiRNA with silenced FAK MCF-7 stable cell line. Increased expression of FAK in isogenic Tet-inducible MCF-7 cells caused increased cell growth, adhesion and soft agar colony formation in vitro, while expression of dominant-negative FAK inhibitor caused inhibition of these cellular processes. To study the role of induced FAK and FAK-CD in vivo, we inoculated these Tet-inducible cells in nude mice to generate tumors in the presence or absence of doxycycline in the drinking water. FAKsiRNA-MCF-7 cells were also injected into nude mice to generate xenograft tumors. Results Induction of FAK resulted in significant increased tumorigenesis, while induced FAK-CD resulted in decreased tumorigenesis. Taq Man Low Density Array assay demonstrated specific induction of FAKmRNA in MCF-7-Tet-ON-FAK cells. DMP1, encoding cyclin D binding myb-like protein 1 was one of the genes specifically affected by Tet-inducible FAK or FAK-CD in breast xenograft tumors. In addition, silencing of FAK in MCF-7 cells with FAK siRNA caused increased cell rounding, decreased cell viability in vitro and inhibited tumorigenesis in vivo. Importantly, Affymetrix microarray gene profiling analysis using Human Genome U133A GeneChips revealed >4300 genes, known to be involved in apoptosis, cell cycle, and adhesion that were significantly down- or up-regulated (p Conclusion Thus, these data for the first time demonstrate the direct effect of FAK expression and function on MCF-7 breast cancer tumorigenesis in vivo and reveal

  14. The influence of cyclic shear fatigue on the bracket-adhesive-enamel complex: an in vitro study.

    Science.gov (United States)

    Daratsianos, Nikolaos; Musabegovic, Ena; Reimann, Susanne; Grüner, Manfred; Jäger, Andreas; Bourauel, Christoph

    2013-05-01

    To describe the effect of fatigue on the strength of the bracket-adhesive-enamel complex and characterize the fatigue behavior of the materials tested. Upper central incisor brackets (Discovery(®), Dentaurum) were bonded with a light-curing (Transbond XT™, 3M Unitek) and a chemically-curing adhesive (Concise™, 3M Unitek) on bovine teeth embedded in cylindrical resign bases and stored in water at 37(±2)°C for 24 (±2)h. The first 15 specimens were tested with a universal testing machine ZMART.PRO(®) (Zwick GmbH & Co. KG, Ulm, Germany) for ultimate shear bond strength according to the DIN-13990-2-standard. The remaining three groups of 20 specimens underwent fatigue staircase testing of 100, 1000 and 3000 cycles at 1Hz with a self-made testing machine. The survived specimens were subjected to shear strength testing. The fatigued specimens showed decreased shear strength with both adhesives at all cycle levels. The shear strength after fatigue for 100, 1000 and 3000 cycles was in the Concise™-groups 34.8%, 59.0%, 47.3% and in the Transbond™ XT-groups 33.6%, 23.1%, 27.3% relative to the ultimate shear strength. The fatigue life of the Concise™-groups decreased with increasing stress and Transbond™ XT showed lower fatigue ratio with no obvious trend. The specimens bonded with Transbond™ XT showed typically favorable fracture modes in contrary to Concise™. Fatigue of the bracket-adhesive-enamel complex decreased its shear strength. The staircase method can provide a standardized experimental protocol for fatigue studies, however testing at various cycle numbers is recommended. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  15. TGF-beta1 modulates focal adhesion kinase expression in rat intestinal epithelial IEC-6 cells via stimulatory and inhibitory Smad binding elements.

    Science.gov (United States)

    Walsh, Mary F; Ampasala, Dinakar R; Rishi, Arun K; Basson, Marc D

    2009-02-01

    TGF-beta and FAK modulate cell migration, differentiation, proliferation and apoptosis, and TGF-beta promotes FAK transcription in intestinal epithelial cells via Smad-dependent and independent pathways. We utilized a 1320 bp FAK promoter-luciferase construct to characterize basal and TGF-beta-mediated FAK gene transcription in IEC-6 cells. Inhibiting JNK or Akt negated TGF-beta-stimulated promoter activity; ERK inhibition did not block the TGF-beta effect but increased basal activity. Co-transfection with Co-Smad4 enhanced the TGF-beta response while the inhibitory Smad7 abolished it. Serial deletions sequentially removing the four Smad binding elements (SBE) in the 5' untranslated region of the promoter revealed that the two most distal SBE's are positive regulators while SBE3 exerts a negative influence. Mutational deletion of two upstream p53 sites enhanced basal but did not affect TGF-beta-stimulated increases in promoter activity. TGF-beta increased DNA binding of Smad4, phospho-Smad2/3 and Runx1/AML1a to the most distal 435 bp containing 3 SBE and 2 AML1a sites by ChIP assay. However, although point mutation of SBE1 ablated the TGF-beta-mediated rise in SV40-promoter activity, mutation of AML1a sites did not. TGF-beta regulation of FAK transcription reflects a complex interplay between positive and negative non-Smad signals and SBE's, the last independent of p53 or AML1a.

  16. A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors.

    Science.gov (United States)

    Shimizu, Toshio; Fukuoka, Kazuya; Takeda, Masayuki; Iwasa, Tutomu; Yoshida, Takeshi; Horobin, Joanna; Keegan, Mitchell; Vaickus, Lou; Chavan, Ajit; Padval, Mahesh; Nakagawa, Kazuhiko

    2016-05-01

    VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2. This phase 1 study evaluated the safety and tolerability, pharmacokinetics, and clinical activity of VS-6063 in Japanese subjects with advanced solid tumor malignancies in a first-in-Asian study setting. VS-6063 was administered orally twice daily (b.i.d.) in 21-day cycles to cohorts of three subjects each with a standard 3 + 3 dose-escalation design until disease progression or unacceptable toxicity. Blood samples for pharmacokinetics were collected on Day 1 and 15. The assessments were performed using CTCAE v4.0 for adverse events (AEs), and the Response Evaluation Criteria In Solid Tumors, version v1.1 (RECIST v1.1) for tumor response. Nine patients were treated across three dose levels (200-600 mg BID). No dose-limiting toxicities were observed at any dose level. Most frequent treatment-related AEs were Grade 1/2 unconjugated hyperbilirubinemia, fatigue, decreased appetite, and diarrhea. Only one subject in the 200 mg BID cohort experienced reversible and transient Grade 3 unconjugated hyperbilirubinemia. PK analyses confirmed that the exposure at the recommended Phase 2 dose (RP2D) of 400 mg BID was comparable with exposures previously reported in non-Japanese subjects. Durable stable disease of approximately 24 weeks was confirmed in two subjects (malignant mesothelioma and rectal cancer). VS-6063 was well tolerated at all dose levels investigated in this first-in-Asian study. These data support the administration of VS-6063 to Japanese subjects at the RP2D in clinical trials involving solid tumor malignancies.

  17. Inhibition of tumor vasculogenic mimicry and prolongation of host survival in highly aggressive gallbladder cancers by norcantharidin via blocking the ephrin type a receptor 2/focal adhesion kinase/paxillin signaling pathway.

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available Vasculogenic mimicry (VM is a newly-defined tumor microcirculation pattern in highly aggressive malignant tumors. We recently reported tumor growth and VM formation of gallbladder cancers through the contribution of the ephrin type a receptor 2 (EphA2/focal adhesion kinase (FAK/Paxillin signaling pathways. In this study, we further investigated the anti-VM activity of norcantharidin (NCTD as a VM inhibitor for gallbladder cancers and the underlying mechanisms. In vivo and in vitro experiments to determine the effects of NCTD on tumor growth, host survival, VM formation of GBC-SD nude mouse xenografts, and vasculogenic-like networks, malignant phenotypes i.e., proliferation, apoptosis, invasion and migration of GBC-SD cells. Expression of VM signaling-related markers EphA2, FAK and Paxillin in vivo and in vitro were examined by immunofluorescence, western blotting and real-time polymerase chain reaction (RT-PCR, respectively. The results showed that after treatment with NCTD, GBC-SD cells were unable to form VM structures when injecting into nude mouse, growth of the xenograft was inhibited and these observations were confirmed by facts that VM formation by three-dimensional (3-D matrix, proliferation, apoptosis, invasion, migration of GBC-SD cells were affected; and survival time of the xenograft mice was prolonged. Furthermore, expression of EphA2, FAK and Paxillin proteins/mRNAs of the xenografts was downregulated. Thus, we concluded that NCTD has potential anti-VM activity against human gallbladder cancers; one of the underlying mechanisms may be via blocking the EphA2/FAK/Paxillin signaling pathway.

  18. A new treatment for focal dystonias: incobotulinumtoxinA (Xeomin®, a botulinum neurotoxin type A free from complexing proteins

    Directory of Open Access Journals (Sweden)

    Jimenez-Shahed J

    2011-12-01

    Full Text Available Joohi Jimenez-ShahedDepartment of Neurology, Baylor College of Medicine, Houston, TX, USAAbstract: Dystonia is a movement disorder of uncertain pathogenesis that is characterized by involuntary and inappropriate muscle contractions which cause sustained abnormal postures and movements of multiple or single (focal body regions. The most common focal dystonias are cervical dystonia (CD and blepharospasm (BSP. The first-line recommended treatment for CD and BSP is injection with botulinum toxin (BoNT, of which two serotypes are available: BoNT type A (BoNT/A and BoNT type B (BoNT/B. Conventional BoNT formulations include inactive complexing proteins, which may increase the risk for antigenicity, possibly leading to treatment failure. IncobotulinumtoxinA (Xeomin®; Merz Pharmaceuticals GmbH, Frankfurt, Germany is a BoNT/A agent that has been recently Food and Drug Administration-approved for the treatment of adults with CD and adults with BSP previously treated with onabotulinumtoxinA (Botox®; Allergen, Inc, Irvine, CA – a conventional BoNT/A. IncobotulinumtoxinA is the only BoNT product that is free of complexing proteins. The necessity of complexing proteins for the effectiveness of botulinum toxin treatment has been challenged by preclinical and clinical studies with incobotulinumtoxinA. These studies have also suggested that incobotulinumtoxinA is associated with a lower risk for stimulating antibody formation than onabotulinumtoxinA. In phase 3 noninferiority trials, incobotulinumtoxinA demonstrated significant improvements in CD and BSP symptoms in both primary and secondary measures, compared with baseline, and met criteria for noninferiority versus onabotulinumtoxinA. In placebo-controlled trials, incobotulinumtoxinA also significantly improved the symptoms of CD and BSP, with robust outcomes in both primary and secondary measures. The use of incobotulinumtoxinA has been well tolerated in all trials, with an adverse event profile similar

  19. Wood : adhesives

    Science.gov (United States)

    A.H. Conner

    2001-01-01

    This chapter on wood adhesives includes: 1) Classification of wood adhesives 2) Thermosetting wood adhesives 3) Thermoplastic adhesives, 4) Wood adhesives based on natural sources 5) Nonconventional bonding of wood 6) Wood bonding.

  20. Microbial Adhesion and Biofilm Formation on Microfiltration Membranes: A Detailed Characterization Using Model Organisms with Increasing Complexity

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    L. Vanysacker

    2013-01-01

    Full Text Available Since many years, membrane biofouling has been described as the Achilles heel of membrane fouling. In the present study, an ecological assay was performed using model systems with increasing complexity: a monospecies assay using Pseudomonas aeruginosa or Escherichia coli separately, a duospecies assay using both microorganisms, and a multispecies assay using activated sludge with or without spiked P. aeruginosa. The microbial adhesion and biofilm formation were evaluated in terms of bacterial cell densities, species richness, and bacterial community composition on polyvinyldifluoride, polyethylene, and polysulfone membranes. The data show that biofouling formation was strongly influenced by the kind of microorganism, the interactions between the organisms, and the changes in environmental conditions whereas the membrane effect was less important. The findings obtained in this study suggest that more knowledge in species composition and microbial interactions is needed in order to understand the complex biofouling process. This is the first report describing the microbial interactions with a membrane during the biofouling development.

  1. Microbial Adhesion and Biofilm Formation on Microfiltration Membranes: A Detailed Characterization Using Model Organisms with Increasing Complexity

    Science.gov (United States)

    Vanysacker, L.; Denis, C.; Declerck, P.; Piasecka, A.; Vankelecom, I. F. J.

    2013-01-01

    Since many years, membrane biofouling has been described as the Achilles heel of membrane fouling. In the present study, an ecological assay was performed using model systems with increasing complexity: a monospecies assay using Pseudomonas aeruginosa or Escherichia coli separately, a duospecies assay using both microorganisms, and a multispecies assay using activated sludge with or without spiked P. aeruginosa. The microbial adhesion and biofilm formation were evaluated in terms of bacterial cell densities, species richness, and bacterial community composition on polyvinyldifluoride, polyethylene, and polysulfone membranes. The data show that biofouling formation was strongly influenced by the kind of microorganism, the interactions between the organisms, and the changes in environmental conditions whereas the membrane effect was less important. The findings obtained in this study suggest that more knowledge in species composition and microbial interactions is needed in order to understand the complex biofouling process. This is the first report describing the microbial interactions with a membrane during the biofouling development. PMID:23986906

  2. Smooth muscle cell rigidity and extracellular matrix organization influence endothelial cell spreading and adhesion formation in coculture.

    Science.gov (United States)

    Wallace, Charles S; Strike, Sophie A; Truskey, George A

    2007-09-01

    Efforts to develop functional tissue-engineered blood vessels have focused on improving the strength and mechanical properties of the vessel wall, while the functional status of the endothelium within these vessels has received less attention. Endothelial cell (EC) function is influenced by interactions between its basal surface and the underlying extracellular matrix. In this study, we utilized a coculture model of a tissue-engineered blood vessel to evaluate EC attachment, spreading, and adhesion formation to the extracellular matrix on the surface of quiescent smooth muscle cells (SMCs). ECs attached to and spread on SMCs primarily through the alpha(5)beta(1)-integrin complex, whereas ECs used either alpha(5)beta(1)- or alpha(v)beta(3)-integrin to spread on fibronectin (FN) adsorbed to plastic. ECs in coculture lacked focal adhesions, but EC alpha(5)beta(1)-integrin bound to fibrillar FN on the SMC surface, promoting rapid fibrillar adhesion formation. As assessed by both Western blot analysis and quantitative real-time RT-PCR, coculture suppressed the expression of focal adhesion proteins and mRNA, whereas tensin protein and mRNA expression were elevated. When attached to polyacrylamide gels with similar elastic moduli as SMCs, focal adhesion formation and the rate of cell spreading increased relative to ECs in coculture. Thus, the elastic properties are only one factor contributing to EC spreading and focal adhesion formation in coculture. The results suggest that the softness of the SMCs and the fibrillar organization of FN inhibit focal adhesions and reduce cell spreading while promoting fibrillar adhesion formation. These changes in the type of adhesions may alter EC signaling pathways in tissue-engineered blood vessels.

  3. Reduction of mitochondrial electron transport complex activity is restricted to the ischemic focus after transient focal cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Christensen, Thomas; Diemer, Nils Henrik

    2003-01-01

    Using histochemical methods offering high topographical resolution for evaluation of changes in the ischemic focus and the penumbra, the mitochondrial electron transport chain (ETC) complexes I, II, and IV were examined in rats subjected to 2 h of proximal occlusion of the middle cerebral artery...

  4. Inhibition on Apoptosis Induced by Elevated Hydrostatic Pressure in Retinal Ganglion Cell-5 via Laminin Upregulating β1-integrin/Focal Adhesion Kinase/Protein Kinase B Signaling Pathway.

    Science.gov (United States)

    Li, Yi; Chen, Yan-Ming; Sun, Ming-Ming; Guo, Xiao-Dan; Wang, Ya-Chen; Zhang, Zhong-Zhi

    2016-04-20

    Glaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells (RGCs). High intraocular pressure (HIOP), the main risk factor, causes the optic nerve damage. However, the precise mechanism of HIOP-induced RGC death is not yet completely understood. This study was conducted to determine apoptosis of RGC-5 cells induced by elevated hydrostatic pressures, explore whether laminin is associated with apoptosis under pressure, whether laminin can protect RGCs from apoptosis and affirm the mechanism that regulates the process of RGCs survival. RGC-5 cells were exposed to 0, 20, 40, and 60 mmHg in a pressurized incubator for 6, 12, and 24 h, respectively. The effect of elevated hydrostatic pressure on RGC-5 cells was measured by Annexin V-fluorescein isothiocyanate/propidium iodide staining, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Western blotting of cleaved caspase-3 protein. Location and expression of laminin were detected by immunofluorescence. The expression of β1-integrin, phosphorylation of focal adhesion kinase (FAK) and protein kinase B (PKB, or AKT) were investigated with real-time polymerase chain reaction and Western blotting analysis. Elevated hydrostatic pressure induced apoptosis in cultured RGC-5 cells. Pressure with 40 mmHg for 24 h induced a maximum apoptosis. Laminin was declined in RGC-5 cells after exposing to 40 mmHg for 24 h. After pretreating with laminin, RGC-5 cells survived from elevated pressure. Furthermore, β1-integrin and phosphorylation of FAK and AKT were increased compared to 40 mmHg group. The data show apoptosis tendency of RGC-5 cells with elevated hydrostatic pressure. Laminin can protect RGC-5 cells against high pressure via β1-integrin/FAK/AKT signaling pathway. These results suggest that the decreased laminin of RGC-5 cells might be responsible for apoptosis induced by elevated hydrostatic pressure, and laminin or activating β1-integrin

  5. Bacterial Adhesion & Blocking Bacterial Adhesion

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk

    2008-01-01

    , which influence the transition from a planktonic lifestyle to a sessile lifestyle, have been studied. Protein conditioning film formation was found to influence bacterial adhesion and subsequent biofilm formation considerable, and an aqueous extract of fish muscle tissue was shown to significantly...... tract to the microbial flocs in waste water treatment facilities. Microbial biofilms may however also cause a wide range of industrial and medical problems, and have been implicated in a wide range of persistent infectious diseases, including implantassociated microbial infections. Bacterial adhesion...... is the first committing step in biofilm formation, and has therefore been intensely scrutinized. Much however, still remains elusive. Bacterial adhesion is a highly complex process, which is influenced by a variety of factors. In this thesis, a range of physico-chemical, molecular and environmental parameters...

  6. Multiple cell adhesion molecules shaping a complex nicotinic synapse on neurons.

    Science.gov (United States)

    Triana-Baltzer, Gallen B; Liu, Zhaoping; Gounko, Natalia V; Berg, Darwin K

    2008-09-01

    Neuroligin, SynCAM, and L1-CAM are cell adhesion molecules with synaptogenic roles in glutamatergic pathways. We show here that SynCAM is expressed in the chick ciliary ganglion, embedded in a nicotinic pathway, and, as shown previously for neuroligin and L1-CAM, acts transcellularly to promote synaptic maturation on the neurons in culture. Moreover, we show that electroporation of chick embryos with dominant negative constructs disrupting any of the three molecules in vivo reduces the total amount of presynaptic SV2 overlaying the neurons expressing the constructs. Only disruption of L1-CAM and neuroligin, however, reduces the number of SV2 puncta specifically overlaying nicotinic receptor clusters. Disrupting L1-CAM and neuroligin together produces no additional decrement, indicating that they act on the same subset of synapses. SynCAM may affect synaptic maturation rather than synapse formation. The results indicate that individual neurons can express multiple synaptogenic molecules with different effects on the same class of nicotinic synapses.

  7. Magnaporthe oryzae Glycine-Rich Secretion Protein, Rbf1 Critically Participates in Pathogenicity through the Focal Formation of the Biotrophic Interfacial Complex.

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    Takeshi Nishimura

    2016-10-01

    Full Text Available Magnaporthe oryzae, the fungus causing rice blast disease, should contend with host innate immunity to develop invasive hyphae (IH within living host cells. However, molecular strategies to establish the biotrophic interactions are largely unknown. Here, we report the biological function of a M. oryzae-specific gene, Required-for-Focal-BIC-Formation 1 (RBF1. RBF1 expression was induced in appressoria and IH only when the fungus was inoculated to living plant tissues. Long-term successive imaging of live cell fluorescence revealed that the expression of RBF1 was upregulated each time the fungus crossed a host cell wall. Like other symplastic effector proteins of the rice blast fungus, Rbf1 accumulated in the biotrophic interfacial complex (BIC and was translocated into the rice cytoplasm. RBF1-knockout mutants (Δrbf1 were severely deficient in their virulence to rice leaves, but were capable of proliferating in abscisic acid-treated or salicylic acid-deficient rice plants. In rice leaves, Δrbf1 inoculation caused necrosis and induced defense-related gene expression, which led to a higher level of diterpenoid phytoalexin accumulation than the wild-type fungus did. Δrbf1 showed unusual differentiation of IH and dispersal of the normally BIC-focused effectors around the short primary hypha and the first bulbous cell. In the Δrbf1-invaded cells, symplastic effectors were still translocated into rice cells but with a lower efficiency. These data indicate that RBF1 is a virulence gene essential for the focal BIC formation, which is critical for the rice blast fungus to suppress host immune responses.

  8. Acute treatment with docosahexaenoic acid complexed to albumin reduces injury after a permanent focal cerebral ischemia in rats.

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    Tiffany N Eady

    Full Text Available Docosahexaenoic acid complexed to albumin (DHA-Alb is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo, but whether a similar effect occurs in permanent MCAo is unknown. Male Sprague-Dawley rats (270-330 g underwent permanent MCAo. Neurological function was evaluated on days 1, 2 and 3 after MCAo. We studied six groups: DHA (5 mg/kg, Alb (0.63 or 1.25 g/kg, DHA-Alb (5 mg/kg+0.63 g/kg or 5 mg/kg+1.25 g/kg or saline. Treatment was administered i.v. at 3 h after onset of stroke (n = 7-10 per group. Ex vivo imaging of brains and histopathology were conducted on day 3. Saline- and Alb-treated rats developed severe neurological deficits but were not significantly different from one another. In contrast, rats treated with low and moderate doses of DHA-Alb showed improved neurological score compared to corresponding Alb groups on days 2 and 3. Total, cortical and subcortical lesion volumes computed from T2 weighted images were reduced following a moderate dose of DHA-Alb (1.25 g/kg by 25%, 22%, 34%, respectively, compared to the Alb group. The total corrected, cortical and subcortical infarct volumes were reduced by low (by 36-40% and moderate doses (by 34-42% of DHA-Alb treatment compared to the Alb groups. In conclusion, DHA-Alb therapy is highly neuroprotective in permanent MCAo in rats. This treatment can provide the basis for future therapeutics for patients suffering from ischemic stroke.

  9. Conformational Plasticity in the Transsynaptic Neurexin-Cerebellin-Glutamate Receptor Adhesion Complex

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Shouqiang; Seven, Alpay B.; Wang, Jing; Skiniotis, Georgios; Özkan, Engin (UC); (Michigan)

    2016-12-01

    Synaptic specificity is a defining property of neural networks. In the cerebellum, synapses between parallel fiber neurons and Purkinje cells are specified by the simultaneous interactions of secreted protein cerebellin with pre-synaptic neurexin and post-synaptic delta-type glutamate receptors (GluD). Here, we determined the crystal structures of the trimeric C1q-like domain of rat cerebellin-1, and the first complete ectodomain of a GluD, rat GluD2. Cerebellin binds to the LNS6 domain of α- and β-neurexin-1 through a high-affinity interaction that involves its highly flexible N-terminal domain. In contrast, we show that the interaction of cerebellin with isolated GluD2 ectodomain is low affinity, which is not simply an outcome of lost avidity when compared with binding with a tetrameric full-length receptor. Rather, high-affinity capture of cerebellin by post-synaptic terminals is likely controlled by long-distance regulation within this transsynaptic complex. Altogether, our results suggest unusual conformational flexibility within all components of the complex.

  10. Cell division orientation is coupled to cell-cell adhesion by the E-cadherin/LGN complex

    NARCIS (Netherlands)

    Gloerich, Martijn; Bianchini, Julie M.; Siemers, Kathleen A.; Cohen, Daniel J.; Nelson, W. James

    2017-01-01

    Both cell-cell adhesion and oriented cell division play prominent roles in establishing tissue architecture, but it is unclear how they might be coordinated. Here, we demonstrate that the cell-cell adhesion protein E-cadherin functions as an instructive cue for cell division orientation. This is

  11. A novel method for rapid and reliable detection of complex vertebral malformation and bovine leukocyte adhesion deficiency in Holstein cattle

    Directory of Open Access Journals (Sweden)

    Zhang Yi

    2012-07-01

    Full Text Available Abstract Background Complex vertebral malformation (CVM and bovine leukocyte adhesion deficiency (BLAD are two autosomal recessive lethal genetic defects frequently occurring in Holstein cattle, identifiable by single nucleotide polymorphisms. The objective of this study is to develop a rapid and reliable genotyping assay to screen the active Holstein sires and determine the carrier frequency of CVM and BLAD in Chinese dairy cattle population. Results We developed real-time PCR-based assays for discrimination of wild-type and defective alleles, so that carriers can be detected. Only one step was required after the DNA extraction from the sample and time consumption was about 2 hours. A total of 587 Chinese Holstein bulls were assayed, and fifty-six CVM-carriers and eight BLAD-carriers were identified, corresponding to heterozygote carrier frequencies of 9.54% and 1.36%, respectively. The pedigree analysis showed that most of the carriers could be traced back to the common ancestry, Osborndale Ivanhoe for BLAD and Pennstate Ivanhoe Star for CVM. Conclusions These results demonstrate that real-time PCR is a simple, rapid and reliable assay for BLAD and CVM defective allele detection. The high frequency of the CVM allele suggests that implementing a routine testing system is necessary to gradually eradicate the deleterious gene from the Chinese Holstein population.

  12. Denture Adhesives

    Science.gov (United States)

    ... Devices Products and Medical Procedures Dental Devices Denture Adhesives Share Tweet Linkedin Pin it More sharing options ... Wearers Reporting Problems to the FDA Background Denture adhesives are pastes, powders or adhesive pads that may ...

  13. Dynamic Regulation of a Cell Adhesion Protein Complex Including CADM1 by Combinatorial Analysis of FRAP with Exponential Curve-Fitting

    Science.gov (United States)

    Sakurai-Yageta, Mika; Maruyama, Tomoko; Suzuki, Takashi; Ichikawa, Kazuhisa; Murakami, Yoshinori

    2015-01-01

    Protein components of cell adhesion machinery show continuous renewal even in the static state of epithelial cells and participate in the formation and maintenance of normal epithelial architecture and tumor suppression. CADM1 is a tumor suppressor belonging to the immunoglobulin superfamily of cell adhesion molecule and forms a cell adhesion complex with an actin-binding protein, 4.1B, and a scaffold protein, MPP3, in the cytoplasm. Here, we investigate dynamic regulation of the CADM1-4.1B-MPP3 complex in mature cell adhesion by fluorescence recovery after photobleaching (FRAP) analysis. Traditional FRAP analysis were performed for relatively short period of around 10min. Here, thanks to recent advances in the sensitive laser detector systems, we examine FRAP of CADM1 complex for longer period of 60 min and analyze the recovery with exponential curve-fitting to distinguish the fractions with different diffusion constants. This approach reveals that the fluorescence recovery of CADM1 is fitted to a single exponential function with a time constant (τ) of approximately 16 min, whereas 4.1B and MPP3 are fitted to a double exponential function with two τs of approximately 40-60 sec and 16 min. The longer τ is similar to that of CADM1, suggesting that 4.1B and MPP3 have two distinct fractions, one forming a complex with CADM1 and the other present as a free pool. Fluorescence loss in photobleaching analysis supports the presence of a free pool of these proteins near the plasma membrane. Furthermore, double exponential fitting makes it possible to estimate the ratio of 4.1B and MPP3 present as a free pool and as a complex with CADM1 as approximately 3:2 and 3:1, respectively. Our analyses reveal a central role of CADM1 in stabilizing the complex with 4.1B and MPP3 and provide insight in the dynamics of adhesion complex formation. PMID:25780926

  14. Breast cancer metastasis suppressor 1 (BRMS1) suppresses attachment and spreading of breast cancer cells on 2D and 3D extracellular matrix components by altering focal adhesion-associated signaling

    Science.gov (United States)

    Metastatic dissemination of cancer cells from primary tumor to secondary sites is a multi-step process that depends heavily on the ability of cancer cells to respond to the microenvironmental cues, such as changes in composition of surrounding extracellular matrix (ECM), by adapting their adhesion a...

  15. Upregulation of adhesion complex proteins and fibronectin by human keratinocytes treated with an aqueous extract from the leaves of Chromolaena odorata (Eupolin).

    Science.gov (United States)

    Phan, T T; Allen, J; Hughes, M A; Cherry, G; Wojnarowska, F

    2000-01-01

    The fresh leaves and extract of the plant Chromolaena odorata are a traditional herbal treatment in developing countries for burns, soft tissue wounds and skin infections. We have previously shown that the extract had an effect on the growth and proliferation of keratinocytes and fibroblasts in culture. This study has demonstrated that Eupolin extract increased expression of several components of the adhesion complex and fibronectin by human keratinocytes. Using indirect immunofluorescence we found increased expression (dose-dependent) of laminin 5, laminin 1, collagen IV, and fibronectin. The expression of the b1 and b4 integrins was upregulated by the extract at low concentrations (0.1 and 1 microg/ml), but the expression was decreased at higher doses of Eupolin (10 microg-150 microg/ml). A number of clinical studies carried out by Vietnamese and international medical investigators have demonstrated the efficacy of this extract on the wound healing process. In this study we have shown that Eupolin stimulated the expression of many proteins of the adhesion complex and fibronectin by human keratinocytes. The adhesion complex proteins are essential to stabilise epithelium and this effect could contribute to the clinical efficacy of Eupolin in healing.

  16. The non-receptor tyrosine kinase Lyn controls neutrophil adhesion by recruiting the CrkL–C3G complex and activating Rap1 at the leading edge

    Science.gov (United States)

    He, Yuan; Kapoor, Ashish; Cook, Sara; Liu, Shubai; Xiang, Yang; Rao, Christopher V.; Kenis, Paul J. A.; Wang, Fei

    2011-01-01

    Establishing new adhesions at the extended leading edges of motile cells is essential for stable polarity and persistent motility. Despite recent identification of signaling pathways that mediate polarity and chemotaxis in neutrophils, little is known about molecular mechanisms governing cell–extracellular-matrix (ECM) adhesion in these highly polarized and rapidly migrating cells. Here, we describe a signaling pathway in neutrophils that is essential for localized integrin activation, leading edge attachment and persistent migration during chemotaxis. This pathway depends upon Gi-protein-mediated activation and leading edge recruitment of Lyn, a non-receptor tyrosine kinase belonging to the Src kinase family. We identified the small GTPase Rap1 as a major downstream effector of Lyn to regulate neutrophil adhesion during chemotaxis. Depletion of Lyn in neutrophil-like HL-60 cells prevented chemoattractant-induced Rap1 activation at the leading edge of the cell, whereas ectopic expression of Rap1 largely rescued the defects induced by Lyn depletion. Furthermore, Lyn controls spatial activation of Rap1 by recruiting the CrkL–C3G protein complex to the leading edge. Together, these results provide novel mechanistic insights into the poorly understood signaling network that controls leading edge adhesion during chemotaxis of neutrophils, and possibly other amoeboid cells. PMID:21628423

  17. Syndecan-4 and integrins: combinatorial signaling in cell adhesion

    DEFF Research Database (Denmark)

    Couchman, J R; Woods, A

    1999-01-01

    It is now becoming clear that additional transmembrane components can modify integrin-mediated adhesion. Syndecan-4 is a transmembrane heparan sulfate proteoglycan whose external glycosaminoglycan chains can bind extracellular matrix ligands and whose core protein cytoplasmic domain can signal...... during adhesion. Two papers in this issue of JCS demonstrate, through transfection studies, that syndecan-4 plays roles in the formation of focal adhesions and stress fibers. Overexpression of syndecan-4 increases focal adhesion formation, whereas a partially truncated core protein that lacks the binding...... site for protein kinase C(&agr;) and phosphatidylinositol 4, 5-bisphosphate acts as a dominant negative inhibitor of focal adhesion formation. Focal adhesion induction does not require interaction between heparan sulfate glycosaminoglycan and ligand but can occur when non-glycanated core protein...

  18. Regulative mechanisms of chondrocyte adhesion

    DEFF Research Database (Denmark)

    Schmal, Hagen; Mehlhorn, Alexander T; Fehrenbach, Miriam

    2006-01-01

    Interaction between chondrocytes and extracellular matrix is considered a key factor in the generation of grafts for matrix-associated chondrocyte transplantation. Therefore, our objective was to study the influence of differentiation status on cellular attachment. Adhesion of chondrocytes...... to collagen type II increased after removal from native cartilage up to the third day in monolayer in a dose-dependent manner. Following dedifferentiation after the second passage, adhesion to collagen types I (-84%) and II (-46%) decreased, whereas adhesion to fibrinogen (+59%) and fibronectin (+43......%) increased. A cartilage construct was developed based on a clinically established collagen type I scaffold. In this matrix, more than 80% of the cells could be immobilized by mechanisms of adhesion, filtration, and cell entrapment. Confocal laser microscopy revealed focal adhesion sites as points of cell...

  19. Mesenchymal stem cell adhesion but not plasticity is affected by high substrate stiffness

    Directory of Open Access Journals (Sweden)

    Janice Kal Van Tam, Koichiro Uto, Mitsuhiro Ebara, Stefania Pagliari, Giancarlo Forte and Takao Aoyagi

    2012-01-01

    Full Text Available The acknowledged ability of synthetic materials to induce cell-specific responses regardless of biological supplies provides tissue engineers with the opportunity to find the appropriate materials and conditions to prepare tissue-targeted scaffolds. Stem and mature cells have been shown to acquire distinct morphologies in vitro and to modify their phenotype when grown on synthetic materials with tunable mechanical properties. The stiffness of the substrate used for cell culture is likely to provide cells with mechanical cues mimicking given physiological or pathological conditions, thus affecting the biological properties of cells. The sensitivity of cells to substrate composition and mechanical properties resides in multiprotein complexes called focal adhesions, whose dynamic modification leads to cytoskeleton remodeling and changes in gene expression. In this study, the remodeling of focal adhesions in human mesenchymal stem cells in response to substrate stiffness was followed in the first phases of cell–matrix interaction, using poly-ε-caprolactone planar films with similar chemical composition and different elasticity. As compared to mature dermal fibroblasts, mesenchymal stem cells showed a specific response to substrate stiffness, in terms of adhesion, as a result of differential focal adhesion assembly, while their multipotency as a bulk was not significantly affected by matrix compliance. Given the sensitivity of stem cells to matrix mechanics, the mechanobiology of such cells requires further investigations before preparing tissue-specific scaffolds.

  20. Switchable bio-inspired adhesives

    Science.gov (United States)

    Kroner, Elmar

    2015-03-01

    Geckos have astonishing climbing abilities. They can adhere to almost any surface and can run on walls and even stick to ceilings. The extraordinary adhesion performance is caused by a combination of a complex surface pattern on their toes and the biomechanics of its movement. These biological dry adhesives have been intensely investigated during recent years because of the unique combination of adhesive properties. They provide high adhesion, allow for easy detachment, can be removed residue-free, and have self-cleaning properties. Many aspects have been successfully mimicked, leading to artificial, bio-inspired, patterned dry adhesives, and were addressed and in some aspects they even outperform the adhesion capabilities of geckos. However, designing artificial patterned adhesion systems with switchable adhesion remains a big challenge; the gecko's adhesion system is based on a complex hierarchical surface structure and on advanced biomechanics, which are both difficult to mimic. In this paper, two approaches are presented to achieve switchable adhesion. The first approach is based on a patterned polydimethylsiloxane (PDMS) polymer, where adhesion can be switched on and off by applying a low and a high compressive preload. The switch in adhesion is caused by a reversible mechanical instability of the adhesive silicone structures. The second approach is based on a composite material consisting of a Nickel- Titanium (NiTi) shape memory alloy and a patterned adhesive PDMS layer. The NiTi alloy is trained to change its surface topography as a function of temperature, which results in a change of the contact area and of alignment of the adhesive pattern towards a substrate, leading to switchable adhesion. These examples show that the unique properties of bio-inspired adhesives can be greatly improved by new concepts such as mechanical instability or by the use of active materials which react to external stimuli.

  1. Focal dermal hypoplasia without focal dermal hypoplasia

    NARCIS (Netherlands)

    Contreras-Capetillo, Silvina N.; Lombardi, Maria Paola; Pinto-Escalante, Doris; Hennekam, Raoul C.

    2014-01-01

    Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome) is an X-linked dominant disorder affecting mainly tissues of ectodermal and mesodermal origin. The phenotype is characterized by hypoplastic linear skin lesions, eye malformations, hair and teeth anomalies, and multiple limbs malformations. The

  2. The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM–EGL-15/FGFR Receptor Complex

    Directory of Open Access Journals (Sweden)

    Carlos A. Díaz-Balzac

    2015-06-01

    Full Text Available Neurite branching is essential for correct assembly of neural circuits, yet it remains a poorly understood process. For example, the neural cell adhesion molecule KAL-1/anosmin-1, which is mutated in Kallmann syndrome, regulates neurite branching through mechanisms largely unknown. Here, we show that KAL-1/anosmin-1 mediates neurite branching as an autocrine co-factor with EGL-17/FGF through a receptor complex consisting of the conserved cell adhesion molecule SAX-7/L1CAM and the fibroblast growth factor receptor EGL-15/FGFR. This protein complex, which appears conserved in humans, requires the immunoglobulin (Ig domains of SAX-7/L1CAM and the FN(III domains of KAL-1/anosmin-1 for formation in vitro as well as function in vivo. The kinase domain of the EGL-15/FGFR is required for branching, and genetic evidence suggests that ras-mediated signaling downstream of EGL-15/FGFR is necessary to effect branching. Our studies establish a molecular pathway that regulates neurite branching during development of the nervous system.

  3. Cellular Adhesion and Adhesion Molecules

    OpenAIRE

    SELLER, Zerrin

    2014-01-01

    In recent years, cell adhesion and cell adhesion molecules have been shown to be important for many normal biological processes, including embryonic cell migration, immune system functions and wound healing. It has also been shown that they contribute to the pathogenesis of a large number of common human disorders, such as rheumatoid arthritis and tumor cell metastasis in cancer. In this review, the basic mechanisms of cellular adhesion and the structural and functional features of adhes...

  4. Adhesion science

    CERN Document Server

    Comyn, John

    1997-01-01

    The use of adhesives is widespread and growing, and there are few modern artefacts, from the simple cereal packet, to the jumbo jet, that are without this means of joining. Adhesion Science provides an illuminating account of the science underlying the use of adhesives, a branch of chemical technology which is fundamental to the science of coatings and composite materials and to the performance of all types of bonded structures. This book guides the reader through the essential basic polymer science, and the chemistry of adhesives in use at present. It discusses surface preparation for adhesive bonding, and the use of primers and coupling agents. There is a detailed chapter on contact angles and what can be predicted from them. A simple guide on stress distribution joints and how this relates to testing is included. It also examines the interaction of adhesives and the environment, including an analysis of the resistance of joints to water, oxygen and ultra-violet light. Adhesion Science provides a comprehens...

  5. Focal retinal phlebitis.

    Science.gov (United States)

    Hoang, Quan V; Freund, K Bailey; Klancnik, James M; Sorenson, John A; Cunningham, Emmett T; Yannuzzi, Lawrence A

    2012-01-01

    To report three cases of solitary, focal retinal phlebitis. An observational case series. Three eyes in three patients were noted to have unilateral decreased vision, macular edema, and a focal retinal phlebitis, which was not at an arteriovenous crossing. All three patients developed a branch retinal vein occlusion at the site of inflammation. These patients had no other evidence of intraocular inflammation, including vitritis, retinitis, retinal vasculitis, or choroiditis, nor was there any systemic disorder associated with inflammation, infection, or coagulation identified. Focal retinal phlebitis appears to be an uncommon and unique entity that produces macular edema and ultimately branch retinal vein occlusion. In our patients, the focal phlebitis and venous occlusion did not occur at an arteriovenous crossing, which is the typical site for branch retinal venous occlusive disease. This suggests that our cases represent a distinct clinical entity, which starts with a focal abnormality in the wall of a retinal venule, resulting in surrounding exudation and, ultimately, ends with branch retinal vein occlusion.

  6. The Molecular Architecture of Cell Adhesion: Dynamic Remodeling Revealed by Videonanoscopy

    Directory of Open Access Journals (Sweden)

    Arnauld eSergé

    2016-05-01

    Full Text Available The plasma membrane delimits the cell, which is the basic unit of living organisms, and is also a privileged site for cell communication with the environment. Cell adhesion can occur through cell-cell and cell-matrix contacts. Adhesion proteins such as integrins and cadherins also constitute receptors for inside-out and outside-in signaling within proteolipidic platforms. Adhesion molecule targeting and stabilization relies on specific features such as preferential segregation by the sub-membrane cytoskeleton meshwork and within membrane proteolipidic microdomains. This review presents an overview of the recent insights brought by the latest developments in microscopy, to unravel the molecular remodeling occurring at cell contacts. The dynamic aspect of cell adhesion was recently highlighted by super-resolution videomicroscopy, also named videonanoscopy. By circumventing the diffraction limit of light, nanoscopy has allowed the monitoring of molecular localization and behavior at the single-molecule level, on fixed and living cells. Accessing molecular-resolution details such as quantitatively monitoring components entering and leaving cell contacts by lateral diffusion and reversible association has revealed an unexpected plasticity. Adhesion structures can be highly specialized, such as focal adhesion in motile cells, as well as immune and neuronal synapses. Spatiotemporal reorganization of adhesion molecules, receptors and adaptors directly relates to structure/function modulation. Assembly of these supramolecular complexes is continuously balanced by dynamic events, remodeling adhesions on various timescales, notably by molecular conformation switches, lateral diffusion within the membrane and endo/exocytosis. Pathological alterations in cell adhesion are involved in cancer evolution, through cancer stem cell interaction with stromal niches, growth, extravasation and metastasis.

  7. The neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Berezin, V; Bock, E; Poulsen, F M

    2000-01-01

    During the past year, the understanding of the structure and function of neural cell adhesion has advanced considerably. The three-dimensional structures of several of the individual modules of the neural cell adhesion molecule (NCAM) have been determined, as well as the structure of the complex...... between two identical fragments of the NCAM. Also during the past year, a link between homophilic cell adhesion and several signal transduction pathways has been proposed, connecting the event of cell surface adhesion to cellular responses such as neurite outgrowth. Finally, the stimulation of neurite...

  8. Recurrent Bilateral Focal Myositis.

    Science.gov (United States)

    Nagafuchi, Hiroko; Nakano, Hiromasa; Ooka, Seido; Takakuwa, Yukiko; Yamada, Hidehiro; Tadokoro, Mamoru; Shimojo, Sadatomo; Ozaki, Shoichi

    This report describes a rare case of recurrent bilateral focal myositis and its successful treatment via methotrexate. A 38-year-old man presented myalgia of the right gastrocnemius in May 2005. Magnetic resonance imaging showed very high signal intensity in the right gastrocnemius on short-tau inversion recovery images. A muscle biopsy revealed inflammatory CD4+ cell-dominant myogenic change. Focal myositis was diagnosed. The first steroid treatment was effective. Tapering of prednisolone, however, repeatedly induced myositis relapse, which progressed to multiple muscle lesions of both lower limbs. Initiation of methotrexate finally allowed successful tapering of prednisolone, with no relapse in the past 4 years.

  9. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion...... in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent...

  10. Focal cortical dysplasia – review

    International Nuclear Information System (INIS)

    Kabat, Joanna; Król, Przemysław

    2012-01-01

    Focal cortical dysplasia is a malformation of cortical development, which is the most common cause of medically refractory epilepsy in the pediatric population and the second/third most common etiology of medically intractable seizures in adults. Both genetic and acquired factors are involved in the pathogenesis of cortical dysplasia. Numerous classifications of the complex structural abnormalities of focal cortical dysplasia have been proposed – from Taylor et al. in 1971 to the last modification of Palmini classification made by Blumcke in 2011. In general, three types of cortical dysplasia are recognized. Type I focal cortical dysplasia with mild symptomatic expression and late onset, is more often seen in adults, with changes present in the temporal lobe. Clinical symptoms are more severe in type II of cortical dysplasia usually seen in children. In this type, more extensive changes occur outside the temporal lobe with predilection for the frontal lobes. New type III is one of the above dysplasias with associated another principal lesion as hippocampal sclerosis, tumor, vascular malformation or acquired pathology during early life. Brain MRI imaging shows abnormalities in the majority of type II dysplasias and in only some of type I cortical dysplasias. The most common findings on MRI imaging include: focal cortical thickening or thinning, areas of focal brain atrophy, blurring of the gray-white junction, increased signal on T2- and FLAIR-weighted images in the gray and subcortical white matter often tapering toward the ventricle. On the basis of the MRI findings, it is possible to differentiate between type I and type II cortical dysplasia. A complete resection of the epileptogenic zone is required for seizure-free life. MRI imaging is very helpful to identify those patients who are likely to benefit from surgical treatment in a group of patients with drug-resistant epilepsy. However, in type I cortical dysplasia, MR imaging is often normal, and also in both

  11. Development of Latent Fingermarks on Nonporous and Semiporous Substrates Using Photoluminescent Eu(Phen)2 Complex Intercalated Clay Hybrids with Enhanced Adhesion.

    Science.gov (United States)

    Kim, Aran; Ryu, Seung-Jin; Lee, Jihye; Jung, Hyun

    2018-03-01

    In forensic science, developing latent fingermarks using powders is a critical, general method to identify individuals. Photoluminescent Eu(Phen) 2 complex intercalated clay hybrids have been used to improve the visualization of fingermarks on nonporous (glass and polymer film) and semiporous (euro and dollar banknotes) substrates. An ion exchange reaction has been successfully used to intercalate Eu(Phen) 2 complex ions into the interlayer spacing of two different Na + -clays, Na + -montmorillonite and Na + -hectorite, with different primary particle sizes. To change the surface properties of the obtained hybrid to be more lipophilic, the hydroxyl groups at the edge of the hectorite hybrid were modified with hexadecyltrimethoxysilane via silylation. We investigated the correlation of the size and surface properties of the hybrids with their adhesion to fingermark residues. Fingermarks were successfully visualized using hybrids under UV illumination. In particular, ridge details on semiporous substrates can be more clearly seen using hybrids with smaller primary particles and greater lipophilicity. © 2018 American Academy of Forensic Sciences.

  12. Hakai reduces cell-substratum adhesion and increases epithelial cell invasion

    International Nuclear Information System (INIS)

    Rodríguez-Rigueiro, Teresa; Valladares-Ayerbes, Manuel; Haz-Conde, Mar; Aparicio, Luis A; Figueroa, Angélica

    2011-01-01

    The dynamic regulation of cell-cell adhesions is crucial for developmental processes, including tissue formation, differentiation and motility. Adherens junctions are important components of the junctional complex between cells and are necessary for maintaining cell homeostasis and normal tissue architecture. E-cadherin is the prototype and best-characterized protein member of adherens junctions in mammalian epithelial cells. Regarded as a tumour suppressor, E-cadherin loss is associated with poor prognosis in carcinoma. The E3 ubiquitin-ligase Hakai was the first reported posttranslational regulator of the E-cadherin complex. Hakai specifically targetted E-cadherin for internalization and degradation and thereby lowered epithelial cell-cell contact. Hakai was also implicated in controlling proliferation, and promoted cancer-related gene expression by increasing the binding of RNA-binding protein PSF to RNAs encoding oncogenic proteins. We sought to investigate the possible implication of Hakai in cell-substratum adhesions and invasion in epithelial cells. Parental MDCK cells and MDCK cells stably overexpressing Hakai were used to analyse cell-substratum adhesion and invasion capabilities. Western blot and immunofluoresecence analyses were performed to assess the roles of Paxillin, FAK and Vinculin in cell-substratum adhesion. The role of the proteasome in controlling cell-substratum adhesion was studied using two proteasome inhibitors, lactacystin and MG132. To study the molecular mechanisms controlling Paxillin expression, MDCK cells expressing E-cadherin shRNA in a tetracycline-inducible manner was employed. Here, we present evidence that implicate Hakai in reducing cell-substratum adhesion and increasing epithelial cell invasion, two hallmark features of cancer progression and metastasis. Paxillin, an important protein component of the cell-matrix adhesion, was completely absent from focal adhesions and focal contacts in Hakai-overexpressing MDCK cells. The

  13. Adhesion molecules

    CERN Document Server

    Preedy, Victor R

    2016-01-01

    This book covers the structure and classification of adhesion molecules in relation to signaling pathways and gene expression. It discusses immunohistochemical localization, neutrophil migration, and junctional, functional, and inflammatory adhesion molecules in pathologies such as leukocyte decompression sickness and ischemia reperfusion injury. Highlighting the medical applications of current research, chapters cover diabetes, obesity, and metabolic syndrome; hypoxia; kidney disease; smoking, atrial fibrillation, and heart disease, the brain and dementia; and tumor proliferation. Finally, it looks at molecular imaging and bioinformatics, high-throughput technologies, and chemotherapy.

  14. Sarcospan integration into laminin-binding adhesion complexes that ameliorate muscular dystrophy requires utrophin and α7 integrin

    Science.gov (United States)

    Marshall, Jamie L.; Oh, Jennifer; Chou, Eric; Lee, Joy A.; Holmberg, Johan; Burkin, Dean J.; Crosbie-Watson, Rachelle H.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene that result in loss of the dystrophin–glycoprotein complex, a laminin receptor that connects the myofiber to its surrounding extracellular matrix. Utrophin, a dystrophin ortholog that is normally localized to the neuromuscular junction, is naturally upregulated in DMD muscle, which partially compensates for the loss of dystrophin. Transgenic overexpression of utrophin causes broad sarcolemma localization of utrophin, restoration of laminin binding and amelioration of disease in the mdx mouse model of DMD. We previously demonstrated that overexpression of sarcospan, a dystrophin- and utrophin-binding protein, ameliorates mdx muscular dystrophy. Sarcospan boosts levels of utrophin to therapeutic levels at the sarcolemma, where attachment to laminin is restored. However, understanding the compensatory mechanism is complicated by concomitant upregulation of α7β1 integrin, which also binds laminin. Similar to the effects of utrophin, transgenic overexpression of α7 integrin prevents DMD disease in mice and is accompanied by increased abundance of utrophin around the extra-synaptic sarcolemma. In order to investigate the mechanisms underlying sarcospan ‘rescue’ of muscular dystrophy, we created double-knockout mice to test the contributions of utrophin or α7 integrin. We show that sarcospan-mediated amelioration of muscular dystrophy in DMD mice is dependent on the presence of both utrophin and α7β1 integrin, even when they are individually expressed at therapeutic levels. Furthermore, we found that association of sarcospan into laminin-binding complexes is dependent on utrophin and α7β1 integrin. PMID:25504048

  15. Focal myositis: A review.

    Science.gov (United States)

    Devic, P; Gallay, L; Streichenberger, N; Petiot, P

    2016-11-01

    Amongst the heterogeneous group of inflammatory myopathies, focal myositis stands as a rare and benign dysimmune disease. Although it can be associated with root and/or nerve lesions, traumatic muscle lesions and autoimmune diseases, its triggering factors remain poorly understood. Defined as an isolated inflammatory pseudotumour usually restricted to one skeletal muscle, clinical presentation of focal myositis is that of a rapidly growing solitary mass within a single muscle, usually in the lower limbs. Electromyography shows spontaneous activity associated with a myopathic pattern. MRI reveals a contrast enhanced enlarged muscle appearing hyper-intense on FAT-SAT T2 weighted images. Adjacent structures are spared and there are no calcifications. Serum creatine kinase (CK) levels are usually moderately augmented and biological markers of systemic inflammation are absent in most cases. Pathological histological features include marked variation in fibre size, inflammatory infiltrates mostly composed of T CD4+ lymphocytes and macrophages, degenerating/regenerating fibres and interstitial fibrosis. Differential diagnoses are numerous and include myositis of other origin with focal onset. Steroid treatment should be reserved for patients who present with major pain, nerve lesions, associated autoimmune disease, or elevated C reactive protein or CK. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Mechanosensing through focal adhesion-anchored intermediate filaments

    Czech Academy of Sciences Publication Activity Database

    Gregor, Martin; Osmanagic-Myers, S.; Burgstaller, G.; Wolfram, M.; Fischer, I.; Walko, G.; Resch, G.P.; Jorgl, A.; Herrmann, H.; Wiche, G.

    2014-01-01

    Roč. 28, č. 2 (2014), s. 715-729 ISSN 0892-6638 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : vimentin * plectin * integrin * activation * cellmotility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.043, year: 2014

  17. CD54/intercellular adhesion molecule 1 and major histocompatibility complex II signaling induces B cells to express interleukin 2 receptors and complements help provided through CD40 ligation

    DEFF Research Database (Denmark)

    Poudrier, J; Owens, T

    1994-01-01

    We have examined signaling roles for CD54 intercellular adhesion molecule 1 and major histocompatibility complex (MHC) II as contact ligands during T help for B cell activation. We used a T helper 1 (Th1)-dependent helper system that was previously shown to be contact as well as interleukin 2 (IL-2......) dependent to demonstrate the relative roles of CD54, MHC II, and CD40 signaling in the events leading to the induction of B cell proliferation and responsiveness to IL-2. Paraformaldehyde-fixed activated Th1-induced expression of IL-2R alpha, IL-2R beta, and B7, and upregulated MHC II and CD54 on B cells...... resulted in the upregulated expression of MHC II and of CD54 and B7, respectively, analogous to the effect of fixed activated Th1 cells. B7 expression was further enhanced by co-cross-linking CD54 and MHC II. Cross-linking of CD40 achieved comparable effects. Strikingly, cross-linking ligation of CD54...

  18. Colloid, adhesive and release properties of nanoparticular ternary complexes between cationic and anionic polysaccharides and basic proteins like bone morphogenetic protein BMP-2.

    Science.gov (United States)

    Petzold, R; Vehlow, D; Urban, B; Grab, A L; Cavalcanti-Adam, E A; Alt, V; Müller, M

    2017-03-01

    Herein we describe an interfacial local drug delivery system for bone morphogenetic protein 2 (BMP-2) based on coatings of polyelectrolyte complex (PEC) nanoparticles (NP). The application horizon is the functionalization of bone substituting materials (BSM) used for the therapy of systemic bone diseases. Nanoparticular ternary complexes of cationic and anionic polysaccharides and BMP-2 or two further model proteins, respectively, were prepared in dependence of the molar mixing ratio, pH value and of the cationic polysaccharide. As further proteins chymotrypsin (CHY) and papain (PAP) were selected, which served as model proteins for BMP-2 due to similar isoelectric points and molecular weights. As charged polysaccharides ethylenediamine modified cellulose (EDAC) and trimethylammonium modified cellulose (PQ10) were combined with cellulose sulphatesulfate (CS). Mixing diluted cationic and anionic polysaccharide and protein solutions according to a slight either anionic or cationic excess charge colloidal ternary dispersions formed, which were cast onto germanium model substrates by water evaporation. Dynamic light scattering (DLS) demonstrated, that these dispersions were colloidally stable for at least one week. Fourier Transform Infrared (FTIR) showed, that the cast protein loaded PEC NP coatings were irreversibly adhesive at the model substrate in contact to HEPES buffer and solely CHY, PAP and BMP-2 were released within long-term time scale. Advantageously, out of the three proteins BMP-2 showed the smallest initial burst and the slowest release kinetics and around 25% of the initial BMP-2 content were released within 14days. Released BMP-2 showed significant activity in the myoblast cells indicating the ability to regulate the formation of new bone. Therefore, BMP-2 loaded PEC NP are suggested as novel promising tool for the functionalization of BSM used for the therapy of systemic bone diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Bio-inspired reversible underwater adhesive.

    Science.gov (United States)

    Zhao, Yanhua; Wu, Yang; Wang, Liang; Zhang, Manman; Chen, Xuan; Liu, Minjie; Fan, Jun; Liu, Junqiu; Zhou, Feng; Wang, Zuankai

    2017-12-20

    The design of smart surfaces with switchable adhesive properties in a wet environment has remained a challenge in adhesion science and materials engineering. Despite intense demands in various industrial applications and exciting progress in mimicking the remarkable wet adhesion through the delicate control of catechol chemistry, polyelectrolyte complex, and supramolecular architectures, the full recapitulation of nature's dynamic function is limited. Here, we show a facile approach to synthesize bioinspired adhesive, which entails the reversible, tunable, and fast regulation of the wet adhesion on diverse surfaces. The smart wet adhesive takes advantage of the host-guest molecular interaction and the adhesive nature of catechol chemistry, as well as the responsive polymer, allowing for screening and activation of the interfacial interaction simply by a local temperature trigger in an on-demand manner. Our work opens up an avenue for the rational design of bioinspired adhesives with performances even beyond nature.

  20. Conformational Dynamics of the Focal Adhesion Targeting Domain Control Specific Functions of Focal Adhesion Kinase in Cells

    KAUST Repository

    Kadaré , Gress; Gervasi, Nicolas; Brami-Cherrier, Karen; Blockus, Heike; El Messari, Said; Arold, Stefan T.; Girault, Jean-Antoine

    2015-01-01

    to bombesin was increased by FAT opening. Although FAK molecules with the mutation favoring FAT opening were poorly recruited at FAs, they efficiently restored FA turnover and cell shape in FAK-deficient cells. In contrast, the mutation preventing H1 opening

  1. CRF2 signaling is a novel regulator of cellular adhesion and migration in colorectal cancer cells.

    Science.gov (United States)

    Ducarouge, Benjamin; Pelissier-Rota, Marjolaine; Lainé, Michèle; Cristina, Nadine; Vachez, Yvan; Scoazec, Jean-Yves; Bonaz, Bruno; Jacquier-Sarlin, Muriel

    2013-01-01

    Stress has been proposed to be a tumor promoting factor through the secretion of specific neuromediators, such as Urocortin2 and 3 (Ucn2/3), however its role in colorectal cancer (CRC) remains elusive. We observed that Ucn2/3 and their receptor the Corticotropin Releasing Factor receptor 2 (CRF2) were up-regulated in high grade and poorly differentiated CRC. This suggests a role for CRF2 in the loss of cellular organization and tumor progression. Using HT-29 and SW620 cells, two CRC cell lines differing in their abilities to perform cell-cell contacts, we found that CRF2 signals through Src/ERK pathway to induce the alteration of cell-cell junctions and the shuttle of p120ctn and Kaiso in the nucleus. In HT-29 cells, this signaling pathway also leads to the remodeling of cell adhesion by i) the phosphorylation of Focal Adhesion Kinase and ii) a modification of actin cytoskeleton and focal adhesion complexes. These events stimulate cell migration and invasion. In conclusion, our findings indicate that CRF2 signaling controls cellular organization and may promote metastatic potential of human CRC cells through an epithelial-mesenchymal transition like process. This contributes to the comprehension of the tumor-promoting effects of stress molecules and designates Ucn2/3-CRF2 tandem as a target to prevent CRC progression and aggressiveness.

  2. Shear bond strength of porcelain laminate veneers to enamel, dentine and enamel-dentine complex bonded with different adhesive luting systems.

    Science.gov (United States)

    Öztürk, Elif; Bolay, Şükran; Hickel, Reinhard; Ilie, Nicoleta

    2013-02-01

    The aim of this study was to evaluate the shear bond strength of porcelain laminate veneers to 3 different surfaces by means of enamel, dentine, and enamel-dentine complex. One hundred thirty-five extracted human maxillary central teeth were used, and the teeth were randomly divided into 9 groups (n=15). The teeth were prepared with 3 different levels for bonding surfaces of enamel (E), dentine (D), and enamel-dentine complex (E-D). Porcelain discs (IPS e.max Press, Ivoclar Vivadent) of 2mm in thickness and 4mm in diameter were luted to the tooth surfaces by using 2 light-curing (RelyX Veneer [RV], 3M ESPE; Variolink Veneer [VV], Ivoclar Vivadent) and a dual-curing (Variolink II [V2], Ivoclar Vivadent) adhesive systems according to the manufacturers' instructions. Shear bond strength test was performed in a universal testing machine at 0.5mm/min until bonding failure. Failure modes were determined under a stereomicroscope, and fracture surfaces were evaluated with a scanning electron microscope. The data were statistically analysed (SPSS 17.0) (p=0.05). Group RV-D exhibited the lowest bond strength value (5.42±6.6MPa). There was statistically no difference among RV-D, V2-D (13.78±8.8MPa) and VV-D (13.84±6.2MPa) groups (p>0.05). Group VV-E exhibited the highest bond strength value (24.76±8.8MPa). The type of tooth structure affected the shear bond strength of the porcelain laminate veneers to the 3 different types of tooth structures (enamel, dentine, and enamel-dentine complex). When dentine exposure is necessary during preparation, enough sound enamel must be protected as much as possible to maintain a good bonding; to obtain maximum bond strength, preparation margins should be on sound enamel. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Bio-active molecules modified surfaces enhanced mesenchymal stem cell adhesion and proliferation

    International Nuclear Information System (INIS)

    Mobasseri, Rezvan; Tian, Lingling; Soleimani, Masoud; Ramakrishna, Seeram; Naderi-Manesh, Hossein

    2017-01-01

    Surface modification of the substrate as a component of in vitro cell culture and tissue engineering, using bio-active molecules including extracellular matrix (ECM) proteins or peptides derived ECM proteins can modulate the surface properties and thereby induce the desired signaling pathways in cells. The aim of this study was to evaluate the behavior of human bone marrow mesenchymal stem cells (hBM-MSCs) on glass substrates modified with fibronectin (Fn), collagen (Coll), RGD peptides (RGD) and designed peptide (R-pept) as bio-active molecules. The glass coverslips were coated with fibronectin, collagen, RGD peptide and R-peptide. Bone marrow mesenchymal stem cells were cultured on different substrates and the adhesion behavior in early incubation times was investigated using scanning electron microscopy (SEM) and confocal microscopy. The MTT assay was performed to evaluate the effect of different bio-active molecules on MSCs proliferation rate during 24 and 72 h. Formation of filopodia and focal adhesion (FA) complexes, two steps of cell adhesion process, were observed in MSCs cultured on bio-active molecules modified coverslips, specifically in Fn coated and R-pept coated groups. SEM image showed well adhesion pattern for MSCs cultured on Fn and R-pept after 2 h incubation, while the shape of cells cultured on Coll and RGD substrates indicated that they might experience stress condition in early hours of culture. Investigation of adhesion behavior, as well as proliferation pattern, suggests R-peptide as a promising bio-active molecule to be used for surface modification of substrate in supporting and inducing cell adhesion and proliferation. - Highlights: • Bioactive molecules modified surface is a strategy to design biomimicry scaffold. • Bi-functional Tat-derived peptide (R-pept) enhanced MSCs adhesion and proliferation. • R-pept showed similar influences to fibronectin on FA formation and attachment.

  4. 'Special K' and a Loss of Cell-To-Cell Adhesion in Proximal Tubule-Derived Epithelial Cells: Modulation of the Adherens Junction Complex by Ketamine

    Science.gov (United States)

    Hills, Claire E.; Jin, Tianrong; Siamantouras, Eleftherios; Liu, Issac K-K; Jefferson, Kieran P.; Squires, Paul E.

    2013-01-01

    Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention. PMID:24009666

  5. IGF-1 Receptor and adhesion signaling: an important axis in determining cancer cell phenotype and therapy resistance.

    Directory of Open Access Journals (Sweden)

    Orla T Cox

    2015-07-01

    Full Text Available IGF-1R expression and activation levels generally cannot be correlated in cancer cells, suggesting that cellular proteins may modulate IGF-1R activity. Strong candidates for such modulation are found in cell-matrix and cell-cell adhesion signaling complexes. Activated IGF-1R is present at focal adhesions, where it can stabilize β1 integrin and participate in signaling complexes that promote invasiveness associated with epithelial mesenchymal transition (EMT, and resistance to therapy. Whether IGF-1R contributes to EMT or to non-invasive tumor growth may be strongly influenced by the degree of ECM engagement and the presence or absence of key proteins in IGF-1R-cell adhesion complexes. One such protein is PDLIM2, which promotes both cell polarization and EMT by regulating the stability of transcription factors including NFκB, STATs and beta catenin. PDLIM2 exhibits tumor suppressor activity, but is also highly expressed in certain invasive cancers. It is likely that distinct adhesion complex proteins modulate IGF-1R signaling during cancer progression or adaptive responses to therapy. Thus, identifying the key modulators will be important for developing effective therapeutic strategies and predictive biomarkers.

  6. Nephrin regulates lamellipodia formation by assembling a protein complex that includes Ship2, filamin and lamellipodin.

    Directory of Open Access Journals (Sweden)

    Madhusudan Venkatareddy

    Full Text Available Actin dynamics has emerged at the forefront of podocyte biology. Slit diaphragm junctional adhesion protein Nephrin is necessary for development of the podocyte morphology and transduces phosphorylation-dependent signals that regulate cytoskeletal dynamics. The present study extends our understanding of Nephrin function by showing in cultured podocytes that Nephrin activation induced actin dynamics is necessary for lamellipodia formation. Upon activation Nephrin recruits and regulates a protein complex that includes Ship2 (SH2 domain containing 5' inositol phosphatase, Filamin and Lamellipodin, proteins important in regulation of actin and focal adhesion dynamics, as well as lamellipodia formation. Using the previously described CD16-Nephrin clustering system, Nephrin ligation or activation resulted in phosphorylation of the actin crosslinking protein Filamin in a p21 activated kinase dependent manner. Nephrin activation in cell culture results in formation of lamellipodia, a process that requires specialized actin dynamics at the leading edge of the cell along with focal adhesion turnover. In the CD16-Nephrin clustering model, Nephrin ligation resulted in abnormal morphology of actin tails in human podocytes when Ship2, Filamin or Lamellipodin were individually knocked down. We also observed decreased lamellipodia formation and cell migration in these knock down cells. These data provide evidence that Nephrin not only initiates actin polymerization but also assembles a protein complex that is necessary to regulate the architecture of the generated actin filament network and focal adhesion dynamics.

  7. Focal femoral condyle resurfacing.

    LENUS (Irish Health Repository)

    Brennan, S A

    2013-03-01

    Focal femoral inlay resurfacing has been developed for the treatment of full-thickness chondral defects of the knee. This technique involves implanting a defect-sized metallic or ceramic cap that is anchored to the subchondral bone through a screw or pin. The use of these experimental caps has been advocated in middle-aged patients who have failed non-operative methods or biological repair techniques and are deemed unsuitable for conventional arthroplasty because of their age. This paper outlines the implant design, surgical technique and biomechanical principles underlying their use. Outcomes following implantation in both animal and human studies are also reviewed. Cite this article: Bone Joint J 2013;95-B:301-4.

  8. Systemic focal epileptogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Marcussen, W.H.

    1986-01-01

    Rats that receive radiation to 0.25 cc of one cerebral hemisphere are clinically and electroencephalographically normal until there is a breakdown of the blood-brain barrier (BBB) at 3 to 6 months postradiation. This BBB lesion can be detected by transient focal seizure activity produced by the BBB-excluded systemic convulsant bicuculline methiodide. In two rats the seizure activity induced by this one injection was self-sustaining. In seven of 15 other rats tested, the subsequent administration of repeated 2 mg/kg injections created a chronic focus that continued to spike with great frequency for 3 weeks or more without further administration of any convulsant. In three of eight other rats, implanted minipumps delivering 180 micrograms/h of bicuculline methiodide produced self-sustaining epileptic activity.

  9. Cell adhesion to cathodic arc plasma deposited CrAlSiN thin films

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Kyu, E-mail: skim@ulsan.ac.kr [School of Materials Science and Engineering, University of Ulsan, Ulsan 680-749 (Korea, Republic of); Pham, Vuong-Hung [Department of Materials Science and Engineering, Seoul National University, Seoul 151-744 (Korea, Republic of); Kim, Chong-Hyun [Department of Food Science, Cornell University, Ithaca, NY 14853 (United States)

    2012-07-01

    Osteoblast cell response (cell adhesion, actin cytoskeleton and focal contact adhesion as well as cell proliferation) to CrN, CrAlSiN and Ti thin films was evaluated in vitro. Cell adhesion and actin stress fibers organization depended on the film composition significantly. Immunofluorescent staining of vinculin in osteoblast cells showed good focal contact adhesion on the CrAlSiN and Ti thin films but not on the CrN thin films. Cell proliferation was significantly greater on the CrAlSiN thin films as well as on Ti thin films than on the CrN thin films.

  10. Focal midbrain tumors in children

    NARCIS (Netherlands)

    Vandertop, W. P.; Hoffman, H. J.; Drake, J. M.; Humphreys, R. P.; Rutka, J. T.; Amstrong, D. C.; Becker, L. E.

    1992-01-01

    The clinical and neuroradiological features of focal midbrain tumors in 12 children are described, and the results of their surgical management are presented. Patients with a focal midbrain tumor usually exhibit either symptoms and signs of raised intracranial pressure caused by an obstructive

  11. Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion.

    Science.gov (United States)

    Ronan, William; Deshpande, Vikram S; McMeeking, Robert M; McGarry, J Patrick

    2014-04-01

    Numerous experimental studies have established that cells can sense the stiffness of underlying substrates and have quantified the effect of substrate stiffness on stress fibre formation, focal adhesion area, cell traction, and cell shape. In order to capture such behaviour, the current study couples a mixed mode thermodynamic and mechanical framework that predicts focal adhesion formation and growth with a material model that predicts stress fibre formation, contractility, and dissociation in a fully 3D implementation. Simulations reveal that SF contractility plays a critical role in the substrate-dependent response of cells. Compliant substrates do not provide sufficient tension for stress fibre persistence, causing dissociation of stress fibres and lower focal adhesion formation. In contrast, cells on stiffer substrates are predicted to contain large amounts of dominant stress fibres. Different levels of cellular contractility representative of different cell phenotypes are found to alter the range of substrate stiffness that cause the most significant changes in stress fibre and focal adhesion formation. Furthermore, stress fibre and focal adhesion formation evolve as a cell spreads on a substrate and leading to the formation of bands of fibres leading from the cell periphery over the nucleus. Inhibiting the formation of FAs during cell spreading is found to limit stress fibre formation. The predictions of this mutually dependent material-interface framework are strongly supported by experimental observations of cells adhered to elastic substrates and offer insight into the inter-dependent biomechanical processes regulating stress fibre and focal adhesion formation.

  12. Diagnostic imaging in focal epilepsy

    International Nuclear Information System (INIS)

    Zlatareva, D.

    2013-01-01

    Focal epilepsies account for 60% of all seizure disorders worldwide. In this review the classic and new classification system of epileptic seizures and syndromes as well as genetic forms are discussed. Magnetic resonance (MR) is the technique of choice for diagnostic imaging in focal epilepsy because of its sensitivity and high tissue contrast. The review is focused on the lack of consensus of imaging protocols and reported findings in refractory epilepsy. The most frequently encountered MRI findings in epilepsy are reported and their imaging characteristics are depicted. Diagnosis of hippocampal sclerosis and malformations of cortical development as two major causes of refractory focal epilepsy is described in details. Some promising new techniques as positron emission tomography computed tomography (PET/CT) and MR and PET/CT fusion are briefly discussed. Also the relevance of adequate imaging in focal epilepsy, some practical points in imaging interpretation and differential diagnosis are highlighted. (author)

  13. Impaired Integrin-mediated Adhesion and Signaling in Fibroblasts Expressing a Dominant-negative Mutant PTP1B

    Science.gov (United States)

    Arregui, Carlos O.; Balsamo, Janne; Lilien, Jack

    1998-01-01

    To investigate the role of nonreceptor protein tyrosine phosphatase 1B (PTP1B) in β1-integrin– mediated adhesion and signaling, we transfected mouse L cells with normal and catalytically inactive forms of the phosphatase. Parental cells and cells expressing the wild-type or mutant PTP1B were assayed for (a) adhesion, (b) spreading, (c) presence of focal adhesions and stress fibers, and (d) tyrosine phosphorylation. Parental cells and cells expressing wild-type PTP1B show similar morphology, are able to attach and spread on fibronectin, and form focal adhesions and stress fibers. In contrast, cells expressing the inactive PTP1B have a spindle-shaped morphology, reduced adhesion and spreading on fibronectin, and almost a complete absence of focal adhesions and stress fibers. Attachment to fibronectin induces tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin in parental cells and cells transfected with the wild-type PTP1B, while in cells transfected with the mutant PTP1B, such induction is not observed. Additionally, in cells expressing the mutant PTP1B, tyrosine phosphorylation of Src is enhanced and activity is reduced. Lysophosphatidic acid temporarily reverses the effects of the mutant PTP1B, suggesting the existence of a signaling pathway triggering focal adhesion assembly that bypasses the need for active PTP1B. PTP1B coimmunoprecipitates with β1-integrin from nonionic detergent extracts and colocalizes with vinculin and the ends of actin stress fibers in focal adhesions. Our data suggest that PTP1B is a critical regulatory component of integrin signaling pathways, which is essential for adhesion, spreading, and formation of focal adhesions. PMID:9813103

  14. Adhesion in microelectronics

    CERN Document Server

    Mittal, K L

    2014-01-01

    This comprehensive book will provide both fundamental and applied aspects of adhesion pertaining to microelectronics in a single and easily accessible source. Among the topics to be covered include; Various theories or mechanisms of adhesionSurface (physical or chemical) characterization of materials as it pertains to adhesionSurface cleaning as it pertains to adhesionWays to improve adhesionUnraveling of interfacial interactions using an array of pertinent techniquesCharacterization of interfaces / interphasesPolymer-polymer adhesionMetal-polymer adhesion  (metallized polymers)Polymer adhesi

  15. Reflections about Adhesive Systems

    OpenAIRE

    de Freitas Borges, Marciano; Diesel, Pâmela Gutheil; Corrêa, Fernanda Gomez; Bernardi, Eledana; Fernandes Montagner, Anelise; Skupien, Jovito Adiel; Susin, Alexandre Henrique

    2010-01-01

    The adhesive systems are responsible for an efficient union between teeth and resin, resulting in a longevity restoration. They are organic molecules di or multifunctional that contain reactive groups that interact with dentin and with the resin monomer of composite resin. The adhesive systems are characterized by wet adhesion, which is a result of presence of hidrophylics radicals in their compositions, to promote a better bond and the best properties of the adhesion. Adhesive systems may us...

  16. Design and fabrication of polymer based dry adhesives inspired by the gecko adhesive system

    Science.gov (United States)

    Jin, Kejia

    There has been significant interest in developing dry adhesives mimicking the gecko adhesive system, which offers several advantages compared to conventional pressure sensitive adhesives. Specifically, gecko adhesive pads have anisotropic adhesion properties: the adhesive pads (spatulae) stick strongly when sheared in one direction but are non-adherent when sheared in the opposite direction. This anisotropy property is attributed to the complex topography of the array of fine tilted and curved columnar structures (setae) that bear the spatulae. In this thesis, easy, scalable methods, relying on conventional and unconventional techniques are presented to incorporate tilt in the fabrication of synthetic polymer-based dry adhesives mimicking the gecko adhesive system, which provide anisotropic adhesion properties. In the first part of the study, the anisotropic adhesion and friction properties of samples with various tilt angles to test the validity of a nanoscale tape-peeling model of spatular function are measured. Consistent with the Peel Zone model, samples with lower tilt angles yielded larger adhesion forces. Contact mechanics of the synthetic array were highly anisotropic, consistent with the frictional adhesion model and gecko-like. Based on the original design, a new design of gecko-like dry adhesives was developed which showed superior tribological properties and furthermore showed anisotropic adhesive properties without the need for tilt in the structures. These adhesives can be used to reversibly suspend weights from vertical surfaces (e.g., walls) and, for the first time to our knowledge, horizontal surfaces (e.g., ceilings) by simultaneously and judiciously activating anisotropic friction and adhesion forces. Furthermore, adhesion properties between artificial gecko-inspired dry adhesives and rough substrates with varying roughness are studied. The results suggest that both adhesion and friction forces on a rough substrate depends significantly on the

  17. Continuously variable focal length lens

    Science.gov (United States)

    Adams, Bernhard W; Chollet, Matthieu C

    2013-12-17

    A material preferably in crystal form having a low atomic number such as beryllium (Z=4) provides for the focusing of x-rays in a continuously variable manner. The material is provided with plural spaced curvilinear, optically matched slots and/or recesses through which an x-ray beam is directed. The focal length of the material may be decreased or increased by increasing or decreasing, respectively, the number of slots (or recesses) through which the x-ray beam is directed, while fine tuning of the focal length is accomplished by rotation of the material so as to change the path length of the x-ray beam through the aligned cylindrical slows. X-ray analysis of a fixed point in a solid material may be performed by scanning the energy of the x-ray beam while rotating the material to maintain the beam's focal point at a fixed point in the specimen undergoing analysis.

  18. Testing of focal plane arrays

    International Nuclear Information System (INIS)

    Merriam, J.D.

    1988-01-01

    Problems associated with the testing of focal plane arrays are briefly examined with reference to the instrumentation and measurement procedures. In particular, the approach and instrumentation used as the Naval Ocean Systems Center is presented. Most of the measurements are made with flooded illumination on the focal plane array. The array is treated as an ensemble of individual pixels, data being taken on each pixel and array averages and standard deviations computed for the entire array. Data maps are generated, showing the pixel data in the proper spatial position on the array and the array statistics

  19. Inverse-designed stretchable metalens with tunable focal distance

    Science.gov (United States)

    Callewaert, Francois; Velev, Vesselin; Jiang, Shizhou; Sahakian, Alan Varteres; Kumar, Prem; Aydin, Koray

    2018-02-01

    In this paper, we present an inverse-designed 3D-printed all-dielectric stretchable millimeter wave metalens with a tunable focal distance. A computational inverse-design method is used to design a flat metalens made of disconnected polymer building blocks with complex shapes, as opposed to conventional monolithic lenses. The proposed metalens provides better performance than a conventional Fresnel lens, using lesser amount of material and enabling larger focal distance tunability. The metalens is fabricated using a commercial 3D-printer and attached to a stretchable platform. Measurements and simulations show that the focal distance can be tuned by a factor of 4 with a stretching factor of only 75%, a nearly diffraction-limited focal spot, and with a 70% relative focusing efficiency, defined as the ratio between power focused in the focal spot and power going through the focal plane. The proposed platform can be extended for design and fabrication of multiple electromagnetic devices working from visible to microwave radiation depending on scaling of the devices.

  20. Thermomechanical architecture of the VIS focal plane for Euclid

    International Nuclear Information System (INIS)

    Martignac, Jerome; Carty, Michael; Tourette, Thierry; Bachet, Damien; Berthe, Michel; Augueres, Jean-Louis; Amiaux, Jerome; Fontignie, Jean; Horeau, Benoit; Renaud, Diana

    2014-01-01

    One of the main challenges for current and near future space experiments is the increase of focal plane complexity in terms of amount of pixels. In the frame work of the ESA Euclid mission to be launched in 2020, the Euclid Consortium is developing an extremely large and stable focal plane for the VIS instrument. CEA has developed the thermomechanical architecture of that Focal Plane taking into account all the very stringent performance and mission related requirements. The VIS Focal Plane Assembly integrates 36 CCDs (operated at 150 K) connected to their front end electronics (operated at 280 K) as to obtain one of the largest focal plane (0.6 billion pixels) ever built for space application after the GAIA one. The CCDs are CCD273 type specially designed and provided by the e2v company under ESA contract, front end electronics is studied and provided by MSSL. In this paper we first recall the specific requirements that have driven the overall architecture of the VIS-FPA and especially the solutions proposed to cope with the scientific needs of an extremely stable focal plane, both mechanically and thermally. The mechanical structure based on SiC material used for the cold sub assembly supporting the CCDs is detailed. We describe also the modular architecture concept that we have selected taking into account AIT-AIV and programmatic constraints. (authors)

  1. Chapter 9:Wood Adhesion and Adhesives

    Science.gov (United States)

    Charles R. Frihart

    2013-01-01

    The recorded history of bonding wood dates back at least 3000 years to the Egyptians (Skeist and Miron 1990, River 1994a), and adhesive bonding goes back to early mankind (Keimel 2003). Although wood and paper bonding are the largest applications for adhesives, some of the fundamental aspects leading to good bonds are not fully understood. Better understanding of these...

  2. THz Properties of Adhesives

    Science.gov (United States)

    Stübling, E.; Gomell, L.; Sommer, S.; Winkel, A.; Kahlmeyer, M.; Böhm, S.; Koch, M.

    2018-06-01

    We determined the THz properties of 12 different adhesives which are mainly used for industrial purposes. The adhesives applied can be classified according to their chemical structure: epoxy resins, acrylic resins, and polyurethane based materials. This work represents a basis for future studies, which will concentrate on aging effects, including the absorption of water of adhesive joints. Thus, the dielectric properties of the unaged adhesives are investigated and the results of these measurements are described herein.

  3. Focal therapy in prostate cancer

    NARCIS (Netherlands)

    van den Bos, W.

    2016-01-01

    Interesting developments took place in the treatment of prostate cancer including focal therapy for less aggressive organ-confined prostate cancer. Fortunately, curative treatment is often still an option for patients suffering from the lower staged tumors. In carefully selected patients, the

  4. Gallbladder adenoma with focal adenocarcinoma.

    Science.gov (United States)

    Ciurea, S; Matei, E; Petrisor, P; Luca, L; Boros, Mirela; Herlea, V; Popescu, I

    2008-01-01

    The majority of polypoid lesions of the gallbladder are cholesterolosis pseudopolyps. True neoplastic GB polyps are represented mainly by adenomas. The case of a 52-year old male patient with an adenomatous polyp of the GB with focal adenocarcinoma is presented.

  5. Charging as a Focal Practice

    DEFF Research Database (Denmark)

    Bødker, Mads

    This position paper reflects on Borgmann’s notion of ‘focal things’ and its applicability in the discourse about interaction with technologies in nature. Using the example of a combined cooking burner and thermoelectric 5W smartphone charger (a BioLite cook stove), this position paper gives...

  6. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  7. Prevention of bacterial adhesion

    DEFF Research Database (Denmark)

    Klemm, Per; Vejborg, Rebecca Munk; Hancock, Viktoria

    2010-01-01

    . As such, adhesion represents the Achilles heel of crucial pathogenic functions. It follows that interference with adhesion can reduce bacterial virulence. Here, we illustrate this important topic with examples of techniques being developed that can inhibit bacterial adhesion. Some of these will become...

  8. Particle adhesion and removal

    CERN Document Server

    Mittal, K L

    2015-01-01

    The book provides a comprehensive and easily accessible reference source covering all important aspects of particle adhesion and removal.  The core objective is to cover both fundamental and applied aspects of particle adhesion and removal with emphasis on recent developments.  Among the topics to be covered include: 1. Fundamentals of surface forces in particle adhesion and removal.2. Mechanisms of particle adhesion and removal.3. Experimental methods (e.g. AFM, SFA,SFM,IFM, etc.) to understand  particle-particle and particle-substrate interactions.4. Mechanics of adhesion of micro- and  n

  9. Differential diagnosis of focal pancreatitis and pancreatic cancer

    NARCIS (Netherlands)

    van Gulik, T. M.; Moojen, T. M.; van Geenen, R.; Rauws, E. A.; Obertop, H.; Gouma, D. J.

    1999-01-01

    The differentiation of focal, chronic pancreatitis (CP) and pancreatic cancer (PAC) poses a diagnostic dilemma. Both conditions may present with the same symptoms and signs. The complexity of differential diagnosis is enhanced because PAC is frequently associated with secondary inflammatory changes

  10. [Focal myositis: An unknown disease].

    Science.gov (United States)

    Gallay, L; Streichenberger, N; Benveniste, O; Allenbach, Y

    2017-10-01

    Focal myositis are inflammatory muscle diseases of unknown origin. At the opposite from the other idiopathic inflammatory myopathies, they are restricted to a single muscle or to a muscle group. They are not associated with extramuscular manifestations, and they have a good prognosis without any treatment. They are characterized by a localized swelling affecting mostly lower limbs. The pseudo-tumor can be painful, but is not associated with a muscle weakness. Creatine kinase level is normal. Muscle MRI shows an inflammation restricted to a muscle or a muscle group. Muscle biopsy and pathological analysis remain necessary for the diagnosis, showing inflammatory infiltrates composed by macrophages and lymphocytes without any specific distribution within the muscle. Focal overexpression of HLA-1 by the muscle fibers is frequently observed. The muscle biopsy permits to rule out differential diagnosis such a malignancy (sarcoma). Spontaneous remission occurs within weeks or months after the first symptoms, relapse is unusual. Copyright © 2017. Published by Elsevier SAS.

  11. Topography on a subcellular scale modulates cellular adhesions and actin stress fiber dynamics in tumor associated fibroblasts

    Science.gov (United States)

    Azatov, Mikheil; Sun, Xiaoyu; Suberi, Alexandra; Fourkas, John T.; Upadhyaya, Arpita

    2017-12-01

    Cells can sense and adapt to mechanical properties of their environment. The local geometry of the extracellular matrix, such as its topography, has been shown to modulate cell morphology, migration, and proliferation. Here we investigate the effect of micro/nanotopography on the morphology and cytoskeletal dynamics of human pancreatic tumor-associated fibroblast cells (TAFs). We use arrays of parallel nanoridges with variable spacings on a subcellular scale to investigate the response of TAFs to the topography of their environment. We find that cell shape and stress fiber organization both align along the direction of the nanoridges. Our analysis reveals a strong bimodal relationship between the degree of alignment and the spacing of the nanoridges. Furthermore, focal adhesions align along ridges and form preferentially on top of the ridges. Tracking actin stress fiber movement reveals enhanced dynamics of stress fibers on topographically patterned surfaces. We find that components of the actin cytoskeleton move preferentially along the ridges with a significantly higher velocity along the ridges than on a flat surface. Our results suggest that a complex interplay between the actin cytoskeleton and focal adhesions coordinates the cellular response to micro/nanotopography.

  12. MDA-MB-231 breast cancer cell viability, motility and matrix adhesion are regulated by a complex interplay of heparan sulfate, chondroitin-/dermatan sulfate and hyaluronan biosynthesis.

    Science.gov (United States)

    Viola, Manuela; Brüggemann, Kathrin; Karousou, Evgenia; Caon, Ilaria; Caravà, Elena; Vigetti, Davide; Greve, Burkhard; Stock, Christian; De Luca, Giancarlo; Passi, Alberto; Götte, Martin

    2017-06-01

    Proteoglycans and glycosaminoglycans modulate numerous cellular processes relevant to tumour progression, including cell proliferation, cell-matrix interactions, cell motility and invasive growth. Among the glycosaminoglycans with a well-documented role in tumour progression are heparan sulphate, chondroitin/dermatan sulphate and hyaluronic acid/hyaluronan. While the mode of biosynthesis differs for sulphated glycosaminoglycans, which are synthesised in the ER and Golgi compartments, and hyaluronan, which is synthesized at the plasma membrane, these polysaccharides partially compete for common substrates. In this study, we employed a siRNA knockdown approach for heparan sulphate (EXT1) and heparan/chondroitin/dermatan sulphate-biosynthetic enzymes (β4GalT7) in the aggressive human breast cancer cell line MDA-MB-231 to study the impact on cell behaviour and hyaluronan biosynthesis. Knockdown of β4GalT7 expression resulted in a decrease in cell viability, motility and adhesion to fibronectin, while these parameters were unchanged in EXT1-silenced cells. Importantly, these changes were associated with a decreased expression of syndecan-1, decreased signalling response to HGF and an increase in the synthesis of hyaluronan, due to an upregulation of the hyaluronan synthases HAS2 and HAS3. Interestingly, EXT1-depleted cells showed a downregulation of the UDP-sugar transporter SLC35D1, whereas SLC35D2 was downregulated in β4GalT7-depleted cells, indicating an intricate regulatory network that connects all glycosaminoglycans synthesis. The results of our in vitro study suggest that a modulation of breast cancer cell behaviour via interference with heparan sulphate biosynthesis may result in a compensatory upregulation of hyaluronan biosynthesis. These findings have important implications for the development of glycosaminoglycan-targeted therapeutic approaches for malignant diseases.

  13. A targeted resequencing gene panel for focal epilepsy.

    Science.gov (United States)

    Hildebrand, Michael S; Myers, Candace T; Carvill, Gemma L; Regan, Brigid M; Damiano, John A; Mullen, Saul A; Newton, Mark R; Nair, Umesh; Gazina, Elena V; Milligan, Carol J; Reid, Christopher A; Petrou, Steven; Scheffer, Ingrid E; Berkovic, Samuel F; Mefford, Heather C

    2016-04-26

    We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of the epilepsies. The targeted resequencing gene panel was designed using molecular inversion probe (MIP) capture technology and sequenced using massively parallel Illumina sequencing. We demonstrated proof of principle that mutations can be detected in 4 previously genotyped focal epilepsy cases. We searched for both germline and somatic mutations in 251 patients with unsolved sporadic or familial focal epilepsy and identified 11 novel or very rare missense variants in 5 different genes: CHRNA4, GRIN2B, KCNT1, PCDH19, and SCN1A. Of these, 2 were predicted to be pathogenic or likely pathogenic, explaining ∼0.8% of the cohort, and 8 were of uncertain significance based on available data. We have developed and validated a targeted resequencing panel for focal epilepsies, the most important clinical class of epilepsies, accounting for about 60% of all cases. Our application of MIP technology is an innovative approach that will be advantageous in the clinical setting because it is highly sensitive, efficient, and cost-effective for screening large patient cohorts. Our findings indicate that mutations in known genes likely explain only a small proportion of focal epilepsy cases. This is not surprising given the established clinical and genetic heterogeneity of these disorders and underscores the importance of further gene discovery studies in this complex syndrome. © 2016 American Academy of Neurology.

  14. Energetics of bacterial adhesion

    International Nuclear Information System (INIS)

    Loosdrecht, M.C.M. van; Zehnder, A.J.B.

    1990-01-01

    For the description of bacterial adhesion phenomena two different physico-chemical approaches are available. The first one, based on a surface Gibbs energy balance, assumes intimate contact between the interacting surfaces. The second approach, based on colloid chemical theories (DLVO theory), allows for two types of adhesion: 1) secondary minimum adhesion, which is often weak and reversible, and 2) irreversible primary minimum adhesion. In the secondary minimum adhesion a thin water film remains present between the interacting surface. The merits of both approaches are discussed in this paper. In addition, the methods available to measure the physico-chemical surface characteristics of bacteria and the influence of adsorbing (in)organic compounds, extracellular polymers and cell surface appendages on adhesion are summarized. (author) 2 figs., 1 tab., 50 refs

  15. Radiation-curable adhesives

    International Nuclear Information System (INIS)

    Woods, J.G.

    1992-01-01

    Radiation-curable adhesives may be classified into two broad categories. In the first category, adhesive bonding occurs as a direct result of irradiation. The second category includes pressure-sensitive and hot-melt adhesives, which are composed of linear or lightly cross-linked polymers prepared by a radiation-induced polymerization reaction. This chapter is mainly concerned with radiation-curable adhesives of the first category. The various adhesive types are discussed and adhesive performance is examined, particularly in relation to the chemistry and chemical technology which underlies the individual materials. A description of a limited number of representative applications is included as is an outline of recent developments of curing and dispensing equipment. 268 refs., 14 figs., 13 tabs

  16. The adhesive strength and initial viscosity of denture adhesives.

    Science.gov (United States)

    Han, Jian-Min; Hong, Guang; Dilinuer, Maimaitishawuti; Lin, Hong; Zheng, Gang; Wang, Xin-Zhi; Sasaki, Keiichi

    2014-11-01

    To examine the initial viscosity and adhesive strength of modern denture adhesives in vitro. Three cream-type denture adhesives (Poligrip S, Corect Cream, Liodent Cream; PGS, CRC, LDC) and three powder-type denture adhesives (Poligrip Powder, New Faston, Zanfton; PGP, FSN, ZFN) were used in this study. The initial viscosity was measured using a controlled-stress rheometer. The adhesive strength was measured according to ISO-10873 recommended procedures. All data were analyzed independently by one-way analysis of variance combined with a Student-Newman-Keuls multiple comparison test at a 5% level of significance. The initial viscosity of all the cream-type denture adhesives was lower than the powder-type adhesives. Before immersion in water, all the powder-type adhesives exhibited higher adhesive strength than the cream-type adhesives. However, the adhesive strength of cream-type denture adhesives increased significantly and exceeded the powder-type denture adhesives after immersion in water. For powder-type adhesives, the adhesive strength significantly decreased after immersion in water for 60 min, while the adhesive strength of the cream-type adhesives significantly decreased after immersion in water for 180 min. Cream-type denture adhesives have lower initial viscosity and higher adhesive strength than powder type adhesives, which may offer better manipulation properties and greater efficacy during application.

  17. Systems considerations in mosaic focal planes

    Science.gov (United States)

    White, K. P., III

    1983-08-01

    Two key reasons for pursuing the development of mosaic focal planes are reviewed and it is shown that rapid frame repetition rate is the only requirement that can be solved no other way than through mosaic focal planes. With the view that spaceborne mosaic focal plane sensors are necessarily 'smart sensors' requiring a lot of onboard processing just to function, it is pointed out that various artificial intelligence techniques may be the most appropriate to incorporate in the data processing. Finally, a novel mosaic focal plane design is proposed, termed a virtual mosaic focal plane, in response to other system constraints.

  18. Synaptic Cell Adhesion

    OpenAIRE

    Missler, Markus; Südhof, Thomas C.; Biederer, Thomas

    2012-01-01

    Chemical synapses are asymmetric intercellular junctions that mediate synaptic transmission. Synaptic junctions are organized by trans-synaptic cell adhesion molecules bridging the synaptic cleft. Synaptic cell adhesion molecules not only connect pre- and postsynaptic compartments, but also mediate trans-synaptic recognition and signaling processes that are essential for the establishment, specification, and plasticity of synapses. A growing number of synaptic cell adhesion molecules that inc...

  19. 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.

  20. 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

  1. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  2. Isolation and biochemical characterization of underwater adhesives from diatoms.

    Science.gov (United States)

    Poulsen, Nicole; Kröger, Nils; Harrington, Matthew J; Brunner, Eike; Paasch, Silvia; Buhmann, Matthias T

    2014-01-01

    Many aquatic organisms are able to colonize surfaces through the secretion of underwater adhesives. Diatoms are unicellular algae that have the capability to colonize any natural and man-made submerged surfaces. There is great technological interest in both mimicking and preventing diatom adhesion, yet the biomolecules responsible have so far remained unidentified. A new method for the isolation of diatom adhesive material is described and its amino acid and carbohydrate composition determined. The adhesive materials from two model diatoms show differences in their amino acid and carbohydrate compositions, but also share characteristic features including a high content of uronic acids, the predominance of hydrophilic amino acid residues, and the presence of 3,4-dihydroxyproline, an extremely rare amino acid. Proteins containing dihydroxyphenylalanine, which mediate underwater adhesion of mussels, are absent. The data on the composition of diatom adhesives are consistent with an adhesion mechanism based on complex coacervation of polyelectrolyte-like biomolecules.

  3. Adhesion and cleaning of foods with complex structure: Effect of oil content and fluoropolymer coating characteristics on the detachment of cake from baking surfaces

    OpenAIRE

    Magens, Ole; Liu, Y; Hofmans, JFA; Nelissen, JA; Wilson, David Ian

    2017-01-01

    The effect of surface coating on the detachment of a complex microstructured food material, was investigated using an improved version of the millimanipulation device described by Ali et al. (2015 $\\textit{Food & Bioproducts Processing}$, Vol. 93, 256–268). The test material was baked sponge cake batter, which contains approximately 27 vol% bubbles in a ‘continuous’ phase of emulsified oil in a flour/syrup suspension. Detachment in the dry state was studied for aluminium, 304 stainless steel ...

  4. Interferon Induced Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Yusuf Kayar

    2016-01-01

    Full Text Available Behçet’s disease is an inflammatory disease of unknown etiology which involves recurring oral and genital aphthous ulcers and ocular lesions as well as articular, vascular, and nervous system involvement. Focal segmental glomerulosclerosis (FSGS is usually seen in viral infections, immune deficiency syndrome, sickle cell anemia, and hyperfiltration and secondary to interferon therapy. Here, we present a case of FSGS identified with kidney biopsy in a patient who had been diagnosed with Behçet’s disease and received interferon-alpha treatment for uveitis and presented with acute renal failure and nephrotic syndrome associated with interferon.

  5. Focal nodular hyperplasia: imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Kehagias, D.; Moulopoulos, L.; Antoniou, A.; Hatziioannou, A.; Smyrniotis, V.; Trakadas, S.; Lahanis, S.; Vlahos, L. [Dept. of Radiology, University of Athens (Greece)

    2001-02-01

    Focal nodular hyperplasia is an uncommon benign hepatic tumor that continues to pose diagnostic dilemmas. Imaging techniques are of great value in diagnosis of this tumor. In this article we present the US, CT, MR imaging, scintigraphy, and angiography findings. The demonstration of a central vascular scar is very helpful. Although the radiologic features may be diagnostic, many atypical cases must be differentiated from other benign or malignant hepatic tumors. In these cases excisional biopsy and histopathologic examination are necessary to determine a definite diagnosis. (orig.)

  6. Focal nodular hyperplasia: imaging findings

    International Nuclear Information System (INIS)

    Kehagias, D.; Moulopoulos, L.; Antoniou, A.; Hatziioannou, A.; Smyrniotis, V.; Trakadas, S.; Lahanis, S.; Vlahos, L.

    2001-01-01

    Focal nodular hyperplasia is an uncommon benign hepatic tumor that continues to pose diagnostic dilemmas. Imaging techniques are of great value in diagnosis of this tumor. In this article we present the US, CT, MR imaging, scintigraphy, and angiography findings. The demonstration of a central vascular scar is very helpful. Although the radiologic features may be diagnostic, many atypical cases must be differentiated from other benign or malignant hepatic tumors. In these cases excisional biopsy and histopathologic examination are necessary to determine a definite diagnosis. (orig.)

  7. SNAP Satellite Focal Plane Development

    International Nuclear Information System (INIS)

    Bebek, C.; Akerlof, C.; Aldering, G.; Amanullah, R.; Astier, P.; Baltay, C.; Barrelet, E.; Basa, S.; Bercovitz, J.; Bergstrom, L.; Berstein, G.P.; Bester, M.; Bohlin, R.; Bonissent, A.; Bower, C.; Campbell, M.; Carithers, W.; Commins, E.; Day, C.; Deustua, S.; DiGennaro, R.; Ealet, A.; Ellis, R.; Emmett, W.; Eriksson, M.; Fouchez, D.; Fruchter, A.; Genat, J-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Heetderks, H.; Holland, S.; Huterer, D.; Johnson, W.; Kadel, R.; Karcher, A.; Kim, A.; Kolbe, W.; Lafever, R.; Lamoureaux, J.; Lampton, M.; Lefevre, O.; Levi, M.; Levin, D.; Linder, E.; Loken, S.; Malina, R.; Mazure, A.; McKay, T.; McKee, S.; Miquel, R.; Morgan, N.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Roe, N.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Prieto, E.; Rabinowitz, D.; Refregier, A.; Rhodes, J.; Schubnell, M.; Sholl, M.; Smadja, G.; Smith, R.; Smoot, G.; Snyder, J.; Spadafora, A.; Szymkowiak, A.; Tarle, G.; Taylor, K.; Tilquin, A.; Tomasch, A.; Vincent, D.; von der Lippe, H.; Walder, J-P.; Wang, G.

    2003-01-01

    The proposed SuperNova/Acceleration Probe (SNAP) mission will have a two-meter class telescope delivering diffraction-limited images to an instrumented 0.7 square degree field in the visible and near-infrared wavelength regime. The requirements for the instrument suite and the present configuration of the focal plane concept are presented. A two year R and D phase, largely supported by the Department of Energy, is just beginning. We describe the development activities that are taking place to advance our preparedness for mission proposal in the areas of detectors and electronics

  8. MRI of focal cortical dysplasia

    International Nuclear Information System (INIS)

    Lee, B.C.P.; Hatfield, G.A.; Bourgeois, B.; Park, T.S.

    1998-01-01

    We studied nine cases of focal cortical dysplasia (FCD) by MRI, with surface-rendered 3D reconstructions. One case was also examined using single-voxel proton MR spectroscopy (MRS). The histological features were reviewed and correlated with the MRI findings. The gyri affected by FCD were enlarged and the signal of the cortex was slightly increased on T1-weighted images. The gray-white junction was indistinct. Signal from the subcortical white matter was decreased on T1- and increased on T2-weighted images in most cases. Contrast enhancement was seen in two cases. Proton MRS showed a spectrum identical to that of normal brain. (orig.) (orig.)

  9. Adhesive interactions with wood

    Science.gov (United States)

    Charles R. Frihart

    2004-01-01

    While the chemistry for the polymerization of wood adhesives has been studied systematically and extensively, the critical aspects of the interaction of adhesives with wood are less clearly understood. General theories of bond formation need to be modified to take into account the porosity of wood and the ability of chemicals to be absorbed into the cell wall....

  10. Adhesive compositions and methods

    Science.gov (United States)

    Allen, Scott D.; Sendijarevic, Vahid; O'Connor, James

    2017-12-05

    The present invention encompasses polyurethane adhesive compositions comprising aliphatic polycarbonate chains. In one aspect, the present invention encompasses polyurethane adhesives derived from aliphatic polycarbonate polyols and polyisocyanates wherein the polyol chains contain a primary repeating unit having a structure:. In another aspect, the invention provides articles comprising the inventive polyurethane compositions as well as methods of making such compositions.

  11. Soy protein adhesives

    Science.gov (United States)

    Charles R. Frihart

    2010-01-01

    In the quest to manufacture and use building materials that are more environmentally friendly, soy adhesives can be an important component. Trees fix and store carbon dioxide in the atmosphere. After the trees are harvested, machinery converts the wood into strands, which are then bonded together with adhesives to form strandboard, used in constructing long-lasting...

  12. Polymeric flat focal field arrayed waveguide grating using electron-beam direct writing

    Science.gov (United States)

    Lu, Si; Yan, Yingbai; Jin, Guofan; Wong, W. H.; Pun, E. Y. B.

    2004-06-01

    A four-channel 400-GHz spacing flat focal field arrayed waveguide grating (AWG) demultiplexer is designed based on polymeric optical waveguide. The waveguide core-layer material is a newly developed negative tone epoxy Novolak resin (ENR) polymer with ultravoilet (UV) cured resin Norland optical adhesive 61 (NOA61) as the cladding layer. The device is fabricated using electron-beam direct writing, which has less processing steps than the reported polymeric AWGs. The experimental result is presented.

  13. RTG diagnostics of dental focal infection

    International Nuclear Information System (INIS)

    Petrasova, A.; Ondrasovicova, J.; Cecctkova, A.

    2008-01-01

    The theory of focal infection has always been and still is a controversial issue for many dentists and scientists. Even though the focal infection does not occupy the first place in modern medicine, its understanding is imperative. The authors summarized the knowledge about dental focal infection and its relationship to systemic the diseases of the whole body in their publication and they also focused on the radiodiagnostics of this disease. (authors)

  14. Periodontitis in patients with focal tuberculosis

    Directory of Open Access Journals (Sweden)

    Alexandrova Е.А.

    2010-12-01

    Full Text Available The research goal is to investigate the mechanisms of formation and peculiarities of periodontitis in patients with focal tuberculosis. Patients with periodontitis and focal tuberculosis are proved to develop local inflammatory reaction with increased infection and activation of proinflammatory cytokines in parodontal pockets fluid. The main risk factor of frequent and durable recurrence of parodontal pathology in case of focal tuberculosis was the development of pathologic process as a cause of disbalance of lipid peroxidation and antioxidant system, endotoxicosis syndrome

  15. Magnetic electroanatomical mapping for ablation of focal atrial tachycardias.

    Science.gov (United States)

    Marchlinski, F; Callans, D; Gottlieb, C; Rodriguez, E; Coyne, R; Kleinman, D

    1998-08-01

    Uniform success for ablation of focal atrial tachycardias has been difficult to achieve using standard catheter mapping and ablation techniques. In addition, our understanding of the complex relationship between atrial anatomy, electrophysiology, and surface ECG P wave morphology remains primitive. The magnetic electroanatomical mapping and display system (CARTO) offers an on-line display of electrical activation and/or signal amplitude related to the anatomical location of the recorded sites in the mapped chamber. A window of electrical interest is established based on signals timed from an electrical reference that usually represents a fixed electrogram recording from the coronary sinus or the atrial appendage. This window of electrical interest is established to include atrial activation prior to the onset of the P wave activity associated with the site of origin of a focal atrial tachycardia. Anatomical and electrical landmarks are defined with limited fluoroscopic imaging support and more detailed global chamber and more focal atrial mapping can be performed with minimal fluoroscopic guidance. A three-dimensional color map representing atrial activation or voltage amplitude at the magnetically defined anatomical sites is displayed with on-line data acquisition. This display can be manipulated to facilitate viewing from any angle. Altering the zoom control, triangle fill threshold, clipping plane, or color range can all enhance the display of a more focal area of interest. We documented the feasibility of using this single mapping catheter technique for localizing and ablating focal atrial tachycardias. In a consecutive series of 8 patients with 9 focal atrial tachycardias, the use of the single catheter CARTO mapping system was associated with ablation success in all but one patient who had a left atrial tachycardia localized to the medial aspect of the orifice of the left atrial appendage. Only low power energy delivery was used in this patient because of the

  16. Flux dynamics in ultrasensitive superconducting focal planes

    Data.gov (United States)

    National Aeronautics and Space Administration — The performance of superconducting focal planes will drive the achievable specifications of ultrasensitive instruments for NASA astrophysics missions, yet they have...

  17. Physics of adhesion

    International Nuclear Information System (INIS)

    Gerberich, W W; Cordill, M J

    2006-01-01

    Adhesion physics was relegated to the lowest echelons of academic pursuit until the advent of three seemingly disconnected events. The first, atomic force microscopy (AFM), eventually allowed fine-scale measurement of adhesive point contacts. The second, large-scale computational materials science, now permits both hierarchical studies of a few thousand atoms from first principles or of billions of atoms with less precise interatomic potentials. The third is a microelectronics industry push towards the nanoscale which has provided the driving force for requiring a better understanding of adhesion physics. In the present contribution, an attempt is made at conjoining these separate events into an updating of how theoretical and experimental approaches are providing new understanding of adhesion physics. While all material couples are briefly considered, the emphasis is on metal/semiconductor and metal/ceramic interfaces. Here, adhesion energies typically range from 1 to 100 J m -2 where the larger value is considered a practical work of adhesion. Experimental emphasis is on thin-film de-adhesion for 10 to 1000 nm thick films. For comparison, theoretical approaches from first principles quantum mechanics to embedded atom methods used in multi-scale modelling are utilized

  18. Game Movement as Enactive Focalization

    Directory of Open Access Journals (Sweden)

    Yotam Shibolet

    2018-01-01

    Full Text Available This paper integrates thought on game narrative and embodied cognition, in order to consider the significance of movement to the embodied narrative experience of games. If games are a mode of ‘environmental storytelling’, determining the player’s mobile situatedness within the gamespace is of crucial importance. The metaphor of game design as narrative architecture should be expanded to include te the design of movement dynamics, alongside geographical gamespace. I suggest a theoretical infrastructure that aims to enable further analysis of movement design’s role in this scope. The theory of enactive perception asserts that all perception is inherently negotiated through embodied understanding of moving within environment. According to this model, by giving meaning to perception, movement is also directly related to the structure of consciousness and thought. Cognitive definitions of ‘narrative’ that integrate embodiment are applied to argue it can relevantly account for part of thought’s role in enactive perception. Mieke Bal’s concept of focalization (1997 broaches narrative perspective by underscoring the constant “movement of the look”. For enactive perception, such mobility should be understood as inseparable from the movement of the body even when perspective could appear detached from embodiment. Therefore, I offer the supplementary concept of “enactive focalization” – narrative perception as interpreted through the interconnected dynamics or perspectival and physical movement. To exemplify my ideas and the potential of future research in this scope, I discuss the uniquely effective and affective movement dynamic design of Journey. This paper concludes by reflecting on enactive focalization in light of the increased utilization of embodiment in the contemporary digital media landscape.

  19. The bio-complex "reaction pattern in vertebrate cells" reduces cytokine-induced cellular adhesion molecule mRNA expression in human endothelial cells by attenuation of NF-kappaB translocation.

    Science.gov (United States)

    Rönnau, Cindy; Liebermann, Herbert E H; Helbig, Franz; Staudt, Alexander; Felix, Stephan B; Ewert, Ralf; Landsberger, Martin

    2009-02-28

    The bio-complex "reaction pattern in vertebrate cells" (RiV) is mainly represented by characteristic exosome-like particles--probably as reaction products of cells to specific stress. The transcription factor NF-kappaB plays a central role in inflammation. We tested the hypothesis that RiV particle preparations (RiV-PP) reduce cellular adhesion molecule (CAM) expression (ICAM-1, VCAM-1, E-selectin) by the attenuation of NF-kappaB translocation in human umbilical vein endothelial cells (HUVEC). After 4 hours, pre-incubation of HUVEC with RiV-PP before stimulation with TNF-alpha significantly reduced ICAM-1 (65.5+/-10.3%) and VCAM-1 (71.1+/-12.3%) mRNA expression compared to TNF-alpha-treated cells (100%, n=7). ICAM-1 surface expression was significantly albeit marginally reduced in RiV/TNF-alpha- treated cells (92.0+/-5.6%, n=4). No significant effect was observed on VCAM-1 surface expression. In RiV/TNF-alpha-treated cells (n=4), NF-kappaB subunits p50 (85.7+/-4.1%) and p65 (85.0+/-1.8%) nuclear translocation was significantly reduced. RiV-PP may exert an anti-inflammatory effect in HUVEC by reducing CAM mRNA expression via attenuation of p50 and p65 translocation.

  20. EB curable laminating adhesives

    International Nuclear Information System (INIS)

    Matsuyama, Asao; Kobayashi, Masahide; Gotoh, Sakiko

    1992-01-01

    New developed solvent free EB curable laminating adhesives have two liquid components, A with hydroxy and acryloyl group, B with isocyanate and acryloyl group in a molecule. These EB laminating adhesives do not need any aging process, which is a big advantage, and are very suitable for environment, safety, and health because of no heating process and solvent free formulas. And we have made basic research about the relation of peel strength or heat seal strength versus Tg of cured film, elongation at break, elastic modulus, and so on. Basic specifications of the new developed adhesives are shown. (author)

  1. Position sensitive proportional counters as focal plane detectors

    International Nuclear Information System (INIS)

    Ford, J.L.C. Jr.

    1979-01-01

    The rise time and charge division techniques for position decoding with RC-line proportional counters are reviewed. The advantages that these detectors offer as focal plane counters for nuclear spectroscopy performed with magnetic spectrographs are discussed. The theory of operation of proportional counters as position sensing devices is summarized, as well as practical aspects affecting their application. Factors limiting the position and energy resolutions obtainable with a focal plane proportional counter are evaluated and measured position and energy loss values are presented for comparison. Detector systems capable of the multiparameter measurements required for particle identification, background suppression and ray-tracing are described in order to illustrate the wide applicability of proportional counters within complex focal plane systems. Examples of the use of these counters other than with magnetic spectrographs are given in order to demonstrate their usefulness in not only nuclear physics but also in fields such as solid state physics, biology, and medicine. The influence of the new focal plane detector systems on future magnetic spectrograph designs is discussed. (Auth.)

  2. A contractile and counterbalancing adhesion system controls the 3D shape of crawling cells.

    Science.gov (United States)

    Burnette, Dylan T; Shao, Lin; Ott, Carolyn; Pasapera, Ana M; Fischer, Robert S; Baird, Michelle A; Der Loughian, Christelle; Delanoe-Ayari, Helene; Paszek, Matthew J; Davidson, Michael W; Betzig, Eric; Lippincott-Schwartz, Jennifer

    2014-04-14

    How adherent and contractile systems coordinate to promote cell shape changes is unclear. Here, we define a counterbalanced adhesion/contraction model for cell shape control. Live-cell microscopy data showed a crucial role for a contractile meshwork at the top of the cell, which is composed of actin arcs and myosin IIA filaments. The contractile actin meshwork is organized like muscle sarcomeres, with repeating myosin II filaments separated by the actin bundling protein α-actinin, and is mechanically coupled to noncontractile dorsal actin fibers that run from top to bottom in the cell. When the meshwork contracts, it pulls the dorsal fibers away from the substrate. This pulling force is counterbalanced by the dorsal fibers' attachment to focal adhesions, causing the fibers to bend downward and flattening the cell. This model is likely to be relevant for understanding how cells configure themselves to complex surfaces, protrude into tight spaces, and generate three-dimensional forces on the growth substrate under both healthy and diseased conditions.

  3. Optical adhesive property study

    Energy Technology Data Exchange (ETDEWEB)

    Sundvold, P.D.

    1996-01-01

    Tests were performed to characterize the mechanical and thermal properties of selected optical adhesives to identify the most likely candidate which could survive the operating environment of the Direct Optical Initiation (DOI) program. The DOI system consists of a high power laser and an optical module used to split the beam into a number of channels to initiate the system. The DOI requirements are for a high shock environment which current military optical systems do not operate. Five candidate adhesives were selected and evaluated using standardized test methods to determine the adhesives` physical properties. EC2216, manufactured by 3M, was selected as the baseline candidate adhesive based on the test results of the physical properties.

  4. Repeated origin and loss of adhesive toepads in geckos.

    Directory of Open Access Journals (Sweden)

    Tony Gamble

    Full Text Available Geckos are well known for their extraordinary clinging abilities and many species easily scale vertical or even inverted surfaces. This ability is enabled by a complex digital adhesive mechanism (adhesive toepads that employs van der Waals based adhesion, augmented by frictional forces. Numerous morphological traits and behaviors have evolved to facilitate deployment of the adhesive mechanism, maximize adhesive force and enable release from the substrate. The complex digital morphologies that result allow geckos to interact with their environment in a novel fashion quite differently from most other lizards. Details of toepad morphology suggest multiple gains and losses of the adhesive mechanism, but lack of a comprehensive phylogeny has hindered efforts to determine how frequently adhesive toepads have been gained and lost. Here we present a multigene phylogeny of geckos, including 107 of 118 recognized genera, and determine that adhesive toepads have been gained and lost multiple times, and remarkably, with approximately equal frequency. The most likely hypothesis suggests that adhesive toepads evolved 11 times and were lost nine times. The overall external morphology of the toepad is strikingly similar in many lineages in which it is independently derived, but lineage-specific differences are evident, particularly regarding internal anatomy, with unique morphological patterns defining each independent derivation.

  5. Repeated origin and loss of adhesive toepads in geckos.

    Science.gov (United States)

    Gamble, Tony; Greenbaum, Eli; Jackman, Todd R; Russell, Anthony P; Bauer, Aaron M

    2012-01-01

    Geckos are well known for their extraordinary clinging abilities and many species easily scale vertical or even inverted surfaces. This ability is enabled by a complex digital adhesive mechanism (adhesive toepads) that employs van der Waals based adhesion, augmented by frictional forces. Numerous morphological traits and behaviors have evolved to facilitate deployment of the adhesive mechanism, maximize adhesive force and enable release from the substrate. The complex digital morphologies that result allow geckos to interact with their environment in a novel fashion quite differently from most other lizards. Details of toepad morphology suggest multiple gains and losses of the adhesive mechanism, but lack of a comprehensive phylogeny has hindered efforts to determine how frequently adhesive toepads have been gained and lost. Here we present a multigene phylogeny of geckos, including 107 of 118 recognized genera, and determine that adhesive toepads have been gained and lost multiple times, and remarkably, with approximately equal frequency. The most likely hypothesis suggests that adhesive toepads evolved 11 times and were lost nine times. The overall external morphology of the toepad is strikingly similar in many lineages in which it is independently derived, but lineage-specific differences are evident, particularly regarding internal anatomy, with unique morphological patterns defining each independent derivation.

  6. Bioinspired pressure actuated adhesive system

    NARCIS (Netherlands)

    Paretkar, D.R.; Kamperman, M.M.G.; Schneider, A.S.; Martina, D.; Creton, C.; Arzt, E.

    2011-01-01

    We developed a dry synthetic adhesive system inspired by gecko feet adhesion that can switch reversibly from adhesion to non-adhesion with applied pressure as external stimulus. Micropatterned polydimethylsiloxane (PDMS) surfaces with pillars of 30 µm length and 10 µm diameter were fabricated using

  7. Many Roles of Wood Adhesives

    Science.gov (United States)

    Charles R. Frihart

    2014-01-01

    Although wood bonding is one of the oldest applications of adhesives, going back to early recorded history (1), some aspects of wood bonds are still not fully understood. Most books in the general area of adhesives and adhesion do not cover wood bonding. However, a clearer understanding of wood bonding and wood adhesives can lead to improved products. This is important...

  8. Cohesion and Adhesion with Proteins

    Science.gov (United States)

    Charles R. Frihart

    2016-01-01

    With increasing interest in bio-based adhesives, research on proteins has expanded because historically they have been used by both nature and humans as adhesives. A wide variety of proteins have been used as wood adhesives. Ancient Egyptians most likely used collagens tobond veneer to wood furniture, then came casein (milk), blood, fish scales, and soy adhesives, with...

  9. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jung Kyu; Cho, Jeong Yeon; Lee, Young Ho; Kim, Ei Jeong; Chun, Yi Kyeong [Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-09-15

    Focal musculoskeletal anomalies are various and may be an isolated finding or may be found in conjunction with numerous associations, including genetic syndromes, Karyotype abnormals, central nervous system anomalies and other general musculoskeletal disorders. Early prenatal diagnosis of these focal musculoskeletal anomalies nor only affects prenatal care and postnatal outcome but also helps in approaching other numerous associated anomalies.

  10. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    International Nuclear Information System (INIS)

    Ryu, Jung Kyu; Cho, Jeong Yeon; Lee, Young Ho; Kim, Ei Jeong; Chun, Yi Kyeong

    2002-01-01

    Focal musculoskeletal anomalies are various and may be an isolated finding or may be found in conjunction with numerous associations, including genetic syndromes, Karyotype abnormals, central nervous system anomalies and other general musculoskeletal disorders. Early prenatal diagnosis of these focal musculoskeletal anomalies nor only affects prenatal care and postnatal outcome but also helps in approaching other numerous associated anomalies.

  11. Early vision and focal attention

    Science.gov (United States)

    Julesz, Bela

    1991-07-01

    At the thirty-year anniversary of the introduction of the technique of computer-generated random-dot stereograms and random-dot cinematograms into psychology, the impact of the technique on brain research and on the study of artificial intelligence is reviewed. The main finding-that stereoscopic depth perception (stereopsis), motion perception, and preattentive texture discrimination are basically bottom-up processes, which occur without the help of the top-down processes of cognition and semantic memory-greatly simplifies the study of these processes of early vision and permits the linking of human perception with monkey neurophysiology. Particularly interesting are the unexpected findings that stereopsis (assumed to be local) is a global process, while texture discrimination (assumed to be a global process, governed by statistics) is local, based on some conspicuous local features (textons). It is shown that the top-down process of "shape (depth) from shading" does not affect stereopsis, and some of the models of machine vision are evaluated. The asymmetry effect of human texture discrimination is discussed, together with recent nonlinear spatial filter models and a novel extension of the texton theory that can cope with the asymmetry problem. This didactic review attempts to introduce the physicist to the field of psychobiology and its problems-including metascientific problems of brain research, problems of scientific creativity, the state of artificial intelligence research (including connectionist neural networks) aimed at modeling brain activity, and the fundamental role of focal attention in mental events.

  12. Dry adhesives with sensing features

    International Nuclear Information System (INIS)

    Krahn, J; Menon, C

    2013-01-01

    Geckos are capable of detecting detachment of their feet. Inspired by this basic observation, a novel functional dry adhesive is proposed, which can be used to measure the instantaneous forces and torques acting on an adhesive pad. Such a novel sensing dry adhesive could potentially be used by climbing robots to quickly realize and respond appropriately to catastrophic detachment conditions. The proposed torque and force sensing dry adhesive was fabricated by mixing Carbon Black (CB) and Polydimethylsiloxane (PDMS) to form a functionalized adhesive with mushroom caps. The addition of CB to PDMS resulted in conductive PDMS which, when under compression, tension or torque, resulted in a change in the resistance across the adhesive patch terminals. The proposed design of the functionalized dry adhesive enables distinguishing an applied torque from a compressive force in a single adhesive pad. A model based on beam theory was used to predict the change in resistance across the terminals as either a torque or compressive force was applied to the adhesive patch. Under a compressive force, the sensing dry adhesive was capable of measuring compression stresses from 0.11 Pa to 20.9 kPa. The torque measured by the adhesive patch ranged from 2.6 to 10 mN m, at which point the dry adhesives became detached. The adhesive strength was 1.75 kPa under an applied preload of 1.65 kPa for an adhesive patch with an adhesive contact area of 7.07 cm 2 . (paper)

  13. Dry adhesives with sensing features

    Science.gov (United States)

    Krahn, J.; Menon, C.

    2013-08-01

    Geckos are capable of detecting detachment of their feet. Inspired by this basic observation, a novel functional dry adhesive is proposed, which can be used to measure the instantaneous forces and torques acting on an adhesive pad. Such a novel sensing dry adhesive could potentially be used by climbing robots to quickly realize and respond appropriately to catastrophic detachment conditions. The proposed torque and force sensing dry adhesive was fabricated by mixing Carbon Black (CB) and Polydimethylsiloxane (PDMS) to form a functionalized adhesive with mushroom caps. The addition of CB to PDMS resulted in conductive PDMS which, when under compression, tension or torque, resulted in a change in the resistance across the adhesive patch terminals. The proposed design of the functionalized dry adhesive enables distinguishing an applied torque from a compressive force in a single adhesive pad. A model based on beam theory was used to predict the change in resistance across the terminals as either a torque or compressive force was applied to the adhesive patch. Under a compressive force, the sensing dry adhesive was capable of measuring compression stresses from 0.11 Pa to 20.9 kPa. The torque measured by the adhesive patch ranged from 2.6 to 10 mN m, at which point the dry adhesives became detached. The adhesive strength was 1.75 kPa under an applied preload of 1.65 kPa for an adhesive patch with an adhesive contact area of 7.07 cm2.

  14. Relation between second-order moment radius of focal spot and near field distribution of laser beam

    International Nuclear Information System (INIS)

    Gao Xueyan; Su Yi; Ye Yidong; Guan Youguang

    2011-01-01

    In order to analyze the effect of aberration of amplitude and phase of laser beam on second-order moment radius of focal spot, based on the Fraunhofer formula for light wave scalar diffraction theory and the definition of second-order moment radius, the general expression for focal spot second-order moment radius depending on the complex amplitude of near field is derived. The second-order moment radius of the focal spot depending on intensity distribution and phase distribution of near field is derived, and its clear physical meaning is described. The second-order moment radius and the divergence angle of focal spot may be easily calculated with the second-order moment radius expression of focal spot. At last, the divergence angles of focal spots of several kinds of Gaussian laser beams are calculated directly, and the results are in accordance with those in the related references. (authors)

  15. Do focal colors look particularly "colorful"?

    Science.gov (United States)

    Witzel, Christoph; Franklin, Anna

    2014-04-01

    If the most typical red, yellow, green, and blue were particularly colorful (i.e., saturated), they would "jump out to the eye." This would explain why even fundamentally different languages have distinct color terms for these focal colors, and why unique hues play a prominent role in subjective color appearance. In this study, the subjective saturation of 10 colors around each of these focal colors was measured through a pairwise matching task. Results show that subjective saturation changes systematically across hues in a way that is strongly correlated to the visual gamut, and exponentially related to sensitivity but not to focal colors.

  16. Proteomic analysis of the dysferlin protein complex unveils its importance for sarcolemmal maintenance and integrity.

    Directory of Open Access Journals (Sweden)

    Antoine de Morrée

    Full Text Available Dysferlin is critical for repair of muscle membranes after damage. Mutations in dysferlin lead to a progressive muscular dystrophy. Recent studies suggest additional roles for dysferlin. We set out to study dysferlin's protein-protein interactions to obtain comprehensive knowledge of dysferlin functionalities in a myogenic context. We developed a robust and reproducible method to isolate dysferlin protein complexes from cells and tissue. We analyzed the composition of these complexes in cultured myoblasts, myotubes and skeletal muscle tissue by mass spectrometry and subsequently inferred potential protein functions through bioinformatics analyses. Our data confirm previously reported interactions and support a function for dysferlin as a vesicle trafficking protein. In addition novel potential functionalities were uncovered, including phagocytosis and focal adhesion. Our data reveal that the dysferlin protein complex has a dynamic composition as a function of myogenic differentiation. We provide additional experimental evidence and show dysferlin localization to, and interaction with the focal adhesion protein vinculin at the sarcolemma. Finally, our studies reveal evidence for cross-talk between dysferlin and its protein family member myoferlin. Together our analyses show that dysferlin is not only a membrane repair protein but also important for muscle membrane maintenance and integrity.

  17. Focal pancreatic enlargement: differentiation between pancreatic adenocarcinoma and focal pancreatitis on CT and ERCP

    International Nuclear Information System (INIS)

    Kim, Eun Kyung; Kim, Ki Whang; Lee, Jong Tae; Kim, Hee Soo; Yoo, Hyung Sik; Yu, Jeong Sik; Yoon, Sang Wook

    1995-01-01

    To differentiate the pancreatic adenocarcinoma from focal pancreatitis on CT and ERCP in cases of focal pancreatic enlargement. We analysed CT findings of 66 patients of pancreatic adenocarcinoma (n = 45) or focal pancreatitis (n = 21) with respect to size, density, calcification, pancreatic or biliary duct dilatation, fat plane obliteration around the vessels, direction of retroperitoneal extension, lymphadenopathy, pseudocyst formation and atrophy of pancreas. ERCP available in 48 patients were analysed in respect to morphologic appearance of CBD and pancreatic duct, and distance between the two ducts. The patients in focal pancreatitis were younger with more common history of alcohol drinking. There was no statistical difference in calcifications of the mass (18% in the adenocarcinoma, 33% in the focal pancreatitis), but a tendency of denser, larger number of calcifications was noted in focal pancreatitis. The finding of fat plane obliteration around the vessels were more common in pancreatic adenocarcinoma, and fascial thickenings were more prominent in focal pancreatitis, although not statistically significant. On ERCP, there were no differential points of CBD, pancreatic duct morphology, but distance between the two ducts at the lesion center was more wider in focal pancreatitis. Differentiating focal pancreatitis from pancreatic adenocarcinoma is difficult. However, we should consider the possibility of focal pancreatitis in cases of patients with young age, having alcoholic history in association with CT findings of large numbers of and dense calcifications, and ERCP findings of prominent separation of two duct at the lesion center

  18. Electrically Conductive Epoxy Adhesives

    Directory of Open Access Journals (Sweden)

    Lan Bai

    2011-02-01

    Full Text Available Conductive adhesives are widely used in electronic packaging applications such as die attachment and solderless interconnections, component repair, display interconnections, and heat dissipation. The effects of film thickness as functions of filler volume fraction, conductive filler size, shape, as well as uncured adhesive matrix viscosity on the electrical conduction behavior of epoxy-based adhesives are presented in this work. For this purpose, epoxy-based adhesives were prepared using conductive fillers of different size, shape, and types, including Ni powder, flakes, and filaments, Ag powder, and Cu powder. The filaments were 20 μm in diameter, and 160 or 260 μm in length. HCl and H3PO4 acid solutions were used to etch and remove the surface oxide layers from the fillers. The plane resistance of filled adhesive films was measured using the four-point method. In all cases of conductive filler addition, the planar resistivity levels for the composite adhesive films increased when the film thickness was reduced. The shape of resistivity-thickness curves was negative exponential decaying type and was modeled using a mathematical relation. The relationships between the conductive film resistivities and the filler volume fractions were also derived mathematically based on the experimental data. Thus, the effects of surface treatment of filler particles, the type, size, shape of fillers, and the uncured epoxy viscosity could be included empirically by using these mathematical relations based on the experimental data. By utilizing the relations we proposed to model thickness-dependent and volume fraction-dependent conduction behaviors separately, we were able to describe the combined and coupled volume fraction-film thickness relationship mathematically based on our experimental data.

  19. Reversible adhesion switching of porous fibrillar adhesive pads by humidity.

    Science.gov (United States)

    Xue, Longjian; Kovalev, Alexander; Dening, Kirstin; Eichler-Volf, Anna; Eickmeier, Henning; Haase, Markus; Enke, Dirk; Steinhart, Martin; Gorb, Stanislav N

    2013-01-01

    We report reversible adhesion switching on porous fibrillar polystyrene-block-poly(2-vinyl pyridine) (PS-b-P2VP) adhesive pads by humidity changes. Adhesion at a relative humidity of 90% was more than nine times higher than at a relative humidity of 2%. On nonporous fibrillar adhesive pads of the same material, adhesion increased only by a factor of ~3.3. The switching performance remained unchanged in at least 10 successive high/low humidity cycles. Main origin of enhanced adhesion at high humidity is the humidity-induced decrease in the elastic modulus of the polar component P2VP rather than capillary force. The presence of spongelike continuous internal pore systems with walls consisting of P2VP significantly leveraged this effect. Fibrillar adhesive pads on which adhesion is switchable by humidity changes may be used for preconcentration of airborne particulates, pollutants, and germs combined with triggered surface cleaning.

  20. Focal skin defect, limb anomalies and microphthalmia.

    NARCIS (Netherlands)

    Jackson, K.E.; Andersson, H.C.

    2004-01-01

    We describe two unrelated female patients with congenital single focal skin defects, unilateral microphthalmia and limb anomalies. Growth and psychomotor development were normal and no brain malformation was detected. Although eye and limb anomalies are commonly associated, clinical anophthalmia and

  1. Genetics Home Reference: focal dermal hypoplasia

    Science.gov (United States)

    ... in people with focal dermal hypoplasia is an omphalocele , which is an opening in the wall of ... Dermal Hypoplasia MedlinePlus Encyclopedia: Ectodermal dysplasia MedlinePlus Encyclopedia: Omphalocele General Information from MedlinePlus (5 links) Diagnostic Tests ...

  2. Focal lesions in the central nervous system

    International Nuclear Information System (INIS)

    Fabrikant, J.I.; Budinger, T.F.; Tobias, C.A.; Born, J.L.

    1980-01-01

    This report reviews the animal and human studies currently in progress at LBL with heavy-ion beams to induce focal lesions in the central nervous system, and discusses the potential future prospects of fundamental and applied brain research with heavy-ion beams. Methods are being developed for producing discrete focal lesions in the central nervous system using the Bragg ionization peak to investigate nerve pathways and neuroendocrine responses, and for treating pathological disorders of the brain

  3. Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion

    Directory of Open Access Journals (Sweden)

    David G. Menter

    2012-01-01

    Full Text Available Prostaglandins exert a profound influence over the adhesive, migratory, and invasive behavior of cells during the development and progression of cancer. Cyclooxygenase-2 (COX-2 and microsomal prostaglandin E2 synthase-1 (mPGES-1 are upregulated in inflammation and cancer. This results in the production of prostaglandin E2 (PGE2, which binds to and activates G-protein-coupled prostaglandin E1-4 receptors (EP1-4. Selectively targeting the COX-2/mPGES-1/PGE2/EP1-4 axis of the prostaglandin pathway can reduce the adhesion, migration, invasion, and angiogenesis. Once stimulated by prostaglandins, cadherin adhesive connections between epithelial or endothelial cells are lost. This enables cells to invade through the underlying basement membrane and extracellular matrix (ECM. Interactions with the ECM are mediated by cell surface integrins by “outside-in signaling” through Src and focal adhesion kinase (FAK and/or “inside-out signaling” through talins and kindlins. Combining the use of COX-2/mPGES-1/PGE2/EP1-4 axis-targeted molecules with those targeting cell surface adhesion receptors or their downstream signaling molecules may enhance cancer therapy.

  4. Switchable Adhesion in Vacuum Using Bio-Inspired Dry Adhesives.

    Science.gov (United States)

    Purtov, Julia; Frensemeier, Mareike; Kroner, Elmar

    2015-11-04

    Suction based attachment systems for pick and place handling of fragile objects like glass plates or optical lenses are energy-consuming and noisy and fail at reduced air pressure, which is essential, e.g., in chemical and physical vapor deposition processes. Recently, an alternative approach toward reversible adhesion of sensitive objects based on bioinspired dry adhesive structures has emerged. There, the switching in adhesion is achieved by a reversible buckling of adhesive pillar structures. In this study, we demonstrate that these adhesives are capable of switching adhesion not only in ambient air conditions but also in vacuum. Our bioinspired patterned adhesive with an area of 1 cm(2) provided an adhesion force of 2.6 N ± 0.2 N in air, which was reduced to 1.9 N ± 0.2 N if measured in vacuum. Detachment was induced by buckling of the structures due to a high compressive preload and occurred, independent of air pressure, at approximately 0.9 N ± 0.1 N. The switch in adhesion was observed at a compressive preload between 5.6 and 6.0 N and was independent of air pressure. The difference between maximum adhesion force and adhesion force after buckling gives a reasonable window of operation for pick and place processes. High reversibility of the switching behavior is shown over 50 cycles in air and in vacuum, making the bioinspired switchable adhesive applicable for handling operations of fragile objects.

  5. Abnormal Cell Properties and Down-Regulated FAK-Src Complex Signaling in B Lymphoblasts of Autistic Subjects

    Science.gov (United States)

    Wei, Hongen; Malik, Mazhar; Sheikh, Ashfaq M.; Merz, George; Ted Brown, W.; Li, Xiaohong

    2011-01-01

    Recent studies suggest that one of the major pathways to the pathogenesis of autism is reduced cell migration. Focal adhesion kinase (FAK) has an important role in neural migration, dendritic morphological characteristics, axonal branching, and synapse formation. The FAK-Src complex, activated by upstream reelin and integrin β1, can initiate a cascade of phosphorylation events to trigger multiple intracellular pathways, including mitogen-activated protein kinase–extracellular signal–regulated kinase and phosphatidylinositol 3-kinase–Akt signaling. In this study, by using B lymphoblasts as a model, we tested whether integrin β1 and FAK-Src signaling are abnormally regulated in autism and whether abnormal FAK-Src signaling leads to defects in B-lymphoblast adhesion, migration, proliferation, and IgG production. To our knowledge, for the first time, we show that protein expression levels of both integrin β1 and FAK are significantly decreased in autistic lymphoblasts and that Src protein expression and the phosphorylation of an active site (Y416) are also significantly decreased. We also found that lymphoblasts from autistic subjects exhibit significantly decreased migration, increased adhesion properties, and an impaired capacity for IgG production. The overexpression of FAK in autistic lymphoblasts countered the adhesion and migration defects. In addition, we demonstrate that FAK mediates its effect through the activation of Src, phosphatidylinositol 3-kinase–Akt, and mitogen-activated protein kinase signaling cascades and that paxillin is also likely involved in the regulation of adhesion and migration in autistic lymphoblasts. PMID:21703394

  6. an Adhesive Patch

    Directory of Open Access Journals (Sweden)

    S. Mojtaba Taghizadeh

    2013-01-01

    Full Text Available Drug-in-adhesive transdermal drug delivery systems  TDDSs containing stimulants, termed as energetic substances, such as caffeine and pantothenic acid, were studied. Caffeine is a white crystalline substance and a stimulant to central nervous system. In humans, caffeine acts as a central nervous system stimulant, temporarily warding off drowsiness and restoring alertness. Pantothenic acid, also recognized as vitamin B5, is a water-soluble vitamin. For many animals, pantothenic acid is an essential nutrient. Animals require pantothenic acid to synthesize and metabolize proteins, carbohydrates and fats. For this purpose caffeine and pantothenic acid were  used  as  drug  components with  6.32%  and  1.12%  loadings,  in  different functional and non-functional acrylic pressure sensitive adhesives (PSAs of 52.89%, respectively. Ethylene glycol as a chemical enhancer was used in all TDDSs with 39.67%. The effect of PSAs  type on  in vitro  release and adhesion properties  (peel strength and tack values from drug delivery devices were evaluated. It was found that TDDS containing -COOH functional PSA showed  the  lowest steady state fux. The adhesion properties of the samples were improved by addition of functional acrylic PSA in formulations.

  7. Leukocyte adhesion deficiencies

    NARCIS (Netherlands)

    van de Vijver, Edith; van den Berg, Timo K.; Kuijpers, Taco W.

    2013-01-01

    During inflammation, leukocytes play a key role in maintaining tissue homeostasis through elimination of pathogens and removal of damaged tissue. Leukocytes migrate to the site of inflammation by crawling over and through the blood vessel wall, into the tissue. Leukocyte adhesion deficiencies (ie,

  8. Adhesive tape exfoliation

    DEFF Research Database (Denmark)

    Bohr, Jakob

    2015-01-01

    Single-crystal graphite can be cleaved by the use of an adhesive tape. This was also the initial route for obtaining graphene, a one-layer thick graphite slab. In this letter a few simple and fun considerations are presented in an attempt to shed some light on why this procedure is successful...

  9. Wood Composite Adhesives

    Science.gov (United States)

    Gomez-Bueso, Jose; Haupt, Robert

    The global environment, in which phenolic resins are being used for wood composite manufacture, has changed significantly during the last decade. This chapter reviews trends that are driving the use and consumption of phenolic resins around the world. The review begins with recent data on volume usage and regional trends, followed by an analysis of factors affecting global markets. In a section on environmental factors, the impact of recent formaldehyde emission regulations is discussed. The section on economics introduces wood composite production as it relates to the available adhesive systems, with special emphasis on the technical requirement to improve phenolic reactivity. Advances in composite process technology are introduced, especially in regard to the increased demands the improvements place upon adhesive system performance. The specific requirements for the various wood composite families are considered in the context of adhesive performance needs. The results of research into current chemistries are discussed, with a review of recent findings regarding the mechanisms of phenolic condensation and acceleration. Also, the work regarding alternate natural materials, such as carbohydrates, lignins, tannins, and proteinaceous materials, is presented. Finally, new developments in alternative adhesive technologies are reported.

  10. Focal lesions in the central nervous system: stereotaxic radioneurosurgery

    International Nuclear Information System (INIS)

    Fabrikant, J.I.; Budinger, T.f.; Hosobuchi, Y.; Born, J.L.; Tobias, C.A.

    1981-01-01

    The application of heavy-ion beams for fundamental and applied brain research has unusual potential. Methods are being developed in our laboratory for producing focal lesions in the central nervous system (e.g., the hypothalamus, thalamus, pituitary gland) to investigate nerve pathways and neuroendocrine responses, and for treating certain pathological disorders of the brain with stereotaxic Bragg peak heavy-ion radiosurgery. Studies in animals are demonstrating the value of this neuroscience tool for investigating mammalian brain response to induction of discrete focal lesions in the hypothalamus or in the cerebral cortex. These studies are also elucidating the neuroendocrinological response follwing ablation of various portions of the midbrain, without requiring complex neurosurgical preparations. Clinical studies are demonstrating the feasibility of stereotaxic neurological radiosurgery for treating certain inoperable vascular disorders of the brain [e.g., arteriovenous malformations (AVM), internal carotid artery-cavernous sinus fistulas and other cerebrovascular disorders] in patients who are already demonstrating progressive neurological deficit. Further applications of focal lesion production with the Bragg ionization peak can be extended to include localized radiation to centers of the brain and spinal cord for treatment of such disorders as Parkinson's disease, pituitary microadenomas, acoustic neuromas, and the control of pain. The eventual application of radioactive beams will provide accurate localization of the stopping points of the beam, thereby making it feasible to stop the beam accurately at a defined depth within the central nervous system

  11. Sighting optics including an optical element having a first focal length and a second focal length

    Science.gov (United States)

    Crandall, David Lynn [Idaho Falls, ID

    2011-08-01

    One embodiment of sighting optics according to the teachings provided herein may include a front sight and a rear sight positioned in spaced-apart relation. The rear sight includes an optical element having a first focal length and a second focal length. The first focal length is selected so that it is about equal to a distance separating the optical element and the front sight and the second focal length is selected so that it is about equal to a target distance. The optical element thus brings into simultaneous focus, for a user, images of the front sight and the target.

  12. Loss of laminin alpha 1 results in multiple structural defects and divergent effects on adhesion during vertebrate optic cup morphogenesis

    Science.gov (United States)

    Bryan, Chase D.; Chien, Chi-Bin; Kwan, Kristen M.

    2016-01-01

    The vertebrate eye forms via a complex set of morphogenetic events. The optic vesicle evaginates and undergoes transformative shape changes to form the optic cup, in which neural retina and retinal pigmented epithelium enwrap the lens. It has long been known that a complex, glycoprotein-rich extracellular matrix layer surrounds the developing optic cup throughout the process, yet the functions of the matrix and its specific molecular components have remained unclear. Previous work established a role for laminin extracellular matrix in particular steps of eye development, including optic vesicle evagination, lens differentiation, and retinal ganglion cell polarization, yet it is unknown what role laminin might play in the early process of optic cup formation subsequent to the initial step of optic vesicle evagination. Here, we use the zebrafish lama1 mutant (lama1UW1) to determine the function of laminin during optic cup morphogenesis. Using live imaging, we find, surprisingly, that loss of laminin leads to divergent effects on focal adhesion assembly in a spatiotemporally-specific manner, and that laminin is required for multiple steps of optic cup morphogenesis, including optic stalk constriction, invagination, and formation of a spherical lens. Laminin is not required for single cell behaviors and changes in cell shape. Rather, in lama1UW1 mutants, loss of epithelial polarity and altered adhesion lead to defective tissue architecture and formation of a disorganized retina. These results demonstrate that the laminin extracellular matrix plays multiple critical roles regulating adhesion and polarity to establish and maintain tissue structure during optic cup morphogenesis. PMID:27339294

  13. Adhesive bonding of wood materials

    Science.gov (United States)

    Charles B. Vick

    1999-01-01

    Adhesive bonding of wood components has played an essential role in the development and growth of the forest products industry and has been a key factor in the efficient utilization of our timber resource. The largest use of adhesives is in the construction industry. By far, the largest amounts of adhesives are used to manufacture building materials, such as plywood,...

  14. The selective role of ECM components on cell adhesion, morphology, proliferation and communication in vitro

    International Nuclear Information System (INIS)

    Schlie-Wolter, Sabrina; Ngezahayo, Anaclet; Chichkov, Boris N.

    2013-01-01

    Cell binding to the extracellular matrix (ECM) is essential for cell and tissue functions. In this context, each tissue consists of a unique ECM composition, which may be responsible for tissue-specific cell responses. Due to the complexity of ECM-cell interactions—which depend on the interplay of inside-out and outside-in signaling cascades, cell and tissue specificity of ECM-guidance is poorly understood. In this paper, we investigate the role of different ECM components like laminin, fibronectin, and collagen type I with respect to the essential cell behaviour patterns: attachment dynamics such as adhesion kinetic and force, formation of focal adhesion complexes, morphology, proliferation, and intercellular communication. A detailed in vitro comparison of fibroblasts, endothelial cells, osteoblasts, smooth muscle cells, and chondrocytes reveals significant differences in their cell responses to the ECM: cell behaviour follows a cell specific ligand priority ranking, which was independent of the cell type origin. Fibroblasts responded best to fibronectin, chondrocytes best to collagen I, the other cell types best to laminin. This knowledge is essential for optimization of tissue-biomaterial interfaces in all tissue engineering applications and gives insight into tissue-specific cell guidance. -- Highlights: • We analyse the impact of ECM components on cell behaviour in vitro. • We compare five different cell types, using the same culture conditions. • The ECM significantly guides all cell responses. • Cell behaviour follows a cell specific ligand-priority ranking. • This gives insight in tissue formation and is essential for biomedical applications

  15. The selective role of ECM components on cell adhesion, morphology, proliferation and communication in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Schlie-Wolter, Sabrina, E-mail: s.schlie@lzh.de [Laser Zentrum Hannover e.V., Hollerithallee 8, 30419 Hannover (Germany); Ngezahayo, Anaclet, E-mail: ngezahayo@biophysik.uni-hannover.de [Institute of Biophysics, Leibniz University Hannover, Herrenhäuser Str. 2, Hannover 30419 (Germany); Chichkov, Boris N., E-mail: b.chichkov@lzh.de [Laser Zentrum Hannover e.V., Hollerithallee 8, 30419 Hannover (Germany)

    2013-06-10

    Cell binding to the extracellular matrix (ECM) is essential for cell and tissue functions. In this context, each tissue consists of a unique ECM composition, which may be responsible for tissue-specific cell responses. Due to the complexity of ECM-cell interactions—which depend on the interplay of inside-out and outside-in signaling cascades, cell and tissue specificity of ECM-guidance is poorly understood. In this paper, we investigate the role of different ECM components like laminin, fibronectin, and collagen type I with respect to the essential cell behaviour patterns: attachment dynamics such as adhesion kinetic and force, formation of focal adhesion complexes, morphology, proliferation, and intercellular communication. A detailed in vitro comparison of fibroblasts, endothelial cells, osteoblasts, smooth muscle cells, and chondrocytes reveals significant differences in their cell responses to the ECM: cell behaviour follows a cell specific ligand priority ranking, which was independent of the cell type origin. Fibroblasts responded best to fibronectin, chondrocytes best to collagen I, the other cell types best to laminin. This knowledge is essential for optimization of tissue-biomaterial interfaces in all tissue engineering applications and gives insight into tissue-specific cell guidance. -- Highlights: • We analyse the impact of ECM components on cell behaviour in vitro. • We compare five different cell types, using the same culture conditions. • The ECM significantly guides all cell responses. • Cell behaviour follows a cell specific ligand-priority ranking. • This gives insight in tissue formation and is essential for biomedical applications.

  16. Transparent meta-analysis: does aging spare prospective memory with focal vs. non-focal cues?

    Directory of Open Access Journals (Sweden)

    Bob Uttl

    Full Text Available BACKGROUND: Prospective memory (ProM is the ability to become aware of a previously-formed plan at the right time and place. For over twenty years, researchers have been debating whether prospective memory declines with aging or whether it is spared by aging and, most recently, whether aging spares prospective memory with focal vs. non-focal cues. Two recent meta-analyses examining these claims did not include all relevant studies and ignored prevalent ceiling effects, age confounds, and did not distinguish between prospective memory subdomains (e.g., ProM proper, vigilance, habitual ProM (see Uttl, 2008, PLoS ONE. The present meta-analysis focuses on the following questions: Does prospective memory decline with aging? Does prospective memory with focal vs. non-focal cues decline with aging? Does the size of age-related declines with focal vs. non-focal cues vary across ProM subdomains? And are age-related declines in ProM smaller than age-related declines in retrospective memory? METHODS AND FINDINGS: A meta-analysis of event-cued ProM using data visualization and modeling, robust count methods, and conventional meta-analysis techniques revealed that first, the size of age-related declines in ProM with both focal and non-focal cues are large. Second, age-related declines in ProM with focal cues are larger in ProM proper and smaller in vigilance. Third, age-related declines in ProM proper with focal cues are as large as age-related declines in recall measures of retrospective memory. CONCLUSIONS: The results are consistent with Craik's (1983 proposal that age-related declines on ProM tasks are generally large, support the distinction between ProM proper vs. vigilance, and directly contradict widespread claims that ProM, with or without focal cues, is spared by aging.

  17. Focal thyroid inferno” on color Doppler ultrasonography: A specific feature of focal Hashimoto's thyroiditis

    International Nuclear Information System (INIS)

    Fu, Xianshui; Guo, Limei; Zhang, Huabin; Ran, Weiqiang; Fu, Peng; Li, Zhiqiang; Chen, Wen; Jiang, Ling; Wang, Jinrui; Jia, Jianwen

    2012-01-01

    Purpose: To evaluate color-Doppler features predictive of focal Hashimoto's thyroiditis. Materials and methods: A total of 521 patients with 561 thyroid nodules that underwent surgeries or gun biopsies were included in this study. These nodules were divided into three groups: focal Hashimoto's thyroiditis (104 nodules in 101 patients), benignity other than focal Hashimoto's thyroiditis (73 nodules in 70 patients), and malignancy (358 nodules in 350 patients). On color Doppler sonography, four vascularity types were determined as: hypovascularity, marked internal flow, marked peripheral flow and focal thyroid inferno. The χ 2 test was performed to seek the potential vascularity type with the predictive ability of certain thyroid pathology. Furthermore, the gray-scale features of each nodule were also studied. Results: The vascularity type I (hypovascularity) was more often seen in focal Hashimoto's thyroiditis than other benignity and malignancy (46% vs. 20.5% and 19%). While the type II (marked internal flow) showed the opposite tendency (26.9% [focal Hashimoto's thyroiditis] vs. 45.2% [other benignity] and 52.8% [malignancy]). However, type III (marked peripheral flow) was unable to predict any thyroid pathology. Importantly, type IV (focal thyroid inferno) was exclusive to focal Hashimoto's thyroiditis. All 8 type IV nodules appeared to be solid, hypoechoic, and well-defined. Using “focal thyroid inferno” as an indicator of FHT, the diagnostic sensitivity and specificity were 7.7% and 100% respectively. Conclusions: The vascularity type of “focal thyroid inferno” is specific for focal Hashimoto thyroiditis. Recognition of this particular feature may avoid unnecessary interventional procedures for some solid hypoechoic thyroid nodules suspicious of malignancy.

  18. Redundant control of migration and adhesion by ERM proteins in vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Baeyens, Nicolas; Latrache, Iman; Yerna, Xavier; Noppe, Gauthier; Horman, Sandrine; Morel, Nicole

    2013-01-01

    Highlights: •The three ERM proteins are expressed in vascular smooth muscle cell. •ERM depletion inhibited PDGF-evoked migration redundantly. •ERM depletion increased cell adhesion redundantly. •ERM depletion did not affect PDGF-evoked Ca signal, Rac1 activation, proliferation. •ERM proteins control PDGF-induced migration by regulating adhesion. -- Abstract: Ezrin, radixin, and moesin possess a very similar structure with a C-terminal actin-binding domain and a N-terminal FERM interacting domain. They are known to be involved in cytoskeleton organization in several cell types but their function in vascular smooth muscle cells (VSMC) is still unknown. The aim of this study was to investigate the role of ERM proteins in cell migration induced by PDGF, a growth factor involved in pathophysiological processes like angiogenesis or atherosclerosis. We used primary cultured VSMC obtained from rat aorta, which express the three ERM proteins. Simultaneous depletion of the three ERM proteins with specific siRNAs abolished the effects of PDGF on cell architecture and migration and markedly increased cell adhesion and focal adhesion size, while these parameters were only slightly affected by depletion of ezrin, radixin or moesin alone. Rac1 activation, cell proliferation, and Ca 2+ signal in response to PDGF were unaffected by ERM depletion. These results indicate that ERM proteins exert a redundant control on PDGF-induced VSMC migration by regulating focal adhesion turn-over and cell adhesion to substrate

  19. Micro–adhesion rings surrounding TCR microclusters are essential for T cell activation

    Science.gov (United States)

    Sakuma, Machie; Yokosuka, Tadashi

    2016-01-01

    The immunological synapse (IS) formed at the interface between T cells and antigen-presenting cells represents a hallmark of initiation of acquired immunity. T cell activation is initiated at T cell receptor (TCR) microclusters (MCs), in which TCRs and signaling molecules assemble at the interface before IS formation. We found that each TCR-MC was transiently bordered by a ring structure made of integrin and focal adhesion molecules in the early phase of activation, which is similar in structure to the IS in microscale. The micro–adhesion ring is composed of LFA-1, focal adhesion molecules paxillin and Pyk2, and myosin II (MyoII) and is supported by F-actin core and MyoII activity through LFA-1 outside-in signals. The formation of the micro–adhesion ring was transient but especially sustained upon weak TCR stimulation to recruit linker for activation of T cells (LAT) and SLP76. Perturbation of the micro–adhesion ring induced impairment of TCR-MC development and resulted in impaired cellular signaling and cell functions. Thus, the synapse-like structure composed of the core TCR-MC and surrounding micro–adhesion ring is a critical structure for initial T cell activation through integrin outside-in signals. PMID:27354546

  20. Redundant control of migration and adhesion by ERM proteins in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Baeyens, Nicolas; Latrache, Iman; Yerna, Xavier [Laboratory of Cell Physiology, IoNS, Université Catholique de Louvain (Belgium); Noppe, Gauthier; Horman, Sandrine [Pôle de Recherche Cardiovasculaire, IREC, Université Catholique de Louvain (Belgium); Morel, Nicole, E-mail: nicole.morel@uclouvain.be [Laboratory of Cell Physiology, IoNS, Université Catholique de Louvain (Belgium)

    2013-11-22

    Highlights: •The three ERM proteins are expressed in vascular smooth muscle cell. •ERM depletion inhibited PDGF-evoked migration redundantly. •ERM depletion increased cell adhesion redundantly. •ERM depletion did not affect PDGF-evoked Ca signal, Rac1 activation, proliferation. •ERM proteins control PDGF-induced migration by regulating adhesion. -- Abstract: Ezrin, radixin, and moesin possess a very similar structure with a C-terminal actin-binding domain and a N-terminal FERM interacting domain. They are known to be involved in cytoskeleton organization in several cell types but their function in vascular smooth muscle cells (VSMC) is still unknown. The aim of this study was to investigate the role of ERM proteins in cell migration induced by PDGF, a growth factor involved in pathophysiological processes like angiogenesis or atherosclerosis. We used primary cultured VSMC obtained from rat aorta, which express the three ERM proteins. Simultaneous depletion of the three ERM proteins with specific siRNAs abolished the effects of PDGF on cell architecture and migration and markedly increased cell adhesion and focal adhesion size, while these parameters were only slightly affected by depletion of ezrin, radixin or moesin alone. Rac1 activation, cell proliferation, and Ca{sup 2+} signal in response to PDGF were unaffected by ERM depletion. These results indicate that ERM proteins exert a redundant control on PDGF-induced VSMC migration by regulating focal adhesion turn-over and cell adhesion to substrate.

  1. Parietal Epithelial Cells Participate in the Formation of Sclerotic Lesions in Focal Segmental Glomerulosclerosis

    Science.gov (United States)

    Smeets, Bart; Kuppe, Christoph; Sicking, Eva-Maria; Fuss, Astrid; Jirak, Peggy; van Kuppevelt, Toin H.; Endlich, Karlhans; Wetzels, Jack F.M.; Gröne, Hermann-Josef; Floege, Jürgen

    2011-01-01

    The pathogenesis of the development of sclerotic lesions in focal segmental glomerulosclerosis (FSGS) remains unknown. Here, we selectively tagged podocytes or parietal epithelial cells (PECs) to determine whether PECs contribute to sclerosis. In three distinct models of FSGS (5/6-nephrectomy + DOCA-salt; the murine transgenic chronic Thy1.1 model; or the MWF rat) and in human biopsies, the primary injury to induce FSGS associated with focal activation of PECs and the formation of cellular adhesions to the capillary tuft. From this entry site, activated PECs invaded the affected segment of the glomerular tuft and deposited extracellular matrix. Within the affected segment, podocytes were lost and mesangial sclerosis developed within the endocapillary compartment. In conclusion, these results demonstrate that PECs contribute to the development and progression of the sclerotic lesions that define FSGS, but this pathogenesis may be relevant to all etiologies of glomerulosclerosis. PMID:21719782

  2. Cell Adhesion on RGD-Displaying Knottins with Varying Numbers of Tryptophan Amino Acids to Tune the Affinity for Assembly on Cucurbit[8]uril Surfaces.

    Science.gov (United States)

    Sankaran, Shrikrishnan; Cavatorta, Emanuela; Huskens, Jurriaan; Jonkheijm, Pascal

    2017-09-05

    Cell adhesion is studied on multivalent knottins, displaying RGD ligands with a high affinity for integrin receptors, that are assembled on CB[8]-methylviologen-modified surfaces. The multivalency in the knottins stems from the number of tryptophan amino acid moieties, between 0 and 4, that can form a heteroternary complex with cucurbit[8]uril (CB[8]) and surface-tethered methylviologen (MV 2+ ). The binding affinity of the knottins with CB[8] and MV 2+ surfaces was evaluated using surface plasmon resonance spectroscopy. Specific binding occurred, and the affinity increased with the valency of tryptophans on the knottin. Additionally, increased multilayer formation was observed, attributed to homoternary complex formation between tryptophan residues of different knottins and CB[8]. Thus, we were able to control the surface coverage of the knottins by valency and concentration. Cell experiments with mouse myoblast (C2C12) cells on the self-assembled knottin surfaces showed specific integrin recognition by the RGD-displaying knottins. Moreover, cells were observed to elongate more on the supramolecular knottin surfaces with a higher valency, and in addition, more pronounced focal adhesion formation was observed on the higher-valency knottin surfaces. We attribute this effect to the enhanced coverage and the enhanced affinity of the knottins in their interaction with the CB[8] surface. Collectively, these results are promising for the development of biomaterials including knottins via CB[8] ternary complexes for tunable interactions with cells.

  3. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    International Nuclear Information System (INIS)

    Ryu, Jung-Kyu; Cho, Jeong-Yeon; Choi, Jong-Sun

    2003-01-01

    Focal musculoskeletal anomalies vary, and can manifest as part of a syndrome or be accompanied by numerous other conditions such as genetic disorders, karyotype abnormalities, central nervous system anomalies and other skeletal anomalies, lsolated focal musculoskeletal anomaly does, however, also occur; its early prenatal diagnosis is important in deciding prenatal care, and also helps in counseling parents about the postnatal effects of numerous possible associated anomalies. We have encountered 50 cases involving focal musculoskeletal anomalies, including total limb dysplasia [radial ray abnormality (n=3), mesomelic dysplasia (n=1)]; anomalies of the hand [polydactyly (n=8), syndactyly (n=3), ectrodactyly (n=1), clinodactyly (n=6), clenched hand (n=5)]; anomalies of the foot [clubfoot (n=10), rockerbottom foot (n=5), sandal gap deformity (n=1), curly toe (n=2)]; amniotic band syndrome (n=3); and anomalies of the focal spine [block vertebra (n=1), hemivertebra (n=1)]. Among these 50 cases, five [polydactyly (n=1), syndactyly (n=2) and curly toe (n=2) were confirmed by postnatal physical evaluation, two (focal spine anomalies) were diagnosed after postnatal radiologic examination, and the remaining 43 were proven at autopsy. For each condition, we describe the prenatal sonographic findings, and include a brief review

  4. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jung-Kyu; Cho, Jeong-Yeon; Choi, Jong-Sun [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2003-12-15

    Focal musculoskeletal anomalies vary, and can manifest as part of a syndrome or be accompanied by numerous other conditions such as genetic disorders, karyotype abnormalities, central nervous system anomalies and other skeletal anomalies, lsolated focal musculoskeletal anomaly does, however, also occur; its early prenatal diagnosis is important in deciding prenatal care, and also helps in counseling parents about the postnatal effects of numerous possible associated anomalies. We have encountered 50 cases involving focal musculoskeletal anomalies, including total limb dysplasia [radial ray abnormality (n=3), mesomelic dysplasia (n=1)]; anomalies of the hand [polydactyly (n=8), syndactyly (n=3), ectrodactyly (n=1), clinodactyly (n=6), clenched hand (n=5)]; anomalies of the foot [clubfoot (n=10), rockerbottom foot (n=5), sandal gap deformity (n=1), curly toe (n=2)]; amniotic band syndrome (n=3); and anomalies of the focal spine [block vertebra (n=1), hemivertebra (n=1)]. Among these 50 cases, five [polydactyly (n=1), syndactyly (n=2) and curly toe (n=2) were confirmed by postnatal physical evaluation, two (focal spine anomalies) were diagnosed after postnatal radiologic examination, and the remaining 43 were proven at autopsy. For each condition, we describe the prenatal sonographic findings, and include a brief review.

  5. Seven tesla MRI improves detection of focal cortical dysplasia in patients with refractory focal epilepsy

    NARCIS (Netherlands)

    Veersema, Tim J; Ferrier, Cyrille H; van Eijsden, Pieter; Gosselaar, Peter H; Aronica, Eleonora; Visser, Fredy; Zwanenburg, Jaco M; de Kort, Gerard A P; Hendrikse, Jeroen; Luijten, Peter R; Braun, Kees P J

    Objective: The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery. Methods: In our center patients are referred for 7 T MRI if lesional focal epilepsy is

  6. Correlation of kidney biopsy findings and clinical manifestations of primary focal and segmental glomerulosclerosis.

    Science.gov (United States)

    Taheri, Diana; Chehrei, Ali; Samanianpour, Pargol; Hassanzadeh, Amar; Sadrarhami, Shohreh; Seyrafian, Shiva

    2009-05-01

    To evaluate the correlation of clinical, laboratory, and pathological features at pre-sentation of focal segmental sclerosis (FSGS), we reviewed in a cross sectional study the pathological findings of kidney biopsies in 64 cases of primary FSGS, and correlated them with the clinical and laboratory data obtained at the time of the biopsies. The data included blood pressure, glomerular filtration rate (GFR), serum albumin, and the level of proteinuria. The mean level of serum creatinine was significantly higher in the biopsies' findings of synechiae (adhesions) in the Bowman's capsule, interstitial fibrosis, and global scars (PBowman's capsule in their biopsies.

  7. Syndecans and cell adhesion

    DEFF Research Database (Denmark)

    Couchman, J R; Chen, L; Woods, A

    2001-01-01

    Now that transmembrane signaling through primary cell-matrix receptors, integrins, is being elucidated, attention is turning to how integrin-ligand interactions can be modulated. Syndecans are transmembrane proteoglycans implicated as coreceptors in a variety of physiological processes, including...... cell adhesion, migration, response to growth factors, development, and tumorigenesis. This review will describe this family of proteoglycans in terms of their structures and functions and their signaling in conjunction with integrins, and indicate areas for future research....

  8. Preliminary crystallographic characterization of the Grb2 SH2 domain in complex with a FAK-derived phosphotyrosyl peptide

    International Nuclear Information System (INIS)

    Chen, Hsiao-Hsin; Chen, Cuei-Wen; Chang, Yu-Yung; Shen, Tang-Long; Hsu, Chun-Hua

    2010-01-01

    Crystals of the Grb2 SH2 domain in complex with a phosphotyrosyl peptide corresponding to residues 921–930 of focal adhesion kinase (FAK) have been obtained using the sitting-drop vapour-diffusion technique. Data have been collected to 2.49 Å resolution. Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein with a single SH2 domain that specifically binds to focal adhesion kinase (FAK) when residue Tyr925 of FAK is phosphorylated. The Grb2–FAK interaction is associated with cellular integrin-activated signal transduction events leading to the activation of the Ras-MAPK pathway. Crystals of the Grb2 SH2 domain in complex with a phosphopeptide corresponding to residues 921–930 of FAK have been obtained using the sitting-drop vapour-diffusion technique. The crystals belonged to space group P3 1 21, with unit-cell parameters a = b = 102.7, c = 127.6 Å, α = β = 90.0, γ = 120.0°. A diffraction data set was collected from a flash-cooled crystal at 100 K to 2.49 Å resolution using synchrotron radiation. Structure determination by molecular replacement and analysis of the detailed structure of the complex are currently in progress

  9. Expansive focal cemento-osseous dysplasia.

    Science.gov (United States)

    Bulut, Emel Uzun; Acikgoz, Aydan; Ozan, Bora; Zengin, Ayse Zeynep; Gunhan, Omer

    2012-01-01

    To present a case of expansive focal cemento-osseous dysplasia and emphasize the importance of differential diagnosis. Cemento-osseous dysplasia is categorized into three subtypes on the basis of the clinical and radiographic features: Periapical, focal and florid. The focal type exhibits a single site of involvement in any tooth-bearing or edentulous area of the jaws. These lesions are usually asymptomatic; therefore, they are frequently diagnosed incidentally during routine radiographic examinations. Lesions are usually benign, show limited growth, and do not require further surgical intervention, but periodic follow-up is recommended because occasionally, this type of dysplasia progresses into florid osseous dysplasia and simple bone cysts are formed. A 24-year-old female patient was referred to our clinic for swelling in the left edentulous mandibular premolarmolar region and felt discomfort when she wore her prosthetics. She had no pain, tenderness or paresthesia. Clinical examination showed that the swelling in the posterior mandible that was firm, nonfluctuant and covered by normal mucosa. On panoramic radiography and computed tomography, a well defined lesion of approximately 1.5 cm in diameter of mixed density was observed. The swelling increased slightly in size over 2 years making it difficult to use prosthetics and, therefore, the lesion was totally excised under local anesthesia, and surgical specimens were submitted for histopathological examination. The histopathological diagnosis was focal cemento-osseous dysplasia. In the present case, because of the increasing size of the swelling making it difficult to use prosthetics, young age of the patient and localization of the lesion, in the initial examination, cemento-ossifying fibroma was suspected, and the lesion was excised surgically; the histopathological diagnosis confirmed it as focal cemento-osseous dysplasia. We present a case of expansive focal cemento-osseous dysplasia. Differential diagnosis

  10. The molecular mechanism of mediation of adsorbed serum proteins to endothelial cells adhesion and growth on biomaterials.

    Science.gov (United States)

    Yang, Dayun; Lü, Xiaoying; Hong, Ying; Xi, Tingfei; Zhang, Deyuan

    2013-07-01

    To explore molecular mechanism of mediation of adsorbed proteins to cell adhesion and growth on biomaterials, this study examined endothelial cell adhesion, morphology and viability on bare and titanium nitride (TiN) coated nickel titanium (NiTi) alloys and chitosan film firstly, and then identified the type and amount of serum proteins adsorbed on the three surfaces by proteomic technology. Subsequently, the mediation role of the identified proteins to cell adhesion and growth was investigated with bioinformatics analyses, and further confirmed by a series of cellular and molecular biological experiments. Results showed that the type and amount of adsorbed serum proteins associated with cell adhesion and growth was obviously higher on the alloys than on the chitosan film, and these proteins mediated endothelial cell adhesion and growth on the alloys via four ways. First, proteins such as adiponectin in the adsorbed protein layer bound with cell surface receptors to generate signal transduction, which activated cell surface integrins through increasing intracellular calcium level. Another way, thrombospondin 1 in the adsorbed protein layer promoted TGF-β signaling pathway activation and enhanced integrins expression. The third, RGD sequence containing proteins such as fibronectin 1, vitronectin and thrombospondin 1 in the adsorbed protein layer bound with activated integrins to activate focal adhesion pathway, increased focal adhesion formation and actin cytoskeleton organization and mediated cell adhesion and spreading. In addition, the activated focal adhesion pathway promoted the expression of cell growth related genes and resulted in cell proliferation. The fourth route, coagulation factor II (F2) and fibronectin 1 in the adsorbed protein layer bound with cell surface F2 receptor and integrin, activated regulation of actin cytoskeleton pathway and regulated actin cytoskeleton organization. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Extensive Focal Epithelial Hyperplasia: A Case Report.

    Science.gov (United States)

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.

  12. Rasmussen's encephalitis presenting as focal cortical dysplasia

    Directory of Open Access Journals (Sweden)

    D.J. O'Rourke

    2014-01-01

    Full Text Available Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD and discuss the literature on this topic.

  13. Rasmussen's encephalitis presenting as focal cortical dysplasia

    Science.gov (United States)

    O'Rourke, D.J.; Bergin, A.; Rotenberg, A.; Peters, J.; Gorman, M.; Poduri, A.; Cryan, J.; Lidov, H.; Madsen, J.; Harini, C.

    2014-01-01

    Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic. PMID:25667877

  14. Actinic Granuloma with Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Ruedee Phasukthaworn

    2016-02-01

    Full Text Available Actinic granuloma is an uncommon granulomatous disease, characterized by annular erythematous plaque with central clearing predominately located on sun-damaged skin. The pathogenesis is not well understood, ultraviolet radiation is recognized as precipitating factor. We report a case of a 52-year-old woman who presented with asymptomatic annular erythematous plaques on the forehead and both cheeks persisting for 2 years. The clinical presentation and histopathologic findings support the diagnosis of actinic granuloma. During that period of time, she also developed focal segmental glomerulosclerosis. The association between actinic granuloma and focal segmental glomerulosclerosis needs to be clarified by further studies.

  15. Focal splenic masses of the extramedullary hematopoiesis

    International Nuclear Information System (INIS)

    Incedayi, M.; Sivrioglu, A.

    2012-01-01

    Full text: Extramedullary hematopoiesis arises from pleuripotential stem cells distributed throughout the body. It is most common in patients with congenital hemolytic anemia, such as thalassemia, sickle cell anemia and hereditary spherocytosis as a response to ineffective red blood cell formation. Although microscopic foci of Extramedullary hematopoiesis are commonly seen in the spleen and liver parenchyma, focal mass-like lesion of extramedullary hematopoiesis in the liver and spleen are rare. We report a case of intrasplenic focal extramedullary hematopoiesis lesions and the imaging features of extramedullary hematopoiesis on computed tomography and magnetic resonance imaging. Extramedullary hematopoiesis should always be considered as a diagnosis in a patient with a known hematological disorder

  16. Fibronectin-bound α5β1 integrins sense load and signal to reinforce adhesion in less than a second

    Science.gov (United States)

    Strohmeyer, Nico; Bharadwaj, Mitasha; Costell, Mercedes; Fässler, Reinhard; Müller, Daniel J.

    2017-12-01

    Integrin-mediated mechanosensing of the extracellular environment allows cells to control adhesion and signalling. Whether cells sense and respond to force immediately upon ligand-binding is unknown. Here, we report that during adhesion initiation, fibroblasts respond to mechanical load by strengthening integrin-mediated adhesion to fibronectin (FN) in a biphasic manner. In the first phase, which depends on talin and kindlin as well as on the actin nucleators Arp2/3 and mDia, FN-engaged α5β1 integrins activate focal adhesion kinase (FAK) and c-Src in less than 0.5 s to steeply strengthen α5β1- and αV-class integrin-mediated adhesion. When the mechanical load exceeds a certain threshold, fibroblasts decrease adhesion and initiate the second phase, which is characterized by less steep adhesion strengthening. This unique, biphasic cellular adhesion response is mediated by α5β1 integrins, which form catch bonds with FN and signal to FN-binding integrins to reinforce cell adhesion much before visible adhesion clusters are formed.

  17. Focal Adhesion Kinase functions as an Akt downstream target in migration of colorectal cancer cells

    Czech Academy of Sciences Publication Activity Database

    Turečková, Jolana; Vojtěchová, Martina; Krausová, Michaela; Šloncová, Eva; Kořínek, Vladimír

    2009-01-01

    Roč. 2, č. 4 (2009), s. 281-290 ISSN 1936-5233 R&D Projects: GA ČR GA204/06/1658; GA MŠk 2B06077 Institutional research plan: CEZ:AV0Z50520514 Keywords : FAK * migration * invasion Subject RIV: EB - Genetics ; Molecular Biology

  18. Focal-adhesion targeting links caveolin-1 to a Rac1-degradation pathway

    NARCIS (Netherlands)

    Nethe, Micha; Anthony, Eloise C.; Fernandez-Borja, Mar; dee, Rob; Geerts, Dirk; Hensbergen, Paul J.; Deelder, André M.; Schmidt, Gudula; Hordijk, Peter L.

    2010-01-01

    Directional cell migration is crucially dependent on the spatiotemporal control of intracellular signalling events. These events regulate polarized actin dynamics, resulting in protrusion at the front of the cell and contraction at the rear. The actin cytoskeleton is regulated through signalling by

  19. Interleukin-8 induces motile behavior and loss of focal adhesions in primary fibroblasts

    DEFF Research Database (Denmark)

    Dunlevy, J R; Couchman, J R

    1995-01-01

    Interleukin-8 (IL-8) is a proinflammatory cytokine that promotes neutrophil migration. Although fibroblasts are known to secrete IL-8, the actions of this cytokine on fibroblasts have not been previously reported. We have found that in subconfluent populations of cultured primary fibroblasts, IL-8...

  20. How to awaken your nanomachines: Site-specific activation of focal adhesion kinases through ligand interactions

    KAUST Repository

    Walkiewicz, Katarzyna Wiktoria; Girault, Jean-Antoine; Arold, Stefan T.

    2015-01-01

    and inhibiting their functions are important for the development of targeted therapy. Because FAK and Pyk2 are involved in many different cellular functions, designing drugs with partial and function-specific inhibitory effects would be desirable. Here, we

  1. Infrared MUSIC from Z technology focal planes

    International Nuclear Information System (INIS)

    Waters, C.R.; Sommese, A.; Johnston, D.; Landau, H.

    1989-01-01

    Presented is the Multiple Signal Classification (MUSIC) algorithm which uses the high frequency differences in sensed time signals to discriminate, count, and accurately locate closely spaced targets. Z technology focal planes allow the implementation of this algorithm and the trade-off between finer spatial resolution systems and systems with coarser resolution but higher sampling rates

  2. Focal dermal hypoplasia: A rare case report

    Directory of Open Access Journals (Sweden)

    Sahana M Srinivas

    2015-01-01

    Full Text Available Focal dermal hypoplasia (Goltz syndrome is a rare genetic multisystem disorder primarily involving the skin, skeletal system, eyes, and face. We report the case of an eight-month-old female child who presented with multiple hypopigmented atrophic macules along the lines of blaschko, skeletal anomalies, umbilical hernia, developmental delay, hypoplastic nails, syndactyly, and lobster claw deformity characteristic of Goltz syndrome.

  3. Combined effects of PEG hydrogel elasticity and cell-adhesive coating on fibroblast adhesion and persistent migration.

    Science.gov (United States)

    Missirlis, Dimitris; Spatz, Joachim P

    2014-01-13

    The development and use of synthetic, cross-linked, macromolecular substrates with tunable elasticity has been instrumental in revealing the mechanisms by which cells sense and respond to their mechanical microenvironment. We here describe a hydrogel based on radical-free, cross-linked poly(ethylene glycol) to study the effects of both substrate elasticity and type of adhesive coating on fibroblast adhesion and migration. Hydrogel elasticity was controlled through the structure and concentration of branched precursors, which efficiently react via Michael-type addition to produce the polymer network. We found that cell spreading and focal adhesion characteristics are dependent on elasticity for all types of coatings (RGD peptide, fibronectin, vitronectin), albeit with significant differences in magnitude. Importantly, fibroblasts migrated slower but more persistently on stiffer hydrogels, with the effects being more pronounced on fibronectin-coated substrates. Therefore, our results validate the hydrogels presented in this study as suitable for future mechanosensing studies and indicate that cell adhesion, polarity, and associated migration persistence are tuned by substrate elasticity and biochemical properties.

  4. Syndecan proteoglycans and cell adhesion

    DEFF Research Database (Denmark)

    Woods, A; Oh, E S; Couchman, J R

    1998-01-01

    It is now becoming clear that a family of transmembrane proteoglycans, the syndecans, have important roles in cell adhesion. They participate through binding of matrix ligand to their glycosaminoglycan chains, clustering, and the induction of signaling cascades to modify the internal microfilament...... organization. Syndecans can modulate the type of adhesive responses induced by other matrix ligand-receptor interactions, such as those involving the integrins, and so contribute to the control of cell morphology, adhesion and migration....

  5. Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting.

    Science.gov (United States)

    Staquicini, Daniela I; Rangel, Roberto; Guzman-Rojas, Liliana; Staquicini, Fernanda I; Dobroff, Andrey S; Tarleton, Christy A; Ozbun, Michelle A; Kolonin, Mikhail G; Gelovani, Juri G; Marchiò, Serena; Sidman, Richard L; Hajjar, Katherine A; Arap, Wadih; Pasqualini, Renata

    2017-06-26

    Cytoskeletal-associated proteins play an active role in coordinating the adhesion and migration machinery in cancer progression. To identify functional protein networks and potential inhibitors, we screened an internalizing phage (iPhage) display library in tumor cells, and selected LGRFYAASG as a cytosol-targeting peptide. By affinity purification and mass spectrometry, intracellular annexin A2 was identified as the corresponding binding protein. Consistently, annexin A2 and a cell-internalizing, penetratin-fused version of the selected peptide (LGRFYAASG-pen) co-localized and specifically accumulated in the cytoplasm at the cell edges and cell-cell contacts. Functionally, tumor cells incubated with LGRFYAASG-pen showed disruption of filamentous actin, focal adhesions and caveolae-mediated membrane trafficking, resulting in impaired cell adhesion and migration in vitro. These effects were paralleled by a decrease in the phosphorylation of both focal adhesion kinase (Fak) and protein kinase B (Akt). Likewise, tumor cells pretreated with LGRFYAASG-pen exhibited an impaired capacity to colonize the lungs in vivo in several mouse models. Together, our findings demonstrate an unrecognized functional link between intracellular annexin A2 and tumor cell adhesion, migration and in vivo grafting. Moreover, this work uncovers a new peptide motif that binds to and inhibits intracellular annexin A2 as a candidate therapeutic lead for potential translation into clinical applications.

  6. Segmental jejunal entrapment, volvulus, and strangulation secondary to intra-abdominal adhesions in a dog.

    Science.gov (United States)

    Di Cicco, Michael F; Bennett, R Avery; Ragetly, Chantal; Sippel, Kate M

    2011-01-01

    A 4 yr old, castrated male dachshund was presented for lethargy, restlessness, a "hunched" posture, and a painful abdomen. A gastric foreign body had been surgically removed 24 mo previously. Exploratory celiotomy revealed a devitalized segment of jejunum with twisted mesentery. Several adhesions and fibrous bands were present within the abdomen, presumptively from the previous gastric foreign body surgery. Histopathology determined that a fibrous tissue band caused entrapment of the segment of intestine and its mesentery resulting in volvulus and ischemic necrosis of the intestine. This case is unique because it involved a focal area of the jejunum that was incarcerated in fibrous adhesions.

  7. Thermography Examination of Abdominal Area Skin Temperatures in Individuals With and Without Focal-Onset Epilepsy.

    Science.gov (United States)

    King, Hollis H; Cayce, Charles Thomas; Herrin, Jeph

    Early osteopathic theory and practice, and the work of the medical intuitive Edgar Cayce suggested that the abdominal areas of individuals with epilepsy would manifest "cold spots." The etiology for this phenomenon was thought to be abdominal adhesions caused by inflammation and viscero-somatic reflexes caused by adhesions or injury to visceral or musculoskeletal system structures. Indeed, until that advent of electroencephalography in the 1930s, medical practice regarding epilepsy focused on abdominal neural and visceral structures. Following two hypotheses were formulated to evaluate any abdominal temperature phenomena: (1) an abdominal quadrant division analysis would find one or more quadrants "colder" in the focal-onset epilepsy group (ICD9-CM 345.4 and 345.5) compared to controls. (2) Total abdominal areas of individuals with focal-onset epilepsy wound be colder than a control group. Overall, 50 patients with the diagnosis of focal-onset epilepsy were recruited from the office of the Epilepsy Foundation of Florida and 50 control subjects with no history of epilepsy were recruited through advertising to the public. Under controlled room conditions all subjects had infrared thermographic images made and recorded by Med-Hot Model MH-731 FLIR equipment. There were no significant demographic difference between experimental patients and control subjects, though the control group tended to be younger and more often male; however, these were controlled for in all analyses. In the quadrant analysis, there were significant differences in that more epileptic patients had colder left upper abdominal quadrant temperatures than the control group (66.8% versus 44.9%; P = .030). In the total abdominal analysis, however, there were no significant differences. The results support the hypothesis that individuals with focal-onset epilepsy have colder abdominal areas. If substantiated in further research, present study results will require further examination of the mechanisms of

  8. DESI focal plate mechanical integration and cooling

    Science.gov (United States)

    Lambert, A. R.; Besuner, R. W.; Claybaugh, T. M.; Silber, J. H.

    2016-08-01

    The Dark Energy Spectroscopic Instrument (DESI) is under construction to measure the expansion history of the Universe using the Baryon Acoustic Oscillation technique[1]. The spectra of 40 million galaxies over 14000 sq. deg will be measured during the life of the experiment. A new prime focus corrector for the KPNO Mayall telescope will deliver light to 5000 fiber optic positioners. The fibers in turn feed ten broad-band spectrographs. This paper describes the mechanical integration of the DESI focal plate and the thermal system design. The DESI focal plate is comprised of ten identical petal assemblies. Each petal contains 500 robotic fiber positioners. Each petal is a complete, self-contained unit, independent from the others, with integrated power supply, controllers, fiber routing, and cooling services. The major advantages of this scheme are: (1) supports installation and removal of complete petal assemblies in-situ, without disturbing the others, (2) component production, assembly stations, and test procedures are repeated and parallelizable, (3) a complete, full-scale prototype can be built and tested at an early date, (4) each production petal can be surveyed and tested as a complete unit, prior to integration, from the fiber tip at the focal surface to the fiber slit at the spectrograph. The ten petal assemblies will be installed in a single integration ring, which is mounted to the DESI corrector. The aluminum integration ring attaches to the steel corrector barrel via a flexured steel adapter, isolating the focal plate from differential thermal expansions. The plate scale will be kept stable by conductive cooling of the petal assembly. The guider and wavefront sensors (one per petal) will be convectively cooled by forced flow of air. Heat will be removed from the system at ten liquid-cooled cold plates, one per petal, operating at ambient temperature. The entire focal plate structure is enclosed in an insulating shroud, which serves as a thermal barrier

  9. Improved Adhesion and Compliancy of Hierarchical Fibrillar Adhesives.

    Science.gov (United States)

    Li, Yasong; Gates, Byron D; Menon, Carlo

    2015-08-05

    The gecko relies on van der Waals forces to cling onto surfaces with a variety of topography and composition. The hierarchical fibrillar structures on their climbing feet, ranging from mesoscale to nanoscale, are hypothesized to be key elements for the animal to conquer both smooth and rough surfaces. An epoxy-based artificial hierarchical fibrillar adhesive was prepared to study the influence of the hierarchical structures on the properties of a dry adhesive. The presented experiments highlight the advantages of a hierarchical structure despite a reduction of overall density and aspect ratio of nanofibrils. In contrast to an adhesive containing only nanometer-size fibrils, the hierarchical fibrillar adhesives exhibited a higher adhesion force and better compliancy when tested on an identical substrate.

  10. Stretchable, Adhesion-Tunable Dry Adhesive by Surface Wrinkling

    KAUST Repository

    Jeong, Hoon Eui

    2010-02-16

    We introduce a simple yet robust method of fabricating a stretchable, adhesion-tunable dry adhesive by combining replica molding and surface wrinkling. By utilizing a thin, wrinkled polydimethyl siloxane (PDMS) sheet with a thickness of 1 mm with built-in micropillars, active, dynamic control of normal and shear adhesion was achieved. Relatively strong normal (∼10.8 N/cm2) and shear adhesion (∼14.7 N/cm2) forces could be obtained for a fully extended (strained) PDMS sheet (prestrain of∼3%), whereas the forces could be rapidly reduced to nearly zero once the prestrain was released (prestrain of ∼0.5%). Moreover, durability tests demonstrated that the adhesion strength in both the normal and shear directions was maintained over more than 100 cycles of attachment and detachment. © 2010 American Chemical Society.

  11. Effect of adhesive thickness on adhesively bonded T-joint

    International Nuclear Information System (INIS)

    Abdullah, A R; Afendi, Mohd; Majid, M S Abdul

    2013-01-01

    The aim of this work is to analyze the effect of adhesive thickness on tensile strength of adhesively bonded stainless steel T-joint. Specimens were made from SUS 304 Stainless Steel plate and SUS 304 Stainless Steel perforated plate. Four T-joint specimens with different adhesive thicknesses (0.5, 1.0, 1.5 and 2.0 mm) were made. Experiment result shows T-joint specimen with adhesive thickness of 1.0 mm yield highest maximum load. Identical T-joint specimen jointed by spot welding was also tested. Tensile test shows welded T-Joint had eight times higher tensile load than adhesively bonded T-joint. However, in low pressure application such as urea granulator chamber, high tensile strength is not mandatory. This work is useful for designer in fertilizer industry and others who are searching for alternative to spot welding

  12. Stretchable, Adhesion-Tunable Dry Adhesive by Surface Wrinkling

    KAUST Repository

    Jeong, Hoon Eui; Kwak, Moon Kyu; Suh, Kahp Y.

    2010-01-01

    We introduce a simple yet robust method of fabricating a stretchable, adhesion-tunable dry adhesive by combining replica molding and surface wrinkling. By utilizing a thin, wrinkled polydimethyl siloxane (PDMS) sheet with a thickness of 1 mm with built-in micropillars, active, dynamic control of normal and shear adhesion was achieved. Relatively strong normal (∼10.8 N/cm2) and shear adhesion (∼14.7 N/cm2) forces could be obtained for a fully extended (strained) PDMS sheet (prestrain of∼3%), whereas the forces could be rapidly reduced to nearly zero once the prestrain was released (prestrain of ∼0.5%). Moreover, durability tests demonstrated that the adhesion strength in both the normal and shear directions was maintained over more than 100 cycles of attachment and detachment. © 2010 American Chemical Society.

  13. Mechanistic study of the rubber-brass adhesion interphase

    Science.gov (United States)

    Ashirgade, Akshay

    Brass-plated steel tire cords form an essential strengthening component of a radial automobile tire. Adhesion between rubber compound and brass-plated steel tire cord is crucial in governing the overall performance of tires. The rubber-brass interfacial adhesion is influenced by the chemical composition and thickness of the interfacial layer. It has been shown that the interfacial layer consists mainly of sulfides and oxides of copper and zinc. This thesis discusses the effect of changes in the chemical composition and the structure of the interfacial layers due to addition of adhesion promoter resins. Grazing incidence X-Ray Diffraction (GIXRD) experiments were run on sulfidized polished brass coupons previously bonded to six experimental rubber compounds. It was confirmed that heat and humidity conditions lead to physical and chemical changes of the rubber-steel tire cord interfacial layer, closely related to the degree of rubber-brass adhesion. Morphological transformation of the interfacial layer led to loss of adhesion after aging. The adhesion promoter resins inhibit unfavorable morphological changes in the interfacial layer thus stabilizing it during aging and prolonging failure. Tire cord adhesion tests illustrated that the one-component resins improved adhesion after aging using a rubber compound with lower cobalt loading. Based on the acquired diffraction profiles, these resins were also found to impede crystallization of the sulfide layer after aging leading to improved adhesion. Secondary Ion Mass Spectrometry (SIMS) depth profiles, SEM micrographs and AFM images strongly corroborated the findings from GIXRD. FTIR was utilized in a novel way to understand the degradation mechanism due to aging. A model for rubber and interfacial layer degradation is proposed to illustrate the effect of aging and the one-component resins. This interfacial analysis adds valuable new information to our understanding of the complex nature of the rubber-brass bonding

  14. Heparan sulfate chain valency controls syndecan-4 function in cell adhesion

    DEFF Research Database (Denmark)

    Gopal, Sandeep; Bober, Adam; Whiteford, James R

    2010-01-01

    , clustering of one-chain syndecan-4 forms with antibodies overcame the block, indicating that valency of interactions with ligands is a key component of syndecan-4 function. Measurements of focal contact/adhesion size and focal adhesion kinase phosphorylation correlated with syndecan-4 status and alpha...... of the core protein cytoplasmic domain, though not interactions with PDZ proteins. A second key requirement is multiple heparan sulfate chains. Mutant syndecan-4 with no chains, or only one chain, failed to restore the wild type phenotype, while those expressing two or three were competent. However......-smooth muscle actin organization, being reduced where syndecan-4 function was compromised by a lack of multiple heparan sulfate chains....

  15. Syndecans, signaling, and cell adhesion

    DEFF Research Database (Denmark)

    Couchman, J R; Woods, A

    1996-01-01

    structures within the heparan sulfate chains, leaving the roles of chondroitin sulfate chains and extracellular portion of the core proteins to be elucidated. Evidence that syndecans are a class of receptor involved in cell adhesion is mounting, and their small cytoplasmic domains may link...... transmembrane signaling from matrix to cytoskeleton, as proposed for other classes of adhesion receptors....

  16. Controlling adhesive behavior during recycling

    Science.gov (United States)

    Carl Houtman; Karen Scallon; Jihui Guo; XinPing Wang; Steve Severtson; Mark Kroll; Mike Nowak

    2004-01-01

    Adhesives can be formulated to facilitate their removal by typical paper recycling unit operations. The investigations described in this paper are focused on determining fundamental properties that control particle size during pulping. While pressure-sensitive adhesives (PSAs) with high elastic moduli tend to survive pulping with larger particles, facestock and...

  17. Radiopneumographic characteristics of focal pneumonia in children

    International Nuclear Information System (INIS)

    Smirnova, A.A.

    1980-01-01

    Zonal ventilation and blood flow were studied by the radiopneumography method in 50 children of school age with lower-lobe-of-the lung focal pneumonia (26 with left-side and 24 with right-side). It is established that during right-side localization of pneumonic focus preserved was the predomination of ventilation of right lung relative to left. Complete normalization of common and regional indexes of ventilation and blood flow was established by the 21st day from the beginning of treatment during right-side focal pneumonias. In case of left-side localization of pneumonic focus only partial reduction of external respiration and perfusion comes. Therefore, compensatory and reducing capabilities of right lung are preferrable

  18. Membership Functions for Fuzzy Focal Elements

    Directory of Open Access Journals (Sweden)

    Porębski Sebastian

    2016-09-01

    Full Text Available The paper presents a study on data-driven diagnostic rules, which are easy to interpret by human experts. To this end, the Dempster-Shafer theory extended for fuzzy focal elements is used. Premises of the rules (fuzzy focal elements are provided by membership functions which shapes are changing according to input symptoms. The main aim of the present study is to evaluate common membership function shapes and to introduce a rule elimination algorithm. Proposed methods are first illustrated with the popular Iris data set. Next experiments with five medical benchmark databases are performed. Results of the experiments show that various membership function shapes provide different inference efficiency but the extracted rule sets are close to each other. Thus indications for determining rules with possible heuristic interpretation can be formulated.

  19. Focal epilepsy in the Belgian shepherd

    DEFF Research Database (Denmark)

    Berendt, Mette; Gulløv, Christina Hedal; Fredholm, Merete

    2009-01-01

    and deceased) were ascertained through a telephone interview using a standardised questionnaire regarding seizure history and phenomenology. Living dogs were invited to a detailed clinical evaluation. Litters more than five years of age, or where epilepsy was present in all offspring before the age of five......, were included in the calculations of inheritance. results: Out of 199 family members, 66 dogs suffered from epilepsy. The prevalence of epilepsy in the family was 33%. Fifty-five dogs experienced focal seizures with or without secondary generalisation, while four dogs experienced primary generalised...... seizures. In seven dogs, seizures could not be classified. The mode of inheritance of epilepsy was simple Mendelian. CLINICAL SIGNIFICANCE: This study identified that the Belgian shepherd suffers from genetically transmitted focal epilepsy. The seizure phenomenology expressed by family members have...

  20. Chest pain in focal musculoskeletal disorders

    DEFF Research Database (Denmark)

    Stochkendahl, Mette Jensen; Christensen, Henrik Wulff

    2010-01-01

    overlapping conditions and syndromes of focal disorders, including Tietze syndrome, costochondritis, chest wall syndrome, muscle tenderness, slipping rib, cervical angina, and segmental dysfunction of the cervical and thoracic spine, have been reported to cause pain. For most of these syndromes, evidence......The musculoskeletal system is a recognized source of chest pain. However, despite the apparently benign origin, patients with musculoskeletal chest pain remain under-diagnosed, untreated, and potentially continuously disabled in terms of anxiety, depression, and activities of daily living. Several...... arises mainly from case stories and empiric knowledge. For segmental dysfunction, clinical features of musculoskeletal chest pain have been characterized in a few clinical trials. This article summarizes the most commonly encountered syndromes of focal musculoskeletal disorders in clinical practice....

  1. Characterization of LIL laser UV focal spot

    International Nuclear Information System (INIS)

    Mangeant, M.; Dubois, J.L.; Behar, G.; Arroyo, P.; Durand, V.; Lahonde, C.

    2006-01-01

    One way to get the fusion of hydrogen in laboratory consists in heating and compressing a DT fuel capsule by using a laser. To reach this aim requires a new generation of high power laser facility. Cea (French board for atomic energy) is developing for this purpose a new 240 laser line facility, the LMJ facility. The LIL which is the prototype of four LMJ laser lines is operational now. In order to confirm the technical choices, a systematic characterization of LIL was carried out. A particular effort has been provided to measure the 3ω high energy focal spot (1.5 kJ/700 ps and 5 ns for one beam) and the synchronization of laser beams onto the target, which are key issues for the plasma production. An experimental device, SAT-3ω (a 3ω laser focal spot analysis) has been designed to perform these measures. That diagnostic which is located at the end of the laser lines delivered its first results during the 2004 quadruplet qualification campaigns. The near field imaging showed no diaphony and vignetting. Low power spots allowed us to control we had no ghost. The energy measurement quality showed the photometric transfer function was perfectly known. Our caustic image are given with an average dynamic range of 800, a spatial resolution of 10 μm and diameter accuracy about 1% for 50% and 3% for 90% of encircled energy. The high energy focal spot diameters are in agreement with low and very low energy diameters. The phase plate and 14 GHz effects are similar to what we had expected. For a laser shot completed with a continuous phase plate at 14 GHz, and for an energy level of 1.5 kJ per beam at 351 nm, the focal beam diameter at 3% of the peak level is (875 ± 45) μm

  2. Proximal focal femoral deficiency: A case report

    Directory of Open Access Journals (Sweden)

    Shashank Sharma

    2015-01-01

    Full Text Available Proximal focal femoral deficiency (PFFD is a rare congenital anomaly resulting in limb shortening and disability in young. The exact cause of the disease is not known and it may present as varying grades of affection involving the proximal femur and the acetabulum. Recognition of this rare abnormality on radiographs can help manage these cases better since early institution of therapy may help in achieving adequate growth of the femur.

  3. The cell adhesion molecule Fasciclin2 regulates brush border length and organization in Drosophila renal tubules

    DEFF Research Database (Denmark)

    Halberg, Kenneth Agerlin; Rainey, Stephanie M.; Veland, Iben Rønn

    2016-01-01

    Multicellular organisms rely on cell adhesion molecules to coordinate cell-cell interactions, and to provide navigational cues during tissue formation. In Drosophila, Fasciclin 2 (Fas2) has been intensively studied due to its role in nervous system development and maintenance; yet, Fas2 is most...... role for this well-known cell adhesion molecule, and propose that Fas2-mediated intermicrovillar homophilic adhesion complexes help stabilize the brush border....

  4. Focal plane scanner with reciprocating spatial window

    Science.gov (United States)

    Mao, Chengye (Inventor)

    2000-01-01

    A focal plane scanner having a front objective lens, a spatial window for selectively passing a portion of the image therethrough, and a CCD array for receiving the passed portion of the image. All embodiments have a common feature whereby the spatial window and CCD array are mounted for simultaneous relative reciprocating movement with respect to the front objective lens, and the spatial window is mounted within the focal plane of the front objective. In a first embodiment, the spatial window is a slit and the CCD array is one-dimensional, and successive rows of the image in the focal plane of the front objective lens are passed to the CCD array by an image relay lens interposed between the slit and the CCD array. In a second embodiment, the spatial window is a slit, the CCD array is two-dimensional, and a prism-grating-prism optical spectrometer is interposed between the slit and the CCD array so as to cause the scanned row to be split into a plurality of spectral separations onto the CCD array. In a third embodiment, the CCD array is two-dimensional and the spatial window is a rectangular linear variable filter (LVF) window, so as to cause the scanned rows impinging on the LVF to be bandpass filtered into spectral components onto the CCD array through an image relay lens interposed between the LVF and the CCD array.

  5. Micromorphological characterization of adhesive interface of sound dentin and total-etch and self-etch adhesives.

    Science.gov (United States)

    Drobac, Milan; Stojanac, Igor; Ramić, Bojana; Premović, Milica; Petrović, Ljubomir

    2015-01-01

    The ultimate goal in restorative dentistry has always been to achieve strong and permanent bond between the dental tissues and filling materials. It is not easy to achieve this task because the bonding process is different for enamel and dentin-dentin is more humid and more organic than enamel. It is moisture and organic nature of dentin that make this hard tissue very complex to achieve adhesive bond. One of the first and most widely used tools for examining the adhesive bond between hard dental tissues and composite restorative materials is scanning electron microscopy. The aim of this study was scanning electron microscopy analyzes the interfacial micro morphology of total-etch and self-etch adhesives. Micro morphological characteristics of interface between total-etch adhesive (Prime & Bond NT) in combination with the corresponding composite (Ceram X Mono) were compared with those of self-etching adhesive (AdheSE One) in, combination with the corresponding composite (Tetric EvoCeram). The specimens were observed under 1000 x magnification of scanning electron microscopy (JEOL, JSM-6460 Low Vacuum). Measurement of the thickness of the hybrid layer of the examined com posite systems was performed with the software of the device used (NIH Image Analyser). Micromorphological analysis of interface showed that the hybrid layer in sound dentin was well formed, its average thickness being 2.68 microm, with a large number of resin tags and a large amount of lateral branches for specimens with a composite system Prime & Bond NT-Ceram X Mono. However, the specimens' with composite systems Adhese One-Tetric EvoCeram did not show the presence of hybrid layer and the resin tags were poorly represented. The results of this study suggest that total-etch adhesives bond better with sound dentin than self-etch adhesive.

  6. Classification of Focal and Non Focal Epileptic Seizures Using Multi-Features and SVM Classifier.

    Science.gov (United States)

    Sriraam, N; Raghu, S

    2017-09-02

    Identifying epileptogenic zones prior to surgery is an essential and crucial step in treating patients having pharmacoresistant focal epilepsy. Electroencephalogram (EEG) is a significant measurement benchmark to assess patients suffering from epilepsy. This paper investigates the application of multi-features derived from different domains to recognize the focal and non focal epileptic seizures obtained from pharmacoresistant focal epilepsy patients from Bern Barcelona database. From the dataset, five different classification tasks were formed. Total 26 features were extracted from focal and non focal EEG. Significant features were selected using Wilcoxon rank sum test by setting p-value (p z > 1.96) at 95% significance interval. Hypothesis was made that the effect of removing outliers improves the classification accuracy. Turkey's range test was adopted for pruning outliers from feature set. Finally, 21 features were classified using optimized support vector machine (SVM) classifier with 10-fold cross validation. Bayesian optimization technique was adopted to minimize the cross-validation loss. From the simulation results, it was inferred that the highest sensitivity, specificity, and classification accuracy of 94.56%, 89.74%, and 92.15% achieved respectively and found to be better than the state-of-the-art approaches. Further, it was observed that the classification accuracy improved from 80.2% with outliers to 92.15% without outliers. The classifier performance metrics ensures the suitability of the proposed multi-features with optimized SVM classifier. It can be concluded that the proposed approach can be applied for recognition of focal EEG signals to localize epileptogenic zones.

  7. Multispectral linear array (MLA) focal plane mechanical and thermal design

    Science.gov (United States)

    Mitchell, A. S.; Kaminski, E. F.

    1982-01-01

    The mechanical and thermal design of an integrated focal plane subsystem of a Multispectral Linear Array (MLA) instrument is discussed in terms of focal-plane alignment, thermoelastic performance, and thermal requirements. The modular construction and thermal control of the focal plane array are discussed.

  8. Universal adhesives: the next evolution in adhesive dentistry?

    Science.gov (United States)

    Alex, Gary

    2015-01-01

    Every so often a new material, technique, or technological breakthrough spurs a paradigm shift in the way dentistry is practiced. The development and evolution of reliable enamel and dentin bonding agents is one such example. Indeed, the so-called "cosmetic revolution" in dentistry blossomed in large part due to dramatic advances in adhesive technology. It is the ability to bond various materials in a reasonably predictable fashion to both enamel and dentin substrates that enables dentists to routinely place porcelain veneers, direct and indirect composites, and a plethora of other restorative and esthetic materials. In fact, the longevity and predictability of many (if not most) current restorative procedures is wholly predicated on the dentist's ability to bond various materials to tooth tissues. Adhesive systems have progressed from the largely ineffective systems of the 1970s and early 1980s to the relatively successful total- and self-etching systems of today. The latest players in the adhesive marketplace are the so-called "universal adhesives." In theory, these systems have the potential to significantly simplify and expedite adhesive protocols and may indeed represent the next evolution in adhesive dentistry. But what defines a universal system, and are all these new systems truly "universal" and everything they are claimed to be? This article will examine the origin, chemistry, strengths, weaknesses, and clinical relevance of this new genre of dental adhesives.

  9. Early cell adhesion events differ between osteoporotic and non-osteoporotic osteoblasts.

    Science.gov (United States)

    Perinpanayagam, H; Zaharias, R; Stanford, C; Brand, R; Keller, J; Schneider, G

    2001-11-01

    In osteoporosis, the regenerative capacity of bone is compromised, which may involve altered osteoblast (OB) activity. This could be attributed to an inappropriate synthesis and assembly of an extracellular matrix (ECM), altered cell adhesion to the ECM, or be due to inappropriate downstream activation of adhesion-mediated signaling cascades through proteins such as focal adhesion kinase (FAK). The purpose of our study was to compare early adhesion-mediated events using previously described and characterized clinically derived OBs obtained from human patients undergoing major joint arthroplasty for osteoporosis or osteoarthritis. The presence or absence of osteoporosis was established with a radiographic index. Using light microscopy and crystal violet staining, we show that OB cells derived from sites of osteoporosis do not attach and spread as well as non-osteoporotic (OP) OB cells. OP cells initially have a more rounded morphology, and show significantly less (P attachment to serum-coated tissue culture plastic over a 24 h time period. Immunofluorescent labeling after 24 h of attachment showed that OP OB focal adhesions (FAs) and stress fibers were less defined, and that the OP cells were smaller and had a more motile phenotype. When normalized protein lysates were Western blotted for phosphotyrosine (PY) a band corresponding to pp125FAK was identified. FAK tyrosine phosphorylation was evident at 6 h in both the OP and non-OP OBs, but decreased or was absent through 24 h in OP OBs. These results suggest early adhesion-mediated events, such as cell adhesion, attachment, and FAK signaling via PY may be altered in OP OBs.

  10. Innovative compact focal plane array for wide field vis and ir orbiting telescopes

    Science.gov (United States)

    Hugot, Emmanuel; Vives, Sébastien; Ferrari, Marc; Gaeremynck, Yann; Jahn, Wilfried

    2017-11-01

    The future generation of high angular resolution space telescopes will require breakthrough technologies to combine large diameters and large focal plane arrays with compactness and lightweight mirrors and structures. Considering the allocated volume medium-size launchers, short focal lengths are mandatory, implying complex optical relays to obtain diffraction limited images on large focal planes. In this paper we present preliminary studies to obtain compact focal plane arrays (FPA) for earth observations on low earth orbits at high angular resolution. Based on the principle of image slicers, we present an optical concept to arrange a 1D FPA into a 2D FPA, allowing the use of 2D detector matrices. This solution is particularly attractive for IR imaging requiring a cryostat, which volume could be considerably reduced as well as the relay optics complexity. Enabling the use of 2D matrices for such an application offers new possibilities. Recent developments on curved FPA allows optimization without concerns on the field curvature. This innovative approach also reduces the complexity of the telescope optical combination, specifically for fast telescopes. This paper will describe the concept and optical design of an F/5 - 1.5m telescope equipped with such a FPA, the performances and the impact on the system with a comparison with an equivalent 1.5m wide field Korsch telescope.

  11. Focal neuronal loss, reversible subcortical focal T2 hypointensity in seizures with a nonketotic hyperglycemic hyperosmolar state

    International Nuclear Information System (INIS)

    Raghavendra, S.; Ashalatha, R.; Thomas, Sanjeev V.; Kesavadas, C.

    2007-01-01

    Neuroimaging in seizures associated with nonketotic hyperglycemia (NKH) is considered normal. We report magnetic resonance imaging (MRI) abnormalities in four patients with NKH and seizures. We prospectively evaluated clinical and radiological abnormalities in four patients with NKH during the period March 2004 to December 2005. All patients presented with seizures, either simple or complex partial seizures or epilepsia partialis continua. Two of them had transient hemianopia. MRI showed subcortical T2 hypointensity in the occipital white matter and in or around the central sulcus (two patients each), T2 hyperintensity of the overlying cortex (two patients), focal overlying cortical enhancement (three patients) and bilateral striatal hyperintensity (one patient). Diffusion-weighted imaging (DWI) performed in three patients showed restricted diffusion. The ictal semiology and electroencephalographic (EEG) findings correlated with the MRI abnormalities. On clinical recovery, the subcortical T2 hypointensity and striatal hyperintensity reversed in all patients. The initial cortical change evolved to FLAIR hyperintensity suggestive of focal cortical gliosis. The radiological differential diagnosis considered initially included encephalitis, malignancy and hemorrhagic infarct rendering a diagnostic dilemma. We identified subcortical T2 hypointensity rather than hyperintensity as a characteristic feature of seizures associated with NKH. Only very few similar reports exist in literature. Reversible bilateral striatal T2 hyperintensity in NKH has not been reported to the best of our knowledge. (orig.)

  12. Focal neuronal loss, reversible subcortical focal T2 hypointensity in seizures with a nonketotic hyperglycemic hyperosmolar state

    Energy Technology Data Exchange (ETDEWEB)

    Raghavendra, S.; Ashalatha, R.; Thomas, Sanjeev V. [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Neurology, Trivandrum, Kerala (India); Kesavadas, C. [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Imaging Sciences and Interventional Radiology, Trivandrum (India)

    2007-04-15

    Neuroimaging in seizures associated with nonketotic hyperglycemia (NKH) is considered normal. We report magnetic resonance imaging (MRI) abnormalities in four patients with NKH and seizures. We prospectively evaluated clinical and radiological abnormalities in four patients with NKH during the period March 2004 to December 2005. All patients presented with seizures, either simple or complex partial seizures or epilepsia partialis continua. Two of them had transient hemianopia. MRI showed subcortical T2 hypointensity in the occipital white matter and in or around the central sulcus (two patients each), T2 hyperintensity of the overlying cortex (two patients), focal overlying cortical enhancement (three patients) and bilateral striatal hyperintensity (one patient). Diffusion-weighted imaging (DWI) performed in three patients showed restricted diffusion. The ictal semiology and electroencephalographic (EEG) findings correlated with the MRI abnormalities. On clinical recovery, the subcortical T2 hypointensity and striatal hyperintensity reversed in all patients. The initial cortical change evolved to FLAIR hyperintensity suggestive of focal cortical gliosis. The radiological differential diagnosis considered initially included encephalitis, malignancy and hemorrhagic infarct rendering a diagnostic dilemma. We identified subcortical T2 hypointensity rather than hyperintensity as a characteristic feature of seizures associated with NKH. Only very few similar reports exist in literature. Reversible bilateral striatal T2 hyperintensity in NKH has not been reported to the best of our knowledge. (orig.)

  13. Model of SNARE-mediated membrane adhesion kinetics.

    Directory of Open Access Journals (Sweden)

    Jason M Warner

    Full Text Available SNARE proteins are conserved components of the core fusion machinery driving diverse membrane adhesion and fusion processes in the cell. In many cases micron-sized membranes adhere over large areas before fusion. Reconstituted in vitro assays have helped isolate SNARE mechanisms in small membrane adhesion-fusion and are emerging as powerful tools to study large membrane systems by use of giant unilamellar vesicles (GUVs. Here we model SNARE-mediated adhesion kinetics in SNARE-reconstituted GUV-GUV or GUV-supported bilayer experiments. Adhesion involves many SNAREs whose complexation pulls apposing membranes into contact. The contact region is a tightly bound rapidly expanding patch whose growth velocity v(patch increases with SNARE density Gamma(snare. We find three patch expansion regimes: slow, intermediate, fast. Typical experiments belong to the fast regime where v(patch ~ (Gamma(snare(2/3 depends on SNARE diffusivities and complexation binding constant. The model predicts growth velocities ~10 - 300 microm/s. The patch may provide a close contact region where SNAREs can trigger fusion. Extending the model to a simple description of fusion, a broad distribution of fusion times is predicted. Increasing SNARE density accelerates fusion by boosting the patch growth velocity, thereby providing more complexes to participate in fusion. This quantifies the notion of SNAREs as dual adhesion-fusion agents.

  14. Physically based principles of cell adhesion mechanosensitivity in tissues

    International Nuclear Information System (INIS)

    Ladoux, Benoit; Nicolas, Alice

    2012-01-01

    The minimal structural unit that defines living organisms is a single cell. By proliferating and mechanically interacting with each other, cells can build complex organization such as tissues that ultimately organize into even more complex multicellular living organisms, such as mammals, composed of billions of single cells interacting with each other. As opposed to passive materials, living cells actively respond to the mechanical perturbations occurring in their environment. Tissue cell adhesion to its surrounding extracellular matrix or to neighbors is an example of a biological process that adapts to physical cues. The adhesion of tissue cells to their surrounding medium induces the generation of intracellular contraction forces whose amplitude adapts to the mechanical properties of the environment. In turn, solicitation of adhering cells with physical forces, such as blood flow shearing the layer of endothelial cells in the lumen of arteries, reinforces cell adhesion and impacts cell contractility. In biological terms, the sensing of physical signals is transduced into biochemical signaling events that guide cellular responses such as cell differentiation, cell growth and cell death. Regarding the biological and developmental consequences of cell adaptation to mechanical perturbations, understanding mechanotransduction in tissue cell adhesion appears as an important step in numerous fields of biology, such as cancer, regenerative medicine or tissue bioengineering for instance. Physicists were first tempted to view cell adhesion as the wetting transition of a soft bag having a complex, adhesive interaction with the surface. But surprising responses of tissue cell adhesion to mechanical cues challenged this view. This, however, did not exclude that cell adhesion could be understood in physical terms. It meant that new models and descriptions had to be created specifically for these biological issues, and could not straightforwardly be adapted from dead matter

  15. Alport's syndrome with focal segmental glomerulosclerosis lesion - Pattern to recognize.

    Science.gov (United States)

    Alsahli, Afnan A; Alshahwan, Sara I; Alotaibi, Amal O; Alsaad, Khaled O; Aloudah, Nourah; Farooqui, Mahfooz; Al Sayyari, Abdullah A

    2018-01-01

    The association between Alport's syndrome (AS) and focal segmental glomerulosclerosis (FSGS) in the same patient is complex and rarely reported. We report a case of a 42-year-old male presenting with proteinuria, microscopic hematuria, elevated serum creatinine and hypertension with unremarkable physical examination apart from obesity. The renal biopsy showed well-established FSGS pattern of injury with mild interstitial fibrosis and tubular atrophy, while the electron microscopic examination demonstrated glomerular basement membranes (GBM) changes compatible with AS. AS can be complicated by segmental glomerular scarring, which can mimic primary FSGS, while familial FSGS can result from mutations in collagen IV network of the GBM. This overlap can complicate histopathological interpretation of renal biopsy, which should be accompanied by mutational analysis for accurate diagnosis and proper therapeutic intervention.

  16. Adhesion and multi-materials

    International Nuclear Information System (INIS)

    Schultz, J.

    1997-01-01

    Adhesion is a multidisciplinary science relevant to many practical fields. The main application of adhesion is bonding by adhesives. This technique is widely used in the industrial world and more specifically in the advanced technical domains. Adhesion is also involved in multi-component materials such as coatings, multilayer materials, polymer blends, composite materials... The multidisciplinary aspect of adhesion is well demonstrated by considering the wide variety of concepts, models and theories proposed for its description. An example of the adhesion between a fiber and a matrix in a composite material will lead to a general model relating the molecular properties of the interface to its capacity of stress transfer and hence to the macroscopic mechanical properties of the composite. This relationship is valid whatever the fiber (glass, carbon, polymeric) or the polymer matrix (thermoplastics, thermosetting). Any deviation from this model can be attributed to the existence of an interfacial zone or interphase exhibiting properties, mainly mechanical properties, different from the bulk matrix. Two examples are examined: the first one deals with the creation of a trans crystalline interphase in a semi-crystalline thermoplastic matrix and the second one is concerned with the formation of a pseudo glassy interphase in an elastomer matrix. These examples stress the need for complementary approaches in the understanding of adhesion phenomena at different levels of knowledge, from molecular to macroscopic. They also show how important it is to understand the mechanisms of formation of inter phases in order to be able to master the performance of multicomponent materials. (Author)

  17. TANNIN ADHESIVES AS AN ALTENATIVE TO THE SYNTHETIC PHENOLIC ADHESIVES

    Directory of Open Access Journals (Sweden)

    Semra Çolak

    2003-04-01

    Full Text Available Recently, increasing attention has been paid industrially to the use of tannin formaldehyde adhesives in production of wood based panel products such as particleboard, fiber board and plywood. The researches on the use of tannin extracts as a wood adhesive started in 1950, however, they proceeded very slowly since the problems associated with the application of them. The idea which tannin extract can be used replace the oil-based phenolic adhesive was the base of several studies after the oil crisis of the 1970s. In the past, the economical aspects were important in the researches on the tannin-based adhesives. Nowadays, however, both economical and ecological factors should have taken into consideration in wood bonding.

  18. Fabrication and Characterization of Gecko-inspired Fibrillar Adhesive

    Science.gov (United States)

    Kim, Yongkwan

    Over the last decade, geckos' remarkable ability to stick to and climb surfaces found in nature has motivated a wide range of scientific interest in engineering gecko-mimetic surface for various adhesive and high friction applications. The high adhesion and friction of its pads have been attributed to a complex array of hairy structures, which maximize surface area for van der Waals interaction between the toes and the counter-surface. While advances in micro- and nanolithography technique have allowed fabrication of increasingly sophisticated gecko mimetic surfaces, it remains a challenge to produce an adhesive as robust as that of the natural gecko pads. In order to rationally design gecko adhesives, understanding the contact behavior of fibrillar interface is critical. The first chapter of the dissertation introduces gecko adhesion and its potential applications, followed by a brief survey of gecko-inspired adhesives. Challenges that limit the performance of the current adhesives are presented. In particular, it is pointed out that almost all testing of gecko adhesives have been on clean, smooth glass, which is ideal for adhesion due to high surface energy and low roughness. Surfaces in application are more difficult to stick to, so the understanding of failure modes in low energy and rough surfaces is important. The second chapter presents a fabrication method for thermoplastic gecko adhesive to be used for a detailed study of fibrillar interfaces. Low-density polyethylene nanofibers are replicated from a silicon nanowire array fabricated by colloidal lithography and metal-catalyzed chemical etching. This process yields a highly ordered array of nanofibers over a large area with control over fiber diameter, length, and number density. The high yield and consistency of the process make it ideal for a systematic study on factors that affect adhesion and friction of gecko adhesives. The following three chapters examine parameters that affect macroscale friction of

  19. Photovoltaic module with adhesion promoter

    Science.gov (United States)

    Xavier, Grace

    2013-10-08

    Photovoltaic modules with adhesion promoters and methods for fabricating photovoltaic modules with adhesion promoters are described. A photovoltaic module includes a solar cell including a first surface and a second surface, the second surface including a plurality of interspaced back-side contacts. A first glass layer is coupled to the first surface by a first encapsulating layer. A second glass layer is coupled to the second surface by a second encapsulating layer. At least a portion of the second encapsulating layer is bonded directly to the plurality of interspaced back-side contacts by an adhesion promoter.

  20. Adhesives from modified soy protein

    Science.gov (United States)

    Sun, Susan [Manhattan, KS; Wang, Donghai [Manhattan, KS; Zhong, Zhikai [Manhattan, KS; Yang, Guang [Shanghai, CN

    2008-08-26

    The present invention provides useful adhesive compositions having similar adhesive properties to conventional UF and PPF resins. The compositions generally include a protein portion and modifying ingredient portion selected from the group consisting of carboxyl-containing compounds, aldehyde-containing compounds, epoxy group-containing compounds, and mixtures thereof. The composition is preferably prepared at a pH level at or near the isoelectric point of the protein. In other preferred forms, the adhesive composition includes a protein portion and a carboxyl-containing group portion.

  1. Structural adhesives directory and databook

    CERN Document Server

    Wilson, Jo

    1996-01-01

    A worldwide directory of commercially available adhesive products for use in a wide range of engineering disciplines. Along with product names and suppliers, basic property data are tabulated and cross-referenced. The book is subdivided according to class of adhesive, with introductions to each class followed by comparison tables and datasheets for each adhesive. The datasheets contain detailed information, from product codes to environmental properties and are therefore of interest across a broad readership. Standardized data will aid the user in cross-comparison between different manufacturers and in easily identifying the required information.

  2. Gecko Adhesion on Wet and Dry Patterned Substrates.

    Directory of Open Access Journals (Sweden)

    Alyssa Y Stark

    Full Text Available Perhaps one of the most astounding characteristics of the gecko adhesive system is its versatility. Geckos can locomote across complex substrates in a variety of conditions with apparent ease. In contrast, many of our synthetic pressure sensitive adhesives fail on substrates that are dirty, wet or rough. Although many studies have investigated the effect of environmental challenges on performance, the interaction of multiple, potentially compromising variables is studied less often. Here we focus on substrate structure and surface water, both of which are highly relevant to the biological system and to synthetic design. To do this we utilized a highly controlled, patterned substrate (Sharklet®, by Sharklet® Technologies Inc.. This allowed us to test independently and jointly the effects of reduced surface area substrates, with a defined pattern, on adhesion in both air and water. Our results show that adhesion is not significantly impaired in air, whereas surface area and pattern significantly affect adhesion in water. These findings highlight the need to study multiple parameters that are relevant to the gecko adhesive system to further improve our understanding of the biological system and to design better, more versatile synthetics.

  3. Dystroglycan versatility in cell adhesion: a tale of multiple motifs

    Directory of Open Access Journals (Sweden)

    Winder Steve J

    2010-02-01

    Full Text Available Abstract Dystroglycan is a ubiquitously expressed heterodimeric adhesion receptor. The extracellular α-subunit makes connections with a number of laminin G domain ligands including laminins, agrin and perlecan in the extracellular matrix and the transmembrane β-subunit makes connections to the actin filament network via cytoskeletal linkers including dystrophin, utrophin, ezrin and plectin, depending on context. Originally discovered as part of the dystrophin glycoprotein complex of skeletal muscle, dystroglycan is an important adhesion molecule and signalling scaffold in a multitude of cell types and tissues and is involved in several diseases. Dystroglycan has emerged as a multifunctional adhesion platform with many interacting partners associating with its short unstructured cytoplasmic domain. Two particular hotspots are the cytoplasmic juxtamembrane region and at the very carboxy terminus of dystroglycan. Regions which between them have several overlapping functions: in the juxtamembrane region; a nuclear localisation signal, ezrin/radixin/moesin protein, rapsyn and ERK MAP Kinase binding function, and at the C terminus a regulatory tyrosine governing WW, SH2 and SH3 domain interactions. We will discuss the binding partners for these motifs and how their interactions and regulation can modulate the involvement of dystroglycan in a range of different adhesion structures and functions depending on context. Thus dystroglycan presents as a multifunctional scaffold involved in adhesion and adhesion-mediated signalling with its functions under exquisite spatio-temporal regulation.

  4. Comparing Soy Flour Wood Adhesives to Purified Soy Protein Adhesives

    Science.gov (United States)

    Charles R. Frihart; Linda F. Lorenz

    2013-01-01

    While economics dictate that soy-based wood adhesives be made with soy flour, much of the recent literature on soy-based wood adhesives has involved using soy protein isolate. The obvious assumption is that the additional carbohydrates in the flour but not in the isolate only serve as inert diluents. Our studies have shown that the isolate can provide 10 times the wet...

  5. Cell Adhesion, the Backbone of the Synapse: “Vertebrate” and “Invertebrate” Perspectives

    OpenAIRE

    Giagtzoglou, Nikolaos; Ly, Cindy V.; Bellen, Hugo J.

    2009-01-01

    Synapses are asymmetric intercellular junctions that mediate neuronal communication. The number, type, and connectivity patterns of synapses determine the formation, maintenance, and function of neural circuitries. The complexity and specificity of synaptogenesis relies upon modulation of adhesive properties, which regulate contact initiation, synapse formation, maturation, and functional plasticity. Disruption of adhesion may result in structural and functional imbalance that may lead to neu...

  6. Lap Shear and Impact Testing of Ochre and Beeswax in Experimental Middle Stone Age Compound Adhesives

    NARCIS (Netherlands)

    Kozowyk, P.R.B.; Langejans, G.; Poulis, J.A.

    2016-01-01

    The production of compound adhesives using disparate ingredients is seen as some of the best evidence of advanced cognition outside of the use of symbolism. Previous field and laboratory testing of adhesives has shown the complexities involved in creating an effective Middle Stone Age glue using

  7. Bacterial endotoxin adhesion to different types of orthodontic adhesives

    Directory of Open Access Journals (Sweden)

    Priscilla Coutinho ROMUALDO

    Full Text Available Abstract Bacterial endotoxin (LPS adhesion to orthodontic brackets is a known contributing factor to inflammation of the adjacent gingival tissues. Objective The aim of this study was to assess whether LPS adheres to orthodontic adhesive systems, comparing two commercial brands. Material and Methods Forty specimens were fabricated from Transbond XT and Light Bond composite and bonding agent components (n=10/component, then contaminated by immersion in a bacterial endotoxin solution. Contaminated and non-contaminated acrylic resin samples were used as positive and negative control groups, respectively. LPS quantification was performed by the Limulus Amebocyte Lysate QCL-1000™ test. Data obtained were scored and subjected to the Chi-square test using a significance level of 5%. Results There was endotoxin adhesion to all materials (p0.05. There was no significant difference (p>0.05 among commercial brands. Affinity of endotoxin was significantly greater for the bonding agents (p=0.0025. Conclusions LPS adhered to both orthodontic adhesive systems. Regardless of the brand, the endotoxin had higher affinity for the bonding agents than for the composites. There is no previous study assessing the affinity of LPS for orthodontic adhesive systems. This study revealed that LPS adheres to orthodontic adhesive systems. Therefore, additional care is recommended to orthodontic applications of these materials.

  8. The Simbol-X Focal Plane

    Science.gov (United States)

    Laurent, P.

    2009-05-01

    The Simbol-X focal plane is designed to detect photons focused by the mirror in the 0.5 to 100 keV energy band. Composed of two detectors, it will measure the position, energy, and arrival time of each incoming X-ray. On top of it will be a collimator to shield all photons not coming from the mirror field of view. The whole system is surrounded by an active and passive shielding in order to ensure the required very low background.

  9. Focal inflammatory diseases of the liver

    International Nuclear Information System (INIS)

    Oto, Aytekin; Akhan, Okan; Oezmen, Mustafa

    1999-01-01

    Inflammatory lesions constitute an important subgroup of focal liver lesions. They may mimic primary or metastatic neoplastic lesions and their differentiation from neoplasia is clinically very important since management of the patient significantly changes. Radiologists should have an important role in both the diagnosis and therapy of these lesions by performing percutaneous aspirations and drainages. In this review we discussed the radiological findings of pyogenic abscesses, amebic abscesses, candidiasis, tuberculosis, hydatic cysts, fascioliasis, ascariasis, schistosomiasis, and sarcoidosis with a special emphasis on US, CT and MR characteristics

  10. Focal inflammatory diseases of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Oto, Aytekin; Akhan, Okan; Oezmen, Mustafa

    1999-10-01

    Inflammatory lesions constitute an important subgroup of focal liver lesions. They may mimic primary or metastatic neoplastic lesions and their differentiation from neoplasia is clinically very important since management of the patient significantly changes. Radiologists should have an important role in both the diagnosis and therapy of these lesions by performing percutaneous aspirations and drainages. In this review we discussed the radiological findings of pyogenic abscesses, amebic abscesses, candidiasis, tuberculosis, hydatic cysts, fascioliasis, ascariasis, schistosomiasis, and sarcoidosis with a special emphasis on US, CT and MR characteristics.

  11. Characterization of DECam focal plane detectors

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, H.Thomas; Angstadt, Robert; Campa, Julia; Cease, Herman; Derylo, Greg; Emes, John H.; Estrada, Juan; Kibik, Donna; Flaugher, Brenna L.; Holland, Steve E.; Jonas, Michelle; /Fermilab /Madrid, CIEMAT /LBL, Berkeley /Argonne /Pennsylvania U.

    2008-06-01

    DECam is a 520 Mpix, 3 square-deg FOV imager being built for the Blanco 4m Telescope at CTIO. This facility instrument will be used for the 'Dark Energy Survey' of the southern galactic cap. DECam has chosen 250 ?m thick CCDs, developed at LBNL, with good QE in the near IR for the focal plane. In this work we present the characterization of these detectors done by the DES team, and compare it to the DECam technical requirements. The results demonstrate that the detectors satisfy the needs for instrument.

  12. Underwater adhesion: The barnacle way

    Digital Repository Service at National Institute of Oceanography (India)

    Khandeparker, L.; Anil, A.C.

    . Understanding of the molecular mechanisms of adhesion, that is bioadhesive bond formation and curing, is essential to develop a more rational approach in designing fouling- release coatings. Silicone biofouling release coatings have been shown...

  13. Lap Shear and Impact Testing of Ochre and Beeswax in Experimental Middle Stone Age Compound Adhesives.

    Science.gov (United States)

    Kozowyk, P R B; Langejans, G H J; Poulis, J A

    2016-01-01

    The production of compound adhesives using disparate ingredients is seen as some of the best evidence of advanced cognition outside of the use of symbolism. Previous field and laboratory testing of adhesives has shown the complexities involved in creating an effective Middle Stone Age glue using Acacia gum. However, it is currently unclear how efficient different adhesive recipes are, how much specific ingredients influence their performance, and how difficult it may have been for those ingredients to be combined to maximum effect. We conducted a series of laboratory-based lap shear and impact tests, following modern adhesion testing standards, to determine the efficacy of compound adhesives, with particular regard to the ingredient ratios. We tested rosin (colophony) and gum adhesives, containing additives of beeswax and ochre in varying ratios. During both lap shear and impact tests compound rosin adhesives performed better than single component rosin adhesives, and pure acacia gum was the strongest. The large difference in performance between each base adhesive and the significant changes in performance that occur due to relatively small changes in ingredient ratios lend further support to the notion that high levels of skill and knowledge were required to consistently produce the most effective adhesives.

  14. Adhesion defective BHK cell mutant has cell surface heparan sulfate proteoglycan of altered properties

    DEFF Research Database (Denmark)

    Couchman, J R; Austria, R; Woods, A

    1988-01-01

    In the light of accumulating data that implicate cell surface heparan sulfate proteoglycans (HSPGs) with a role in cell interactions with extracellular matrix molecules such as fibronectin, we have compared the properties of these molecules in wild-type BHK cells and an adhesion-defective ricin......-resistant mutant (RicR14). Our results showed that the mutant, unlike BHK cells, cannot form focal adhesions when adherent to planar substrates in the presence of serum. Furthermore, while both cell lines possess similar amounts of cell surface HSPG with hydrophobic properties, that of RicR14 cells had decreased...... sulfation, reduced affinity for fibronectin and decreased half-life on the cell surface when compared to the normal counterpart. Our conclusions based on this data are that these altered properties may, in part, account for the adhesion defect in the ricin-resistant mutant. Whether this results from...

  15. Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization.

    Science.gov (United States)

    Dzamba, Bette J; Jakab, Karoly R; Marsden, Mungo; Schwartz, Martin A; DeSimone, Douglas W

    2009-03-01

    In this study we demonstrate that planar cell polarity signaling regulates morphogenesis in Xenopus embryos in part through the assembly of the fibronectin (FN) matrix. We outline a regulatory pathway that includes cadherin adhesion and signaling through Rac and Pak, culminating in actin reorganization, myosin contractility, and tissue tension, which, in turn, directs the correct spatiotemporal localization of FN into a fibrillar matrix. Increased mechanical tension promotes FN fibril assembly in the blastocoel roof (BCR), while reduced BCR tension inhibits matrix assembly. These data support a model for matrix assembly in tissues where cell-cell adhesions play an analogous role to the focal adhesions of cultured cells by transferring to integrins the tension required to direct FN fibril formation at cell surfaces.

  16. Mechanisms of adhesion in geckos.

    Science.gov (United States)

    Autumn, Kellar; Peattie, Anne M

    2002-12-01

    The extraordinary adhesive capabilities of geckos have challenged explanation for millennia, since Aristotle first recorded his observations. We have discovered many of the secrets of gecko adhesion, yet the millions of dry, adhesive setae on the toes of geckos continue to generate puzzling new questions and valuable answers. Each epidermally-derived, keratinous seta ends in hundreds of 200 nm spatular tips, permitting intimate contact with rough and smooth surfaces alike. Prior studies suggested that adhesive force in gecko setae was directly proportional to the water droplet contact angle (θ) , an indicator of the free surface energy of a substrate. In contrast, new theory suggests that adhesion energy between a gecko seta and a surface (W(GS)) is in fact proportional to (1 + cosθ), and only for θ > 60°. A reanalysis of prior data, in combination with our recent study, support the van der Waals hypothesis of gecko adhesion, and contradict surface hydrophobicity as a predictor of adhesion force. Previously, we and our collaborators measured the force production of a single seta. Initial efforts to attach a seta failed because of improper 3D orientation. However, by simulating the dynamics of gecko limbs during climbing (based on force plate data) we discovered that, in single setae, a small normal preload, combined with a 5 μm displacement yielded a very large adhesive force of 200 microNewton (μN), 10 times that predicted by whole-animal measurements. 6.5 million setae of a single tokay gecko attached maximally could generate 130 kg force. This raises the question of how geckos manage to detach their feet in just 15 ms. We discovered that simply increasing the angle that the setal shaft makes with the substrate to 30° causes detachment. Understanding how simultaneous attachment and release of millions of setae are controlled will require an approach that integrates levels ranging from molecules to lizards.

  17. Bio-Inspired Controllable Adhesive

    Science.gov (United States)

    2008-12-01

    pad of the tarsus – which act as a sort of hydraulic suspension. The lamellae contain rows of thin slender fibers , called setae, approximately 130 µm...in length and 20 µm in diameter (Hildebrand, 1988), Fig.1. The terminus of each seta branches into thousands of smaller fibers , or spatular stalks...ADHESION TESTING The structures were characterized (Northen et al., 2008) using a home-built adhesion test apparatus ( Basalt - II) with C. Greiner

  18. Protein-based underwater adhesives and the prospects for their biotechnological production.

    Science.gov (United States)

    Stewart, Russell J

    2011-01-01

    Biotechnological approaches to practical production of biological protein-based adhesives have had limited success over the last several decades. Broader efforts to produce recombinant adhesive proteins may have been limited by early disappointments. More recent synthetic polymer approaches have successfully replicated some aspects of natural underwater adhesives. For example, synthetic polymers, inspired by mussels, containing the catecholic functional group of 3,4-L-dihydroxyphenylalanine adhere strongly to wet metal oxide surfaces. Synthetic complex coacervates inspired by the Sandcastle worm are water-borne adhesives that can be delivered underwater without dispersing. Synthetic approaches offer several advantages, including versatile chemistries and scalable production. In the future, more sophisticated mimetic adhesives may combine synthetic copolymers with recombinant or agriculture-derived proteins to better replicate the structural and functional organization of natural adhesives.

  19. Fibrillar Adhesive for Climbing Robots

    Science.gov (United States)

    Pamess, Aaron; White, Victor E.

    2013-01-01

    A climbing robot needs to use its adhesive patches over and over again as it scales a slope. Replacing the adhesive at each step is generally impractical. If the adhesive or attachment mechanism cannot be used repeatedly, then the robot must carry an extra load of this adhesive to apply a fresh layer with each move. Common failure modes include tearing, contamination by dirt, plastic deformation of fibers, and damage from loading/ unloading. A gecko-like fibrillar adhesive has been developed that has been shown useful for climbing robots, and may later prove useful for grasping, anchoring, and medical applications. The material consists of a hierarchical fibrillar structure that currently contains two levels, but may be extended to three or four levels in continuing work. The contacting level has tens of thousands of microscopic fibers made from a rubberlike material that bend over and create intimate contact with a surface to achieve maximum van der Waals forces. By maximizing the real area of contact that these fibers make and minimizing the bending energy necessary to achieve that contact, the net amount of adhesion has been improved dramatically.

  20. Association of membrane/lipid rafts with the platelet cytoskeleton and the caveolin PY14: participation in the adhesion process.

    Science.gov (United States)

    Cerecedo, Doris; Martínez-Vieyra, Ivette; Maldonado-García, Deneb; Hernández-González, Enrique; Winder, Steve J

    2015-11-01

    Platelets are the most prominent elements of blood tissue involved in hemostasis at sites of blood vessel injury. Platelet cytoskeleton is responsible for their shape modifications observed during activation and adhesion to the substratum; therefore the interactions between cytoskeleton and plasma membrane are critical to modulate blood platelet functions. Several cytoskeletal components and binding partners, as well as enzymes that regulate the cytoskeleton, localize to membrane/lipid rafts (MLR) and regulate lateral diffusion of membrane proteins and lipids. Resting, thrombin-activated, and adherent human platelets were processed for biochemical studies including western-blot and immunprecipitation assays and confocal analysis were performed to characterize the interaction of MLR with the main cytoskeleton elements and β-dystroglycan as well as with the association of caveolin-1 PY14 with focal adhesion proteins. We transfected a megakaryoblast cell line (Meg-01) to deplete β-dystroglycan, subsequent to their differentiation to the platelet progenitors. Our data showed a direct interaction of the MLR with cytoskeleton to regulate platelet shape, while an association of caveolin-1 PY14 with vinculin is needed to establish focal adhesions, which are modulated for β-dystroglycan. In conclusion, caveolin-1 PY14 in association with platelet cytoskeleton participate in focal adhesions dynamics. © 2015 Wiley Periodicals, Inc.

  1. Idiopathic focal epilepsies: the "lost tribe".

    Science.gov (United States)

    Pal, Deb K; Ferrie, Colin; Addis, Laura; Akiyama, Tomoyuki; Capovilla, Giuseppe; Caraballo, Roberto; de Saint-Martin, Anne; Fejerman, Natalio; Guerrini, Renzo; Hamandi, Khalid; Helbig, Ingo; Ioannides, Andreas A; Kobayashi, Katsuhiro; Lal, Dennis; Lesca, Gaetan; Muhle, Hiltrud; Neubauer, Bernd A; Pisano, Tiziana; Rudolf, Gabrielle; Seegmuller, Caroline; Shibata, Takashi; Smith, Anna; Striano, Pasquale; Strug, Lisa J; Szepetowski, Pierre; Valeta, Thalia; Yoshinaga, Harumi; Koutroumanidis, Michalis

    2016-09-01

    The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many "treats" for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age-related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow-wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro-temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau-Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro-clinical features warranting inclusion. In addition, a number of less well-defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The

  2. Laparoscopic Partial Hepatectomy of Focal Nodular Hyperplasia

    Directory of Open Access Journals (Sweden)

    Mayu Sakata

    2012-11-01

    Full Text Available Focal nodular hyperplasia is a benign liver lesion incidentally discovered with increasing frequency because of the proliferation of imaging studies. Radiographic characterization can diagnose this pathologic lesion and nonoperative therapy is the standard of care. However, surgical resection may be required for diagnostic reasons or symptomatic patients. Depending on the anatomic location of the lesion, biopsy and/or resection can be performed laparoscopically. We herein report the case of a 26-year-old Japanese woman with a hepatic tumor who required a medical examination. Her medical history was negative for alcohol abuse, oral contraceptive administration and trauma. Clinical examination showed no significant symptoms. Ultrasonography, computed tomography and magnetic resonance imaging showed a mass located in the left lateral segment of the liver with a diameter of about 40 mm. It was difficult to diagnose the tumor definitively from these imaging studies, so we performed laparoscopic partial hepatectomy with successive firing of endoscopic staplers. The histopathological diagnosis was focal nodular hyperplasia. Surgical procedures and postoperative course were uneventful and the patient was discharged from the hospital on postoperative day 5.

  3. CT scan findings in focal epilepsy

    International Nuclear Information System (INIS)

    Kobayashi, Eiki; Mihara, Tadahiro; Yamamoto, Kunimitsu; Yamashita, Kenji; Asakura, Tetsuhiko

    1980-01-01

    In 80 cases of focal epilepsy, excluding such cases as late onset after the age of 30 and traumatic or expansive lesions, the epileptogenic foci have been studied by comparing the CT findings with the seizure types and the EEG findings. The results were as follows: (1) Abnormal CT findings were observed in 36% of the patients. (2) These findings were classified into 4 large groups: localized cerebral atrophy, localized low density, localized high density with contrast enhancement and diffuse cerebral atrophy. (3) The incidence of CT abnormality was higher in the cases with continuous and localized EEG abnormality than in the cases with other types of EEG abnormality. In 48% of the cases, the location of the abnormal CT findings coincided with their EEG foci. (4) In the cases of temporal lobe epilepsy without abnormal CT images, the print-out data compared with the bilateral promised temporal regions, before and after contrast enhancement. The EMI-No. of the medial temporal focus increased more than that of the contralateral side in 3 cases out of 4 after contrast-media injection. (5) Moreover, for the purpose of comparing the CT findings on general seizures with those in focal seizures, we have studied 80 cases of general seizures. In the cases of the general seizures, abnormal CT findings were observed in only 16%. These abnormal findings were diffuse in 5 cases, localized in 6 cases, and combined in 3 cases. (author)

  4. The Sentinel-4 UVN focal plane assemblies

    Science.gov (United States)

    Hinger, Jürgen; Hohn, Rüdiger; Gebhardt, Eyk; Reichardt, Jörg

    2017-09-01

    The Sentinel-4 UVN Instrument is a dispersive imaging spectrometer covering the UV-VIS and the NIR wavelength. It is developed and built under an ESA contract by an industrial consortium led by Airbus Defence and Space. It will be accommodated on board of the MTG-S (Meteosat Third Generation - Sounder) satellite that will be placed in a geostationary orbit over Europe sampling data for generating two-dimensional maps of a number of atmospheric trace gases. The incoming light is dispersed by reflective gratings and detected by the two (UVVIS and NIR) CCDs mounted inside the focal plane assemblies. Both CCD detectors acquire spectral channels and spatial sampling in two orthogonal directions and will be operated at about 215 K mainly to minimize random telegraph signal effects and to reduce dark current. Stringent detector temperature as well as alignment stability requirements of less than +/-0.1 K per day respectively of less than 2 micrometers/2 arcseconds from ground to orbit are driving the FPA thermo-mechanical design. A specific FPA design feature is the redundant LED-calibration system for bad pixel detection as well as pixel gain and linearity monitoring. This paper reports on the design and qualification of the Focal Plane Assemblies with emphasis on thermo-mechanical as well as alignment stability verification.

  5. The Sentinel 4 focal plane subsystem

    Science.gov (United States)

    Hohn, Rüdiger; Skegg, Michael P.; Hermsen, Markus; Hinger, Jürgen; Williges, Christian; Reulke, Ralf

    2017-09-01

    The Sentinel 4 instrument is an imaging spectrometer, developed by Airbus under ESA contract in the frame of the joint European Union (EU)/ESA COPERNICUS program with the objective of monitoring trace gas concentrations. Sentinel 4 will provide accurate measurements of key atmospheric constituents such as ozone, nitrogen dioxide, sulfur dioxide, formaldehyde, as well as aerosol and cloud properties. Sentinel 4 is unique in being the first geostationary UVN mission. The SENTINEL 4 space segment will be integrated on EUMETSAT's Meteosat Third Generation Sounder satellite (MTG-S). Sentinel 4 will provide coverage of Europe and adjacent regions. The Sentinel 4 instrument comprises as a major element two Focal Plane Subsystems (FPS) covering the wavelength ranges 305 nm to 500 nm (UVVIS) and 750 nm to 775 nm (NIR) respectively. The paper describes the Focal Plane Subsystems, comprising the detectors, the optical bench and the control electronics. Further the design and development approach will be presented as well as first measurement results of FPS Qualification Model.

  6. Focal CT abnormality and epileptogenic focus

    International Nuclear Information System (INIS)

    Yagi, Kazuichi; Mihara, Tadahiro; Tottori, Takayasu; Matsuda, Kazumi; Watanabe, Yutaka; Seino, Masakazu

    1989-01-01

    In 31 patients with temporal lobe epilepsy, the precise site of epileptogenic focus was determined by means of a depth EEG recording as one of the presurgical evaluations. In 13 patients, a CT scan revealed focal lesions; 7 in the left temporal lobe and 6 in the right temporal lobe. In 5 of the 7 patients and in 5 of the 6 patients the epileptogenic foci were determined in the temporal lobe on the side of a CT lesion. However, in 2 of the patients with a CT lesion in the left temporal lobe, independent epileptogenic foci were found in both the temporal lobes, and in the other patient with a CT lesion in the right temporal lobe, they were found in the right frontal and left temporal lobes. Thus, the CT lesions agreed in lateralization and focality with the epileptogenic foci in 10 of the 13 patients (77%), but they disagreed in 3 (23%). A CT lesion disclosed in the temporal lobe does not necessarily indicate the side and/or site where the epileptogenic focus may be localized. Although exceptions may be made, spatial disagreement was exemplified between the CT lesion and epileptogenic focus. Therefore, extreme caution has to be taken on the side and/or site of the epileptogenic focus when functional surgical indication is to be made. (author)

  7. Serial neuroradiological studies in focal cerebritis

    International Nuclear Information System (INIS)

    Hatta, S.; Mochizuki, H.; Kuru, Y.; Miwa, H.; Kondo, T.; Mori, H.; Mizuno, Y.

    1994-01-01

    We report serial neuroradiological studies in a patient with focal cerebritis in the head of the left caudate nucleus. On the day after the onset of symptoms, CT showed an ill-defined low density lesion. The lack of contrast enhancement appeared to be the most important finding for differentiating focal cerebritis from an encapsulated brain abscess or a tumour. MRI two days later revealed the centre of the lesion to be of slightly low intensity on T1-weighted inversion recovery (IR) images and very low intensity on T2-weighted spin echo images, which appeared to correspond to the early cerebritis stage of experimentally induced cerebritis and brain abscess. Ten days after the onset of symptoms, CT revealed a thin ring of enhancement in the head of the caudate nucleus, and a similar small ring was seen in the hypothalamus 16 days after the onset, corresponding to the late cerebritis stage. MRI nine days later revealed ill-defined high signal lesions within the involved area on the T1-weighted IR images. To our knowledge, this is the first published MRI documentation of the early cerebritis stage developing into an encapsulated brain abscess. The mechanisms underlying of these radiographic changes are discussed. (orig.)

  8. Structural and effective connectivity in focal epilepsy

    Directory of Open Access Journals (Sweden)

    Christopher S. Parker

    2018-01-01

    Full Text Available Patients with medically-refractory focal epilepsy may be candidates for neurosurgery and some may require placement of intracranial EEG electrodes to localise seizure onset. Assessing cerebral responses to single pulse electrical stimulation (SPES may give diagnostically useful data. SPES produces cortico-cortical evoked potentials (CCEPs, which infer effective brain connectivity. Diffusion-weighted images and tractography may be used to estimate structural brain connectivity. This combination provides the opportunity to observe seizure onset and its propagation throughout the brain, spreading contiguously along the cortex explored with electrodes, or non-contiguously. We analysed CCEPs and diffusion tractography in seven focal epilepsy patients and reconstructed the effective and structural brain networks. We aimed to assess the inter-modal similarity of the networks at a large scale across the cortex, the effective and structural connectivity of the ictal-onset zone, and investigate potential mechanisms of non-contiguous seizure spread. We found a significant overlap between structural and effective networks. Effective network CCEP amplitude, baseline variation, and outward connectivity was higher at ictal-onset zones, while structural connection strength within the ictal-onset zone tended to be higher. These findings support the concept of hyperexcitable cortex being associated with seizure generation. The high prevalence of structural and effective connections from the ictal-onset zone to sites of non-contiguous spread suggests that macroscopic structural and effective connections are plausible routes for non-contiguous seizure spread.

  9. Ultrasound elastographic techniques in focal liver lesions.

    Science.gov (United States)

    Conti, Clara Benedetta; Cavalcoli, Federica; Fraquelli, Mirella; Conte, Dario; Massironi, Sara

    2016-03-07

    Elastographic techniques are new ultrasound-based imaging techniques developed to estimate tissue deformability/stiffness. Several ultrasound elastographic approaches have been developed, such as static elastography, transient elastography and acoustic radiation force imaging methods, which include point shear wave and shear wave imaging elastography. The application of these methods in clinical practice aims at estimating the mechanical tissues properties. One of the main settings for the application of these tools has been liver stiffness assessment in chronic liver disease, which has been studied mainly using transient elastography. Another field of application for these techniques is the assessment of focal lesions, detected by ultrasound in organs such as pancreas, prostate, breast, thyroid, lymph nodes. Considering the frequency and importance of the detection of focal liver lesions through routine ultrasound, some studies have also aimed to assess the role that elestography can play in studying the stiffness of different types of liver lesions, in order to predict their nature and thus offer valuable non-invasive methods for the diagnosis of liver masses.

  10. Focal fatty infiltra- tion and focal fatty sparing of the liver

    African Journals Online (AJOL)

    Enrique

    Department of Radiology. Nelson Mandela School of Health Sciences. Durban. Fig. 1a. Unenhanced CT of the liver in case 1 demonstrates multiple focal low density regions in both lobes of the liver. Region of interest 1 over the fatty left lobe measured 10 HU while region of interest 2 over the right lobe measure 40 HU in.

  11. Proteomic dataset of the sea urchin Paracentrotus lividus adhesive organs and secreted adhesive

    NARCIS (Netherlands)

    Lebesgue, Nicolas; da Costa, Gonçalo; Ribeiro, Raquel Mesquita; Ribeiro-Silva, Cristina; Martins, Gabriel G; Matranga, Valeria; Scholten, Arjen; Cordeiro, Carlos; Heck, Albert J R; Santos, Romana

    Sea urchins have specialized adhesive organs called tube feet, which mediate strong but reversible adhesion. Tube feet are composed by a disc, producing adhesive and de-adhesive secretions for substratum attachment, and a stem for movement. After detachment the secreted adhesive remains bound to the

  12. Fracture analysis of adhesive joints in wind turbine blades

    DEFF Research Database (Denmark)

    Eder, Martin Alexander; Bitsche, Robert

    2015-01-01

    Modern wind turbine rotor blades are usually made from fibre-reinforced composite subcomponents. In the final assembly stage, these subcomponents are bonded together by several adhesive joints. One important adhesive joint is situated at the trailing edge, which refers to the downstream edge where...... the air-flow rejoins and leaves the blade. Maintenance inspections of wind turbine rotor blades show that among other forms of damage, local debonding of the shells along the trailing edge is a frequent failure type. The cause of trailing edge failure in wind turbine blades is complex, and detailed...

  13. CT appearance of focal fatty infiltration of the liver

    International Nuclear Information System (INIS)

    Halvorsen, R.A.; Korobkin, M.; Ram, P.C.; Thompson, W.M.

    1982-01-01

    Focal fatty infiltration of the liver is an entity that may be confused with liver metastasis on computed tomography (CT). The imaging results and medical records of 16 patients with CT appearance suggestive of focal fatty liver were reviewed, three of whom had the simultaneous presence of metastitic liver disease. Focal fatty liver often has a distinctive appearance with CT, usually with a nonspherical shape, absence of mass effect, and density close to water. Liver metastases are usually round or oval, and unless cystic or necrotic, they have CT attenuation values closer to normal liver parenchyma than water. A radionuclide liver scan almost always resolves any confusion about the differential diagnosis of focal fatty liver: a well defined focus of photon deficiency is due to neoplasm rather than focal fatty infiltration. Sonography sometimes helps to confirm the CT impression, but may be misleading if the diagnosis of focal or diffuse fatty infiltration is not suspected before the examination

  14. The study of the focal trough in panoramic radiograph

    International Nuclear Information System (INIS)

    Park, C. S.; Kim, H. P.

    1982-01-01

    In the study of the focal trough of panoramic radiograph, using the Moritta company Panex EC a series of 48 exposures were taken with the 6-18 brass pins placed in the holes of the plastic model plate, then evaluated by 4 observers. The author analyzed the focal trough defined by the sharpness criteria and calculated the vertical and horizontal magnification range in the corrected focal trough. The results were as follows; 1. Continuous focal trough was not defined in the anterior region using a very high degree of sharpness. 2. As degree of sharpness used in the analysis became less, focal trough was continuous in the anterior and posterior regions, symmetrized bilaterally, and the widths of the focal trough increased more in the posterior region. 3. As sharpness criteria were reduced, the percentage range of image magnification increased in both vertical and horizontal magnification, and especially the percentage range of horizontal magnification was greater than that of vertical magnification.

  15. Multi-focal Vision and Gaze Control Improve Navigation Performance

    Directory of Open Access Journals (Sweden)

    Kolja Kuehnlenz

    2008-11-01

    Full Text Available Multi-focal vision systems comprise cameras with various fields of view and measurement accuracies. This article presents a multi-focal approach to localization and mapping of mobile robots with active vision. An implementation of the novel concept is done considering a humanoid robot navigation scenario where the robot is visually guided through a structured environment with several landmarks. Various embodiments of multi-focal vision systems are investigated and the impact on navigation performance is evaluated in comparison to a conventional mono-focal stereo set-up. The comparative studies clearly show the benefits of multi-focal vision for mobile robot navigation: flexibility to assign the different available sensors optimally in each situation, enhancement of the visible field, higher localization accuracy, and, thus, better task performance, i.e. path following behavior of the mobile robot. It is shown that multi-focal vision may strongly improve navigation performance.

  16. Denture adhesives: a systematic review.

    Science.gov (United States)

    Papadiochou, Sofia; Emmanouil, Ioannis; Papadiochos, Ioannis

    2015-05-01

    Denture adhesives have been the objective of scientific research for over half a century. Although they are used by denture wearers worldwide, investigations of their effectiveness and biocompatibility have led to controversial conclusions. The purpose of this study was to review the literature data with regard to the effectiveness and biocompatibility of denture adhesives as well as the attitudes of both patients and dental professionals toward these materials. An electronic search of English peer-reviewed dental literature in the Medline database was conducted to evaluate the effectiveness and biocompatibility of denture adhesives. There was no limitation in publication year, so the search included all the available scientific evidence included in that particular database until March 2014. Specific inclusion criteria were used for the selection of the appropriate articles. A manual search of the citations of the obtained articles followed to extend the electronic search. A full text review was carried out for only 32 articles. Of the 32 articles, 21 examined the efficacy of denture adhesives in terms of retention and stability and masticatory performance, 6 evaluated the issue of the biocompatibility of denture adhesives, and 5 presented the attitudes of either professionals or patients toward these materials. The majority of clinical studies supported the fact that denture adhesives enhance the retention, stability, and masticatory performance of a removable prosthesis. In terms of biocompatibility, long-term in vivo studies to investigate potential harmful effects were lacking. Patients are satisfied with denture adhesives that meet their needs. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  17. The Role of TSC Proteins in Regulating Cell Adhesion and Motility

    National Research Council Canada - National Science Library

    Krymskaya, Vera P

    2006-01-01

    The goal of this project was to define the molecular signaling mechanisms by which TSCI and TSC2 proteins regulate cell adhesion and motility as it relates to the genetic disorder tuberous sclerosis complex (TSC...

  18. Selective inhibition of prostaglandin E2 receptors EP2 and EP4 inhibits adhesion of human endometriotic epithelial and stromal cells through suppression of integrin-mediated mechanisms.

    Science.gov (United States)

    Lee, JeHoon; Banu, Sakhila K; Burghardt, Robert C; Starzinski-Powitz, Anna; Arosh, Joe A

    2013-03-01

    Endometriosis is a chronic gynecological disease of reproductive age women characterized by the presence of functional endometrial tissues outside the uterine cavity. Interactions between the endometriotic cells and the peritoneal extracellular matrix proteins (ECM) are crucial mechanisms that allow adhesion of the endometriotic cells into peritoneal mesothelia. Prostaglandin E2 (PGE2) plays an important role in the pathogenesis of endometriosis. In previous studies, we have reported that selective inhibition of PGE2 receptors PTGER2 and PTGER4 decreases survival and invasion of human endometriotic epithelial and stromal cells through multiple mechanisms. Results of the present study indicates that selective inhibition of PTGER2- and PTGER4-mediated PGE2 signaling 1) decreases the expression and/or activity of specific integrin receptor subunits Itgb1 (beta1) and Itgb3 (beta3) but not Itgb5 (beta5), Itga1 (alpha1), Itga2 (alpha2), Itga5 (alpha5), and Itgav (alphav); 2) decreases integrin-signaling components focal adhesion kinase or protein kinase 2 (PTK2) and talin proteins; 3) inhibits interactions between Itgb1/Itgb3 subunits, PTK2, and talin and PTGER2/PTGER4 proteins through beta-arrestin-1 and Src kinase protein complex in human endometriotic epithelial cells 12Z and stromal cells 22B; and 4) decreases adhesion of 12Z and 22B cells to ECM collagen I, collagen IV, fibronectin, and vitronectin in a substrate-specific manner. These novel findings provide an important molecular framework for further evaluation of selective inhibition of PTGER2 and PTGER4 as potential nonsteroidal therapy to expand the spectrum of currently available treatment options for endometriosis in child-bearing age women.

  19. Innovative Electrostatic Adhesion Technologies

    Science.gov (United States)

    Bryan, Tom; Macleod, Todd; Gagliano, Larry; Williams, Scott; McCoy, Brian

    2015-01-01

    Developing specialized Electro-Static grippers (commercially used in Semiconductor Manufacturing and in package handling) will allow gentle and secure Capture, Soft Docking, and Handling of a wide variety of materials and shapes (such as upper-stages, satellites, arrays, and possibly asteroids) without requiring physical features or cavities for a pincher or probe or using harpoons or nets. Combined with new rigid boom mechanisms or small agile chaser vehicles, flexible, high speed Electro-Static Grippers can enable compliant capture of spinning objects starting from a safe stand-off distance. Electroadhesion (EA) can enable lightweight, ultra-low-power, compliant attachment in space by using an electrostatic force to adhere similar and dissimilar surfaces. A typical EA enabled device is composed of compliant space-rated materials, such as copper-clad polyimide encapsulated by polymers. Attachment is induced by strong electrostatic forces between any substrate material, such as an exterior satellite panel and a compliant EA gripper pad surface. When alternate positive and negative charges are induced in adjacent planar electrodes in an EA surface, the electric fields set up opposite charges on the substrate and cause an electrostatic adhesion between the electrodes and the induced charges on the substrate. Since the electrodes and the polymer are compliant and can conform to uneven or rough surfaces, the electrodes can remain intimately close to the entire surface, enabling high clamping pressures. Clamping pressures of more than 3 N/cm2 in shear can be achieved on a variety of substrates with ultra-low holding power consumption (measured values are less than 20 microW/Newton weight held). A single EA surface geometry can be used to clamp both dielectric and conductive substrates, with slightly different physical mechanisms. Furthermore EA clamping requires no normal force be placed on the substrate, as conventional docking requires. Internally funded research and

  20. Focal cemento-osseous dysplasia of mandible.

    Science.gov (United States)

    Cankaya, Abdülkadir Burak; Erdem, Mehmet Ali; Olgac, Vakur; Firat, Deniz Refia

    2012-09-03

    Fibro-osseous lesions are disturbances in bone metabolism in which normal bone is replaced by a connective tissue matrix that then gradually develops into cemento-osseous tissue. Typically, the lesion is asymptomatic and is detected on routine radiographic examination. Radiologically, this lesion has three stages of maturation: pure radiolucent, radiopaque/mixed radiolucent, and radiopaque appearance. During these stages the lesion can be misdiagnosed. In this case report a 69-year- old patient with a a complaint of painless swelling of the left mandibular molar and premolar area is presented along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia.

  1. Strong reducing of the laser focal volume

    CSIR Research Space (South Africa)

    Godin, T

    2011-08-01

    Full Text Available equal to -1 or +1 modeled on the p light rings of the incident TEMp0 beam. The transformation quality of a 30TEM beam into a single-lobed pattern in the focal plane is shown in Fig. 3. It is clear that the intensity pattern of the rectified beam... DOE (blue solid line), rectified 30TEM (red solid line) -3 -2 -1 0 1 2 3 0 1 2 3 4 z=0 z=f DOE Fig. 2 -60 -50 -40 -30 -20 -10 0 10 20 30 40 50 60 0,0 0,2 0,4 0,6 0,8 1,0 TEM30 without DOE "rectified" TEM30 TEM00 In te ns...

  2. Smart trigger logic for focal plane arrays

    Science.gov (United States)

    Levy, James E; Campbell, David V; Holmes, Michael L; Lovejoy, Robert; Wojciechowski, Kenneth; Kay, Randolph R; Cavanaugh, William S; Gurrieri, Thomas M

    2014-03-25

    An electronic device includes a memory configured to receive data representing light intensity values from pixels in a focal plane array and a processor that analyzes the received data to determine which light values correspond to triggered pixels, where the triggered pixels are those pixels that meet a predefined set of criteria, and determines, for each triggered pixel, a set of neighbor pixels for which light intensity values are to be stored. The electronic device also includes a buffer that temporarily stores light intensity values for at least one previously processed row of pixels, so that when a triggered pixel is identified in a current row, light intensity values for the neighbor pixels in the previously processed row and for the triggered pixel are persistently stored, as well as a data transmitter that transmits the persistently stored light intensity values for the triggered and neighbor pixels to a data receiver.

  3. Pharmacological response of systemically derived focal epileptic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Sigvardt, K.; Marcussen, W.H.

    1986-11-01

    Focal epileptic lesions were made in rats by systemic focal epileptogenesis. In this method, a focal lesion of the blood-brain barrier (BBB) is produced by focal alpha irradiation followed by repeated systemic injection of a convulsant drug that cannot cross the normal BBB, resulting in a chronic epileptic focus. Changes in the spike frequency of these foci in response to various drugs was recorded. The controls, saline and chlorpromazine, produced no change. Phenytoin, phenobarbital, chlordiazepoxide, and valproic acid produced the expected decrease in spike frequency. Pentobarbital and diazepam produced a paradoxical increase in spike frequency.

  4. Focal cryotherapy: step by step technique description

    Directory of Open Access Journals (Sweden)

    Cristina Redondo

    Full Text Available ABSTRACT Introduction and objective: Focal cryotherapy emerged as an efficient option to treat favorable and localized prostate cancer (PCa. The purpose of this video is to describe the procedure step by step. Materials and methods: We present the case of a 68 year-old man with localized PCa in the anterior aspect of the prostate. Results: The procedure is performed under general anesthesia, with the patient in lithotomy position. Briefly, the equipment utilized includes the cryotherapy console coupled with an ultrasound system, argon and helium gas bottles, cryoprobes, temperature probes and an urethral warming catheter. The procedure starts with a real-time trans-rectal prostate ultrasound, which is used to outline the prostate, the urethra and the rectal wall. The cryoprobes are pretested and placed in to the prostate through the perineum, following a grid template, along with the temperature sensors under ultrasound guidance. A cystoscopy confirms the right positioning of the needles and the urethral warming catheter is installed. Thereafter, the freeze sequence with argon gas is started, achieving extremely low temperatures (-40°C to induce tumor cell lysis. Sequentially, the thawing cycle is performed using helium gas. This process is repeated one time. Results among several series showed a biochemical disease-free survival between 71-93% at 9-70 month- follow-up, incontinence rates between 0-3.6% and erectile dysfunction between 0-42% (1–5. Conclusions: Focal cryotherapy is a feasible procedure to treat anterior PCa that may offer minimal morbidity, allowing good cancer control and better functional outcomes when compared to whole-gland treatment.

  5. Polyurethane adhesives in flat roofs

    Directory of Open Access Journals (Sweden)

    Bogárová Markéta

    2017-01-01

    Full Text Available It is necessary to stabilize individual layers of flat roofs, mainly because of wind suction. Apart from anchoring and surcharge, these layers can be secured by bonding. At present gluing is an indispensable and widely used stabilization method. On our market we can found many types of adhesives, most widely used are based on polyurethane. This paper focuses on problematic about stabilization thermal insulation from expanded polystyrene to vapor barrier from bitumen. One of the main issues is to calculate the exact amount of adhesive, which is required to guarantee the resistance against wind suction. In this problematic we can not find help neither in technical data sheets provided by the manufactures. Some of these data sheets contain at least information about amount of adhesive depending on location in roof plane and building height, but they do not specify the strength of such connection. It was therefore resorted to select several representatives polyurethane adhesives and their subsequent testing on specimens simulating the flat roof segment. The paper described the test methodology and results for two types of polyurethane adhesives.

  6. Preliminary results on adhesion improvement using Ion Beam Sputtering Deposition

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yonggi; Kim, Bomsok; Lee, Jaesang [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-05-15

    Sputtering is an established technique for depositing films with smooth surfaces and interfaces and good thick control. Ejection of articles from a condensed matter due to impingement of high energy particles, termed as sputtering was observed as early as in 1852, however, it is only recently that the complex process of sputtering system. Coating adhesion and environmental stability of the ion beam sputtering deposition coatings performed very well. High-energy high-current ion beam thin film synthesis of adhesion problems can be solved by using. Enhancement of adhesion in thin film synthesis, using high energy and high current ion beam, of mobile phones, car parts and other possible applications in the related industry Alternative technology of wet chrome plating, considering environment and unit cost, for car parts and esthetic improvement on surface of domestic appliances.

  7. Preliminary results on adhesion improvement using Ion Beam Sputtering Deposition

    International Nuclear Information System (INIS)

    Kim, Yonggi; Kim, Bomsok; Lee, Jaesang

    2013-01-01

    Sputtering is an established technique for depositing films with smooth surfaces and interfaces and good thick control. Ejection of articles from a condensed matter due to impingement of high energy particles, termed as sputtering was observed as early as in 1852, however, it is only recently that the complex process of sputtering system. Coating adhesion and environmental stability of the ion beam sputtering deposition coatings performed very well. High-energy high-current ion beam thin film synthesis of adhesion problems can be solved by using. Enhancement of adhesion in thin film synthesis, using high energy and high current ion beam, of mobile phones, car parts and other possible applications in the related industry Alternative technology of wet chrome plating, considering environment and unit cost, for car parts and esthetic improvement on surface of domestic appliances

  8. Adhesion Dynamics in Probing Micro- and Nanoscale Thin Solid Films

    Directory of Open Access Journals (Sweden)

    Xiaoling He

    2008-01-01

    Full Text Available This study focuses on modeling the probe dynamics in scratching and indenting thin solid films at micro- and nanoscales. The model identifies bifurcation conditions that define the stick-slip oscillation patterns of the tip. It is found that the local energy fluctuations as a function of the inelastic deformation, defect formation, material properties, and contact parameters determine the oscillation behavior. The transient variation of the localized function makes the response nonlinear at the adhesion junction. By quantifying the relation between the bifurcation parameters and the oscillation behavior, this model gives a realistic representation of the complex adhesion dynamics. Specifically, the model establishes the link between the stick-slip behavior and the inelastic deformation and the local potentials. This model justifies the experimental observations and the molecular dynamics simulation of the adhesion and friction dynamics in both the micro- and nanoscale contact.

  9. The diminishing dominance of the dominant hemisphere: Language fMRI in focal epilepsy

    Directory of Open Access Journals (Sweden)

    Chris Tailby

    2017-01-01

    Our data highlight the importance of considering language as a complex task where lateralisation varies at the subhemispheric scale. This is especially important for presurgical planning for focal resections where the concept of ‘hemispheric dominance’ may be misleading. This is a precision medicine approach that enables objective evaluation of language dominance within specific brain regions and can reveal surprising and unexpected anomalies that may be clinically important for individual cases.

  10. Focal cortical dysplasia of the temporal lobe with late-onset partial epilepsy: serial quantitative MRI

    Energy Technology Data Exchange (ETDEWEB)

    Rademacher, J.; Seitz, R.J. [Department of Neurology, Heinrich-Heine University Duesseldorf (Germany); Aulich, A. [Department of Radiology, Heinrich-Heine University, Duesseldorf (Germany); Reifenberger, G. [Department of Neuropathology, Heinrich-Heine University, Duesseldorf (Germany); Kiwit, J.C.W. [Department of Neurosurgery, Heinrich-Heine University, Duesseldorf (Germany); Langen, K.J.; Schmidt, D. [Institute of Medicine, Research Center Juelich, Heinrich-Heine University, Duesseldorf (Germany)

    2000-06-01

    We describe serial studies of focal cortical dysplasia causing temporal lobe seizures and progressive aphasia in a 54-year-old woman. Initially, MRI volumetry of the temporal lobes showed significant left cortical thickening corresponding to an elevated aminoacid uptake in the left temporoparietal and inferior frontal cortex on SPECT using 3-[{sup 123}I]iodo-{alpha}-methyl-l-tyrosine (IMT). After 1 year there was severe shrinkage of the left temporal lobe, possibly the result of recurrent complex partial seizures. (orig.)

  11. Focal cortical dysplasia of the temporal lobe with late-onset partial epilepsy: serial quantitative MRI

    International Nuclear Information System (INIS)

    Rademacher, J.; Seitz, R.J.; Aulich, A.; Reifenberger, G.; Kiwit, J.C.W.; Langen, K.J.; Schmidt, D.

    2000-01-01

    We describe serial studies of focal cortical dysplasia causing temporal lobe seizures and progressive aphasia in a 54-year-old woman. Initially, MRI volumetry of the temporal lobes showed significant left cortical thickening corresponding to an elevated aminoacid uptake in the left temporoparietal and inferior frontal cortex on SPECT using 3-[ 123 I]iodo-α-methyl-l-tyrosine (IMT). After 1 year there was severe shrinkage of the left temporal lobe, possibly the result of recurrent complex partial seizures. (orig.)

  12. SYSTEMATIC ANALYSIS OF REAL-WORLD DRIVING BEHAVIOR FOLLOWING FOCAL BRAIN LESIONS

    OpenAIRE

    Thompson, Kelsey; Read, Katherine; Anderson, Steven; Rizzo, Matthew

    2011-01-01

    Many patients with circumscribed brain injuries, such as those caused by stroke or focal trauma, return to driving after a period of acute recovery. These persons often have chronic residual cognitive deficits that may impact on driving safety, but little is known about their driving behavior in the real world. Extant studies tend to rely on driving simulators or controlled on-road drives. These methods of observation are not able to capture the complexities of the typical driving environment...

  13. Comparison of different approaches to the numerical calculation of the LMJ focal

    Directory of Open Access Journals (Sweden)

    Bourgeade A.

    2013-11-01

    Full Text Available The beam smoothing in the focal plane of high power lasers is of particular importance to laser-plasma interaction studies in order to minimize plasma parametric and hydrodynamic instabilities on the target. Here we investigate the focal spot structure in different geometrical configurations where standard paraxial hypotheses are no longer verified. We present numerical studies in the cases of single flat top square beam, LMJ quadruplet and complete ring of quads with large azimuth angle. Different calculations are made with Fresnel diffraction propagation model in the paraxial approximation and full vector Maxwell's equations. The first model is based on Fourier transform from near to far field method. The second model uses first spherical wave decomposition in plane waves with Fourier transform and propagates them to the focal spot. These two different approaches are compared with Miró [1] modeling results using paraxial or Feit and Fleck options. The methods presented here are generic for focal spot calculations. They can be used for other complex geometric configurations and various smoothing techniques. The results will be used as boundary conditions in plasma interaction computations.

  14. Deriving the effective focal plane for the CBM-RICH detector

    Energy Technology Data Exchange (ETDEWEB)

    Kres, Ievgenii [Wuppertal University (Germany); Collaboration: CBM-Collaboration

    2016-07-01

    The Compressed Baryonic Matter (CBM) experiment at the future FAIR complex will investigate the phase diagram of strongly interacting matter at high baryon density and moderate temperatures in A+A collisions from 2-11 AGeV (SIS100). A central component of the proposed detector setup is a ring imaging Cherenkov detector (RICH) using CO2 as radiator gas, and a focussing optic with a large spherical mirror. In the present design, the optimal focal plane is approximated using four individual, flat detection surfaces. However, the exact shape and position of the ideal focal plane is subject to further optimization due to effects from tilting the focussing mirror and from momentum dependant deflection of the electron tracks in the magnetic stray field. In this talk, we present a new approach to derive the effective 3-dimensional shape of the focal plane based on a set of Monte Carlo simulations, comparing the ring sharpness at each point of a preliminary focal plane as function of z-position.

  15. The FRIABLE1 gene product affects cell adhesion in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Lutz Neumetzler

    Full Text Available Cell adhesion in plants is mediated predominantly by pectins, a group of complex cell wall associated polysaccharides. An Arabidopsis mutant, friable1 (frb1, was identified through a screen of T-DNA insertion lines that exhibited defective cell adhesion. Interestingly, the frb1 plants displayed both cell and organ dissociations and also ectopic defects in organ separation. The FRB1 gene encodes a Golgi-localized, plant specific protein with only weak sequence similarities to known proteins (DUF246. Unlike other cell adhesion deficient mutants, frb1 mutants do not have reduced levels of adhesion related cell wall polymers, such as pectins. Instead, FRB1 affects the abundance of galactose- and arabinose-containing oligosaccharides in the Golgi. Furthermore, frb1 mutants displayed alteration in pectin methylesterification, cell wall associated extensins and xyloglucan microstructure. We propose that abnormal FRB1 action has pleiotropic consequences on wall architecture, affecting both the extensin and pectin matrices, with consequent changes to the biomechanical properties of the wall and middle lamella, thereby influencing cell-cell adhesion.

  16. Lignin-Furfural Based Adhesives

    Directory of Open Access Journals (Sweden)

    Prajakta Dongre

    2015-07-01

    Full Text Available Lignin recovered from the hot-water extract of sugar maple (Acer saccharum is used in this study to synthesize adhesive blends to replace phenol-formaldehyde (PF resin. Untreated lignin is characterized by lignin content and nuclear magnetic resonance (NMR analysis. The molecular weight distribution of the lignin and the blends are characterized by size exclusion chromatography (SEC. The effect of pH (0.3, 0.65 and 1, ex situ furfural, and curing conditions on the tensile properties of adhesive reinforced glass fibers is determined and compared to the reinforcement level of commercially available PF resin. The adhesive blend prepared at pH = 0.65 with no added furfural exhibits the highest tensile properties and meets 90% of the PF tensile strength.

  17. A low-cost, high-yield fabrication method for producing optimized biomimetic dry adhesives

    International Nuclear Information System (INIS)

    Sameoto, D; Menon, C

    2009-01-01

    We present a low-cost, large-scale method of fabricating biomimetic dry adhesives. This process is useful because it uses all photosensitive polymers with minimum fabrication costs or complexity to produce molds for silicone-based dry adhesives. A thick-film lift-off process is used to define molds using AZ 9260 photoresist, with a slow acting, deep UV sensitive material, PMGI, used as both an adhesion promoter for the AZ 9260 photoresist and as an undercutting material to produce mushroom-shaped fibers. The benefits to this process are ease of fabrication, wide range of potential layer thicknesses, no special surface treatment requirements to demold silicone adhesives and easy stripping of the full mold if process failure does occur. Sylgard® 184 silicone is used to cast full sheets of biomimetic dry adhesives off 4'' diameter wafers, and different fiber geometries are tested for normal adhesion properties. Additionally, failure modes of the adhesive during fabrication are noted and strategies for avoiding these failures are discussed. We use this fabrication method to produce different fiber geometries with varying cap diameters and test them for normal adhesion strengths. The results indicate that the cap diameters relative to post diameters for mushroom-shaped fibers dominate the adhesion properties

  18. Sighting optics including an optical element having a first focal length and a second focal length and methods for sighting

    Science.gov (United States)

    Crandall, David Lynn

    2011-08-16

    Sighting optics include a front sight and a rear sight positioned in a spaced-apart relation. The rear sight includes an optical element having a first focal length and a second focal length. The first focal length is selected so that it is about equal to a distance separating the optical element and the front sight and the second focal length is selected so that it is about equal to a target distance. The optical element thus brings into simultaneous focus for a user images of the front sight and the target.

  19. Fibrous hyaluronic acid hydrogels that direct MSC chondrogenesis through mechanical and adhesive cues.

    Science.gov (United States)

    Kim, Iris L; Khetan, Sudhir; Baker, Brendon M; Chen, Christopher S; Burdick, Jason A

    2013-07-01

    Electrospinning has recently gained much interest due to its ability to form scaffolds that mimic the nanofibrous nature of the extracellular matrix, such as the size and depth-dependent alignment of collagen fibers within hyaline cartilage. While much progress has been made in developing bulk, isotropic hydrogels for tissue engineering and understanding how the microenvironment of such scaffolds affects cell response, these effects have not been extensively studied in a nanofibrous system. Here, we show that the mechanics (through intrafiber crosslink density) and adhesivity (through RGD density) of electrospun hyaluronic acid (HA) fibers significantly affect human mesenchymal stem cell (hMSC) interactions and gene expression. Specifically, hMSC spreading, proliferation, and focal adhesion formation were dependent on RGD density, but not on the range of fiber mechanics investigated. Moreover, traction-mediated fiber displacements generally increased with more adhesive fibers. The expression of chondrogenic markers, unlike trends in cell spreading and cytoskeletal organization, was influenced by both fiber mechanics and adhesivity, in which softer fibers and lower RGD densities generally enhanced chondrogenesis. This work not only reveals concurrent effects of mechanics and adhesivity in a fibrous context, but also highlights fibrous HA hydrogels as a promising scaffold for future cartilage repair strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Increasing mouse embryonic fibroblast cells adhesion on superhydrophilic vertically aligned carbon nanotube films

    Energy Technology Data Exchange (ETDEWEB)

    Lobo, A.O., E-mail: loboao@yahoo.com [Laboratory of Biomedical Nanotechnology (NanoBio), Instituto de Pesquisa e Desenvolvimento (IP and D), Universidade do Vale do Paraiba UniVap, Avenida Shishima Hifumi 2911, Sao Jose dos Campos, 12244-000, SP (Brazil) and Laboratory of Biomedical Vibrational Spectroscopy (LEVB), Instituto de Pesquisa e Desenvolvimento (IP and D), Universidade do Vale do Paraiba UniVap, Avenida Shishima Hifumi 2911, Sao Jose dos Campos, 12244-000, SP (Brazil); Marciano, F.R. [Laboratory of Biomedical Nanotechnology (NanoBio), Instituto de Pesquisa e Desenvolvimento (IP and D), Universidade do Vale do Paraiba UniVap, Avenida Shishima Hifumi 2911, Sao Jose dos Campos, 12244-000, SP (Brazil); Laboratory of Biomedical Vibrational Spectroscopy LEVB, Instituto de Pesquisa e Desenvolvimento (IP and D), Universidade do Vale do Paraiba (UniVap), Avenida Shishima Hifumi 2911, Sao Jose dos Campos, 12244-000, SP (Brazil); Ramos, S.C. [Laboratorio Associado de Sensores e Materiais (LAS), Instituto Nacional de Pesquisas Espaciais (INPE), Avenida dos Astronautas 1758, Sao Jose dos Campos, 12.245-970, SP (Brazil); Machado, M.M. [Centro Multidisciplinar para Investigacao Biologica na Area da Ciencia em Animais de Laboratorio (CEMIB), Universidade Estadual de Campinas (UNICAMP), Rua 05 de Junho s/no, Cidade Universitaria ' Zeferino Vaz' , 13083-877, Campinas (Brazil); Corat, E.J. [Laboratorio Associado de Sensores e Materiais (LAS), Instituto Nacional de Pesquisas Espaciais (INPE), Avenida dos Astronautas 1758, Sao Jose dos Campos, 12.245-970, SP (Brazil); Corat, M.A.F. [Centro Multidisciplinar para Investigacao Biologica na Area da Ciencia em Animais de Laboratorio (CEMIB), Universidade Estadual de Campinas (UNICAMP), Rua 05 de Junho s/no, Cidade Universitaria ' Zeferino Vaz' , 13083-877, Campinas (Brazil)

    2011-10-10

    We have analyzed the adhesion of mouse embryonic fibroblasts (MEFs) genetically modified by green fluorescence protein (GFP) gene cultured on vertically-aligned carbon nanotubes (VACNTs) after 6 days. The VACNTs films grown on Ti were obtained by microwave plasma chemical vapor deposition process using Fe catalyst and submitted to an oxygen plasma treatment, for 2 min, at 400 V and 80 mTorr, to convert them to superhydrophilic. Cellular adhesion and morphology were analyzed by scanning electron, fluorescence microscopy, and thermodynamics analysis. Characterizations of superhydrophilic VACNTs films were evaluated by contact angle and X-Ray Photoelectron Spectroscopy. Differences of crowd adhered cells, as well as their spreading on superhydrophilic VACNTs scaffolds, were evaluated using focal adhesion analysis. This study was the first to demonstrate, in real time, that the wettability of VACNTs scaffolds might have enhanced and differential adherence patterns to the MEF-GFP on VACNTs substrates. Highlights: {yields} A simple oxygen plasma treatment was used to obtain superhydrophilic CNT films. {yields} Superhydrophilic CNTs films were successfully produced by incorporation of carboxylic groups. {yields} Cellular adhesion on superhydrophilic VACNT films was analyzed in real time. {yields} Wettability of CNT films directly affects the cellular migration, proliferation and adhesion.

  1. Modeling cell-substrate de-adhesion dynamics under fluid shear

    Science.gov (United States)

    Maan, Renu; Rani, Garima; Menon, Gautam I.; Pullarkat, Pramod A.

    2018-07-01

    Changes in cell-substrate adhesion are believed to signal the onset of cancer metastasis, but such changes must be quantified against background levels of intrinsic heterogeneity between cells. Variations in cell-substrate adhesion strengths can be probed through biophysical measurements of cell detachment from substrates upon the application of an external force. Here, we investigate, theoretically and experimentally, the detachment of cells adhered to substrates when these cells are subjected to fluid shear. We present a theoretical framework within which we calculate the fraction of detached cells as a function of shear stress for fast ramps as well as the decay in this fraction at fixed shear stress as a function of time. Using HEK and 3T3 fibroblast cells as experimental model systems, we extract characteristic force scales for cell adhesion as well as characteristic detachment times. We estimate force-scales of  ∼500 pN associated to a single focal contact, and characteristic time-scales of s representing cell-spread-area dependent mean first passage times to the detached state at intermediate values of the shear stress. Variations in adhesion across cell types are especially prominent when cell detachment is probed by applying a time-varying shear stress. These methods can be applied to characterizing changes in cell adhesion in a variety of contexts, including metastasis.

  2. Cell-substrate interaction with cell-membrane-stress dependent adhesion.

    Science.gov (United States)

    Jiang, H; Yang, B

    2012-01-10

    Cell-substrate interaction is examined in a two-dimensional mechanics model. The cell and substrate are treated as a shell and an elastic solid, respectively. Their interaction through adhesion is treated using nonlinear springs. Compared to previous cell mechanics models, the present model introduces a cohesive force law that is dependent not only on cell-substrate distance but also on internal cell-membrane stress. It is postulated that a living cell would establish focal adhesion sites with density dependent on the cell-membrane stress. The formulated mechanics problem is numerically solved using coupled finite elements and boundary elements for the cell and the substrate, respectively. The nodes in the adhesion zone from either side are linked by the cohesive springs. The specific cases of a cell adhering to a homogeneous substrate and a heterogeneous bimaterial substrate are examined. The analyses show that the substrate stiffness affects the adhesion behavior significantly and regulates the direction of cell adhesion, in good agreement with the experimental results in the literature. By introducing a reactive parameter (i.e., cell-membrane stress) linking biological responses of a living cell to a mechanical environment, the present model offers a unified mechanistic vehicle for characterization and prediction of living cell responses to various kinds of mechanical stimuli including local extracellular matrix and neighboring cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Radiologic manifestations of focal cerebral hyperemia in acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Skriver, E B; Herning, M

    1991-01-01

    In 16 acute stroke patients with focal cerebral hyperemia angiography and regional cerebral blood flow (rCBF) were studied 1 to 4 days post stroke. CT was performed twice with and without contrast enhancement 3 +/- 1 days and 16 +/- 4 days post stroke. Angiographic evidence of focal cerebral hype...

  4. Focal decompositions for linear differential equations of the second order

    Directory of Open Access Journals (Sweden)

    L. Birbrair

    2003-01-01

    two-points problems to itself such that the image of the focal decomposition associated to the first equation is a focal decomposition associated to the second one. In this paper, we present a complete classification for linear second-order equations with respect to this equivalence relation.

  5. Focal necrotizing pneumonia is a distinct entity from lung abscess.

    Science.gov (United States)

    Seo, Hyewon; Cha, Seung-Ick; Shin, Kyung-Min; Lim, Jaekwang; Yoo, Seung-Soo; Lee, Jaehee; Lee, Shin-Yup; Kim, Chang-Ho; Park, Jae-Yong

    2013-10-01

    'Focal necrotizing pneumonia' was defined as a localized type of necrotizing pneumonia characterized by a single or few cavities of low density without rim enhancement on computed tomography (CT) scan. The purpose of this study was to investigate the clinical features and course of patients with focal necrotizing pneumonia, thereby elucidating its clinical relevance. The present study was conducted retrospectively in patients who had been interpreted as having lung abscess or necrotizing pneumonia on CT scan. Clinical and radiological characteristics were compared between the focal necrotizing pneumonia and lung abscess groups. Overall, 68 patients with focal necrotizing pneumonia (n = 35) or lung abscess (n = 33) were included in the present study. The frequency of risk factors for aspiration was significantly lower in the focal necrotizing group, compared with the lung abscess group (14.3% vs 45.5%, P = 0.005). Compared with lung abscess, focal necrotizing pneumonia was observed more commonly in non-gravity-dependent segments (66% vs 36%, P lung abscess group (31% vs 12%, P = 0.08). However, in terms of treatment outcomes, a similar high rate of success was observed in both groups: 97%, respectively. Compared to lung abscess, focal necrotizing pneumonia occurs more commonly in non-gravity-dependent segments with lower incidence of risk factors for aspiration. Similar to lung abscess, the rate of success for treatment of focal necrotizing pneumonia was high. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

  6. Proximal Focal Femoral Deficiency in Ibadan a Developing ...

    African Journals Online (AJOL)

    The cultural aversion to amputation in our environment makes it difficult to employ that option of treatment. Proximal focal femoral deficiency in Ibadan a developing country's perspective and a review of the literature. Keywords: Proximal focal femoral deficiency , congenital malformations , limb malformations , lower limb ...

  7. Concordance of MRI and EEG Focal Slowing in Nonsyndromic Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-04-01

    Full Text Available Investigators at the Kangwon National University, Korea, and The Epilepsy Center, Lurie Children’s Hospital of Chicago, USA studied the correlation and significance of EEG focal slowing and focal MRI abnormalities in 253 children with nonsyndromic epilepsy.

  8. Involvement of rho-gtpases in fibroblast adhesion and fibronectine fibrillogenesis under stretch

    Science.gov (United States)

    Guignandon, A.; Lambert, C.; Rattner, A.; Servotte, S.; Lapiere, C.; Nusgens, B.; Vico, L.

    The Rho family small GTPases play a crucial role in mediating cellular adaptation to mechanical stimulation (MS), and possibly to microgravity (μg), through effects on the cytoskeleton and cell adhesion which is, in turn, mainly regulated by fibronectin fibrillogenesis (FnF). It remains unclear how mechanical stimulation is transduced to the Rho signaling pathways and how it impacts on fibronectin (fbn) fibrillogenesis (FnF). μg (2 days, mission STS-095) led to de-adhesion of fibroblasts and modification of the underlying extracellular matrix. To determine whether GTPases modulated FnF, we generated stable cell lines expressing high level of activated RhoA and Rac1 (QL) as compared to wild type (WI26-WT). After MS application [8% deformation, 1Hz, 15 min., 3 times/day for 1-2 days], we quantified focal adhesion (vinculin, paxillin, FAKY397), f-actin stress fibers (Sf) and FnF with home-developed softwares. We reported that after MS, Sf are more rapidly (30min) formed under the nucleus in Wi26-WT (+100%) and Rac1 (+200%) than in RhoA (+20%). Vinculin & paxillin were only restricted to the cell edge in static conditions and homogeneously distributed after MS in WT and Rac1. The relative area of contacts (vinculin & paxillin) was more dramatically enhanced by MS in Rac1 (+80%) than in WT (+40%) and RhoA (+25%) indicating that new focal contacts are formed under MS and supported the presence of Sf. MS Activation of FAK (FAKY397) was clear in WT and Rac1 and reduced in RhoA. FnF was restricted to cell-cell contacts zone without any change in the relative area of fbn after a 2-days MS. However we found more numerous spots of fbn at the cell center in Rac1 as compared with RhoA & WT suggesting that these fibrillar contacts will grow upon maturation and modulate FnF. The results indicate that MS induces formation of Sf and focal adhesions and enhances FF. RhoA has been shown to induce the formation of Sf and focal adhesions, and Rac1 activation decreases Rho activity in

  9. Hysteroscopic Management Of Intrauterin Adhesion

    Directory of Open Access Journals (Sweden)

    Ayşegül Dikmen

    2013-03-01

    Full Text Available Objective: Assessment of preoperative and postoperative outcomes of patients that were performed hysterescopic intrauterine adhesiolysis. Material and method: We reviewed 24 patients that underwent hysterescopy with the complaints of amenorrhea, hypomenorrhea, recurrent pregnancy loss between 2004-2008. The most complaints of patients were infertilty amenorrhea. Results: Adhesions occurs mainly as a result of trauma to the gravid uterine cavity in 14 patients. When classifying patients with their intrauterine adhesions, Grade 3 was the most frequently seen. Adhesiolisis was performed with hysteresopic scissors in all patients. In postoperative period following synechiolysis, 10 patients were treated with estrogen and progestogen, 11 of them used intrauterine device with estrogen and progestogen therapy, foley catheter was used in 3 patients. Hysterescopy was performed in 5 patients for second time because of adhesion suspicions. The re-adhesiolysis performed to 3 patients because of determined to mild adhesion. Conclusion: After hysterescopic adhesiolysis, all patients with the complaint of amenorrhea had regular menstruation. Pregnancy after treatment occured in 4 patients but live birth rate was 75%.

  10. Candida biofilms: is adhesion sexy?

    Science.gov (United States)

    Soll, David R

    2008-08-26

    The development of Candida albicans biofilms requires two types of adhesion molecule - the Als proteins and Hwp1. Mutational analyses have recently revealed that these molecules play complementary roles, and their characteristics suggest that they may have evolved from primitive mating agglutinins.

  11. Influence of Blood Contamination During Multimode Adhesive ...

    African Journals Online (AJOL)

    2018-01-30

    Jan 30, 2018 ... (μTBS) of multimode adhesives to dentin when using the self‑etch approach. Materials and Methods: ... adhesion, the collagen fibers collapse during the. Introduction ..... The failure mode was determined using an optical.

  12. RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1.

    Science.gov (United States)

    Meyer Zum Büschenfelde, Uta; Brandenstein, Laura Isabel; von Elsner, Leonie; Flato, Kristina; Holling, Tess; Zenker, Martin; Rosenberger, Georg; Kutsche, Kerstin

    2018-05-01

    RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS.

  13. An empirical assessment of the focal species hypothesis.

    Science.gov (United States)

    Lindenmayer, D B; Lane, P W; Westgate, M J; Crane, M; Michael, D; Okada, S; Barton, P S

    2014-12-01

    Biodiversity surrogates and indicators are commonly used in conservation management. The focal species approach (FSA) is one method for identifying biodiversity surrogates, and it is underpinned by the hypothesis that management aimed at a particular focal species will confer protection on co-occurring species. This concept has been the subject of much debate, in part because the validity of the FSA has not been subject to detailed empirical assessment of the extent to which a given focal species actually co-occurs with other species in an assemblage. To address this knowledge gap, we used large-scale, long-term data sets of temperate woodland birds to select focal species associated with threatening processes such as habitat isolation and loss of key vegetation attributes. We quantified co-occurrence patterns among focal species, species in the wider bird assemblage, and species of conservation concern. Some, but not all, focal species were associated with high levels of species richness. One of our selected focal species was negatively associated with the occurrence of other species (i.e., it was an antisurrogate)-a previously undescribed property of nominated focal species. Furthermore, combinations of focal species were not associated with substantially elevated levels of bird species richness, relative to levels associated with individual species. Our results suggest that although there is some merit to the underpinning concept of the FSA, there is also a need to ensure that actions are sufficiently flexible because management tightly focused on a given focal species may not benefit some other species, including species of conservation concern, such of which might not occur in species-rich assemblages. © 2014 Society for Conservation Biology.

  14. Stress regimes in the northwest of Iran from stress inversion of earthquake focal mechanisms

    Science.gov (United States)

    Afra, Mahsa; Moradi, Ali; Pakzad, Mehrdad

    2017-11-01

    Northwestern Iran is one of the seismically active regions with a high seismic risk in the world. This area is a part of the complex tectonic system due to the interaction between Arabia, Anatolia and Eurasia. The purpose of this study is to deduce the stress regimes in the northwestern Iran and surrounding regions from stress inversion of earthquake focal mechanisms. We compile 92 focal mechanisms data from the Global CMT catalogue and other sources and also determine the focal mechanisms of 14 earthquakes applying the moment tensor inversion. We divide the studied region into 9 zones using similarity of the horizontal GPS velocities and existing focal mechanisms. We implement two stress inversion methods, Multiple Inverse Method and Iterative Joint Inversion Method, which provide comparable results in terms of orientations of maximum horizontal stress axes SHmax. The similar results of the two methods should make us more confident about the interpretations. We consider zones of exclusion surrounding all the earthquakes according to independent focal mechanisms hypothesis. The hypothesis says that the inversion should involve events that are far enough from each other in order that any previous event doesn't affect the stress field near the earthquake under consideration. Accordingly we deal with the matter by considering zones of exclusion around all the events. The result of exclusion is only significant for eastern Anatolia. The stress regime in this region changes from oblique to strike slip faulting because of the exclusion. In eastern Anatolia, the direction of maximum horizontal stress is nearly north-south. The direction alters to east-west in Talesh region. Errors of σ1 are lower in all zones comparing with errors of σ2 and σ3 and there is a trade-off between data resolution and covariance of the model. The results substantiate the strike-slip and thrust faulting stress regimes in the northwest of Iran.

  15. Landsat 9 OLI 2 focal plane subsystem: design, performance, and status

    Science.gov (United States)

    Malone, Kevin J.; Schrein, Ronald J.; Bradley, M. Scott; Irwin, Ronda; Berdanier, Barry; Donley, Eric

    2017-09-01

    The Landsat 9 mission will continue the legacy of Earth remote sensing that started in 1972. The Operational Land Imager 2 (OLI 2) is one of two instruments on the Landsat 9 satellite. The OLI 2 instrument is essentially a copy of the OLI instrument flying on Landsat 8. A key element of the OLI 2 instrument is the focal plane subsystem, or FPS, which consists of the focal plane array (FPA), the focal plane electronics (FPE) box, and low-thermal conductivity cables. This paper presents design details of the OLI 2 FPS. The FPA contains 14 critically-aligned focal plane modules (FPM). Each module contains 6 visible/near-IR (VNIR) detector arrays and three short-wave infrared (SWIR) arrays. A complex multi-spectral optical filter is contained in each module. Redundant pixels for each array provide exceptional operability. Spare detector modules from OLI were recharacterized after six years of storage. Radiometric test results are presented and compared with data recorded in 2010. Thermal, optical, mechanical and structural features of the FPA will be described. Special attention is paid to the thermal design of the FPA since thermal stability is crucial to ensuring low-noise and low-drift operation of the detectors which operate at -63°C. The OLI 2 FPE provides power, timing, and control to the focal plane modules. It also digitizes the video data and formats it for the solid-state recorder. Design improvements to the FPA-FPE cables will be discussed and characterization data will be presented. The paper will conclude with the status of the flight hardware assembly and testing.

  16. [Sotos syndrome associated with focal dystonia].

    Science.gov (United States)

    Bravo, M; Chacón, J; Bautista, E; Pérez-Camacho, I; Trujillo, A; Grande, M A

    Sotos syndrome is a form of infantile gigantism characterized by excessive body size from the time of birth, particular facies, acromegalic changes and signs of non-progressive cerebral involvement. The etiology is unknown. Diagnosis is based on somatometric data and the particular phenotype traits. Biochemical and endocrine studies are normal. Torticollis is a focal dystonia and therefore more common in adults. A 20 year old woman with macrosomic features since birth presented with: weight 104 kg, height 182 cm; prognathism, hypertelorism, a broad over hanging forehead with a high hair line; large ears, hands and feet; torticollis towards the right with elevation and anteroversion of the right shoulder which caused symptomatic scoliosis. She was bradypsychic and rather slow in speech. The complementary tests done (cerebral and cervical CT and MR, bone gammography, evoked potentials, EMG-ENG, sural nerve biopsy, biopsy of skin and muscle, EEG and hormone and biochemistry studies) were normal. The torticollis was treated with botulinus toxin and improved considerably, as did the scoliosis. To date, dystonia has not been described in association with Sotos syndrome. This may be a causal association, or even perhaps hereditary, since the patient's mother had dystonia (in the form of blepharospasm).

  17. Depression in focal, segmental and generalized dystonia.

    Science.gov (United States)

    Lewis, L; Butler, A; Jahanshahi, M

    2008-11-01

    Dystonia causes body disfigurement in the majority of those affected. Our aim was to test the hypothesis that low self-esteem resulting from the sense of disfigurement is an important component of self-reported depression in focal, segmental and generalized dystonia. Questionnaires to assess self-reported depression, self-esteem, body concept, disfigurement, disability and quality of life were completed by 329 community based dystonia patients. Moderate to severe depression was reported by 30 %. Self-reported depression had a strong somatic component, but patients also showed a specific concern with self-image. Extent of dystonia, body parts affected and marital status influenced self-reported depression in dystonia. Self esteem, body concept, disfigurement and quality of life emerged as factors which accounted for the variance of self-reported depression in dystonia. These results suggest that in dystonia, disfigurement, negative body concept, low self-esteem, and the impact of the disease on quality of life make important contributions to depression. However, longitudinal followup is required to firmly establish the direction of causality between depression and these psychosocial variables in dystonia.

  18. Visual agnosia and focal brain injury.

    Science.gov (United States)

    Martinaud, O

    Visual agnosia encompasses all disorders of visual recognition within a selective visual modality not due to an impairment of elementary visual processing or other cognitive deficit. Based on a sequential dichotomy between the perceptual and memory systems, two different categories of visual object agnosia are usually considered: 'apperceptive agnosia' and 'associative agnosia'. Impaired visual recognition within a single category of stimuli is also reported in: (i) visual object agnosia of the ventral pathway, such as prosopagnosia (for faces), pure alexia (for words), or topographagnosia (for landmarks); (ii) visual spatial agnosia of the dorsal pathway, such as cerebral akinetopsia (for movement), or orientation agnosia (for the placement of objects in space). Focal brain injuries provide a unique opportunity to better understand regional brain function, particularly with the use of effective statistical approaches such as voxel-based lesion-symptom mapping (VLSM). The aim of the present work was twofold: (i) to review the various agnosia categories according to the traditional visual dual-pathway model; and (ii) to better assess the anatomical network underlying visual recognition through lesion-mapping studies correlating neuroanatomical and clinical outcomes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Nonhuman primate models of focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Jingjing Fan

    2017-01-01

    Full Text Available Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

  20. Evaluation of Hemodynamics in Focal Steatosis and Focal Spared Lesion of the Liver Using Contrast-Enhanced Ultrasonography with Sonazoid

    International Nuclear Information System (INIS)

    Shiozawa, K.; Watanabe, M.; Ikehara, T.; Kogame, M.; Shinohara, M.; Shinohara, M.; Ishii, K.; Igarashi, Y.; Sumino, Y.; Shiozawa, K.; Makino, H.

    2014-01-01

    We aim to investigate the hemodynamics in focal steatosis and focal spared lesion of the liver using contrast-enhanced ultrasonography (CEUS) with Sonazoid. The subjects were 47 patients with focal steatosis and focal spared lesion. We evaluated enhancement patterns (hyper enhancement, iso enhancement, and hypo enhancement) in the vascular phase and the presence or absence of a hypoechoic area in the post vascular phase for these lesions using CEUS. Of the 24 patients with focal steatosis, the enhancement pattern was iso enhancement in 19 and hypo enhancement in 5. Hypoechoic areas were noted in the post vascular phase in 3 patients. Of the 23 patients with focal spared lesions, the enhancement pattern was iso enhancement in 18 and hyper enhancement in 5. No hypoechoic areas were noted in the post vascular phase in any patient. The hemodynamics in focal steatosis and focal spared lesions in non diffuse fatty liver can be observed using low-invasive procedures in real-time by CEUS. It was suggested that differences in the dynamics of enhancement in the vascular phase of CEUS were influenced by the fat deposits in the target lesion, the surrounding liver parenchyma, and the third inflow.

  1. Integrative systems and synthetic biology of cell-matrix adhesion sites.

    Science.gov (United States)

    Zamir, Eli

    2016-09-02

    The complexity of cell-matrix adhesion convolves its roles in the development and functioning of multicellular organisms and their evolutionary tinkering. Cell-matrix adhesion is mediated by sites along the plasma membrane that anchor the actin cytoskeleton to the matrix via a large number of proteins, collectively called the integrin adhesome. Fundamental challenges for understanding how cell-matrix adhesion sites assemble and function arise from their multi-functionality, rapid dynamics, large number of components and molecular diversity. Systems biology faces these challenges in its strive to understand how the integrin adhesome gives rise to functional adhesion sites. Synthetic biology enables engineering intracellular modules and circuits with properties of interest. In this review I discuss some of the fundamental questions in systems biology of cell-matrix adhesion and how synthetic biology can help addressing them.

  2. Aspirin augments hyaluronidase induced adhesion inhibition ...

    African Journals Online (AJOL)

    Postoperative adhesions occur after virtually all abdomino-pelvic surgery and are the leading cause of intestinal obstruction and other gynaecologic problems. We used an animal model to test the efficacy of combined administration of aspirin and hyaluronidase on adhesion formation. Adhesions were induced using ...

  3. Potential for Biobased Adhesives in Wood Bonding

    Science.gov (United States)

    Charles R. Frihart

    2016-01-01

    There has been a resurgence of interest and research on using bio-based materials as wood adhesives; however, they have achieved only limited market acceptance. To better understand this low level of replacement, it is important to understand why adhesives work or fail in moisture durability tests. A holistic model for wood adhesives has been developed that clarifies...

  4. Current dental adhesives systems. A narrative review.

    Science.gov (United States)

    Milia, Egle; Cumbo, Enzo; Cardoso, Rielson Jose A; Gallina, Giuseppe

    2012-01-01

    Adhesive dentistry is based on the development of materials which establish an effective bond with the tooth tissues. In this context, adhesive systems have attracted considerable research interest in recent years. Successful adhesive bonding depends on the chemistry of the adhesive, on appropriate clinical handling of the material as well as on the knowledge of the morphological changes caused on dental tissue by different bonding procedures. This paper outlines the status of contemporary adhesive systems, with particular emphasis on chemical characteristics and mode of interaction of the adhesives with enamel and dentinal tissues. Dental adhesives are used for several clinical applications and they can be classified based on the clinical regimen in "etch-and-rinse adhesives" and "self-etch adhesives". Other important considerations concern the different anatomical characteristics of enamel and dentine which are involved in the bonding procedures that have also implications for the technique used as well as for the quality of the bond. Etch-and-rinse adhesive systems generally perform better on enamel than self-etching systems which may be more suitable for bonding to dentine. In order to avoid a possible loss of the restoration, secondary caries or pulp damage due to bacteria penetration or due to cytotoxicity effects of eluted adhesive components, careful consideration of several factors is essential in selecting the suitable bonding procedure and adhesive system for the individual patient situation.

  5. Influence of substrate modulus on gecko adhesion

    Science.gov (United States)

    Klittich, Mena R.; Wilson, Michael C.; Bernard, Craig; Rodrigo, Rochelle M.; Keith, Austin J.; Niewiarowski, Peter H.; Dhinojwala, Ali

    2017-03-01

    The gecko adhesion system fascinates biologists and materials scientists alike for its strong, reversible, glue-free, dry adhesion. Understanding the adhesion system’s performance on various surfaces can give clues as to gecko behaviour, as well as towards designing synthetic adhesive mimics. Geckos encounter a variety of surfaces in their natural habitats; tropical geckos, such as Gekko gecko, encounter hard, rough tree trunks as well as soft, flexible leaves. While gecko adhesion on hard surfaces has been extensively studied, little work has been done on soft surfaces. Here, we investigate for the first time the influence of macroscale and nanoscale substrate modulus on whole animal adhesion on two different substrates (cellulose acetate and polydimethylsiloxane) in air and find that across 5 orders of magnitude in macroscale modulus, there is no change in adhesion. On the nanoscale, however, gecko adhesion is shown to depend on substrate modulus. This suggests that low surface-layer modulus may inhibit the gecko adhesion system, independent of other influencing factors such as macroscale composite modulus and surface energy. Understanding the limits of gecko adhesion is vital for clarifying adhesive mechanisms and in the design of synthetic adhesives for soft substrates (including for biomedical applications and wearable electronics).

  6. Focal plane mechanical design of the NISP/Euclid instrument

    Science.gov (United States)

    Bonnefoi, Anne; Bon, William; Niclas, Mathieu; Solheim, Bjarte G. B.; Torvanger, Oyvind; Schistad, Robert; Foulon, Benjamin; Garcia, José; Vives, Sébastien

    2016-07-01

    Currently in phase C, the Euclid mission selected by ESA in the Cosmic Vision program is dedicated to understand dark energy and dark matter. NISP (standing for Near Infrared Spectro-Photometer) is one of the two instruments of the mission. NISP will combine a photometer and a spectrometer working in the near-IR (0.9-2 microns). Its detection subsystem (called NI-DS) is based on a mosaic of 16 IR detectors cooled down to 90K which are supported by a molybdenum plate. The front-end readout electronics (working at 130K) are supported by another structure in Aluminum. The NI-DS is mounted on the rest of the instrument thanks to a panel in Silicon Carbide (SiC). Finally an optical baffle in Titanium will prevent the rogue light to reach the detectors. On top of the complexity due to the wide range of temperatures and the various materials imposed at the interfaces; the NI-DS has also to incorporate an internal adjustment capability of the position of the focal plane in tip/tilt and focus. This article will present current status of the development of the detection system of NISP.

  7. Focal plane based wavefront sensing with random DM probes

    Science.gov (United States)

    Pluzhnik, Eugene; Sirbu, Dan; Belikov, Ruslan; Bendek, Eduardo; Dudinov, Vladimir N.

    2017-09-01

    An internal coronagraph with an adaptive optical system for wavefront control is being considered for direct imaging of exoplanets with upcoming space missions and concepts, including WFIRST, HabEx, LUVOIR, EXCEDE and ACESat. The main technical challenge associated with direct imaging of exoplanets is to control of both diffracted and scattered light from the star so that even a dim planetary companion can be imaged. For a deformable mirror (DM) to create a dark hole with 10-10 contrast in the image plane, wavefront errors must be accurately measured on the science focal plane detector to ensure a common optical path. We present here a method that uses a set of random phase probes applied to the DM to obtain a high accuracy wavefront estimate even for a dynamically changing optical system. The presented numerical simulations and experimental results show low noise sensitivity, high reliability, and robustness of the proposed approach. The method does not use any additional optics or complex calibration procedures and can be used during the calibration stage of any direct imaging mission. It can also be used in any optical experiment that uses a DM as an active optical element in the layout.

  8. Strong composition dependence of adhesive properties of ultraviolet curing adhesives with modified acrylates

    Science.gov (United States)

    Feng, Yefeng; Li, Yandong; Wang, Fupeng; Peng, Cheng; Xu, Zhichao; Hu, Jianbing

    2018-05-01

    Ultraviolet (UV) curable adhesives have been widely researched in fields of health care and electronic components. UV curing systems with modified acrylic ester prepolymers have been frequently employed. In order to clarify composition dependence of adhesive properties of adhesives containing modified acrylates, in this work, several UV curing adhesives bearing urethane and epoxy acrylates were designed and fabricated. The effects of prepolymer, diluent, feed ratio, initiator and assistant on adhesive performances were investigated. This work might offer a facile route to gain promising high-performance UV curable adhesives with desired adhesive traits through regulating their compositions.

  9. Polyurethane structural adhesives applied in automotive composite joints

    Directory of Open Access Journals (Sweden)

    Josue Garcia Quini

    2012-06-01

    Full Text Available In recent years structural adhesives technology has demonstrated great potential for application due to its capacity to transform complex structures into solid unitary and monolithic assemblies using different materials. Thus, seams or joints integrate these structures providing, besides a reduction in weight, a considerable increase in the mechanical resistance and stiffness. The increase in the industrial use of structural adhesives is mainly due to their ability to efficiently bond different materials in an irreversible manner, even replacing systems involving mechanical joints. In the automobile industry structural adhesives have been widely used for the bonding of metal substrates, thermoplastics and composites, frequently employing these in combination, particularly glass fiber and polyester resin composites molded using RTM and SMC processes. However, the use of urethane structural adhesives in applications involving composites and thermoplastics has been the subject of few investigations. In this study the effects of temperature and time on the shear strength of RTM, SMC and ABS joints, applying temperatures of -40, 25, 80, 120 and 177 °C and times of 20 minutes and 500 hours, were determined. The objective was to evaluate the performance under extreme conditions of use in order to assess whether these joints could be used in passenger or off-road vehicles. The results showed that the urethane structural adhesive promoted the efficient bonding of these materials, considering that due to the high adhesive strength the failures occurred in the substrates without adversely affecting the bonded area. For each test condition the joint failure modes were also determined.

  10. Focal-plane change triggered video compression for low-power vision sensor systems.

    Directory of Open Access Journals (Sweden)

    Yu M Chi

    Full Text Available Video sensors with embedded compression offer significant energy savings in transmission but incur energy losses in the complexity of the encoder. Energy efficient video compression architectures for CMOS image sensors with focal-plane change detection are presented and analyzed. The compression architectures use pixel-level computational circuits to minimize energy usage by selectively processing only pixels which generate significant temporal intensity changes. Using the temporal intensity change detection to gate the operation of a differential DCT based encoder achieves nearly identical image quality to traditional systems (4dB decrease in PSNR while reducing the amount of data that is processed by 67% and reducing overall power consumption reduction of 51%. These typical energy savings, resulting from the sparsity of motion activity in the visual scene, demonstrate the utility of focal-plane change triggered compression to surveillance vision systems.

  11. EFFICACY OF RUFINAMIDE IN THE TREATMENT OF DRUG-RESISTANT FOCAL EPILEPSIES IN PAEDIATRIC PRACTICE

    Directory of Open Access Journals (Sweden)

    I. O. Shchederkina

    2016-01-01

    Full Text Available Among drug-resistant epilepsies, epileptic syndromes, characterized by combination of several types of seizures, are considered to be the most difficult in terms of treatment. Lennox–Gastaut syndrome is one of them. It manifests with polymorphic seizures (tonic axial, myatonic, atypical absence seizures, status epilepticus of minor motor seizures, myoclonic, generalized convulsive, and focal seizures. This is a heterogeneous disease, represented by a complex of clinical and electroencephalographic manifestations with various etiology. Current review is devoted to a novel antiepileptic drug rufinamide, which has a new mechanism of action. The drug has been registered in Russia in 2015. The authors also describe their own experience of rufinamide usage in the treatment of drug-resistant focal epilepsy as a part of multicomponent therapy for polymorphic seizures. One patient achieved clinical remission for 16 months; the second one had more than 50 % decrease in seizures frequency with a remission of drop-attacks.

  12. Focal Atrichia: A Diagnostic Clue in Female Pattern Hair Loss.

    Science.gov (United States)

    Olsen, Elise A; Whiting, David A

    2017-10-07

    Focal atrichia is a common clinical finding in female pattern hair loss whose specificity and histologic findings need further clarification. To determine the frequency of focal atrichia in various types of hair loss and its histologic characteristics in female pattern hair loss. Part 1: Review of 250 consecutive female patients seen with hair loss for the presence of focal atrichia and Part 2: paired biopsies of haired areas vs focal atrichia in 18 subjects with female pattern hair loss RESULTS: Focal atrichia was seen in 46/104 (44%) of women with female pattern hair loss, including 67% of late onset vs 15% of early onset, compared to 3/146 (2%) of those with other hair disorders Biopsy findings of focal atrichia in female pattern hair loss showed primarily a more progressive miniaturization process than that of haired areas of the scalp. Some women with female pattern hair loss may have had concomitant chronic telogen effluvium CONCLUSIONS: When present, focal atrichia is a clinical clue to the diagnosis of female pattern hair loss, particularly late onset subtype. Copyright © 2017. Published by Elsevier Inc.

  13. The semiology of febrile seizures: Focal features are frequent.

    Science.gov (United States)

    Takasu, Michihiko; Kubota, Tetsuo; Tsuji, Takeshi; Kurahashi, Hirokazu; Numoto, Shingo; Watanabe, Kazuyoshi; Okumura, Akihisa

    2017-08-01

    To clarify the semiology of febrile seizures (FS) and to determine the frequency of FS with symptoms suggestive of focal onset. FS symptoms in children were reported within 24h of seizure onset by the parents using a structured questionnaire consisting principally of closed-ended questions. We focused on events at seizure commencement, including changes in behavior and facial expression, and ocular and oral symptoms. We also investigated the autonomic and motor symptoms developing during seizures. The presence or absence of focal and limbic features was determined for each patient. The associations of certain focal and limbic features with patient characteristics were assessed. Information was obtained on FS in 106 children. Various events were recorded at seizure commencement. Behavioral changes were observed in 35 children, changes in facial expression in 53, ocular symptoms in 78, and oral symptoms in 90. In terms of events during seizures, autonomic symptoms were recognized in 78, and convulsive motor symptoms were recognized in 68 children. Focal features were evident in 81 children; 38 children had two or more such features. Limbic features were observed in 44 children, 9 of whom had two or more such features. There was no significant relationship between any patient characteristic and the numbers of focal or limbic features. The semiology of FS varied widely among children, and symptoms suggestive of focal onset were frequent. FS of focal onset may be more common than is generally thought. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. The dispersion-focalization theory of sound systems

    Science.gov (United States)

    Schwartz, Jean-Luc; Abry, Christian; Boë, Louis-Jean; Vallée, Nathalie; Ménard, Lucie

    2005-04-01

    The Dispersion-Focalization Theory states that sound systems in human languages are shaped by two major perceptual constraints: dispersion driving auditory contrast towards maximal or sufficient values [B. Lindblom, J. Phonetics 18, 135-152 (1990)] and focalization driving auditory spectra towards patterns with close neighboring formants. Dispersion is computed from the sum of the inverse squared inter-spectra distances in the (F1, F2, F3, F4) space, using a non-linear process based on the 3.5 Bark critical distance to estimate F2'. Focalization is based on the idea that close neighboring formants produce vowel spectra with marked peaks, easier to process and memorize in the auditory system. Evidence for increased stability of focal vowels in short-term memory was provided in a discrimination experiment on adult French subjects [J. L. Schwartz and P. Escudier, Speech Comm. 8, 235-259 (1989)]. A reanalysis of infant discrimination data shows that focalization could well be the responsible for recurrent discrimination asymmetries [J. L. Schwartz et al., Speech Comm. (in press)]. Recent data about children vowel production indicate that focalization seems to be part of the perceptual templates driving speech development. The Dispersion-Focalization Theory produces valid predictions for both vowel and consonant systems, in relation with available databases of human languages inventories.

  15. Widespread EEG changes precede focal seizures.

    Directory of Open Access Journals (Sweden)

    Piero Perucca

    Full Text Available The process by which the brain transitions into an epileptic seizure is unknown. In this study, we investigated whether the transition to seizure is associated with changes in brain dynamics detectable in the wideband EEG, and whether differences exist across underlying pathologies. Depth electrode ictal EEG recordings from 40 consecutive patients with pharmacoresistant lesional focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Predefined EEG sections were selected immediately before (immediate preictal, and 30 seconds before the earliest EEG sign suggestive of seizure activity (baseline. Spectral analysis, visual inspection and discrete wavelet transform were used to detect standard (delta, theta, alpha, beta and gamma and high-frequency bands (ripples and fast ripples. At the group level, each EEG frequency band activity increased significantly from baseline to the immediate preictal section, mostly in a progressive manner and independently of any modification in the state of vigilance. Preictal increases in each frequency band activity were widespread, being observed in the seizure-onset zone and lesional tissue, as well as in remote regions. These changes occurred in all the investigated pathologies (mesial temporal atrophy/sclerosis, local/regional cortical atrophy, and malformations of cortical development, but were more pronounced in mesial temporal atrophy/sclerosis. Our findings indicate that a brain state change with distinctive features, in the form of unidirectional changes across the entire EEG bandwidth, occurs immediately prior to seizure onset. We postulate that these changes might reflect a facilitating state of the brain which enables a susceptible region to generate seizures.

  16. Focal Segmental Glomerulosclerosis: A Single Center Experience

    Directory of Open Access Journals (Sweden)

    Yavuz Ayar

    2016-09-01

    Full Text Available Aim: Focal segmental glomerulosclerosis (FSGS is one of the most common glomerulonephritis (GNP worldwide. Despite treatment, it may progress to end-stage renal disease. In the present study, we compared clinical and histopathological data on FSGS with primary and secondary GNP retrospectively. Methods: We retrospectively analyzed data on clinical and laboratory findings, treatment response, and risk factors associated with mortality in patients, who had been diagnosed with FSGS and other GNP via renal biopsy between January 2009 and December 2014. The average follow-up time was 22 (8-76 months. Results: FSGS and primary GNP were more frequently seen in males than in females (55.9% vs. 65.3%, p=0.033. Nephrotic syndrome was more common in patients with FSGS (41.2% and primary GNP (57.7%, while chronic renal disease was more frequent in patients with secondary GNP (35%. In FSGS, the complete remission rate was 54.4%. 63.2% of patients had continued to receive treatment. According to the biopsy findings, interstitial inflammation and fibrosis were observed in 100% and 98.5% of patients with FSGS, respectively (p=0.010 and p<0.001, respectively. Serum albumin level was found to be increased and proteinuria, total cholesterol, triglyceride, and LDL levels to be decreased after treatment (p<0.001. Serum creatinine levels and type of GNP (secondary GNP were detected to be 1.48 and 8.14 fold increased in mortality analysis, respectively. Conclusion: Renal biopsy is the gold standard for the diagnosis of glomerular diseases. Renal function at the time of diagnosis, follow-up and appropriate immunosuppressive therapy have effects on mortality and clinical progress in FSGS as is the case in all GNPs.

  17. Differential Expression of Adhesion-Related Proteins and MAPK Pathways Lead to Suitable Osteoblast Differentiation of Human Mesenchymal Stem Cells Subpopulations.

    Science.gov (United States)

    Leyva-Leyva, Margarita; López-Díaz, Annia; Barrera, Lourdes; Camacho-Morales, Alberto; Hernandez-Aguilar, Felipe; Carrillo-Casas, Erika M; Arriaga-Pizano, Lourdes; Calderón-Pérez, Jaime; García-Álvarez, Jorge; Orozco-Hoyuela, Gabriel; Piña-Barba, Cristina; Rojas-Martínez, Augusto; Romero-Díaz, Víktor; Lara-Arias, Jorge; Rivera-Bolaños, Nancy; López-Camarillo, César; Moncada-Saucedo, Nidia; Galván-De los Santos, Alejandra; Meza-Urzúa, Fátima; Villarreal-Gómez, Luis; Fuentes-Mera, Lizeth

    2015-11-01

    Cellular adhesion enables communication between cells and their environment. Adhesion can be achieved throughout focal adhesions and its components influence osteoblast differentiation of human mesenchymal stem cells (hMSCs). Because cell adhesion and osteoblast differentiation are closely related, this article aimed to analyze the expression profiles of adhesion-related proteins during osteoblastic differentiation of two hMSCs subpopulations (CD105(+) and CD105(-)) and propose a strategy for assembling bone grafts based on its adhesion ability. In vitro experiments of osteogenic differentiation in CD105(-) cells showed superior adhesion efficiency and 2-fold increase of α-actinin expression compared with CD105(+) cells at the maturation stage. Interestingly, levels of activated β1-integrin increased in CD105(-) cells during the process. Additionally, the CD105(-) subpopulation showed 3-fold increase of phosphorylated FAK(Y397) compared to CD105(+) cells. Results also indicate that ERK1/2 was activated during CD105(-) bone differentiation and participation of mitogen-activated protein kinase (MAPK)-p38 in CD105(+) differentiation through a focal adhesion kinase (FAK)-independent pathway. In vivo trial demonstrated that grafts containing CD105(-) showed osteocytes embedded in a mineralized matrix, promoted adequate graft integration, increased host vascular infiltration, and efficient intramembranous repairing. In contrast, grafts containing CD105(+) showed deficient endochondral ossification and fibrocartilaginous tissue. Based on the expression of α-actinin, FAKy,(397) and ERK1/2 activation, we define maturation stage as critical for bone graft assembling. By in vitro assays, CD105(-) subpopulation showed superior adhesion efficiency compared to CD105(+) cells. Considering in vitro and in vivo assays, this study suggests that integration of a scaffold with CD105(-) subpopulation at the maturation stage represents an attractive strategy for clinical use in

  18. Adhesives for fixed orthodontic bands.

    Science.gov (United States)

    Millett, Declan T; Glenny, Anne-Marie; Mattick, Rye Cr; Hickman, Joy; Mandall, Nicky A

    2016-10-25

    Orthodontic treatment involves using fixed or removable appliances (dental braces) to correct the positions of teeth. It has been shown that the quality of treatment result obtained with fixed appliances is much better than with removable appliances. Fixed appliances are, therefore, favoured by most orthodontists for treatment. The success of a fixed orthodontic appliance depends on the metal attachments (brackets and bands) being attached securely to the teeth so that they do not become loose during treatment. Brackets are usually attached to the front and side teeth, whereas bands (metal rings that go round the teeth) are more commonly used on the back teeth (molars). A number of adhesives are available to attach bands to teeth and it is important to understand which group of adhesives bond most reliably, as well as reducing or preventing dental decay during the treatment period. To evaluate the effectiveness of the adhesives used to attach bands to teeth during fixed appliance treatment, in terms of:(1) how often the bands come off during treatment; and(2) whether they protect the banded teeth against decay during fixed appliance treatment. The following electronic databases were searched: Cochrane Oral Health's Trials Register (searched 2 June 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5) in the Cochrane Library (searched 2 June 2016), MEDLINE Ovid (1946 to 2 June 2016) and EMBASE Ovid (1980 to 2 June 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised and controlled clinical trials (RCTs and CCTs) (including split-mouth studies) of adhesives used to attach orthodontic bands to molar teeth were selected. Patients with full arch fixed orthodontic appliance(s) who had bands attached to molars were included. All review authors

  19. Focal Length Affects Depicted Shape and Perception of Facial Images.

    Directory of Open Access Journals (Sweden)

    Vít Třebický

    Full Text Available Static photographs are currently the most often employed stimuli in research on social perception. The method of photograph acquisition might affect the depicted subject's facial appearance and thus also the impression of such stimuli. An important factor influencing the resulting photograph is focal length, as different focal lengths produce various levels of image distortion. Here we tested whether different focal lengths (50, 85, 105 mm affect depicted shape and perception of female and male faces. We collected three portrait photographs of 45 (22 females, 23 males participants under standardized conditions and camera setting varying only in the focal length. Subsequently, the three photographs from each individual were shown on screen in a randomized order using a 3-alternative forced-choice paradigm. The images were judged for attractiveness, dominance, and femininity/masculinity by 369 raters (193 females, 176 males. Facial width-to-height ratio (fWHR was measured from each photograph and overall facial shape was analysed employing geometric morphometric methods (GMM. Our results showed that photographs taken with 50 mm focal length were rated as significantly less feminine/masculine, attractive, and dominant compared to the images taken with longer focal lengths. Further, shorter focal lengths produced faces with smaller fWHR. Subsequent GMM revealed focal length significantly affected overall facial shape of the photographed subjects. Thus methodology of photograph acquisition, focal length in this case, can significantly affect results of studies using photographic stimuli perhaps due to different levels of perspective distortion that influence shapes and proportions of morphological traits.

  20. Differential and Cooperative Cell Adhesion Regulates Cellular Pattern in Sensory Epithelia.

    Science.gov (United States)

    Togashi, Hideru

    2016-01-01

    Animal tissues are composed of multiple cell types arranged in complex and elaborate patterns. In sensory epithelia, including the auditory epithelium and olfactory epithelium, different types of cells are arranged in unique mosaic patterns. These mosaic patterns are evolutionarily conserved, and are thought to be important for hearing and olfaction. Recent progress has provided accumulating evidence that the cellular pattern formation in epithelia involves cell rearrangements, movements, and shape changes. These morphogenetic processes are largely mediated by intercellular adhesion systems. Differential adhesion and cortical tension have been proposed to promote cell rearrangements. Many different types of cells in tissues express various types of cell adhesion molecules. Although cooperative mechanisms between multiple adhesive systems are likely to contribute to the production of complex cell patterns, our current understanding of the cooperative roles between multiple adhesion systems is insufficient to entirely explain the complex mechanisms underlying cellular patterning. Recent studies have revealed that nectins, in cooperation with cadherins, are crucial for the mosaic cellular patterning in sensory organs. The nectin and cadherin systems are interacted with one another, and these interactions provide cells with differential adhesive affinities for complex cellular pattern formations in sensory epithelia, which cannot be achieved by a single mechanism.

  1. An innovative wheel–rail contact model for railway vehicles under degraded adhesion conditions

    International Nuclear Information System (INIS)

    Meli, E.; Ridolfi, A.

    2015-01-01

    The accurate modelling of the wheel–rail contact plays a fundamental role in the railway field since the contact forces heavily affect the vehicle dynamics, the wear of the contact surfaces and the vehicle safety. Concerning the wheel–rail contact, an important open problem is represented by the degraded adhesion. A realistic adhesion model is quite difficult to obtain because of the complex and highly non-linear behaviour of the adhesion coefficient and the presence of external unknown contaminants (the third body); this is especially true when degraded adhesion and large sliding between the wheel and rail contact surfaces occur.In this work the authors present an adhesion model particularly developed to describe degraded adhesion conditions. The new approach will have to be suitable to be employed within the wheel–rail contact models typical of the multibody applications. In other words, the contact model, comprising the new adhesion model, will have to guarantee a good accuracy and, at the same time, a high numerical efficiency to be implemented directly online inside the general multibody model of the vehicles (e.g. in Matlab-Simulink or Simpack environments) ( www.mathworks.com http://www.mathworks.com , 2012; www.simpack.com http://www.simpack.com , 2012).The model analysed in the paper is based on some of the main phenomena characterising the degraded adhesion, such as large sliding at the contact interface, high energy dissipation, the consequent cleaning effect on the contact surfaces and the final adhesion recovery due to the removal of external unknown contaminants.The adhesion model has been validated because of the experimental data provided by Trenitalia S.p.A. coming from on-track tests performed in Velim (Czech Republic). The tests have been carried out on a straight railway track under degraded adhesion conditions with the railway vehicle UIC-Z1 equipped with a fully-working Wheel Slide Protection (WSP) system.The validation highlighted the

  2. An innovative wheel–rail contact model for railway vehicles under degraded adhesion conditions

    Energy Technology Data Exchange (ETDEWEB)

    Meli, E., E-mail: enrico.meli@unifi.it; Ridolfi, A., E-mail: a.ridolfi@unifi.it [University of Florence, Department of Industrial Engineering (Italy)

    2015-03-15

    The accurate modelling of the wheel–rail contact plays a fundamental role in the railway field since the contact forces heavily affect the vehicle dynamics, the wear of the contact surfaces and the vehicle safety. Concerning the wheel–rail contact, an important open problem is represented by the degraded adhesion. A realistic adhesion model is quite difficult to obtain because of the complex and highly non-linear behaviour of the adhesion coefficient and the presence of external unknown contaminants (the third body); this is especially true when degraded adhesion and large sliding between the wheel and rail contact surfaces occur.In this work the authors present an adhesion model particularly developed to describe degraded adhesion conditions. The new approach will have to be suitable to be employed within the wheel–rail contact models typical of the multibody applications. In other words, the contact model, comprising the new adhesion model, will have to guarantee a good accuracy and, at the same time, a high numerical efficiency to be implemented directly online inside the general multibody model of the vehicles (e.g. in Matlab-Simulink or Simpack environments) ( www.mathworks.com http://www.mathworks.com , 2012; www.simpack.com http://www.simpack.com , 2012).The model analysed in the paper is based on some of the main phenomena characterising the degraded adhesion, such as large sliding at the contact interface, high energy dissipation, the consequent cleaning effect on the contact surfaces and the final adhesion recovery due to the removal of external unknown contaminants.The adhesion model has been validated because of the experimental data provided by Trenitalia S.p.A. coming from on-track tests performed in Velim (Czech Republic). The tests have been carried out on a straight railway track under degraded adhesion conditions with the railway vehicle UIC-Z1 equipped with a fully-working Wheel Slide Protection (WSP) system.The validation highlighted the

  3. Elastic coupling of nascent apCAM adhesions to flowing actin networks.

    Science.gov (United States)

    Mejean, Cecile O; Schaefer, Andrew W; Buck, Kenneth B; Kress, Holger; Shundrovsky, Alla; Merrill, Jason W; Dufresne, Eric R; Forscher, Paul

    2013-01-01

    Adhesions are multi-molecular complexes that transmit forces generated by a cell's acto-myosin networks to external substrates. While the physical properties of some of the individual components of adhesions have been carefully characterized, the mechanics of the coupling between the cytoskeleton and the adhesion site as a whole are just beginning to be revealed. We characterized the mechanics of nascent adhesions mediated by the immunoglobulin-family cell adhesion molecule apCAM, which is known to interact with actin filaments. Using simultaneous visualization of actin flow and quantification of forces transmitted to apCAM-coated beads restrained with an optical trap, we found that adhesions are dynamic structures capable of transmitting a wide range of forces. For forces in the picoNewton scale, the nascent adhesions' mechanical properties are dominated by an elastic structure which can be reversibly deformed by up to 1 µm. Large reversible deformations rule out an interface between substrate and cytoskeleton that is dominated by a number of stiff molecular springs in parallel, and favor a compliant cross-linked network. Such a compliant structure may increase the lifetime of a nascent adhesion, facilitating signaling and reinforcement.

  4. Elastic coupling of nascent apCAM adhesions to flowing actin networks.

    Directory of Open Access Journals (Sweden)

    Cecile O Mejean

    Full Text Available Adhesions are multi-molecular complexes that transmit forces generated by a cell's acto-myosin networks to external substrates. While the physical properties of some of the individual components of adhesions have been carefully characterized, the mechanics of the coupling between the cytoskeleton and the adhesion site as a whole are just beginning to be revealed. We characterized the mechanics of nascent adhesions mediated by the immunoglobulin-family cell adhesion molecule apCAM, which is known to interact with actin filaments. Using simultaneous visualization of actin flow and quantification of forces transmitted to apCAM-coated beads restrained with an optical trap, we found that adhesions are dynamic structures capable of transmitting a wide range of forces. For forces in the picoNewton scale, the nascent adhesions' mechanical properties are dominated by an elastic structure which can be reversibly deformed by up to 1 µm. Large reversible deformations rule out an interface between substrate and cytoskeleton that is dominated by a number of stiff molecular springs in parallel, and favor a compliant cross-linked network. Such a compliant structure may increase the lifetime of a nascent adhesion, facilitating signaling and reinforcement.

  5. Influence of tip indentation on the adhesive behavior of viscoelastic polydimethylsiloxane networks studied by atomic force microscopy

    NARCIS (Netherlands)

    Pickering, J.P.; Vancso, Gyula J.

    2001-01-01

    A commercial atomic force microscope (AFM) outfitted with a custom control and data acquisition system was used to investigate the adhesive nature of a viscoelastic polydimethylsiloxane (PDMS) network. Due to the complex dependence of the adhesion of this sample on factors such as indentation,

  6. The design of LMJ focal spots for indirect drive experiments

    International Nuclear Information System (INIS)

    Le Garrec, B J; Sajer, J M

    2008-01-01

    LMJ is a 240 high power laser beam facility for achieving laser matter interaction experiments, high energy density science, including the demonstration of fusion ignition through Inertial Confinement. The Laser Integration Line (LIL) facility is currently a 4-beam prototype for LMJ. The intensity I 0 at the focal spot centre drives hydrodynamic and plasma instabilities and the intensity in the wings must be low to go through the laser entrance Hohlraum. A simple model has been developed to compute the LMJ focal spot. The model gives the intensity at the centre as a function of the focal spot area at 3% of the maximum

  7. Focal cemento-osseous dysplasia: review and a case report.

    Science.gov (United States)

    Salem, Y M Y; Osman, Y I; Norval, E J G

    2010-10-01

    Focal cemento-osseous dysplasia is a benign fibro-osseous condition that can be seen in dentate and edentulous patients. It is an asymptomatic lesion and needs no treatment; however follow-up is essential due to the possibility that focal cemento-osseous dysplasia can progress to a condition called florid osseous dysplasia that involves multiple sites. A case report is presented here, along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia.

  8. Benign focal liver lesions: discrimination from malignant mimickers.

    Science.gov (United States)

    Alobaidi, Mohammad; Shirkhoda, Ali

    2004-01-01

    Focal lesions of the liver often have various imaging characteristics which may be interpreted as either benign or malignant. Understanding the underlying pathophysiology of these liver lesions may lead to characteristic imaging manifestations, which direct the radiologist to the diagnosis. Benign lesions include congenital hepatic cyst, autosomal dominant polycystic disease, hemangioma, focal nodular hyperplasia (FNH), hepatic adenoma, inflammatory pseudotumor, peliosis hepatis, focal fatty infiltration, hamartoma, and infectious processes such as hepatic abscess, echinococcal cyst, and candidiasis. Characteristic imaging features, clinical symptoms, and treatment/prognosis will be discussed. Emphasis will be placed on key reliable features of each disease to develop a method of discriminating these lesions from other benign and malignant disorders.

  9. Gecko adhesion pad: a smart surface?

    Science.gov (United States)

    Pesika, Noshir S.; Zeng, Hongbo; Kristiansen, Kai; Zhao, Boxin; Tian, Yu; Autumn, Kellar; Israelachvili, Jacob

    2009-11-01

    Recently, it has been shown that humidity can increase the adhesion of the spatula pads that form the outermost (adhesive) surface of the tokay gecko feet by 50% relative to the main adhesion mechanism (i.e. van der Waals adhesive forces), although the mechanism by which the enhancement is realized is still not well understood. A change in the surface hydrophobicity of a gecko setal array is observed when the array, which supports the spatulae, is exposed to a water drop for more than 20 min, suggesting a change in the hydrophilic-lyophilic balance (HLB), and therefore of the conformation of the surface proteins. A surface force apparatus (SFA) was used to quantify these changes, i.e. in the adhesion and friction forces, while shearing the setal array against a silica surface under (i) dry conditions, (ii) 100% humidity and (iii) when fully immersed in water. The adhesion increased in the humid environment but greatly diminished in water. Although the adhesion forces changed significantly, the friction forces remained unaffected, indicating that the friction between these highly textured surfaces is 'load-controlled' rather than 'adhesion-controlled'. These results demonstrate that the gecko adhesive pads have the ability to exploit environmental conditions to maximize their adhesion and stabilize their friction forces. Future designs of synthetic dry adhesives inspired by the gecko can potentially include similar 'smart' surfaces that adapt to their environment.

  10. Gecko adhesion pad: a smart surface?

    Energy Technology Data Exchange (ETDEWEB)

    Pesika, Noshir S [Chemical and Biomolecular Engineering Department, Tulane University, New Orleans, LA 70118 (United States); Zeng Hongbo [Chemical and Materials Engineering Department, University of Alberta, Edmonton, AB, T6G 2V4 (Canada); Kristiansen, Kai; Israelachvili, Jacob [Chemical Engineering Department, University of California, Santa Barbara, CA 93117 (United States); Zhao, Boxin [Chemical Engineering Department and Waterloo Institute of Nanotechnology, University of Waterloo, Ontario, N2L 3G1 (Canada); Tian Yu [State Key Laboratory of Tribology, Department of Precision Instruments, Tsinghua University, Beijing 100084 (China); Autumn, Kellar, E-mail: npesika@tulane.ed [Department of Biology, Lewis and Clark College, Portland, OR 97219 (United States)

    2009-11-18

    Recently, it has been shown that humidity can increase the adhesion of the spatula pads that form the outermost (adhesive) surface of the tokay gecko feet by 50% relative to the main adhesion mechanism (i.e. van der Waals adhesive forces), although the mechanism by which the enhancement is realized is still not well understood. A change in the surface hydrophobicity of a gecko setal array is observed when the array, which supports the spatulae, is exposed to a water drop for more than 20 min, suggesting a change in the hydrophilic-lyophilic balance (HLB), and therefore of the conformation of the surface proteins. A surface force apparatus (SFA) was used to quantify these changes, i.e. in the adhesion and friction forces, while shearing the setal array against a silica surface under (i) dry conditions, (ii) 100% humidity and (iii) when fully immersed in water. The adhesion increased in the humid environment but greatly diminished in water. Although the adhesion forces changed significantly, the friction forces remained unaffected, indicating that the friction between these highly textured surfaces is 'load-controlled' rather than 'adhesion-controlled'. These results demonstrate that the gecko adhesive pads have the ability to exploit environmental conditions to maximize their adhesion and stabilize their friction forces. Future designs of synthetic dry adhesives inspired by the gecko can potentially include similar 'smart' surfaces that adapt to their environment.

  11. Gecko adhesion pad: a smart surface?

    International Nuclear Information System (INIS)

    Pesika, Noshir S; Zeng Hongbo; Kristiansen, Kai; Israelachvili, Jacob; Zhao, Boxin; Tian Yu; Autumn, Kellar

    2009-01-01

    Recently, it has been shown that humidity can increase the adhesion of the spatula pads that form the outermost (adhesive) surface of the tokay gecko feet by 50% relative to the main adhesion mechanism (i.e. van der Waals adhesive forces), although the mechanism by which the enhancement is realized is still not well understood. A change in the surface hydrophobicity of a gecko setal array is observed when the array, which supports the spatulae, is exposed to a water drop for more than 20 min, suggesting a change in the hydrophilic-lyophilic balance (HLB), and therefore of the conformation of the surface proteins. A surface force apparatus (SFA) was used to quantify these changes, i.e. in the adhesion and friction forces, while shearing the setal array against a silica surface under (i) dry conditions, (ii) 100% humidity and (iii) when fully immersed in water. The adhesion increased in the humid environment but greatly diminished in water. Although the adhesion forces changed significantly, the friction forces remained unaffected, indicating that the friction between these highly textured surfaces is 'load-controlled' rather than 'adhesion-controlled'. These results demonstrate that the gecko adhesive pads have the ability to exploit environmental conditions to maximize their adhesion and stabilize their friction forces. Future designs of synthetic dry adhesives inspired by the gecko can potentially include similar 'smart' surfaces that adapt to their environment.

  12. The adhesive bonding of beryllium structural components

    International Nuclear Information System (INIS)

    Fullerton-Batten, R.C.

    1977-01-01

    Where service conditions permit, adhesive bonding is a highly recommendable, reliable means of joining beryllium structural parts. Several important programs have successfully used adhesive bonding for joining structural and non-structural beryllium components. Adhesive bonding minimizes stress concentrations associated with other joining techniques and considerably improves fatigue resistance. In addition, no degradation of base metal properties occur. In many instances, structural joints can be fabricated more cheaply by adhesive bonding or in combination with adhesive bonding than by any other method used alone. An evaluation program on structural adhesive bonding of beryllium sheet components is described. A suitable surface pretreatment for beryllium adherends prior to bonding is given. Tensile shear strength and fatigue properties of FM 1000 and FM 123-5 adhesive bonded joints are reviewed and compared with data obtained from riveted joints of similar geometry. (author)

  13. Focal changes of the spleen in one case of Gaucher disease - assessed by ultrasonography, CT, MRI and angiography

    International Nuclear Information System (INIS)

    Aspestrand, F.; Charania, B.; Scheel, B.; Kolmannskog, F.; Jacobsen, M.

    1989-01-01

    Focal lesions of the spleen in one case of Gaucher disease are demonstrated by ultrasonography, CT, MRI and angiography. The sonographic and angiographic features differ from the findings presented in previous reports. The Gaucher manifestations in the spleen as demonstrated by CT, do not seem to have been reported previously. An earlier report on the MR findings in the liver and spleen in this disease did not disclose any focal abnormalities. In this case, ultrasonography and MRI revealed a targetlike configuration of the focal lesions. An attempt is made to analyze the more complex patterns disclosed by MRI against the background of the manifestations by the other imaging modalities and previous reports. (orig.) [de

  14. Focal relationships and the environment of project marketing. A literature review with suggestions for practitioners and future research

    DEFF Research Database (Denmark)

    Skaates, Maria Anne; Tikkanen, Henrikki

    2000-01-01

    of the review is upon the connection between focal relationships and the wider environment in which project marketing and systems selling takes place. First, several common definitions of projects and project marketing are presented and discussed. Second, the implications of three specific features of project......Project marketing is an important mode of business-to-business marketing today. This paper assesses recent project marketing contributions, including predominantly those of members of the (mainly European) International Network for Project Marketing and Systems Selling (INPM). The emphasis...... business - discontinuity, uniqueness, and complexity - for the focal relationship and the broader marketing environment are considered at the level of multiple projects. Third, three overlapping types of postures that project-selling firms can adopt in relation to their focal relationships...

  15. Dual-layer electrode-driven liquid crystal lens with electrically tunable focal length and focal plane

    Science.gov (United States)

    Zhang, Y. A.; Lin, C. F.; Lin, J. P.; Zeng, X. Y.; Yan, Q.; Zhou, X. T.; Guo, T. L.

    2018-04-01

    Electric-field-driven liquid crystal (ELC) lens with tunable focal length and their depth of field has been extensively applied in 3D display and imaging systems. In this work, a dual-layer electrode-driven liquid crystal (DELC) lens with electrically tunable focal length and controllable focal plane is demonstrated. ITO-SiO2-AZO electrodes with the dual-layer staggered structure on the top substrate are used as driven electrodes within a LC cell, which permits the establishment of an alternative controllability. The focal length of the DELC lens can be adjusted from 1.41 cm to 0.29 cm when the operating voltage changes from 15 V to 40 V. Furthermore, the focal plane of the DELC lens can selectively move by changing the driving method of the applied voltage to the next driven electrodes. This work demonstrates that the DELC lens has potential applications in imaging systems because of electrically tunable focal length and controllable focal plane.

  16. Polyurethane adhesives in flat roofs

    OpenAIRE

    Bogárová Markéta; Stodůlka Jindřich; Šuhajda Karel

    2017-01-01

    It is necessary to stabilize individual layers of flat roofs, mainly because of wind suction. Apart from anchoring and surcharge, these layers can be secured by bonding. At present gluing is an indispensable and widely used stabilization method. On our market we can found many types of adhesives, most widely used are based on polyurethane. This paper focuses on problematic about stabilization thermal insulation from expanded polystyrene to vapor barrier from bitumen. One of the main issues is...

  17. Adhesives for fixed orthodontic brackets.

    Science.gov (United States)

    Mandall, N A; Millett, D T; Mattick, C R; Hickman, J; Macfarlane, T V; Worthington, H V

    2003-01-01

    Bonding of orthodontic brackets to teeth is important to enable effective and efficient treatment with fixed appliances. The problem is bracket failure during treatment which increases operator chairside time and lengthens treatment time. A prolonged treatment is likely to increase the oral health risks of orthodontic treatment with fixed appliances one of which is irreversible enamel decalcification. To evaluate the effectiveness of different orthodontic adhesives for bonding. Electronic databases: the Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Date of most recent searches: August 2002 (CENTRAL) (The Cochrane Library Issue 2, 2002). Trials were selected if they met the following criteria: randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing two different adhesive groups. Participants were patients with fixed orthodontic appliances. The interventions were adhesives that bonded stainless steel brackets to all teeth except the molars. The primary outcome was debond or bracket failure. Data were recorded on decalcification as a secondary outcome, if present. Information regarding methods, participants, interventions, outcome measures and results were extracted in duplicate by pairs of reviewers (Nicky Mandall (NM) and Rye Mattick (CRM); Declan Millett (DTM) and Joy Hickman (JH2)). Since the data were not presented in a form that was amenable to meta-analysis, the results of the review are presented in narrative form only. Three trials satisfied the inclusion criteria. A chemical cured composite was compared with a light cure composite (one trial), a conventional glass ionomer cement (one trial) and a polyacid-modified resin composite (compomer) (one trial). The quality of the trial reports was generally poor. It is difficult to draw any conclusions from this review, however, suggestions are made for methods of improving future research involving

  18. Polymer Nanocarriers for Dentin Adhesion

    Science.gov (United States)

    Osorio, R.; Osorio, E.; Medina-Castillo, A.L.; Toledano, M.

    2014-01-01

    To obtain more durable adhesion to dentin, and to protect collagen fibrils of the dentin matrix from degradation, calcium- and phosphate-releasing particles have been incorporated into the dental adhesive procedure. The aim of the present study was to incorporate zinc-loaded polymeric nanocarriers into a dental adhesive system to facilitate inhibition of matrix metalloproteinases (MMPs)-mediated collagen degradation and to provide calcium ions for mineral deposition within the resin-dentin bonded interface. PolymP-nActive nanoparticles (nanoMyP) were zinc-loaded through 30-minute ZnCl2 immersion and tested for bioactivity by means of 7 days’ immersion in simulated body fluid solution (the Kokubo test). Zinc-loading and calcium phosphate depositions were examined by scanning and transmission electron microscopy, elemental analysis, and x-ray diffraction. Nanoparticles in ethanol solution infiltrated into phosphoric-acid-etched human dentin and Single Bond (3M/ESPE) were applied to determine whether the nanoparticles interfered with bonding. Debonded sticks were analyzed by scanning electron microscopy. A metalloproteinase collagen degradation assay was also performed in resin-infiltrated dentin with and without nanoparticles, measuring C-terminal telopeptide of type I collagen (ICTP) concentration in supernatants, after 4 wk of immersion in artificial saliva. Numerical data were analyzed by analysis of variance (ANOVA) and Student-Newman-Keuls multiple comparisons tests (p calcium regardless of zinc incorporation. Nanoparticles failed to infiltrate demineralized intertubular dentin and remained on top of the hybrid layer, without altering bond strength. Calcium and phosphorus were found covering nanoparticles at the hybrid layer, after 24 h. Nanoparticle application in etched dentin also reduced MMP-mediated collagen degradation. Tested nanoparticles may be incorporated into dental adhesive systems to provide the appropriate environment in which dentin MMP

  19. Expression of metastasis suppressor BRMS1 in breast cancer cells results in a marked delay in cellular adhesion to matrix.

    Science.gov (United States)

    Khotskaya, Yekaterina B; Beck, Benjamin H; Hurst, Douglas R; Han, Zhenbo; Xia, Weiya; Hung, Mien-Chie; Welch, Danny R

    2014-12-01

    Metastatic dissemination is a multi-step process that depends on cancer cells' ability to respond to microenvironmental cues by adapting adhesion abilities and undergoing cytoskeletal rearrangement. Breast Cancer Metastasis Suppressor 1 (BRMS1) affects several steps of the metastatic cascade: it decreases survival in circulation, increases susceptibility to anoikis, and reduces capacity to colonize secondary organs. In this report, BRMS1 expression is shown to not significantly alter expression levels of integrin monomers, while time-lapse and confocal microscopy revealed that BRMS1-expressing cells exhibited reduced activation of both β1 integrin and focal adhesion kinase, and decreased localization of these molecules to sites of focal adhesions. Short-term plating of BRMS1-expressing cells onto collagen or fibronectin markedly decreased cytoskeletal reorganization and formation of cellular adhesion projections. Under 3D culture conditions, BRMS1-expressing cells remained rounded and failed to reorganize their cytoskeleton and form invasive colonies. Taken together, BRMS1-expressing breast cancer cells are greatly attenuated in their ability to respond to microenvironment changes. © 2013 Wiley Periodicals, Inc. © 2013 Wiley Periodicals, Inc.

  20. Osteoblast Adhesion on Cathodic Arc Plasma Deposited Nano-Multilayered TiCrAlSiN Thin Films

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Kyu [University of Ulsan, Ulsan (Korea, Republic of); Pham, Vuong Hung [Hanoi University of Science and Technology (HUST), Hanoi (Viet Nam)

    2014-03-15

    Adhesion of osteoblast cells to TiCrAlSiN thin films was evaluated in vitro. Ti and TiCrAlSiN thin films were deposited on glass substrates by cathodic arc deposition. Surface roughness and chemistry of the TiCrAlSiN thin films was characterized by AFM and EPMA, respectively. Ti and TiCrAlSiN thin films and glass coverslips were cultured with human osteoblast cells (hFOB 1.19). The cell cytoskeleton was analyzed by observing the organization of actin stress fibers and microtubules. Cell proliferation was investigated by MTT assay and visualization. Focal contact adhesion was studied by observing the vinculin density. The results indicated that the TiCrAlSiN coating significantly influenced the actin cytoskeleton and microtubule organization. Human osteoblasts hFOB attached and proliferated better on TiCrAlSiN thin films with more focal contact adhesions than on Ti thin films or glass surfaces. These results suggest that TiCrAlSiN thin films can be an implantable material where the maximum cell adhesion is required.