Investigating the Influence of the Initial Biomass Distribution and Injection Strategies on Biofilm-Mediated Calcite Precipitation in Porous Media

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hommel, Johannes; Lauchnor, Ellen; Gerlach, Robin

Attachment of bacteria in porous media is a complex mixture of processes resulting in the transfer and immobilization of suspended cells onto a solid surface within the porous medium. However, quantifying the rate of attachment is difficult due to the many simultaneous processes possibly involved in attachment, including straining, sorption, and sedimentation, and the difficulties in measuring metabolically active cells attached to porous media. Preliminary experiments confirmed the difficulty associated with measuring active Sporosarcina pasteurii cells attached to porous media. However, attachment is a key process in applications of biofilm-mediated reactions in the subsurface such as microbially induced calcite precipitation.more » Independent of the exact processes involved, attachment determines both the distribution and the initial amount of attached biomass and as such the initial reaction rate. As direct experimental investigations are difficult, this study is limited to a numerical investigation of the effect of various initial biomass distributions and initial amounts of attached biomass. This is performed for various injection strategies, changing the injection rate as well as alternating between continuous and pulsed injections. The results of this study indicate that, for the selected scenarios, both the initial amount and the distribution of attached biomass have minor influence on the Ca 2+ precipitation efficiency as well as the distribution of the precipitates compared to the influence of the injection strategy. The influence of the initial biomass distribution on the resulting final distribution of the precipitated calcite is limited, except for the continuous injection at intermediate injection rate. But even for this injection strategy, the Ca 2+ precipitation efficiency shows no significant dependence on the initial biomass distribution.« less

Potential for Aedes albopictus and Ochlerotatus j. japonicus to Change the Field Ecology of Arboviruses of Human Health Importance in the Mid-Atlantic Region of the United States

DTIC Science & Technology

2001-10-16

attachment, the viral attachment proteins on the surface of the virion bind to receptors on the microvillar membrane of the mosquito s midgut ...Penetration refers to the process through which the virions enter the midgut cells; arboviruses enter cell through receptor -mediated endocytosis. During...inactivation of the virus by digestive enzymes in the lumen of the midgut , and the absence or reduced number of cellular receptor sites for virus attachment

The chemotaxis-like Che1 pathway has an indirect role in adhesive cell properties of Azospirillum brasilense.

PubMed

Siuti, Piro; Green, Calvin; Edwards, Amanda Nicole; Doktycz, Mitchel J; Alexandre, Gladys

2011-10-01

The Azospirillum brasilense chemotaxis-like Che1 signal transduction pathway was recently shown to modulate changes in adhesive cell surface properties that, in turn, affect cell-to-cell aggregation and flocculation behaviors rather than flagellar-mediated chemotaxis. Attachment to surfaces and root colonization may be functions related to flocculation. Here, the conditions under which A. brasilense wild-type Sp7 and che1 mutant strains attach to abiotic and biotic surfaces were examined using in vitro attachment and biofilm assays combined with atomic force microscopy and confocal microscopy. The nitrogen source available for growth is found to be a major modulator of surface attachment by A. brasilense and could be promoted in vitro by lectins, suggesting that it depends on interaction with surface-exposed residues within the extracellular matrix of cells. However, Che1-dependent signaling is shown to contribute indirectly to surface attachment, indicating that distinct mechanisms are likely underlying flocculation and attachment to surfaces in A. brasilense. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Bit-1 Mediates Integrin-dependent Cell Survival through Activation of the NFκB Pathway*

PubMed Central

Griffiths, Genevieve S.; Grundl, Melanie; Leychenko, Anna; Reiter, Silke; Young-Robbins, Shirley S.; Sulzmaier, Florian J.; Caliva, Maisel J.; Ramos, Joe W.; Matter, Michelle L.

2011-01-01

Loss of properly regulated cell death and cell survival pathways can contribute to the development of cancer and cancer metastasis. Cell survival signals are modulated by many different receptors, including integrins. Bit-1 is an effector of anoikis (cell death due to loss of attachment) in suspended cells. The anoikis function of Bit-1 can be counteracted by integrin-mediated cell attachment. Here, we explored integrin regulation of Bit-1 in adherent cells. We show that knockdown of endogenous Bit-1 in adherent cells decreased cell survival and re-expression of Bit-1 abrogated this effect. Furthermore, reduction of Bit-1 promoted both staurosporine and serum-deprivation induced apoptosis. Indeed knockdown of Bit-1 in these cells led to increased apoptosis as determined by caspase-3 activation and positive TUNEL staining. Bit-1 expression protected cells from apoptosis by increasing phospho-IκB levels and subsequently bcl-2 gene transcription. Protection from apoptosis under serum-free conditions correlated with bcl-2 transcription and Bcl-2 protein expression. Finally, Bit-1-mediated regulation of bcl-2 was dependent on focal adhesion kinase, PI3K, and AKT. Thus, we have elucidated an integrin-controlled pathway in which Bit-1 is, in part, responsible for the survival effects of cell-ECM interactions. PMID:21383007

Silencing by nuclear matrix attachment distinguishes cell-type specificity: association with increased proliferation capacity

PubMed Central

Linnemann, Amelia K.; Krawetz, Stephen A.

2009-01-01

DNA loop organization by nuclear scaffold/matrix attachment is a key regulator of gene expression that may provide a means to modulate phenotype. We have previously shown that attachment of genes to the NaCl-isolated nuclear matrix correlates with their silencing in HeLa cells. In contrast, expressed genes were associated with the lithium 3,5-diiodosalicylate (LIS)-isolated nuclear scaffold. To define their role in determining phenotype matrix attached regions (MARs) on human chromosomes 14–18 were identified as a function of expression in a primary cell line. The locations of MARs in aortic adventitial fibroblast (AoAF) cells were very stable (r = 0.909) and 96% of genes attached at MARs are silent (P < 0.001). Approximately one-third of the genes uniquely expressed in AoAF cells were associated with the HeLa cell nuclear matrix and silenced. Comparatively, 81% were associated with the AoAF cell nuclear scaffold (P < 0.001) and expressed. This suggests that nuclear scaffold/matrix association mediates a portion of cell type-specific gene expression thereby modulating phenotype. Interestingly, nuclear matrix attachment and thus silencing of specific genes that regulate proliferation and maintain the integrity of the HeLa cell genome suggests that transformation may at least in part be achieved through aberrant nuclear matrix attachment. PMID:19276204

Pili-taxis: Clustering of Neisseria gonorrhoeae bacteria

NASA Astrophysics Data System (ADS)

Taktikos, Johannes; Zaburdaev, Vasily; Biais, Nicolas; Stark, Holger; Weitz, David A.

2012-02-01

The first step of colonization of Neisseria gonorrhoeae bacteria, the etiological agent of gonorrhea, is the attachment to human epithelial cells. The attachment of N. gonorrhoeae bacteria to surfaces or other cells is primarily mediated by filamentous appendages, called type IV pili (Tfp). Cycles of elongation and retraction of Tfp are responsible for a common bacterial motility called twitching motility which allows the bacteria to crawl over surfaces. Experimentally, N. gonorrhoeae cells initially dispersed over a surface agglomerate into round microcolonies within hours. It is so far not known whether this clustering is driven entirely by the Tfp dynamics or if chemotactic interactions are needed. Thus, we investigate whether the agglomeration may stem solely from the pili-mediated attraction between cells. By developing a statistical model for pili-taxis, we try to explain the experimental measurements of the time evolution of the mean cluster size, number of clusters, and area fraction covered by the cells.

Importance of Extracellular Polymeric Substances from Thiobacillus ferrooxidans for Bioleaching

PubMed Central

Gehrke, Tilman; Telegdi, Judit; Thierry, Dominique; Sand, Wolfgang

1998-01-01

Leaching bacteria such as Thiobacillus ferrooxidans attach to pyrite or sulfur by means of extracellular polymeric substances (EPS) (lipopolysaccharides). The primary attachment to pyrite at pH 2 is mediated by exopolymer-complexed iron(III) ions in an electrochemical interaction with the negatively charged pyrite surface. EPS from sulfur cells possess increased hydrophobic properties and do not attach to pyrite, indicating adaptability to the substrate or substratum. PMID:9647862

Microbial cell surface characteristics: Elucidating attachment/detachment using hydrophobicity and electrokinetic measurements

EPA Science Inventory

The surface properties of microorganisms play an important role in their behavior within the environment. Electrophoretic mobility and cell surface hydrophobicity of bacterial cells influence their initial interaction with surfaces and mediate their stability within an aqueous su...

Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: a Sticky Virus Makes a Slick Getaway

PubMed Central

Gardner, Thomas J.

2016-01-01

SUMMARY The prototypic herpesvirus human cytomegalovirus (CMV) exhibits the extraordinary ability to establish latency and maintain a chronic infection throughout the life of its human host. This is even more remarkable considering the robust adaptive immune response elicited by infection and reactivation from latency. In addition to the ability of CMV to exist in a quiescent latent state, its persistence is enabled by a large repertoire of viral proteins that subvert immune defense mechanisms, such as NK cell activation and major histocompatibility complex antigen presentation, within the cell. However, dissemination outside the cell presents a unique existential challenge to the CMV virion, which is studded with antigenic glycoprotein complexes targeted by a potent neutralizing antibody response. The CMV virion envelope proteins, which are critical mediators of cell attachment and entry, possess various characteristics that can mitigate the humoral immune response and prevent viral clearance. Here we review the CMV glycoprotein complexes crucial for cell attachment and entry and propose inherent properties of these proteins involved in evading the CMV humoral immune response. These include viral glycoprotein polymorphism, epitope competition, Fc receptor-mediated endocytosis, glycan shielding, and cell-to-cell spread. The consequences of CMV virion glycoprotein-mediated immune evasion have a major impact on persistence of the virus in the population, and a comprehensive understanding of these evasion strategies will assist in designing effective CMV biologics and vaccines to limit CMV-associated disease. PMID:27307580

UV laser-ablated surface textures as potential regulator of cellular response.

PubMed

Chandra, Prafulla; Lai, Karen; Sung, Hak-Joon; Murthy, N Sanjeeva; Kohn, Joachim

2010-06-01

Textured surfaces obtained by UV laser ablation of poly(ethylene terephthalate) films were used to study the effect of shape and spacing of surface features on cellular response. Two distinct patterns, cones and ripples with spacing from 2 to 25 μm, were produced. Surface features with different shapes and spacings were produced by varying pulse repetition rate, laser fluence, and exposure time. The effects of the surface texture parameters, i.e., shape and spacing, on cell attachment, proliferation, and morphology of neonatal human dermal fibroblasts and mouse fibroblasts were studied. Cell attachment was the highest in the regions with cones at ∼4 μm spacing. As feature spacing increased, cell spreading decreased, and the fibroblasts became more circular, indicating a stress-mediated cell shrinkage. This study shows that UV laser ablation is a useful alternative to lithographic techniques to produce surface patterns for controlling cell attachment and growth on biomaterial surfaces.

Attachment, emotion regulation, and adaptation to breast cancer: assessment of a mediational hypothesis.

PubMed

Ávila, Marisa; Brandão, Tânia; Teixeira, Joana; Coimbra, Joaquim Luis; Matos, Paula Mena

2015-11-01

This study examines the links between attachment, adaptation to breast cancer, and the mediating role played by emotional regulation processes. Participants were 127 women with breast cancer recruited in two public hospitals of Porto and at the Portuguese Cancer League. Women completed measures of attachment, quality of life, and emotion regulation. Path models were used to examine the associations between the constructs and to test the mediational hypotheses. Significant associations were found between attachment and adaptation. Dimensions of emotion regulation totally or partially mediated the associations between attachment and adaptation outcomes. Attachment security effects on interpersonal relations were totally mediated by communicating emotions. Also, attachment anxiety effect on physical well-being was totally mediated by rumination. Attachment avoidance effects on psychological outcomes were totally mediated by emotional control and partially mediated by communicating emotions for the case of interpersonal relations. This study highlights the importance of addressing emotional regulation jointly with attachment to deepen the comprehension of the relational processes implicated in adaptation to breast cancer. Results supported a mediational hypothesis, presenting emotional regulation processes as relevant dimensions for the understanding of attachment associations with adaptation to breast cancer. Copyright © 2015 John Wiley & Sons, Ltd.

Collagen Scaffolds in Bone Sialoprotein-Mediated Bone Regeneration

PubMed Central

Kruger, Thomas E.; Miller, Andrew H.; Wang, Jinxi

2013-01-01

Decades of research in bioengineering have resulted in the development of many types of 3-dimentional (3D) scaffolds for use as drug delivery systems (DDS) and for tissue regeneration. Scaffolds may be comprised of different natural fibers and synthetic polymers as well as ceramics in order to exert the most beneficial attributes including biocompatibility, biodegradability, structural integrity, cell infiltration and attachment, and neovascularization. Type I collagen scaffolds meet most of these criteria. In addition, type I collagen binds integrins through RGD and non-RGD sites which facilitates cell migration, attachment, and proliferation. Type I collagen scaffolds can be used for bone tissue repair when they are coated with osteogenic proteins such as bone morphogenic protein (BMP) and bone sialoprotein (BSP). BSP, a small integrin-binding ligand N-linked glycoprotein (SIBLING), has osteogenic properties and plays an essential role in bone formation. BSP also mediates mineral deposition, binds type I collagen with high affinity, and binds αvβ 3 and αvβ 5 integrins which mediate cell signaling. This paper reviews the emerging evidence demonstrating the efficacy of BSP-collagen scaffolds in bone regeneration. PMID:23653530

Collagen scaffolds in bone sialoprotein-mediated bone regeneration.

PubMed

Kruger, Thomas E; Miller, Andrew H; Wang, Jinxi

2013-01-01

Decades of research in bioengineering have resulted in the development of many types of 3-dimentional (3D) scaffolds for use as drug delivery systems (DDS) and for tissue regeneration. Scaffolds may be comprised of different natural fibers and synthetic polymers as well as ceramics in order to exert the most beneficial attributes including biocompatibility, biodegradability, structural integrity, cell infiltration and attachment, and neovascularization. Type I collagen scaffolds meet most of these criteria. In addition, type I collagen binds integrins through RGD and non-RGD sites which facilitates cell migration, attachment, and proliferation. Type I collagen scaffolds can be used for bone tissue repair when they are coated with osteogenic proteins such as bone morphogenic protein (BMP) and bone sialoprotein (BSP). BSP, a small integrin-binding ligand N-linked glycoprotein (SIBLING), has osteogenic properties and plays an essential role in bone formation. BSP also mediates mineral deposition, binds type I collagen with high affinity, and binds α v β 3 and α v β 5 integrins which mediate cell signaling. This paper reviews the emerging evidence demonstrating the efficacy of BSP-collagen scaffolds in bone regeneration.

Serotype-specific differences in inhibition of reovirus infectivity by human-milk glycans are determined by viral attachment protein σ1.

PubMed

Iskarpatyoti, Jason A; Morse, E Ashley; McClung, R Paul; Ikizler, Miné; Wetzel, J Denise; Contractor, Nikhat; Dermody, Terence S

2012-11-25

Human milk contains many bioactive components, including secretory IgA, oligosaccharides, and milk-associated proteins. We assessed the antiviral effects of several components of milk against mammalian reoviruses. We found that glucocerebroside (GCB) inhibited the infectivity of reovirus strain type 1 Lang (T1L), whereas gangliosides GD3 and GM3 and 3'-sialyllactose (3SL) inhibited the infectivity of reovirus strain type 3 Dearing (T3D). Agglutination of erythrocytes mediated by T1L and T3D was inhibited by GD3, GM3, and bovine lactoferrin. Additionally, α-sialic acid, 3SL, 6'-sialyllactose, sialic acid, human lactoferrin, osteopontin, and α-lactalbumin inhibited hemagglutination mediated by T3D. Using single-gene reassortant viruses, we found that serotype-specific differences segregate with the gene encoding the viral attachment protein. Furthermore, GD3, GM3, and 3SL inhibit T3D infectivity by blocking binding to host cells, whereas GCB inhibits T1L infectivity post-attachment. These results enhance an understanding of reovirus cell attachment and define a mechanism for the antimicrobial activity of human milk. Copyright © 2012 Elsevier Inc. All rights reserved.

The lutheran/basal cell adhesion molecule promotes tumor cell migration by modulating integrin-mediated cell attachment to laminin-511 protein.

PubMed

Kikkawa, Yamato; Ogawa, Takaho; Sudo, Ryo; Yamada, Yuji; Katagiri, Fumihiko; Hozumi, Kentaro; Nomizu, Motoyoshi; Miner, Jeffrey H

2013-10-25

Cell-matrix interactions are critical for tumor cell migration. Lutheran (Lu), also known as basal cell adhesion molecule (B-CAM), competes with integrins for binding to laminin α5, a subunit of LM-511, a major component of basement membranes. Here we show that the preferential binding of Lu/B-CAM to laminin α5 promotes tumor cell migration. The attachment of Lu/B-CAM transfectants to LM-511 was slightly weaker than that of control cells, and this was because Lu/B-CAM disturbed integrin binding to laminin α5. Lu/B-CAM induced a spindle cell shape with pseudopods and promoted cell migration on LM-511. In addition, blocking with an anti-Lu/B-CAM antibody led to a flat cell shape and inhibited migration on LM-511, similar to the effects of an activating integrin β1 antibody. We conclude that tumor cell migration on LM-511 requires that Lu/B-CAM competitively modulates cell attachment through integrins. We suggest that this competitive interaction is involved in a balance between static and migratory cell behaviors.

Impact of pre-incubation time of silk fibroin scaffolds in culture medium on cell proliferation and attachment.

PubMed

Amirikia, Mehdi; Shariatzadeh, Seyed Mohammad Ali; Jorsaraei, Seyed Gholam Ali; Soleimani Mehranjani, Malek

2017-12-01

Cell behaviours such as proliferation and attachment can be affected by the length of pre-incubation period of the scaffolds in the culture medium for long term. The aim of this study was to investigate the long term pre-incubation of 3D silk fibroin scaffolds in complete culture medium on cell attachment and proliferation. After the preparation of silk fibroin scaffolds by the technique of freeze drying, the scaffolds were pre-incubated in complete culture medium for 2 d, 6 d or 10 d before apical papilla stem cells (SCAP) seeding. Modifications of the scaffold surface and wettability were examined by FE-SEM and water contact angle, respectively. Results showed a decrease both in roughness and water contact angle as pre-incubation time increases. DNA measurement after 18h and 10 d cell seeding showed a significant increase of DNA concentration which represents better attachment and proliferation with pre-incubation time increase. Qualitative examination, live&dead assay or H&E staining method after 30h and 10 d cell seeding respectively, indicated that pre-incubation of scaffolds has time dependent effect on cell proliferation and attachment. This suggests that improvement of cell attachment and proliferation may be mediated by differences in the amount of wettability (decreased water contact angle) after exposure of scaffold to culture medium for long term which, in turn, causes more protein adsorption in the surface of silk fibroin scaffold (decreased roughness). Copyright © 2017. Published by Elsevier Ltd.

Recent advances in engineering topography mediated antibacterial surfaces

PubMed Central

Hasan, Jafar

2015-01-01

The tendency of bacterial cells to adhere and colonize a material surface leading to biofilm formation is a fundamental challenge underlying many different applications including microbial infections associated with biomedical devices and products. Although, bacterial attachment to surfaces has been extensively studied in the past, the effect of surface topography on bacteria–material interactions has received little attention until more recently. We review the recent progress in surface topography based approaches for engineering antibacterial surfaces. Biomimicry of antibacterial surfaces in nature is a popular strategy. Whereas earlier endeavors in the field aimed at minimizing cell attachment, more recent efforts have focused on developing bactericidal surfaces. However, not all such topography mediated bactericidal surfaces are necessarily cytocompatible thus underscoring the need for continued efforts for research in this area for developing antibacterial and yet cytocompatible surfaces for use in implantable biomedical applications. This mini-review provides a brief overview of the current strategies and challenges in the emerging field of topography mediated antibacterial surfaces. PMID:26372264

Recent advances in engineering topography mediated antibacterial surfaces

NASA Astrophysics Data System (ADS)

Hasan, Jafar; Chatterjee, Kaushik

2015-09-01

The tendency of bacterial cells to adhere and colonize a material surface leading to biofilm formation is a fundamental challenge underlying many different applications including microbial infections associated with biomedical devices and products. Although, bacterial attachment to surfaces has been extensively studied in the past, the effect of surface topography on bacteria-material interactions has received little attention until more recently. We review the recent progress in surface topography based approaches for engineering antibacterial surfaces. Biomimicry of antibacterial surfaces in nature is a popular strategy. Whereas earlier endeavors in the field aimed at minimizing cell attachment, more recent efforts have focused on developing bactericidal surfaces. However, not all such topography mediated bactericidal surfaces are necessarily cytocompatible thus underscoring the need for continued efforts for research in this area for developing antibacterial and yet cytocompatible surfaces for use in implantable biomedical applications. This mini-review provides a brief overview of the current strategies and challenges in the emerging field of topography mediated antibacterial surfaces.

Identification of Putative Cytoskeletal Protein Homologues in the Protozoan Host Hartmannella vermiformis as Substrates for Induced Tyrosine Phosphatase Activity upon Attachment to the Legionnaires' Disease Bacterium, Legionella pneumophila

PubMed Central

Venkataraman, Chandrasekar; Gao, Lian-Yong; Bondada, Subbarao; Kwaik, Yousef Abu

1998-01-01

The Legionnaires' disease bacterium, Legionella pneumophila, is a facultative intracellular pathogen that invades and replicates within two evolutionarily distant hosts, free living protozoa and mammalian cells. Invasion and intracellular replication within protozoa are thought to be major factors in the transmission of Legionnaires' disease. We have recently reported the identification of a galactose/N-acetyl-d-galactosamine (Gal/GalNAc) lectin in the protozoan host Hartmannella vermiformis as a receptor for attachment and invasion by L. pneumophila (Venkataraman, C., B.J. Haack, S. Bondada, and Y.A. Kwaik. 1997. J. Exp. Med. 186:537–547). In this report, we extended our studies to the effects of bacterial attachment and invasion on the cytoskeletal proteins of H. vermiformis. We first identified the presence of many protozoan cytoskeletal proteins that were putative homologues to their mammalian counterparts, including actin, pp125FAK, paxillin, and vinculin, all of which were basally tyrosine phosphorylated in resting H. vermiformis. In addition to L. pneumophila–induced tyrosine dephosphorylation of the lectin, bacterial attachment and invasion was associated with tyrosine dephosphorylation of paxillin, pp125FAK, and vinculin, whereas actin was minimally affected. Inhibition of bacterial attachment to H. vermiformis by Gal or GalNAc monomers blocked bacteria-induced tyrosine dephosphorylation of detergent-insoluble proteins. In contrast, inhibition of bacterial invasion but not attachment failed to block bacteria-induced tyrosine dephosphorylation of H. vermiformis proteins. This was further supported by the observation that 10 mutants of L. pneumophila that were defective in invasion of H. vermiformis were capable of inducing tyrosine dephosphorylation of H. vermiformis proteins. Entry of L. pneumophila into H. vermiformis was predominantly mediated by noncoated receptor-mediated endocytosis (93%) but coiling phagocytosis was infrequently observed (7%). We conclude that attachment but not invasion by L. pneumophila into H. vermiformis was sufficient and essential to induce protein tyrosine dephosphorylation in H. vermiformis. These manipulations of host cell processes were associated with, or followed by, entry of the bacteria by a noncoated receptor-mediated endocytosis. A model for attachment and entry of L. pneumophila into H. vermiformis is proposed. PMID:9687528

The role of endothelial cell attachment to elastic fibre molecules in the enhancement of monolayer formation and retention, and the inhibition of smooth muscle cell recruitment.

PubMed

Williamson, Matthew R; Shuttleworth, Adrian; Canfield, Ann E; Black, Richard A; Kielty, Cay M

2007-12-01

The endothelium is an essential modulator of vascular tone and thrombogenicity and a critical barrier between the vessel wall and blood components. In tissue-engineered small-diameter vascular constructs, endothelial cell detachment in flow can lead to thrombosis and graft failure. The subendothelial extracellular matrix provides stable endothelial cell anchorage through interactions with cell surface receptors, and influences the proliferation, migration, and survival of both endothelial cells and smooth muscle cells. We have tested the hypothesis that these desired physiological characteristics can be conferred by surface coatings of natural vascular matrix components, focusing on the elastic fiber molecules, fibrillin-1, fibulin-5 and tropoelastin. On fibrillin-1 or fibulin-5-coated surfaces, endothelial cells exhibited strong integrin-mediated attachment in static conditions (82% and 76% attachment, respectively) and flow conditions (67% and 78% cell retention on fibrillin-1 or fibulin-5, respectively, at 25 dynes/cm2), confluent monolayer formation, and stable functional characteristics. Adhesion to these two molecules also strongly inhibited smooth muscle cell migration to the endothelial monolayer. In contrast, on elastin, endothelial cells attached poorly, did not spread, and had markedly impaired functional properties. Thus, fibrillin-1 and fibulin-5, but not elastin, can be exploited to enhance endothelial stability, and to inhibit SMC migration within vascular graft scaffolds. These findings have important implications for the design of vascular graft scaffolds, the clinical performance of which may be enhanced by exploiting natural cell-matrix biology to regulate cell attachment and function.

A Single Regulator Mediates Strategic Switching between Attachment/Spread and Growth/Virulence in the Plant Pathogen Ralstonia solanacearum

PubMed Central

Khokhani, Devanshi; Lowe-Power, Tiffany M.; Tran, Tuan Minh

2017-01-01

ABSTRACT The PhcA virulence regulator in the vascular wilt pathogen Ralstonia solanacearum responds to cell density via quorum sensing. To understand the timing of traits that enable R. solanacearum to establish itself inside host plants, we created a ΔphcA mutant that is genetically locked in a low-cell-density condition. Comparing levels of gene expression of wild-type R. solanacearum and the ΔphcA mutant during tomato colonization revealed that the PhcA transcriptome includes an impressive 620 genes (>2-fold differentially expressed; false-discovery rate [FDR], ≤0.005). Many core metabolic pathways and nutrient transporters were upregulated in the ΔphcA mutant, which grew faster than the wild-type strain in tomato xylem sap and on dozens of specific metabolites, including 36 found in xylem. This suggests that PhcA helps R. solanacearum to survive in nutrient-poor environmental habitats and to grow rapidly during early pathogenesis. However, after R. solanacearum reaches high cell densities in planta, PhcA mediates a trade-off from maximizing growth to producing costly virulence factors. R. solanacearum infects through roots, and low-cell-density-mode-mimicking ΔphcA cells attached to tomato roots better than the wild-type cells, consistent with their increased expression of several adhesins. Inside xylem vessels, ΔphcA cells formed aberrantly dense mats. Possibly as a result, the mutant could not spread up or down tomato stems as well as the wild type. This suggests that aggregating improves R. solanacearum survival in soil and facilitates infection and that it reduces pathogenic fitness later in disease. Thus, PhcA mediates a second strategic switch between initial pathogen attachment and subsequent dispersal inside the host. PhcA helps R. solanacearum optimally invest resources and correctly sequence multiple steps in the bacterial wilt disease cycle. PMID:28951474

Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1

PubMed Central

Dios-Esponera, Ana; Isern de Val, Soledad; Sevilla-Movilla, Silvia; García-Verdugo, Rosa; García-Bernal, David; Arellano-Sánchez, Nohemí; Cabañas, Carlos; Teixidó, Joaquin

2015-01-01

Stimulation by chemokines of integrin α4β1–dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase–inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76–, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation. PMID:26202465

Attachment insecurity as a mediator of the relationship between childhood trauma and adult dissociation.

PubMed

Kong, Seong Sook; Kang, Dae Ryong; Oh, Min Jung; Kim, Nam Hee

2018-01-01

This study aimed to investigate whether attachment insecurity mediates the relationship between childhood trauma and adult dissociation, specifically with regard to individual forms of childhood maltreatment. Psychiatric outpatients who visited a specialized trauma clinic (n = 115) participated in the study. Data were collected via the Childhood Trauma Questionnaire, Revised Adult Attachment Scale, and Dissociative Experience Scale. Structural equation modeling and path analysis were performed to analyze the mediating effects of attachment insecurity on the relationship between childhood trauma and adult dissociation. Greater childhood trauma was associated with higher dissociation, and the relationship between them was fully mediated by attachment anxiety. In path analysis of trauma subtypes, the effects of emotional abuse, physical abuse, and physical neglect as a child on adult dissociation were found to be fully mediated by attachment anxiety. The effect of sexual abuse on dissociation was mediated by a synergistic effect from both attachment anxiety and attachment avoidance. Regarding emotional neglect, a countervailing interaction was discovered between the direct and indirect effects thereof on dissociation; the indirect effect of emotional neglect on dissociation was partially mediated by attachment insecurity. Specific aspects of attachment insecurity may help explain the relationships between individual forms of childhood trauma and adult dissociative symptoms. Tailored treatments based on affected areas of attachment insecurity may improve outcomes among patients with dissociative symptoms and a history of childhood trauma.

Does insecure attachment mediate the relationship between trauma and voice-hearing in psychosis?

PubMed

Pilton, Marie; Bucci, Sandra; McManus, James; Hayward, Mark; Emsley, Richard; Berry, Katherine

2016-12-30

This study extends existing research and theoretical developments by exploring the potential mediating role of insecure attachment within the relationship between trauma and voice-hearing. Fifty-five voice hearers with a psychosis-related diagnosis completed comprehensive assessments of childhood trauma, adult attachment, voice-related severity and distress, beliefs about voices and relationships with voices. Anxious attachment was significantly associated with the voice-hearing dimensions examined. More sophisticated analysis showed that anxious attachment mediated the relationship between childhood sexual and emotional abuse and voice-related severity and distress, voice-malevolence, voice-omnipotence, voice-resistance and hearer-dependence. Anxious attachment also mediated the relationship between childhood physical neglect and voice-related severity and distress and hearer-dependence. Furthermore, consistent with previous research, the relationship between anxious attachment and voice-related distress was mediated by voice-malevolence, voice-omnipotence and voice-resistance. We propose a model whereby anxious attachment mediates the well-established relationship between trauma and voice-hearing. In turn, negative beliefs about voices may mediate the association between anxious attachment and voice-related distress. Findings presented here highlight the need to assess and formulate the impact of attachment patterns upon the voice-hearing experience in psychosis and the potential to alleviate voice-related distress by fostering secure attachments to therapists or significant others. Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.

Attachment and exploration in adulthood: the mediating effect of social support.

PubMed

Wu, Chia-huei; Yang, Cheng-Ta

2012-01-01

Research examining the relationship between adult attachment styles and exploratory behavior has shown that anxious and avoidant attachment styles are negatively related to exploration. However, little research has been conducted on the mediation process between adult attachment styles and exploration. Given that perceived social support has been shown to be the basis for secure attachment and may be related to exploration behavior, the current study examines whether perceived social support mediates the relationship between adult attachment and exploration. University students in Taiwan (N = 168) completed questionnaires that assessed attachment styles; perceived social support from their father, mother, and best friend; and their intellectual, social, and environmental exploration. Our results revealed that perceived social support mediates the relationship between avoidant attachment and exploration behavior.

Substratum interfacial energetic effects on the attachment of marine bacteria

NASA Astrophysics Data System (ADS)

Ista, Linnea Kathryn

Biofilms represent an ancient, ubiquitous and influential form of life on earth. Biofilm formation is initiated by attachment of bacterial cells from an aqueous suspension onto a suitable attachment substratum. While in certain, well studied cases initial attachment and subsequent biofilm formation is mediated by specific ligand-receptor pairs on the bacteria and attachment substratum, in the open environment, including the ocean, it is assumed to be non-specific and mediated by processes similar to those that drive adsorption of colloids at the water-solid interface. Colloidal principles are studied to determine the molecular and physicochemical interactions involved in the attachment of the model marine bacterium, Cobetia marina to model self-assembled monolayer surfaces. In the simplest application of colloidal principles the wettability of attachment substrata, as measured by the advancing contact angle of water (theta AW) on the surface, is frequently used as an approximation for the surface tension. We demonstrate the applicability of this approach for attachment of C. marina and algal zoospores and extend it to the development of a means to control attachment and release of microorganisms by altering and tuning surface thetaAW. In many cases, however, thetaAW does not capture all the information necessary to model attachment of bacteria to attachment substrata; SAMs with similar thetaAW attach different number of bacteria. More advanced colloidal models of initial bacterial attachment have evolved over the last several decades, with the emergence of the model proposed by van Oss, Chaudhury and Good (VCG) as preeminent. The VCG model enables calculation of interfacial tensions by dividing these into two major interactions thought to be important at biointerfaces: apolar, Lifshitz-van der Waals and polar, Lewis acid-base (including hydrogen bonding) interactions. These interfacial tensions are combined to yield DeltaGadh, the free energy associated with attachment of bacteria to a substratum. We use VCG to model DeltaGadh and interfacial tensions as they relate to model bacterial attachment on SAMs that accumulate cells to different degrees. Even with the more complex interactions measured by VCG, surface energy of the attachment substratum alone was insufficient to predict attachment. VCG was then employed to model attachment of C. marina to a series of SAMs varying systematically in the number of ethylene glycol residues present in the molecule; an identical series has been previously shown to vary dramatically in the number of cells attached as a function of ethylene glycols present. Our results indicate that while VCG adequately models the interfacial tension between water and ethylene glycol SAMs in a manner that predicts bacterial attachment, DeltaGadh as calculated by VCG neither qualitatively nor quantitatively reflects the attachment data. The VCG model, thus, fails to capture specific information regarding the interactions between the attaching bacteria, water, and the SAM. We show that while hydrogen-bond accepting interactions are very well captured by this model, the ability for SAMs and bacteria to donate hydrogen bonds is not adequately described as the VCG model is currently applied. We also describe ways in which VCG fails to capture two specific biological aspects that may be important in bacterial attachment to surfaces:1.) specific interactions between molecules on the surface and bacteria and 2.) bacterial cell surface heterogeneities that may be important in differential attachment to different substrata.

Affect Regulation as a Mediator of Attachment and Deliberate Self-Harm

ERIC Educational Resources Information Center

Kimball, Joan S.; Diddams, Margaret

2007-01-01

The authors used structural equation modeling to test the mediational role of affect regulation on attachment and deliberate self-harm in 216 undergraduates. Results suggest that affect regulation mediates the relationship between attachment and deliberate self-harm, providing support for the theoretical importance of attachment and affect…

The Globoside Receptor Triggers Structural Changes in the B19 Virus Capsid That Facilitate Virus Internalization▿

PubMed Central

Bönsch, Claudia; Zuercher, Christoph; Lieby, Patricia; Kempf, Christoph; Ros, Carlos

2010-01-01

Globoside (Gb4Cer), Ku80 autoantigen, and α5β1 integrin have been identified as cell receptors/coreceptors for human parvovirus B19 (B19V), but their role and mechanism of interaction with the virus are largely unknown. In UT7/Epo cells, expression of Gb4Cer and CD49e (integrin alpha-5) was high, but expression of Ku80 was insignificant. B19V colocalized with Gb4Cer and, to a lesser extent, with CD49e. However, only anti-Gb4Cer antibodies could disturb virus attachment. Only a small proportion of cell-bound viruses were internalized, while the majority became detached from the receptor. When added to uninfected cells, the receptor-detached virus showed superior cell binding capacity and infectivity. Attachment of B19V to cells triggered conformational changes in the capsid leading to the accessibility of the N terminus of VP1 (VP1u) to antibodies, which was maintained in the receptor-detached virus. VP1u became similarly accessible to antibodies following incubation of B19V particles with increasing concentrations of purified Gb4Cer. The receptor-mediated exposure of VP1u is critical for virus internalization, since capsids lacking VP1 could bind to cells but were not internalized. Moreover, an antibody against the N terminus of VP1u disturbed virus internalization, but only when present during and not after virus attachment, indicating the involvement of this region in binding events required for internalization. These results suggest that Gb4Cer is not only the primary receptor for B19V attachment but also the mediator of capsid rearrangements required for subsequent interactions leading to virus internalization. The capacity of the virus to detach and reattach again would enhance the probability of productive infections. PMID:20826697

Fluorescence polarization-based assay using N-glycan-conjugated quantum dots for screening in hemagglutinin blockers for influenza A viruses.

PubMed

Okamatsu, Masatoshi; Feng, Fei; Ohyanagi, Tatsuya; Nagahori, Noriko; Someya, Kazuhiko; Sakoda, Yoshihiro; Miura, Nobuaki; Nishimura, Shin-Ichiro; Kida, Hiroshi

2013-02-01

Attachment of influenza virus to susceptible cells is mediated by viral protein hemagglutinin (HA), which recognizes cell surface glycoconjugates that terminate in α-sialosides. To develop anti-influenza drugs based on inhibition of HA-mediated infection, novel fluorescent nanoparticles displaying multiple biantennary N-glycan chains with α-sialosides (A2-PC-QDs) that have high affinity for the HA were designed and constructed. The A2-PC-QDs enabled an easy and efficient fluorescence polarization (FP) assay for detection of interaction with the HA and competitive inhibition even by small molecule compounds against A2-PC-QDs-HA binding. The quantum dot (QD)-based FP assay established in the present study is a useful tool for high-throughput screening and to accelerate the development of novel and more effective blockers of the viral attachment of influenza virus. Copyright © 2012 Elsevier B.V. All rights reserved.

Calcium carbonate mineralization mediated by in vitro cultured mantle cells from Pinctada fucata.

PubMed

Kong, Wei; Li, Shiguo; Xiang, Liang; Xie, Liping; Zhang, Rongqing

2015-08-07

Formation of the molluscan shell is believed to be an extracellular event mediated by matrix proteins. We report calcium carbonate mineralization mediated by Pinctada fucata mantle cells. Crystals only appeared when mantle cells were present in the crystallization solution. These crystals were piled up in highly ordered units and showed the typical characteristics of biomineralization products. A thin organic framework was observed after dissolving the crystals in EDTA. Some crystals had etched surfaces with a much smoother appearance than other parts. Mantle cells were observed to be attached to some of these smooth surfaces. These results suggest that mantle cells may be directly involved in the nucleation and remodeling process of calcium carbonate mineralization. Our result demonstrate the practicability of studying the mantle cell mechanism of biomineralization and contribute to the overall understanding of the shell formation process. Copyright © 2015 Elsevier Inc. All rights reserved.

Preconditioning with cations increases the attachment of Anoxybacillus flavithermus and Geobacillus species to stainless steel.

PubMed

Somerton, Ben; Flint, Steve; Palmer, Jon; Brooks, John; Lindsay, Denise

2013-07-01

Preconditioning of Anoxybacillus flavithermus E16 and Geobacillus sp. strain F75 with cations prior to attachment often significantly increased (P ≤ 0.05) the number of viable cells that attached to stainless steel (by up to 1.5 log CFU/cm(2)) compared with unconditioned bacteria. It is proposed that the transition of A. flavithermus and Geobacillus spp. from milk formulations to stainless steel product contact surfaces in milk powder manufacturing plants is mediated predominantly by bacterial physiological factors (e.g., surface-exposed adhesins) rather than the concentrations of cations in milk formulations surrounding bacteria.

Attachment to parents and peers as a risk factor for adolescent depressive disorders: the mediating role of emotion regulation.

PubMed

Kullik, Angelika; Petermann, Franz

2013-08-01

This study examined emotion regulation as a mediator in the relationship of attachment and depression in adolescents. Participants (N girls = 127; M age = 14.50; N boys = 121; M age = 14.31) completed self-report questionnaires of attachment to parents and peers, emotion regulation and depression. Models with dysfunctional emotion regulation as a mediation variable were tested via hierarchical multiple regression analyses and bootstrapping procedure. Results revealed significant relations between attachment to parents and peers, dysfunctional emotion regulation and depression. For girls, internal-dysfunctional emotion regulation was a mediator in the relation of attachment to parents and depression and partly mediated the association of attachment to peers. For boys, internal- and external-dysfunctional emotion regulation acted as partly mediators in association of attachment to parents and depression. Results indicate important mechanisms that contribute to the refinement of conceptual models and provide indications for gender specific prevention and intervention for depressive disorders.

Shielding of a lipooligosaccharide IgM epitope allows evasion of neutrophil-mediated killing of an invasive strain of nontypeable Haemophilus influenzae.

PubMed

Langereis, Jeroen D; Weiser, Jeffrey N

2014-07-22

Nontypeable Haemophilus influenzae is a frequent cause of noninvasive mucosal inflammatory diseases but may also cause invasive diseases, such as sepsis and meningitis, especially in children and the elderly. Infection by nontypeable Haemophilus influenzae is characterized by recruitment of neutrophilic granulocytes. Despite the presence of a large number of neutrophils, infections with nontypeable Haemophilus influenzae are often not cleared effectively by the antimicrobial activity of these immune cells. Herein, we examined how nontypeable Haemophilus influenzae evades neutrophil-mediated killing. Transposon sequencing (Tn-seq) was used on an isolate resistant to neutrophil-mediated killing to identify genes required for its survival in the presence of human neutrophils and serum, which provided a source of complement and antibodies. Results show that nontypeable Haemophilus influenzae prevents complement-dependent neutrophil-mediated killing by expression of surface galactose-containing oligosaccharide structures. These outer-core structures block recognition of an inner-core lipooligosaccharide epitope containing glucose attached to heptose HepIII-β1,2-Glc by replacement with galactose attached to HepIII or through shielding HepIII-β1,2-Glc by phase-variable attachment of oligosaccharide chain extensions. When the HepIII-β1,2-Glc-containing epitope is expressed and exposed, nontypeable Haemophilus influenzae is opsonized by naturally acquired IgM generally present in human serum and subsequently phagocytosed and killed by human neutrophils. Clinical nontypeable Haemophilus influenzae isolates containing galactose attached to HepIII that are not recognized by this IgM are more often found to cause invasive infections. Importance: Neutrophils are white blood cells that specialize in killing pathogens and are recruited to sites of inflammation. However, despite the presence of large numbers of neutrophils in the middle ear cavity and lungs of patients with otitis media or chronic obstructive pulmonary disease, respectively, the bacterium nontypeable Haemophilus influenzae is often not effectively cleared from these locations by these immune cells. In order to understand how nontypeable Haemophilus influenzae is able to cause inflammatory diseases in the presence of neutrophils, we determined the mechanism that underlies resistance to neutrophil-mediated killing. We have shown that nontypeable Haemophilus influenzae prevents binding of antibodies of the IgM subtype through changes in their surface lipooligosaccharide structure, thereby preventing complement activation and clearance by human neutrophils. Copyright © 2014 Langereis and Weiser.

Exposure to family violence and attachment styles as predictors of dating violence perpetration among men and women: a mediational model.

PubMed

Lee, Mary; Reese-Weber, Marla; Kahn, Jeffrey H

2014-01-01

This study examined a multiple mediator model explaining how sibling perpetration and one's attachment style mediate the relation between parent-to-child victimization and dating violence perpetration. A sample of undergraduate students (n = 392 women, n = 89 men) completed measures of the aforementioned variables on an Internet survey. For men, path analyses found no mediation; parent-to-child victimization had a direct association with dating violence perpetration, no association was found between sibling perpetration and dating violence perpetration, and attachment anxiety, but not attachment avoidance, was positively associated with dating violence perpetration for men. For women, the hypothesized mediation model was supported; parent-to-child victimization had a direct association with dating violence perpetration, and sibling perpetration and attachment anxiety served as mediating variables. Attachment avoidance was not associated with dating violence perpetration for women. Implications for future research and clinical practice are discussed.

Host cell recognition by the henipaviruses: Crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Kai; Rajashankar, Kanagalaghatta R.; Chan, Yee-Peng

2008-07-28

Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus Henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotein (NiV-G) that facilitates attachment to host cells and the fusion (F) glycoprotein that mediates membrane merger. The henipavirus G glycoproteins lack both hemagglutinating and neuraminidase activities and, instead, engage the highly conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry receptors. Here, we report the crystal structures of the NiV-G both in its receptor-unbound statemore » and in complex with ephrin-B3, providing, to our knowledge, the first view of a paramyxovirus attachment complex in which a cellular protein is used as the virus receptor. Complex formation generates an extensive protein-protein interface around a protruding ephrin loop, which is inserted in the central cavity of the NiV-G {beta}-propeller. Analysis of the structural data reveals the molecular basis for the highly specific interactions of the henipavirus G glycoproteins with only two members (ephrin-B2 and ephrin-B3) of the very large ephrin family and suggests how they mediate in a unique fashion both cell attachment and the initiation of membrane fusion during the virus infection processes. The structures further suggest that the NiV-G/ephrin interactions can be effectively targeted to disrupt viral entry and provide the foundation for structure-based antiviral drug design.« less

Childhood maltreatment, adult attachment and psychotic symptomatology: a study in patients, siblings and controls.

PubMed

van Dam, D S; Korver-Nieberg, N; Velthorst, E; Meijer, C J; de Haan, L

2014-11-01

The association between childhood maltreatment (ChM) and psychotic disorders is well established. However, there is an ongoing debate about which factors account for this relationship. One explanation is that the relationship between ChM and psychosis is mediated by adult attachment style. Therefore, in this study, we aimed to investigate whether adult attachment style mediates the relationship between ChM and positive and negative symptomatology. We investigated the relation between ChM and psychotic symptoms, taking into account levels of (insecure) attachment, in 131 patients with psychotic illness, 123 siblings and 72 controls. ChM was assessed with the Childhood Trauma Questionnaire (CTQ). Attachment dimensions of anxiety and avoidance were measured using the Psychosis Attachment Measure (PAM). In both patients and siblings, ChM predicted positive symptoms and this relationship was partly mediated by attachment style. This relationship was found to be stronger for siblings than for patients. ChM predicted negative symptoms in patients and siblings. In the patient sample, attachment style did not mediate the relationship between ChM and negative symptoms, whereas attachment style was found to be a mediator in the sibling sample. ChM was associated with positive and negative symptomatology in both patients and siblings. Particularly in siblings, the relationship between ChM and psychosis seems to be mediated by adult attachment style. Perhaps attachment style may play a more prominent role on a subclinical level.

Infant attachment, adult attachment, and maternal sensitivity: revisiting the intergenerational transmission gap.

PubMed

Behrens, Kazuko Y; Haltigan, John D; Bahm, Naomi I Gribneau

2016-08-01

This study investigated the intergenerational transmission of attachment, utilizing the Adult Attachment Interview (AAI), the Strange Situation Procedure (SSP), and the Maternal Behavioral Q-Set (MBQS). We revisited fundamental questions in attachment theory and research by examining: (1) the level of intergenerational agreement between maternal attachment representations and infant attachment security, and (2) whether maternal sensitivity serves as an intergenerational mediator between adult and infant attachment security. Significant categorical matches between the AAI and the SSP as well as mean differences for MBQS scores between adult attachment secure-insecure groups were found. Consistent with earlier intergenerational research, maternal sensitivity only partially mediated the AAI-SSP link, indicating the transmission gap remains. Consistent with recent mediation studies, using more contemporary analytical techniques, it was confirmed that maternal sensitivity did mediate the direct pathway between AAI security and SSP security. Thus, the transmission gap appears somewhat different depending on the statistical method used to measure mediation. Post hoc analyses considered mothers' childhood experiences of separation/divorce and this helped make sense of intergenerational mismatches.

Attachment style and suicide behaviors in high risk psychiatric inpatients following hospital discharge: The mediating role of entrapment.

PubMed

Li, Shuang; Galynker, Igor I; Briggs, Jessica; Duffy, Molly; Frechette-Hagan, Anna; Kim, Hae-Joon; Cohen, Lisa J; Yaseen, Zimri S

2017-11-01

Insecure attachment is associated with suicidal behavior. This relationship and its possible mediators have not been examined in high-risk psychiatric inpatients with respect to the critical high-risk period following hospital discharge. Attachment styles and perception of entrapment were assessed in 200 high-risk adult psychiatric inpatients hospitalized following suicidal ideation or suicide attempt. Suicidal behaviors were evaluated with the Columbia Suicide Severity Rating Scale at 1-2 months post-discharge. Associations between different attachment styles and suicidal behaviors were assessed and mediation of attachment effects by entrapment was modeled. Fearful attachment was associated with post-discharge suicidal behavior and there was a trend-level negative association for secure attachment. In addition, entrapment mediated the relationship between fearful attachment and suicidal behavior. The current study highlights the mediating role of perceptions of entrapment in the contribution of fearful attachment to suicidal behavior in high-risk patients, suggesting entrapment as potential therapeutic target to prevent suicidal behavior in these individuals. Further research is warranted to establish the mechanisms by which entrapment experiences emerge in patients with insecure attachment styles. Copyright © 2017 Elsevier B.V. All rights reserved.

Disorganized attachment in young adulthood as a partial mediator of relations between severity of childhood abuse and dissociation.

PubMed

Byun, Sooyeon; Brumariu, Laura E; Lyons-Ruth, Karlen

2016-01-01

Disorganized attachment has been proposed as a mediating mechanism in the relation between childhood abuse and dissociation. However, support for mediation has been mixed when interview or self-report measures of attachment have been used. In the current work, relations among severity of abuse, attachment disorganization, and dissociation were assessed in young adulthood using both interview and interaction-based measures of attachment. A total of 112 low-income young adults were assessed for socioeconomic stresses, abusive experiences in childhood, and attachment disorganization at age 20. Attachment disorganization was assessed with the Adult Attachment Interview, coded independently for Unresolved states of mind and for Hostile-Helpless states of mind. Attachment disorganization was also measured using a newly validated assessment of young adult-parent interaction during a conflict discussion. Mediation analyses revealed that the link between childhood abuse and dissociation was partially explained by disturbances in young adult-parent interaction. Narrative disturbances on the Adult Attachment Interview were related to abuse and to dissociation but did not mediate the link between the two. Results are discussed in relation to the role of parent-child communication processes in pathways to dissociation.

Establishment of highly metastatic KRAS mutant lung cancer cell sublines in long-term three-dimensional low attachment cultures

PubMed Central

Nakano, Tomoyuki; Kanai, Yoshihiko; Amano, Yusuke; Yoshimoto, Taichiro; Matsubara, Daisuke; Shibano, Tomoki; Tamura, Tomoko; Oguni, Sachiko; Katashiba, Shizuka; Ito, Takeshi; Murakami, Yoshinori; Fukayama, Masashi; Murakami, Takashi; Endo, Shunsuke; Niki, Toshiro

2017-01-01

Decreased cell-substratum adhesion is crucially involved in metastasis. Previous studies demonstrated that lung cancer with floating cell clusters in histology is more likely to develop metastasis. In the present study, we investigated whether cancer cells in long-term, three-dimensional low attachment cultures acquire high metastatic potential; these cells were then used to examine the mechanisms underlying metastasis. Two KRAS-mutated adenocarcinoma cell lines (A549 and H441) were cultured and selected on ultra-low attachment culture dishes, and the resulting cells were defined as FL (for floating) sublines. Cancer cells were inoculated into NOD/SCID mice via an intracardiac injection, and metastasis was evaluated using luciferase-based imaging and histopathology. In vitro cell growth (in attachment or suspension cultures), migration, and invasion were assayed. A whole genomic analysis was performed to identify key molecular alterations in FL sublines. Upon detachment on low-binding dishes, parental cells initially formed rounded spheroids with limited growth activity. However, over time in cultures, cells gradually formed smaller spheroids that grew slowly, and, after 3–4 months, we obtained FL sublines that regained prominent growth potential in suspension cultures. On ordinary dishes, FL cells reattached and exhibited a more spindle-shaped morphology than parental cells. No marked differences were observed in cell growth with attachment, migration, or invasion between FL sublines and parental cell lines; however, FL cells exhibited markedly increased growth potential under suspended conditions in vitro and stronger metastatic abilities in vivo. A genomic analysis identified epithelial-mesenchymal transition (EMT) and c-Myc amplification in A549-FL and H441-FL cells, respectively, as candidate mechanisms for metastasis. The growth potential of FL cells was markedly inhibited by lentiviral ZEB1 knockdown in A549-FL cells and by the inhibition of c-Myc through lentiviral knockdown or the pharmacological inhibitor JQ1 in H441-FL cells. Long-term three-dimensional low attachment cultures may become a useful method for investigating the mechanisms underlying metastasis mediated by decreased cell-substratum adhesion. PMID:28786996

Role of E-cadherin in membrane-cortex interaction probed by nanotube extrusion.

PubMed

Tabdanov, Erdem; Borghi, Nicolas; Brochard-Wyart, Françoise; Dufour, Sylvie; Thiery, Jean-Paul

2009-03-18

This study aims to define the role of E-cadherin (Ecad) engagement in cell-cell contact during membrane-cortex interaction. As a tool, we used a hydrodynamic membrane tube extrusion technique to characterize the mechanical interaction between the plasma membrane and the underlying cortical cytoskeleton. Cells were anchored on 4.5 microm beads coated with polylysine (PL) to obtain nonspecific cell adhesion or with an antibody against Ecad to mimic specific Ecad-mediated cell adhesion. We investigated tube length dynamics L(t) over time and through successive extrusions applied to the cell at regular time intervals. A constant slow velocity was observed for the first extrusion, for PL-attached cells. Subsequent extrusions had two phases: an initial high-velocity regime followed by a low-velocity regime. Successive extrusions gradually weakened the binding of the membrane around the tube neck to the underlying cortical cytoskeleton. Cells specifically attached via Ecad first exhibited a very low extrusion velocity regime followed by a faster extrusion regime similar to nonspecific extrusion. This indicates that Ecad strengthens the membrane-cortical cytoskeleton interaction, but only in a restricted area corresponding to the site of contact between the cell and the bead. Occasional giant "cortex" tubes were extruded with specifically anchored cells, demonstrating that the cortex remained tightly bound to the membrane through Ecad-mediated adhesion at the contact site.

Role of E-Cadherin in Membrane-Cortex Interaction Probed by Nanotube Extrusion

PubMed Central

Tabdanov, Erdem; Borghi, Nicolas; Brochard-Wyart, Françoise; Dufour, Sylvie; Thiery, Jean-Paul

2009-01-01

This study aims to define the role of E-cadherin (Ecad) engagement in cell-cell contact during membrane-cortex interaction. As a tool, we used a hydrodynamic membrane tube extrusion technique to characterize the mechanical interaction between the plasma membrane and the underlying cortical cytoskeleton. Cells were anchored on 4.5 μm beads coated with polylysine (PL) to obtain nonspecific cell adhesion or with an antibody against Ecad to mimic specific Ecad-mediated cell adhesion. We investigated tube length dynamics L(t) over time and through successive extrusions applied to the cell at regular time intervals. A constant slow velocity was observed for the first extrusion, for PL-attached cells. Subsequent extrusions had two phases: an initial high-velocity regime followed by a low-velocity regime. Successive extrusions gradually weakened the binding of the membrane around the tube neck to the underlying cortical cytoskeleton. Cells specifically attached via Ecad first exhibited a very low extrusion velocity regime followed by a faster extrusion regime similar to nonspecific extrusion. This indicates that Ecad strengthens the membrane-cortical cytoskeleton interaction, but only in a restricted area corresponding to the site of contact between the cell and the bead. Occasional giant “cortex” tubes were extruded with specifically anchored cells, demonstrating that the cortex remained tightly bound to the membrane through Ecad-mediated adhesion at the contact site. PMID:19289070

Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1.

PubMed

Dios-Esponera, Ana; Isern de Val, Soledad; Sevilla-Movilla, Silvia; García-Verdugo, Rosa; García-Bernal, David; Arellano-Sánchez, Nohemí; Cabañas, Carlos; Teixidó, Joaquin

2015-09-15

Stimulation by chemokines of integrin α4β1-dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase-inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76-, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation. © 2015 Dios-Esponera, Isern de Val, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Rumen bacteria: interaction with particulate dietary components and response to dietary variation.

PubMed

Cheng, K J; Akin, D E; Costerton, J W

1977-02-01

The bovine rumen resembles many other ecosystems in that its component bacterial cells are universally surrounded and protected by extracellular structures. The most common form of these structures is a fibrous carbohydrate slime that extends away from the cell and may mediate the attachment of the bacterium to a surface. This attachment is relatively specific and it may occur at the surface of the rumen epithelium or on the cell walls of a specific tissue within the plant-derived food of the animal. The production of the extracellular slime is under nutritional control and slime may be overproduced when soluble carbohydrates are available in high concentration. This overproduction results in cell-cell adhesion among the rumen bacteria with the eventual formation of slime-enclosed microcolonies and, in extreme cases, the generation of sufficient viscosity to cause feedlot bloat.

The mediating role of social environmental factors in the associations between attachment styles and basic needs satisfaction.

PubMed

Felton, Luke; Jowett, Sophia

2013-01-01

The present study aimed to explore the mediating role of social factors on the associations between attachment styles and basic psychological needs satisfaction within two relational contexts. Athletes (N = 215) completed a multi-section questionnaire pertaining to attachment styles, basic needs satisfied within the coaching and the parental relational context, and such social factors as social support, interpersonal conflict, autonomy and controlling behaviours. Bootstrap mediation analysis revealed that the association between avoidant attachment style and basic needs satisfaction with the coach was mediated by social support and autonomy-related behaviours from the coach. The association between avoidant attachment style and basic needs satisfaction with the parent on the other hand was mediated by all social factors investigated. Finally, the association between anxious attachment style and basic needs satisfaction from the parent was mediated by conflict and controlling behaviours. Overall, the findings of the current study suggest that social factors play an important role in explaining the associations between attachment styles and basic needs satisfaction within two central relational contexts athletes operate in, and thus should be targeted in future interventions.

Relationship authenticity partially mediates the effects of attachment on relationship satisfaction.

PubMed

Rasco, Danney; Warner, Rebecca M

2017-01-01

Individuals with anxious and avoidant attachment tend to experience less satisfaction in their relationships. Past research suggests the negative effects of attachment on relationship satisfaction may be partially mediated by self-disclosure and self-concealment; the present study evaluated relationship authenticity as a potential additional mediator. Confirmatory factor analysis indicated that relationship authenticity is distinct from self-disclosure and self-concealment. Relationship authenticity predicted additional variance in relationship satisfaction controlling for attachment, self-disclosure, and self-concealment. The results were consistent with relationship authenticity, along with self-disclosure and self-concealment, partially mediating the effects of attachment on relationship satisfaction. These findings suggest that relationship authenticity may play a unique role in understanding how attachment influences relationship satisfaction. Theoretical and clinical implications are discussed.

Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria

PubMed Central

Das, Soumita; Owen, Katherine A.; Ly, Kim T.; Park, Daeho; Black, Steven G.; Wilson, Jeffrey M.; Sifri, Costi D.; Ravichandran, Kodi S.; Ernst, Peter B.; Casanova, James E.

2011-01-01

Bacterial recognition by host cells is essential for initiation of infection and the host response. Bacteria interact with host cells via multiple pattern recognition receptors that recognize microbial products or pathogen-associated molecular patterns. In response to this interaction, host cell signaling cascades are activated that lead to inflammatory responses and/or phagocytic clearance of attached bacteria. Brain angiogenesis inhibitor 1 (BAI1) is a receptor that recognizes apoptotic cells through its conserved type I thrombospondin repeats and triggers their engulfment through an ELMO1/Dock/Rac1 signaling module. Because thrombospondin repeats in other proteins have been shown to bind bacterial surface components, we hypothesized that BAI1 may also mediate the recognition and clearance of pathogenic bacteria. We found that preincubation of bacteria with recombinant soluble BAI1 ectodomain or knockdown of endogenous BAI1 in primary macrophages significantly reduced binding and internalization of the Gram-negative pathogen Salmonella typhimurium. Conversely, overexpression of BAI1 enhanced attachment and engulfment of Salmonella in macrophages and in heterologous nonphagocytic cells. Bacterial uptake is triggered by the BAI1-mediated activation of Rac through an ELMO/Dock-dependent mechanism, and inhibition of the BAI1/ELMO1 interaction prevents both Rac activation and bacterial uptake. Moreover, inhibition of ELMO1 or Rac function significantly impairs the proinflammatory response to infection. Finally, we show that BAI1 interacts with a variety of Gram-negative, but not Gram-positive, bacteria through recognition of their surface lipopolysaccharide. Together these findings identify BAI1 as a pattern recognition receptor that mediates nonopsonic phagocytosis of Gram-negative bacteria by macrophages and directly affects the host response to infection. PMID:21245295

Adult attachment, perceived social support, cultural orientation, and depressive symptoms: A moderated mediation model.

PubMed

Zhu, Wenzhen; Wang, Chiachih Dc; Chong, Chu Chian

2016-11-01

In the current study, we tested a moderated mediation model in which cultural orientation moderated the mediation model of adult attachment-perceived social support-depressive symptoms, using 2 comparable cross-cultural samples of college students recruited from China and the U.S. (n = 363 for each group). Results indicated that perceived social support mediated the effect of attachment anxiety on depressive symptoms as well as the link between attachment avoidance and depression in both samples. Moderated mediation analyses using PROCESS revealed that interdependent self-construal significantly buffered the indirect effect of attachment avoidance (via perceived social support) on depressive symptoms. The findings indicated significant differences in the mediation models between the U.S. and China groups and interdependent self-construal accounted for the between-country differences. Limitations, implications of the findings, and future research directions are discussed from the perspectives of cross-cultural variation of adult attachment functioning. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Structural Equation Model of Smartphone Addiction Based on Adult Attachment Theory: Mediating Effects of Loneliness and Depression.

PubMed

Kim, EunYoung; Cho, Inhyo; Kim, Eun Joo

2017-06-01

This study investigated the mediating effects of loneliness and depression on the relationship between adult attachment and smartphone addiction in university students. A total of 200 university students participated in this study. The data was analysed using descriptive statistics, correlation analysis, and structural equation modeling. There were significant positive relationships between attachment anxiety, loneliness, depression, and smartphone addiction. However, attachment anxiety was not significantly correlated with smartphone addiction. The results also showed that loneliness did not directly mediate between attachment anxiety and smartphone addiction. In addition, loneliness and depression serially mediated between attachment anxiety and smartphone addiction. The results suggest there are mediating effects of loneliness and depression in the relationship between attachment anxiety and smartphone addiction. The hypothesized model was found to be a suitable model for predicting smartphone addiction among university students. Future study is required to find a causal path to prevent smartphone addiction among university students. Copyright © 2017. Published by Elsevier B.V.

Sexuality examined through the lens of attachment theory: attachment, caregiving, and sexual satisfaction.

PubMed

Péloquin, Katherine; Brassard, Audrey; Lafontaine, Marie-France; Shaver, Phillip R

2014-01-01

Attachment researchers have proposed that the attachment, caregiving, and sexual behavioral systems are interrelated in adult love relationships (Mikulincer & Shaver, 2007 ). This study examined whether aspects of partners' caregiving (proximity, sensitivity, control, compulsive caregiving) mediated the association between their attachment insecurities (anxiety and avoidance) and each other's sexual satisfaction in two samples of committed couples (Study 1: 126 cohabiting or married couples from the general community; Study 2: 55 clinically distressed couples). Partners completed the Experiences in Close Relationships measure (Brennan, Clark, & Shaver, 1998 ), the Caregiving Questionnaire (Kunce & Shaver, 1994 ), and the Global Measure of Sexual Satisfaction (Lawrance & Byers, 1998 ). Path analyses based on the actor-partner interdependence model (APIM) revealed that caregiving proximity mediated the association between low attachment avoidance and partners' sexual satisfaction in distressed and nondistressed couples. Sensitivity mediated this association in nondistressed couples only. Control mediated the association between men's insecurities (attachment-related avoidance and anxiety) and their partners' low sexual satisfaction in nondistressed couples. Attachment anxiety predicted compulsive caregiving, but this caregiving dimension was not a significant mediator. These results are discussed in light of attachment theory and their implications for treating distressed couples.

Identification of a Gal/GalNAc Lectin in the Protozoan Hartmannella vermiformis as a Potential Receptor for Attachment and Invasion by the Legionnaires' Disease Bacterium

PubMed Central

Venkataraman, Chandrasekar; Haack, Bradley J.; Bondada, Subbarao; Kwaik, Yousef Abu

1997-01-01

The Legionnaire's disease bacterium, Legionella pneumophila, is a facultative intracellular pathogen which invades and replicates within two evolutionarily distant hosts, free-living protozoa and mammalian cells. Invasion and intracellular replication within protozoa are thought to be major factors in the transmission of Legionnaire's disease. Although attachment and invasion of human macrophages by L. pneumophila is mediated in part by the complement receptors CR1 and CR3, the protozoan receptor involved in bacterial attachment and invasion has not been identified. To define the molecular events involved in invasion of protozoa by L. pneumophila, we examined the role of protein tyrosine phosphorylation of the protozoan host Hartmannella vermiformis upon attachment and invasion by L. pneumophila. Bacterial attachment and invasion were associated with a time-dependent tyrosine dephosphorylation of multiple host cell proteins. This host cell response was highly specific for live L. pneumophila, required contact with viable bacteria, and was completely reversible following washing off the bacteria from the host cell surface. Tyrosine dephosphorylation of host proteins was blocked by a tyrosine phosphatase inhibitor but not by tyrosine kinase inhibitors. One of the tyrosine dephosphorylated proteins was identified as the 170-kD galactose/N-acetylgalactosamine–inhibitable lectin (Gal/GalNAc) using immunoprecipitation and immunoblotting by antibodies generated against the Gal/GalNAc lectin of the protozoan Entamoeba histolytica. This Gal/GalNAc–inhibitable lectin has been shown previously to mediate adherence of E. histolytica to mammalian epithelial cells. Uptake of L. pneumophila by H. vermiformis was specifically inhibited by two monovalent sugars, Gal and GalNAc, and by mABs generated against the 170-kD lectin of E. histolytica. Interestingly, inhibition of invasion by Gal and GalNAc was associated with inhibition of bacterial-induced tyrosine dephosphorylation of H. vermiformis proteins. High stringency DNA hybridization confirmed the presence of the 170-kD lectin gene in H. vermiformis. We conclude that attachment of L. pneumophila to the H. vermiformis 170-kD lectin is required for invasion and is associated with tyrosine dephosphorylation of the Gal lectin and other host proteins. This is the first demonstration of a potential receptor used by L. pneumophila to invade protozoa. PMID:9254652

Adolescent-Parent Attachment and Externalizing Behavior: The Mediating Role of Individual and Social Factors.

PubMed

de Vries, Sanne L A; Hoeve, Machteld; Stams, Geert Jan J M; Asscher, Jessica J

2016-02-01

The aim of this study was to test whether the associations between adolescent-parent attachment and externalizing problem behavior of adolescents were mediated by adolescent cognitive distortions, self-esteem, parental monitoring and association with deviant peers. A total of 102 adolescents (71 % male; aged 12-19 years) at risk for developing delinquent behaviors reported on attachment, parental monitoring, aggressive and delinquent behavior and peers. Mediation effects were tested by using structural equation modeling. Different pathways were found depending on the type of externalizing behavior. The association between attachment and direct and indirect aggressive behavior was mediated by cognitive distortions. The relation between attachment and delinquency was mediated by deviant peers and parental monitoring. We argue that clinical practice should focus on the attachment relationship between adolescent and parents in order to positively affect risk and protective factors for adolescents' aggressive and delinquent behavior.

Preconditioning with Cations Increases the Attachment of Anoxybacillus flavithermus and Geobacillus Species to Stainless Steel

PubMed Central

Flint, Steve; Palmer, Jon; Brooks, John; Lindsay, Denise

2013-01-01

Preconditioning of Anoxybacillus flavithermus E16 and Geobacillus sp. strain F75 with cations prior to attachment often significantly increased (P ≤ 0.05) the number of viable cells that attached to stainless steel (by up to 1.5 log CFU/cm2) compared with unconditioned bacteria. It is proposed that the transition of A. flavithermus and Geobacillus spp. from milk formulations to stainless steel product contact surfaces in milk powder manufacturing plants is mediated predominantly by bacterial physiological factors (e.g., surface-exposed adhesins) rather than the concentrations of cations in milk formulations surrounding bacteria. PMID:23645192

Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling

PubMed Central

Baljinnyam, Erdene; Umemura, Masanari; Chuang, Christine; De Lorenzo, Mariana S; Iwatsubo, Mizuka; Chen, Suzie; Goydos, James S; Ishikawa, Yoshihiro; Whitelock, John M; Iwatsubo, Kousaku

2014-01-01

Fibroblast growth factor (FGF2) regulates endothelial and melanoma cell migration. The binding of FGF2 to its receptor requires N-sulfated heparan sulfate (HS) glycosamine. We have previously reported that Epac1, an exchange protein activated by cAMP, increases N-sulfation of HS in melanoma. Therefore, we examined whether Epac1 regulates FGF2-mediated cell–cell communication. Conditioned medium (CM) of melanoma cells with abundant expression of Epac1 increased migration of human umbilical endothelial cells (HUVEC) and melanoma cells with poor expression of Epac1. CM-induced increase in migration was inhibited by antagonizing FGF2, by the removal of HS and by the knockdown of Epac1. In addition, knockdown of Epac1 suppressed the binding of FGF2 to FGF receptor in HUVEC, and in vivo angiogenesis in melanoma. Furthermore, knockdown of Epac1 reduced N-sulfation of HS chains attached to perlecan, a major secreted type of HS proteoglycan that mediates the binding of FGF2 to FGF receptor. These data suggested that Epac1 in melanoma cells regulates melanoma progression via the HS–FGF2-mediated cell–cell communication. PMID:24725364

Lactoferrin and lactoferrin chimera inhibit damage caused by enteropathogenic Escherichia coli in HEp-2 cells.

PubMed

Flores-Villaseñor, Héctor; Canizalez-Román, Adrian; de la Garza, Mireya; Nazmi, Kamran; Bolscher, Jan G M; Leon-Sicairos, Nidia

2012-09-01

Enteropathogenic Escherichia coli (EPEC) is an important cause of infant diarrhea in developing countries. It produces a characteristic intestinal histopathological lesion on enterocytes known as 'attaching and effacing' (A/E), and these two steps are mediated by a type-III secretory system. In the present study, we evaluated the effect on the initial host cell attachment step produced by bovine lactoferrin (bLF) and three synthetic peptides: lactoferricin (LFcin), lactoferrampin (LFampin) and LFchimera. A special focus was given to the hemolytic activity and EPEC-induced actin polymerization in HEp-2 cells, as well as to the espA gene expression, which produces the protein responsible for primary contact with the host cells. Results show that EPEC attachment to HEp-2 cells was significantly suppressed by bLF and LFchimera at 125 and 40 μM, respectively. EPEC-mediated actin polymerization was blocked by bLF and LFchimera at 88 and 99%, respectively. LFchimera inhibited the attachment and A/E lesion caused by EPEC in a dose-dependent manner. In the presence of 125 μM bLF, the expression level of the espA gene was decreased by 50% compared to the untreated control. LFchimera at concentrations of 20 μM and 40 μM diminished the level of espA gene expression 100 and 1000 fold, respectively (P < 0.001). Although bLF, LFchimera, LFcin, and LFampin all significantly blocked the hemolysis produced by EPEC (P < 0.001), the two former compounds produced this effect at lower concentrations. These two compounds, bLF and LFchimera, were able to inhibit the first steps of the mechanism of the damage used by EPEC. This data suggests that LFchimera could provide protection against enteropathogens that share this mechanism. Crown Copyright © 2012. Published by Elsevier Masson SAS. All rights reserved.

Attachment, Perceived Conflict, and Couple Satisfaction: Test of a Mediational Dyadic Model

ERIC Educational Resources Information Center

Brassard, Audrey; Lussier, Yvan; Shaver, Phillip R.

2009-01-01

Attachment insecurities (anxiety and avoidance) are often associated with relationship dissatisfaction, but the mediators have been unclear. We examined the mediating role of perceived conflict in 274 French-Canadian couples who completed measures of attachment insecurities, perception of conflict, and relationship satisfaction. Partners' own…

The role of membrane microdomains in transmembrane signaling through the epithelial glycoprotein Gp140/CDCP1

PubMed Central

Alvares, Stacy M.; Dunn, Clarence A.; Brown, Tod A.; Wayner, Elizabeth E.; Carter, William G.

2008-01-01

Cell adhesion to the extracellular matrix (ECM) via integrin adhesion receptors initiates signaling cascades leading to changes in cell behavior. While integrin clustering is necessary to initiate cell attachment to the matrix, additional membrane components are necessary to mediate the transmembrane signals and the cell adhesion response that alter downstream cell behavior. Many of these signaling components reside in glycosphingolipid-rich and cholesterol-rich membrane domains such as Tetraspanin Enriched Microdomains (TEMs)/Glycosynapse 3 and Detergent-Resistant Microdomains (DRMs), also known as lipid rafts. In the following article, we will review examples of how components in these membrane microdomains modulate integrin adhesion after initial attachment to the ECM. Additionally, we will present data on a novel adhesion-responsive transmembrane glycoprotein Gp140/CUB Domain Containing Protein 1, which clusters in epithelial cell-cell contacts. Gp140 can then be phosphorylated by Src Family Kinases at tyrosine 734 in response to outside-in signals- possibly through interactions involving the extracellular CUB domains. Data presented here suggests that outside-in signals through Gp140 in cell-cell contacts assemble membrane clusters that associate with membrane microdomains to recruit and activate SFKs. Active SFKs then mediate phosphorylation of Gp140, SFK and PKCδ with Gp140 acting as a transmembrane scaffold for these kinases. We propose that the clustering of Gp140 and signaling components in membrane microdomains in cell-cell contacts contributes to changes in cell behavior. PMID:18269919

Influence of employees' attachment styles on their life satisfaction as mediated by job satisfaction and burnout.

PubMed

Reizer, Abira

2015-01-01

The aim of this study was to obtain better insight into the associations between attachment styles and employees' life satisfaction. This was achieved by examining the mediating roles of burnout and job satisfaction. Three hundred and thirty-nine employees, from a convenience community sample, participated in the current study. Results of the mediation model indicated that the associations between avoidance and life satisfaction were mediated by burnout and job satisfaction. However, the associations between attachment anxiety and life satisfaction were mediated by burnout but not by job satisfaction. Theoretical and practical implications for organizations and for attachment theory at work are discussed.

Attachment and social cognition in borderline personality disorder: Specificity in relation to antisocial and avoidant personality disorders.

PubMed

Beeney, Joseph E; Stepp, Stephanie D; Hallquist, Michael N; Scott, Lori N; Wright, Aidan G C; Ellison, William D; Nolf, Kimberly A; Pilkonis, Paul A

2015-07-01

Theory and research point to the role of attachment difficulties in borderline personality disorder (BPD). Attachment insecurity is believed to lead to chronic problems in social relationships, attributable, in part, to impairments in social cognition, which comprise maladaptive mental representations of self, others, and self in relation to others. However, few studies have attempted to identify social-cognitive mechanisms that link attachment insecurity to BPD and to assess whether such mechanisms are specific to the disorder. For the present study, empirically derived indices of mentalization, self-other boundaries, and identity diffusion were tested as mediators between attachment style and personality disorder symptoms. In a cross-sectional structural equation model, mentalization and self-other boundaries mediated the relationship between attachment anxiety and BPD. Mentalization partially mediated the relationship between attachment anxiety and antisocial personality disorder (PD) symptoms, and self-other boundaries mediated the relationship between attachment anxiety. (c) 2015 APA, all rights reserved).

The mediating role of perceived peer support in the relation between quality of attachment and internalizing problems in adolescence: a longitudinal perspective.

PubMed

Pace, Ugo; Zappulla, Carla; Di Maggio, Rosanna

2016-10-01

The study was aimed to verify, from a longitudinal perspective, whether perceived peer support would mediate the relationship between attachment and internalizing problems. Longitudinal participants included 482 adolescents (245 boys) aged 14-15 years in Wave 1 and 17-18 years in Wave 2. Participants in Wave 1 completed the Relationship Questionnaire, and those in Wave 2 completed the Social Support Questionnaire and the Youth Self-Report. Results showed that secure attachment positively predicted high levels of perceived peer support and negatively predicted internalizing problems, whereas fearful and preoccupied attachment negatively predicted perceived peer support and positively predicted internalizing problems. The mediation models showed that perceived peer support partially mediated the relationship between secure attachment and internalizing problems as well as between preoccupied attachment and internalizing problems and between fearful attachment and internalizing problems. Our results confirm the role of subjective perception of peer support in contributing to the prediction of internalizing problems beyond attachment styles.

Viral Capsid DNA Aptamer Conjugates as Multivalent Cell Targeting Vehicles

PubMed Central

Tong, Gary J.; Hsiao, Sonny C.; Carrico, Zachary M.; Francis, Matthew B.

2009-01-01

Nucleic acid aptamers offer significant potential as convenient and evolvable targeting groups for drug delivery. To attach them to the surface of a genome-free viral capsid carrier, an efficient oxidative coupling strategy has been developed. The method involves the periodate-mediated reaction of phenylene diamine substituted oligonucleotides with aniline groups installed on the outer surface of the capsid shells. Up to 60 DNA strands can be attached to each viral capsid with no apparent loss of base-pairing capabilities or protein stability. The ability of the capsids to bind specific cellular targets was demonstrated through the attachment of a 41-nucleotide sequence that targets a tyrosine kinase receptor on Jurkat T cells. After the installation of a fluorescent dye on the capsid interior, capsids bearing the cell-targeting sequence showed significant levels of binding to the cells relative to control samples. Colocalization experiments using confocal microscopy indicated that the capsids were endocytosed and trafficked to lysosomes for degradation. These observations suggest that aptamer-labeled capsids could be used for the targeted drug delivery of acid-labile prodrugs that would be preferentially released upon lysosomal acidification. PMID:19603808

β1 Integrin is an Adhesion Protein for Sperm Binding to Eggs

PubMed Central

Baessler, Keith A.; Lee, Younjoo; Sampson, Nicole S.

2009-01-01

We investigated the role of β1 integrin in mammalian fertilization and the mode of inhibition of fertilinβ-derived polymers. We determined that polymers displaying the Glu-Cys-Asp peptide from the fertilinβ disintegrin domain mediate inhibition of mammalian fertilization through a β1 integrin receptor on the egg surface. Inhibition of fertilization is a consequence of competition with sperm binding to the cell surface, not activation of an egg-signaling pathway. The presence of the β1 integrin on the egg surface increases the rate of sperm attachment, but does not alter the total number of sperm that can attach or fuse to the egg. We conclude that the presence of β1 integrin enhances the initial adhesion of sperm to the egg plasma membrane and that subsequent attachment and fusion are mediated by additional egg and sperm proteins present in the β1 integrin complex. Therefore, the mechanisms by which sperm fertilize wild-type and β1 knockout eggs are different. PMID:19338281

Antigenic properties of the human immunodeficiency virus envelope glycoprotein gp120 on virions bound to target cells.

PubMed

Mengistu, Meron; Ray, Krishanu; Lewis, George K; DeVico, Anthony L

2015-03-01

The HIV-1 envelope glycoprotein, gp120, undergoes multiple molecular interactions and structural rearrangements during the course of host cell attachment and viral entry, which are being increasingly defined at the atomic level using isolated proteins. In comparison, antigenic markers of these dynamic changes are essentially unknown for single HIV-1 particles bound to target cells. Such markers should indicate how neutralizing and/or non-neutralizing antibodies might interdict infection by either blocking infection or sensitizing host cells for elimination by Fc-mediated effector function. Here we address this deficit by imaging fluorescently labeled CCR5-tropic HIV-1 pseudoviruses using confocal and superresolution microscopy to track the exposure of neutralizing and non-neutralizing epitopes as they appear on single HIV-1 particles bound to target cells. Epitope exposure was followed under conditions permissive or non-permissive for viral entry to delimit changes associated with virion binding from those associated with post-attachment events. We find that a previously unexpected array of gp120 epitopes is exposed rapidly upon target cell binding. This array comprises both neutralizing and non-neutralizing epitopes, the latter being hidden on free virions yet capable of serving as potent targets for Fc-mediated effector function. Under non-permissive conditions for viral entry, both neutralizing and non-neutralizing epitope exposures were relatively static over time for the majority of bound virions. Under entry-permissive conditions, epitope exposure patterns changed over time on subsets of virions that exhibited concurrent variations in virion contents. These studies reveal that bound virions are distinguished by a broad array of both neutralizing and non-neutralizing gp120 epitopes that potentially sensitize a freshly engaged target cell for destruction by Fc-mediated effector function and/or for direct neutralization at a post-binding step. The elucidation of these epitope exposure patterns during viral entry will help clarify antibody-mediated inhibition of HIV-1 as it is measured in vitro and in vivo.

Surface Proteins of Gram-Positive Pathogens: Using Crystallography to Uncover Novel Features in Drug and Vaccine Candidates

NASA Astrophysics Data System (ADS)

Baker, Edward N.; Proft, Thomas; Kang, Haejoo

Proteins displayed on the cell surfaces of pathogenic organisms are the front-line troops of bacterial attack, playing critical roles in colonization, infection and virulence. Although such proteins can often be recognized from genome sequence data, through characteristic sequence motifs, their functions are often unknown. One such group of surface proteins is attached to the cell surface of Gram-positive pathogens through the action of sortase enzymes. Some of these proteins are now known to form pili: long filamentous structures that mediate attachment to human cells. Crystallographic analyses of these and other cell surface proteins have uncovered novel features in their structure, assembly and stability, including the presence of inter- and intramolecular isopeptide crosslinks. This improved understanding of structures on the bacterial cell surface offers opportunities for the development of some new drug targets and for novel approaches to vaccine design.

The use of plasma-activated covalent attachment of early domains of tropoelastin to enhance vascular compatibility of surfaces

PubMed Central

Hiob, Matti A.; Wise, Steven G.; Kondyurin, Alexey; Waterhouse, Anna; Bilek, Marcela M.; Ng, Martin K. C.; Weiss, Anthony S.

2013-01-01

All current metallic vascular prostheses, including stents, exhibit suboptimal biocompatibility. Improving the re-endothelialization and reducing the thrombogenicity of these devices would substantially improve their clinical efficacy. Tropoelastin (TE), the soluble precursor of elastin, mediates favorable endothelial cell interactions while having low thrombogenicity. Here we show that constructs of TE corresponding to the first 10 (“N10”) and first 18 (“N18”) N-terminal domains of the molecule facilitate endothelial cell attachment and proliferation equivalent to the performance of full-length TE. This N-terminal ability contrasts with the known role of the C-terminus of TE in facilitating cell attachment, particularly of fibroblasts. When immobilized on a plasma-activated coating (“PAC”), N10 and N18 retained their bioactivity and endothelial cell interactive properties, demonstrating attachment and proliferation equivalent to full-length TE. In whole blood assays, both N10 and N18 maintained the low thrombogenicity of PAC. Furthermore, these N-terminal constructs displayed far greater resistance to protease degradation by blood serine proteases kallikrein and thrombin than did full-length TE. When immobilized onto a PAC surface, these shorter constructs form a modified metal interface to establish a platform technology for biologically compatible, implantable cardiovascular devices. PMID:23863453

Autobiographical Memory Phenomenology and Content Mediate Attachment Style and Psychological Distress

PubMed Central

Sutin, Angelina R.; Gillath, Omri

2009-01-01

In two studies, the present research tested the phenomenology and content of autobiographical memory as distinct mediators between attachment avoidance and anxiety and depressive symptoms. In Study 1, participants (N = 454) completed measures of attachment and depressive symptoms in one session, and retrieved and rated two self-defining memories of romantic relationships in a separate session. In Study 2, participants (N = 534) were primed with attachment security, attachment insecurity, or a control prime and then retrieved and rated a self-defining relationship memory. Memory phenomenology, specifically memory coherence and emotional intensity, mediated the association between attachment avoidance and depressive symptoms, whereas the negative affective content of the memory mediated the association between attachment anxiety and depressive symptoms. Priming attachment security led to retrieval of a more coherent relationship memory, whereas insecurity led to the retrieval of a more incoherent relationship memory. Discussion focuses on the construction and recollection of memories as underlying mechanisms of adult attachment and psychological distress, the importance of memory coherence, and the implications for counseling research and practice. PMID:20706555

Insecure attachment is associated with paranoia but not hallucinations in psychotic patients: the mediating role of negative self-esteem.

PubMed

Wickham, S; Sitko, K; Bentall, R P

2015-05-01

A growing body of research has investigated associations between insecure attachment styles and psychosis. However, despite good theoretical and epidemiological reasons for hypothesising that insecure attachment may be specifically implicated in paranoid delusions, few studies have considered the role it plays in specific symptoms. We examined the relationship between attachment style, paranoid beliefs and hallucinatory experiences in a sample of 176 people with a diagnosis of schizophrenia spectrum disorders and 113 healthy controls. We also investigated the possible role of negative self-esteem in mediating this association. Insecure attachment predicted paranoia but not hallucinations after co-morbidity between the symptoms was controlled for. Negative self-esteem partially mediated the association between attachment anxiety and clinical paranoia, and fully mediated the relationship between attachment avoidance and clinical paranoia. It may be fruitful to explore attachment representations in psychological treatments for paranoid patients. If future research confirms the importance of disrupted attachment as a risk factor for persecutory delusions, consideration might be given to how to protect vulnerable young people, for example those raised in children's homes.

On the Relation between Maternal State of Mind and Sensitivity in the Prediction of Infant Attachment Security

ERIC Educational Resources Information Center

Atkinson, Leslie; Goldberg, Susan; Raval, Vaishali; Pederson, David; Benoit, Diane; Moran, Greg; Poulton, Lori; Myhal, Natalie; Zwiers, Michael; Leung, Eman

2005-01-01

Attachment theorists assume that maternal mental representations influence responsivity, which influences infant attachment security. However, primary studies do not support this mediation model. The authors tested mediation using 2 mother-infant samples and found no evidence of mediation. Therefore, the authors explored sensitivity as a…

Control of Surface Chemistry, Substrate Stiffness, and Cell Function in a Novel Terpolymer Methacrylate Library

PubMed Central

Joy, Abraham; Cohen, Daniel M.; Luk, Arnold; Anim-Danso, Emmanuel; Chen, Christopher; Kohn, Joachim

2011-01-01

A focused library of methacrylate terpolymers was synthesized to explore the effects of varying surface chemistry and adhesive peptide ligands on cell function. The chemical diversity of methacrylate monomers enabled construction of a library of polymers in which one can systematically vary the chemical composition to achieve a wide range of contact angle, Young's modulus, and Tg values. Furthermore, the materials were designed to allow surface immobilization of bioactive peptides. We then examined the effects of these material compositions on protein adsorption and cell attachment, proliferation, and differentiation. We observed that chemical composition of the polymers was an important determinant for NIH 3T3 cell attachment and proliferation, as well as human mesenchymal stem cell differentiation, and correlated directly with the ability of the polymers to adsorb proteins that mediate cell adhesion. Importantly, functionalization of the methacrylate terpolymer library with an adhesive GRGDS peptide normalized cellular responses. RGD-functionalized polymers uniformly exhibited robust attachment, proliferation, and differentiation irrespective of the underlying substrate chemistry. These studies provide a library-based approach to rapidly explore the biological functionality of biomaterials with a wide range of compositions, and highlights the importance of cell and protein cell adhesion in predicting their performance. PMID:21226505

Dihydroartemisinin induces endothelial cell anoikis through the activation of the JNK signaling pathway

PubMed Central

Zhang, Jiao; Guo, Ling; Zhou, Xia; Dong, Fengyun; Li, Liqun; Cheng, Zuowang; Xu, Yinghua; Liang, Jiyong; Xie, Qi; Liu, Ju

2016-01-01

Angiogenesis is required for the growth and metastasis of solid tumors. The anti-malarial agent dihydroartemisinin (DHA) demonstrates potent anti-angiogenic activity, but the underlying molecular mechanisms are not yet fully understood. During the process of angiogenesis, endothelial cells migrating from existing capillaries may undergo programmed cell death after detaching from the extracellular matrix, a process that is defined as anchorage-dependent apoptosis or anoikis. In the present study, DHA-induced cell death was compared in human umbilical vein endothelial cells (HUVECs) cultured in suspension and attached to culture plates. In suspended HUVECs, the cell viability was decreased and apoptosis was increased with the treatment of 50 µM DHA for 5 h, while the same treatment did not affect the attached HUVECs. In addition, 50 µM DHA increased the phosphorylation of c-Jun N-terminal kinase (JNK) in suspended HUVECs, but not in attached HUVECs, for up to 5 h of treatment. The JNK inhibitor, SP600125, reversed DHA-induced cell death in suspended HUVECs, suggesting that the JNK pathway may mediate DHA-induced endothelial cell anoikis. The data from the present study indicates a novel mechanism for understanding the anti-angiogenic effects of DHA, which may be used as a component for chemotherapy. PMID:27602117

Adult attachment, hostile conflict, and relationship adjustment among couples facing multiple sclerosis.

PubMed

Crangle, Cassandra J; Hart, Tae L

2017-11-01

Couples facing multiple sclerosis (MS) report significantly elevated rates of relationship distress, yet the effects of attachment have never been examined in this population. We examined whether hostile conflict mediated the dyadic effects of attachment on relationship adjustment in couples facing MS and whether these associations were moderated by gender or role. We also explored whether dyadic adjustment mediated the relationship between attachment and hostile conflict. The study was cross-sectional and included 103 couples in which one partner had been diagnosed with MS. Participants completed the Experiences in Close Relationships-Revised, Dyadic Adjustment Scale, and Aversive Interactions Scale, as well as demographic variables. We used the actor-partner interdependence model for data analysis. There were significant actor and partner effects of greater anxious attachment and worse dyadic adjustment. Actor and partner effects of anxious attachment were significantly mediated by greater hostile conflict. Gender significantly moderated the effects between avoidant attachment and dyadic adjustment. The actor effect was significant for males and females; the partner effect was only significant for females. The actor effect for females but not males was significantly mediated by greater hostile conflict. Role was not a significant moderator. Exploratory analyses also showed that dyadic adjustment mediated the relationship between anxious and avoidant attachment and hostile conflict. Findings highlight the important effects of attachment on relationship adjustment in MS couples. Both hostile conflict and dyadic adjustment appear to be mechanisms through which insecure attachment has a detrimental effect. Statement of contribution What is already known on this subject? Despite higher-than-normal rates of marital distress and separation/divorce, the effects of attachment on relationship adjustment among couples facing multiple sclerosis have never been examined. Prior studies within healthy populations have supported within-person and cross-dyadic associations between attachment and relationship adjustment; however, they have failed to use dyadic analyses. Hostile conflict has been associated with both insecure attachment and relationship adjustment and therefore may be an important mediator to help understand these relationships. What does this study add? Women were more negatively affected by their partner's avoidant attachment then men. Hostile conflict mediated the effects of anxious attachment on dyadic adjustment for individuals and across dyads. Hostile conflict accounted for the individual effect of avoidant attachment on dyadic adjustment for women. © 2017 The British Psychological Society.

Interview Investigation of Insecure Attachment Styles as Mediators between Poor Childhood Care and Schizophrenia-Spectrum Phenomenology.

PubMed

Sheinbaum, Tamara; Bifulco, Antonia; Ballespí, Sergi; Mitjavila, Mercè; Kwapil, Thomas R; Barrantes-Vidal, Neus

2015-01-01

Insecure attachment styles have received theoretical attention and some initial empirical support as mediators between childhood adverse experiences and psychotic phenomena; however, further specificity needs investigating. The present interview study aimed to examine (i) whether two forms of poor childhood care, namely parental antipathy and role reversal, were associated with subclinical positive and negative symptoms and schizophrenia-spectrum personality disorder (PD) traits, and (ii) whether such associations were mediated by specific insecure attachment styles. A total of 214 nonclinical young adults were interviewed for subclinical symptoms (Comprehensive Assessment of At-Risk Mental States), schizophrenia-spectrum PDs (Structured Clinical Interview for DSM-IV Axis II Disorders), poor childhood care (Childhood Experience of Care and Abuse Interview), and attachment style (Attachment Style Interview). Participants also completed the Beck Depression Inventory-II and all the analyses were conducted partialling out the effects of depressive symptoms. Both parental antipathy and role reversal were associated with subclinical positive symptoms and with paranoid and schizotypal PD traits. Role reversal was also associated with subclinical negative symptoms. Angry-dismissive attachment mediated associations between antipathy and subclinical positive symptoms and both angry-dismissive and enmeshed attachment mediated associations of antipathy with paranoid and schizotypal PD traits. Enmeshed attachment mediated associations of role reversal with paranoid and schizotypal PD traits. Attachment theory can inform lifespan models of how adverse developmental environments may increase the risk for psychosis. Insecure attachment provides a promising mechanism for understanding the development of schizophrenia-spectrum phenomenology and may offer a useful target for prophylactic intervention.

Attachment insecurities and women's sexual function and satisfaction: the mediating roles of sexual self-esteem, sexual anxiety, and sexual assertiveness.

PubMed

Brassard, Audrey; Dupuy, Emmanuelle; Bergeron, Sophie; Shaver, Phillip R

2015-01-01

We examined the potential role of three mediators--sexual self-esteem, sexual anxiety, and sexual assertiveness--of the association between romantic attachment insecurities (anxiety and avoidance) and two aspects of women's sexual functioning: sexual function and sexual satisfaction. A sample of 556 women aged 18 to 30 agreed to complete an online series of validated questionnaires assessing attachment insecurities and several aspects of sexual functioning. Lower sexual self-esteem and higher sexual anxiety mediated the associations between attachment anxiety and lower sexual function and satisfaction. Lower sexual self-esteem and higher sexual anxiety also partially mediated the links between attachment-related avoidance and the two sexual functioning variables. Sexual assertiveness, however, did not mediate these associations. A significant interaction between attachment anxiety and avoidance was also found to predict sexual satisfaction, with women high in avoidance and low in anxiety being the least satisfied. Results are discussed in terms of theoretical and clinical implications.

Interpersonal trauma, attachment insecurity and anxiety in an inpatient psychiatric population.

PubMed

Wiltgen, Anika; Arbona, Consuelo; Frankel, Leslie; Frueh, B Christopher

2015-10-01

Current research suggests that interpersonal trauma has an impact on insecure attachment and anxiety. Some research further suggests that attachment may play a mediating role between traumatic events and psychopathology. The purpose of this study was to examine the relationship between the experience of interpersonal trauma, attachment anxiety, attachment avoidance and clinical anxiety severity among adult psychiatric inpatients who reported having experienced interpersonal trauma after the age of 16. It was hypothesized that attachment anxiety and attachment avoidance would mediate the relationship between interpersonal trauma and clinical anxiety level. This study used archival data on 414 adult psychiatric inpatients in a large city in the Southwest U.S. Results suggest that interpersonal trauma was correlated to attachment avoidance but not to attachment anxiety and that attachment avoidance partially mediated the relation of interpersonal trauma to anxiety. The attachment framework appositely explains how a negative model of other contributes to the relation between experiences of interpersonal trauma and anxiety in adulthood. Copyright © 2015 Elsevier Ltd. All rights reserved.

Attachment and alcohol use amongst athletes: the mediating role of conscientiousness and alexithymia.

PubMed

Andres, Fanny; Castanier, Carole; Le Scanff, Christine

2014-02-01

The present study aims to explore the mediating effects of conscientiousness and alexithymia in the relationship between parental attachment style and alcohol use in a large sample of athletic young people. Participants included 434 French sport sciences students. Alcohol use, parental attachment style, conscientiousness and alexithymia were assessed. The hypotheses were tested by using regression and bootstrapping mediation analyses. Maternal insecure attachment style is positively associated with alcohol use. The current study highlights a multiple pathway in this relationship. The results reveal the mediating effect of low conscientiousness and alexithymia between maternal insecure attachment and alcohol use. Athletes' alcohol use seems to be the result of a complex association of underlying psychological factors. © 2013.

The Mediating Role of Rumination in the Relation between Quality of Attachment Relations and Depressive Symptoms in Non-Clinical Adolescents

ERIC Educational Resources Information Center

Ruijten, Tamara; Roelofs, Jeffrey; Rood, Lea

2011-01-01

This study examined associations between indices of the quality of attachment relationships of adolescents with parents and peers, rumination, and symptoms of depression. More specifically, a mediation model was investigated in which rumination was hypothesized to mediate the relation between quality of attachment relations and symptoms of…

The paths leading from attachment to ageism: a structural equation model approach.

PubMed

Bodner, Ehud; Cohen-Fridel, Sara

2014-01-01

The study introduces a model in which attachment patterns serve as predictors, empathy and fear of death as mediators, and ageism as the predicted variable. Data were collected from young adults (N = 440). Anxious attachment was directly and positively correlated with ageism, and also indirectly and positively by the mediator "fear of death." Avoidant attachment was indirectly and negatively correlated with ageism by the mediator "empathy". It is suggested that interventions for reducing ageist attitudes among younger adults would focus on existential fears, as well as on empathic ability, according to the attachment tendencies of these individuals.

Frazzled/DCC facilitates cardiac cell outgrowth and attachment during Drosophila dorsal vessel formation.

PubMed

Macabenta, Frank D; Jensen, Amber G; Cheng, Yi-Shan; Kramer, Joseph J; Kramer, Sunita G

2013-08-15

Drosophila embryonic dorsal vessel (DV) morphogenesis is a highly stereotyped process that involves the migration and morphogenesis of 52 pairs of cardioblasts (CBs) in order to form a linear tube. This process requires spatiotemporally-regulated localization of signaling and adhesive proteins in order to coordinate the formation of a central lumen while maintaining simultaneous adhesion between CBs. Previous studies have shown that the Slit/Roundabout and Netrin/Unc5 repulsive signaling pathways facilitate site-specific loss of adhesion between contralateral CBs in order to form a luminal space. However, the concomitant mechanism by which attraction initiates CB outgrowth and discrete localization of adhesive proteins remains poorly understood. Here we provide genetic evidence that Netrin signals through DCC (Deleted in Colorectal Carcinoma)/UNC-40/Frazzled (Fra) to mediate CB outgrowth and attachment and that this function occurs prior to and independently of Netrin/UNC-5 signaling. fra mRNA is expressed in the CBs prior to and during DV morphogenesis. Loss-of-fra-function results in significant defects in cell shape and alignment between contralateral CB rows. In addition, CB outgrowth and attachment is impaired in both fra loss- and gain-of-function mutants. Deletion of both Netrin genes (NetA and NetB) results in CB attachment phenotypes similar to fra mutants. Similar defects are also seen when both fra and unc5 are deleted. Finally we show that Fra accumulates at dorsal and ventral leading edges of paired CBs, and this localization is dependent upon Netrin. We propose that while repulsive guidance mechanisms contribute to lumen formation by preventing luminal domains from coming together, site-specific Netrin/Frazzled signaling mediates CB attachment. Copyright © 2013 Elsevier Inc. All rights reserved.

Explaining the relationship between attachment anxiety, eating behaviour and BMI.

PubMed

Wilkinson, Laura L; Rowe, Angela C; Robinson, Eric; Hardman, Charlotte A

2018-05-05

Previous research indicates that attachment anxiety (fear of abandonment) is predictive of overeating and higher body mass index (BMI). The current study explored the nature of the mechanisms underpinning this relationship. Study 1 assessed the relative contribution of 'emotional eating', 'susceptibility to hunger' and 'uncontrolled eating'. Study 2 assessed whether misperception of emotion and poor emotion management would mediate the relationship between attachment anxiety and stress-induced eating (and then BMI). Two cross-sectional online questionnaire studies were conducted (Study 1 N = 665, & Study 2 N = 548), in UK and US-based samples, which assessed attachment orientation and BMI alongside the potential mediators. The relative contribution of emotional eating, susceptibility to hunger and uncontrolled eating (Study 1) and difficulties in emotion regulation and stress-induced eating (Study 2) as mediators of this relationship were examined. In Study 1, parallel multiple mediation analysis (PROCESS) showed that emotional eating and susceptibility to hunger (but not uncontrolled eating) were significant mediators of the relationship between attachment anxiety and BMI. In Study 2, serial mediation analysis showed that difficulties in 'engaging with goal directed behaviours when upset' and stress-induced eating operated in series to significantly mediate the relationship between attachment anxiety and BMI. These findings suggest that attachment anxious individuals feel less capable in disengaging from negative emotions and go on to try to soothe themselves through eating which has a negative impact on their BMI. There was less support for an explanation of the relationship between attachment anxiety and BMI based around the misperception of emotion. Taken together, the findings highlight attachment anxiety and emotion regulation strategies as key targets for interventions that aim to reduce overeating and excess body weight. Copyright © 2018 Elsevier Ltd. All rights reserved.

Kon-tiki enhances PS2 integrin adhesion and localizes its ligand, Thrombospondin, in the myotendinous junction.

PubMed

Pérez-Moreno, Juan J; Espina-Zambrano, Agueda G; García-Calderón, Clara B; Estrada, Beatriz

2017-03-01

Cell-extracellular-matrix adhesion is mediated by cell receptors, mainly integrins and transmembrane proteoglycans, which can functionally interact. How these receptors are regulated and coordinated is largely unknown. We show that the conserved transmembrane Drosophila proteoglycan Kon-tiki (Kon, also known as Perdido) interacts with the αPS2βPS integrin (αPS2 is encoded by inflated and βPS by myospheroid ) to mediate muscle-tendon adhesion. kon and inflated double mutant embryos show a synergistic increase in muscle detachment. Furthermore, Kon modulates αPS2βPS signaling at the muscle attachment, since phosphorylated Fak is reduced in kon mutants. This reduction in integrin signaling can be rescued by the expression of a truncated Kon protein containing its transmembrane and extracellular domains, suggesting that these domains are sufficient to mediate this signaling. We show that these domains are sufficient to properly localize the αPS2βPS ligand, Thrombospondin, to the muscle attachment, and to partially rescue Kon-dependent muscle-tendon adhesion. We propose that Kon can engage in a protein complex with αPS2βPS and enhance integrin-mediated signaling and adhesion by recruiting its ligand, which would increase integrin-binding affinity to the extracellular matrix, resulting in the consolidation of the myotendinous junction. © 2017. Published by The Company of Biologists Ltd.

Positive and Negative Emotions and Coping as Mediators of Mother-Child Attachment and Peer Relationships

ERIC Educational Resources Information Center

Abraham, Michelle M.; Kerns, Kathryn A.

2013-01-01

This study examined whether emotions and coping explain (mediate) the association between mother-child attachment and peer relationships. Attachment, positive and negative emotion experience, coping, and peer relationships were examined in 106 fourth-grade through sixth-grade girls attending a 6-day residential camp. Attachment, experience of…

Coping style as a mediator between attachment and mental and physical health in patients suffering from morbid obesity.

PubMed

Aarts, Floor; Hinnen, Chris; Gerdes, Victor E A; Acherman, Yair; Brandjes, Dees P M

2014-01-01

The presence of mental health problems and limitations in physical functioning is high in patients suffering from morbid obesity. The purpose of the current study was to examine the mediating role of coping style in the relationship between attachment representations and mental health and physical functioning in a morbidly obese population. A total of 299 morbidly obese patients who were referred to the Slotervaart bariatric surgery unit in Amsterdam, the Netherlands, completed self-report questionnaires assessing adult attachment style (Experiences in Close Relationship-Revised Questionnaire), coping style (Utrecht Coping List), and patients physical functioning and mental health (Short Form-36). Attachment anxiety (beta = -.490, p < .001) and attachment avoidance (3 = -.387, p < .001) were both found to be related to mental health. In addition, attachment anxiety was also found to be related to physical functioning (beta = - .188,p < .001). Coping style partly mediated these associations. Findings suggest that coping mediates the association between attachment anxiety and attachment avoidance on the one hand and mental health and physical functioning in patients with morbid obesity on the other hand.

Parental Attachment and Adolescents' Perception of School Alienation: The Mediation Role of Self-Esteem and Adjustment.

PubMed

Kocayörük, Ercan; Şimşek, Ömer Faruk

2016-01-01

The present study examined the relationship between adolescents' attachment to parents and their feelings of alienation in the school context by considering the mediating role of adjustment and self-esteem. It was proposed that the degree of attachment to one's parents was associated with adjustment and self-esteem, which in turn predicted possible school alienation. A total of 227 students completed self-report measures on parental attachment, adjustment, self-esteem, and alienation from school. Results were consistent with the attachment theory and related literature that posits that (a) secure attachment to parents was associated with adjustment and self-esteem, (b) secure attachment to parents was negatively associated with feelings of school alienation, and (c) adjustment and self-esteem were a crucial mediators between attachment to parents and school alienation. In addition to enhanced adjustment, the self-esteem of adolescents may be an additional factor in reducing alienation at school. The results also supported the mediator role of self-esteem in the relationship between attachment to parents and adjustment. Finally, the relationship between self-esteem and school alienation were shown to be fully mediated by adjustment. The results were discussed in the context of responsibilities of teachers and school counselors, which may provide both students and parents with the skills to improve social functioning in the school context.

The mediating role of mentalizing capacity between parents and peer attachment and adolescent borderline personality disorder.

PubMed

Beck, Emma; Sharp, Carla; Poulsen, Stig; Bo, Sune; Pedersen, Jesper; Simonsen, Erik

2017-01-01

Insecure attachment is a precursor and correlate of borderline personality disorder. According to the mentalization-based theory of borderline personality disorder, the presence of insecure attachment derails the development of the capacity to mentalize, potentially resulting in borderline pathology. While one prior study found support for this notion in adolescents, it neglected a focus on peer attachment. Separation from primary caregivers and formation of stronger bonds to peers are key developmental achievements during adolescence and peer attachment warrants attention as a separate concept. In a cross-sectional study, female outpatients (M age 15.78=, SD = 1.04) who fulfilled DSM-5 criteria for BPD ( N  = 106) or met at least 4 BPD criteria ( N  = 4) completed self-reports on attachment to parents and peers, mentalizing capacity (reflective function) and borderline personality features. Our findings suggest that in a simple mediational model, mentalizing capacity mediated the relation between attachment to peers and borderline features. In the case of attachment to parents, the mediational model was not significant. The current study is the first to evaluate this mediational model with parent and peer attachment as separate concepts and the first to do so in a sample of adolescents who meet full or sub-threshold criteria for borderline personality disorder. Findings incrementally support that mentalizing capacity and attachment insecurity, also in relation to peers, are important concepts in theoretical approaches to the development of borderline personality disorder in adolescence. Clinical implications are discussed.

Suggestive evidence of a vesicle-mediated mode of cell degranulation in chromaffin cells. A high-resolution scanning electron microscopy investigation

PubMed Central

Crivellato, Enrico; Solinas, Paola; Isola, Raffaella; Ribatti, Domenico; Riva, Alessandro

2010-01-01

In this study we used a modified osmium maceration method for high-resolution scanning electron microscopy to study some ultrastructural details fitting the schema of piecemeal degranulation in chromaffin cells. Piecemeal degranulation refers to a particulate pattern of cell secretion that is accomplished by vesicle-mediated extracellular transport of granule-stored material. We investigated adrenal samples from control and angiotensin II-treated rats, and identified a variable proportion of smooth, 30–60-nm-diameter vesicles in the cytoplasm of chromaffin cells. A percentage of these vesicles were interspersed in the cytosol among chromaffin granules but the majority appeared to be attached to granules. Remarkably, the number of unattached cytoplasmic vesicles was greatly increased in chromaffin cells from angiotensin II-treated animals. Vesicles of the same structure and dimension were detected close to or attached to the cytoplasmic face of the plasma membrane; these, too, were increased in number in chromaffin cells from rats stimulated with angiotensin II. In specimens shaken with a rotating agitator during maceration, the cytoplasmic organelles could be partially removed and the fine structure of the vesicular interaction with the inner side of the plasma membrane emerged most clearly. A proportion of chromaffin granules showed protrusions that we interpreted as vesicular structures budding from the granular envelope. In some instances, the transection plane intersected granules with putative vesicles emerging from the surfaces. In these cases, the protrusions of budding vesicles could be observed from the internal side. This study provides high-resolution scanning electron microscopy images compatible with a vesicle-mediated degranulation mode of cell secretion in adrenal chromaffin cells. The data indicating an increase in the number of vesicles observed in chromaffin cells after stimulation with the chromaffin cell secretagogue angiotensin II suggests that this secretory process may be susceptible to fine regulation. PMID:20136671

Adult attachment as mediator between recollections of childhood and satisfaction with life.

PubMed

Hinnen, Chris; Sanderman, Robbert; Sprangers, Mirjam A G

2009-01-01

In accordance with attachment theory, the present study investigates whether internal working models of attachment mediated the association between childhood memories and satisfaction about life in adulthood. A convenient sample of 437 participants completed questionnaires assessing a broad range of childhood memories, working models of attachment and life satisfaction. After controlling for demographics, relational status and living condition, Baron and Kenny's mediation criteria were met for the association between memories about childhood, adult attachment and life satisfaction. That is, family warmth and harmony and parental support were associated with attachment security while parental rejection and adverse childhood events (e.g., abuse, parental psychopathology) were associated with an insecure attachment style. More securely attached individuals were in turn more satisfied about their current life than insecurely attached individuals. Sobel test confirmed these findings. These finding are in accordance with attachment theory and highlight the importance of this theory for understanding how early childhood experiences may impact adult life.

Secure attachment and eudaimonic well-being in late adulthood: The mediating role of self-compassion.

PubMed

Homan, Kristin J

2018-03-01

Attachment style refers to a systematic pattern of emotions, behaviors, and expectations that people have for how others will respond in relationships. Extensive evidence has documented the importance of attachment security in infants, children, adolescents, and adults, but the effects of attachment among exclusively older adult populations have received less attention. The present study explored the relationships between attachment style in late adulthood and eudaimonic well-being, which refers to a life replete with meaning, productive activity, and striving to reach one's potential. It also explored the mediating role of self-compassion, which can be described as a kind and forgiving attitude toward the self. A sample of 126 community-dwelling older adults (mean age = 70.40 years) completed measures tapping adult attachment, self-compassion, and six theoretically derived markers of eudaimonic well-being. Attachment anxiety and avoidance were inversely related to self-acceptance, personal growth, interpersonal relationship quality, purpose in life, and environmental mastery. Mediation analyses showed that self-compassion mediated each of these relationships. Results support the importance of attachment orientation for psychological well-being in late life and indicate that secure attachment facilitates an attitude of kindness and acceptance toward the self.

Type XVII collagen (BP180) can function as a cell-matrix adhesion molecule via binding to laminin 332

PubMed Central

Van den Bergh, F.; Eliason, S.L.; Giudice, G.J.

2010-01-01

Collagen XVII (COL17) is a transmembrane glycoprotein that is expressed on the basal surface of basal epidermal keratinocytes. Previous observations have led to the hypothesis that an interaction between COL17 and laminin 332, an extracellular matrix protein, contributes to the attachment of the basal keratinocyte to the basement membrane. In order to isolate and manipulate COL17 interactions with ECM components, we induced COL17 expression in two cells lines, SK-MEL1 and K562, that exhibit little or no capacity to attach to our test substrates, including laminin 332, types I and IV collagen, and fibronectin. Cells expressing high levels of COL17 preferentially adhered to a laminin 332 matrix, and, to a lesser extent, type IV collagen, while showing little or no binding to type I collagen or fibronectin. A quantitative analysis of cell adhesive forces revealed that, compared with COL17-negative cells, COL17-positive cells required over 7-fold greater force to achieve 50% detachment from a laminin 332 substrate. When a cell preparation (either K562 or SK-MEL1) with heterogeneous COL17 expression levels was allowed to attach to a laminin 332 matrix, the COL17-positive and COL17-negative cells differentially sorted to the bound and unbound cell fractions, respectively. COL17-dependent attachment to laminin 332 could be reduced or abolished by siRNA-mediated knockdown of COL17 expression or by adding to the assay wells specific antibodies against COL17 or laminin 332. These findings provide strong support for the hypothesis that cell surface COL17 can interact with laminin 332 and, together, participate in the adherence of a cell to the extracellular matrix. PMID:21034821

Psychological Dysregulation During Adolescence Mediates the Association of Parent-Child Attachment in Childhood and Substance Use Disorder in Adulthood1

PubMed Central

Zhai, Zu Wei; Kirisci, Levent; Tarter, Ralph E.; Ridenour, Ty A.

2015-01-01

Objective This prospective study tested the hypothesis that psychological dysregulation in mid-adolescence (age 16) mediates the association between parent-child attachment in late childhood (age 10-12) and development of substance use disorder (SUD) in adulthood (age 22). Method The Youth Attachment to Parents Scale (YAPS) was developed in 10-12 year old boys and girls (N = 694) at baseline residing in western Pennsylvania. Psychological dysregulation was measured by the neurobehavior disinhibition trait. Substance use was assessed at ages 10-12, 12-14, 16 and 19. SUD was diagnosed at age 22 using the Structured Clinical Interview for DSM Disorders. The mediation of parent-child attachment and SUD by neurobehavior disinhibition was tested separately for mothers and fathers while controlling for baseline substance use. Results Psychological dysregulation mediates the association between attachment to mothers and SUD, and partially mediates the association between attachment to fathers and SUD. Significant mediation effects remains after controlling for baseline substance use. Conclusion Optimal prevention of SUD should include ameliorating both psychological dysregulation predisposing to SUD and quality of the parent-child relationship. PMID:24359508

Attachment Styles and Suicide-Related Behaviors in Adolescence: The Mediating Role of Self-Criticism and Dependency

PubMed Central

Falgares, Giorgio; Marchetti, Daniela; De Santis, Sandro; Carrozzino, Danilo; Kopala-Sibley, Daniel C.; Fulcheri, Mario; Verrocchio, Maria Cristina

2017-01-01

Insecure attachment and the personality dimensions of self-criticism and dependency have been proposed as risk factors for suicide in adolescents. The present study examines whether self-criticism and dependency mediate the relationship between insecure attachment styles and suicidality. A sample of 340 high-school students (73.2% females), ranging in age from 13 to 20 years (M = 16.47, SD = 1.52), completed the Depressive Experiences Questionnaire for Adolescents, the Depressive Experiences Questionnaire for Adolescents, the Attachment Style Questionnaire, and the Suicidal Behaviors Questionnaire-Revised. The results partially support the expected mediation effects. Self-criticism, but not dependency, mediates the link between insecure attachment (anxiety and avoidance) and suicide-related behaviors. Implications for suicide risk assessment and management are discussed. PMID:28344562

Perceived Parenting Styles Fail to Mediate Between Anxiety and Attachment Styles in Adult Siblings of Individuals with Developmental Disabilities.

PubMed

O'Neill, Linda P; Murray, Lindsay E

2016-09-01

Adult siblings of individuals with developmental disabilities often experience higher levels of anxiety than individuals in the general population. The present study tested whether perceived parenting could mediate the relationship between attachment styles and anxiety in the sibling group compared to a control group. Little association was found between perceived parenting and attachment styles or anxiety for the siblings but there were robust and expected findings for the control. Adult attachment-related-anxiety was a significant unique predictor of anxiety in the sibling group but there was no mediational role for perceived parenting. Conversely, the majority of parenting styles significantly mediated the relationship between attachment and anxiety in the control. Implications for the atypical findings in the sibling group are discussed.

Fusion activation through attachment protein stalk domains indicates a conserved core mechanism of paramyxovirus entry into cells.

PubMed

Bose, Sayantan; Song, Albert S; Jardetzky, Theodore S; Lamb, Robert A

2014-04-01

Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA viruses causing important diseases in humans and animals. Two viral integral membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. However, the sequence of events that closely links the timing of receptor recognition by HN, H, or G and the "triggering" interaction of the attachment protein with F is unclear. F activation results in F undergoing a series of irreversible conformational rearrangements to bring about membrane merger and virus entry. By extensive study of properties of multiple paramyxovirus HN proteins, we show that key features of F activation, including the F-activating regions of HN proteins, flexibility within this F-activating region, and changes in globular head-stalk interactions are highly conserved. These results, together with functionally active "headless" mumps and Newcastle disease virus HN proteins, provide insights into the F-triggering process. Based on these data and very recently published data for morbillivirus H and henipavirus G proteins, we extend our recently proposed "stalk exposure model" to other paramyxoviruses and propose an "induced fit" hypothesis for F-HN/H/G interactions as conserved core mechanisms of paramyxovirus-mediated membrane fusion. Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA viruses causing important diseases in humans and animals. Two viral integral membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes. We describe here the molecular mechanism by which HN activates the F protein such that virus-cell fusion is controlled and occurs at the right time and the right place. We extend our recently proposed "stalk exposure model" first proposed for parainfluenza virus 5 to other paramyxoviruses and propose an "induced fit" hypothesis for F-HN/H/G interactions as conserved core mechanisms of paramyxovirus-mediated membrane fusion.

Fusion Activation through Attachment Protein Stalk Domains Indicates a Conserved Core Mechanism of Paramyxovirus Entry into Cells

PubMed Central

Bose, Sayantan; Song, Albert S.; Jardetzky, Theodore S.

2014-01-01

ABSTRACT Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA viruses causing important diseases in humans and animals. Two viral integral membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. However, the sequence of events that closely links the timing of receptor recognition by HN, H, or G and the “triggering” interaction of the attachment protein with F is unclear. F activation results in F undergoing a series of irreversible conformational rearrangements to bring about membrane merger and virus entry. By extensive study of properties of multiple paramyxovirus HN proteins, we show that key features of F activation, including the F-activating regions of HN proteins, flexibility within this F-activating region, and changes in globular head-stalk interactions are highly conserved. These results, together with functionally active “headless” mumps and Newcastle disease virus HN proteins, provide insights into the F-triggering process. Based on these data and very recently published data for morbillivirus H and henipavirus G proteins, we extend our recently proposed “stalk exposure model” to other paramyxoviruses and propose an “induced fit” hypothesis for F-HN/H/G interactions as conserved core mechanisms of paramyxovirus-mediated membrane fusion. IMPORTANCE Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA viruses causing important diseases in humans and animals. Two viral integral membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes. We describe here the molecular mechanism by which HN activates the F protein such that virus-cell fusion is controlled and occurs at the right time and the right place. We extend our recently proposed “stalk exposure model” first proposed for parainfluenza virus 5 to other paramyxoviruses and propose an “induced fit” hypothesis for F-HN/H/G interactions as conserved core mechanisms of paramyxovirus-mediated membrane fusion. PMID:24453369

TIM-1 Promotes Hepatitis C Virus Cell Attachment and Infection.

PubMed

Wang, Jing; Qiao, Luhua; Hou, Zhouhua; Luo, Guangxiang

2017-01-15

Human TIM and TAM family proteins were recently found to serve as phosphatidylserine (PS) receptors which promote infections by many different viruses, including dengue virus, West Nile virus, Ebola virus, Marburg virus, and Zika virus. In the present study, we provide substantial evidence demonstrating that TIM-1 is important for efficient infection by hepatitis C virus (HCV). The knockdown of TIM-1 expression significantly reduced HCV infection but not HCV RNA replication. Likewise, TIM-1 knockout in Huh-7.5 cells remarkably lowered HCV cell attachment and subsequent HCV infection. More significantly, the impairment of HCV infection in the TIM-1 knockout cells could be restored completely by ectopic expression of TIM-1 but not TIM-3 or TIM-4. Additionally, HCV infection and cell attachment were inhibited by PS but not by phosphatidylcholine (PC), demonstrating that TIM-1-mediated enhancement of HCV infection is PS dependent. The exposure of PS on the HCV envelope was confirmed by immunoprecipitation of HCV particles with a PS-specific monoclonal antibody. Collectively, these findings demonstrate that TIM-1 promotes HCV infection by serving as an attachment receptor for binding to PS exposed on the HCV envelope. TIM family proteins were recently found to enhance infections by many different viruses, including several members of the Flaviviridae family. However, their importance in HCV infection has not previously been examined experimentally. The TIM family proteins include three members in humans: TIM-1, TIM-3, and TIM-4. The findings derived from our studies demonstrate that TIM-1, but not TIM-3 or TIM-4, promotes HCV infection by functioning as an HCV attachment factor. Knockout of the TIM-1 gene resulted in a remarkable reduction of HCV cell attachment and infection. PS-containing liposomes blocked HCV cell attachment and subsequent HCV infection. HCV particles could also be precipitated with a PS-specific monoclonal antibody. These findings suggest that TIM-1 and its binding ligand, PS, may serve as novel targets for antiviral intervention. Copyright © 2017 American Society for Microbiology.

Xylella fastidiosa Afimbrial Adhesins Mediate Cell Transmission to Plants by Leafhopper Vectors▿

PubMed Central

Killiny, Nabil; Almeida, Rodrigo P. P.

2009-01-01

The interactions between the economically important plant-pathogenic bacterium Xylella fastidiosa and its leafhopper vectors are poorly characterized. We used different approaches to determine how X. fastidiosa cells interact with the cuticular surface of the foreguts of vectors. We demonstrate that X. fastidiosa binds to different polysaccharides with various affinities and that these interactions are mediated by cell surface carbohydrate-binding proteins. In addition, competition assays showed that N-acetylglucosamine inhibits bacterial adhesion to vector foregut extracts and intact wings, demonstrating that attachment to leafhopper surfaces is affected in the presence of specific polysaccharides. In vitro experiments with several X. fastidiosa knockout mutants indicated that hemagglutinin-like proteins are associated with cell adhesion to polysaccharides. These results were confirmed with biological experiments in which hemagglutinin-like protein mutants were transmitted to plants by vectors at lower rates than that of the wild type. Furthermore, although these mutants were defective in adhesion to the cuticle of vectors, their growth rate once attached to leafhoppers was similar to that of the wild type, suggesting that these proteins are important for initial adhesion of X. fastidiosa to leafhoppers. We propose that X. fastidiosa colonization of leafhopper vectors is a complex, stepwise process similar to the formation of biofilms on surfaces. PMID:19011051

Adolescent survivors of childhood sexual abuse: the mediating role of attachment style and coping in psychological and interpersonal functioning.

PubMed

Shapiro, D L; Levendosky, A A

1999-11-01

To examine attachment style and coping strategies as potential mediating variables between childhood sexual abuse (CSA) and psychological and interpersonal functioning in an attempt to explain variability in extent of disorder and level of functioning. Eighty adolescent females, aged 14-16 years, answered questions regarding abuse history, attachment style, coping with an interpersonal stressor, depression and trauma symptomatology, and conflict with a best friend. Structural equation modeling analyses indicated that attachment style mediates the effects of CSA and child abuse and neglect on coping and psychological distress. The indirect effects of CSA and other abuse through attachment accounted for most of the effects on coping and psychological distress. Avoidant and cognitive coping strategies also served as mediators in the models, accounting for most of the effects of the other variables on interpersonal conflict. The findings indicate that attachment style and coping strategies influence psychological and interpersonal functioning, mediating the direct effects of CSA and other types of child abuse and neglect. These results have implications for therapeutic intervention with children and adolescents who have experienced child abuse.

Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions.

PubMed

Wine, Eytan; Shen-Tu, Grace; Gareau, Mélanie G; Goldberg, Harvey A; Licht, Christoph; Ngan, Bo-Yee; Sorensen, Esben S; Greenaway, James; Sodek, Jaro; Zohar, Ron; Sherman, Philip M

2010-09-01

Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN(+/+) and OPN(-/-) fibroblasts were incubated with C. rodentium and attaching-effacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN(-/-) mice, and spleen enlargement by infection was absent in OPN(-/-) mice. Rectal administration of OPN to OPN(-/-) mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN(-/-) mice, compared with wild-type mice, which was accompanied by reduced attaching-effacing lesions, both in infected OPN(-/-) mice and OPN(-/-) mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN(-/-) cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses.

Idiosyncratic Mòjiāng virus attachment glycoprotein directs a host-cell entry pathway distinct from genetically related henipaviruses.

PubMed

Rissanen, Ilona; Ahmed, Asim A; Azarm, Kristopher; Beaty, Shannon; Hong, Patrick; Nambulli, Sham; Duprex, W Paul; Lee, Benhur; Bowden, Thomas A

2017-07-12

In 2012, cases of lethal pneumonia among Chinese miners prompted the isolation of a rat-borne henipavirus (HNV), Mòjiāng virus (MojV). Although MojV is genetically related to highly pathogenic bat-borne henipaviruses, the absence of a conserved ephrin receptor-binding motif in the MojV attachment glycoprotein (MojV-G) indicates a differing host-cell recognition mechanism. Here we find that MojV-G displays a six-bladed β-propeller fold bearing limited similarity to known paramyxoviral attachment glycoproteins, in particular at host receptor-binding surfaces. We confirm the inability of MojV-G to interact with known paramyxoviral receptors in vitro, indicating an independence from well-characterized ephrinB2/B3, sialic acid and CD150-mediated entry pathways. Furthermore, we find that MojV-G is antigenically distinct, indicating that MojV would less likely be detected in existing large-scale serological screening studies focused on well-established HNVs. Altogether, these data indicate a unique host-cell entry pathway for this emerging and potentially pathogenic HNV.

Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium

PubMed Central

Elzarrad, M Khair; Haroon, Abu; Willecke, Klaus; Dobrowolski, Radoslaw; Gillespie, Mark N; Al-Mehdi, Abu-Bakr

2008-01-01

Background The modulation of gap junctional communication between tumor cells and between tumor and vascular endothelial cells during tumorigenesis and metastasis is complex. The notion of a role for loss of gap junctional intercellular communication in tumorigenesis and metastasis has been controversial. While some of the stages of tumorigenesis and metastasis, such as uncontrolled cell division and cellular detachment, would necessitate the loss of intercellular junctions, other stages, such as intravasation, endothelial attachment, and vascularization, likely require increased cell-cell contact. We hypothesized that, in this multi-stage scheme, connexin-43 is centrally involved as a cell adhesion molecule mediating metastatic tumor attachment to the pulmonary endothelium. Methods Tumor cell attachment to pulmonary vasculature, tumor growth, and connexin-43 expression was studied in metastatic lung tumor sections obtained after tail-vein injection into nude mice of syngeneic breast cancer cell lines, overexpressing wild type connexin-43 or dominant-negatively mutated connexin-43 proteins. High-resolution immunofluorescence microscopy and Western blot analysis was performed using a connexin-43 monoclonal antibody. Calcein Orange Red AM dye transfer by fluorescence imaging was used to evaluate the gap junction function. Results Adhesion of breast cancer cells to the pulmonary endothelium increased with cancer cells overexpressing connexin-43 and markedly decreased with cells expressing dominant-negative connexin-43. Upregulation of connexin-43 was observed in tumor cell-endothelial cell contact areas in vitro and in vivo, and in areas of intratumor blood vessels and in micrometastatic foci. Conclusion Connexin-43 facilitates metastatic 'homing' by increasing adhesion of cancer cells to the lung endothelial cells. The marked upregulation of connexin-43 in tumor cell-endothelial cell contact areas, whether in preexisting 'homing' vessels or in newly formed tumor vessels, suggests that connexin-43 can serve as a potential marker of micrometastases and tumor vasculature and that it may play a role in the early incorporation of endothelial cells into small tumors as seeds for vasculogenesis. PMID:18647409

Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium.

PubMed

Elzarrad, M Khair; Haroon, Abu; Willecke, Klaus; Dobrowolski, Radoslaw; Gillespie, Mark N; Al-Mehdi, Abu-Bakr

2008-07-22

The modulation of gap junctional communication between tumor cells and between tumor and vascular endothelial cells during tumorigenesis and metastasis is complex. The notion of a role for loss of gap junctional intercellular communication in tumorigenesis and metastasis has been controversial. While some of the stages of tumorigenesis and metastasis, such as uncontrolled cell division and cellular detachment, would necessitate the loss of intercellular junctions, other stages, such as intravasation, endothelial attachment, and vascularization, likely require increased cell-cell contact. We hypothesized that, in this multi-stage scheme, connexin-43 is centrally involved as a cell adhesion molecule mediating metastatic tumor attachment to the pulmonary endothelium. Tumor cell attachment to pulmonary vasculature, tumor growth, and connexin-43 expression was studied in metastatic lung tumor sections obtained after tail-vein injection into nude mice of syngeneic breast cancer cell lines, overexpressing wild type connexin-43 or dominant-negatively mutated connexin-43 proteins. High-resolution immunofluorescence microscopy and Western blot analysis was performed using a connexin-43 monoclonal antibody. Calcein Orange Red AM dye transfer by fluorescence imaging was used to evaluate the gap junction function. Adhesion of breast cancer cells to the pulmonary endothelium increased with cancer cells overexpressing connexin-43 and markedly decreased with cells expressing dominant-negative connexin-43. Upregulation of connexin-43 was observed in tumor cell-endothelial cell contact areas in vitro and in vivo, and in areas of intratumor blood vessels and in micrometastatic foci. Connexin-43 facilitates metastatic 'homing' by increasing adhesion of cancer cells to the lung endothelial cells. The marked upregulation of connexin-43 in tumor cell-endothelial cell contact areas, whether in preexisting 'homing' vessels or in newly formed tumor vessels, suggests that connexin-43 can serve as a potential marker of micrometastases and tumor vasculature and that it may play a role in the early incorporation of endothelial cells into small tumors as seeds for vasculogenesis.

Inhibitory effects of OK-432 (Picibanil) on cellular proliferation and adhesive capacity of breast carcinoma cells.

PubMed

Horii, Yoshio; Iino, Yuichi; Maemura, Michio; Horiguchi, Jun; Morishita, Yasuo

2005-02-01

We investigated the potent inhibitory effects of OK-432 (Picibanil) on both cellular adhesion and cell proliferation of estrogen-dependent (MCF-7) or estrogen-independent (MDA-MB-231) breast carcinoma cells. Cellular proliferation of both MCF-7 and MDA-MB-231 cells was markedly inhibited in a dose-dependent manner, when the carcinoma cells were exposed to OK-432. Cell attachment assay demonstrated that incubation with OK-432 for 24 h reduced integrin-mediated cellular adhesion of both cell types. However, fluorescence activated cell sorter (FACS) analysis revealed that incubation with OK-432 for 24 h did not decrease the cell surface expressions of any integrins. These results suggest that the binding avidity of integrins is reduced by OK-432 without alteration of the integrin expression. We conclude that OK-432 inhibits integrin-mediated cellular adhesion as well as cell proliferation of breast carcinoma cells regardless of estrogen-dependence, and that these actions of OK-432 contribute to prevention or inhibition of breast carcinoma invasion and metastasis.

Cell-mediated remodeling of biomimetic encapsulating hydrogels triggered by adipogenic differentiation of adipose stem cells.

PubMed

Clevenger, Tracy N; Luna, Gabriel; Boctor, Daniel; Fisher, Steven K; Clegg, Dennis O

2016-01-01

One of the most common regenerative therapies is autologous fat grafting, which frequently suffers from unexpected volume loss. One approach is to deliver adipose stem cells encapsulated in the engineered hydrogels supportive of cell survival, differentiation, and integration after transplant. We describe an encapsulating, biomimetic poly(ethylene)-glycol hydrogel, with embedded peptides for attachment and biodegradation. Poly(ethylene)-glycol hydrogels containing an Arg-Gly-Asp attachment sequence and a matrix metalloprotease 3/10 cleavage site supported adipose stem cell survival and showed remodeling initiated by adipogenic differentiation. Arg-Gly-Asp-matrix metalloprotease 3/10 cleavage site hydrogels showed an increased number and area of lacunae or holes after adipose stem cell differentiation. Image analysis of adipose stem cells in Arg-Gly-Asp-matrix metalloprotease 3/10 cleavage site hydrogels showed larger Voronoi domains, while cell density remained unchanged. The differentiated adipocytes residing within these newly remodeled spaces express proteins and messenger RNAs indicative of adipocytic differentiation. These engineered scaffolds may provide niches for stem cell differentiation and could prove useful in soft tissue regeneration.

Cell-mediated remodeling of biomimetic encapsulating hydrogels triggered by adipogenic differentiation of adipose stem cells

PubMed Central

Clevenger, Tracy N; Luna, Gabriel; Boctor, Daniel; Fisher, Steven K; Clegg, Dennis O

2016-01-01

One of the most common regenerative therapies is autologous fat grafting, which frequently suffers from unexpected volume loss. One approach is to deliver adipose stem cells encapsulated in the engineered hydrogels supportive of cell survival, differentiation, and integration after transplant. We describe an encapsulating, biomimetic poly(ethylene)-glycol hydrogel, with embedded peptides for attachment and biodegradation. Poly(ethylene)-glycol hydrogels containing an Arg–Gly–Asp attachment sequence and a matrix metalloprotease 3/10 cleavage site supported adipose stem cell survival and showed remodeling initiated by adipogenic differentiation. Arg–Gly–Asp–matrix metalloprotease 3/10 cleavage site hydrogels showed an increased number and area of lacunae or holes after adipose stem cell differentiation. Image analysis of adipose stem cells in Arg–Gly–Asp–matrix metalloprotease 3/10 cleavage site hydrogels showed larger Voronoi domains, while cell density remained unchanged. The differentiated adipocytes residing within these newly remodeled spaces express proteins and messenger RNAs indicative of adipocytic differentiation. These engineered scaffolds may provide niches for stem cell differentiation and could prove useful in soft tissue regeneration. PMID:27733898

Associations between specific psychotic symptoms and specific childhood adversities are mediated by attachment styles: an analysis of the National Comorbidity Survey.

PubMed

Sitko, Katarzyna; Bentall, Richard P; Shevlin, Mark; O'Sullivan, Noreen; Sellwood, William

2014-07-30

Accumulated evidence over the past decade consistently demonstrates a relationship between childhood adversity and psychosis in adulthood. There is some evidence of specific associations between childhood sexual abuse and hallucinations, and between insecure attachment and paranoia. Data from the National Comorbidity Survey were used in assessing whether current attachment styles influenced the association between adverse childhood experiences and psychotic symptoms in adulthood. Hallucinations and paranoid beliefs were differentially associated with sexual abuse (rape and sexual molestation) and neglect, respectively. Sexual abuse and neglect were also associated with depression. The relationship between neglect and paranoid beliefs was fully mediated via anxious and avoidant attachment. The relationship between sexual molestation and hallucinations was independent of attachment style. The relationship between rape and hallucinations was partially mediated via anxious attachment; however this effect was no longer present when depression was included as a mediating variable. The findings highlight the importance of addressing and understanding childhood experiences within the context of current attachment styles in clinical interventions for patients with psychosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Mediating Role of Emotion Dysregulation in the Relations Between Childhood Trauma History and Adult Attachment and Borderline Personality Disorder Features: A Study of Italian Nonclinical Participants.

PubMed

Fossati, Andrea; Gratz, Kim L; Somma, Antonella; Maffei, Cesare; Borroni, Serena

2016-10-01

In order to evaluate if emotion dysregulation significantly mediates the relationships between childhood abuse and adult attachment and borderline personality disorder features, 354 community Italian adults were administered the Borderline Personality Inventory (Leichsenring, 1999a), the Difficulties in Emotion Regulation Scale (Gratz & Roemer, 2004), the Child Abuse and Trauma Scale (Sanders & Becker-Lausen, 1995), and the Attachment Style Questionnaire (Feeney, Noller, & Hanrahan, 1994). Hierarchical regression analyses showed that both childhood abuse and adult attachment were positively associated with emotion dysregulation and borderline personality features; however, only emotional abuse and the attachment dimension of need for approval were common predictors of both dependent variables. No significant interaction effects were detected in regression analyses. Mediation analyses provided support for partial mediation, revealing a significant mediating role of emotion dysregulation in the relationships between both emotional abuse and need for approval and borderline personality features in this community sample.

Biofuel Cells Select for Microbial Consortia That Self-Mediate Electron Transfer

PubMed Central

Rabaey, Korneel; Boon, Nico; Siciliano, Steven D.; Verhaege, Marc; Verstraete, Willy

2004-01-01

Microbial fuel cells hold great promise as a sustainable biotechnological solution to future energy needs. Current efforts to improve the efficiency of such fuel cells are limited by the lack of knowledge about the microbial ecology of these systems. The purposes of this study were (i) to elucidate whether a bacterial community, either suspended or attached to an electrode, can evolve in a microbial fuel cell to bring about higher power output, and (ii) to identify species responsible for the electricity generation. Enrichment by repeated transfer of a bacterial consortium harvested from the anode compartment of a biofuel cell in which glucose was used increased the output from an initial level of 0.6 W m−2 of electrode surface to a maximal level of 4.31 W m−2 (664 mV, 30.9 mA) when plain graphite electrodes were used. This result was obtained with an average loading rate of 1 g of glucose liter−1 day−1 and corresponded to 81% efficiency for electron transfer from glucose to electricity. Cyclic voltammetry indicated that the enhanced microbial consortium had either membrane-bound or excreted redox components that were not initially detected in the community. Dominant species of the enhanced culture were identified by denaturing gradient gel electrophoresis and culturing. The community consisted mainly of facultative anaerobic bacteria, such as Alcaligenes faecalis and Enterococcus gallinarum, which are capable of hydrogen production. Pseudomonas aeruginosa and other Pseudomonas species were also isolated. For several isolates, electrochemical activity was mainly due to excreted redox mediators, and one of these mediators, pyocyanin produced by P. aeruginosa, could be characterized. Overall, the enrichment procedure, irrespective of whether only attached or suspended bacteria were examined, selected for organisms capable of mediating the electron transfer either by direct bacterial transfer or by excretion of redox components. PMID:15345423

Targeted p120-catenin ablation disrupts dental enamel development.

PubMed

Bartlett, John D; Dobeck, Justine M; Tye, Coralee E; Perez-Moreno, Mirna; Stokes, Nicole; Reynolds, Albert B; Fuchs, Elaine; Skobe, Ziedonis

2010-09-16

Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E- and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows.

C-type lectins do not act as functional receptors for filovirus entry into cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsuno, Keita; Nakayama, Eri; Noyori, Osamu

2010-12-03

Research highlights: {yields} Filovirus glycoprotein (GP) having a deficient receptor binding region were generated. {yields} Mutant GPs mediated virus entry less efficiently than wild-type GP. {yields} Mutant GPs bound to C-type lectins but not mediated entire steps of cellular entry. {yields} C-type lectins do not independently mediate filovirus entry into cells. {yields} Other molecule(s) are required for C-type lectin-mediated entry of filoviruses. -- Abstract: Cellular C-type lectins have been reported to facilitate filovirus infection by binding to glycans on filovirus glycoprotein (GP). However, it is not clearly known whether interaction between C-type lectins and GP mediates all the steps ofmore » virus entry (i.e., attachment, internalization, and membrane fusion). In this study, we generated vesicular stomatitis viruses pseudotyped with mutant GPs that have impaired structures of the putative receptor binding regions and thus reduced ability to infect the monkey kidney cells that are routinely used for virus propagation. We found that infectivities of viruses with the mutant GPs dropped in C-type lectin-expressing cells, parallel with those in the monkey kidney cells, whereas binding activities of these GPs to the C-type lectins were not correlated with the reduced infectivities. These results suggest that C-type lectin-mediated entry of filoviruses requires other cellular molecule(s) that may be involved in virion internalization or membrane fusion.« less

Attachment, self-compassion, empathy, and subjective well-being among college students and community adults.

PubMed

Wei, Meifen; Liao, Kelly Yu-Hsin; Ku, Tsun-Yao; Shaffer, Phillip A

2011-02-01

Research on subjective well-being suggests that it is only partly a function of environmental circumstances. There may be a personality characteristic or a resilient disposition toward experiencing high levels of well-being even in unfavorable circumstances. Adult attachment may contribute to this resilient disposition. This study examined whether the association between attachment anxiety and subjective well-being was mediated by Neff's (2003a, 2003b) concept of self-compassion. It also examined empathy toward others as a mediator in the association between attachment avoidance and subjective well-being. In Study 1, 195 college students completed self-report surveys. In Study 2, 136 community adults provided a cross-validation of the results. As expected, across these 2 samples, findings suggested that self-compassion mediated the association between attachment anxiety and subjective well-being, and emotional empathy toward others mediated the association between attachment avoidance and subjective well-being. © 2011 The Authors. Journal of Personality © 2011, Wiley Periodicals, Inc.

Social Support, Attachment, and Chronic Stress as Correlates of Latina Mother and Daughter Drug Use Behaviors

PubMed Central

Niyonsenga, Theophile; Blackson, Timothy C.; De La Rosa, Mario; Rojas, Patria; Dillon, Frank; Ganapati, Emel N.

2017-01-01

This cross-sectional study examined three social determinants (sociodemographics, chronic stress, and social support) and the quality of attachment among a community-based sample of Latina mother–daughter dyads (N = 158 dyads) to document the relationship between those factors and their respective drug use. Hypotheses were: (a) the quality of mother–daughter attachment will mediate the relationship between their social support and drug use and (b) the effects of mothers’ and daughters’ chronic stress on their drug use is mediated by their social support which, in turn, is also mediated by the quality of their attachment after taking into account socio-demographic variables. Structural equation modeling was used with dyads as the units of analyses. Our preliminary results show: (a) transgenerational dyadic concordance among the variables, (b) mothers’ higher quality of attachment scores mediated the relationship between their chronic stress and social support scores on their lower drug use scores, and (c) daughters’ attachment scores mediated the relationship between their social support scores and their lower drug use scores. Limitations are discussed. Our preliminary results provide a useful first step towards understanding the processes linking stress, social support, and attachment with drug use behaviors among Latina mothers and daughters from a culturally relevant and transgenerational perspective. PMID:22332860

Parental attachment as a mediator between parental social support and self-esteem as perceived by Korean sports middle and high school athletes.

PubMed

Kang, Sangwook; Jeon, Hyunsoo; Kwon, Sungho; Park, Seungha

2015-02-01

This study examined whether parental attachment mediates the relationship between parental social support and self-esteem in Korean middle and high school athletes. 591 sports athletes attending middle and high schools that specialize in sport volunteered. Parental social support and parental attachment had a significant positive effect on self-esteem; parental attachment had a greater effect on self-esteem. In the structural relationship, direct effects of parental social support on self-esteem were weak, but indirect effects through parental attachment were strong. Therefore, parental attachment complementally mediated the relationship between parental social support and self-esteem. Metric invariance was supported for groups categorized by sex, region, and school level, confirming that the model could be applied to various groups.

Patient-provider relationship as mediator between adult attachment and self-management in primary care patients with multiple chronic conditions.

PubMed

Brenk-Franz, Katja; Strauß, Bernhard; Tiesler, Fabian; Fleischhauer, Christian; Schneider, Nico; Gensichen, Jochen

2017-06-01

The conceptual model of attachment theory has been applied to understand the predispositions of patients in medical care and the patient-provider relationship. In patients with chronic conditions insecure attachment was connected to poorer self-management. The patient-provider relationship is associated with a range of health related outcomes and self-management skills. We determined whether the quality of the patient-provider relationship mediates the link between adult attachment and self-management among primary care patients with multiple chronic diseases. 209 patients with a minimum of three chronic diseases (including type II diabetes, hypertension and at least one other chronic condition) between the ages of 50 and 85 from eight general practices were included in the APRICARE cohort study. Adult attachment was measured via self-report (ECR-RD), self-management skills by the FERUS and the patient-provider relationship by the PRA-D. The health status and chronicity were assessed by the GP. Multiple mediation analyses were used to examine whether aspects of the patient-provider relationship (communication, information, affectivity) are a mediators of associations between adult attachment and self-management. The analysis revealed that the quality of the patient-provider relationship mediated the effect of attachment on self-management in patients with multiple chronic conditions. Particularly the quality of communication and information over the course of treatment has a significant mediating influence. A personalized, attachment-related approach that promotes active patient-provider communication and gives information about the treatment to the patient may improve self-management skills in patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Developmental trajectories and longitudinal mediation effects of self-esteem, peer attachment, child maltreatment and depression on early adolescents.

PubMed

Ju, Soyoung; Lee, Yanghee

2018-02-01

The purpose of this study is to identify the developmental trajectories of peer attachment, self-esteem, depression, and child maltreatment, and to understand the longitudinal mediation effects that peer attachment and self-esteem have on the influence of perceived abuse on early adolescent depression. This study uses Year 1 to Year 5 data of the 4th grader panel of the Korea Youth Panel Survey (KYPS) and utilizes a multivariate latent growth model to analyze the main variables in the applicable data between 5th (i.e., Year 2) and 8th (i.e., Year 5) grades. The results indicate that from the 5th to the 8th grade, the degree of abuse and depression increases while self-esteem gradually decreases with slowly lowering peer attachment. A significant distribution of the initial values and the rate of change were present for all main variables of the study, confirming individual differences in time wise changes. Further, more exposure to abuse correlated with a decrease in self-esteem, while an increase in self-esteem greatly reduced depression. The initial value of self-esteem showed a partial mediation effect, whereas the rate of change indicated a full mediation effect with a significant longitudinal mediation effect. More experience of abuse during early adolescence indicated a lower degree of peer attachment, and a higher peer attachment was related to decreased depression. A significant partial mediation effect was present for both the initial value and the rate of change of peer attachment, and a longitudinal mediation effect was present. This study confirmed that self-esteem in early adolescents is an important protective factor that can greatly reduce the degree of depression, and suggests continuous interventions conducted to increase self-esteem in adolescence. Furthermore, by determining that peer attachment decreases the degree of depression in children at risk, the study emphasizes the healing aspect of adolescent peer attachment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Monocyte-mediated delivery of polymeric backpacks to inflamed tissues: a generalized strategy to deliver drugs to treat inflammation.

PubMed

Anselmo, Aaron C; Gilbert, Jonathan B; Kumar, Sunny; Gupta, Vivek; Cohen, Robert E; Rubner, Michael F; Mitragotri, Samir

2015-02-10

Targeted delivery of drugs and imaging agents to inflamed tissues, as in the cases of cancer, Alzheimer's disease, Parkinson's disease, and arthritis, represents one of the major challenges in drug delivery. Monocytes possess a unique ability to target and penetrate into sites of inflammation. Here, we describe a broad approach to take advantage of the natural ability of monocytes to target and deliver flat polymeric particles ("Cellular Backpacks") to inflamed tissues. Cellular backpacks attach strongly to the surface of monocytes but do not undergo phagocytosis due to backpack's size, disk-like shape and flexibility. Following attachment of backpacks, monocytes retain important cellular functions including transmigration through an endothelial monolayer and differentiation into macrophages. In two separate in vivo inflammation models, backpack-laden monocytes exhibit increased targeting to inflamed tissues. Cellular backpacks, and their abilities to attach to monocytes without impairing monocyte functions and 'hitchhike' to a variety of inflamed tissues, offer a new platform for both cell-mediated therapies and broad targeting of inflamed tissues. Copyright © 2014 Elsevier B.V. All rights reserved.

Biosurfactant mannosyl-erythritol lipid inhibits secretion of inflammatory mediators from RBL-2H3 cells.

PubMed

Morita, Yosuke; Tadokoro, Satoshi; Sasai, Masao; Kitamoto, Dai; Hirashima, Naohide

2011-12-01

Biosurfactant mannosyl-erythritol lipids (MELs) are glycolipids produced by microbes that have various biological activities. It has been reported that MELs exhibit excellent surface-activity and also various bioactivities, such as induction of cell differentiation and apoptosis. However, little is known about their action related to drug discovery or drug seeds. We investigated the effects of MELs on the secretion of inflammatory mediators from mast cells that play a central role in allergic responses. Mast cells secrete three kinds of inflammatory mediators and we quantified these secreted mediators by photometer or ELISA. The action mechanisms of MELs were studied by Ca(2+)-sensitive fluorescence dye and Western blotting of phosphorylated proteins. MELs inhibited exocytotic release by antigen stimulation in a dose-dependent manner. We also found that MELs inhibited antigen-induced secretion of leukotriene C(4) and cytokine TNF-α (tumor necrosis factor-α). The inhibitory action of MELs on mediator secretion was mediated by inhibition of Ca(2+) increase, phosphorylation of MAP kinases and SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) that serve as a molecular machinery for exocytotic membrane fusion. MELs have anti-inflammatory action inhibiting the secretion of inflammatory mediators from mast cells. MELs affects two of major intracellular signaling pathways including Ca(2+) increase and MAP kinases. MELs also inhibited the phosphorylation of SNARE proteins that is crucial for not only exocytosis but also intracellular vesicular trafficking. 2011 Elsevier B.V. All rights reserved.

Quality of life and adolescents' communication with their significant others (mother, father, and best friend): the mediating effect of attachment to pets.

PubMed

Marsa-Sambola, Ferran; Williams, Joanne; Muldoon, Janine; Lawrence, Alistair; Connor, Melanie; Currie, Candace

2017-06-01

The relationship between adolescents' communication with their significant others (mother, father, and best friend) and quality of life (KIDSCREEN) was investigated in 2262 Scottish adolescent pet owners. The variable attachment to pets was also tested and assessed as a mediator of this relationship. A positive relationship between adolescents' communication with their significant other (mother, father, and best friend) and quality of life decreased when controlling for attachment to dogs. In cat owners, a positive relationship between communication with a best friend and quality of life decreased when controlling for attachment to cats. In cat and dog owners, attachment to these pets predicted higher levels of quality of life. Higher attachment to dogs and cats was explained by good best friend (IV) and attachment to pets (DV) and best friends. Mediation effects of attachment to dogs and cats might be explained in terms of the caring activities associated with these types of pets.

Marital conflict and the quality of young children's peer play behavior: the mediating and moderating role of parent-child emotional reciprocity and attachment security.

PubMed

Lindsey, Eric W; Caldera, Yvonne M; Tankersley, Laura

2009-04-01

Parent-child attachment security and dyadic measures of parent-child positive and negative emotional reciprocity were examined as possible mediators and moderators of the connection between marital conflict and children's peer play behavior. Eighty parents were observed in a laboratory play session with their 15- to 18-month-old child. Subsequently, at 36 months children were observed interacting with peers at their child care setting. Connections between marital conflict and children's positive peer interaction were mediated by mother-child attachment security, mother-child positive emotional reciprocity, and father-child negative emotional reciprocity. Connections between marital conflict and children's negative peer interaction were mediated by mother-child positive emotional reciprocity and father-child attachment security. Parent-child attachment security and negative emotional reciprocity emerged as important moderators of the connection between marital conflict and children's peer play behavior.

Interrelationships of adult attachment orientations, health status and worrying among fibromyalgia patients.

PubMed

Oliveira, Paula; Costa, Maria Emilía

2009-11-01

This study examined associations between adult attachment dimensions, perceived health status and worrying (coping strategy with chronic pain), and explored whether worrying mediated observed relationships between attachment dimensions and health outcomes within a sample of 128 Portuguese female fibromyalgia patients. Physical health status was inversely correlated with dependence and worrying; mental health status was positively correlated with trust, and inversely related to attachment-related ambivalence, dependence and worrying. Finally, worrying mediated relationships between dependence and both physical and mental health status; moreover, worrying partially mediated the relationship between ambivalence and mental health status. Implications of the findings are discussed.

Adaptive and Maladaptive Perfectionism as Mediators of Adult Attachment Styles and Depression, Hopelessness, and Life Satisfaction

ERIC Educational Resources Information Center

Gnilka, Philip B.; Ashby, Jeffrey S.; Noble, Christina M.

2013-01-01

This study examined the relationships between adaptive and maladaptive perfectionism, anxious and avoidant adult attachment styles, depression, hopelessness, and life satisfaction among a sample of 180 undergraduate students. Maladaptive perfectionism mediated the relationship between both forms of adult attachment and depression, hopelessness,…

Dynamic protein coronas revealed as a modulator of silver nanoparticle sulphidation in vitro

NASA Astrophysics Data System (ADS)

Miclăuş, Teodora; Beer, Christiane; Chevallier, Jacques; Scavenius, Carsten; Bochenkov, Vladimir E.; Enghild, Jan J.; Sutherland, Duncan S.

2016-06-01

Proteins adsorbing at nanoparticles have been proposed as critical toxicity mediators and are included in ongoing efforts to develop predictive tools for safety assessment. Strongly attached proteins can be isolated, identified and correlated to changes in nanoparticle state, cellular association or toxicity. Weakly attached, rapidly exchanging proteins are also present at nanoparticles, but are difficult to isolate and have hardly been examined. Here we study rapidly exchanging proteins and show for the first time that they have a strong modulatory effect on the biotransformation of silver nanoparticles. Released silver ions, known for their role in particle toxicity, are found to be trapped as silver sulphide nanocrystals within the protein corona at silver nanoparticles in serum-containing cell culture media. The strongly attached corona acts as a site for sulphidation, while the weakly attached proteins reduce nanocrystal formation in a serum-concentration-dependent manner. Sulphidation results in decreased toxicity of Ag NPs.

Designing a Binding Interface for Control of Cancer Cell Adhesion via 3D Topography and Metabolic Oligosaccharide Engineering

PubMed Central

Du, Jian; Che, Pao-Lin; Wang, Zhi-Yun; Aich, Udayanath; Yarema, Kevin J.

2011-01-01

This study combines metabolic oligosaccharide engineering (MOE), a technology where the glycocalyx of living cells is endowed with chemical features not normally found in sugars, with custom-designed three dimensional biomaterial substrates to enhance the adhesion of cancer cells and control their morphology and gene expression. Specifically, Ac5ManNTGc, a thiol-bearing analogue of N-acetyl-d-mannosamine (ManNAc) was used to introduce thiolated sialic acids into the glycocalyx of human Jurkat T-lymphoma derived cells. In parallel 2D films and 3D electrospun nanofibrous scaffolds were prepared from polyethersulfone (PES) and (as controls) left unmodified or aminated. Alternately, the materials were malemided or gold-coated to provide bioorthogonal binding partners for the thiol groups newly expressed on the cell surface. Cell attachment was modulated by both the topography of the substrate surface and by the chemical compatibility of the binding interface between the cell and the substrate; a substantial increase in binding for normally non-adhesive Jurkat line for 3D scaffold compared to 2D surfaces with an added degree of adhesion resulting from chemoselective binding to malemidede-derivatived or gold-coated surfaces. In addition, the morphology of the cells attached to the 3D scaffolds via MOE-mediated adhesion was dramatically altered and the expression of genes involved in cell adhesion changed in a time-dependent manner. This study showed that cell adhesion could be enhanced, gene expression modulated, and cell fate controlled by introducing the 3D topograhical cues into the growth substrate and by creating a glycoengineered binding interface where the chemistry of both the cell surface and biomaterials scaffold was controlled to facilitate a new mode of carbohydrate-mediated adhesion. PMID:21549424

Streptococcus mutans Adherence: Presumptive Evidence for Protein-Mediated Attachment Followed by Glucan-Dependent Cellular Accumulation

PubMed Central

Staat, Robert H.; Langley, Sharon D.; Doyle, R. J.

1980-01-01

Adherence of Streptococcus mutans to smooth surfaces has been attributed to the production of sucrose-derived d-glucans. However, several studies indicate that the bacterium will adhere in the absence of sucrose. The present data confirmed that S. mutans adherence to saliva-coated hydroxyapatite beads in the absence of sucrose is described by the Langmuir equation. The nature of the sucrose-independent adherence was studied with the Persea americana agglutinin as a selective adherence inhibitor. Pretreatment of the bacterium with P. americana agglutinin caused a 10-fold reduction in adherence, and the inhibition was not reversed with the addition of sucrose. Pretreatment of S. mutans with proteases also reduced adherence, regardless of the sucrose content, whereas periodate oxidation and glucanohydrolase treatment of the bacteria reduced sucrose-mediated adherence to the levels found for sucrose-independent adherence. The P. americana agglutinin, glucanohydrolase, and pepsin pretreatment of the cells did not eliminate sucrose-induced agglutination. Scanning electron microscopy showed that short streptococcal chains were bound to saliva-coated hydroxyapatite crystals in the sucrose-independent system, whereas the presence of sucrose caused larger bacterial clumps to be found. A two-reaction model of S. mutans adherence was developed from these data. It is proposed that one reaction is attachment to the tooth pellicle which is mediated by cell-surface proteins rather than glucans or teichoic acids. The other reaction is cellular accumulation mediated by sucrose-derived d-glucans and cell surface lectins. A series of sequential adherence experiments with P. americana agglutinin as a selective inhibitor provided presumptive evidence for the validity of our model of S. mutans adherence. Images Fig. 1 PMID:7380545

Parent-adolescent attachment and procrastination: The mediating role of self-worth.

PubMed

Chen, Bin-Bin

2017-01-01

Within the theoretical framework of attachment theory, the author examined associations between adolescents' procrastination and their attachment relationships with both mothers and fathers, and explored the potential mediation role of self-worth in these associations. Participants were 384 Chinese adolescents (49.6% boys, average age 15.13 years) from public schools in Shanghai, China. They completed self-report measures of 3 dimensions of parental attachment (i.e., trust, communication, and alienation), general self-worth, and procrastination. The results indicated that both paternal and maternal trust and paternal communication were negatively associated with higher levels of procrastination whereas both paternal and maternal alienation were positively associated with procrastination. In addition, self-worth mediated the associations among 3 dimensions of parental attachment and procrastination. The findings highlighted the importance of parental attachment-based intervention strategies to reduce procrastination among adolescents.

A longitudinal study of interpersonal relationships among lesbian, gay, and bisexual adolescents and young adults: Mediational pathways from attachment to romantic relationship quality

PubMed Central

Starks, Tyrel J.; Newcomb, Michael E.; Mustanski, Brian

2016-01-01

The current study examined the potential for mental health to mediate associations between earlier attachment to parents and peers and later relationship adjustment during adolescence and young adulthood in a sample of sexual minority youth. Secondarily, the study examined associations between peer and parental attachment and relationship/dating milestones. Participants included 219 lesbian, gay, and bisexual youth who participated in six waves of data collection over 3.5 years. Parental attachment was associated with an older age of dating initiation, while peer attachment was associated with longer relationship length. Both peer and parental attachment were significantly associated with mental health in later adolescence and young adulthood. Mental health mediated the association between peer attachment and main partner relationship quality. While the total indirect effect of parental attachment on main partner relationship quality was statistically significant, specific indirect effects were not. Implications for the application of attachment theory and integration of interpersonal factors into mental health intervention with sexual minority youth are discussed. PMID:26108898

Attachment and prejudice.

PubMed

Carnelley, Katherine B; Boag, Elle M

2018-04-16

There is a paucity of research that examines prejudice from an attachment theory perspective. Herein we make theoretical links between attachment patterns and levels of prejudice. Perceptions of outgroup threat, which activate the attachment system, are thought to lead to fear and prejudice for those high in attachment anxiety, and to distancing and prejudice for those high in attachment avoidance. We review the literature that examines the associations between attachment patterns and prejudice; evidence from attachment priming studies suggests a causal role of attachment security in reducing prejudice. We identify several mediators of these links: empathy, negative emotions, trust, social dominance orientation, romanticism, and contact quality. Future research should manipulate potential mediators and use psychophysiological assessments of threat. Copyright © 2018 Elsevier Ltd. All rights reserved.

Novel surface attachment mechanism of the Streptococcus pneumoniae protein PspA.

PubMed Central

Yother, J; White, J M

1994-01-01

Pneumococcal surface protein A (PspA) of Streptococcus pneumoniae has been found to utilize a novel mechanism for anchoring to the bacterial cell surface. In contrast to that of surface proteins from other gram-positive bacteria, PspA anchoring required choline-mediated interactions between the membrane-associated lipoteichoic acid and the C-terminal repeat region of PspA. Release of PspA from the cell surface could be effected by deletion of 5 of the 10 C-terminal repeat units, by high concentrations of choline, or by growth in choline-deficient medium. Other pneumococcal proteins, including autolysin, which has a similar C-terminal repeat region, were not released by these treatments. The attachment mechanism utilized by PspA thus appears to be uniquely adapted to exploit the unusual structure of the pneumococcal cell surface. Further, it has provided the means for rapid and simple isolation of immunogenic PspA from S. pneumoniae. Images PMID:7910604

Highly specific detection of H2O2-dependent luminol chemiluminescence in stimulated human leukocytes using polyvinyl films.

PubMed

Moriguchi, K; Ohno, N; Ogawa, T; Hirai, K

1999-01-01

When human polymorphonuclear leukocytes (PMN) were attached to glass coverslips, cells always spread and formed reactive oxygen species prior to any experimental stimulation. To avoid this, a polyvinylidine chloride film was used as an inactive substance to place the cells. Cells engaged in phagocytosis on the film exhibited a specific H2O2-mediated luminol chemiluminescence (LCL) at the cell-particle interface; the cells stimulated with 12-O-tetradecanoylphorbol-13-acetate became aggregated and the LCL was observed at the cell-cell contact. These results corresponded well with those obtained by an electron microscopic H2O2-demonstration method.

Adult attachment and approaches to activity engagement in chronic pain

PubMed Central

Andrews, Nicole E; Meredith, Pamela J; Strong, Jenny; Donohue, Genevieve F

2014-01-01

BACKGROUND: The way in which individuals with chronic pain habitually approach activity engagement has been shown to impact daily functioning, with both avoidance of one’s daily activities and overactivity (activity engagement that significantly exacerbates pain) associated with more pain, higher levels of physical disability and poorer psychological functioning. OBJECTIVE: To provide insight into the development of maladaptive habitual approaches to activity engagement in chronic pain by applying an attachment theory framework. METHODS: A sample of 164 adults with chronic pain completed selfreport measures of attachment, approach to activity and pain cognitions. Mediation analyses were undertaken to examine the direct association between attachment variables and maladaptive approaches to activity, and to test for the mediating role of pain cognitions (catastrophizing and thought suppression). RESULTS: Results demonstrated that higher levels of secure attachment were associated with lower levels of activity avoidance, which was fully mediated by lower levels of pain catastrophizing; higher levels of preoccupied or fearful attachment were directly associated with higher levels overactivity; higher levels of preoccupied attachment were associated with higher levels of activity avoidance, which was partially mediated by higher levels of pain catastrophizing; and higher levels of fearful attachment were indirectly associated with higher levels of activity avoidance through higher levels of catastrophizing. CONCLUSIONS: These results provide preliminary support for the suggestion that insecure attachment may be a source of vulnerability to the development of disabling activity patterns in chronic pain. PMID:25337857

Attachment and thought problems in an adolescent inpatient sample: The mediational role of theory of mind.

PubMed

Hart, Jessica R; Venta, Amanda; Sharp, Carla

2017-10-01

Previous research has documented increased incidence of insecure attachment and theory of mind (ToM) deficits in individuals experiencing psychotic disorders. ToM has been theorized as a possible mediator of the relation between attachment and psychosis (Korver-Nieberg et al., 2014). The current study sought to extend this area of research to adolescents for the first time by examining adolescent-parent attachment and ToM in inpatient adolescents. Participants were 362 inpatient adolescents and their parents; participants completed the Child Attachment Interview, Movie for the Assessment of Social Cognition, Youth Self Report, and Child Behavior Checklist. Bivariate correlations indicated that attachment coherence (a marker of security) was significantly and positively correlated with ToM abilities, and that low attachment coherence and poor ToM performance were each associated with increased youth- and parent-reported thought problems. Mediational models indicated that ToM mediated the relation between insecure attachment and thought problems according to both parent- and self-report. The results of the current study provide support for a model in which impairments in ToM contribute to the frequently documented association between insecure attachment and emerging psychotic symptoms. Theoretical and clinical implications of these results are discussed, including the potential support for ToM-based interventions for early psychotic symptoms. Copyright © 2017 Elsevier Inc. All rights reserved.

Mutation of the dengue virus type 2 envelope protein heparan sulfate binding sites or the domain III lateral ridge blocks replication in Vero cells prior to membrane fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roehrig, John T., E-mail: jtr1@cdc.gov; Butrapet, Siritorn; Liss, Nathan M.

Using an infectious cDNA clone we engineered seven mutations in the putative heparan sulfate- and receptor-binding motifs of the envelope protein of dengue virus serotype 2, strain 16681. Four mutant viruses, KK122/123EE, E202K, G304K, and KKK305/307/310EEE, were recovered following transfection of C6/36 cells. A fifth mutant, KK291/295EE, was recovered from C6/36 cells with a compensatory E295V mutation. All mutants grew in and mediated fusion of virus-infected C6/36 cells, but three of the mutants, KK122/123EE, E202K, G304K, did not grow in Vero cells without further modification. Two Vero cell lethal mutants, KK291/295EV and KKK307/307/310EEE, failed to replicate in DC-SIGN-transformed Raji cellsmore » and did not react with monoclonal antibodies known to block DENV attachment to Vero cells. Additionally, both mutants were unable to initiate negative-strand vRNA synthesis in Vero cells by 72 h post-infection, suggesting that the replication block occurred prior to virus-mediated membrane fusion. - Highlights: • Heparan sulfate- and receptor-binding motifs of DENV2 envelope protein were mutated. • Four mutant viruses were isolated—all could fuse C6/36 cells. • Two of these mutants were lethal in Vero cells without further modification. • Lethal mutations were KK291/295EV and KKK305/307/310EEE. • Cell attachment was implicated as the replication block for both mutants.« less

Attachment and prejudice: The mediating role of empathy.

PubMed

Boag, Elle M; Carnelley, Katherine B

2016-06-01

In two studies, we examined the novel hypothesis that empathy is a mechanism through which the relationship between attachment patterns and prejudice can be explained. Study 1 examined primed attachment security (vs. neutral prime), empathy, and prejudice towards immigrants. Study 2 examined primed attachment patterns (secure, avoidant, anxious), empathy subscales (perspective taking, empathic concern, personal distress), and prejudice towards Muslims. Across both studies, empathy mediated the relationship between primed attachment security and low prejudice levels. The findings suggest that enhancing felt security and empathic skills in individuals high in attachment-avoidance may lead to reduced prejudice. © 2015 The British Psychological Society.

Attachment orientations as mediators in the intergenerational transmission of marital satisfaction.

PubMed

Jarnecke, Amber M; South, Susan C

2013-08-01

Previous research suggests that there is an intergenerational transmission of marital satisfaction, such that parents' marital satisfaction predicts their adult child's marital satisfaction. The mechanisms that explain this phenomenon remain relatively unknown. In the current study, we examined the role of parent-child attachment orientations and romantic relationship attachment orientations as mediators in the intergenerational transmission of marital satisfaction. Participants (N = 199) were cohabiting newlywed couples who had been married for 12 months or less. All participants separately completed measures of own marital satisfaction, attachment orientations to romantic partners, attachment orientations to rearing parents, and perceptions of parents' marital satisfaction. Data was analyzed using the actor-partner interdependence model in a structural equation modeling framework to account for the nonindependent nature of the data. This allowed for examination of gender differences across husbands and wives and provided overall fit of the hypothesized model. Results supported a partially mediating effect of parent-child attachment and romantic partner attachment on the intergenerational transmission of marital satisfaction, although effects differed by gender. For husbands, the direct effect from parents' marital satisfaction to own satisfaction was partially mediated through anxious attachment styles. There was no direct effect from parents to own marital satisfaction for wives; however, there were significant links from parent's satisfaction to attachment orientations in childhood and adulthood, which in turn impacted wives satisfaction. Findings from this study provide an integrated look at the implications that attachment has on the intergenerational transmission of marital functioning. © 2013 American Psychological Association

Cytohesin 1 regulates homing and engraftment of human hematopoietic stem and progenitor cells.

PubMed

Rak, Justyna; Foster, Katie; Potrzebowska, Katarzyna; Talkhoncheh, Mehrnaz Safaee; Miharada, Natsumi; Komorowska, Karolina; Torngren, Therese; Kvist, Anders; Borg, Åke; Svensson, Lena; Bonnet, Dominique; Larsson, Jonas

2017-02-23

Adhesion is a key component of hematopoietic stem cell regulation mediating homing and retention to the niche in the bone marrow. Here, using an RNA interference screen, we identify cytohesin 1 (CYTH1) as a critical mediator of adhesive properties in primary human cord blood-derived hematopoietic stem and progenitor cells (HSPCs). Knockdown of CYTH1 disrupted adhesion of HSPCs to primary human mesenchymal stroma cells. Attachment to fibronectin and ICAM1, 2 integrin ligands, was severely impaired, and CYTH1-deficient cells showed a reduced integrin β1 activation response, suggesting that CYTH1 mediates integrin-dependent functions. Transplantation of CYTH1-knockdown cells to immunodeficient mice resulted in significantly lower long-term engraftment levels, associated with a reduced capacity of the transplanted cells to home to the bone marrow. Intravital microscopy showed that CYTH1 deficiency profoundly affects HSPC mobility and localization within the marrow space and thereby impairs proper lodgment into the niche. Thus, CYTH1 is a novel major regulator of adhesion and engraftment in human HSPCs through mechanisms that, at least in part, involve the activation of integrins. © 2017 by The American Society of Hematology.

Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses.

PubMed

Richard, Audrey Stéphanie; Zhang, Adam; Park, Sun-Jin; Farzan, Michael; Zong, Min; Choe, Hyeryun

2015-11-24

Phosphatidylserine (PS) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine (PE) is also a ligand for PS receptors and that this phospholipid mediates phagocytosis and viral entry. We show that a subset of PS receptors, including T-cell immunoglobulin (Ig) mucin domain protein 1 (TIM1), efficiently bind PE. We further show that PE is present in the virions of flaviviruses and filoviruses, and that the PE-specific cyclic peptide lantibiotic agent Duramycin efficiently inhibits the entry of West Nile, dengue, and Ebola viruses. The inhibitory effect of Duramycin is specific: it inhibits TIM1-mediated, but not L-SIGN-mediated, virus infection, and it does so by blocking virus attachment to TIM1. We further demonstrate that PE is exposed on the surface of apoptotic cells, and promotes their phagocytic uptake by TIM1-expressing cells. Together, our data show that PE plays a key role in TIM1-mediated virus entry, suggest that disrupting PE association with PS receptors is a promising broad-spectrum antiviral strategy, and deepen our understanding of the process by which apoptotic cells are cleared.

Role of attachment in response to pet loss.

PubMed

Field, Nigel P; Orsini, Lisa; Gavish, Roni; Packman, Wendy

2009-04-01

This study examined the impact of attachment on grief severity following the death of a pet. Seventy-one participants who had lost a dog or cat within the past year completed a set of measures that included an attachment measure assessing individual differences in attachment anxiety and avoidance, strength of the past attachment to the pet, the continuing bond with the deceased pet, social support, and complicated grief symptoms. Attachment anxiety and strength of the past attachment to the pet were each uniquely predictive of more severe grief. Furthermore, the continuing bond to the deceased pet partially mediated the impact of strength of the past attachment to the pet on grief severity. No significant mediators of the effect of attachment anxiety on grief were found, however. The results highlight the importance of distinguishing strength of attachment from attachment security in examining the effect of attachment on response to pet loss.

PEGylated graphene oxide-mediated quercetin-modified collagen hybrid scaffold for enhancement of MSCs differentiation potential and diabetic wound healing.

PubMed

Chu, Jing; Shi, Panpan; Yan, Wenxia; Fu, Jinping; Yang, Zhi; He, Chengmin; Deng, Xiaoyuan; Liu, Hanping

2018-05-24

Nanoscale delivery based on polyethylene glycol (PEG)ylated graphene oxide (GO-PEG) merits attention for biomedical applications owing to its functional surface modification, superior solubility/biocompatibility and controllable drug release capability. However, impaired skin regeneration in applications of these fascinating nanomaterials in diabetes is still limited, and critical issues need to be addressed regarding insufficient collagen hyperplasia and inadequate blood supply. Therefore, a high-performance tissue engineering scaffold with biocompatible and biodegradable properties is essential for diabetic wound healing. Natural and artificial acellular dermal matrix (ADM) scaffolds with spatially organized collagen fibers can provide a suitable architecture and environment for cell attachment and proliferation. Here, a novel collagen-nanomaterial-drug hybrid scaffold was constructed from GO-PEG-mediated quercetin (GO-PEG/Que)-modified ADM (ADM-GO-PEG/Que). The resulting unique and versatile hybrid scaffold exhibited multiple advantages, including the following: a biocompatible, cell-adhesive surface for accelerating mesenchymal stem cell (MSC) attachment and proliferation; superior stability and adjustability of the conduction potential of quercetin for inducing the differentiation of MSCs into adipocytes and osteoblasts; and a biodegradable nanofiber interface for promoting collagen deposition and angiogenesis in diabetic wound repair. This study provides new prospects for the design of innovative GO-PEG-based collagen hybrid scaffolds for application in efficient therapeutic drug delivery, stem cell-based therapies, tissue engineering and regenerative medicine.

Parenting, Marital Conflict and Adjustment from Early- To Mid-Adolescence: Mediated by Adolescent Attachment Style?

ERIC Educational Resources Information Center

Doyle, Anna Beth; Markiewicz, Dorothy

2005-01-01

Contributions of 3 dimensions of parenting (psychological control, warmth, and behavioural control), marital conflict, and attachment style (anxiety and avoidance) to adjustment from early to middle adolescence were assessed. Mediation of marital conflict effects by parenting, and of parenting effects by attachment were examined. Adolescents (n =…

Autobiographical Memory Phenomenology and Content Mediate Attachment Style and Psychological Distress

ERIC Educational Resources Information Center

Sutin, Angelina R.; Gillath, Omri

2009-01-01

In 2 studies, the present research tested the phenomenology and content of autobiographical memory as distinct mediators between attachment avoidance and anxiety and depressive symptoms. In Study 1, participants (N = 454) completed measures of attachment and depressive symptoms in 1 session and retrieved and rated 2 self-defining memories of…

Insecure Attachment and Career Indecision: Mediating Effects of Anxiety and Pessimism

ERIC Educational Resources Information Center

Braunstein-Bercovitz, Hedva; Benjamin, Benny A.; Asor, Shiri; Lev, Maya

2012-01-01

The purpose of this study was to examine a theoretically-based model in which insecure attachment is related to career indecision through the mediation of negative emotions. Two hundred college students completed questionnaires measuring anxious and avoidant dimensions of insecure attachment, negative emotions (trait and career-choice anxiety,…

Parental Attachment, Separation-Individuation, and College Student Adjustment: A Structural Equation Analysis of Mediational Effects

ERIC Educational Resources Information Center

Mattanah, Jonathan F.; Hancock, Gregory R.; Brand, Bethany L.

2004-01-01

Secure parental attachment and healthy levels of separation-individuation have been consistently linked to greater college student adjustment. The present study proposes that the relation between parental attachment and college adjustment is mediated by healthy separation-individuation. The authors gathered data on maternal and paternal…

Differences in the capacity of reovirus strains to induce apoptosis are determined by the viral attachment protein sigma 1.

PubMed Central

Tyler, K L; Squier, M K; Rodgers, S E; Schneider, B E; Oberhaus, S M; Grdina, T A; Cohen, J J; Dermody, T S

1995-01-01

Reoviruses are important models for studies of viral pathogenesis; however, the mechanisms by which these viruses produce cytopathic effects in infected cells have not been defined. In this report, we show that murine L929 (L) cells infected with prototype reovirus strains type 1 Lang (TIL) and type 3 Dearing (T3D) undergo apoptosis and that T3D induces apoptosis to a substantially greater extent than T1L. Using T1L x T3D reassortant viruses, we found that differences in the capacity of T1L and T3D to induce apoptosis are determined by the viral S1 gene segment, which encodes the viral attachment protein sigma 1 and the non-virion-associated protein sigma 1s. Apoptosis was induced by UV-inactivated, replication-incompetent reovirus virions, which do not contain sigma 1s and do not mediate its synthesis in infected cells. Additionally, T3D-induced apoptosis was inhibited by anti-reovirus monoclonal antibodies that inhibit T3D cell attachment and disassembly. These results indicate that sigma 1, rather than sigma 1s, is required for induction of apoptosis by the reovirus and suggest that interaction of virions with cell surface receptors is an essential step in this mechanism of cell killing. PMID:7474116

Surface glycosaminoglycans mediate adherence between HeLa cells and Lactobacillus salivarius Lv72.

PubMed

Martín, Rebeca; Martín, Carla; Escobedo, Susana; Suárez, Juan E; Quirós, Luis M

2013-09-17

The adhesion of lactobacilli to the vaginal surface is of paramount importance to develop their probiotic functions. For this reason, the role of HeLa cell surface proteoglycans in the attachment of Lactobacillus salivarius Lv72, a mutualistic strain of vaginal origin, was investigated. Incubation of cultures with a variety of glycosaminoglycans (chondroitin sulfate A and C, heparin and heparan sulfate) resulted in marked binding interference. However, no single glycosaminoglycan was able to completely abolish cell binding, the sum of all having an additive effect that suggests cooperation between them and recognition of specific adhesins on the bacterial surface. In contrast, chondroitin sulfate B enhanced cell to cell attachment, showing the relevance of the stereochemistry of the uronic acid and the sulfation pattern on binding. Elimination of the HeLa surface glycosaminoglycans with lyases also resulted in severe adherence impairment. Advantage was taken of the Lactobacillus-glycosaminoglycans interaction to identify an adhesin from the bacterial surface. This protein, identify as a soluble binding protein of an ABC transporter system (OppA) by MALDI-TOF/(MS), was overproduced in Escherichia coli, purified and shown to interfere with L. salivarius Lv72 adhesion to HeLa cells. These data suggest that glycosaminoglycans play a fundamental role in attachment of mutualistic bacteria to the epithelium that lines the cavities where the normal microbiota thrives, OppA being a bacterial adhesin involved in the process.

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

PubMed Central

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

He loves her, he loves her not: attachment style as a personality antecedent to men's ambivalent sexism.

PubMed

Hart, Joshua; Hung, Jacqueline A; Glick, Peter; Dinero, Rachel E

2012-11-01

The authors present an integrative account of how attachment insecurities relate to sexism. Two studies showed that attachment avoidance predisposes men to endorse hostile but to reject benevolent sexism (BS), whereas attachment anxiety predisposes men toward ambivalent (both hostile and benevolent) sexism. The authors also tested predicted mediators, finding that men's social dominance orientation (a competitive intergroup ideology) mediated the avoidance to hostile sexism link. In addition, romanticism (an idealized interpersonal ideology) mediated attachment insecurity to BS links: (a) Avoidant men tended to reject romanticism (i.e., were cynical about romance) and, in turn, were likely to reject BS, whereas (b) anxious men tended to endorse romanticism (i.e., were idealistic about romance) and, in turn, likely to endorse BS. The authors conclude that men's sexism stems in part from dispositional attachment working models, both directly and through the interpersonal and intergroup ideologies they generate.

Parental attachment, self-control, and depressive symptoms in Chinese and Italian adolescents: Test of a mediation model.

PubMed

Li, Jian-Bin; Delvecchio, Elisa; Lis, Adriana; Nie, Yan-Gang; Di Riso, Daniela

2015-08-01

The current study investigated the relationship between parental attachment and depressive symptoms as well as the mediating effect of self-control in two different cultures. Samples were 1305 Chinese and 1327 Italian adolescents. They completed the Inventory of Parental and Peer Attachment, the Self-Restraint Subscale of the Adolescents' Self-Consciousness Scale, and the Children's Depression Inventory that assessed parental attachment, self-control, and depressive symptoms, respectively. Results showed that: (1) Few cultural differences in depressive symptom were observed. (2) Parental attachment and self-control were negatively related to depressive symptoms in both cultures. (3) Self-control mediated the relations between parental attachment and depressive symptoms in both cultures. (4) The direct and indirect effects were invariant across cultures. In conclusion, parental attachment and self-control are important for adolescents' depressive symptoms in Chinese and Italian adolescents. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

The physical boundaries of public goods cooperation between surface-attached bacterial cells

PubMed Central

Weigert, Michael; Kümmerli, Rolf

2017-01-01

Bacteria secrete a variety of compounds important for nutrient scavenging, competition mediation and infection establishment. While there is a general consensus that secreted compounds can be shared and therefore have social consequences for the bacterial collective, we know little about the physical limits of such bacterial social interactions. Here, we address this issue by studying the sharing of iron-scavenging siderophores between surface-attached microcolonies of the bacterium Pseudomonas aeruginosa. Using single-cell fluorescent microscopy, we show that siderophores, secreted by producers, quickly reach non-producers within a range of 100 µm, and significantly boost their fitness. Producers in turn respond to variation in sharing efficiency by adjusting their pyoverdine investment levels. These social effects wane with larger cell-to-cell distances and on hard surfaces. Thus, our findings reveal the boundaries of compound sharing, and show that sharing is particularly relevant between nearby yet physically separated bacteria on soft surfaces, matching realistic natural conditions such as those encountered in soft tissue infections. PMID:28701557

All-trans-retinoic acid inhibits collapsin response mediator protein-2 transcriptional activity during SH-SY5Y neuroblastoma cell differentiation.

PubMed

Fontán-Gabás, Lorena; Oliemuller, Erik; Martínez-Irujo, Juan José; de Miguel, Carlos; Rouzaut, Ana

2007-01-01

Neurons are highly polarized cells composed of two structurally and functionally distinct parts, the axon and the dendrite. The establishment of this asymmetric structure is a tightly regulated process. In fact, alterations in the proteins involved in the configuration of the microtubule lattice are frequent in neuro-oncologic diseases. One of these cytoplasmic mediators is the protein known as collapsin response mediator protein-2, which interacts with and promotes tubulin polymerization. In this study, we investigated collapsin response mediator protein-2 transcriptional regulation during all-trans-retinoic acid-induced differentiation of SH-SY5Y neuroblastoma cells. All-trans-retinoic acid is considered to be a potential preventive and therapeutic agent, and has been extensively used to differentiate neuroblastoma cells in vitro. Therefore, we first demonstrated that collapsin response mediator protein-2 mRNA levels are downregulated during the differentiation process. After completion of deletion construct analysis and mutagenesis and mobility shift assays, we concluded that collapsin response mediator protein-2 basal promoter activity is regulated by the transcription factors AP-2 and Pax-3, whereas E2F, Sp1 and NeuroD1 seem not to participate in its regulation. Furthermore, we finally established that reduced expression of collapsin response mediator protein-2 after all-trans-retinoic acid exposure is associated with impaired Pax-3 and AP-2 binding to their consensus sequences in the collapsin response mediator protein-2 promoter. Decreased attachment of AP-2 is a consequence of its accumulation in the cytoplasm. On the other hand, Pax-3 shows lower binding due to all-trans-retinoic acid-mediated transcriptional repression. Unraveling the molecular mechanisms behind the action of all-trans-retinoic acid on neuroblastoma cells may well offer new perspectives for its clinical application.

Accelerated Bone Repair After Plasma Laser Corticotomies

PubMed Central

Leucht, Philipp; Lam, Kentson; Kim, Jae-Beom; Mackanos, Mark A.; Simanovskii, Dmitrii M.; Longaker, Michael T.; Contag, Christopher H.; Schwettman, H Alan; Helms, Jill A.

2007-01-01

Objective: To reveal, on a cellular and molecular level, how skeletal regeneration of a corticotomy is enhanced when using laser-plasma mediated ablation compared with conventional mechanical tissue removal. Summary Background Data: Osteotomies are well-known for their most detrimental side effect: thermal damage. This thermal and mechanical trauma to adjacent bone tissue can result in the untoward consequences of cell death and eventually in a delay in healing. Methods: Murine tibial corticotomies were performed using a conventional saw and a Ti:Sapphire plasma-generated laser that removes tissue with minimal thermal damage. Our analyses began 24 hours after injury and proceeded to postsurgical day 6. We investigated aspects of wound repair ranging from vascularization, inflammation, cell proliferation, differentiation, and bone remodeling. Results: Histology of mouse corticotomy sites uncovered a significant difference in the onset of bone healing; whereas laser corticotomies showed abundant bone matrix deposition at postsurgical day 6, saw corticotomies only exhibited undifferentiated tissue. Our analyses uncovered that cutting bone with a saw caused denaturation of the collagen matrix due to thermal effects. This denatured collagen represented an unfavorable scaffold for subsequent osteoblast attachment, which in turn impeded deposition of a new bony matrix. The matrix degradation induced a prolonged inflammatory reaction at the cut edge to create a surface favorable for osteochondroprogenitor cell attachment. Laser corticotomies were absent of collagen denaturation, therefore osteochondroprogenitor cell attachment was enabled shortly after surgery. Conclusion: In summary, these data demonstrate that corticotomies performed with Ti:Sapphire lasers are associated with a reduced initial inflammatory response at the injury site leading to accelerated osteochondroprogenitor cell migration, attachment, differentiation, and eventually matrix deposition. PMID:17592303

Baculovirus GP64-mediated entry into mammalian cells.

PubMed

Kataoka, Chikako; Kaname, Yuuki; Taguwa, Shuhei; Abe, Takayuki; Fukuhara, Takasuke; Tani, Hideki; Moriishi, Kohji; Matsuura, Yoshiharu

2012-03-01

The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) serves as an efficient viral vector, not only for abundant gene expression in insect cells, but also for gene delivery into mammalian cells. Lentivirus vectors pseudotyped with the baculovirus envelope glycoprotein GP64 have been shown to acquire more potent gene transduction than those with vesicular stomatitis virus (VSV) envelope glycoprotein G. However, there are conflicting hypotheses about the molecular mechanisms of the entry of AcMNPV. Moreover, the mechanisms of the entry of pseudotyped viruses bearing GP64 into mammalian cells are not well characterized. Determination of the entry mechanisms of AcMNPV and the pseudotyped viruses bearing GP64 is important for future development of viral vectors that can deliver genes into mammalian cells with greater efficiency and specificity. In this study, we generated three pseudotyped VSVs, NPVpv, VSVpv, and MLVpv, bearing envelope proteins of AcMNPV, VSV, and murine leukemia virus, respectively. Depletion of membrane cholesterol by treatment with methyl-β-cyclodextrin, which removes cholesterol from cellular membranes, inhibited GP64-mediated internalization in a dose-dependent manner but did not inhibit attachment to the cell surface. Treatment of cells with inhibitors or the expression of dominant-negative mutants for dynamin- and clathrin-mediated endocytosis abrogated the internalization of AcMNPV and NPVpv into mammalian cells, whereas inhibition of caveolin-mediated endocytosis did not. Furthermore, inhibition of macropinocytosis reduced GP64-mediated internalization. These results suggest that cholesterol in the plasma membrane, dynamin- and clathrin-dependent endocytosis, and macropinocytosis play crucial roles in the entry of viruses bearing baculovirus GP64 into mammalian cells.

Scaffold attachment factor B suppresses HIV-1 infection of CD4+ cells by preventing binding of RNA polymerase II to HIV-1's long terminal repeat.

PubMed

Ma, Li; Sun, Li; Jin, Xia; Xiong, Si-Dong; Wang, Jian-Hua

2018-06-10

The 5' end of HIV-1 long terminal repeat (LTR) promoter plays an essential role in driving viral transcription and productive infection. Multiple host and viral factors regulate LTR activity and modulate HIV-1 latency. Manipulation of the HIV-1 LTR provides a potential therapeutic strategy for combating HIV-1 persistence. In this study, we identified an RNA-/DNA-binding protein, Scaffold Attachment Factor B (SAFB1) as a host-cell factor that represses HIV-1 transcription. We found that SAFB1 bound to HIV-1 5`-LTR and significantly repressed 5`-LTR-driven-viral transcription and HIV-1 infection of CD4 + T cells. Mechanistically, SAFB1-mediated repression of HIV-1 transcription and infection was independent of its RNA- and DNA-binding capacities, instead, by binding to phosphorylated RNA polymerase II (RNA pol II), SAFB1 blocked its recruitment to the HIV-1 LTR. Of note, the SAFB1-mediated repression of HIV-1 transcription from proviral DNA maintained HIV-1 latency in CD4 + T cells. In summary, our findings reveal that SAFB1 binds to HIV-1-LTR and physically interacts with phosphorylated RNA pol II, repressing HIV-1 transcription initiation and elongation. Our findings improve the understanding of host modulation of HIV-1 transcription and latency and provide a new host-cell target for improved anti-HIV-1 therapies. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

POSTPARTUM BONDING DIFFICULTIES AND ADULT ATTACHMENT STYLES: THE MEDIATING ROLE OF POSTPARTUM DEPRESSION AND CHILDBIRTH-RELATED PTSD.

PubMed

S Hairston, Ilana; E Handelzalts, Jonathan; Assis, Chen; Kovo, Michal

2018-03-01

Despite decades of research demonstrating the role of adult attachment styles and early mother-infant bonding in parenting behaviors and maternal mental health, these constructs have seldom been studied together. The present study aimed to investigate the relationship between attachment styles and specific bonding difficulties of mothers. In addition, as postpartum depression and childbirth-related posttraumatic stress symptoms have been associated with both constructs, we explored their possible mediation effect. One hundred fourteen mothers, 4 to 12 weeks' postpartum, completed a demographic questionnaire, the Adult Attachment Style Questionnaire (M. Mikulincer, V. Florian, & A. Tolmacz, 1990), the Postpartum Bonding Questionnaire (L.F. Brockington, C. Fraser, & D. Wilson, 2006), the Modified Perinatal Posttraumatic Stress Disorder Questionnaire (J.L. Callahan, S.E. Borja, & M.T. Hynan, 2006), and the Edinburgh Postnatal Depression Scale (J.L. Cox, G. Chapman, D. Murray, & P. Jones, 1996), using an online survey system. As predicted, insecure attachment styles were associated with bonding difficulties wherein anxious/ambivalent attachment was associated with greater infant-focused anxiety, mediated by postpartum depression but not childbirth-related PTSD symptoms. In contrast, greater avoidant attachment style was associated with greater rejection and anger, mediated by childbirth-related posttraumatic stress disorder (PTSD), but not depression symptoms. The current study confirmed the association of different attachment styles with bonding as well as the mediating roles of childbirth-related PTSD and postpartum depression symptoms. Future psychological interventions may utilize such evidence to target interventions for bonding disorders in accordance with individual differences. © 2018 Michigan Association for Infant Mental Health.

Targeted p120-Catenin Ablation Disrupts Dental Enamel Development

PubMed Central

Bartlett, John D.; Dobeck, Justine M.; Tye, Coralee E.; Perez-Moreno, Mirna; Stokes, Nicole; Reynolds, Albert B.; Fuchs, Elaine; Skobe, Ziedonis

2010-01-01

Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E- and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows. PMID:20862276

Avoidant/ambivalent attachment style as a mediator between abusive childhood experiences and adult relationship difficulties.

PubMed

McCarthy, G; Taylor, A

1999-03-01

The role of attachment style, self-esteem, and relationship attributions as possible mediators between abusive childhood experiences and difficulties in establishing supportive love relationships in adulthood were investigated in a sample of women known to be at risk of experiencing relationship problems. Measures of child abuse, the quality of love relationships, and the three potential mediators were made concurrently in adulthood. Participants who had experienced child abuse were found to be six times more likely to be experiencing difficulties in the domain of adult love relationships than those who had not. Self-esteem and relationship attributions were not found to be related to child abuse. When both child abuse and avoidant/ambivalent attachment style were considered together avoidant/ambivalent attachment style, but not child abuse, was found to be related to relationship difficulties. These findings indicate that avoidant/ambivalent attachment style, but not self-esteem and relationship attributions, is a mediating factor in the route from child abuse to adult relationship abilities.

How the Attachment Styles Associated with Student Alienation: The Mediation Role of Emotional Well-Being

ERIC Educational Resources Information Center

Kocayörük, Ercan; Uzman, Ersin; Mert, Abdullah

2014-01-01

The present study examined emotional well-being as a mediator between parental attachment (mother and father) and student alienation. A total of 227 high school students from the city of Ankara completed the self-report measures of parental attachment, positive and negative affect, and alienation. Using structural equation modeling, a model was…

Inter-Relationships among Attachment to Mother and Father, Self-Esteem, and Career Indecision

ERIC Educational Resources Information Center

Emmanuelle, Vignoli

2009-01-01

This study investigated the mediating role of adolescents' global self-esteem, based on the relationship between adolescents' mother or father attachment and their career indecision; as well as the mediating role of adolescents' career indecision on the relationship between mother or father attachment and self-esteem. Two hundred and forty-one…

Mother-Child Attachment and Cognitive Performance in Middle Childhood: An Examination of Mediating Mechanisms

ERIC Educational Resources Information Center

West, Katara K.; Mathews, Brittany L.; Kerns, Kathryn A.

2013-01-01

Although mother-child attachment has been shown to predict cognitive performance, there has been a lack of attention to the mediating mechanisms that explain these associations. In the present study, we investigated relations of early mother-child attachment and cognitive performance in middle childhood (the latter in terms of both academic…

Peer Attachment, Coping, and Self-Esteem in Institutionalized Adolescents: The Mediating Role of Social Skills

ERIC Educational Resources Information Center

Mota, Catarina Pinheiro; Matos, Paula Mena

2013-01-01

This study analyzes the contribution of peer attachment in predicting active coping and self-esteem in a sample of 109 institutionalized adolescents. It also explores the mediating role of social skills in the association between peer attachment, coping, and self-esteem. Structural equation modeling identified a model able to predict a positive…

Structural and mechanistic studies of measles virus illuminate paramyxovirus entry.

PubMed

Plemper, Richard K; Brindley, Melinda A; Iorio, Ronald M

2011-06-01

Measles virus (MeV), a member of the paramyxovirus family of enveloped RNA viruses and one of the most infectious viral pathogens identified, accounts for major pediatric morbidity and mortality worldwide although coordinated efforts to achieve global measles control are in place. Target cell entry is mediated by two viral envelope glycoproteins, the attachment (H) and fusion (F) proteins, which form a complex that achieves merger of the envelope with target cell membranes. Despite continually expanding knowledge of the entry strategies employed by enveloped viruses, our molecular insight into the organization of functional paramyxovirus fusion complexes and the mechanisms by which the receptor binding by the attachment protein triggers the required conformational rearrangements of the fusion protein remain incomplete. Recently reported crystal structures of the MeV attachment protein in complex with its cellular receptors CD46 or SLAM and newly developed functional assays have now illuminated some of the fundamental principles that govern cell entry by this archetype member of the paramyxovirus family. Here, we review these advances in our molecular understanding of MeV entry in the context of diverse entry strategies employed by other members of the paramyxovirus family.

Examining the role of attachment in the relationship between childhood adversity, psychological distress and subjective well-being.

PubMed

Corcoran, Mark; McNulty, Muireann

2018-02-01

Childhood adversity is associated with a wide range of detrimental psychological consequences. This study examined the mediating role of relationship-specific attachment (avoidance and anxiety) in the associations between childhood adversity and both psychological distress and subjective well-being. University students (N=190) across the Republic of Ireland completed self-report measures including the Adverse Childhood Experiences scale, Experiences in Close Relationships - Relationship Structures scale, Depression Anxiety and Stress scales and measures of subjective well-being. One hundred and twenty-eight participants (67.4%) reported experiencing at least one adverse childhood experience. Childhood adversity was associated with symptoms of psychological distress and subjective well-being. All such associations were mediated by certain relationship-specific attachment dimensions. Of these, attachment anxiety in general relationships was the most prominent mediator for both psychological distress and subjective well-being. Attachment to one's father and to one's romantic partner did not mediate any association. These findings indicate that attachment, in particular relationships, is an important factor in the associations between childhood adversity and both psychological distress and subjective well-being as an adult. One's attachment anxiety in general relationships is particularly important in these associations. Therapeutic interventions addressing these attachment domains may offset the detrimental effects of childhood adversity. Future research is required using a longitudinal design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Formation of Monocrystalline 1D and 2D Architectures via Epitaxial Attachment: Bottom-Up Routes through Surfactant-Mediated Arrays of Oriented Nanocrystals.

PubMed

Nakagawa, Yoshitaka; Kageyama, Hiroyuki; Oaki, Yuya; Imai, Hiroaki

2015-06-09

Monocrystalline architectures with well-defined shapes were achieved by bottom-up routes through epitaxial attachment of Mn3O4 nanocrystals. The crystallographically continuous 1D chains elongated in the a axis and 2D panels having large a or c faces were obtained by removal of the organic mediator from surfactant-mediated 1D and 2D arrays of Mn3O4 nanocrystals, respectively. Our basal approach indicates that the epitaxial attachment through the surfactant-mediated arrays is utilized for fabrication of a wide variety of micrometric architectures from nanometric crystalline units.

Subjective happiness among mothers of children with disabilities: The role of stress, attachment, guilt and social support.

PubMed

Findler, Liora; Klein Jacoby, Ayelet; Gabis, Lidia

2016-08-01

Parenting a child with disabilities might affect the happiness of the mothers. Hence we adapted Wallander, Varni, Babani, Banis, and Wilcox's (1989) disability-stress-coping model to examine the impact of risk factors (specific stressors related to the child's disability) on the mother's adaptation (happiness). Intrapersonal factors (attachment) and social-ecological factors (social support) were hypothesized to predict adaptation. Both constitute 'risk-resistant' factors, which are mediated by the mother's perceived general stress and guilt. 191 mothers of a child with a developmental disability (ages 3-7) answered questionnaires on happiness, specific and general stress, attachment, guilt and social support. Attachment avoidance was directly and negatively associated with mothers' happiness. General stress was negatively associated with happiness, and mediated the association between anxious attachment, support, and specific stress with happiness. Guilt was negatively associated with happiness, and served as a mediator between attachment anxiety and support and happiness. The findings of the current research show direct and indirect associations of risk factors with happiness and the role of general stress and feelings of guilt as mediators. This study stresses the importance of attachment and social support to happiness and sheds light on the unique role of guilt in promoting or inhibiting happiness. Copyright © 2016 Elsevier Ltd. All rights reserved.

Patterns of attachment and parents' adjustment to the death of their child.

PubMed

Wijngaards-de Meij, Leoniek; Stroebe, Margaret; Schut, Henk; Stroebe, Wolfgang; van den Bout, Jan; van der Heijden, Peter G M; Dijkstra, Iris

2007-04-01

The impact of adult attachment on psychological adjustment among bereaved parents and the mediating effect of relationship satisfaction were examined among a sample of 219 couples of parents. Data collection took place 6, 13, and 20 months after loss. Use of the actor partner interdependence model in multilevel regression analysis enabled exploration of both individual as well as partner attachment as predictors of grief and depression. Results indicated that the more insecurely attached parents were (on both avoidance and anxiety attachment), the higher the symptoms of grief and depression. Neither the attachment pattern of the partner nor similarity of attachment within the couple had any influence on psychological adjustment of the parent. Marital satisfaction partially mediated the association of anxious attachment with symptomatology. Contrary to previous research findings, avoidant attachment was associated with high grief intensity. These findings challenge the notion that the avoidantly attached are resilient.

Attachment's Links With Adolescents' Social Emotions: The Roles of Negative Emotionality and Emotion Regulation.

PubMed

Murphy, Tia Panfile; Laible, Deborah J; Augustine, Mairin; Robeson, Lindsay

2015-01-01

Recent research has attempted to explain the mechanisms through which parental attachment affects social and emotional outcomes (e.g., Burnette, Taylor, Worthington, & Forsyth, 2007 ; Panfile & Laible, 2012 ). The authors' goal was to examine negative emotionality and emotion regulation as mediators of the associations that attachment has with empathy, forgiveness, guilt, and jealousy. One hundred forty-eight adolescents reported their parental attachment security, general levels of negative emotionality and abilities to regulate emotional responses, and tendencies to feel empathy, forgiveness, guilt, and jealousy. Results revealed that attachment security was associated with higher levels of empathy, forgiveness, and guilt, but lower levels of jealousy. In addition, emotion regulation mediated the links attachment shared with both empathy and guilt, such that higher levels of attachment security were linked with greater levels of emotion regulation, which led to greater levels of empathy and guilt. Alternatively, negative emotionality mediated the links attachment shared with both forgiveness and jealousy, such that higher levels of attachment security were associated with lower levels of negative emotionality, which in turn was linked to lower levels of forgiveness and higher levels of jealousy. This study provides a general picture of how attachment security may play a role in shaping an individual's levels of social emotions.

Mothers' Personal and Interpersonal Function as Potential Mediators Between Maternal Maltreatment History and Child Behavior Problems.

PubMed

Pereira, Jessica; Ludmer, Jaclyn A; Gonzalez, Andrea; Atkinson, Leslie

2018-05-01

This study examined maternal depressive symptoms, social support, parenting, and adult attachment as mediators explaining the relation between maternal childhood maltreatment and child behavior in offspring. We assessed a community sample of 96 mother-child dyads. At child age 16 months, mothers self-reported maltreatment history, adult attachment, depressive symptoms, and social support, and maternal sensitivity was assessed via 2 hr of direct behavioral observation. Maternal reports of child behavior were collected at 5 years. Single and parallel mediation models were constructed. Only maternal depressive symptoms mediated the relation between maternal maltreatment history and children's internalizing problems. Maternal sensitivity emerged as a suppressor variable. With respect to the relation between maternal maltreatment history and children's externalizing problems, when entered singly, maternal depressive symptoms, social support, and avoidant attachment emerged as mediators. When examined in parallel, only maternal depressive symptoms and avoidant attachment accounted for unique mediating variance. Findings have implications with respect to important maternal factors that might be targeted to reduce the probability of maladaptive child behavior.

Why are people with insecure attachments unhappy? The mediation of meaning in life.

PubMed

Yen, Chih-Long

2014-10-01

This study explores the mediating role of meaning in life with respect to the relationship between adult attachment and psychological well-being. This study proposed that because people with insecure attachments have difficulty in connecting with the external world, this may decrease their ability to attain meaning in life, which may in turn diminish their well-being. Two studies (N = 155 and 234, respectively, with age range from 18 to 31) were conducted. Participants completed self-report measures of attachment, well-being and meaning in life. The results consistently revealed a full mediation effect of meaning in life on the relationship between attachment and well-being. The findings suggested that a deeper sense of meaning in life comes from one's connection with the external world, especially with other people. © 2014 International Union of Psychological Science.

Recombinant Spider Silk Functionalized with a Motif from Fibronectin Mediates Cell Adhesion and Growth on Polymeric Substrates by Entrapping Cells During Self-Assembly.

PubMed

Tasiopoulos, Christos Panagiotis; Widhe, Mona; Hedhammar, My

2018-05-02

In vitro endothelialization of synthetic grafts or engineered vascular constructs is considered a promising alternative to overcome shortcomings in the availability of autologous vessels and in-graft complications with synthetics. A number of cell-seeding techniques have been implemented to render vascular grafts accessible for cells to attach, proliferate, and spread over the surface area. Nonetheless, seeding efficiency and the time needed for cells to adhere varies dramatically. Herein, we investigated a novel cell-seeding approach (denoted co-seeding) that enables cells to bind to a motif from fibronectin included in a recombinant spider silk protein. Entrapment of cells occurs at the same time as the silk assembles into a nanofibrillar coating on various substrates. Cell adhesion analysis showed that the technique can markedly improve cell-seeding efficiency to nonfunctionalized polystyrene surfaces, as well as establish cell attachment and growth of human dermal microvascular endothelial cells on bare polyethylene terephthalate and polytetrafluoroethylene (PTFE) substrates. Scanning electron microscopy images revealed a uniform endothelial cell layer and cell-substratum compliance with the functionalized silk protein to PTFE surfaces. The co-seeding technique holds a great promise as a method to reliably and quickly cellularize engineered vascular constructs as well as to in vitro endothelialize commercially available cardiovascular grafts.

Near-complete genome sequence of the cellulolytic Bacterium Bacteroides ( Pseudobacteroides) cellulosolvens ATCC 35603

DOE PAGES

Dassa, Bareket; Utturkar, Sagar M.; Hurt, Richard A.; ...

2015-09-24

We report the single-contig genome sequence of the anaerobic, mesophilic, cellulolytic bacterium, Bacteroides cellulosolvens. The bacterium produces a particularly elaborate cellulosome system, whereas the types of cohesin-dockerin interactions are opposite of other known cellulosome systems: cell-surface attachment is thus mediated via type-I interactions whereas enzymes are integrated via type-II interactions.

The role of attachment insecurity in the emergence of anxiety symptoms in children and adolescents with migraine: an empirical study.

PubMed

Williams, Riccardo; Leone, Luigi; Faedda, Noemi; Natalucci, Giulia; Bellini, Benedetta; Salvi, Elisa; Verdecchia, Paola; Cerutti, Rita; Arruda, Marco; Guidetti, Vincenzo

2017-12-01

It is widely recognised that there are associations between headache, psychiatric comorbidity and attachment insecurity in both adults and children. The aims of this study were: 1) to compare perceived attachment security and anxiety in children and adolescents with migraine without aura and a healthy control group; 2) to test whether the child's perceived security of attachment to the mother and the father mediated the association between migraine and anxiety. One hundred children and adolescents with Migraine without Aura were compared with a control group of 100 children without headache. The Security Scale (measures perceived security of attachments) and the Self-Administered Psychiatric Scales for Children and Adolescents, a measure of anxiety symptoms, were administered to all participants. The clinical group had lower attachment security than the control group and higher scores on all anxiety scales. Anxiety was negatively correlated with attachment. Children's attachment to their mother mediated the increase in global anxiety in the clinical group. Insecure paternal attachment was associated with greater insecurity in maternal attachment, suggesting that there is a complex pathway from migraine to anxiety symptoms mediated by perceived insecurity of paternal attachment and hence also by perceived insecurity of maternal attachment. These results suggest that insecure parental attachment may exacerbate anxiety in children and adolescents with migraine and point to the importance of multimodal interventions, perhaps taking account of family relationships, for children and adolescents with migraine.

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

PubMed Central

LaFoya, Bryce; Munroe, Jordan A.; Miyamoto, Alison; Detweiler, Michael A.; Crow, Jacob J.; Gazdik, Tana

2018-01-01

The traditional view of integrins portrays these highly conserved cell surface receptors as mediators of cellular attachment to the extracellular matrix (ECM), and to a lesser degree, as coordinators of leukocyte adhesion to the endothelium. These canonical activities are indispensable; however, there is also a wide variety of integrin functions mediated by non-ECM ligands that transcend the traditional roles of integrins. Some of these unorthodox roles involve cell-cell interactions and are engaged to support immune functions such as leukocyte transmigration, recognition of opsonization factors, and stimulation of neutrophil extracellular traps. Other cell-cell interactions mediated by integrins include hematopoietic stem cell and tumor cell homing to target tissues. Integrins also serve as cell-surface receptors for various growth factors, hormones, and small molecules. Interestingly, integrins have also been exploited by a wide variety of organisms including viruses and bacteria to support infectious activities such as cellular adhesion and/or cellular internalization. Additionally, the disruption of integrin function through the use of soluble integrin ligands is a common strategy adopted by several parasites in order to inhibit blood clotting during hematophagy, or by venomous snakes to kill prey. In this review, we strive to go beyond the matrix and summarize non-ECM ligands that interact with integrins in order to highlight these non-traditional functions of integrins. PMID:29393909

The Multifaceted Role of Attachment during Preschool: Moderator of Its Indirect Effect on Empathy through Emotion Regulation

ERIC Educational Resources Information Center

Stefan, Catrinel A.; Avram, Julia

2018-01-01

The aims of the current study were (1) to replicate findings regarding the mediator role of emotion regulation (ER) between attachment and empathy; (2) to extend current knowledge by testing the moderator effect of ER on the relationship between attachment and empathy; and (3) to test an integrative moderated mediation model in which attachment…

Adolescent Survivors of Childhood Sexual Abuse: The Mediating Role of Attachment Style and Coping in Psychological and Interpersonal Functioning.

ERIC Educational Resources Information Center

Shapiro, Deborah L.; Levendosky, Alytia A.

1999-01-01

A study of 80 adolescent females found that attachment style mediates the effects of child sexual abuse (CSA) and child abuse and neglect on coping and psychological distress. The indirect effects of CSA and other abuse through attachment accounted for most of the effects on coping and psychological distress. (Author/CR)

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

PubMed

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.

Photoinitiator-Free Synthesis of Endothelial Cell Adhesive and Enzymatically Degradable Hydrogels

PubMed Central

Jones, Derek R.; Marchant, Roger E.; von Recum, Horst; Gupta, Anirban Sen; Kottke-Marchant, Kandice

2015-01-01

We report on a photoinitiator-free synthetic method of incorporating bioactivity into poly(ethylene glycol) (PEG) hydrogels in order to control physical properties, enzymatic biodegradability and cell-specific adhesiveness of the polymer network, while eliminating the need for UV-mediated photopolymerization. To accomplish this, hydrogel networks were polymerized using Michael addition with four-arm PEG acrylate (10 kDa), using a collagenase sensitive peptide (CSP) as a crosslinker, and introducing an endothelial cell adhesive peptide either terminally (RGD) or attached to the crosslinking peptide sequence (CSP-RGD). The efficiency of the Michael addition reactions were determined by NMR and Ellman’s assay. Successful decoupling of cell adhesivity and physical properties was demonstrated by quantifying and comparing the swelling ratios and Young’s Moduli of various hydrogel formulations. Degradation profiles were established by incubating functionalized hydrogels in collagenase solutions (0.0 – 1.0 µg/mL), demonstrating that functionalized hydrogels degraded at a rate dependent upon collagenase concentration. Moreover, it was shown that the degradation rate was independent of CSP-RGD concentration. Cell attachment and proliferation on functionalized hydrogels were compared for various RGD concentrations, providing evidence that cell attachment and proliferation were directly related to relative amounts of the CSP-RGD combination peptide. An increase in cell viability was achieved using Michael addition techniques when compared to UV-polymerization, and was assessed by a LIVE/DEAD fluorescence assay. This photoinitiator-free method shows promise in creating hydrogel-based tissue engineering scaffolds allow for decoupled cell adhesivity and physical properties and that render greater cell viability. PMID:25462848

Novel INTeraction of MUC4 and galectin: potential pathobiological implications for metastasis in lethal pancreatic cancer.

PubMed

Senapati, Shantibhusan; Chaturvedi, Pallavi; Chaney, William G; Chakraborty, Subhankar; Gnanapragassam, Vinayaga S; Sasson, Aaron R; Batra, Surinder K

2011-01-15

Several studies have reported aberrant expression of MUC4 in pancreatic cancer (PC), which is associated with tumorigenicity and metastasis. Mechanisms through which MUC4 promote metastasis of PC cells to distant organs are poorly defined. Identification of MUC4-galectin-3 interaction and its effect on the adhesion of cancer cells to endothelial cells were done by immunoprecipitation and cell-cell adhesion assays, respectively. Serum galectin-3 level for normal and PC patients were evaluated through ELISA. In the present study, we have provided clinical evidence that the level of galectin-3 is significantly elevated in the sera of PC patients with metastatic disease compared with patients without metastasis (P = 0.04) and healthy controls (P = 0.00001). Importantly, for the first time, we demonstrate that MUC4 present on the surface of circulating PC cells plays a significant role in the transient and reversible attachment (docking) of circulating tumor cells to the surface of endothelial cells. Further, exogenous galectin-3 at concentrations similar to that found in the sera of PC patients interacts with MUC4 via surface glycans such as T antigens, which results in the clustering of MUC4 on the cell surface and a stronger attachment (locking) of circulating tumor cells to the endothelium. Altogether, these findings suggest that PC cell-associated MUC4 helps in the docking of tumor cells on the endothelial surface. During cancer progression, MUC4-galectin-3 interaction-mediated clustering of MUC4 may expose the surface adhesion molecules, which in turn promotes a stronger attachment (locking) of tumor cells to the endothelial surface. ©2010 AACR.

Gold Nanoparticle Mediated Laser Transfection for Efficient siRNA Mediated Gene Knock Down

PubMed Central

Heinemann, Dag; Schomaker, Markus; Kalies, Stefan; Schieck, Maximilian; Carlson, Regina; Escobar, Hugo Murua; Ripken, Tammo; Meyer, Heiko; Heisterkamp, Alexander

2013-01-01

Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types. PMID:23536802

The relationship between adult attachment orientation and child self-regulation in eating: The mediating role of persuasive-controlling feeding practices.

PubMed

Powell, Elisabeth M; Frankel, Leslie A; Umemura, Tomo; Hazen, Nancy

2017-08-01

The present study examines the hypothesis that adult attachment orientation, specifically anxious attachment, is related to children's diminished ability to self-regulate their food intake, and that this relationship is mediated by parents' persuasive-controlling feeding practices. Two hundred and sixty five mothers and fathers of preschool children completed online questionnaires that included measures of Adult Attachment Orientation, Parental Persuasive-Controlling Feeding Practices, and Child Self-Regulation of Eating. Structural equation modeling revealed a significant relationship between parental anxious attachment and child self-regulatory abilities, which was fully mediated by parental persuasive-controlling feeding. Also as predicted, parents' avoidant attachment was found to be unrelated to persuasive-controlling feeding and child self-regulated eating. Findings suggest that parents with an anxious attachment orientation may be more likely than other parents to try to use persuasive techniques to control their children's food intake, which may impair children's ability to regulate their food intake, increasing their obesity risk. Implications for intervention are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Parental bonds and body dissatisfaction in a clinical sample: The mediating roles of attachment anxiety and media internalization.

PubMed

Grenon, Renee; Tasca, Giorgio A; Maxwell, Hilary; Balfour, Louise; Proulx, Genevieve; Bissada, Hany

2016-12-01

We evaluated an attachment theory model in which mother and father care were hypothesized to be indirectly related to body dissatisfaction mediated by attachment anxiety and media internalization. Participants were 232 women diagnosed with an eating disorder who completed a retrospective measure of parental bonds, and measures of attachment anxiety, media internalization, and body image. Mother care was negatively associated with body dissatisfaction, suggesting that recollection of mothers as less caring was directly related to poorer body image. Lower father care, was indirectly associated with greater body dissatisfaction mediated by higher attachment anxiety and higher media internalization. That is, women with an eating disorder who recollected fathers as less caring had higher attachment anxiety, which was related to greater internalizing of media-related thin ideals, that in turn was associated with poorer body image. Mothers and fathers may impact body dissatisfaction by differing mechanisms in clinical samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adolescent-parent attachment as a mediator of relations between parenting and adolescent social behavior and wellbeing in China.

PubMed

Cai, Mengfei; Hardy, Sam A; Olsen, Joseph A; Nelson, David A; Yamawaki, Niwako

2013-01-01

The purpose of this study was to examine links between parenting dimensions (authoritative parenting, psychological control, and parental authority) and adolescent wellbeing (self-esteem, autonomy, and peer attachments) as mediated by parent-teen attachment, among Chinese families. The sample included 298 Chinese adolescents, ages 15-18 years (M(age) = 16.36, SD = .68; 60% female). The mediation model was examined using path analyses (one model with parental authority as overprotection, and one with it as perceived behavioral control). To improve model fit a direct path was added from authoritative parenting to autonomy. Authoritative parenting was positively predictive of attachment, while psychological control and overprotection (but not behavioral control) were negative predictors. In turn, adolescent-parent attachment was positively related to the three outcomes. Lastly, the model paths did not differ by adolescent gender. These findings suggest that parenting behaviors may play a crucial role in adolescent social behaviors and wellbeing via adolescent-parent attachment.

Experiential avoidance mediates the link between maternal attachment style and theory of mind.

PubMed

Vanwoerden, Salome; Kalpakci, Allison H; Sharp, Carla

2015-02-01

Theoretical and empirical models suggest a relation between attachment style and theory of mind (ToM) in childhood and adulthood; however, this link has not been evaluated to the same extent in adolescence. Additionally, these models typically fail to consider mechanisms by which attachment style affects ToM abilities. The present study sought to test a mediational model in which experiential avoidance mediates the relation between maternal attachment style and ToM. A sample of 282 adolescents (Mage=15.42years, SD=1.44, 62.8% female) was recruited from an inpatient psychiatric hospital. Findings revealed that maternal attachment style in females was related to ToM, through experiential avoidance. Specifically, those with a disorganized maternal attachment were most likely to engage in experiential avoidant cognitive and emotional strategies, which in turn related to lower levels of ToM ability. Implications and areas for future research are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Multi-risk infants: predicting attachment security from sociodemographic, psychosocial, and health risk among African-American preterm infants.

PubMed

Candelaria, Margo; Teti, Douglas M; Black, Maureen M

2011-08-01

Ecological and transactional theories link child outcomes to accumulated risk. This study hypothesized that cumulative risk was negatively related to attachment, and that maternal sensitivity mediated linkages between risk and attachment. One hundred and twelve high-risk African-American premature infant-mother dyads participated. Psychosocial (maternal depression, stress and self-efficacy) and sociodemographic risk (poverty, maternal education, marital status) were maternal self-report (0-4 months). Infant health risk was obtained from hospital charts. Infant-mother attachment (12 months) and maternal sensitivity (4 months) were assessed with Q-sort measures. Psychosocial and sociodemographic risk, but not infant health risk, negatively related to attachment. Both were mediated by maternal sensitivity. The impact of risk domains on attachment security was mediated by maternal sensitivity. Results emphasize the need for early intervention programs targeting premature infants to identify and address environmental and personal factors that place parenting at risk. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

Parental attachment and Chinese adolescents' delinquency: The mediating role of moral disengagement.

PubMed

Bao, Zhenzhou; Zhang, Wei; Lai, Xuefen; Sun, Wenqiang; Wang, Yanhui

2015-10-01

There is substantial literature documenting the negative association between secure parental attachment and lower adolescent delinquency, but little is known about the mediating mechanisms (i.e., how does parental attachment relate to delinquency?) underlying this relation. The present study examined whether secure parental attachment would be indirectly related to lower adolescent delinquency through lower adolescent moral disengagement. A total of 1766 adolescents (44% male; mean age = 14.25 years, SD = 1.54) living in an urban area of southern China completed anonymous questionnaires regarding parental attachment, moral disengagement and delinquency. After controlling for gender, age, socioeconomic status, and school variable, it was found that secure parental attachment was negatively associated with adolescent delinquency and this negative association was fully mediated by the extent of adolescent moral disengagement. These findings contribute to an understanding of the mechanisms underlying the development of adolescent delinquency and have important implications for intervention. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Eating psychopathology amongst athletes: links to current attachment styles.

PubMed

Shanmugam, Vaithehy; Jowett, Sophia; Meyer, Caroline

2012-01-01

The aims of the study were two-fold; first to determine the associations between current attachment styles, and eating psychopathology amongst athletes, and second to simultaneously assess the mediating effects of self-esteem, perfectionism, and depression in this association. Four hundred and eleven British athletes completed self-report instruments pertaining to eating psychopathology, attachment styles, self-esteem, depression, and perfectionism. Athletes who scored highly on both avoidant and anxious attachment styles, reported elevated eating psychopathology scores. However, such associations were indirect and mediated via athletes' levels of self-esteem, self-critical perfectionism, and depression, with self-esteem and depression identified as more salient mediators than self-critical perfectionism. The current findings provide evidence to suggest that insecure attachment styles influence athletes' eating psychopathology via their impact on self-esteem, depression, and self-critical perfectionism. Moreover, self-esteem and depression may play more significant role in transferring the impact of insecure attachment styles on elevated eating psychopathology. Copyright © 2011 Elsevier Ltd. All rights reserved.

Role of a bacillus Calmette-Guérin fibronectin attachment protein in BCG-induced antitumor activity.

PubMed

Zhao, W; Schorey, J S; Bong-Mastek, M; Ritchey, J; Brown, E J; Ratliff, T L

2000-04-01

Intravesical Mycobacterium bovis bacillus Calmette-Gu*erin (BCG) is the treatment of choice for superficial bladder cancer. Previous studies showed that attachment of BCG to fibronectin within the bladder was necessary for mediation of the antitumor response. Further studies identified a bacterial receptor, fibronectin attachment protein (FAP), as an important mediator of BCG attachment to fibronectin. In vitro studies showed that a stable BCG/fibronectin interaction was dependent on FAP binding to fibronectin; however, no role for FAP in the attachment of BCG in vivo has been characterized. We now report the cloning of the M. bovis BCG FAP (FAP-B) and demonstrate an important role for FAP in the in vivo attachment of BCG to the bladder wall and in the induction of BCG-mediated antitumor activity. The predicted amino acid sequence for FAP-B shows 61% and 71% homology, respectively, with Mycobacterium avium FAP (FAP-A) and Mycobacterium leprae FAP (FAP-L). Rabbit polyclonal antibodies against Mycobacterium vaccae FAP (FAP-V) reacted with all 3 recombinant FAP proteins on Western blots. Functional studies show FAP-B to bind fibronectin via the highly conserved attachment regions previously identified for FAP-A and FAP-L and also to competitively inhibit attachment of BCG to matrix fibronectin. In vivo studies show FAP to be a necessary protein for the stable attachment of BCG to the bladder wall. Moreover, stable binding of BCG via FAP was shown to be necessary for the expression of BCG-induced antitumor activity. Our results demonstrate a biological role for FAP in the mediation of BCG-induced antitumor activity.

Young adult's attachment style as a partial mediator between maternal functioning and young adult offsprings' functioning.

PubMed

Ruiz, Sarah K; Harris, Susan J; Martinez, Pedro; Gold, Philip M; Klimes-Dougan, Bonnie

2018-05-01

The quality of our early attachment relationships with primary caregivers is carried forward to new developmental domains, including interpersonal contexts in adulthood. One of the factors that can disrupt early attachment is maternal depression, which may be associated with less responsive care and may impede the development of a secure attachment. Moreover, this disruption in secure attachment may act as a mechanism by which offspring of depressed mothers are more likely to experience their own psychopathology. In this study we predicted that attachment anxiety and avoidance would mediate the relationship between maternal depression diagnosis and functional impairment predicting young adult offspring's functional impairment. This study utilized longitudinal data from 98 families with clinically diagnosed depressed and well mothers, and two of their young adult children, an older and younger sibling (N = 123, Female = 75, Mage = 22.09, SD = 2.57). Mother's and young adult children's functioning was based on clinical ratings on the Global Assessment Scale. Attachment was based on the young adult's self-report on the Experiences in Close Relationships. Results indicate that maternal diagnosis and functional impairment predicted offspring's functional impairment. This relationship was partially mediated through offspring's attachment anxiety, but not attachment avoidance. The mediator and outcome variable were measured concurrently, thus causal implications are limited. Our study provides critical evidence that early experiences with depressed mothers may have influence into young adulthood in typical and atypical domains of development. This work extends our understanding of the impact of early experiences in long-term development, and may have treatment implications for intervening on both maternal and romantic relationships to improve attachment. Copyright © 2018 Elsevier B.V. All rights reserved.

Stressful Life Events and Depressive Symptomatology Among Basque Adolescents: The Mediating Role of Attachment Representations.

PubMed

Aliri, Jone; Muela, Alexander; Gorostiaga, Arantxa; Balluerka, Nekane; Aritzeta, Aitor; Soroa, Goretti

2018-01-01

The occurrence of stressful life events is a risk factor for psychopathology in adolescence. Depression is a problem of notable clinical importance that has a negative psychosocial impact on adolescents and which has considerable social, educational, and economic costs. The aim of this study was to examine the relationship between stressful life events and depressive symptomatology in adolescence, taking into account the effect that attachment representations may have on this relation. Participants were 1653 adolescents (951 girls) aged between 13 and 18 years. The sample was selected by means of a random sampling procedure based on the availability of schools to participate. Data were collected at two time points: attachment and stressful life events were assessed first, and symptoms of depression were evaluated eight to nine months later. Two time points were used in order to better analyze the mediating role of attachment security. Stressful life events were recorded using the Inventory of Stressful Life Events, attachment was evaluated by the Inventory of Parent and Peer Attachment (mother, father, and peer versions), and depressive symptomatology was assessed through the Children's Depression Scale. In all cases, the Basque version of these scales was used. The results indicated that attachment to parents was a mediating variable in the relationship between stressful life events and depressive symptomatology. Contrary to what we expected, the results indicate that stressful life events did not have a negative effect on peer attachment, and neither did the latter variable act as a mediator of the relationship between stressful life events and depressive symptoms. It can be concluded that attachment-based interventions may be especially useful for reducing depression symptoms among adolescents. The findings also suggest a role for interventions that target parent-child attachment relationships.

Assaying effector function in planta using double-barreled particle bombardment.

PubMed

Kale, Shiv D; Tyler, Brett M

2011-01-01

The biolistic transient gene expression assay is a beneficial tool for studying gene function in vivo. However, biolistic transient assay systems have inherent pitfalls that often cause experimental inaccuracies such as poor transformation efficiency, which can be confused with biological phenomena. The double-barreled gene gun device is an inexpensive and highly effective attachment that enables statistically significant data to be obtained with one-tenth the number of experimental replicates compared to conventional biolistic assays. The principle behind the attachment is to perform two simultaneous bombardments with control and test DNA preparations onto the same leaf. The control bombardment measures the efficiency of the transformation while the ratio of the test bombardment to the control bombardment measures the activity of the gene of interest. With care, the ratio between the pair of bombardments can be highly reproducible from bombardment to bombardment. The double-barreled attachment has been used to study plant resistance (R) gene-mediated responses to effectors, induction and suppression of cell death by a wide variety of pathogen and host molecules, and the role of oömycete effector RXLR motifs in cell reentry.

Effects of Adult Romantic Attachment and Social Support on Resilience and Depression in Individuals with Spinal Cord Injuries

PubMed Central

Dodd, Zane; Warren, Ann Marie; Riggs, Shelley; Clark, Mike

2015-01-01

Background: Spinal cord injury (SCI) can cause psychological consequences that negatively affect quality of life. It is increasingly recognized that factors such as resilience and social support may produce a buffering effect and are associated with improved health outcomes. However the influence of adult attachment style on an individual’s ability to utilize social support after SCI has not been examined. Objective: The purpose of this study was to examine relationships between adult romantic attachment perceived social support depression and resilience in individuals with SCI. In addition we evaluated potential mediating effects of social support and adult attachment on resilience and depression. Methods: Participants included 106 adults with SCI undergoing inpatient rehabilitation. Individuals completed measures of adult attachment (avoidance and anxiety) social support resilience and depression. Path analysis was performed to assess for presence of mediation effects. Results: When accounting for the smaller sample size support was found for the model (comparative fit index = .927 chi square = 7.86 P = .01 β = -0.25 standard error [SE] = -2.93 P < .05). The mediating effect of social support on the association between attachment avoidance and resilience was the only hypothesized mediating effect found to be significant (β = -0.25 SE = -2.93 P < .05). Conclusion: Results suggest that individuals with SCI with higher levels of attachment avoidance have lower perceived social support which relates to lower perceived resilience. Assessing attachment patterns during inpatient rehabilitation may allow therapists to intervene to provide greater support. PMID:26364285

Childhood maltreatment and problematic social media use: The role of attachment and depression.

PubMed

Worsley, Joanne D; McIntyre, Jason C; Bentall, Richard P; Corcoran, Rhiannon

2018-05-25

Childhood maltreatment is associated with many maladaptive outcomes. This study sought to examine the association between childhood maltreatment and problematic social media use using a cross-sectional sample of young adults aged 17-25 years (n = 1029). Specifically, we studied whether the relationship is mediated through (i) attachment anxiety, (ii) attachment avoidance, or (iii) both attachment dimensions operating in series with depressive symptoms. Results revealed that a history of childhood maltreatment was significantly associated with more problematic social media use. Both anxious and avoidant attachment dimensions independently mediated the relationship between childhood maltreatment and problematic use of social media, but in opposing directions. Avoidant attachment was associated with less problematic social media use, whilst anxious attachment was associated with more problematic social media use. Avoidant attachment and depressive symptoms in series accounted for part of the relationship between childhood maltreatment and problematic social media use. Anxious attachment and depressive symptoms in series fully mediated the relationship between childhood maltreatment and problematic social media use. The results suggest that childhood maltreatment may influence social media use directly, but also indirectly. People experiencing depressive symptoms may overuse social media in an attempt to alleviate their distress. However, causality cannot be established with the current design. Copyright © 2018. Published by Elsevier B.V.

Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression.

PubMed

Mack, D R; Michail, S; Wei, S; McDougall, L; Hollingsworth, M A

1999-04-01

Probiotic agents, live microorganisms with beneficial effects for the host, may offer an alternative to conventional antimicrobials in the treatment and prevention of enteric infections. The probiotic agents Lactobacillus plantarum 299v and Lactobacillus rhamnosus GG quantitatively inhibited the adherence of an attaching and effacing pathogenic Escherichia coli to HT-29 intestinal epithelial cells but did not inhibit adherence to nonintestinal HEp-2 cells. HT-29 cells were grown under conditions that induced high levels of either MUC2 or MUC3 mRNA, but HEp-2 cells expressed only minimal levels of MUC2 and no MUC3 mRNA. Media enriched for MUC2 and MUC3 mucin were added exogenously to binding assays and were shown to be capable of inhibiting enteropathogen adherence to HEp-2 cells. Incubation of L. plantarum 299v with HT-29 cells increased MUC2 and MUC3 mRNA expression levels. From these in vitro studies, we propose the hypothesis that the ability of probiotic agents to inhibit adherence of attaching and effacing organisms to intestinal epithelial cells is mediated through their ability to increase expression of MUC2 and MUC3 intestinal mucins.

Internalized Homophobia and Drug Use in a National Cohort of Gay and Bisexual Men: Examining Depression, Sexual Anxiety, and Gay Community Attachment as Mediating Factors.

PubMed

Moody, Raymond L; Starks, Tyrel J; Grov, Christian; Parsons, Jeffrey T

2018-05-01

The minority stress process of internalized homophobia (IH) has been associated with a range of adverse health outcomes among gay and bisexual men (GBM). However, evidence is mixed regarding the effect of IH on drug use, suggesting the potential role of multiple mediated pathways. Researchers have linked depression, sexual anxiety, and gay community attachment with IH. Depression, sexual anxiety, and gay community attachment have also been linked with drug use and drug-related problems suggesting potential mediating roles. A U.S. national sample of 1071 HIV-negative GBM completed at-home surveys, including measures of sociodemographic characteristics, IH, depression, sexual anxiety, gay community attachment, and drug use and associated problems. Adjusting for sociodemographic characteristics, depression mediated the association between IH and recent drug use. IH was positively associated with depression, and depression was positively associated with recent drug use. Gay community attachment partially mediated drug-related problems. IH had a positive direct association with drug-related problems and a negative direct association with gay community attachment. Gay community attachment had a positive association with drug-related problems. IH was positively associated with sexual anxiety, but sexual anxiety was not associated with either drug outcome. Efforts to reduce IH among HIV-negative GBM are likely to have a positive impact on mental health problems, as well as reduce risk for drug use and drug-related problems. Gay communities could provide the social support necessary for reducing IH; however, emphasis on community level interventions that address factors that increase risk for drug-related problems remains important.

Nanoparticle bioconjugate for controlled cellular delivery of doxorubicin

NASA Astrophysics Data System (ADS)

Sangtani, Ajmeeta; Petryayeva, Eleonora; Wu, Miao; Susumu, Kimihiro; Oh, Eunkeu; Huston, Alan L.; Lasarte-Aragones, Guillermo; Medintz, Igor L.; Algar, W. Russ; Delehanty, James B.

2018-02-01

Nanoparticle (NP)-mediated drug delivery offers the potential to overcome limitations of systemic delivery, including the ability to specifically target cargo and control release of NP-associated drug cargo. Doxorubicin (DOX) is a widely used FDA-approved cancer therapeutic; however, multiple side effects limit its utility. Thus, there is wide interest in modulating toxicity after cell delivery. Our goal here was to realize a NP-based DOX-delivery system that can modulate drug toxicity by controlling the release kinetics of DOX from the surface of a hard NP carrier. To achieve this, we employed a quantum dot (QD) as a central scaffold which DOX was appended via three different peptidyl linkages (ester, disulfide, hydrazone) that are cleavable in response to various intracellular conditions. Attachment of a cell penetrating peptide (CPP) containing a positively charged polyarginine sequence facilitates endocytosis of the ensemble. Polyhistidine-driven metal affinity coordination was used to self-assemble both peptides to the QD surface, allowing for fine control over both the ratio of peptides attached to the QD as well as DOX dose delivered to cells. Microplate-based Förster resonance energy transfer assays confirmed the successful ratiometric assembly of the conjugates and functionality of the linkages. Cell delivery experiments and cytotoxicity assays were performed to compare the various cleavable linkages to a control peptide where DOX is attached through an amide bond. The role played by various attachment chemistries used in QD-peptide-drug assemblies and their implications for the rationale in design of NPbased constructs for drug delivery is described here.

HaCaT anchorage blockade leads to oxidative stress, DNA damage and DNA methylation changes.

PubMed

da Silva, Rodrigo A; Sammartino Mariano, Flavia; Planello, Aline C; Line, Sergio R P; de Souza, Ana Paula

2015-07-01

Cell adhesion plays an important role in neoplastic transformation. Thus, anchorage-independent growth and epithelial-mesenchymal transition, which are features associated to anoikis-resistance, are vital steps in cancer progression and metastatic colonization. Cell attachment loss may induce intracellular oxidative stress, which triggers DNA damage as methylation changes. HaCaT lineage cells were submitted to periods of 1, 3, 5 and 24 h of anchorage blockage with the purpose of study of oxidative stress effect on changes in the DNA methylation pattern, derived from attachment blockade. Through this study, HaCaT anchorage blockage-induced oxidative stress was reported to mediate alterations in global DNA methylation changes and into TP53 gene promoter pattern during anoikis-resistance acquisition. Furthermore, at the first experimental time-periods (1, 3 and 5 h), genome hypermethylation was found; however, genome hypomethylation was observed in later time-periods (24 h) of attachment impediment. The TP 53 methylation analyses were performed after 24 h of replated anoikis-resistance cells and same methylation pattern was observed, occurring an early (1 and 3 h) hypermethylation that was followed by late (5 and 24 h) hypomethylation. However, LINE-1, a marker of genomic instability, was perceived in time-dependent hypomethylation. The mRNA levels of the DNMTs enzymes were influenced by cell attachment blockage, but non-conclusive results were obtained in order to match DNMTs transcription to pattern methylation results. In conclusion, DNA damage was found, leaded by oxidative stress that has come up from HaCaT anchorage blockade, which rises a global genome hypomethylation tendency as consequence, which might denote genomic instability.

Predictors of satisfaction in geographically close and long-distance relationships.

PubMed

Lee, Ji-yeon; Pistole, M Carole

2012-04-01

In this study, the authors examined geographically close (GCRs) and long-distance (LDRs) romantic relationship satisfaction as explained by insecure attachment, self-disclosure, gossip, and idealization. After college student participants (N = 536) completed a Web survey, structural equation modeling (SEM) multigroup analysis revealed that the GCR and LDR models were nonequivalent, as expected. Self-disclosure mediated the insecure attachment-idealization path differently in GCRs and in LDRs. Self-disclosure was positively associated with idealization in GCRs and negatively associated with idealization in LDRs, with the insecure attachment-idealization and the insecure attachment-satisfaction paths negative for both GCRs and LDRs. Furthermore, the insecure attachment-idealization path was stronger than the mediated path, especially for LDRs; the insecure attachment-satisfaction path was stronger than the mediation model for GCRs and LDRs. In other words, the GCR and LDR models differed despite some similarities. For both, with higher insecure (i.e., anxious and avoidant) attachment, the person discloses less to the partner, idealizes the partner less, and is less satisfied with the relationship. Also, people who idealize are more satisfied. In contrast, in LDRs only, with higher insecure attachment, the people tend to gossip more. With higher insecure attachment and with higher self-disclosure, people idealize more in GCRs but idealize less in LDRs. Overall, attachment insecurity explained more idealization and satisfaction in LDRs than in GCRs. Implications are discussed.

Ligand-targeted delivery of small interfering RNAs to malignant cells and tissues.

PubMed

Thomas, Mini; Kularatne, Sumith A; Qi, Longwu; Kleindl, Paul; Leamon, Christopher P; Hansen, Michael J; Low, Philip S

2009-09-01

Potential clinical applications of small interfering RNA (siRNA) are hampered primarily by delivery issues. We have successfully addressed the delivery problems associated with off-site targeting of highly toxic chemotherapeutic agents by attaching the drugs to tumor-specific ligands that will carry the attached cargo into the desired cancer cell. Indeed, several such tumor-targeted drugs are currently undergoing human clinical trials. We now show that efficient targeting of siRNA to malignant cells and tissues can be achieved by covalent conjugation of small-molecular-weight, high-affinity ligands, such as folic acid and DUPA (2-[3-(1, 3-dicarboxy propyl)-ureido] pentanedioic acid), to siRNA. The former ligand binds a folate receptor that is overexpressed on a variety of cancers, whereas the latter ligand binds to prostate-specific membrane antigen that is overexpressed specifically on prostate cancers and the neovasculature of all solid tumors. Using these ligands, we show remarkable receptor-mediated targeting of siRNA to cancer tissues in vitro and in vivo.

Glycosaminoglycans mediate retention of the poxvirus type I interferon binding protein at the cell surface to locally block interferon antiviral responses

PubMed Central

Montanuy, Imma; Alejo, Ali; Alcami, Antonio

2011-01-01

Eradication of smallpox was accomplished 30 yr ago, but poxviral infections still represent a public health concern due to the potential release of variola virus or the emergence of zoonotic poxviruses, such as monkeypox virus. A critical determinant of poxvirus virulence is the inhibition of interferons (IFNs) by the virus-encoded type I IFN-binding protein (IFNα/βBP). This immunomodulatory protein is secreted and has the unique property of interacting with the cell surface in order to prevent IFN-mediated antiviral responses. However, the mechanism of its attachment to the cell surface remains unknown. Using surface plasmon resonance and cell-binding assays, we report that the IFNα/βBP from vaccinia virus, the smallpox vaccine, interacts with cell surface glycosaminoglycans (GAGs). Analysis of the contribution of different regions of the protein to cell surface binding demonstrated that clusters of basic residues in the first immunoglobulin domain mediate GAG interactions. Furthermore, mutation of the GAG-interaction motifs does not affect its IFN-binding and -blocking capacity. Functional conservation of GAG-binding sites is demonstrated for the IFNα/βBP from variola and monkeypox viruses, extending our understanding of immune modulation by the most virulent human poxviruses. These results are relevant for the design of improved vaccines and intervention strategies.—Montanuy, I., Alejo, A., Alcami, A. Glycosaminoglycans mediate retention of the poxvirus type I interferon binding protein at the cell surface to locally block interferon antiviral responses. PMID:21372110

O Antigen Modulates Insect Vector Acquisition of the Bacterial Plant Pathogen Xylella fastidiosa

PubMed Central

Rapicavoli, Jeannette N.; Kinsinger, Nichola; Perring, Thomas M.; Backus, Elaine A.; Shugart, Holly J.; Walker, Sharon

2015-01-01

Hemipteran insect vectors transmit the majority of plant pathogens. Acquisition of pathogenic bacteria by these piercing/sucking insects requires intimate associations between the bacterial cells and insect surfaces. Lipopolysaccharide (LPS) is the predominant macromolecule displayed on the cell surface of Gram-negative bacteria and thus mediates bacterial interactions with the environment and potential hosts. We hypothesized that bacterial cell surface properties mediated by LPS would be important in modulating vector-pathogen interactions required for acquisition of the bacterial plant pathogen Xylella fastidiosa, the causative agent of Pierce's disease of grapevines. Utilizing a mutant that produces truncated O antigen (the terminal portion of the LPS molecule), we present results that link this LPS structural alteration to a significant decrease in the attachment of X. fastidiosa to blue-green sharpshooter foreguts. Scanning electron microscopy confirmed that this defect in initial attachment compromised subsequent biofilm formation within vector foreguts, thus impairing pathogen acquisition. We also establish a relationship between O antigen truncation and significant changes in the physiochemical properties of the cell, which in turn affect the dynamics of X. fastidiosa adhesion to the vector foregut. Lastly, we couple measurements of the physiochemical properties of the cell with hydrodynamic fluid shear rates to produce a Comsol model that predicts primary areas of bacterial colonization within blue-green sharpshooter foreguts, and we present experimental data that support the model. These results demonstrate that, in addition to reported protein adhesin-ligand interactions, O antigen is crucial for vector-pathogen interactions, specifically in the acquisition of this destructive agricultural pathogen. PMID:26386068

O antigen modulates insect vector acquisition of the bacterial plant pathogen Xylella fastidiosa.

PubMed

Rapicavoli, Jeannette N; Kinsinger, Nichola; Perring, Thomas M; Backus, Elaine A; Shugart, Holly J; Walker, Sharon; Roper, M Caroline

2015-12-01

Hemipteran insect vectors transmit the majority of plant pathogens. Acquisition of pathogenic bacteria by these piercing/sucking insects requires intimate associations between the bacterial cells and insect surfaces. Lipopolysaccharide (LPS) is the predominant macromolecule displayed on the cell surface of Gram-negative bacteria and thus mediates bacterial interactions with the environment and potential hosts. We hypothesized that bacterial cell surface properties mediated by LPS would be important in modulating vector-pathogen interactions required for acquisition of the bacterial plant pathogen Xylella fastidiosa, the causative agent of Pierce's disease of grapevines. Utilizing a mutant that produces truncated O antigen (the terminal portion of the LPS molecule), we present results that link this LPS structural alteration to a significant decrease in the attachment of X. fastidiosa to blue-green sharpshooter foreguts. Scanning electron microscopy confirmed that this defect in initial attachment compromised subsequent biofilm formation within vector foreguts, thus impairing pathogen acquisition. We also establish a relationship between O antigen truncation and significant changes in the physiochemical properties of the cell, which in turn affect the dynamics of X. fastidiosa adhesion to the vector foregut. Lastly, we couple measurements of the physiochemical properties of the cell with hydrodynamic fluid shear rates to produce a Comsol model that predicts primary areas of bacterial colonization within blue-green sharpshooter foreguts, and we present experimental data that support the model. These results demonstrate that, in addition to reported protein adhesin-ligand interactions, O antigen is crucial for vector-pathogen interactions, specifically in the acquisition of this destructive agricultural pathogen. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Parent relationship quality and infant-mother attachment.

PubMed

Finger, Brent; Hans, Sydney L; Bernstein, Victor J; Cox, Suzanne M

2009-05-01

This project examined interrelations between father-mother conflict, father support of mother, maternal behavior, and infant-mother attachment within a sample of 79 African American families living in a highly stressed urban community. Father support of mother was not related to maternal parenting behavior or infant attachment. Conflicted mother-father relationships were associated with problematic maternal behavior, low maternal sensitivity, infant attachment insecurity, and infant attachment disorganization. The associations between parental conflict and both infant attachment disorganization and insecurity were buffered in families in which fathers co-resided with the mother. Consistent with theory and prior research, links were also observed between maternal sensitive-responsiveness and infant attachment security and between problematic maternal parenting and infant attachment disorganization. However, maternal parenting behavior did not mediate the relation between parental conflict and infant attachment. Results are discussed with respect to whether and under what circumstances child exposure to parent conflict can have a direct effect on infant-mother attachment that is not mediated through dyadic infant-mother interaction.

Micro and Nano-mediated 3D Cardiac Tissue Engineering

DTIC Science & Technology

2012-09-01

as many forms of heart disease involve stiff scar tissue in the heart. Research Group: Larry Schook Period Sept ’11 to Sept ‘12 Deliverables...to their influence on cell attachment. Modeling disease systems and using recently developed biomaterials on PC biosensors with this new technique...will allow new insight into these problems, enabling researchers to develop more successful therapeutic approaches to clinical disease . VII

Dyadic adjustment and parenting stress in internationally adoptive mothers and fathers: the mediating role of adult attachment dimensions

PubMed Central

Salcuni, Silvia; Miconi, Diana; Altoè, Gianmarco; Moscardino, Ughetta

2015-01-01

Previous research has shown that a positive marital functioning represents a resource in adoptive families, leading to a decrease in parenting stress, but little is known about the factors mediating such a relationship. This study aimed to explore whether adult attachment avoidance and anxiety mediate the effect of dyadic functioning on parenting stress in 90 internationally adoptive couples (mothers and fathers) who had adopted a child (aged 3–10 years) in the last 36 months. Participants completed self-report measures of dyadic adjustment, adult attachment, and parenting stress. A series of path analyses supported the mediation hypothesis, but differentially for mothers and fathers. Among mothers, there was a direct and negative relationship between dyadic adjustment and parenting stress. In addition, a better dyadic adjustment was related to lower levels of attachment anxiety, which in turn were associated with less parenting stress. Among fathers, increased dyadic adjustment was related to lower levels of attachment avoidance, which in turn were associated with reduced parenting stress. These findings suggest the importance of including both mothers and fathers in adoption research. Adoptive parents could benefit from specific interventions aimed at reducing attachment avoidance and anxiety by supporting parental sense of competence and involvement for mothers and fathers, respectively. PMID:26388799

Good partner, good parent: responsiveness mediates the link between romantic attachment and parenting style.

PubMed

Millings, Abigail; Walsh, Judi; Hepper, Erica; O'Brien, Margaret

2013-02-01

This cross-sectional, dyadic questionnaire study examined the contribution of romantic attachment and responsive caregiving to parenting style, investigating both gender and partner effects. One hundred and twenty-five couples with children aged 7 to 8 years completed measures of attachment styles, responsive caregiving toward partner, and parenting styles. Structural Equation Modeling was used to examine the intra- and interpersonal associations between romantic attachment, caregiving responsiveness, and parenting styles. Attachment avoidance and anxiety were both negatively associated with responsive caregiving to partner, which in turn was positively associated with authoritative (optimal) parenting styles and negatively associated with authoritarian and permissive (nonoptimal) parenting styles. Responsive caregiving mediated all links between attachment and parenting, with an additional direct association between attachment anxiety and nonoptimal parenting styles that was not explained by caregiving responsiveness. Findings are discussed with reference to attachment theory.

Adolescent insecure attachment as a predictor of maladaptive coping and externalizing behaviors in emerging adulthood

PubMed Central

Dawson, Anne E.; Allen, Joseph P.; Marston, Emily G.; Hafen, Christopher A.; Schad, Megan M.

2014-01-01

This study investigated whether insecure adolescent attachment organization (i.e., preoccupied and dismissing) longitudinally predicted self- and peer-reported externalizing behavior in emerging adulthood. Secondarily, maladaptive coping strategies were examined for their potential role in mediating the relationship between insecure attachment and future externalizing behaviors. Target participants (N = 184) were given the Adult Attachment Interview (AAI) at age 14 and re-interviewed seven and eight years later with their closest peer. Qualities of both preoccupied and dismissing attachment organization predicted self-reported externalizing behaviors in emerging adulthood eight years later, but only preoccupation was predictive of close-peer reports of emerging adult externalizing behavior. Maladaptive coping strategies only mediated the relationship between a dismissing stance toward attachment and future self-reported externalizing behaviors. Understanding the role of coping and emotional regulation in attachment may help us to understand the unique aspects of both dismissing and preoccupied stances toward attachment. PMID:24995478

Transferrin Receptor 1 Facilitates Poliovirus Permeation of Mouse Brain Capillary Endothelial Cells.

PubMed

Mizutani, Taketoshi; Ishizaka, Aya; Nihei, Coh-Ichi

2016-02-05

As a possible route for invasion of the CNS, circulating poliovirus (PV) in the blood is believed to traverse the blood-brain barrier (BBB), resulting in paralytic poliomyelitis. However, the underlying mechanism is poorly understood. In this study, we demonstrated that mouse transferrin receptor 1 (mTfR1) is responsible for PV attachment to the cell surface, allowing invasion into the CNS via the BBB. PV interacts with the apical domain of mTfR1 on mouse brain capillary endothelial cells (MBEC4) in a dose-dependent manner via its capsid protein (VP1). We found that F-G, G-H, and H-I loops in VP1 are important for this binding. However, C-D, D-E, and E-F loops in VP1-fused Venus proteins efficiently penetrate MBEC4 cells. These results imply that the VP1 functional domain responsible for cell attachment is different from that involved in viral permeation of the brain capillary endothelium. We observed that co-treatment of MBEC4 cells with excess PV particles but not dextran resulted in blockage of transferrin transport into cells. Using the Transwell in vitro BBB model, transferrin co-treatment inhibited permeation of PV into MBEC4 cells and delayed further viral permeation via mTfR1 knockdown. With mTfR1 as a positive mediator of PV-host cell attachment and PV permeation of MBEC4 cells, our results indicate a novel role of TfR1 as a cellular receptor for human PV receptor/CD155-independent PV invasion of the CNS. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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