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Sample records for filamin cooperatively enhance

  1. Filamin A Regulates Caveolae Internalization and Trafficking in Endothelial Cells

    PubMed Central

    Sverdlov, Maria; Shinin, Vasily; Place, Aaron T.; Castellon, Maricela

    2009-01-01

    Transcytosis via caveolae is critical for maintaining vascular homeostasis by regulating the tissue delivery of macromolecules, hormones, and lipids. In the present study, we test the hypothesis that interactions between F-actin cross-linking protein filamin A and caveolin-1 facilitate the internalization and trafficking of caveolae. Small interfering RNA-mediated knockdown of filamin A, but not filamin B, reduced the uptake and transcytosis of albumin by ∼35 and 60%, respectively, without altering the actin cytoskeletal structure or cell–cell adherens junctions. Mobility of both intracellular caveolin-1–green fluorescent protein (GFP)-labeled vesicles measured by fluorescence recovery after photobleaching and membrane-associated vesicles measured by total internal reflection-fluorescence microscopy was decreased in cells with reduced filamin A expression. In addition, in melanoma cells that lack filamin A (M2 cells), the majority of caveolin-1-GFP was localized on the plasma membrane, whereas in cells in which filamin A expression was reconstituted (A7 cells and M2 cells transfected with filamin A-RFP), caveolin-1-GFP was concentrated in intracellular vesicles. Filamin A association with caveolin-1 in endothelial cells was confirmed by cofractionation of these proteins in density gradients, as well as by coimmunoprecipitation. Moreover, this interaction was enhanced by Src activation, associated with increased caveolin-1 phosphorylation, and blocked by Src inhibition. Taken together, these data suggest that filamin A association with caveolin-1 promotes caveolae-mediated transport by regulating vesicle internalization, clustering, and trafficking. PMID:19759182

  2. Does Facial Resemblance Enhance Cooperation?

    PubMed Central

    Giang, Trang; Bell, Raoul; Buchner, Axel

    2012-01-01

    Facial self-resemblance has been proposed to serve as a kinship cue that facilitates cooperation between kin. In the present study, facial resemblance was manipulated by morphing stimulus faces with the participants' own faces or control faces (resulting in self-resemblant or other-resemblant composite faces). A norming study showed that the perceived degree of kinship was higher for the participants and the self-resemblant composite faces than for actual first-degree relatives. Effects of facial self-resemblance on trust and cooperation were tested in a paradigm that has proven to be sensitive to facial trustworthiness, facial likability, and facial expression. First, participants played a cooperation game in which the composite faces were shown. Then, likability ratings were assessed. In a source memory test, participants were required to identify old and new faces, and were asked to remember whether the faces belonged to cooperators or cheaters in the cooperation game. Old-new recognition was enhanced for self-resemblant faces in comparison to other-resemblant faces. However, facial self-resemblance had no effects on the degree of cooperation in the cooperation game, on the emotional evaluation of the faces as reflected in the likability judgments, and on the expectation that a face belonged to a cooperator rather than to a cheater. Therefore, the present results are clearly inconsistent with the assumption of an evolved kin recognition module built into the human face recognition system. PMID:23094095

  3. G Protein-Coupled Receptors Directly Bind Filamin A with High Affinity and Promote Filamin Phosphorylation

    PubMed Central

    2015-01-01

    Although interaction of a few G protein-coupled receptors (GPCRs) with Filamin A, a key actin cross-linking and biomechanical signal transducer protein, has been observed, a comprehensive structure–function analysis of this interaction is lacking. Through a systematic sequence-based analysis, we found that a conserved filamin binding motif is present in the cytoplasmic domains of >20% of the 824 GPCRs encoded in the human genome. Direct high-affinity interaction of filamin binding motif peptides of select GPCRs with the Ig domain of Filamin A was confirmed by nuclear magnetic resonance spectroscopy and isothermal titration calorimetric experiments. Engagement of the filamin binding motif with the Filamin A Ig domain induced the phosphorylation of filamin by protein kinase A in vitro. In transfected cells, agonist activation as well as constitutive activation of representative GPCRs dramatically elicited recruitment and phosphorylation of cellular Filamin A, a phenomenon long known to be crucial for regulating the structure and dynamics of the cytoskeleton. Our data suggest a molecular mechanism for direct GPCR–cytoskeleton coupling via filamin. Until now, GPCR signaling to the cytoskeleton was predominantly thought to be indirect, through canonical G protein-mediated signaling cascades involving GTPases, adenylyl cyclases, phospholipases, ion channels, and protein kinases. We propose that the GPCR-induced filamin phosphorylation pathway is a conserved, novel biochemical signaling paradigm. PMID:26460884

  4. Enhancing Thinking through Cooperative Learning.

    ERIC Educational Resources Information Center

    Davidson, Neil, Ed.; Worsham, Toni, Ed.

    This collection of papers provides a theoretical foundation on current practice in cooperative thinking. The papers offer many practical methods that can be applied to a full range of classroom settings. After an introduction, "HOTSICLE: Higher Order Thinking Skills in Cooperative Learning Environments" (Neil Davidson and Toni Worsham), there are…

  5. The increased risk of predation enhances cooperation

    PubMed Central

    Krams, Indrikis; Bērziņš, Arnis; Krama, Tatjana; Wheatcroft, David; Igaune, Kristīne; Rantala, Markus J.

    2010-01-01

    Theory predicts that animals in adverse conditions can decrease individual risks and increase long-term benefits by cooperating with neighbours. However, some empirical studies suggest that animals often focus on short-term benefits, which can reduce the likelihood that they will cooperate with others. In this experimental study, we tested between these two alternatives by evaluating whether increased predation risk (as a correlate of environmental adversity) enhances or diminishes the occurrence of cooperation in mobbing, a common anti-predator behaviour, among breeding pied flycatchers Ficedula hypoleuca. We tested whether birds would join their mobbing neighbours more often and harass a stuffed predator placed near their neighbours' nests more intensely in areas with a higher perceived risk of predation. Our results show that birds attended mobs initiated by their neighbours more often, approached the stuffed predator significantly more closely, and mobbed it at a higher intensity in areas where the perceived risk of predation was experimentally increased. In such high-risk areas, birds also were more often involved in between-pair cooperation. This study demonstrates the positive impact of predation risk on cooperation in breeding songbirds, which might help in explaining the emergence and evolution of cooperation. PMID:19846454

  6. Enhancing regional security agreements through cooperative monitoring

    SciTech Connect

    Pregenzer, A.L.

    1995-05-01

    This paper proposes that strengthening regional capabilities for formulating and implementing arms control and confidence-building measures is a tangible method of enhancing regional security. It discusses the importance of developing a regional infrastructure for arms control and confidence building and elucidates the role of technology in facilitating regional arms control and confidence-building agreements. In addition, it identifies numerous applications for regional cooperative monitoring in the areas of arms control, resource management, international commerce and disaster response. The Cooperative Monitoring Center at Sandia National Laboratories, whose aim is to help individual countries and regions acquire the tools they need to develop their own solutions to regional problems, is discussed briefly. The paper ends with recommendations for establishing regional cooperative monitoring centers.

  7. Phosphorylation of filamin A by Cdk1 regulates filamin A localization and daughter cell separation.

    PubMed

    Szeto, Sandy G Y; Williams, Elizabeth C; Rudner, Adam D; Lee, Jonathan M

    2015-01-15

    In cell culture, many adherent mammalian cells undergo substantial actin cytoskeleton rearrangement prior to mitosis as they detach from the extracellular matrix and become spherical. At the end of mitosis, the actin cytoskeleton is required for cytokinesis and the reassembly of interphase structures as cells spread and reattach to substrate. To understand the processes regulating mitotic cytoskeletal remodeling, we studied how mitotic phosphorylation regulates filamin A (FLNa). FLNa is an actin-crosslinking protein that was previously identified as a cyclin-dependent kinase 1 (Cdk1) binding partner and substrate in vitro. Using quantitative label-based mass spectrometry, we find that FLNa serines 1084, 1459 and 1533 are phosphorylated in mitotic HeLa cells and all three sites match the phosphorylation consensus sequence of Cdk1. To investigate the functional role of mitotic FLNa phosphorylation, we mutated serines 1084, 1459 and 1533 to nonphosphorylatable alanine residues and expressed GFP-tagged FLNa(S1084A,S1459A,S1533A) (FLNa-AAA GFP) in a FLNa-deficient human melanoma cell line called M2. M2 cells expressing FLNa-AAA GFP have enhanced FLNa-AAA GFP and actin localization at sites of contact between daughter cells, impaired post-mitotic daughter cell separation and defects in cell migration. Therefore, mitotic phosphorylation of FLNa is important for successful cell division and interphase cell behavior. PMID:25445790

  8. Structural Interaction and Functional Regulation of Polycystin-2 by Filamin

    PubMed Central

    Wang, Qian; Dai, Xiao-Qing; Li, Qiang; Wang, Zuocheng; Cantero, María del Rocío; Li, Shu; Shen, Ji; Tu, Jian-Cheng; Cantiello, Horacio; Chen, Xing-Zhen

    2012-01-01

    Filamins are important actin cross-linking proteins implicated in scaffolding, membrane stabilization and signal transduction, through interaction with ion channels, receptors and signaling proteins. Here we report the physical and functional interaction between filamins and polycystin-2, a TRP-type cation channel mutated in 10–15% patients with autosomal dominant polycystic kidney disease. Yeast two-hybrid and GST pull-down experiments demonstrated that the C-termini of filamin isoforms A, B and C directly bind to both the intracellular N- and C-termini of polycystin-2. Reciprocal co-immunoprecipitation experiments showed that endogenous polycystin-2 and filamins are in the same complexes in renal epithelial cells and human melanoma A7 cells. We then examined the effect of filamin on polycystin-2 channel function by electrophysiology studies with a lipid bilayer reconstitution system and found that filamin-A substantially inhibits polycystin-2 channel activity. Our study indicates that filamins are important regulators of polycystin-2 channel function, and further links actin cytoskeletal dynamics to the regulation of this channel protein. PMID:22802962

  9. Enhancing Adult Learning through Cooperative Small Groups.

    ERIC Educational Resources Information Center

    Millis, Barbara J.

    1991-01-01

    Cooperative learning is a structured form of small group work based on interdependence, accountability, group processing, and social skills. In continuing education, cooperative learning can positively affect achievement, multiethnic relationships, self-esteem, retention, and attitudes. (SK)

  10. A meckelin-filamin A interaction mediates ciliogenesis.

    PubMed

    Adams, Matthew; Simms, Roslyn J; Abdelhamed, Zakia; Dawe, Helen R; Szymanska, Katarzyna; Logan, Clare V; Wheway, Gabrielle; Pitt, Eva; Gull, Keith; Knowles, Margaret A; Blair, Edward; Cross, Sally H; Sayer, John A; Johnson, Colin A

    2012-03-15

    MKS3, encoding the transmembrane receptor meckelin, is mutated in Meckel-Gruber syndrome (MKS), an autosomal-recessive ciliopathy. Meckelin localizes to the primary cilium, basal body and elsewhere within the cell. Here, we found that the cytoplasmic domain of meckelin directly interacts with the actin-binding protein filamin A, potentially at the apical cell surface associated with the basal body. Mutations in FLNA, the gene for filamin A, cause periventricular heterotopias. We identified a single consanguineous patient with an MKS-like ciliopathy that presented with both MKS and cerebellar heterotopia, caused by an unusual in-frame deletion mutation in the meckelin C-terminus at the region of interaction with filamin A. We modelled this mutation and found it to abrogate the meckelin-filamin A interaction. Furthermore, we found that loss of filamin A by siRNA knockdown, in patient cells, and in tissues from Flna(Dilp2) null mouse embryos results in cellular phenotypes identical to those caused by meckelin loss, namely basal body positioning and ciliogenesis defects. In addition, morpholino knockdown of flna in zebrafish embryos significantly increases the frequency of dysmorphology and severity of ciliopathy developmental defects caused by mks3 knockdown. Our results suggest that meckelin forms a functional complex with filamin A that is disrupted in MKS and causes defects in neuronal migration and Wnt signalling. Furthermore, filamin A has a crucial role in the normal processes of ciliogenesis and basal body positioning. Concurrent with these processes, the meckelin-filamin A signalling axis may be a key regulator in maintaining correct, normal levels of Wnt signalling. PMID:22121117

  11. ASB2 targets filamins A and B to proteasomal degradation

    PubMed Central

    Heuzé, Mélina L.; Lamsoul, Isabelle; Baldassarre, Massimiliano; Lad, Yatish; Lévêque, Sophie; Razinia, Ziba; Moog-Lutz, Christel; Calderwood, David A.

    2008-01-01

    The ordered series of proliferation and differentiation from hematopoietic progenitor cells is disrupted in leukemia, resulting in arrest of differentiation at immature proliferative stages. Characterizing the molecular basis of hematopoietic differentiation is therefore important for understanding and treating disease. Retinoic acid induces expression of ankyrin repeat-containing protein with a suppressor of cytokine signaling box 2 (ASB2) in acute promyelocytic leukemia cells, and ASB2 expression inhibits growth and promotes commitment, recapitulating an early step critical for differentiation. ASB2 is the specificity subunit of an E3 ubiquitin ligase complex and is proposed to exert its effects by regulating the turnover of specific proteins; however, no ASB2 substrates had been identified. Here, we report that ASB2 targets the actin-binding proteins filamin A and B for proteasomal degradation. Knockdown of endogenous ASB2 in leukemia cells delays retinoic acid-induced differentiation and filamin degradation; conversely, ASB2 expression in leukemia cells induces filamin degradation. ASB2 expression inhibits cell spreading, and this effect is recapitulated by knocking down both filamin A and filamin B. Thus, we suggest that ASB2 may regulate hematopoietic cell differentiation by modulating cell spreading and actin remodeling through targeting of filamins for degradation. PMID:18799729

  12. Cooperative synchronized assemblies enhance orientation discrimination

    PubMed Central

    Samonds, Jason M.; Allison, John D.; Brown, Heather A.; Bonds, A. B.

    2004-01-01

    There is no clear link between the broad tuning of single neurons and the fine behavioral capabilities of orientation discrimination. We recorded from populations of cells in the cat visual cortex (area 17) to examine whether the joint activity of cells can support finer discrimination than found in individual responses. Analysis of joint firing yields a substantial advantage (i.e., cooperation) in fine-angle discrimination. This cooperation increases to more considerable levels as the population of an assembly is increased. The cooperation in a population of six cells provides encoding of orientation with an information advantage that is at least 2-fold in terms of requiring either fewer cells or less time than independent coding. This cooperation suggests that correlated or synchronized activity can increase information. PMID:15096595

  13. Teaching Cooperation to Enhance Creativity--Theoretical Rationale.

    ERIC Educational Resources Information Center

    Herrick, James; Herrick, Penny

    The paper discusses the major components of creativity, the relationship of competition and cooperation to creativity, and a model for teaching cooperation to enhance creativity. Creative behavior is directed toward the imaginative construction of what is desired and its eventual actualization in everyday life. Components of creativity include…

  14. Ureaplasma parvum infection alters filamin a dynamics in host cells

    PubMed Central

    2011-01-01

    Background Ureaplasmas are among the most common bacteria isolated from the human urogenital tract. Ureaplasmas can produce asymptomatic infections or disease characterized by an exaggerated inflammatory response. Most investigations have focused on elucidating the pathogenic potential of Ureaplasma species, but little attention has been paid to understanding the mechanisms by which these organisms are capable of establishing asymptomatic infection. Methods We employed differential proteome profiling of bladder tissues from rats experimentally infected with U. parvum in order to identify host cell processes perturbed by colonization with the microbe. Tissues were grouped into four categories: sham inoculated controls, animals that spontaneously cleared infection, asymptomatic urinary tract infection (UTI), and complicated UTI. One protein that was perturbed by infection (filamin A) was used to further elucidate the mechanism of U. parvum-induced disruption in human benign prostate cells (BPH-1). BPH-1 cells were evaluated by confocal microscopy, immunoblotting and ELISA. Results Bladder tissue from animals actively colonized with U. parvum displayed significant alterations in actin binding proteins (profilin 1, vinculin, α actinin, and filamin A) that regulate both actin polymerization and cell cytoskeletal function pertaining to focal adhesion formation and signal transduction (Fisher's exact test, P < 0.004; ANOVA, P < 0.02). This phenomenon was independent of clinical profile (asymptomatic vs. complicated UTI). We selected filamin A as a target for additional studies. In the BPH-1 model, we confirmed that U. parvum perturbed the regulation of filamin A. Specifically, infected BPH-1 cells exhibited a significant increase in filamin A phosphorylated at serine2152 (P ≤ 0.01), which correlated with impaired proteolysis of the protein and its normal intracellular distribution. Conclusion Filamin A dynamics were perturbed in both models of infection

  15. Peer pressure: Enhancement of cooperation through mutual punishment

    NASA Astrophysics Data System (ADS)

    Yang, Han-Xin; Wu, Zhi-Xi; Rong, Zhihai; Lai, Ying-Cheng

    2015-02-01

    An open problem in evolutionary game dynamics is to understand the effect of peer pressure on cooperation in a quantitative manner. Peer pressure can be modeled by punishment, which has been proved to be an effective mechanism to sustain cooperation among selfish individuals. We investigate a symmetric punishment strategy, in which an individual will punish each neighbor if their strategies are different, and vice versa. Because of the symmetry in imposing the punishment, one might intuitively expect the strategy to have little effect on cooperation. Utilizing the prisoner's dilemma game as a prototypical model of interactions at the individual level, we find, through simulation and theoretical analysis, that proper punishment, when even symmetrically imposed on individuals, can enhance cooperation. Also, we find that the initial density of cooperators plays an important role in the evolution of cooperation driven by mutual punishment.

  16. Peer pressure: enhancement of cooperation through mutual punishment.

    PubMed

    Yang, Han-Xin; Wu, Zhi-Xi; Rong, Zhihai; Lai, Ying-Cheng

    2015-02-01

    An open problem in evolutionary game dynamics is to understand the effect of peer pressure on cooperation in a quantitative manner. Peer pressure can be modeled by punishment, which has been proved to be an effective mechanism to sustain cooperation among selfish individuals. We investigate a symmetric punishment strategy, in which an individual will punish each neighbor if their strategies are different, and vice versa. Because of the symmetry in imposing the punishment, one might intuitively expect the strategy to have little effect on cooperation. Utilizing the prisoner's dilemma game as a prototypical model of interactions at the individual level, we find, through simulation and theoretical analysis, that proper punishment, when even symmetrically imposed on individuals, can enhance cooperation. Also, we find that the initial density of cooperators plays an important role in the evolution of cooperation driven by mutual punishment. PMID:25768472

  17. Enhancing Global Understanding: A Call for Cooperation.

    ERIC Educational Resources Information Center

    Naylor, David T.

    Social studies education will improve if educators favoring global education and law-related education replace counterproductive competition with mutual respect and cooperation. As two of the many curricular approaches clamoring for a just share of elementary and secondary school social studies programs, global education and law-related education…

  18. Enhancing Cooperative Learning in TESOL Teacher Education

    ERIC Educational Resources Information Center

    DelliCarpini, Margo Delli

    2009-01-01

    This paper discusses how a TESOL teacher educator took reflective action in an ESL methods class with the goal of increasing pre-service and in-service teachers' use of cooperative learning (CL) activities in their own ESL classrooms. CL has been at the forefront of educational research and is a frequent topic in methodology textbooks, teacher…

  19. Identification of a filamin docking site on PTP-PEST.

    PubMed

    Playford, Martin P; Lyons, Patrick D; Sastry, Sarita K; Schaller, Michael D

    2006-11-10

    PTP-PEST is a cytoplasmic protein-tyrosine phosphatase (PTP) implicated in the regulation of biological processes such as cell motility, cytokinesis, focal adhesion disassembly, and lymphocyte activation. Using a proteomics approach, filamin-A was identified as a novel interacting protein that bound to GST-PTP-PEST. This interaction was confirmed in vitro and in cells by coimmunoprecipitation. The site of filamin interaction on PTP-PEST was mapped to the fourth proline-rich region (Pro4). PTP-PEST has previously been implicated in the regulation of cytokinesis. In further support of this finding, expression of PTP-PEST in HeLa cells resulted in the formation of multinucleated cells. A PTP-PEST mutant lacking Pro4 and unable to bind filamin-A failed to induce the multinucleated phenotype. Further, depletion of filamin-A in HeLa cells was found to reduce the PTP-PEST-dependent multinucleation phenotype. Hence, we conclude that the interaction of PTP-PEST with filamin-A may function in the control of cytokinesis in mammalian cells. PMID:16973606

  20. Evidence for the mechanosensor function of filamin in tissue development.

    PubMed

    Huelsmann, Sven; Rintanen, Nina; Sethi, Ritika; Brown, Nicholas H; Ylänne, Jari

    2016-01-01

    Cells integrate mechanical properties of their surroundings to form multicellular, three-dimensional tissues of appropriate size and spatial organisation. Actin cytoskeleton-linked proteins such as talin, vinculin and filamin function as mechanosensors in cells, but it has yet to be tested whether the mechanosensitivity is important for their function in intact tissues. Here we tested, how filamin mechanosensing contributes to oogenesis in Drosophila. Mutations that require more or less force to open the mechanosensor region demonstrate that filamin mechanosensitivity is important for the maturation of actin-rich ring canals that are essential for Drosophila egg development. The open mutant was more tightly bound to the ring canal structure while the closed mutant dissociated more frequently. Thus, our results show that an appropriate level of mechanical sensitivity is required for filamins' function and dynamics during Drosophila egg growth and support the structure-based model in which the opening and closing of the mechanosensor region regulates filamin binding to cellular components. PMID:27597179

  1. Filamin-A and Rheological Properties of Cultured Melanoma Cells

    PubMed Central

    Coughlin, Mark F.; Puig-de-Morales, Marina; Bursac, Predrag; Mellema, Matthew; Millet, Emil; Fredberg, Jeffrey J.

    2006-01-01

    Here we report the rheological properties of cultured hsFLNa (filamin-A)-expressing (FIL+) and hsFLNa-deficient (FIL−) melanoma cells. Using magnetic twisting cytometry over a wide range of probing frequencies, and targeting either cortical or deeper cytoskeletal structures, we found that differences in stiffness of FIL+ versus FIL− cells were remarkably small. When probed through deep cytoskeletal structures, FIL+ cells were, at most, 30% stiffer than FIL− cells, whereas when probed through more peripheral cytoskeletal structures FIL− cells were not different except at very high frequencies. The loss tangent, expressed as an effective cytoskeletal temperature, was systematically greater in FIL− than FIL+ cells, but these differences were small and showed that the FIL+ cells were only slightly closer to a solidlike state. To quantify cytoskeletal remodeling, we measured spontaneous motions of beads bound to cortical cytoskeletal structures and found no difference in FIL+ versus FIL− cells. Although mechanical differences between FIL+ and FIL− cells were evident both in cortical and deeper structures, these differences were far smaller than expected based on measurements of the rheology of purified actin-filamin solutions. These findings do not rule out an important contribution of filamin to the mechanical properties of the cortical cytoskeleton, but suggest that effects of filamin in the cortex are not exerted on the length scale of the probe used here. These findings would appear to rule out any important contribution of filamin to the bulk mechanical properties of the cytoplasm, however. Although filamin is present in the cytoplasm, it may be inactive, its mechanical effects may be small compared with other crosslinkers, or mechanical properties of the matrix may be dominated by an overriding role of cytoskeletal prestress. PMID:16387775

  2. Evidence for the mechanosensor function of filamin in tissue development

    PubMed Central

    Huelsmann, Sven; Rintanen, Nina; Sethi, Ritika; Brown, Nicholas H.; Ylänne, Jari

    2016-01-01

    Cells integrate mechanical properties of their surroundings to form multicellular, three-dimensional tissues of appropriate size and spatial organisation. Actin cytoskeleton-linked proteins such as talin, vinculin and filamin function as mechanosensors in cells, but it has yet to be tested whether the mechanosensitivity is important for their function in intact tissues. Here we tested, how filamin mechanosensing contributes to oogenesis in Drosophila. Mutations that require more or less force to open the mechanosensor region demonstrate that filamin mechanosensitivity is important for the maturation of actin-rich ring canals that are essential for Drosophila egg development. The open mutant was more tightly bound to the ring canal structure while the closed mutant dissociated more frequently. Thus, our results show that an appropriate level of mechanical sensitivity is required for filamins’ function and dynamics during Drosophila egg growth and support the structure-based model in which the opening and closing of the mechanosensor region regulates filamin binding to cellular components. PMID:27597179

  3. Enhancing Instruction through Constructivism, Cooperative Learning, and Cloud Computing

    ERIC Educational Resources Information Center

    Denton, David W.

    2012-01-01

    Cloud computing technologies, such as Google Docs and Microsoft Office Live, have the potential to enhance instructional methods predicated on constructivism and cooperative learning. Cloud-based application features like file sharing and online publishing are prompting departments of education across the nation to adopt these technologies.…

  4. New role for space station—Enhanced cooperation with Russia?

    NASA Astrophysics Data System (ADS)

    Leath, Audrey T.

    The Clinton administration's recent discussions with Russia on enhanced space cooperation and a possible joint space station prompted a two-part hearing by the House Science Subcommittee on Space, held on October 6 and 14. Subcommittee members, citing rumors and news stories about a joint station, questioned Presidential Science Advisor Jack Gibbons and NASA Administrator Daniel Goldin on the status of the proposed cooperation and heard from additional witnesses regarding the feasibility of and support for the concept.Gibbons reassured subcommittee members that no decision has yet been made on Russian cooperation, and that Congress would be consulted in the process. He explained that, after the Vancouver Summit, establishment of a Joint Commission headed by Vice President Gore and Russian Prime Minister Chernomyrdin provided an opportunity for enhanced cooperation in space, as well as in such other areas as energy, nuclear safety, the environment, business development, science and technology, and defense diversification. Gibbons testified that the study of a cooperative station program took place concurrently with NASA's work on defining the redesigned U.S. space station, now being referred to as “Alpha.” He affirmed that while Alpha's modular design made it adaptable to a joint effort, it could “be built independent of any Russian participation.”

  5. Mutations in the N-terminal Actin-Binding Domain of Filamin C Cause a Distal Myopathy

    PubMed Central

    Duff, Rachael M.; Tay, Valerie; Hackman, Peter; Ravenscroft, Gianina; McLean, Catriona; Kennedy, Paul; Steinbach, Alina; Schöffler, Wiebke; van der Ven, Peter F.M.; Fürst, Dieter O.; Song, Jaeguen; Djinović-Carugo, Kristina; Penttilä, Sini; Raheem, Olayinka; Reardon, Katrina; Malandrini, Alessandro; Gambelli, Simona; Villanova, Marcello; Nowak, Kristen J.; Williams, David R.; Landers, John E.; Brown, Robert H.; Udd, Bjarne; Laing, Nigel G.

    2011-01-01

    Linkage analysis of the dominant distal myopathy we previously identified in a large Australian family demonstrated one significant linkage region located on chromosome 7 and encompassing 18.6 Mbp and 151 genes. The strongest candidate gene was FLNC because filamin C, the encoded protein, is muscle-specific and associated with myofibrillar myopathy. Sequencing of FLNC cDNA identified a c.752T>C (p.Met251Thr) mutation in the N-terminal actin-binding domain (ABD); this mutation segregated with the disease and was absent in 200 controls. We identified an Italian family with the same phenotype and found a c.577G>A (p.Ala193Thr) filamin C ABD mutation that segregated with the disease. Filamin C ABD mutations have not been described, although filamin A and filamin B ABD mutations cause multiple musculoskeletal disorders. The distal myopathy phenotype and muscle pathology in the two families differ from myofibrillar myopathies caused by filamin C rod and dimerization domain mutations because of the distinct involvement of hand muscles and lack of pathological protein aggregation. Thus, like the position of FLNA and B mutations, the position of the FLNC mutation determines disease phenotype. The two filamin C ABD mutations increase actin-binding affinity in a manner similar to filamin A and filamin B ABD mutations. Cell-culture expression of the c.752T>C (p.Met251)Thr mutant filamin C ABD demonstrated reduced nuclear localization as did mutant filamin A and filamin B ABDs. Expression of both filamin C ABD mutants as full-length proteins induced increased aggregation of filamin. We conclude filamin C ABD mutations cause a recognizable distal myopathy, most likely through increased actin affinity, similar to the pathological mechanism of filamin A and filamin B ABD mutations. PMID:21620354

  6. Mutations in the N-terminal actin-binding domain of filamin C cause a distal myopathy.

    PubMed

    Duff, Rachael M; Tay, Valerie; Hackman, Peter; Ravenscroft, Gianina; McLean, Catriona; Kennedy, Paul; Steinbach, Alina; Schöffler, Wiebke; van der Ven, Peter F M; Fürst, Dieter O; Song, Jaeguen; Djinović-Carugo, Kristina; Penttilä, Sini; Raheem, Olayinka; Reardon, Katrina; Malandrini, Alessandro; Gambelli, Simona; Villanova, Marcello; Nowak, Kristen J; Williams, David R; Landers, John E; Brown, Robert H; Udd, Bjarne; Laing, Nigel G

    2011-06-10

    Linkage analysis of the dominant distal myopathy we previously identified in a large Australian family demonstrated one significant linkage region located on chromosome 7 and encompassing 18.6 Mbp and 151 genes. The strongest candidate gene was FLNC because filamin C, the encoded protein, is muscle-specific and associated with myofibrillar myopathy. Sequencing of FLNC cDNA identified a c.752T>C (p.Met251Thr) mutation in the N-terminal actin-binding domain (ABD); this mutation segregated with the disease and was absent in 200 controls. We identified an Italian family with the same phenotype and found a c.577G>A (p.Ala193Thr) filamin C ABD mutation that segregated with the disease. Filamin C ABD mutations have not been described, although filamin A and filamin B ABD mutations cause multiple musculoskeletal disorders. The distal myopathy phenotype and muscle pathology in the two families differ from myofibrillar myopathies caused by filamin C rod and dimerization domain mutations because of the distinct involvement of hand muscles and lack of pathological protein aggregation. Thus, like the position of FLNA and B mutations, the position of the FLNC mutation determines disease phenotype. The two filamin C ABD mutations increase actin-binding affinity in a manner similar to filamin A and filamin B ABD mutations. Cell-culture expression of the c.752T>C (p.Met251)Thr mutant filamin C ABD demonstrated reduced nuclear localization as did mutant filamin A and filamin B ABDs. Expression of both filamin C ABD mutants as full-length proteins induced increased aggregation of filamin. We conclude filamin C ABD mutations cause a recognizable distal myopathy, most likely through increased actin affinity, similar to the pathological mechanism of filamin A and filamin B ABD mutations. PMID:21620354

  7. Cooperation enhanced by moderate tolerance ranges in myopically selective interactions

    NASA Astrophysics Data System (ADS)

    Chen, Xiaojie; Wang, Long

    2009-10-01

    We present a mode of myopically selective interaction to study the evolutionary prisoner’s dilemma game in scale-free networks. Each individual has a reputation-based tolerance range and only tends to interact with the neighbors whose reputation is within its tolerance range. Moreover, its reputation is assessed in response to the interactions in the neighborhood. Interestingly, we show that moderate values of tolerance range can result in the best promotion of cooperation due to the emergence of group selection mechanism. Furthermore, we study the effects of weighting factor in the assessment rule of reputation on the evolution of cooperation. We also show how cooperation evolves in some extended situations, where an interaction stimulus payment is considered for individuals, and where the strategy and reputation of individuals can spread simultaneously. Our results may enhance the understanding of evolutionary dynamics in graph-structured populations where individuals conditionally play with their neighbors according to some myopic selection criteria.

  8. Local and nonlocal conductance enhancement due to Cooper pair splitting

    NASA Astrophysics Data System (ADS)

    Wei, Jian; Chandrasekhar, V.

    2012-12-01

    Enhanced local conductance due to Andreev reflection is well known for high transparency Normal metal-Superconductor (NS) interface. For low transparency NS junctions, observation of two-electron tunneling contribution (enhanced Andreev reflection) to current was also reported previously. In our recent work [J Wei and V Chandrasekhar, Nat. Phys. 6, 494 (2010)], for a three-terminal Cooper pair splitter geometry, i.e., with two closely placed NS junctions sharing the same S terminal, we were able do a 2D scan of both local and nonlocal differential resistance, since for our ideal tunneling junctions there is little current redistribution (flow from one normal-metal lead to the other via the superconducting lead). In contrast to previous 1D nonlocal resistance measurements, 2D scans clearly show regime with pronounced contribution of the nonlocal processes to both local and nonlocal conductance enhancement. The enhanced local conductance and negative nonlocal resistance are consistent with enhanced Cooper pair splitting, and dynamical Coulomb blockade could be the origin of this enhancement.

  9. Documentation and localization of force-mediated filamin A domain perturbations in moving cells

    NASA Astrophysics Data System (ADS)

    Nakamura, Fumihiko; Song, Mia; Hartwig, John H.; Stossel, Thomas P.

    2014-08-01

    Endogenously and externally generated mechanical forces influence diverse cellular activities, a phenomenon defined as mechanotransduction. Deformation of protein domains by application of stress, previously documented to alter macromolecular interactions in vitro, could mediate these effects. We engineered a photon-emitting system responsive to unfolding of two repeat domains of the actin filament (F-actin) crosslinker protein filamin A (FLNA) that binds multiple partners involved in cell signalling reactions and validated the system using F-actin networks subjected to myosin-based contraction. Expressed in cultured cells, the sensor-containing FLNA construct reproducibly reported FLNA domain unfolding strikingly localized to dynamic, actively protruding, leading cell edges. The unfolding signal depends upon coherence of F-actin-FLNA networks and is enhanced by stimulating cell contractility. The results establish protein domain distortion as a bona fide mechanism for mechanotransduction in vivo.

  10. Nonequilibrium enhancement of Cooper pairing in cold fermion systems

    SciTech Connect

    Robertson, Andrew; Galitski, Victor M.

    2009-12-15

    Nonequilibrium stimulation of superfluidity in trapped Fermi gases is discussed by analogy to the work of Eliashberg [Nonequilibrium Superconductivity, edited by D. N. Langenberg and A. I. Larkin (North-Holland, New York, 1986)] on the microwave enhancement of superconductivity. Optical excitation of the fermions balanced by heat loss due to thermal contact with a boson bath and/or evaporative cooling enables stationary nonequilibrium states to exist. Such a state manifests as a shift of the quasiparticle spectrum to higher energies and this effectively raises the pairing transition temperature. As an illustration, we calculate the effective enhancement of Cooper pairing and superfluidity in both the normal and superfluid phases for a mixture of {sup 87}Rb and {sup 6}Li in the limit of small departure from equilibrium. It is argued that in experiment the desirable effect is not limited to such small perturbations and the effective enhancement of the pairing temperature may be quite large.

  11. Does copy-resistance enhance cooperation in spatial prisoner's dilemma?

    NASA Astrophysics Data System (ADS)

    Shigaki, K.; Kokubo, S.; Tanimoto, J.; Hagishima, A.; Ikegaya, N.

    2012-05-01

    We propose a novel idea for the so-called pairwise-Fermi process by considering copy-resistance when an agent copies a neighbor's strategy, which implies that the focal agent with relatively affluent payoff vis-à-vis social average might be negative to copy her neighbor's strategy even if her payoff is less than the neighbor's payoff. Simulation results reveal that this idea with a revised strategy adaptation process significantly enhances cooperation for prisoner's dilemma games played on time-constant networks.

  12. 75 FR 77821 - Agricultural Water Enhancement Program and Cooperative Conservation Partnership Initiative

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-14

    ...; ] DEPARTMENT OF AGRICULTURE Commodity Credit Corporation Agricultural Water Enhancement Program and Cooperative... agreements with the Natural Resources Conservation Service (NRCS) through either the Agricultural Water... Agricultural Water Enhancement Program Legislative Authority The Agricultural Water Enhancement Program...

  13. DNA supercoiling enhances cooperativity and efficiency of an epigenetic switch

    PubMed Central

    Norregaard, Kamilla; Andersson, Magnus; Sneppen, Kim; Nielsen, Peter Eigil; Brown, Stanley; Oddershede, Lene B.

    2013-01-01

    Bacteriophage λ stably maintains its dormant prophage state but efficiently enters lytic development in response to DNA damage. The mediator of these processes is the λ repressor protein, CI, and its interactions with λ operator DNA. This λ switch is a model on the basis of which epigenetic switch regulation is understood. Using single molecule analysis, we directly examined the stability of the CI-operator structure in its natural, supercoiled state. We marked positions adjacent to the λ operators with peptide nucleic acids and monitored their movement by tethered particle tracking. Compared with relaxed DNA, the presence of supercoils greatly enhances juxtaposition probability. Also, the efficiency and cooperativity of the λ switch is significantly increased in the supercoiled system compared with a linear assay, increasing the Hill coefficient. PMID:24101469

  14. DNA supercoiling enhances cooperativity and efficiency of an epigenetic switch.

    PubMed

    Norregaard, Kamilla; Andersson, Magnus; Sneppen, Kim; Nielsen, Peter Eigil; Brown, Stanley; Oddershede, Lene B

    2013-10-22

    Bacteriophage λ stably maintains its dormant prophage state but efficiently enters lytic development in response to DNA damage. The mediator of these processes is the λ repressor protein, CI, and its interactions with λ operator DNA. This λ switch is a model on the basis of which epigenetic switch regulation is understood. Using single molecule analysis, we directly examined the stability of the CI-operator structure in its natural, supercoiled state. We marked positions adjacent to the λ operators with peptide nucleic acids and monitored their movement by tethered particle tracking. Compared with relaxed DNA, the presence of supercoils greatly enhances juxtaposition probability. Also, the efficiency and cooperativity of the λ switch is significantly increased in the supercoiled system compared with a linear assay, increasing the Hill coefficient. PMID:24101469

  15. Cooperative Learning and Enhanced Communication: Effects on Student Performance, Retention, and Attitudes in General Chemistry.

    ERIC Educational Resources Information Center

    Dougherty, R. C.; And Others

    1995-01-01

    Examines the effects of cooperative learning and enhanced communication on student performance, retention, and attitudes in general chemistry. Results indicate that cooperative homework, cooperative quizzes, electronic-mail communication, and open office hours were associated with significantly higher student retention and higher performance on…

  16. Enhancing Student Performance through Cooperative Learning in Physical Sciences

    ERIC Educational Resources Information Center

    Gupta, Madan L.

    2004-01-01

    Students in a physical sciences course were introduced to cooperative learning at the University of Queensland, Gatton Campus. Groups of four to five students worked together in tutorial and practical sessions. Mid-term and practical examinations were abolished and 40% of total marks were allocated to the cooperative learning activities. A peer-…

  17. Filamin Interacts with Epithelial Sodium Channel and Inhibits Its Channel Function*

    PubMed Central

    Wang, Qian; Dai, Xiao-Qing; Li, Qiang; Tuli, Jagdeep; Liang, Gengqing; Li, Shayla S.; Chen, Xing-Zhen

    2013-01-01

    Epithelial sodium channel (ENaC) in the kidneys is critical for Na+ balance, extracellular volume, and blood pressure. Altered ENaC function is associated with respiratory disorders, pseudohypoaldosteronism type 1, and Liddle syndrome. ENaC is known to interact with components of the cytoskeleton, but the functional roles remain largely unclear. Here, we examined the interaction between ENaC and filamins, important actin filament components. We first discovered by yeast two-hybrid screening that the C termini of ENaC α and β subunits bind filamin A, B, and C, and we then confirmed the binding by in vitro biochemical assays. We demonstrated by co-immunoprecipitation that ENaC, either overexpressed in HEK, HeLa, and melanoma A7 cells or natively expressed in LLC-PK1 and IMCD cells, is in the same complex with native filamin. Furthermore, the biotinylation and co-immunoprecipitation combined assays showed the ENaC-filamin interaction on the cell surface. Using Xenopus oocyte expression and two-electrode voltage clamp electrophysiology, we found that co-expression of an ENaC-binding domain of filamin substantially reduces ENaC channel function. Western blot and immunohistochemistry experiments revealed that the filamin A C terminus (FLNAC) modestly reduces the expression of the ENaC α subunit in oocytes and A7 cells. After normalizing the current by plasma membrane expression, we found that FLNAC results in ∼50% reduction in the ENaC channel activity. The inhibitory effect of FLNAC was confirmed by lipid bilayer electrophysiology experiments using purified ENaC and FLNAC proteins, which showed that FLNAC substantially reduces ENaC single channel open probability. Taken together, our study demonstrated that filamin reduces ENaC channel function through direct interaction on the cell surface. PMID:23161538

  18. Filamin C: a novel component of the KCNE2 interactome during hypoxia

    PubMed Central

    Neethling, Annika; Mouton, Jomien; Corfield, Valerie; de Villiers, Carin; Kinnear, Craig; Loos, Ben

    2016-01-01

    Summary Aim KCNE2 encodes for the potassium voltage-gated channel, KCNE2. Mutations in KCNE2 have been associated with long-QT syndrome (LQTS). While KCNE2 has been extensively studied, the functions of its C-terminal domain remain inadequately described. Here, we aimed to elucidate the functions of this domain by identifying its protein interactors using yeast two-hybrid analysis. Methods The C-terminal domain of KCNE2 was used as bait to screen a human cardiac cDNA library for putative interacting proteins. Co-localisation and co-immunoprecipitation analyses were used for verification. Results Filamin C (FLNC) was identified as a putative interactor with KCNE2. FLNC and KCNE2 co-localised within the cell, however, a physical interaction was only observed under hypoxic conditions. Conclusion The identification of FLNC as a novel KCNE2 ligand not only enhances current understanding of ion channel function and regulation, but also provides valuable information about possible pathways likely to be involved in LQTS pathogenesis. PMID:26956495

  19. Hypoxia-induced and calpain-dependent cleavage of filamin A regulates the hypoxic response.

    PubMed

    Zheng, Xiaowei; Zhou, Alex-Xianghua; Rouhi, Pegah; Uramoto, Hidetaka; Borén, Jan; Cao, Yihai; Pereira, Teresa; Akyürek, Levent M; Poellinger, Lorenz

    2014-02-18

    The cellular response to hypoxia is regulated by hypoxia-inducible factor-1α and -2α (HIF-1α and -2α). We have discovered that filamin A (FLNA), a large cytoskeletal actin-binding protein, physically interacts with HIF-1α and promotes tumor growth and angiogenesis. Hypoxia induces a calpain-dependent cleavage of FLNA to generate a naturally occurring C-terminal fragment that accumulates in the cell nucleus. This fragment interacts with the N-terminal portion of HIF-1α spanning amino acid residues 1-390 but not with HIF-2α. In hypoxia this fragment facilitates the nuclear localization of HIF-1α, is recruited to HIF-1α target gene promoters, and enhances HIF-1α function, resulting in up-regulation of HIF-1α target gene expression in a hypoxia-dependent fashion. These results unravel an important mechanism that selectively regulates the nuclear accumulation and function of HIF-1α and potentiates angiogenesis and tumor progression. PMID:24550283

  20. Filamin A Protein Interacts with Human Immunodeficiency Virus Type 1 Gag Protein and Contributes to Productive Particle Assembly*

    PubMed Central

    Cooper, JoAnn; Liu, Ling; Woodruff, Elvin A.; Taylor, Harry E.; Goodwin, J. Shawn; D'Aquila, Richard T.; Spearman, Paul; Hildreth, James E. K.; Dong, Xinhong

    2011-01-01

    HIV-1 Gag precursor directs virus particle assembly and release. In a search for Gag-interacting proteins that are involved in late stages of the HIV-1 replication cycle, we performed yeast two-hybrid screening against a human cDNA library and identified the non-muscle actin filament cross-linking protein filamin A as a novel Gag binding partner. The 280-kDa filamin A regulates cortical actin network dynamics and participates in the anchoring of membrane proteins to the actin cytoskeleton. Recent studies have shown that filamin A facilitates HIV-1 cell-to-cell transmission by binding to HIV receptors and coreceptors and regulating their clustering on the target cell surface. Here we report a novel role for filamin A in HIV-1 Gag intracellular trafficking. We demonstrate that filamin A interacts with the capsid domain of HIV-1 Gag and that this interaction is involved in particle release in a productive manner. Disruption of this interaction eliminated Gag localization at the plasma membrane and induced Gag accumulation within internal compartments. Moreover, blocking clathrin-dependent endocytic pathways did not relieve the restriction to particle release induced by filamin A depletion. These results suggest that filamin A is involved in the distinct step of the Gag trafficking pathway. The discovery of the Gag-filamin A interaction may provide a new therapeutic target for the treatment of HIV infection. PMID:21705339

  1. An Enhanced Genetic Approach to Composing Cooperative Learning Groups for Multiple Grouping Criteria

    ERIC Educational Resources Information Center

    Hwang, Gwo-Jen; Yin, Peng-Yeng; Hwang, Chi-Wei; Tsai, Chin-Chung

    2008-01-01

    Cooperative learning is known to be an effective educational strategy in enhancing the learning performance of students. The goal of a cooperative learning group is to maximize all members' learning efficacy. This is accomplished via promoting each other's success, through assisting, sharing, mentoring, explaining, and encouragement. To achieve…

  2. Using Technology-Enhanced, Cooperative, Group-Project Learning for Student Comprehension and Academic Performance

    ERIC Educational Resources Information Center

    Tlhoaele, Malefyane; Suhre, Cor; Hofman, Adriaan

    2016-01-01

    Cooperative learning may improve students' motivation, understanding of course concepts, and academic performance. This study therefore enhanced a cooperative, group-project learning technique with technology resources to determine whether doing so improved students' deep learning and performance. A sample of 118 engineering students, randomly…

  3. Kids Working with Nature: A Cooperative Wildlife Habitat Enhancement Project in the Connelly Creek Nature Area.

    ERIC Educational Resources Information Center

    Scherrer, Wendy Wollam

    1988-01-01

    Describes a project in the Bellingham Cooperative School (Washington) in which teachers and students, along with parents and community volunteers, are involved in a 24-acre wildlife enhancement effort. (TW)

  4. 77 FR 73 - Cooperative Conservation Partnership Initiative and Wetlands Reserve Enhancement Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-03

    ...; ] DEPARTMENT OF AGRICULTURE Natural Resources Conservation Service Commodity Credit Corporation Cooperative Conservation Partnership Initiative and Wetlands Reserve Enhancement Program AGENCY: Natural Resources...). SUMMARY: The Natural Resources Conservation Service (NRCS) announces the availability of...

  5. Filamin A and Big2: a shared endocytic pathway.

    PubMed

    Sheen, Volney L

    2014-01-01

    Neural proliferation, migration and differentiation require reorganization of the actin cytoskeleton and regulation of vesicle trafficking to provide stability in maintaining cell adhesions, allow for changes in cell shape, and establishing cell polarity. Human disorders involving the actin-binding Filamin A (FLNA) and vesicle trafficking Brefeldin-associated guanine exchange factor 2 (BIG2 is encoded by the ARFGEF2 gene) proteins are implicated in these various developmental processes, resulting in a malformation of cortical development called periventricular heterotopia (nodules along the ventricular lining) and microcephaly (small brain). Here we discuss several recent reports from our laboratory that demonstrate a shared role for both proteins in actin-associated vesicle trafficking, which is required to maintain the expression and stability of cell adhesion and cell cycle associated molecules during cortical development. While changes in FLNA and BIG2 have first been linked to disorders involving the central nervous system, increasing reports suggest they are associated with aberrant development of various other organ systems in the body. These studies suggest that vesicle trafficking defects in FLN-GEF dependent pathways may contribute to a much broader phenotype than previously realized. PMID:24709996

  6. Arterial Myogenic Activation through Smooth Muscle Filamin A.

    PubMed

    Retailleau, Kevin; Arhatte, Malika; Demolombe, Sophie; Peyronnet, Rémi; Baudrie, Véronique; Jodar, Martine; Bourreau, Jennifer; Henrion, Daniel; Offermanns, Stefan; Nakamura, Fumihiko; Feng, Yuanyi; Patel, Amanda; Duprat, Fabrice; Honoré, Eric

    2016-03-01

    Mutations in the filamin A (FlnA) gene are frequently associated with severe arterial abnormalities, although the physiological role for this cytoskeletal element remains poorly understood in vascular cells. We used a conditional mouse model to selectively delete FlnA in smooth muscle (sm) cells at the adult stage, thus avoiding the developmental effects of the knockout. Basal blood pressure was significantly reduced in conscious smFlnA knockout mice. Remarkably, pressure-dependent tone of the resistance caudal artery was lost, whereas reactivity to vasoconstrictors was preserved. Impairment of the myogenic behavior was correlated with a lack of calcium influx in arterial myocytes upon an increase in intraluminal pressure. Notably, the stretch activation of CaV1.2 was blunted in the absence of smFlnA. In conclusion, FlnA is a critical upstream element of the signaling cascade underlying the myogenic tone. These findings allow a better understanding of the molecular basis of arterial autoregulation and associated disease states. PMID:26923587

  7. Cooperative Clustering Digitizes Biochemical Signaling and Enhances its Fidelity.

    PubMed

    Roob, Edward; Trendel, Nicola; Rein Ten Wolde, Pieter; Mugler, Andrew

    2016-04-12

    Many membrane-bound molecules in cells form small clusters. It has been hypothesized that these clusters convert an analog extracellular signal into a digital intracellular signal and that this conversion increases signaling fidelity. However, the mechanism by which clusters digitize a signal and the subsequent effects on fidelity remain poorly understood. Here we demonstrate using a stochastic model of cooperative cluster formation that sufficient cooperation leads to digital signaling. We show that despite reducing the number of output states, which decreases fidelity, digitization also reduces noise in the system, which increases fidelity. The tradeoff between these effects leads to an optimal cluster size that agrees with experimental measurements. PMID:27074690

  8. Expression, crystallization and preliminary crystallographic data analysis of filamin A repeats 14–16

    SciTech Connect

    Aguda, Adeleke Halilu; Sakwe, Amos Malle; Rask, Lars; Robinson, Robert Charles

    2007-04-01

    The crystallization and crystallographic data analysis of filamin repeats 14–16 are reported. Human filamin A is a 280 kDa protein involved in actin-filament cross-linking. It is structurally divided into an actin-binding headpiece (ABD) and a rod domain containing 24 immunoglobulin-like (Ig) repeats. A fragment of human filamin A (Ig repeats 14–16) was cloned and expressed in Escherichia coli and the purified protein was crystallized in 1.6 M ammonium sulfate, 2% PEG 1000 and 100 mM HEPES pH 7.5. The crystals diffracted to 1.95 Å and belong to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 50.63, b = 52.10, c = 98.46 Å, α = β = γ = 90°.

  9. Filamin A negatively regulates the transcriptional activity of p73{alpha} in the cytoplasm

    SciTech Connect

    Kim, Eun-Joo; Park, Jong-Sup; Um, Soo-Jong

    2007-11-03

    The transcription regulator p73{alpha} is structurally different from p53 in that it possesses a unique C-terminal domain, which has been implicated in transcriptional repression. To dissect the mechanism of repression by this domain, we performed a yeast two-hybrid screen of a HeLa cDNA library using residues 487-636 of p73{alpha} as bait and isolated a cDNA clone encoding the C-terminal portion (residues 2210-2647) of filamin A, a 280-kDa actin-binding protein. Additional yeast two-hybrid assays indicated that filamin A specifically interacts with the p73{alpha} C-terminus, which is lacking in p53 and p73{beta}. The interaction was confirmed by GST pull-down assays in vitro and by immunoprecipitation analysis in vivo. Immunofluorescence microscopy revealed that p73{alpha} remained in the cytoplasm in A7 melanoma cells stably expressing filamin A, whereas it was localized in the nucleus of filamin A-deficient M2 cells. Deletion of the C-terminus of p73{alpha} (residues 487-636) resulted in nuclear localization in both cell types. Consistent with our interaction data, transient co-expression of filamin A resulted in the down-regulation of p73{alpha}, but not of p53, transcriptional activity on various p53-responsive promoters. Taken together, our data suggest that p73{alpha} is sequestered in the cytoplasm by filamin A, thereby inhibiting its transcriptional activity.

  10. Enhancing US-Japan Cooperation to Combat Antimicrobial Resistance

    PubMed Central

    2014-01-01

    The Global Health Security Agenda (GHSA) is aimed at preventing, detecting, and responding to infectious disease threats. To move toward these goals, the United States has committed to partner with at least 30 countries around the world. One of the objectives of the GHSA includes “[p]reventing the emergence and spread of antimicrobial drug resistant organisms.” Antimicrobial resistance (AMR) has become a growing global health security problem, with inappropriate use of antimicrobial medications in humans and animals and a lack of new antimicrobial medications contributing to this problem. While AMR is a growing global concern, working on it regionally can make this multifaceted problem more manageable. The United States and Japan, both world leaders in the life sciences, are close allies that have established cooperative programs in medical research and global health that can be used to work on combating AMR and advance the GHSA. Although the United States and Japan have cooperated on health issues in the past, their cooperation on the growing problem of AMR has been limited. Their existing networks, cooperative programs, and close relationships can and should be used to work on combating this expanding problem. PMID:25470465

  11. Enhancing US-Japan cooperation to combat antimicrobial resistance.

    PubMed

    Gerbin, C Sachi

    2014-01-01

    The Global Health Security Agenda (GHSA) is aimed at preventing, detecting, and responding to infectious disease threats. To move toward these goals, the United States has committed to partner with at least 30 countries around the world. One of the objectives of the GHSA includes "[p]reventing the emergence and spread of antimicrobial drug resistant organisms." Antimicrobial resistance (AMR) has become a growing global health security problem, with inappropriate use of antimicrobial medications in humans and animals and a lack of new antimicrobial medications contributing to this problem. While AMR is a growing global concern, working on it regionally can make this multifaceted problem more manageable. The United States and Japan, both world leaders in the life sciences, are close allies that have established cooperative programs in medical research and global health that can be used to work on combating AMR and advance the GHSA. Although the United States and Japan have cooperated on health issues in the past, their cooperation on the growing problem of AMR has been limited. Their existing networks, cooperative programs, and close relationships can and should be used to work on combating this expanding problem. PMID:25470465

  12. Using technology-enhanced, cooperative, group-project learning for student comprehension and academic performance

    NASA Astrophysics Data System (ADS)

    Tlhoaele, Malefyane; Suhre, Cor; Hofman, Adriaan

    2016-05-01

    Cooperative learning may improve students' motivation, understanding of course concepts, and academic performance. This study therefore enhanced a cooperative, group-project learning technique with technology resources to determine whether doing so improved students' deep learning and performance. A sample of 118 engineering students, randomly divided into two groups, participated in this study and provided data through questionnaires issued before and after the experiment. The results, obtained through analyses of variance and structural equation modelling, reveal that technology-enhanced, cooperative, group-project learning improves students' comprehension and academic performance.

  13. Cooperative MPC&A Enhancements at Russian Navy Sites

    SciTech Connect

    Nelson, N N; O'Shell, P; Hendrickson, S; Sukhoruchkin, V; Antipov, S; Melkhov, E; Ponomarev-Stepnoi, N; Yurasov, N

    2001-05-30

    U.S. MPC&A cooperation with the Russian Federation (RF) Navy is based on a Joint Statement signed in 1996 to protect Highly Enriched Uranium (HEU) fresh fuel used for nuclear propulsion. The Russian Federation Navy is the largest owner in Russia of highly enriched uranium, both in the form of fresh nuclear fuel, and in the form of slightly irradiated fuel with a long cooling time after irradiation. As a result of this agreement, projects began at the Northern Fleet Fresh Fuel Storage Facility (Site 49) and Refueling Ship PM-63. Initial projects provided upgrades for RF Navy HEU fresh fuel storage facilities, beginning with a land-based facility near Murmansk and later adding other land-based and ship-based fresh fuel storage facilities. Additional protocols (December 1997, January 1999, and March 2000) significantly expanded cooperation to include all HEU fuel under RF Navy control. To date, it is estimated that tens of metric tons of HEU have been secured - enough to construct hundreds of nuclear devices. It was determined that the cooperation would be coordinated by the Russian Research Center, Kurchatov Institute. This paper describes the history of the Program development, its stages, current status, scale of the work and prospects.

  14. Regulation of AQP0 water permeability is enhanced by cooperativity.

    PubMed

    Németh-Cahalan, Karin L; Clemens, Daniel M; Hall, James E

    2013-03-01

    Aquaporin 0 (AQP0), essential for lens clarity, is a tetrameric protein composed of four identical monomers, each of which has its own water pore. The water permeability of AQP0 expressed in Xenopus laevis oocytes can be approximately doubled by changes in calcium concentration or pH. Although each monomer pore functions as a water channel, under certain conditions the pores act cooperatively. In other words, the tetramer is the functional unit. In this paper, we show that changes in external pH and calcium can induce an increase in water permeability that exhibits either a positive cooperativity switch-like increase in water permeability or an increase in water permeability in which each monomer acts independently and additively. Because the concentrations of calcium and hydrogen ions increase toward the center of the lens, a concentration signal could trigger a regulatory change in AQP0 water permeability. It thus seems plausible that the cooperative modes of water permeability regulation by AQP0 tetramers mediated by decreased pH and elevated calcium are the physiologically important ones in the living lens. PMID:23440275

  15. Filamin C-related myopathies: pathology and mechanisms.

    PubMed

    Fürst, Dieter O; Goldfarb, Lev G; Kley, Rudolf A; Vorgerd, Matthias; Olivé, Montse; van der Ven, Peter F M

    2013-01-01

    The term filaminopathy was introduced after a truncating mutation in the dimerization domain of filamin C (FLNc) was shown to be responsible for a devastating muscle disease. Subsequently, the same mutation was found in patients from diverse ethnical origins, indicating that this specific alteration is a mutational hot spot. Patients initially present with proximal muscle weakness, while distal and respiratory muscles become affected with disease progression. Muscle biopsies of these patients show typical signs of myofibrillar myopathy, including disintegration of myofibrils and aggregation of several proteins into distinct intracellular deposits. Highly similar phenotypes were observed in patients with other mutations in Ig-like domains of FLNc that result in expression of a noxious protein. Biochemical and biophysical studies showed that the mutated domains acquire an abnormal structure causing decreased stability and eventually becoming a seed for abnormal aggregation with other proteins. The disease usually presents only after the fourth decade of life possibly as a result of ageing-related impairments in the machinery that is responsible for disposal of damaged proteins. This is confirmed by mutations in components of this machinery that cause a highly similar phenotype. Transfection studies of cultured muscle cells reflect the events observed in patient muscles and, therefore, may provide a helpful model for testing future dedicated therapeutic strategies. More recently, FLNC mutations were also found in families with a distal myopathy phenotype, caused either by mutations in the actin-binding domain of FLNc that result in increased actin-binding and non-specific myopathic abnormalities without myofibrillar myopathy pathology, or a nonsense mutation in the rod domain that leads to RNA instability, haploinsufficiency with decreased expression levels of FLNc in the muscle fibers and myofibrillar abnormalities, but not to the formation of desmin-positive protein

  16. Filamin A-Hinge Region 1-EGFP: A Novel Tool for Tracking the Cellular Functions of Filamin A in Real-Time

    PubMed Central

    Pons, Mónica; Myhren, Lene; Garrido, Georgina; Aragay, Anna M.

    2012-01-01

    Abstract Background Filamin A (FLNa) is an actin-crosslinking protein necessary for stabilizing the cell surface, organizing protrusive activity and for promoting efficient cellular translocation. Recently, our group demonstrated the requirement of FLNa for the internalization of the chemokine receptor CCR2B. Methodology and Principal Findings In order to study the role of FLNa in vitro and in real-time, we have developed a fluorescent FLNa-EGFP construct. In this novel imaging tool, we introduced the EGFP-tag inside the flexible hinge 1 region of FLNa between two calpain cleavage sites. Our findings indicate that the FLNa-EGFP construct was correctly expressed, cleaved by calpain and colocalized with actin filaments as shown by immunostaining experiments in the human melanoma cell lines A7 (FLNa-repleted) and M2 (FLNa-deficient). In addition, scanning-electron microscopy (SEM) and micropatterning studies also provided clear evidence that the cell rigidity was restored. FLNa-EGFP allowed us to demonstrate the interaction of FLNa with the chemokine receptor CCR2B in endocytic vesicles after CCL2 ligand stimulation. Through live-cell imaging studies we show that the CCR2B receptor in Rab5-positive vesicles moves along filamin A-positive fibers. Significance Taken together, these results outline the functionality of the FLNa-EGFP and the importance of filamin A for receptor internalization and movement into endocytic vesicles. PMID:22870205

  17. Helping enhances productivity in campo flicker ( Colaptes campestris) cooperative groups

    NASA Astrophysics Data System (ADS)

    Dias, Raphael Igor; Webster, Michael S.; Macedo, Regina H.

    2015-06-01

    Reproductive adults in many bird species are assisted by non-breeding auxiliary helpers at the nest, yet the impact of auxiliaries on reproduction is variable and not always obvious. In this study, we tested Hamilton's rule and evaluated the effect of auxiliaries on productivity in the facultative cooperative breeder campo flicker ( Colaptes campestris campestris). Campo flickers have a variable mating system, with some groups having auxiliaries and others lacking them (i.e., unassisted pairs). Most auxiliaries are closely related to the breeding pair (primary auxiliaries), but some auxiliaries (secondary auxiliaries) are unrelated females that joined established groups. We found no effect of breeder quality (body condition) or territory quality (food availability) on group productivity, but the presence of auxiliaries increased the number of fledglings produced relative to unassisted pairs. Nonetheless, the indirect benefit of helping was small and did not outweigh the costs of delayed breeding and so seemed insufficient to explain the evolution of cooperative breeding in campo flickers. We concluded that some ecological constraints must limit dispersal or independent breeding, making staying in the group a "best-of-a-bad-job" situation for auxiliaries.

  18. Helping enhances productivity in campo flicker (Colaptes campestris) cooperative groups.

    PubMed

    Dias, Raphael Igor; Webster, Michael S; Macedo, Regina H

    2015-06-01

    Reproductive adults in many bird species are assisted by non-breeding auxiliary helpers at the nest, yet the impact of auxiliaries on reproduction is variable and not always obvious. In this study, we tested Hamilton's rule and evaluated the effect of auxiliaries on productivity in the facultative cooperative breeder campo flicker (Colaptes campestris campestris). Campo flickers have a variable mating system, with some groups having auxiliaries and others lacking them (i.e., unassisted pairs). Most auxiliaries are closely related to the breeding pair (primary auxiliaries), but some auxiliaries (secondary auxiliaries) are unrelated females that joined established groups. We found no effect of breeder quality (body condition) or territory quality (food availability) on group productivity, but the presence of auxiliaries increased the number of fledglings produced relative to unassisted pairs. Nonetheless, the indirect benefit of helping was small and did not outweigh the costs of delayed breeding and so seemed insufficient to explain the evolution of cooperative breeding in campo flickers. We concluded that some ecological constraints must limit dispersal or independent breeding, making staying in the group a "best-of-a-bad-job" situation for auxiliaries. PMID:26004264

  19. Drosophila Ten-m and Filamin Affect Motor Neuron Growth Cone Guidance

    PubMed Central

    Zheng, Lihua; Michelson, Yehudit; Freger, Vita; Avraham, Ziva; Venken, Koen J. T.; Bellen, Hugo J.; Justice, Monica J.; Wides, Ron

    2011-01-01

    The Drosophila Ten-m (also called Tenascin-major, or odd Oz (odz)) gene has been associated with a pair-rule phenotype. We identified and characterized new alleles of Drosophila Ten-m to establish that this gene is not responsible for segmentation defects but rather causes defects in motor neuron axon routing. In Ten-m mutants the inter-segmental nerve (ISN) often crosses segment boundaries and fasciculates with the ISN in the adjacent segment. Ten-m is expressed in the central nervous system and epidermal stripes during the stages when the growth cones of the neurons that form the ISN navigate to their targets. Over-expression of Ten-m in epidermal cells also leads to ISN misrouting. We also found that Filamin, an actin binding protein, physically interacts with the Ten-m protein. Mutations in cheerio, which encodes Filamin, cause defects in motor neuron axon routing like those of Ten-m. During embryonic development, the expression of Filamin and Ten-m partially overlap in ectodermal cells. These results suggest that Ten-m and Filamin in epidermal cells might together influence growth cone progression. PMID:21857973

  20. In Silico Modeling of Human α2C-Adrenoreceptor Interaction with Filamin-2

    PubMed Central

    Pawlowski, Marcin; Saraswathi, Saras; Motawea, Hanaa K. B.; Chotani, Maqsood A.; Kloczkowski, Andrzej

    2014-01-01

    Vascular smooth muscle α2C-adrenoceptors (α2C-ARs) mediate vasoconstriction of small blood vessels, especially arterioles. Studies of endogenous receptors in human arteriolar smooth muscle cells (referred to as microVSM) and transiently transfected receptors in heterologous HEK293 cells show that the α2C-ARs are perinuclear receptors that translocate to the cell surface under cellular stress and elicit a biological response. Recent studies in microVSM unraveled a crucial role of Rap1A-Rho-ROCK-F-actin pathways in receptor translocation, and identified protein-protein interaction of α2C-ARs with the actin binding protein filamin-2 as an essential step in the process. To better understand the molecular nature and specificity of this interaction, in this study, we constructed comparative models of human α2C-AR and human filamin-2 proteins. Finally, we performed in silico protein-protein docking to provide a structural platform for the investigation of human α2C-AR and filamin-2 interactions. We found that electrostatic interactions seem to play a key role in this complex formation which manifests in interactions between the C-terminal arginines of α2C-ARs (particularly R454 and R456) and negatively charged residues from filamin-2 region between residues 1979 and 2206. Phylogenetic and sequence analysis showed that these interactions have evolved in warm-blooded animals. PMID:25110951

  1. RNase L Interacts with Filamin A To Regulate Actin Dynamics and Barrier Function for Viral Entry

    PubMed Central

    Siddiqui, Mohammad Adnan; Dayal, Shubham; Naji, Merna; Ezelle, Heather J.; Zeng, Chun; Zhou, Aimin; Hassel, Bret A.

    2014-01-01

    ABSTRACT The actin cytoskeleton and its network of associated proteins constitute a physical barrier that viruses must circumvent to gain entry into cells for productive infection. The mechanisms by which the physical signals of infection are sensed by the host to activate an innate immune response are not well understood. The antiviral endoribonuclease RNase L is ubiquitously expressed in a latent form and activated upon binding 2-5A, a unique oligoadenylate produced during viral infections. We provide evidence that RNase L in its inactive form interacts with the actin-binding protein Filamin A to modulate the actin cytoskeleton and inhibit virus entry. Cells lacking either RNase L or Filamin A displayed increased virus entry which was exacerbated in cells lacking both proteins. RNase L deletion mutants that reduced Filamin A interaction displayed a compromised ability to restrict virus entry, supporting the idea of an important role for the RNase L-Filamin A complex in barrier function. Remarkably, both the wild type and a catalytically inactive RNase L mutant were competent to reduce virus entry when transfected into RNase L-deficient cells, indicating that this novel function of RNase L is independent of its enzymatic activity. Virus infection and RNase L activation disrupt its association with Filamin A and release RNase L to mediate its canonical nuclease-dependent antiviral activities. The dual functions of RNase L as a constitutive component of the actin cytoskeleton and as an induced mediator of antiviral signaling and effector functions provide insights into its mechanisms of antiviral activity and opportunities for the development of novel antiviral agents. PMID:25352621

  2. Model of a six immunoglobulin-like domain fragment of filamin A (16-21) built using residual dipolar couplings.

    PubMed

    Tossavainen, Helena; Koskela, Outi; Jiang, Pengju; Ylänne, Jari; Campbell, Iain D; Kilpeläinen, Ilkka; Permi, Perttu

    2012-04-18

    Filamins are actin-binding proteins that participate in a wide range of cell functions, including cell morphology, locomotion, membrane protein localization, and intracellular signaling. The three filamin isoforms found in humans, filamins A, B, and C, are highly homologous, and their roles are partly complementary. In addition to actin, filamins interact with dozens of other proteins that have roles as membrane receptors and channels, enzymes, signaling intermediates, and transcription factors. Filamins are composed of an N-terminal actin-binding domain and 24 filamin-type immunoglobulin-like domains (FLN) that form tail-to-tail dimers with their C-terminal FLN domain. Many of the filamin interactions including those for glycoprotein Ibα and integrins have been mapped to the region comprising FLN domains 16-21. Traditionally, FLN domains have been viewed as independent folding units, arranged in a linear chain joined with flexible linkers. Recent structural findings have shown that consecutive FLNs form more intricate superstructures. The crystal structure of filamin A domains 19-21 (FLNa19-21) revealed that domains 20 and 21 fold together and that the domain interaction can be autoregulatory. The solution structure of domains 18-19 showed a similar domain interaction, whereas domain pair 16-17 has a completely different domain packing mode. In this study, we characterize the domain organization of the FLNa domain sextet 16-21 using NMR spectroscopy. A structure model of this 60-kDa protein has been built using residual dipolar coupling restraints. RDCs and (15)N relaxation data have been used to characterize interdomain motions. PMID:22452512

  3. Enhancing the Performance of Medical Implant Communication Systems through Cooperative Diversity

    PubMed Central

    Hegyi, Barnabás; Levendovszky, János

    2010-01-01

    Battery-operated medical implants—such as pacemakers or cardioverter-defibrillators—have already been widely used in practical telemedicine and telecare applications. However, no solution has yet been found to mitigate the effect of the fading that the in-body to off-body communication channel is subject to. In this paper, we reveal and assess the potential of cooperative diversity to combat fading—hence to improve system performance—in medical implant communication systems. In the particular cooperative communication scenario we consider, multiple cooperating receiver units are installed across the room accommodating the patient with a medical implant inside his/her body. Our investigations have shown that the application of cooperative diversity is a promising approach to enhance the performance of medical implant communication systems in various aspects such as implant lifetime and communication link reliability. PMID:20379346

  4. Velocity-enhanced cooperation of moving agents playing public goods games

    NASA Astrophysics Data System (ADS)

    Cardillo, Alessio; Meloni, Sandro; Gómez-Gardeñes, Jesús; Moreno, Yamir

    2012-06-01

    In this paper we study the evolutionary dynamics of the public goods game in a population of mobile agents embedded in a two-dimensional space. In this framework, the backbone of interactions between agents changes in time, allowing us to study the impact that mobility has on the emergence of cooperation in structured populations. Our results point out that a low degree of mobility enhances cooperation in the system. In addition, we study the impact of the size of the groups in which games are played on cooperation. Again we find a rise and fall of cooperation related to the percolation point of the instant interaction networks created by the set of mobile agents.

  5. Mobility enhances cooperation in the presence of decision-making mistakes on complex networks

    NASA Astrophysics Data System (ADS)

    Yu, Wenjian

    2011-02-01

    Human migration has profound effects on social change. The introduction of success-driven migration to selfish individuals has revealed significant effects on the promotion of cooperation in spatial evolutionary games. In this study, we generalize the interaction structure from a spatial lattice to complex networks, such as Erdős-Renyi random networks and Barabási-Albert scale-free networks. Keeping the topology of networks, we investigate the robustness of cooperation when individuals can make decision errors. Numerical simulations demonstrate the effectiveness of success-driven migration on the enhancement of cooperation confronted with individual decision-making mistakes. In contrast, even a very low probability of decision errors can decrease the level of cooperation without mobility. Statistical analysis further exhibits the relation between network topology and migratory behavior.

  6. Enhancing the performance of cooperative face detector by NFGS

    NASA Astrophysics Data System (ADS)

    Yesugade, Snehal; Dave, Palak; Srivastava, Srinkhala; Das, Apurba

    2015-07-01

    Computerized human face detection is an important task of deformable pattern recognition in today's world. Especially in cooperative authentication scenarios like ATM fraud detection, attendance recording, video tracking and video surveillance, the accuracy of the face detection engine in terms of accuracy, memory utilization and speed have been active areas of research for the last decade. The Haar based face detection or SIFT and EBGM based face recognition systems are fairly reliable in this regard. But, there the features are extracted in terms of gray textures. When the input is a high resolution online video with a fairly large viewing area, Haar needs to search for face everywhere (say 352×250 pixels) and every time (e.g., 30 FPS capture all the time). In the current paper we have proposed to address both the aforementioned scenarios by a neuro-visually inspired method of figure-ground segregation (NFGS) [5] to result in a two-dimensional binary array from gray face image. The NFGS would identify the reference video frame in a low sampling rate and updates the same with significant change of environment like illumination. The proposed algorithm would trigger the face detector only when appearance of a new entity is encountered into the viewing area. To address the detection accuracy, classical face detector would be enabled only in a narrowed down region of interest (RoI) as fed by the NFGS. The act of updating the RoI would be done in each frame online with respect to the moving entity which in turn would improve both FR (False Rejection) and FA (False Acceptance) of the face detection system.

  7. Using the Microcomputer to Enhance Language Experiences and the Development of Cooperative Play among Preschool Children.

    ERIC Educational Resources Information Center

    Muhlstein, Eleanor A.; Croft, Doreen J.

    Current interest and controversy about the use of microcomputers with young children led to a study of 13 3- to 5-year-old girls and boys enrolled at the De Anza College Child Development Center in Cupertino, California. Designed to determine the effectiveness of the computer in enhancing language experiences and development of cooperative play…

  8. The Role of Structured Cooperative Learning Groups for Enhancing Chinese Primary Students' Reading Comprehension

    ERIC Educational Resources Information Center

    Law, Yin-Kum

    2014-01-01

    The present study aimed to compare the effectiveness of two types of cooperative learning groups used in reciprocal teaching (RT) classes (i.e. high-structured vs. low-structured groups) for enhancing students' reading comprehension. The participants were 235 Hong Kong Chinese Grade 6 students in nine classes. Reading comprehension tests and…

  9. Grade/Study-Performance Contracts, Enhanced Communication, Cooperative Learning, and Student Performance in Undergraduate Organic Chemistry.

    ERIC Educational Resources Information Center

    Dougherty, Ralph C.

    1997-01-01

    Describes and evaluates a teaching strategy, designed to increase student retention while maintaining academic performance levels in undergraduate organic chemistry, that uses grade/study-performance contracts, enhanced communication using electronic mail, and cooperative learning. Concludes that a series of interventions can substantially…

  10. Project CREATE Final Report. Cooperative Resources To Enhance Access to Technology Education.

    ERIC Educational Resources Information Center

    Hampden County Employment and Training Consortium, Springfield, MA.

    These materials have been developed by Project CREATE (Cooperative Resources to Enhance Access to Jobs through Technical Education), a demonstration program designed to develop a network, specific activities, and resources that would provide education and support services to a wide audience. A 13-page final report describes the hands-on training…

  11. Payoff-related migration enhances cooperation in the prisoner's dilemma game

    NASA Astrophysics Data System (ADS)

    Cheng, Hongyan; Dai, Qionglin; Li, Haihong; Zhu, Yun; Zhang, Mei; Yang, Junzhong

    2011-04-01

    In reality, migration of an individual usually correlates with the individual's financial or social status. Here, we consider the situation where migration of a player depends on the player's payoff to an evolutionary prisoner's dilemma game. When the mobility of a player is positively correlated with the player's normalized payoff, Pi, where the mobility of player i is defined as μi=Piα, we found that cooperation could be promoted strongly in the case of a high density of players because of the introduction of this kind of migration. Moreover, the system could reach a state of complete cooperation in a large region on the given parameter space. Interestingly, enhancement of cooperation shows a non-monotonic behavior with an increase in α. We also found that the positive effects of this kind of migration on cooperation are robust in the face of changes to the network structure and the strategy-updating rule. In addition, we consider another situation where the mobility of a player is anti-correlated with the player's normalized payoff, and we observe that cooperation enhancement still exists.

  12. Prestressed F-actin networks cross-linked by hinged filamins replicate mechanical properties of cells

    NASA Astrophysics Data System (ADS)

    Gardel, M. L.; Nakamura, F.; Hartwig, J. H.; Crocker, J. C.; Stossel, T. P.; Weitz, D. A.

    2006-02-01

    We show that actin filaments, shortened to physiological lengths by gelsolin and cross-linked with recombinant human filamins (FLNs), exhibit dynamic elastic properties similar to those reported for live cells. To achieve elasticity values of comparable magnitude to those of cells, the in vitro network must be subjected to external prestress, which directly controls network elasticity. A molecular requirement for the strain-related behavior at physiological conditionsis a flexible hinge found in FLNa and some FLNb molecules. Basic physical properties of the in vitro filamin-F-actin network replicate the essential mechanical properties of living cells. This physical behavior could accommodate passive deformation and internal organelle trafficking at low strains yet resist externally or internally generated high shear forces. cytoskeleton | cell mechanics | nonlinear rheology

  13. Smooth muscle filamin A is a major determinant of conduit artery structure and function at the adult stage.

    PubMed

    Retailleau, Kevin; Arhatte, Malika; Demolombe, Sophie; Jodar, Martine; Baudrie, Véronique; Offermanns, Stefan; Feng, Yuanyi; Patel, Amanda; Honoré, Eric; Duprat, Fabrice

    2016-07-01

    Human mutations in the X-linked FLNA gene are associated with a remarkably diverse phenotype, including severe arterial morphological anomalies. However, the role for filamin A (FlnA) in vascular cells remains partially understood. We used a smooth muscle (sm)-specific conditional mouse model to delete FlnA at the adult stage, thus avoiding the developmental effects of the knock-out. Inactivation of smFlnA in adult mice significantly lowered blood pressure, together with a decrease in pulse pressure. However, both the aorta and carotid arteries showed a major outward hypertrophic remodeling, resistant to losartan, and normally occurring in hypertensive conditions. Notably, arterial compliance was significantly enhanced in the absence of smFlnA. Moreover, reactivity of thoracic aorta rings to a variety of vasoconstrictors was elevated, while basal contractility in response to KCl depolarization was reduced. Enhanced reactivity to the thromboxane A2 receptor agonist U46619 was fully reversed by the ROCK inhibitor Y27632. We discuss the possibility that a reduction in arterial stiffness upon smFlnA inactivation might cause a compensatory increase in conduit artery diameter for normalization of parietal tension, independently of the ROCK pathway. In conclusion, deletion of smFlnA in adult mice recapitulates the vascular phenotype of human bilateral periventricular nodular heterotopia, culminating in aortic dilatation. PMID:27023351

  14. Filamin-A Increases the Stability and Plasma Membrane Expression of Polycystin-2

    PubMed Central

    Wang, Qian; Zheng, Wang; Wang, Zuocheng; Yang, JungWoo; Hussein, Shaimaa; Tang, Jingfeng; Chen, Xing-Zhen

    2015-01-01

    Polycystin-2 (PC2), encoded by the PKD2 gene, is mutated in ~15% of autosomal dominant polycystic kidney disease. Filamins are actin-binding proteins implicated in scaffolding and membrane stabilization. Here we studied the effects of filamin on PC2 stability using filamin-deficient human melanoma M2, filamin-A (FLNA)-replete A7, HEK293 and IMCD cells together with FLNA siRNA/shRNA knockdown (KD). We found that the presence of FLNA is associated with higher total and plasma membrane PC2 protein expression. Western blotting analysis in combination with FLNA KD showed that FLNA in A7 cells represses PC2 degradation, prolonging the half-life from 2.3 to 4.4 hours. By co-immunoprecipitation and Far Western blotting we found that the FLNA C-terminus (FLNAC) reduces the FLNA-PC2 binding and PC2 expression, presumably through competing with FLNA for binding PC2. We further found that FLNA mediates PC2 binding with actin through forming complex PC2-FLNA-actin. FLNAC acted as a blocking peptide and disrupted the link of PC2 with actin through disrupting the PC2-FLNA-actin complex. Finally, we demonstrated that the physical interaction of PC2-FLNA is Ca-dependent. Taken together, our current study indicates that FLNA anchors PC2 to the actin cytoskeleton through complex PC2-FLNA-actin to reduce degradation and increase stability, and possibly regulate PC2 function in a Ca-dependent manner. PMID:25861040

  15. Filamin-a increases the stability and plasma membrane expression of polycystin-2.

    PubMed

    Wang, Qian; Zheng, Wang; Wang, Zuocheng; Yang, JungWoo; Hussein, Shaimaa; Tang, Jingfeng; Chen, Xing-Zhen

    2015-01-01

    Polycystin-2 (PC2), encoded by the PKD2 gene, is mutated in ~15% of autosomal dominant polycystic kidney disease. Filamins are actin-binding proteins implicated in scaffolding and membrane stabilization. Here we studied the effects of filamin on PC2 stability using filamin-deficient human melanoma M2, filamin-A (FLNA)-replete A7, HEK293 and IMCD cells together with FLNA siRNA/shRNA knockdown (KD). We found that the presence of FLNA is associated with higher total and plasma membrane PC2 protein expression. Western blotting analysis in combination with FLNA KD showed that FLNA in A7 cells represses PC2 degradation, prolonging the half-life from 2.3 to 4.4 hours. By co-immunoprecipitation and Far Western blotting we found that the FLNA C-terminus (FLNAC) reduces the FLNA-PC2 binding and PC2 expression, presumably through competing with FLNA for binding PC2. We further found that FLNA mediates PC2 binding with actin through forming complex PC2-FLNA-actin. FLNAC acted as a blocking peptide and disrupted the link of PC2 with actin through disrupting the PC2-FLNA-actin complex. Finally, we demonstrated that the physical interaction of PC2-FLNA is Ca-dependent. Taken together, our current study indicates that FLNA anchors PC2 to the actin cytoskeleton through complex PC2-FLNA-actin to reduce degradation and increase stability, and possibly regulate PC2 function in a Ca-dependent manner. PMID:25861040

  16. Grb7 and Filamin-a associate and are colocalized to cell membrane ruffles upon EGF stimulation.

    PubMed

    Paudyal, Prakash; Shrestha, Sanjay; Madanayake, Thushara; Shuster, Charles B; Rohrschneider, Larry R; Rowland, Aaron; Lyons, Barbara A

    2013-11-01

    Grb7 is an adaptor molecule mediating signal transduction from multiple cell surface receptors to diverse downstream pathways. Grb7, along with Grb10 and Grb14, make up the Grb7 protein family. This protein family has been shown to be overexpressed in certain cancers and cancer cell lines. Grb7 and a receptor tyrosine kinase, ErbB2, are overexpressed in 20-30% of breast cancers. Grb7 overexpression has been linked to enhanced cell migration and metastasis, although the participants in these pathways have not been fully determined. In this study, we report the Grb7 protein interacts with Filamin-a, an actin-crosslinking component of the cell cytoskeleton. Additionally, we have demonstrated the interaction between Grb7 and Flna is specific to the RA-PH domains of Grb7, and the immunoglobulin-like repeat 16-19 domains of Flna. We demonstrate that full-length Grb7 and Flna interact in the mammalian cellular environment, as well as in vitro. Immunofluorescent microscopy shows potential co-localization of Grb7 and Flna in membrane ruffles upon epidermal growth factor stimulation. These studies are amongst the first to establish a clear connection between Grb7 signaling and cytoskeletal remodeling. PMID:24089360

  17. Grb7 and Filamin-a associate and are colocalized to cell membrane ruffles upon EGF stimulation

    PubMed Central

    Paudyal, Prakash; Shrestha, Sanjay; Madanayake, Thushara; Shuster, Charles B.; Rohrschneider, Larry R.; Rowland, Aaron; Lyons, Barbara A.

    2013-01-01

    Grb7 is an adaptor molecule mediating signal transduction from multiple cell surface receptors to diverse downstream pathways. Grb7, along with Grb10 and Grb14, make up the Grb7 protein family. This protein family has been shown to be overexpressed in certain cancers and cancer cell lines. Grb7 and a receptor tyrosine kinase, ErbB2, are overexpressed in 20–30% of breast cancers. Grb7 overexpression has been linked to enhanced cell migration and metastasis, although the participants in these pathways have not been fully determined. In this study, we report the Grb7 protein interacts with Filamin-a, an actin-crosslinking component of the cell cytoskeleton. Additionally, we have demonstrated the interaction between Grb7 and Flna is specific to the RA-PH domains of Grb7, and the immunoglobulin-like repeat 16–19 domains of Flna. We demonstrate that full-length Grb7 and Flna interact in the mammalian cellular environment, as well as in vitro. Immunofluorescent microscopy shows potential co-localization of Grb7 and Flna in membrane ruffles upon epidermal growth factor stimulation. These studies are amongst the first to establish a clear connection between Grb7 signaling and cytoskeletal remodeling. PMID:24089360

  18. Filamin A (FLNA) modulates chemosensitivity to docetaxel in triple-negative breast cancer through the MAPK/ERK pathway.

    PubMed

    Zhao, Pengxin; Ma, Weiyuan; Hu, Zhigang; Zang, Leilei; Tian, Zhisheng; Zhang, Kaili

    2016-04-01

    A previous RNA interference (RNAi) screen identified filamin A (FLNA) as a potential biomarker to predict chemosensitivity in triple-negative breast cancer (TNBC). However, its ability to modulate chemosensitivity and the underlying mechanism has not been investigated. Genetic manipulation of FLNA expression has been performed in an immortalized noncancerous human mammary epithelial cell line and four TNBC cell lines to investigate its effect on chemosensitivity. Western blot analysis was performed to identify the potential signaling pathway involved. Xenograft mouse model was used to examine the in vivo role of FLNA in modulating chemosensitivity. Overexpression of FLNA conferred chemoresistance to docetaxel in noncancerous human mammary epithelial cells. Knockdown of FLNA sensitized four TNBC cell lines, MDA-MB-231, HCC38, Htb126, and HCC1937 to docetaxel which was reversed by reconstituted FLNA expression. Decreased FLNA expression correlated with decreased activation of ERK. Constitutive activation of ERK2 reversed siFLNA-induced chemosensitization. Inhibition of MEK1 recapitulates the effect of FLNA knockdown. MDA-MB-231 xenograft with FLNA knockdown showed enhanced response to docetaxel compared with control xenograft with increased apoptosis. FLNA can function as a modulator of chemosensitivity to docetaxel in TNBC cells through regulation of the MAPK/ERK pathway both in vitro and in vivo. FLNA may serve as a novel therapeutic target for improvement of chemotherapy efficacy in TNBC. PMID:26546439

  19. Highly Enhanced Cooperative Upconversion Luminescence through Energy Transfer Optimization and Quenching Protection.

    PubMed

    Xue, Meng; Zhu, Xingjun; Qiu, Xiaochen; Gu, Yuyang; Feng, Wei; Li, Fuyou

    2016-07-20

    Upconversion luminescence nanomaterials have shown great potential in biological and physical applications because of their unique properties. However, limited research exists on the cooperative sensitization upconversion emission in Tb(3+) ions over Er(3+) ions and Tm(3+) ions because of its low efficiency. Herein, by optimizing the doping ratio of sensitizer and activator to maximize the utilization of the photon energy and introducing the CaF2 inert shell to shield sensitizer from quenchers, we synthesize ultrasmall NaYbF4:Tb@CaF2 nanoparticles with a significant enhancement (690-fold) in cooperative sensitization upconversion emission intensity, compared with the parent NaYbF4:Tb. The lifetime of Tb(3+) emission in NaYbF4:Tb@CaF2 nanoparticles is prolonged extensively to ∼3.5 ms. Furthermore, NaYbF4:Tb@CaF2 was applied in in vitro and in vivo bioimaging. The presented luminescence enhancement strategy provides cooperative sensitization upconversion with new opportunities for bioapplication. PMID:27347810

  20. Terminal osseous dysplasia with pigmentary defects (TODPD) due to a recurrent filamin A (FLNA) mutation

    PubMed Central

    Brunetti-Pierri, Nicola; Torrado, Maria; Fernandez, Maria del Carmen; Tello, Ana Maria; Arberas, Claudia L; Cardinale, Antonella; Piccolo, Pasquale; Bacino, Carlos A

    2014-01-01

    Terminal osseous dysplasia with pigmentary defects (TODPD) is an X-linked dominant syndrome with distal limb anomalies, pigmentary skin defects, digital fibromas, and generalized bone involvement due to a recurrent mutation in the filamin A (FLNA) gene. We here report the mutation c.5217G>A in FLNA in three families with TODPD and we found possible germline and somatic mosaicism in two out of the three families. The occurrence of somatic and germline mosaicism for TODPD indicates that caution should be taken in counseling recurrence risks for these conditions upon presentation of an isolated case. PMID:25614868

  1. Terminal osseous dysplasia with pigmentary defects (TODPD) due to a recurrent filamin A (FLNA) mutation.

    PubMed

    Brunetti-Pierri, Nicola; Torrado, Maria; Fernandez, Maria Del Carmen; Tello, Ana Maria; Arberas, Claudia L; Cardinale, Antonella; Piccolo, Pasquale; Bacino, Carlos A

    2014-11-01

    Terminal osseous dysplasia with pigmentary defects (TODPD) is an X-linked dominant syndrome with distal limb anomalies, pigmentary skin defects, digital fibromas, and generalized bone involvement due to a recurrent mutation in the filamin A (FLNA) gene. We here report the mutation c.5217G>A in FLNA in three families with TODPD and we found possible germline and somatic mosaicism in two out of the three families. The occurrence of somatic and germline mosaicism for TODPD indicates that caution should be taken in counseling recurrence risks for these conditions upon presentation of an isolated case. PMID:25614868

  2. Partially Redundant Enhancers Cooperatively Maintain Mammalian Pomc Expression Above a Critical Functional Threshold

    PubMed Central

    Lam, Daniel D.; de Souza, Flavio S. J.; Nasif, Sofia; Yamashita, Miho; López-Leal, Rodrigo; Meece, Kana; Sampath, Harini; Mercer, Aaron J.; Wardlaw, Sharon L.

    2015-01-01

    Cell-specific expression of many genes is conveyed by multiple enhancers, with each individual enhancer controlling a particular expression domain. In contrast, multiple enhancers drive similar expression patterns of some genes involved in embryonic development, suggesting regulatory redundancy. Work in Drosophila has indicated that functionally overlapping enhancers canalize development by buffering gene expression against environmental and genetic disturbances. However, little is known about regulatory redundancy in vertebrates and in genes mainly expressed during adulthood. Here we study nPE1 and nPE2, two phylogenetically conserved mammalian enhancers that drive expression of the proopiomelanocortin gene (Pomc) to the same set of hypothalamic neurons. The simultaneous deletion of both enhancers abolished Pomc expression at all ages and induced a profound metabolic dysfunction including early-onset extreme obesity. Targeted inactivation of either nPE1 or nPE2 led to very low levels of Pomc expression during early embryonic development indicating that both enhancers function synergistically. In adult mice, however, Pomc expression is controlled additively by both enhancers, with nPE1 being responsible for ∼80% and nPE2 for ∼20% of Pomc transcription. Consequently, nPE1 knockout mice exhibit mild obesity whereas nPE2-deficient mice maintain a normal body weight. These results suggest that nPE2-driven Pomc expression is compensated by nPE1 at later stages of development, essentially rescuing the earlier phenotype of nPE2 deficiency. Together, these results reveal that cooperative interactions between the enhancers confer robustness of Pomc expression against gene regulatory disturbances and preclude deleterious metabolic phenotypes caused by Pomc deficiency in adulthood. Thus, our study demonstrates that enhancer redundancy can be used by genes that control adult physiology in mammals and underlines the potential significance of regulatory sequence mutations in

  3. Filamin A regulates neuronal migration through brefeldin A-inhibited guanine exchange factor 2-dependent Arf1 activation.

    PubMed

    Zhang, Jingping; Neal, Jason; Lian, Gewei; Hu, Jianjun; Lu, Jie; Sheen, Volney

    2013-10-01

    Periventricular heterotopias is a malformation of cortical development, characterized by ectopic neuronal nodules around ventricle lining and caused by an initial migration defect during early brain development. Human mutations in the Filamin A (FLNA) and ADP-ribosylation factor guanine exchange factor 2 [ARFGEF2; encoding brefeldin-A-inhibited guanine exchange factor-2 (BIG2)] genes give rise to this disorder. Previously, we have reported that Big2 inhibition impairs neuronal migration and binds to FlnA, and its loss promotes FlnA phosphorylation. FlnA phosphorylation dictates FlnA-actin binding affinity and consequently alters focal adhesion size and number to effect neuronal migration. Here we show that FlnA loss similarly impairs migration, reciprocally enhances Big2 expression, but also alters Big2 subcellular localization in both null and conditional FlnA mice. FlnA phosphorylation promotes relocalization of Big2 from the Golgi toward the lipid ruffles, thereby activating Big2-dependent Arf1 at the cell membrane. Loss of FlnA phosphorylation or Big2 function impairs Arf1-dependent vesicle trafficking at the periphery, and Arf1 is required for maintenance of cell-cell junction connectivity and focal adhesion assembly. Loss of Arf1 activity disrupts neuronal migration and cell adhesion. Collectively, these studies demonstrate a potential mechanism whereby coordinated interactions between actin (through FlnA) and vesicle trafficking (through Big2-Arf) direct the assembly and disassembly of membrane protein complexes required for neuronal migration and neuroependymal integrity. PMID:24089482

  4. Grade/Performance Contracts, Enhanced Communication, Cooperative Learning and Student Performance in Undergraduate Organic Chemistry

    NASA Astrophysics Data System (ADS)

    Dougherty, Ralph C.

    1997-06-01

    This paper describes a grade/study-performance contract that was designed to increase student retention while maintaining academic performance levels in undergraduate organic chemistry. The experimental course included enhanced communication using electronic mail, and cooperative learning in addition to grade/study-performance contracts. The objective of the grade/study-performance contract was the development of learning skills with creation of a basis for unobtrusive auditing of performance. The retention rate in the experimental course was 0.82 for the first term and 0.93 for the second term. The overall retention was 0.76. This value was 3.8 times the average retention for the same sequence in the previous five years at the same institution. It was seven standard deviations away from the previous mean. The ACS Organic Chemistry Examination percentile score for the control section was 46+25 (n=117). The corresponding data for the experimental section was 53+23 (n=143). When the course was offered with the same instructor, cooperative learning, e-mail, but no grade/study-performance contract the ACS Exam percentile average 37+29. This represents a drop of 9.9 standard deviations for comparison of the means. We conclude that grade/study-performance contracts can be effective in increasing both student performance and retention in undergraduate organic chemistry.

  5. How actin crosslinking and bundling proteins cooperate to generate an enhanced cell mechanical response

    NASA Technical Reports Server (NTRS)

    Tseng, Yiider; Kole, Thomas P.; Lee, Jerry S H.; Fedorov, Elena; Almo, Steven C.; Schafer, Benjamin W.; Wirtz, Denis

    2005-01-01

    Actin-crosslinking proteins organize actin filaments into dynamic and complex subcellular scaffolds that orchestrate important mechanical functions, including cell motility and adhesion. Recent mutation studies have shown that individual crosslinking proteins often play seemingly non-essential roles, leading to the hypothesis that they have considerable redundancy in function. We report live-cell, in vitro, and theoretical studies testing the mechanical role of the two ubiquitous actin-crosslinking proteins, alpha-actinin and fascin, which co-localize to stress fibers and the basis of filopodia. Using live-cell particle tracking microrheology, we show that the addition of alpha-actinin and fascin elicits a cell mechanical response that is significantly greater than that originated by alpha-actinin or fascin alone. These live-cell measurements are supported by quantitative rheological measurements with reconstituted actin filament networks containing pure proteins that show that alpha-actinin and fascin can work in concert to generate enhanced cell stiffness. Computational simulations using finite element modeling qualitatively reproduce and explain the functional synergy of alpha-actinin and fascin. These findings highlight the cooperative activity of fascin and alpha-actinin and provide a strong rationale that an evolutionary advantage might be conferred by the cooperative action of multiple actin-crosslinking proteins with overlapping but non-identical biochemical properties. Thus the combination of structural proteins with similar function can provide the cell with unique properties that are required for biologically optimal responses.

  6. A Tool to Enhance Cooperation and Knowledge Transfer among Software Developers

    NASA Astrophysics Data System (ADS)

    Aydin, Seçil; Mishra, Deepti

    Software developers have been successfully tailoring software development methods according to the project situation and more so in small scale software development organizations. There is a need to share this knowledge with other developers who may be facing the same project situation so that they can benefit from other people experiences. In this paper, an approach to enhance cooperation among software developers, in terms of sharing the knowledge that was used successfully in past projects, is proposed. A web-based tool is developed that can assist in creation, storage and extraction of methods related with requirement elicitation phase. These methods are categorized according to certain criteria which helps in searching a method that will be most appropriate in a given project situation. This approach and tool can also be used for other software development activities.

  7. Hydrophobic/Hydrophilic Cooperative Janus System for Enhancement of Fog Collection.

    PubMed

    Cao, Moyuan; Xiao, Jiasheng; Yu, Cunming; Li, Kan; Jiang, Lei

    2015-09-01

    Harvesting micro-droplets from fog is a promising method for solving global freshwater crisis. Different types of fog collectors have been extensively reported during the last decade. The improvement of fog collection can be attributed to the immediate transportation of harvested water, the effective regeneration of the fog gathering surface, etc. Through learning from the nature's strategy for water preservation, the hydrophobic/hydrophilic cooperative Janus system that achieved reinforced fog collection ability is reported here. Directional delivery of the surface water, decreased re-evaporation rate of the harvested water, and thinner boundary layer of the collecting surface contribute to the enhancement of collection efficiency. Further designed cylinder Janus collector can facilely achieve a continuous process of efficient collection, directional transportation, and spontaneous preservation of fog water. This Janus fog harvesting system should improve the understanding of micro-droplet collection system and offer ideas to solve water resource crisis. PMID:26088210

  8. Coevolutionary, coexisting learning and teaching agents model for prisoner’s dilemma games enhancing cooperation with assortative heterogeneous networks

    NASA Astrophysics Data System (ADS)

    Tanimoto, Jun

    2013-07-01

    Unlike other natural network systems, assortativity can be observed in most human social networks, although it has been reported that a social dilemma situation represented by the prisoner’s dilemma favors dissortativity to enhance cooperation. We established a new coevolutionary model for both agents’ strategy and network topology, where teaching and learning agents coexist. Remarkably, this model enables agents’ enhancing cooperation more than a learners-only model on a time-frozen scale-free network and produces an underlying assortative network with a fair degree of power-law distribution. The model may imply how and why assortative networks are adaptive in human society.

  9. Filamin A mutation may be associated with diffuse lung disease mimicking bronchopulmonary dysplasia in premature newborns.

    PubMed

    Lord, Amanda; Shapiro, Adam J; Saint-Martin, Christine; Claveau, Martine; Melançon, Serge; Wintermark, Pia

    2014-11-01

    Bronchopulmonary dysplasia (BPD) is a common long-term complication in premature newborns requiring ventilatory support and is the most common cause of chronic diffuse lung disease in this population. We present the clinical course of a premature newborn with a complicated neonatal respiratory course that was initially thought to be related to BPD, but it did not respond to the typical therapies for this condition. Due to the findings of periventricular nodular heterotopia, the diagnosis of a filamin A gene mutation was eventually made, which explained the respiratory pathology of this patient. When time of onset and clinical course do not correlate with typical BPD, one should consider alternative diagnoses in premature infants, including neonatal diffuse lung disease. PMID:25053830

  10. The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A.

    PubMed

    Segura, Inmaculada; Lange, Christian; Knevels, Ellen; Moskalyuk, Anastasiya; Pulizzi, Rocco; Eelen, Guy; Chaze, Thibault; Tudor, Cicerone; Boulegue, Cyril; Holt, Matthew; Daelemans, Dirk; Matondo, Mariette; Ghesquière, Bart; Giugliano, Michele; Ruiz de Almodovar, Carmen; Dewerchin, Mieke; Carmeliet, Peter

    2016-03-22

    Neuronal function is highly sensitive to changes in oxygen levels, but how hypoxia affects dendritic spine formation and synaptogenesis is unknown. Here we report that hypoxia, chemical inhibition of the oxygen-sensing prolyl hydroxylase domain proteins (PHDs), and silencing of Phd2 induce immature filopodium-like dendritic protrusions, promote spine regression, reduce synaptic density, and decrease the frequency of spontaneous action potentials independently of HIF signaling. We identified the actin cross-linker filamin A (FLNA) as a target of PHD2 mediating these effects. In normoxia, PHD2 hydroxylates the proline residues P2309 and P2316 in FLNA, leading to von Hippel-Lindau (VHL)-mediated ubiquitination and proteasomal degradation. In hypoxia, PHD2 inactivation rapidly upregulates FLNA protein levels because of blockage of its proteasomal degradation. FLNA upregulation induces more immature spines, whereas Flna silencing rescues the immature spine phenotype induced by PHD2 inhibition. PMID:26972007

  11. The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A

    PubMed Central

    Segura, Inmaculada; Lange, Christian; Knevels, Ellen; Moskalyuk, Anastasiya; Pulizzi, Rocco; Eelen, Guy; Chaze, Thibault; Tudor, Cicerone; Boulegue, Cyril; Holt, Matthew; Daelemans, Dirk; Matondo, Mariette; Ghesquière, Bart; Giugliano, Michele; Ruiz de Almodovar, Carmen; Dewerchin, Mieke; Carmeliet, Peter

    2016-01-01

    Summary Neuronal function is highly sensitive to changes in oxygen levels, but how hypoxia affects dendritic spine formation and synaptogenesis is unknown. Here we report that hypoxia, chemical inhibition of the oxygen-sensing prolyl hydroxylase domain proteins (PHDs), and silencing of Phd2 induce immature filopodium-like dendritic protrusions, promote spine regression, reduce synaptic density, and decrease the frequency of spontaneous action potentials independently of HIF signaling. We identified the actin cross-linker filamin A (FLNA) as a target of PHD2 mediating these effects. In normoxia, PHD2 hydroxylates the proline residues P2309 and P2316 in FLNA, leading to von Hippel-Lindau (VHL)-mediated ubiquitination and proteasomal degradation. In hypoxia, PHD2 inactivation rapidly upregulates FLNA protein levels because of blockage of its proteasomal degradation. FLNA upregulation induces more immature spines, whereas Flna silencing rescues the immature spine phenotype induced by PHD2 inhibition. PMID:26972007

  12. Filamin and Phospholipase C-ε Are Required for Calcium Signaling in the Caenorhabditis elegans Spermatheca

    PubMed Central

    Kovacevic, Ismar; Orozco, Jose M.; Cram, Erin J.

    2013-01-01

    The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter, are fertilized, and exit into the uterus. FLN-1/filamin, a stretch-sensitive structural and signaling scaffold, and PLC-1/phospholipase C-ε, an enzyme that generates the second messenger IP3, are required for embryos to exit normally after fertilization. Using GCaMP, a genetically encoded calcium indicator, we show that entry of an oocyte into the spermatheca initiates a distinctive series of IP3-dependent calcium oscillations that propagate across the tissue via gap junctions and lead to constriction of the spermatheca. PLC-1 is required for the calcium release mechanism triggered by oocyte entry, and FLN-1 is required for timely initiation of the calcium oscillations. INX-12, a gap junction subunit, coordinates propagation of the calcium transients across the spermatheca. Gain-of-function mutations in ITR-1/IP3R, an IP3-dependent calcium channel, and loss-of-function mutations in LFE-2, a negative regulator of IP3 signaling, increase calcium release and suppress the exit defect in filamin-deficient animals. We further demonstrate that a regulatory cassette consisting of MEL-11/myosin phosphatase and NMY-1/non-muscle myosin is required for coordinated contraction of the spermatheca. In summary, this study answers long-standing questions concerning calcium signaling dynamics in the C. elegans spermatheca and suggests FLN-1 is needed in response to oocyte entry to trigger calcium release and coordinated contraction of the spermathecal tissue. PMID:23671426

  13. Enhancing Learning--and More!--Through Cooperative Learning. IDEA Paper.

    ERIC Educational Resources Information Center

    Millis, Barbara J.

    This paper describes cooperative learning, an instructional approach designed to promote deep learning, encourage self-esteem and the acceptance of others, and improve interpersonal effectiveness. Cooperative learning entails small groups working on specific tasks, carefully structured. The premises underlying cooperative learning and the theory…

  14. Enhancement of environment and resources engineering studies through an international cooperation network

    NASA Astrophysics Data System (ADS)

    Caporali, E.; Tuneski, A.

    2012-12-01

    Higher education plays a very important role in the modern societies development, enhancing social, cultural and economic development for a sustainable growth, environment respectful. In this framework, the European Commission promotes the TEMPUS-Trans European Mobility Programme for University Studies. Curricula harmonization and lifelong learning programme development in higher education are among the focused aspects of the TEMPUS programme. The DEREL-Development of Environment and Resources Engineering Learning, is a three years TEMPUS project coordinated by the University of Firenze, in cooperation with colleagues of the Ss Cyril and Methodius University, Skopje financed and activated since October 2010. The DEREL Project Consortium consists of 4 EU Universities (from Italy, Greece, Germany and Austria), 7 Partner Countries (PC) Universities (from FYR of Macedonia, Serbia and Albania), and 1 PC Ministry, 4 PC National Agencies, 1 PC non governmental organization and 1 PC enterprise. In cooperation with the same 4 EU Universities and the same Macedonian Institutions, in the period 2005-2008 also a TEMPUS JEP entitled DEREC-Development of Environmental and Resources Engineering Curriculum, was also carried out by the University of Firenze in cooperation with colleagues of the Ss Cyril and Methodius University. Within DEREC a new three-years first cycle curriculum in Environmental and Resources Engineering was opened at the University Ss Cyril and Methodius, Skopje, and the necessary conditions for offering a Joint Degree Title, on the basis of an agreement between the Ss. Cyril and Methodius University and the University of Firenze, were fulfilled. The running DEREL project, as a continuation of DEREC, is aimed to introduce a new, up-to-date, postgraduate second cycle curriculum in Environment and Resources Engineering at the Ss Cyril and Methodius University in Skopje, FYR of Macedonia, University of Novi Sad, Serbia and Polytechnic University of Tirana, Albania

  15. U.S./Russian cooperative efforts to enhance nuclear MPC&A at VNIITF, (Chelyabinsk-70)

    SciTech Connect

    Abramson, B; Apt, K; Blasy, J; Bukin, D; Churikov, Y; Eras, A; Magda, E; Neymotin, L; Schultz, F; Slankas, T; Tsygankov, G; Zuev, V

    1998-09-01

    The All Russian Scientific Research Institute of Technical Physics (VNIITF) is one of the major sites in the nuclear weapons complex in Russia. The site contains a number of research facilities which use nuclear material as well as assembly, disassembly, and testing of prototypes (pilot samples) of nuclear weapons. VNIITF also has ties to the major nuclear materials production facilities in the Urals region of Russia. The objective of the U.S./Russian Materials Protection Control and Accounting (MPC&A) cooperative program between the US Department of Energy and Russia's Ministry of Atomic Eneryy, at VNIITF is to improve the protection and accountability of nuclear material at VNIITF. Enhanced safeguards systems have been implemented at a reactor test area called the Pulse Research Reactor Facility (PRR) in Area 20. The area contains three pulse reactors with associated storage areas. The integrated MPC&A system at the PRR was demonstrated to US and Russian audiences in May, 1998. Expansion of work into several new facilities is underway both in Area 20 and at other locations. These include processing and production facilities some of which are considered sensitive facilities, by the Russian side. Methods have been developed to assure that work is done as agreed without actually having access to the buildings. C-70 has developed an extensive computerized system which integrates the physical security alarm station with elements of the nuclear material control system. Under the MPC&A program, the existing systems have been augmented with Russian and US technologies. This paper will describe the work completed at the PRR, and the on-going activities and cooperative effort between the Lawrence Livermore, Los Alamos, Sandia, Oak Ridge, Pacific Northwest, and Brookhaven US Department of Energy National Laboratories in support of VNIITF.

  16. Enhanced Old-New Recognition and Source Memory for Faces of Cooperators and Defectors in a Social-Dilemma Game

    ERIC Educational Resources Information Center

    Bell, Raoul; Buchner, Axel; Musch, Jochen

    2010-01-01

    A popular assumption in evolutionary psychology is that the human mind comprises specialized cognitive modules for social exchange, including a module that serves to enhance memory for faces of cheaters. In the present study, participants played a trust game with computerized opponents, who either defected or cooperated. In a control condition, no…

  17. Longitudinal Echocardiographic Evaluation of an Unusual Presentation of X-Linked Myxomatous Valvular Dystrophy Caused by Filamin A Mutation.

    PubMed

    Ma, Peter H; Sachdeva, Ritu; Wilson, Elizabeth C; Guzzetta, Nina A

    2016-09-01

    Polyvalvar myxomatous valve degeneration is a clinical pathology rarely encountered during cardiac anesthesia, but, when present, most commonly occurs in the context of a connective tissue disorder. Filamin A mutations have begun to be recognized as a source of progressive myxomatous mitral and tricuspid valve degeneration. These lesions can be diagnosed by echo, but their clinical presentation can be equivocal. We present a patient with significant echocardiographic findings of mitral and tricuspid valvar regurgitation, aortic dilatation, and intraoperative findings of aortic ectasia. In our case, a detailed family history led to a preoperative echocardiogram revealing myxomatous mitral and tricuspid valve degeneration with significant regurgitation and aortic dilatation. Genetic evaluation led to the diagnosis of a Filamin A mutation. Pre- and postrepair echocardiographic assessments of valvar function played a key role in the management of this patient. Continued surveillance of his aortic dilation and evaluation of postrepair valve function warrants close follow-up with a high likelihood for further surgical intervention. PMID:27004951

  18. Positive cooperativity between the thrombin and bradykinin B2 receptors enhances arachidonic acid release

    PubMed Central

    Hecquet, Claudie; Biyashev, Dauren; Tan, Fulong; Erdös, Ervin G.

    2006-01-01

    Bradykinin (BK) or kallikreins activate B2 receptors (R) which couple Gαi and Gαq proteins to release arachidonic acid (AA) and elevate [Ca2+]i. Thrombin cleaves the protease-activated-receptor-1 (PAR1) that couples Gαi, Gαq and Gα12/13 proteins. In CHO cells stably transfected with human B2R, thrombin liberated little AA, but it significantly potentiated AA release by B2R agonists. We explored mechanisms of cooperativity between constitutively expressed PAR1 and B2R. We also examined human endothelial cells expressing both Rs constitutively. The PAR1 agonist hexapeptide (TRAP) was as effective as thrombin. Inhibitors of components of Gαi, Gαq and Gα12/13 signaling pathways, and a PKCα inhibitor, Gö6976 blocked potentiation while phorbol, an activator, enhanced it. Several inhibitors, including a RhoA kinase inhibitor, a [Ca2+]i antagonist, and an inositol-(1,3,4)-trisphosphate R antagonist, reduced mobilization of [Ca2+]i by thrombin and blocked potentiation of AA release by B2R agonists. Because either a non-selective inhibitor (isotetrandrine) of phospholipase A2 (PLA2) or a Ca2+-dependent PLA2 inhibitor abolished potentiation of AA release by thrombin, while a Ca2+-independent PLA2 inhibitor did not, we concluded that the mechanism involves Ca2+-dependent PLA2 activation. Both thrombin and TRAP modified activation and phosphorylation of the B2R induced by BK. In lower concentrations they enhanced it, while higher concentrations inhibited phosphorylation and diminished B2R activation. Protection of the N-terminal Ser1-Phe2 bond of TRAP by an aminopeptidase inhibitor made this peptide much more active than the unprotected agonist. Thus, PAR1 activation enhances AA release by B2R agonists through signal transduction pathway. PMID:16183725

  19. Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of cartilaginous skeletal elements.

    PubMed

    Mizuhashi, Koji; Kanamoto, Takashi; Moriishi, Takeshi; Muranishi, Yuki; Miyazaki, Toshihiro; Terada, Koji; Omori, Yoshihiro; Ito, Masako; Komori, Toshihisa; Furukawa, Takahisa

    2014-06-01

    Mutations of Filamin genes, which encode actin-binding proteins, cause a wide range of congenital developmental malformations in humans, mainly skeletal abnormalities. However, the molecular mechanisms underlying Filamin functions in skeletal system formation remain elusive. In our screen to identify skeletal development molecules, we found that Cfm (Fam101) genes, Cfm1 (Fam101b) and Cfm2 (Fam101a), are predominantly co-expressed in developing cartilage and intervertebral discs (IVDs). To investigate the functional role of Cfm genes in skeletal development, we generated single knockout mice for Cfm1 and Cfm2, as well as Cfm1/Cfm2 double-knockout (Cfm DKO) mice, by targeted gene disruption. Mice with loss of a single Cfm gene displayed no overt phenotype, whereas Cfm DKO mice showed skeletal malformations including spinal curvatures, vertebral fusions and impairment of bone growth, showing that the phenotypes of Cfm DKO mice resemble those of Filamin B (Flnb)-deficient mice. The number of cartilaginous cells in IVDs is remarkably reduced, and chondrocytes are moderately reduced in Cfm DKO mice. We observed increased apoptosis and decreased proliferation in Cfm DKO cartilaginous cells. In addition to direct interaction between Cfm and Filamin proteins in developing chondrocytes, we showed that Cfm is required for the interaction between Flnb and Smad3, which was reported to regulate Runx2 expression. Furthermore, we found that Cfm DKO primary chondrocytes showed decreased cellular size and fewer actin bundles compared with those of wild-type chondrocytes. These results suggest that Cfms are essential partner molecules of Flnb in regulating differentiation and proliferation of chondryocytes and actin dynamics. PMID:24436304

  20. Active and inactive enhancers co-operate to exert localized and long-range control of gene regulation

    PubMed Central

    Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

    2016-01-01

    V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage and stage specific manner. Unexpectedly we find that both active and inactive AgR enhancers co-operate to disseminate their effects in a localized and long-range manner. Here we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. We further establish that in T cells long-range contact and co-operation between the inactive Igk enhancer, MiEκ and the active Tcrb enhancer, Eβ, alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage and stage specific control. PMID:27239026

  1. Cooperative antiproliferative and differentiation-enhancing activity of medicinal plant extracts in acute myeloid leukemia cells.

    PubMed

    Zhamanbayeva, Gulzhan T; Aralbayeva, Araylim N; Murzakhmetova, Maira K; Tuleukhanov, Sultan T; Danilenko, Michael

    2016-08-01

    Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with poor prognosis and limited treatment options. Sea buckthorn (Hippophae rhamnoides) berries, dog rose (Rosa canina) rosehips, and garden sage (Salvia officinalis) and oregano (Origanum vulgare) aerial parts are widely used in traditional medicine and exhibit antitumor effects in preclinical models. However, these plants remain scarcely tested for antileukemic activity. Here, we show that their water-ethanol leaf extracts reduced the growth and viability of AML cells and, at non-cytotoxic doses, potentiated cell differentiation induced by a low concentration of 1α,25-dihydroxyvitamin D3, the hormonal form of vitamin D, in a cell type-dependent manner. The latter effect was accompanied by upregulation of the vitamin D receptor protein components and its transcriptional activity. Furthermore, at minimally effective doses the extracts cooperated with one another to produce marked cytostatic effects associated with a partial S-phase arrest and a modest induction of apoptosis. In contrast, these combinations only slightly affected the growth and viability of proliferating normal human peripheral blood mononuclear cells. In addition, the extracts strongly inhibited microsomal lipid peroxidation and protected normal erythrocytes against hypoosmotic shock. Our results suggest that further exploration of the enhanced antileukemic effects of the combinations tested here may lead to the development of alternative therapeutic and preventive approaches against AML. PMID:27470342

  2. Tryptophan enhancement/depletion and reactions to failure on a cooperative computer game.

    PubMed

    Wingrove, J; Bond, A J; Cleare, A J

    1999-12-01

    Twenty-eight high trait hostility male volunteers played a "cooperative" computer game 4.5 hours after an amino acid drink enhanced with, or depleted of, tryptophan. Each trial involved steering a tank through minefields following directions from an unknown "partner." Failure was experienced when the tank hit a mine or when time ran out. Subjects' moods, verbal aggression, attributions of blame, vocal acoustics, and blood pressure were assessed. Differences between tryptophan groups were not significant for primary measures of anger and verbal aggression. However, depleted subjects reported greater increases in feelings of restlessness and incompetence, were less successful in avoiding mines and showed greater increases in blood pressure during the game. Subjects in both groups sent more negative ratings when they lost the game by virtue of hitting a mine rather than losing by running out of time. However, ratings of the depleted group were less influenced by the reason for losing the game. Also, vocal acoustics showed a group X reason-for-losing interaction in the high-frequency band. Tryptophan-depleted subjects with high scores on Behavioral-Activation-System-Drive were most likely to send negative ratings and those scoring high on Buss-Durkee Hostility Inventory Assault and Guilt to report increased anger after the game. PMID:10633481

  3. The Effect of Using Cooperative and Individual Weblog to Enhance Writing Performance

    ERIC Educational Resources Information Center

    Karsak, H. Gulhan Orhan; Fer, Seval; Orhan, Feza

    2014-01-01

    Academic writing, whether individual or cooperative, is an essential skill for today's graduates. However, motivating and helping students to learn to write effectively, either in cooperative or individual scenarios, poses many challenges, many of which can be overcome by technical means. The aim of this study is to investigate the effect of…

  4. Enhancing Outcomes in School Science for Pupils during Transition from Elementary School Using Cooperative Learning

    ERIC Educational Resources Information Center

    Thurston, Allen; Christie, Donald; Karagiannidou, Eleni; Murray, Pauline; Tolmie, Andrew; Topping, Keith

    2010-01-01

    This article reports data from a 2-year longitudinal study on cooperative learning in school science. The study reported the effects of cooperative learning in science on science attainment, effective development and social connectedness, and interactions during transition from elementary to high school in rural and urban school settings. The…

  5. Implementing Strategies of Cooperation for Enhancing Intrinsic Motivation towards English Language Learning

    ERIC Educational Resources Information Center

    Zapata, Julian Esteban

    2007-01-01

    This action research paper dealt with how to increase motivation towards English language learning through cooperative work in a public school in Medellín, Colombia. It was necessary to explore the concepts of teachers' beliefs, social teaching, collaborative and cooperative learning, to understand the conditions and activities that favored…

  6. Filamin A regulates monocyte migration through Rho small GTPases during osteoclastogenesis.

    PubMed

    Leung, Roland; Wang, Yongqiang; Cuddy, Karl; Sun, Chunxiang; Magalhaes, Joyce; Grynpas, Marc; Glogauer, Michael

    2010-05-01

    Osteoclastogenesis (OCG) results from the fusion of monocytes after stimulation with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). Migration of monocytes into close proximity precedes critical fusion events that are required for osteoclast formation. Cellular migration requires leading-edge actin cytoskeleton assembly that drives cellular locomotion. Filamin A (FLNa) cross-links F-actin filaments in the leading edge of migrating cells and also has been shown to regulate signal transduction during cell migration. However, little is known about the possible role of FLNa in osteoclastogenesis. Our objective in this study was to investigate the role of FLNa in osteoclastogenesis. Bone marrow monocytes isolated from the tibiae and femora of wild type (WT) and Flna-null mice were cultured for 6 days with M-CSF and RANKL, and osteoclasts were identified by tartrate-resistant acid phosphatase (TRACP) staining. The Flna-null mouse skeletal phenotype was characterized using dual-energy X-ray absorptiometry (DXA) to analyze the skeleton, as well as tests on blood chemistry. Osteoclast levels in vivo were quantified by counting of TRACP-stained histologic sections of distal femora. To elucidate the mechanisms by which Flna regulates osteoclastogenesis, migration, actin polymerization, and activation of Rho GTPases, Rac1, Cdc42, and RhoA were assessed in monocytes during in vitro OCG. Deficiencies in migration were rescued using constitutively active Rac1 and Cdc42 TAT fusion proteins. The RANKL signaling pathway was evaluated for activation by monitoring nuclear translocation of NF kappaB and c-jun and expression of key osteoclast genes using quantitative real-time polymerase chain reaction (qRT-PCR). Our results show that Flna-null monocytes formed fewer osteoclasts in vitro, and those that were formed were smaller with fewer nuclei. Decreased OCG was reflected in vivo in TRACP-stained histologic bone sections. Flna

  7. Cooperative Monitoring Center Occasional Paper/12: ENTNEA: A Concept for Enhancing Nuclear Transparency for Confidence Building in Northeast Asia

    SciTech Connect

    Nam, Man-Kwon; Shin, Sung-Tack

    1999-06-01

    Nuclear energy continues to be a strong and growing component of economic development in Northeast Asia. A broad range of nuclear energy systems already exists across the region and vigorous growth is projected. Associated with these capabilities and plans are various concerns about operational safety, environmental protection, and accumulation of spent fuel and other nuclear materials. We consider cooperative measures that might address these concerns. The confidence building measures suggested here center on the sharing of information to lessen concerns about nuclear activities or to solve technical problems. These activities are encompassed by an Enhanced Nuclear Transparency in Northeast Asia (ENTNEA) concept that would be composed of near-term, information-sharing activities and an eventual regional institution. The near-term activities would address specific concerns and build a tradition of cooperation; examples include radiation measurements for public safety and emergency response, demonstration of safe operations at facilities and in transportation, and material security in the back end of the fuel cycle. Linkages to existing efforts and organizations would be sought to maximize the benefits of cooperation. In the longer term, the new cooperative tradition might evolve into an ENTNEA institution. In institutional form, ENTNEA could combine the near-term activities and new cooperative activities, which might require an institutional basis, for the mutual benefit and security of regional parties.

  8. Comparative study of an externship program versus a corporate-academic cooperation program for enhancing nursing competence of graduating students

    PubMed Central

    2013-01-01

    Background New graduates report intense stress during the transition from school to their first work settings. Managing this transition is important to reduce turnover rates. This study compared the effects of an externship program and a corporate-academic cooperation program on enhancing junior college students’ nursing competence and retention rates in the first 3 months and 1 year of initial employment. Methods This two-phase study adopted a pretest and posttest quasi-experimental design. All participants were graduating students drawn from a 5-year junior nursing college in Taiwan. There were 19 and 24 students who participated in the phase I externship program and phase II corporate-academic cooperation program, respectively. The nursing competence of the students had to be evaluated by mentors within 48 hours of practicum training and after practicum training. The retention rate was also surveyed at 3 months and 1 year after beginning employment. Results Students who participated in the corporate-academic cooperation program achieved a statistically significant improvement in nursing competence and retention rates relative to those who participated in the externship program (p < 0.01 and p < 0.05, respectively). Conclusions The corporate-academic cooperation program facilitates the transition of junior college nursing students into independent staff nurses, enhances their nursing competence, and boosts retention rates. PMID:23945287

  9. [Enhancement of quality by employing qualification-oriented staff and team-oriented cooperation].

    PubMed

    Meyenburg-Altwarg, Iris; Tecklenburg, Andreas

    2010-01-01

    Taking three practical examples from a university hospital the present article describes how quality can be improved by linking deployment of qualification-oriented staff with team-oriented cooperation, especially with regard to the professional groups of physicians and nurses. In the first example, a cross-professional work group defined tasks which--in a legally acceptable manner--allow selected activities to be transferred from physicians to nurses, improving the work processes of all persons concerned. Work and duty profiles, training and modified work processes were created and implemented according to the PDCA circle-based process. The first evaluation took place after nine months using interviews, questionnaires (patients, physicians, and nurses) as well as CIRS. In the second example, emphasis was placed on offers of supplementary services for private patients resulting in a lightening of the workload on the nursing staff. These supplementary services are intended to enhance the wellbeing of the patients. Special external-service staff provide high standard hotel services. These services consistently receive high ratings from the patients. The methods used for introduction and evaluation are analogous to those used in the first example. The third example is concerned with the extension of nursing care and patient empowerment beyond the boundaries of ward and hospital. The guidelines were the implementation of the national expert standard for discharge management according to the DNQP. The methods of introduction were analogous to those used in example 1. For the evaluation interviews were conducted with all participating groups. In all examples actual quantitative measures (key ratios) are not yet available; however, the data collected from the interviews and questionnaires of all the participants are promising. PMID:20369442

  10. Cooperative integrin/ITAM signaling in platelets enhances thrombus formation in vitro and in vivo

    PubMed Central

    Zhi, Huiying; Rauova, Lubica; Hayes, Vincent; Gao, Cunji; Boylan, Brian; Newman, Debra K.; McKenzie, Steven E.; Cooley, Brian C.; Poncz, Mortimer; Newman, Peter J.

    2013-01-01

    The integrin family is composed of a series of 24 αβ heterodimer transmembrane adhesion receptors that mediate cell-cell and cell-extracellular matrix interactions. Adaptor molecules bearing immunoreceptor tyrosine-based activation motifs (ITAMs) have recently been shown to cooperate with specific integrins to increase the efficiency of transmitting ligand-binding–induced signals into cells. In human platelets, Fc receptor γ-chain IIa (FcγRIIa) has been identified as an ITAM-bearing transmembrane receptor responsible for mediating “outside-in” signaling through αIIbβ3, the major adhesion receptor on the platelet surface. To explore the importance of FcγRIIa in thrombosis and hemostasis, we subjected FcγRIIa-negative and FcγRIIa-positive murine platelets to a number of well-accepted models of platelet function. Compared with their FcγRIIa-negative counterparts, FcγRIIa-positive platelets exhibited increased tyrosine phosphorylation of Syk and phospholipase Cγ2 and increased spreading upon interaction with immobilized fibrinogen, retracted a fibrin clot faster, and showed markedly enhanced thrombus formation when perfused over a collagen-coated flow chamber under conditions of arterial and venous shear. They also displayed increased thrombus formation and fibrin deposition in in vivo models of vascular injury. Taken together, these data establish FcγRIIa as a physiologically important functional conduit for αIIbβ3-mediated outside-in signaling, and suggest that modulating the activity of this novel integrin/ITAM pair might be effective in controlling thrombosis. PMID:23264598

  11. Thrombocytopenia resulting from mutations in filamin A can be expressed as an isolated syndrome.

    PubMed

    Nurden, Paquita; Debili, Najet; Coupry, Isabelle; Bryckaert, Marijke; Youlyouz-Marfak, Ibtissam; Solé, Guilhem; Pons, Anne-Cécile; Berrou, Eliane; Adam, Frédéric; Kauskot, Alexandre; Lamazière, Jean-Marie Daniel; Rameau, Philippe; Fergelot, Patricia; Rooryck, Caroline; Cailley, Dorothée; Arveiler, Benoît; Lacombe, Didier; Vainchenker, William; Nurden, Alan; Goizet, Cyril

    2011-11-24

    Filaminopathies A caused by mutations in the X-linked FLNA gene are responsible for a wide spectrum of rare diseases including 2 main phenotypes, the X-linked dominant form of periventricular nodular heterotopia (FLNA-PVNH) and the otopalatodigital syndrome spectrum of disorders. In platelets, filamin A (FLNa) tethers the principal receptors ensuring the platelet-vessel wall interaction, glycoprotein Ibα and integrin αIIbβ3, to the underlying cytoskeleton. Hemorrhage, coagulopathy, and thrombocytopenia are mentioned in several reports on patients with FLNA-PVNH. Abnormal platelet morphology in 2 patients with FLNA-PVNH prompted us to examine a third patient with similar platelet morphology previously diagnosed with immunologic thrombocytopenic purpura. Her enlarged platelets showed signs of FLNa degradation in Western blotting, and a heterozygous missense mutation in FLNA was detected. An irregular distribution of FLNa within the total platelet population was shown by confocal microscopy for all 3 patients. In vitro megakaryocyte cultures showed an abnormal differentiation, including an irregular distribution of FLNa with a frayed aspect, the presence of enlarged α-granules, and an abnormal fragmentation of the cytoplasm. Mutations in FLNA may represent an unrecognized cause of macrothrombocytopenia with an altered platelet production and a modified platelet-vessel wall interaction. PMID:21960593

  12. Cytoskeletal protein filamin A is a nucleolar protein that suppresses ribosomal RNA gene transcription.

    PubMed

    Deng, Wensheng; Lopez-Camacho, Cesar; Tang, Jen-Yang; Mendoza-Villanueva, Daniel; Maya-Mendoza, Apolinar; Jackson, Dean A; Shore, Paul

    2012-01-31

    Filamin A (FLNA) is an actin-binding protein with a well-established role in the cytoskeleton, where it determines cell shape and locomotion by cross-linking actin filaments. Mutations in FLNA are associated with a wide range of genetic disorders. Here we demonstrate a unique role for FLNA as a nucleolar protein that associates with the RNA polymerase I (Pol I) transcription machinery to suppress rRNA gene transcription. We show that depletion of FLNA by siRNAs increased rRNA expression, rDNA promoter activity and cell proliferation. Immunodepletion of FLNA from nuclear extracts resulted in a decrease in rDNA promoter-driven transcription in vitro. FLNA coimmunoprecipitated with the Pol I components actin, TIF-IA, and RPA40, and their occupancy of the rDNA promoter was increased in the absence of FLNA in vivo. The FLNA actin-binding domain is essential for the suppression of rRNA expression and for inhibiting recruitment of the Pol I machinery to the rDNA promoter. These findings reveal an additional role for FLNA as a regulator of rRNA gene expression and have important implications for our understanding of the role of FLNA in human disease. PMID:22307607

  13. Filamin A mutation associated with normal reading skills and dyslexia in a family with periventricular heterotopia.

    PubMed

    Reinstein, Eyal; Chang, Bernard S; Robertson, Stephen P; Rimoin, David L; Katzir, Tami

    2012-08-01

    Periventricular heterotopia (PH) is a disorder of neuronal migration during fetal development that is characterized by morphologically normal neurons being located in an anatomically abnormal position in the mature brain. PH is usually diagnosed in patients presenting with a seizure disorder, when neuroimaging demonstrates the ectopically placed nodules of neurons. PH is a genetically and phenotypically heterogeneous disorder. The most commonly identified genetic cause is the X-linked dominant inheritance of mutations in the Filamin A (FLNA) gene. Multiple lines of evidence support the contribution of genetic factors in dyslexia. As dyslexia does not show a single-gene pattern of inheritance, it is classified as a complex genetic disorder. We have recently identified a specific reading fluency deficit in a variable group of patients with PH, in the context of normal intelligence. Here, we present a study of a mother-daughter pair who share bilateral widespread gray matter heterotopia caused by a novel mutation in FLNA and the same pattern of X-chromosome inactivation but who exhibit divergent reading and cognitive profiles. This novel observation highlights the uncertainty of using heterotopia anatomy in clinical practice to predict behavioral outcome. PMID:22740120

  14. Platelet functional alterations in a Bernard-Soulier syndrome patient with filamin A mutation.

    PubMed

    Li, Jiaming; Dai, KeSheng; Wang, Zhaoyue; Cao, Lijuan; Bai, Xia; Ruan, Changgeng

    2015-01-01

    Defects in filamin A (FLNA) gene could lead to low platelet counts and decreased surface expression of glycoprotein (GP) Ibα. Here, we report and investigate the FLNA genomic alteration of a case with Bernard-Soulier syndrome (BSS), a rare hereditary bleeding disorder caused by quantitative or qualitative abnormalities in the GP Ib-IX-V receptor. DNA sequencing analysis reveals the presence of a GP Ibα c.987G > A mutation and a FLNA c.1582 G > A mutation in this patient. Transient transfection studies show that GP Ibα c.987G > A mutation abolishes the surface expression of GP Ibα on the transfected CHO cells. On the other hand, abnormal responses to collagen, including the platelet aggregation, secretion, and GP VI signaling pathways, are associated with FLNA c.1582G > A mutation. Our findings confirm a central role for FLNA in platelet-adhesive functions. The interaction between FLNA and GP Ibα in platelets deserves to be investigated. PMID:26133172

  15. Brefeldin A-inhibited guanine exchange factor 2 regulates filamin A phosphorylation and neuronal migration.

    PubMed

    Zhang, Jingping; Neal, Jason; Lian, Gewei; Shi, Bingxing; Ferland, Russell J; Sheen, Volney

    2012-09-01

    Periventricular heterotopia (PH) is a human malformation of cortical development associated with gene mutations in ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2 encodes for Big2 protein) and Filamin A (FLNA). PH is thought to derive from neuroependymal disruption, but the extent to which neuronal migration contributes to this phenotype is unknown. Here, we show that Arfgef2 null mice develop PH and exhibit impaired neural migration with increased protein expression for both FlnA and phosphoFlnA at Ser2152. Big2 physically interacts with FlnA and overexpression of phosphomimetic Ser2512 FLNA impairs neuronal migration. FlnA phosphorylation directs FlnA localization toward the cell cytoplasm, diminishes its binding affinity to actin skeleton, and alters the number and size of paxillin focal adhesions. Collectively, our results demonstrate a molecular mechanism whereby Big2 inhibition promotes phosphoFlnA (Ser2152) expression, and increased phosphoFlnA impairs its actin binding affinity and the distribution of focal adhesions, thereby disrupting cell intrinsic neuronal migration. PMID:22956851

  16. Filamin depletion blocks endoplasmic spreading and destabilizes force-bearing adhesions.

    PubMed

    Lynch, Christopher D; Gauthier, Nils C; Biais, Nicolas; Lazar, Andre M; Roca-Cusachs, Pere; Yu, Cheng-Han; Sheetz, Michael P

    2011-04-15

    Cell motility is an essential process that depends on a coherent, cross-linked actin cytoskeleton that physically coordinates the actions of numerous structural and signaling molecules. The actin cross-linking protein, filamin (Fln), has been implicated in the support of three-dimensional cortical actin networks capable of both maintaining cellular integrity and withstanding large forces. Although numerous studies have examined cells lacking one of the multiple Fln isoforms, compensatory mechanisms can mask novel phenotypes only observable by further Fln depletion. Indeed, shRNA-mediated knockdown of FlnA in FlnB(-/-) mouse embryonic fibroblasts (MEFs) causes a novel endoplasmic spreading deficiency as detected by endoplasmic reticulum markers. Microtubule (MT) extension rates are also decreased but not by peripheral actin flow, because this is also decreased in the Fln-depleted system. Additionally, Fln-depleted MEFs exhibit decreased adhesion stability that appears in increased ruffling of the cell edge, reduced adhesion size, transient traction forces, and decreased stress fibers. FlnA(-/-) MEFs, but not FlnB(-/-) MEFs, also show a moderate defect in endoplasm spreading, characterized by initial extension followed by abrupt retractions and stress fiber fracture. FlnA localizes to actin linkages surrounding the endoplasm, adhesions, and stress fibers. Thus we suggest that Flns have a major role in the maintenance of actin-based mechanical linkages that enable endoplasmic spreading and MT extension as well as sustained traction forces and mature focal adhesions. PMID:21325628

  17. An adventitious interaction of filamin A with RhoGDI2(Tyr153Glu).

    PubMed

    Song, Mia; He, Qianjing; Berk, Benjamin-Andreas; Hartwig, John H; Stossel, Thomas P; Nakamura, Fumihiko

    2016-01-15

    Filamin A (FLNA) is an actin filament crosslinking protein with multiple intracellular binding partners. Mechanical force exposes cryptic FLNA binding sites for some of these ligands. To identify new force-dependent binding interactions, we used a fusion construct composed of two FLNA domains, one of which was previously identified as containing a force-dependent binding site as a bait in a yeast two-hybrid system and identified the Rho dissociation inhibitor 2 (RhoGDI2) as a potential interacting partner. A RhoGDI2 truncate with 81 N-terminal amino acid residues and a phosphomimetic mutant, RhoGDI(Tyr153Glu) interacted with the FLNA construct. However, neither wild-type or full-length RhoGDI2 phosphorylated at Y153 interacted with FLNA. Our interpretation of these contradictions is that truncation and/or mutation of RhoGDI2 perturbs its conformation to expose a site that adventitiously binds FLNA and is not a bona-fide interaction. Therefore, previous studies reporting that a RhoGDI(Y153E) mutant suppresses the metastasis of human bladder cancer cells must be reinvestigated in light of artificial interaction of this point mutant with FLNA. PMID:26707877

  18. Enhancing efficiency and power of quantum-dots resonant tunneling thermoelectrics in three-terminal geometry by cooperative effects

    SciTech Connect

    Jiang, Jian-Hua

    2014-11-21

    We propose a scheme of multilayer thermoelectric engine where one electric current is coupled to two temperature gradients in three-terminal geometry. This is realized by resonant tunneling through quantum dots embedded in two thermal and electrical resisting polymer matrix layers between highly conducting semiconductor layers. There are two thermoelectric effects, one of which is pertaining to inelastic transport processes (if energies of quantum dots in the two layers are different), while the other exists also for elastic transport processes. These two correspond to the transverse and longitudinal thermoelectric effects, respectively, and are associated with different temperature gradients. We show that cooperation between the two thermoelectric effects leads to markedly improved figure of merit and power factor, which is confirmed by numerical calculation using material parameters. Such enhancement is robust against phonon heat conduction and energy level broadening. Therefore, we demonstrated cooperative effect as an additional way to effectively improve performance of thermoelectrics in three-terminal geometry.

  19. China-Japan enhance joint research cooperation for drug discoveries and development: News from CJMWDDT 2007 in Jinan, China.

    PubMed

    Liu, X Y; Qu, X J; Tang, W

    2007-08-01

    Viral hepatitis is currently a major global cause of morbidity and mortality. In some Asian countries like China and Japan, Hepatitis B and C in particular are the most common extremely infectious diseases and are likely to develop into liver cirrhosis. Furthermore, statistics indicate that patients with liver cirrhosis resulting from hepatitis B and C have an increased risk of developing hepatocellular carcinoma (HCC). Scientists have worked tirelessly to find curative therapeutic strategies to control chronic hepatitis and liver cirrhosis, accompanied by improvements in public health and living conditions. China's Shandong University and the University of Tokyo in Japan previously established a longterm cooperative relationship. Cooperative programs include co-training of postgraduates, exchanges of visiting scholars, academic symposia, and a bilateral international joint research program. Some substantive progress has been made as a result of bilateral endeavors. For instance, the Shandong University China-Japan Cooperation Center for Drug Discovery & Screening (SDU-DDSC) has enhanced to serve as an important platform for further close cooperation. At the same time, the International Advancement Center for Medicine & Health Research (IACMHR) - "Drug Discoveries and Therapeutics" and International Research and Cooperation Association for Bio & Socio-Sciences Advancement (IRCA-BSSA) - "BioScience Trends" were established (Visit http://www.ddtjournal.com and http://www.biosciencetrends.com ). The first China-Japan conference on new drug discoveries and therapeutics (CJMWDDT 2007) was recently held in Jinan, China May 27-29, 2007, which provided opportunities for further communication and cooperation and increased knowledge of new drug research and clinical cures for hepatitis. Financially supported by the National Natural Science Foundation of China (NSFC) and the Japan Society for the Promotion of Science (JSPS), the conference covered a wide range of topics in

  20. Binding of pro-prion to filamin A: by design or an unfortunate blunder

    PubMed Central

    Li, C; Xin, W; Sy, M-S

    2011-01-01

    Over the last decades, cancer research has focused on tumor suppressor genes and oncogenes. Genes in other cellular pathways has received less attention. Between 0.5% to 1% of the mammalian genome encodes for proteins that are tethered on the cell membrane via a glycosylphosphatidylinositol (GPI)-anchor. The GPI modification pathway is complex and not completely understood. Prion (PrP), a GPI-anchored protein, is infamous for being the only normal protein that when misfolded can cause and transmit a deadly disease. Though widely expressed and highly conserved, little is known about the functions of PrP. Pancreatic cancer and melanoma cell lines express PrP. However, in these cell lines the PrP exists as a pro-PrP as defined by retaining its GPI anchor peptide signal sequence (GPI-PSS). Unexpectedly, the GPI-PSS of PrP has a filamin A (FLNA) binding motif and binds FLNA. FLNA is a cytolinker protein, and an integrator of cell mechanics and signaling. Binding of pro-PrP to FLNA disrupts the normal FLNA functions. Although normal pancreatic ductal cells lack PrP, about 40% of patients with pancreatic ductal cell adenocarcinoma express PrP in their cancers. These patients have significantly shorter survival time compared with patients whose cancers lack PrP. Pro-PrP is also detected in melanoma in situ but is undetectable in normal melanocyte, and invasive melanoma expresses more pro-PrP. In this review, we will discuss the underlying mechanisms by which binding of pro-PrP to FLNA disrupts normal cellular physiology and contributes to tumorigenesis, and the potential mechanisms that cause the accumulation of pro-PrP in cancer cells. PMID:20697352

  1. Filamin A mediated Big2 dependent endocytosis: From apical abscission to periventricular heterotopia.

    PubMed

    Sheen, Volney L

    2014-01-01

    Periventricular heterotopia (PH) is one of the most common malformations of cortical development (MCD). Nodules along the lateral ventricles of the brain, disruption of the ventricular lining, and a reduced brain size are hallmarks of this disorder. PH results in a disruption of the neuroependyma, inhibition of neural proliferation and differentiation, and altered neuronal migration. Human mutations in the genes encoding the actin-binding Filamin A (FLNA) and the vesicle trafficking Brefeldin A-associated guanine exchange factor 2 (BIG2 is encoded by the ARFGEF2 gene) proteins are implicated in PH formation. Recent studies have shown that the transition from proliferating neural progenitors to post-mitotic neurons relies on apical abscission along the neuroepithelium. This mechanism involves an actin dependent contraction of the apical portion of a neural progenitor along the ventricular lining to complete abscission. Actin also maintains stability of various cell adhesion molecules along the neuroependyma. Loss of cadherin directs disassembly of the primary cilium, which transduces sonic-hedgehog (Shh) signaling. Shh signaling is required for continued proliferation. In this context, apical abscission regulates neuronal progenitor exit and migration from the ventricular zone by detachment from the neuroependyma, relies on adhesion molecules that maintain the integrity of the neuroepithelial lining, and directs neural proliferation. Each of these processes is disrupted in PH, suggesting that genes causal for this MCD, may fundamentally mediate apical abscission in cortical development. Here we discuss several recent reports that demonstrate a coordinated role for actin and vesicle trafficking in modulating neural development along the neurepithelium, and potentially the neural stem cell to neuronal transition. PMID:25097827

  2. Filamin a regulates neural progenitor proliferation and cortical size through Wee1-dependent Cdk1 phosphorylation.

    PubMed

    Lian, Gewei; Lu, Jie; Hu, Jianjun; Zhang, Jingping; Cross, Sally H; Ferland, Russell J; Sheen, Volney L

    2012-05-30

    Cytoskeleton-associated proteins play key roles not only in regulating cell morphology and migration but also in proliferation. Mutations in the cytoskeleton-associated gene filamin A (FlnA) cause the human disorder periventricular heterotopia (PH). PH is a disorder of neural stem cell development that is characterized by disruption of progenitors along the ventricular epithelium and subsequent formation of ectopic neuronal nodules. FlnA-dependent regulation of cytoskeletal dynamics is thought to direct neural progenitor migration and proliferation. Here we show that embryonic FlnA-null mice exhibited a reduction in brain size and decline in neural progenitor numbers over time. The drop in the progenitor population was not attributable to cell death or changes in premature differentiation, but to prolonged cell cycle duration. Suppression of FlnA led to prolongation of the entire cell cycle length, principally in M phase. FlnA loss impaired degradation of cyclin B1-related proteins, thereby delaying the onset and progression through mitosis. We found that the cdk1 kinase Wee1 bound FlnA, demonstrated increased expression levels after loss of FlnA function, and was associated with increased phosphorylation of cdk1. Phosphorylation of cdk1 inhibited activation of the anaphase promoting complex degradation system, which was responsible for cyclin B1 degradation and progression through mitosis. Collectively, our results demonstrate a molecular mechanism whereby FlnA loss impaired G2 to M phase entry, leading to cell cycle prolongation, compromised neural progenitor proliferation, and reduced brain size. PMID:22649246

  3. A glial origin for periventricular nodular heterotopia caused by impaired expression of Filamin-A.

    PubMed

    Carabalona, Aurelie; Beguin, Shirley; Pallesi-Pocachard, Emilie; Buhler, Emmanuelle; Pellegrino, Christophe; Arnaud, Karen; Hubert, Philippe; Oualha, Mehdi; Siffroi, Jean Pierre; Khantane, Sabrina; Coupry, Isabelle; Goizet, Cyril; Gelot, Antoinette Bernabe; Represa, Alfonso; Cardoso, Carlos

    2012-03-01

    Periventricular nodular heterotopia (PH) is a human brain malformation caused by defective neuronal migration that results in ectopic neuronal nodules lining the lateral ventricles beneath a normal appearing cortex. Most affected patients have seizures and their cognitive level varies from normal to severely impaired. Mutations in the Filamin-A (or FLNA) gene are the main cause of PH, but the underlying pathological mechanism remains unknown. Although two FlnA knockout mouse strains have been generated, none of them showed the presence of ectopic nodules. To recapitulate the loss of FlnA function in the developing rat brain, we used an in utero RNA interference-mediated knockdown approach and successfully reproduced a PH phenotype in rats comparable with that observed in human patients. In FlnA-knockdown rats, we report that PH results from a disruption of the polarized radial glial scaffold in the ventricular zone altering progression of neural progenitors through the cell cycle and impairing migration of neurons into the cortical plate. Similar alterations of radial glia are observed in human PH brains of a 35-week fetus and a 3-month-old child, harboring distinct FLNA mutations not previously reported. Finally, juvenile FlnA-knockdown rats are highly susceptible to seizures, confirming the reliability of this novel animal model of PH. Our findings suggest that the disorganization of radial glia is the leading cause of PH pathogenesis associated with FLNA mutations. Rattus norvegicus FlnA mRNA (GenBank accession number FJ416060). PMID:22076441

  4. R-Ras interacts with filamin a to maintain endothelial barrier function.

    PubMed

    Griffiths, G S; Grundl, M; Allen, J S; Matter, M L

    2011-09-01

    The molecular mechanisms regulating vascular barrier integrity remain incompletely elucidated. We have previously reported an association between the GTPase R-Ras and repeat 3 of Filamin A (FLNa). Loss of FLNa has been linked to increased vascular permeability. We sought to determine whether FLNa's association with R-Ras affects endothelial barrier function. We report that in endothelial cells endogenous R-Ras interacts with endogenous FLNa as determined by co-immunoprecipitations and pulldowns with the FLNa-GST fusion protein repeats 1-10. Deletion of FLNa repeat 3 (FLNaΔ3) abrogated this interaction. In these cells FLNa and R-Ras co-localize at the plasma membrane. Knockdown of R-Ras and/or FLNa by siRNA promotes vascular permeability, as determined by TransEndothelial Electrical Resistance and FITC-dextran transwell assays. Re-expression of FLNa restored endothelial barrier function in cells lacking FLNa whereas re-expression of FLNaΔ3 did not. Immunostaining for VE-Cadherin in cells with knocked down R-Ras and FLNa demonstrated a disorganization of VE-Cadherin at adherens junctions. Loss of R-Ras and FLNa or blocking R-Ras function via GGTI-2133, a selective R-Ras inhibitor, induced vascular permeability and increased phosphorylation of VE-Cadherin (Y731) and Src (Y416). Expression of dominant negative R-Ras promoted vascular permeability that was blocked by the Src inhibitor PP2. These findings demonstrate that maintaining endothelial barrier function is dependent upon active R-Ras and association between R-Ras and FLNa and that loss of this interaction promotes VE-Cadherin phosphorylation and changes in downstream effectors that lead to endothelial leakiness. PMID:21660952

  5. MVP-Associated Filamin A Mutations Affect FlnA-PTPN12 (PTP-PEST) Interactions

    PubMed Central

    Duval, Damien; Labbé, Pauline; Bureau, Léa; Le Tourneau, Thierry; Norris, Russell A.; Markwald, Roger R.; Levine, Robert; Schott, Jean-Jacques; Mérot, Jean

    2015-01-01

    Although the genetic basis of mitral valve prolapse (MVP) has now been clearly established, the molecular and cellular mechanisms involved in the pathological processes associated to a specific mutation often remain to be determined. The FLNA gene (encoding Filamin A; FlnA) was the first gene associated to non-syndromic X-linked myxomatous valvular dystrophy, but the impacts of the mutations on its function remain un-elucidated. Here, using the first repeats (1–8) of FlnA as a bait in a yeast two-hybrid screen, we identified the tyrosine phosphatase PTPN12 (PTP-PEST) as a specific binding partner of this region of FlnA protein. In addition, using yeast two-hybrid trap assay pull down and co-immunoprecipitation experiments, we showed that the MVP-associated FlnA mutations (G288R, P637Q, H743P) abolished FlnA/PTPN12 interactions. PTPN12 is a key regulator of signaling pathways involved in cell-extracellular matrix (ECM) crosstalk, cellular responses to mechanical stress that involve integrins, focal adhesion transduction pathways, and actin cytoskeleton dynamics. Interestingly, we showed that the FlnA mutations impair the activation status of two PTPN12 substrates, the focal adhesion associated kinase Src, and the RhoA specific activating protein p190RhoGAP. Together, these data point to PTPN12/FlnA interaction and its weakening by FlnA mutations as a mechanism potentially involved in the physiopathology of FlnA-associated MVP. PMID:26594644

  6. Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours.

    PubMed

    Vitali, Eleonora; Cambiaghi, Valeria; Zerbi, Alessandro; Carnaghi, Carlo; Colombo, Piergiuseppe; Peverelli, Erika; Spada, Anna; Mantovani, Giovanna; Lania, Andrea G

    2016-03-01

    Somatostatin receptor type 2 (SST2) is the main pharmacological target of somatostatin (SS) analogues widely used in patients with pancreatic neuroendocrine tumours (P-NETs), this treatment being ineffective in a subset of patients. Since it has been demonstrated that Filamin A (FLNA) is involved in mediating GPCR expression, membrane anchoring and signalling, we investigated the role of this cytoskeleton protein in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in human P-NETs and in QGP1 cell line. We demonstrated that FLNA silencing was not able to affect SST2 expression in P-NET cells in basal conditions. Conversely, a significant reduction in SST2 expression (-43 ± 21%, P < 0.05 vs untreated cells) was observed in FLNA silenced QGP1 cells after long term SST2 activation with BIM23120. Moreover, the inhibitory effect of BIM23120 on cyclin D1 expression (-46 ± 18%, P < 0.05 vs untreated cells), P-ERK1/2 levels (-42 ± 14%; P < 0.05 vs untreated cells), cAMP accumulation (-24 ± 3%, P < 0.05 vs untreated cells), VEGF expression (-31 ± 5%, P < 0.01 vs untreated cells) and in vitro release (-40 ± 24%, P < 0.05 vs untreated cells) was completely lost after FLNA silencing. Interestingly, BIM23120 promoted cell adhesion (+86 ± 45%, P < 0.05 vs untreated cells) and inhibited cell migration (-24 ± 2%, P < 0.00001 vs untreated cells) in P-NETs cells and these effects were abolished in FLNA silenced cells. In conclusion, we demonstrated that FLNA plays a crucial role in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in P-NETs and in QGP1 cell line, suggesting a possible role of FLNA in determining the different responsiveness to SS analogues observed in P-NET patients. PMID:26733502

  7. Building Workplace Learning with Polytechnics in Finland: Multiple Goals and Cooperation in Enhancing Connectivity

    ERIC Educational Resources Information Center

    Virolainen, M.; Stenström, M.-L.

    2013-01-01

    This article examines the goals of employers when they organise work placements for students. It explores how far, in cooperating with polytechnics, employers adhere to a connective model of students' work experiences within their organisations. The paper makes use of a quantitative study based on employers' responses to a questionnaire…

  8. A sequential-move game for enhancing safety and security cooperation within chemical clusters.

    PubMed

    Pavlova, Yulia; Reniers, Genserik

    2011-02-15

    The present paper provides a game theoretic analysis of strategic cooperation on safety and security among chemical companies within a chemical industrial cluster. We suggest a two-stage sequential move game between adjacent chemical plants and the so-called Multi-Plant Council (MPC). The MPC is considered in the game as a leader player who makes the first move, and the individual chemical companies are the followers. The MPC's objective is to achieve full cooperation among players through establishing a subsidy system at minimum expense. The rest of the players rationally react to the subsidies proposed by the MPC and play Nash equilibrium. We show that such a case of conflict between safety and security, and social cooperation, belongs to the 'coordination with assurance' class of games, and we explore the role of cluster governance (fulfilled by the MPC) in achieving a full cooperative outcome in domino effects prevention negotiations. The paper proposes an algorithm that can be used by the MPC to develop the subsidy system. Furthermore, a stepwise plan to improve cross-company safety and security management in a chemical industrial cluster is suggested and an illustrative example is provided. PMID:21146296

  9. Using Strategy Cards to Enhance Cooperative Learning for Students with Learning Disabilities.

    ERIC Educational Resources Information Center

    Goor, Mark; And Others

    1996-01-01

    The classroom technique of using strategy cards in cooperative learning situations for students with learning disabilities is explained. Guidelines and a script on how to instruct students to use the cards are provided. An example of a strategy card is illustrated. (CR)

  10. 78 FR 35323 - Solicitation for a Cooperative Agreement-Gender-Informed Research (Women): Enhanced Approaches to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-12

    ... National Institute of Corrections Solicitation for a Cooperative Agreement--Gender-Informed Research (Women... gender-informed knowledge specific to women that will both inform a future research agenda and define a... specific to justice-involved women and the most significant innovation in policy, practice, and...

  11. Generative Teaching: An Enhancement Strategy for the Learning of Economics in Cooperative Groups.

    ERIC Educational Resources Information Center

    Kourilsky, Marilyn; Wittrock, Merlin C.

    1992-01-01

    Increasing the learning of economics among 76 public high school seniors from lower socioeconomic levels by teaching them to use generative comprehension procedures in cooperative learning groups was attempted. Comparison with 66 controls indicated facilitative effects of generative teaching in increasing confidence in correctness of answers and…

  12. Computer-Supported Cooperative Prewriting for Enhancing Young EFL Learners' Writing Performance

    ERIC Educational Resources Information Center

    Lan, Yu-Ju; Sung, Yao-Ting; Cheng, Chia-Chun; Chang, Kuo-En

    2015-01-01

    The current study investigated the effects of different computer-supported cooperative prewriting strategies (text-based brainstorming, drawing, and mind mapping) on the writing performance of elementary-school EFL (English as a foreign language) learners in Taiwan. Three intact classes of fifth graders (N = 81 students; 27 per prewriting strategy…

  13. Enhanced DSSCs efficiency via Cooperate co-absorbance (CdS QDs) and plasmonic core-shell nanoparticle (Ag@PVP)

    PubMed Central

    Amiri, Omid; Salavati-Niasari, Masoud; Bagheri, Samira; Yousefi, Amin Termeh

    2016-01-01

    This paper describes cooperate the co-absorbance (CdS QDs) and the plasmonic core-shell nanoparticles (Ag@PVP) of dye synthesized solar cells in which CdS QDs and Ag@PVP are incorporated into the TiO2 layer. Cooperative nanoparticles show superior behavior on enhancing light absorption in comparison with reference cells. Cooperated DSSC exhibits the best performance with the power conversion efficiency of 7.64% which is superior to that of the free–modified DSSC with the PCE of 5%. Detailed studies offer an effective approach to enhance the efficiency of dye synthesized solar cells. PMID:27143126

  14. Enhanced DSSCs efficiency via Cooperate co-absorbance (CdS QDs) and plasmonic core-shell nanoparticle (Ag@PVP).

    PubMed

    Amiri, Omid; Salavati-Niasari, Masoud; Bagheri, Samira; Yousefi, Amin Termeh

    2016-01-01

    This paper describes cooperate the co-absorbance (CdS QDs) and the plasmonic core-shell nanoparticles (Ag@PVP) of dye synthesized solar cells in which CdS QDs and Ag@PVP are incorporated into the TiO2 layer. Cooperative nanoparticles show superior behavior on enhancing light absorption in comparison with reference cells. Cooperated DSSC exhibits the best performance with the power conversion efficiency of 7.64% which is superior to that of the free-modified DSSC with the PCE of 5%. Detailed studies offer an effective approach to enhance the efficiency of dye synthesized solar cells. PMID:27143126

  15. Enhanced DSSCs efficiency via Cooperate co-absorbance (CdS QDs) and plasmonic core-shell nanoparticle (Ag@PVP)

    NASA Astrophysics Data System (ADS)

    Amiri, Omid; Salavati-Niasari, Masoud; Bagheri, Samira; Yousefi, Amin Termeh

    2016-05-01

    This paper describes cooperate the co-absorbance (CdS QDs) and the plasmonic core-shell nanoparticles (Ag@PVP) of dye synthesized solar cells in which CdS QDs and Ag@PVP are incorporated into the TiO2 layer. Cooperative nanoparticles show superior behavior on enhancing light absorption in comparison with reference cells. Cooperated DSSC exhibits the best performance with the power conversion efficiency of 7.64% which is superior to that of the free–modified DSSC with the PCE of 5%. Detailed studies offer an effective approach to enhance the efficiency of dye synthesized solar cells.

  16. 75 FR 73027 - Cooperative Conservation Partnership Initiative and Wetlands Reserve Enhancement Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-29

    ... Wetlands Reserve Enhancement Program AGENCY: Commodity Credit Corporation and Natural Resources... Wetlands Reserve Enhancement Program (WREP) through the Mississippi River Basin Healthy Watersheds... watersheds of the Mississippi River Basin, as well as improve wildlife habitat and restore wetlands....

  17. A reduced propensity to cooperate under enhanced exploitation risk in a social mammal.

    PubMed

    Ferrari, Manuela; Lindholm, Anna K; König, Barbara

    2016-05-11

    Conditional adjustment of cooperativeness to the expected pay-off might be a useful strategy to avoid being exploited in public good situations. Parental care provided towards all offspring in a communal nest (containing offspring of several females) resembles a public good. Females indiscriminately caring for all young share the costs equally, but the pay-off may vary depending on their contribution to the joint nest (number of own offspring). Females with fewer offspring in the joint nest will be exploited and overinvest relative to their contribution. We experimentally created a situation of high conflict in communally nursing house mice, by using a genetic tool to create a difference in birth litter sizes. Females in the high conflict situation (unequal litter sizes at birth) showed a reduced propensity to give birth as part of a communal nest, therefore adjusting their cooperativeness to the circumstances. PMID:27170710

  18. Cooperation enhanced by the difference between interaction and learning neighborhoods for evolutionary spatial prisoner's dilemma games

    NASA Astrophysics Data System (ADS)

    Wu, Zhi-Xi; Wang, Ying-Hai

    2007-04-01

    We study an evolutionary prisoner’s dilemma game with two layered graphs, where the lower layer is the physical infrastructure on which the interactions are taking place and the upper layer represents the connections for the strategy adoption (learning) mechanism. This system is investigated by means of Monte Carlo simulations and an extended pair-approximation method. We consider the average density of cooperators in the stationary state for a fixed interaction graph, while varying the number of edges in the learning graph. According to the Monte Carlo simulations, the cooperation is modified substantially in a way resembling a coherence-resonance-like behavior when the number of learning edges is increased. This behavior is reproduced by the analytical results.

  19. Enhancement of beta-sheet assembly by cooperative hydrogen bonds potential

    PubMed Central

    Levy-Moonshine, Ami; Amir, El-ad David; Keasar, Chen

    2009-01-01

    Motivation: The roughness of energy landscapes is a major obstacle to protein structure prediction, since it forces conformational searches to spend much time struggling to escape numerous traps. Specifically, beta-sheet formation is prone to stray, since many possible combinations of hydrogen bonds are dead ends in terms of beta-sheet assembly. It has been shown that cooperative terms for backbone hydrogen bonds ease this problem by augmenting hydrogen bond patterns that are consistent with beta sheets. Here, we present a novel cooperative hydrogen-bond term that is both effective in promoting beta sheets and computationally efficient. In addition, the new term is differentiable and operates on all-atom protein models. Results: Energy optimization of poly-alanine chains under the new term led to significantly more beta-sheet content than optimization under a non-cooperative term. Furthermore, the optimized structure included very few non-native patterns. Availability: The new term is implemented within the MESHI package and is freely available at http://cs.bgu.ac.il/∼meshi. Contact: chen.keasar@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19628506

  20. Cooperative Enhancement of Cost Threshold in the Spatial N-Person Snowdrift Game

    NASA Astrophysics Data System (ADS)

    Lu, Dong-Liang; Zhang, Hong-Bin; Ge, Juan; Xu, Chen

    2012-08-01

    We study the cooperative behaviour of the N-person snowdrift game on a square lattice with different neighbourhoods and the cost threshold M for the cooperators. We apply the imitation mechanism for the players and find that there is an optimal frequency of cooperation fC as M varies in the game and the peak of fC shifts to higher M when more neighbours on the lattice are involved in the game. For a given cost-to-benefit ratio r, the system shows discontinuous phase transitions and the behaviour of fC vs M shows step-like structures. We construct payoff level structures and find that the above features can be understood by analyzing the transition behaviour between the payoff levels. The variations of r and M are equivalent to tune the payoff level structures. The plateaus in the step-like structure have similar payoff level structures and the discontinuous jumps correspond to different payoff level structures.

  1. Filamin A Expression Negatively Regulates Sphingosine-1-Phosphate-Induced NF-κB Activation in Melanoma Cells by Inhibition of Akt Signaling

    PubMed Central

    Campos, Ludmila S.; Rodriguez, Yamila I.; Leopoldino, Andreia M.; Hait, Nitai C.; Lopez Bergami, Pablo; Castro, Melina G.; Sanchez, Emilse S.; Maceyka, Michael

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that regulates many processes in inflammation and cancer. S1P is a ligand for five G-protein-coupled receptors, S1PR1 to -5, and also has important intracellular actions. Previously, we showed that intracellular S1P is involved in tumor necrosis factor alpha (TNF)-induced NF-κB activation in melanoma cell lines that express filamin A (FLNA). Here, we show that extracellular S1P activates NF-κB only in melanoma cells that lack FLNA. In these cells, S1P, but not TNF, promotes IκB kinase (IKK) and p65 phosphorylation, IκBα degradation, p65 nuclear translocation, and NF-κB reporter activity. NF-κB activation induced by S1P was mediated via S1PR1 and S1PR2. Exogenous S1P enhanced the phosphorylation of protein kinase Cδ (PKCδ), and its downregulation reduced S1P-induced the phosphorylation of IKK and p65. In addition, silencing of Bcl10 also inhibited S1P-induced IKK phosphorylation. Surprisingly, S1P reduced Akt activation in melanoma cells that express FLNA, whereas in the absence of FLNA, high phosphorylation levels of Akt were maintained, enabling S1P-mediated NF-κB signaling. In accord, inhibition of Akt suppressed S1P-mediated IKK and p65 phosphorylation and degradation of IκBα. Hence, these results support a negative role of FLNA in S1P-mediated NF-κB activation in melanoma cells through modulation of Akt. PMID:26552704

  2. Filamin A Expression Negatively Regulates Sphingosine-1-Phosphate-Induced NF-κB Activation in Melanoma Cells by Inhibition of Akt Signaling.

    PubMed

    Campos, Ludmila S; Rodriguez, Yamila I; Leopoldino, Andreia M; Hait, Nitai C; Lopez Bergami, Pablo; Castro, Melina G; Sanchez, Emilse S; Maceyka, Michael; Spiegel, Sarah; Alvarez, Sergio E

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that regulates many processes in inflammation and cancer. S1P is a ligand for five G-protein-coupled receptors, S1PR1 to -5, and also has important intracellular actions. Previously, we showed that intracellular S1P is involved in tumor necrosis factor alpha (TNF)-induced NF-κB activation in melanoma cell lines that express filamin A (FLNA). Here, we show that extracellular S1P activates NF-κB only in melanoma cells that lack FLNA. In these cells, S1P, but not TNF, promotes IκB kinase (IKK) and p65 phosphorylation, IκBα degradation, p65 nuclear translocation, and NF-κB reporter activity. NF-κB activation induced by S1P was mediated via S1PR1 and S1PR2. Exogenous S1P enhanced the phosphorylation of protein kinase Cδ (PKCδ), and its downregulation reduced S1P-induced the phosphorylation of IKK and p65. In addition, silencing of Bcl10 also inhibited S1P-induced IKK phosphorylation. Surprisingly, S1P reduced Akt activation in melanoma cells that express FLNA, whereas in the absence of FLNA, high phosphorylation levels of Akt were maintained, enabling S1P-mediated NF-κB signaling. In accord, inhibition of Akt suppressed S1P-mediated IKK and p65 phosphorylation and degradation of IκBα. Hence, these results support a negative role of FLNA in S1P-mediated NF-κB activation in melanoma cells through modulation of Akt. PMID:26552704

  3. Testosterone is associated with cooperation during intergroup competition by enhancing parochial altruism.

    PubMed

    Reimers, Luise; Diekhof, Esther K

    2015-01-01

    The steroid hormone testosterone is widely associated with negative behavioral effects, such as aggression or dominance. However, recent studies applying economic exchange tasks revealed conflicting results. While some point to a prosocial effect of testosterone by increasing altruistic behavior, others report that testosterone promotes antisocial tendencies. Taking into account additional factors such as parochial altruism (i.e., ingroup favoritism and outgroup hostility) might help to explain this contradiction. First evidence for a link between testosterone and parochial altruism comes from recently reported data of male soccer fans playing the ultimatum game. In this study high levels of endogenous testosterone predicted increased altruistic punishment during outgroup interactions and at the same time heightened ingroup generosity. Here, we report findings of another experimental task, the prisoner's dilemma, applied in the same context to examine the role of testosterone on parochial tendencies in terms of cooperation. In this task, 50 male soccer fans were asked to decide whether or not they wanted to cooperate with partners marked as either fans of the subject's own favorite team (ingroup) or fans of other teams (outgroups). Our results show that high testosterone levels were associated with increased ingroup cooperation during intergroup competition. In addition, subjects displaying a high degree of parochialism during intergroup competition had significantly higher levels of testosterone than subjects who did not differentiate much between the different groups. In sum, the present data demonstrate that the behavioral effects of testosterone are not limited to aggressive and selfish tendencies but may imply prosocial aspects depending on the context. By this means, our results support the previously reported findings on testosterone-dependent intergroup bias and indicate that this social hormone might be an important factor driving parochial altruism. PMID

  4. Testosterone is associated with cooperation during intergroup competition by enhancing parochial altruism

    PubMed Central

    Reimers, Luise; Diekhof, Esther K.

    2015-01-01

    The steroid hormone testosterone is widely associated with negative behavioral effects, such as aggression or dominance. However, recent studies applying economic exchange tasks revealed conflicting results. While some point to a prosocial effect of testosterone by increasing altruistic behavior, others report that testosterone promotes antisocial tendencies. Taking into account additional factors such as parochial altruism (i.e., ingroup favoritism and outgroup hostility) might help to explain this contradiction. First evidence for a link between testosterone and parochial altruism comes from recently reported data of male soccer fans playing the ultimatum game. In this study high levels of endogenous testosterone predicted increased altruistic punishment during outgroup interactions and at the same time heightened ingroup generosity. Here, we report findings of another experimental task, the prisoner's dilemma, applied in the same context to examine the role of testosterone on parochial tendencies in terms of cooperation. In this task, 50 male soccer fans were asked to decide whether or not they wanted to cooperate with partners marked as either fans of the subject's own favorite team (ingroup) or fans of other teams (outgroups). Our results show that high testosterone levels were associated with increased ingroup cooperation during intergroup competition. In addition, subjects displaying a high degree of parochialism during intergroup competition had significantly higher levels of testosterone than subjects who did not differentiate much between the different groups. In sum, the present data demonstrate that the behavioral effects of testosterone are not limited to aggressive and selfish tendencies but may imply prosocial aspects depending on the context. By this means, our results support the previously reported findings on testosterone-dependent intergroup bias and indicate that this social hormone might be an important factor driving parochial altruism. PMID

  5. Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring

    PubMed Central

    1990-01-01

    Actin-binding protein (ABP-280, nonmuscle filamin) is a ubiquitous dimeric actin cross-linking phosphoprotein of peripheral cytoplasm, where it promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. The complete nucleotide sequence of human endothelial cell ABP cDNA predicts a polypeptide subunit chain of 2,647 amino acids, corresponding to 280 kD, also the mass derived from physical measurements of the native protein. The actin-binding domain is near the amino-terminus of the subunit where the amino acid sequence is similar to other actin filament binding proteins, including alpha-actinin, beta-spectrin, dystrophin, and Dictyostelium abp-120. The remaining 90% of the sequence comprises 24 repeats, each approximately 96 residues long, predicted to have stretches of beta-sheet secondary structure interspersed with turns. The first 15 repeats may have substantial intrachain hydrophobic interactions and overlap in a staggered fashion to yield a backbone with mechanical resilience. Sequence insertions immediately before repeats 16 and 24 predict two hinges in the molecule near points where rotary-shadowed molecules appear to swivel in electron micrographs. Both putative hinge regions are susceptible to cleavage by proteases and the second also contains the site that binds the platelet glycoprotein Ib/IX complex. Phosphorylation consensus sequences are also located in the hinges or near them. Degeneracy within every even- numbered repeat between 16 and 24 and the insertion before repeat 24 may convert interactions within chains to interactions between chains to account for dimer formation within a domain of 7 kD at the carboxy- terminus. The structure of ABP dimers resembles a leaf spring. Interchain interactions hold the leaves firmly together at one end, whereas intrachain hydrophobic bonds reinforce the arms of the spring where the leaves diverge, making it sufficiently stiff to promote high- angle branching of actin

  6. Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring.

    PubMed

    Gorlin, J B; Yamin, R; Egan, S; Stewart, M; Stossel, T P; Kwiatkowski, D J; Hartwig, J H

    1990-09-01

    Actin-binding protein (ABP-280, nonmuscle filamin) is a ubiquitous dimeric actin cross-linking phosphoprotein of peripheral cytoplasm, where it promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. The complete nucleotide sequence of human endothelial cell ABP cDNA predicts a polypeptide subunit chain of 2,647 amino acids, corresponding to 280 kD, also the mass derived from physical measurements of the native protein. The actin-binding domain is near the amino-terminus of the subunit where the amino acid sequence is similar to other actin filament binding proteins, including alpha-actinin, beta-spectrin, dystrophin, and Dictyostelium abp-120. The remaining 90% of the sequence comprises 24 repeats, each approximately 96 residues long, predicted to have stretches of beta-sheet secondary structure interspersed with turns. The first 15 repeats may have substantial intrachain hydrophobic interactions and overlap in a staggered fashion to yield a backbone with mechanical resilience. Sequence insertions immediately before repeats 16 and 24 predict two hinges in the molecule near points where rotary-shadowed molecules appear to swivel in electron micrographs. Both putative hinge regions are susceptible to cleavage by proteases and the second also contains the site that binds the platelet glycoprotein Ib/IX complex. Phosphorylation consensus sequences are also located in the hinges or near them. Degeneracy within every even-numbered repeat between 16 and 24 and the insertion before repeat 24 may convert interactions within chains to interactions between chains to account for dimer formation within a domain of 7 kD at the carboxy-terminus. The structure of ABP dimers resembles a leaf spring. Interchain interactions hold the leaves firmly together at one end, whereas intrachain hydrophobic bonds reinforce the arms of the spring where the leaves diverge, making it sufficiently stiff to promote high-angle branching of actin

  7. Cooperation between two ClpB isoforms enhances the recovery of the recombinant {beta}-galactosidase from inclusion bodies

    SciTech Connect

    Guenther, Izabela; Zolkiewski, Michal; Kedzierska-Mieszkowska, Sabina

    2012-10-05

    Highlights: Black-Right-Pointing-Pointer An important role of synergistic cooperation between the two ClpB isoforms. Black-Right-Pointing-Pointer Both ClpB isoforms are associated with IBs of {beta}-galactosidase. Black-Right-Pointing-Pointer ClpB is a key chaperone in IB protein release. -- Abstract: Bacterial ClpB is a molecular chaperone that solubilizes and reactivates aggregated proteins in cooperation with the DnaK chaperone system. The mechanism of protein disaggregation mediated by ClpB is linked to translocation of substrates through the central channel within the ring-hexameric structure of ClpB. Two isoforms of ClpB are produced in vivo: the full-length ClpB95 and the truncated ClpB80 (ClpB{Delta}N), which does not contain the N-terminal domain. The functional specificity of the two ClpB isoforms and the biological role of the N-terminal domain are still not fully understood. Recently, it has been demonstrated that ClpB may achieve its full potential as an aggregate-reactivating chaperone through the functional interaction and synergistic cooperation of its two isoforms. It has been found that the most efficient resolubilization and reactivation of stress-aggregated proteins occurred in the presence of both ClpB95 and ClpB80. In this work, we asked if the two ClpB isoforms functionally cooperate in the solubilization and reactivation of proteins from insoluble inclusion bodies (IBs) in Escherichia coli cells. Using the model {beta}-galactosidase fusion protein (VP1LAC), we found that solubilization and reactivation of enzymes entrapped in IBs occurred more efficiently in the presence of ClpB95 with ClpB80 than with either ClpB95 or ClpB80 alone. The two isoforms of ClpB chaperone acting together enhanced the solubility and enzymatic activity of {beta}-galactosidase sequestered into IBs. Both ClpB isoforms were associated with IBs of {beta}-galactosidase, what demonstrates their affinity to this type of aggregates. These results demonstrate a synergistic

  8. U.S./Russian cooperative efforts to enhance nuclear MPC&A at VNIITF, (Chelyabinsk-70)

    SciTech Connect

    Abramson, B; Apt, K; Blasy, J; Bukin, D; Churikov, Y; Curtis, D; Eras, A; Magda, E; Neymotin, L; Shultz, F; Slankas, T; Tittemore, G; Tsygankov, G; Zuev, V

    1999-04-20

    The work described here is part of an effort called the Nuclear Materials Protection, Control, and Accounting (MPC&A) Program, a cooperative program between the US Department of Eenrgy (DOE) and Russia's Ministry of Atomic Energy (MinAtom). The objective of the program is to reduce the risk of nuclear proliferation by strengthening MPC&A systems at Russian nuclear Facilities. This paper describes that portion of the MPC&A program that is directed specifically to the needs of the All Russian Scientific Research Institute of Technical Physics (VNIITF), also called Chelyabinsk-70. A major MPC&A milestone was met at VNIITF when the MPC&A improvements were commissioned at the Pulse Research Reactor Facility in May of this year.

  9. Dielectric permittivity enhancement in hydroxyl functionalized polyolefins via cooperative interactions with water

    NASA Astrophysics Data System (ADS)

    Wang, C. C.; Pilania, G.; Ramprasad, R.; Agarwal, Manish; Misra, Mayank; Kumar, Sanat; Yuan, Xuepei; Mike Chung, T. C.

    2013-04-01

    Recent experiments have shown that polypropylene (PP) with a small fraction of hydroxyl (-OH) side groups displays a two-fold increase in the dielectric permittivity. It has been suggested that both the -OH groups and trapped water molecules may contribute to the dielectric constant increase. In this first principles computational study, using short polyolefin chains as models of PP, we shed light on the role played by -OH functional groups and the trapped moisture. Our results reveal that the trapped water molecules will inevitably accompany -OH incorporation (due to hydrogen bonding) and that both the -OH groups and water molecules will contribute cooperatively to the increase of the PP dielectric constant. These findings also provide insights into the effects of moisture on other molecularly functionalized materials systems.

  10. Hairy/Enhancer-of-Split MEGANE and Proneural MASH1 Factors Cooperate Synergistically in Midbrain GABAergic Neurogenesis.

    PubMed

    Wende, Clara-Zoe; Zoubaa, Saida; Blak, Alexandra; Echevarria, Diego; Martinez, Salvador; Guillemot, François; Wurst, Wolfgang; Guimera, Jordi

    2015-01-01

    GABAergic neurons are the primary inhibitory cell type in the mature brain and their dysfunction is associated with important neurological conditions like schizophrenia and anxiety. We aimed to discover the underlying mechanisms for dorsal/ventral midbrain GABAergic neurogenesis. Previous work by us and others has provided crucial insights into the key function of Mgn and Mash1 genes in determining GABAergic neurotransmitter fate. Induction of dorsal midbrain GABAergic neurons does not take place at any time during development in either of the single mutant mice. However, GABAergic neurons in the ventral midbrain remained unchanged. Thus, the similarities in MB-GABAergic phenotype observed in the Mgn and Mash1 single mutants suggest the existence of other factors that take over the function of MGN and MASH1 in the ventral midbrain or the existence of different molecular mechanisms. We show that this process essentially depends on heterodimers and homodimers formed by MGN and MASH1 and deciphered the in vivo relevance of the interaction by phenotypic analysis of Mgn/Mash1 double knockout and compound mice. Furthermore, the combination of gain- and loss-of-function experiments in the developing midbrain showed co-operative roles for Mgn and Mash1 genes in determining GABAergic identity. Transcription factors belonging to the Enhancer-of-split-related and proneural families have long been believed to counterpart each other's function. This work uncovers a synergistic cooperation between these two families, and provides a novel paradigm for how these two families cooperate for the acquisition of MB-GABAergic neuronal identity. Understanding their molecular mechanisms is essential for cell therapy strategies to amend GABAergic deficits. PMID:25993409

  11. Hairy/Enhancer-of-Split MEGANE and Proneural MASH1 Factors Cooperate Synergistically in Midbrain GABAergic Neurogenesis

    PubMed Central

    Wende, Clara-Zoe; Zoubaa, Saida; Blak, Alexandra; Echevarria, Diego; Martinez, Salvador; Guillemot, François; Wurst, Wolfgang; Guimera, Jordi

    2015-01-01

    GABAergic neurons are the primary inhibitory cell type in the mature brain and their dysfunction is associated with important neurological conditions like schizophrenia and anxiety. We aimed to discover the underlying mechanisms for dorsal/ventral midbrain GABAergic neurogenesis. Previous work by us and others has provided crucial insights into the key function of Mgn and Mash1 genes in determining GABAergic neurotransmitter fate. Induction of dorsal midbrain GABAergic neurons does not take place at any time during development in either of the single mutant mice. However, GABAergic neurons in the ventral midbrain remained unchanged. Thus, the similarities in MB-GABAergic phenotype observed in the Mgn and Mash1 single mutants suggest the existence of other factors that take over the function of MGN and MASH1 in the ventral midbrain or the existence of different molecular mechanisms. We show that this process essentially depends on heterodimers and homodimers formed by MGN and MASH1 and deciphered the in vivo relevance of the interaction by phenotypic analysis of Mgn/Mash1 double knockout and compound mice. Furthermore, the combination of gain- and loss-of-function experiments in the developing midbrain showed co-operative roles for Mgn and Mash1 genes in determining GABAergic identity. Transcription factors belonging to the Enhancer-of-split-related and proneural families have long been believed to counterpart each other’s function. This work uncovers a synergistic cooperation between these two families, and provides a novel paradigm for how these two families cooperate for the acquisition of MB-GABAergic neuronal identity. Understanding their molecular mechanisms is essential for cell therapy strategies to amend GABAergic deficits. PMID:25993409

  12. Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity.

    PubMed

    Lazareno, S; Dolezal, V; Popham, A; Birdsall, N J M

    2004-01-01

    Thiochrome (2,7-dimethyl-5H-thiachromine-8-ethanol), an oxidation product and metabolite of thiamine, has little effect on the equilibrium binding of l-[3H]N-methyl scopolamine ([3H]NMS) to the five human muscarinic receptor subtypes (M1-M5) at concentrations up to 0.3 mM. In contrast, it inhibits [3H]NMS dissociation from M1 to M4 receptors at submillimolar concentrations and from M5 receptors at 1 mM. These results suggest that thiochrome binds allosterically to muscarinic receptors and has approximately neutral cooperativity with [3H]NMS at M1 to M4 and possibly M5 receptors. Thiochrome increases the affinity of acetylcholine (ACh) 3- to 5-fold for inhibiting [3H]NMS binding to M4 receptors but has no effect on ACh affinity at M1 to M3 or M5 receptors. Thiochrome (0.1 mM) also increases the direct binding of [3H]ACh to M4 receptors but decreases it slightly at M2 receptors. In agreement with the binding data, thiochrome does not affect the potency of ACh for stimulating the binding of guanosine 5'-O-(3-[35S]thiotriphosphate) ([35S]GTPgammaS) to membranes containing M1 to M3 receptors, but it increases ACh potency 3.5-fold at M4 receptors. It also selectively reduces the release of [3H]ACh from potassium-stimulated slices of rat striatum, which contain autoinhibitory presynaptic M4 receptors, but not from hippocampal slices, which contain presynaptic M2 receptors. We conclude that thiochrome is a selective M4 muscarinic receptor enhancer of ACh affinity and has neutral cooperativity with ACh at M1 to M3 receptors; it therefore demonstrates a powerful new form of selectivity, "absolute subtype selectivity", which is derived from cooperativity rather than from affinity. PMID:14722259

  13. Cyclic AMP-Rap1A signaling mediates cell surface translocation of microvascular smooth muscle α2C-adrenoceptors through the actin-binding protein filamin-2

    PubMed Central

    Motawea, Hanaa K. B.; Jeyaraj, Selvi C.; Eid, Ali H.; Mitra, Srabani; Unger, Nicholas T.; Ahmed, Amany A. E.; Flavahan, Nicholas A.

    2013-01-01

    The second messenger cyclic AMP (cAMP) plays a vital role in vascular physiology, including vasodilation of large blood vessels. We recently demonstrated cAMP activation of Epac-Rap1A and RhoA-Rho-associated kinase (ROCK)-F-actin signaling in arteriolar-derived smooth muscle cells increases expression and cell surface translocation of functional α2C-adrenoceptors (α2C-ARs) that mediate vasoconstriction in small blood vessels (arterioles). The Ras-related small GTPAse Rap1A increased expression of α2C-ARs and also increased translocation of perinuclear α2C-ARs to intracellular F-actin and to the plasma membrane. This study examined the mechanism of translocation to better understand the role of these newly discovered mediators of blood flow control, potentially activated in peripheral vascular disorders. We utilized a yeast two-hybrid screen with human microvascular smooth muscle cells (microVSM) cDNA library and the α2C-AR COOH terminus to identify a novel interaction with the actin cross-linker filamin-2. Yeast α-galactosidase assays, site-directed mutagenesis, and coimmunoprecipitation experiments in heterologous human embryonic kidney (HEK) 293 cells and in human microVSM demonstrated that α2C-ARs, but not α2A-AR subtype, interacted with filamin. In Rap1-stimulated human microVSM, α2C-ARs colocalized with filamin on intracellular filaments and at the plasma membrane. Small interfering RNA-mediated knockdown of filamin-2 inhibited Rap1-induced redistribution of α2C-ARs to the cell surface and inhibited receptor function. The studies suggest that cAMP-Rap1-Rho-ROCK signaling facilitates receptor translocation and function via phosphorylation of filamin-2 Ser2113. Together, these studies extend our previous findings to show that functional rescue of α2C-ARs is mediated through Rap1-filamin signaling. Perturbation of this signaling pathway may lead to alterations in α2C-AR trafficking and physiological function. PMID:23864608

  14. Force-dependent isomerization kinetics of a highly conserved proline switch modulates the mechanosensing region of filamin

    PubMed Central

    Rognoni, Lorenz; Möst, Tobias; Žoldák, Gabriel; Rief, Matthias

    2014-01-01

    Proline switches, controlled by cis–trans isomerization, have emerged as a particularly effective regulatory mechanism in a wide range of biological processes. In this study, we use single-molecule mechanical measurements to develop a full kinetic and energetic description of a highly conserved proline switch in the force-sensing domain 20 of human filamin and how prolyl isomerization modulates the force-sensing mechanism. Proline isomerization toggles domain 20 between two conformations. A stable cis conformation with slow unfolding, favoring the autoinhibited closed conformation of filamin’s force-sensing domain pair 20–21, and a less stable, uninhibited conformation promoted by the trans form. The data provide detailed insight into the folding mechanisms that underpin the functionality of this binary switch and elucidate its remarkable efficiency in modulating force-sensing, thus combining two previously unconnected regulatory mechanisms, proline switches and mechanosensing. PMID:24706888

  15. Enhanced bandwidth of a microstrip antenna using a parasitic mushroom-like metamaterial structure for multi-robot cooperative navigation

    NASA Astrophysics Data System (ADS)

    Lee, Cherl-Hee; Lee, Jonghun; Kim, Yoon-Gu; An, Jinung

    2015-01-01

    The broadband design of a microstrip patch antenna is presented and experimentally studied for multi-robot cooperation. A parasitic mushroom-like metamaterial (MTM) patch close to a microstrip top patch is excited through gap-coupling, thereby producing a resonance frequency. Because of the design, the resonance frequency of the parasitic MTM patch is adjacent to that of the main patch, and the presented antenna can achieve an enhanced bandwidth of 450 MHz, which is about two times the bandwidth of a conventional patch antenna without the MTM parasitic patch. The error rate of packet transmissions for measuring the distance between a leader robot and a follower robot was also improved by almost two-fold.

  16. Chicken stem cell factor enhances primordial germ cell proliferation cooperatively with fibroblast growth factor 2

    PubMed Central

    MIYAHARA, Daichi; OISHI, Isao; MAKINO, Ryuichi; KURUMISAWA, Nozomi; NAKAYA, Ryuma; ONO, Tamao; KAGAMI, Hiroshi; TAGAMI, Takahiro

    2015-01-01

    An in vitro culture system of chicken primordial germ cells (PGCs) has been recently developed, but the growth factor involved in the proliferation of PGCs is largely unknown. In the present study, we investigated the growth effects of chicken stem cell factor (chSCF) on the in vitro proliferation of chicken PGCs. We established two feeder cell lines (buffalo rat liver cells; BRL cells) that stably express the putative secreted form of chSCF (chSCF1-BRL) and membrane bound form of chSCF (chSCF2-BRL). Cultured PGC lines were incubated on chSCF1 or chSCF2-BRL feeder cells with fibroblast growth factor 2 (FGF2), and growth effects of each chSCF isoform were investigated. The in vitro proliferation rate of the PGCs cultured on chSCF2-BRL at 20 days of culture was more than threefold higher than those cultured on chSCF1-BRL cells and more than fivefold higher than those cultured on normal BRL cells. Thus, use of chSCF2-BRL feeder layer was effective for in vitro proliferation of chicken PGCs. However, the acceleration of PGC proliferation on chSCF2-BRL was not observed without FGF2, suggesting that chSCF2 would act as a proliferation co-factor of FGF2. We transferred the PGCs cultured on chSCF2-BRL cells to recipient embryos, generated germline chimeric chickens and assessed the germline competency of cultured PGCs by progeny test. Donor-derived progenies were obtained, and the frequency of germline transmission was 3.39%. The results of this study demonstrate that chSCF2 induces hyperproliferation of chicken PGCs retaining germline competency in vitro in cooperation with FGF2. PMID:26727404

  17. The Effects of Cooperative Learning on Enhancing Hong Kong Fifth Graders' Achievement Goals, Autonomous Motivation and Reading Proficiency

    ERIC Educational Resources Information Center

    Law, Yin-Kum

    2011-01-01

    Research indicates that cooperative learning with teacher-guided instruction is more effective in helping young children to learn than cooperative learning with minimal guidance. In the present study, two different cooperative learning activities (jigsaw and drama) and a control condition (a traditional teacher-led approach) were compared. The…

  18. Twisted Thiophene-Based Chromophores with Enhanced Intramolecular Charge Transfer for Cooperative Amplification of Third-Order Optical Nonlinearity.

    PubMed

    Teran, Natasha B; He, Guang S; Baev, Alexander; Shi, Yanrong; Swihart, Mark T; Prasad, Paras N; Marks, Tobin J; Reynolds, John R

    2016-06-01

    Exploiting synergistic cooperation between multiple sources of optical nonlinearity, we report the design, synthesis, and nonlinear optical properties of a series of electron-rich thiophene-containing donor-acceptor chromophores with condensed π-systems and sterically regulated inter-aryl twist angles. These structures couple two key mechanisms underlying optical nonlinearity, namely, (i) intramolecular charge transfer, greatly enhanced by increased electron density and reduced aromaticity at chromophore thiophene rings and (ii) a twisted chromophore geometry, producing a manifold of close-lying excited states and dipole moment changes between ground and excited states that are nearly twice that of untwisted systems. Spectroscopic, electrochemical, and nonlinear Z-scan measurements, combined with quantum chemical calculations, illuminate relationships between molecular structure and mechanisms of enhancement of the nonlinear refractive index. Experiment and calculations together reveal ground-state structures that are strongly responsive to the solvent polarity, leading to substantial negative solvatochromism (Δλ ≈ 10(2) nm) and prevailing zwitterionic/aromatic structures in the solid state and in polar solvents. Ground-to-excited-state energy gaps below 2.0 eV are obtained in condensed π-systems, with lower energy gaps for twisted versus untwisted systems. The real part of the second hyperpolarizability in the twisted structures is much greater than the imaginary part, with the highest twist angle chromophore giving |Re(γ)/Im(γ)| ≈ 100, making such chromophores very promising for all-optical-switching applications. PMID:27232098

  19. Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila.

    PubMed

    Oliva, Carlos; Molina-Fernandez, Claudia; Maureira, Miguel; Candia, Noemi; López, Estefanía; Hassan, Bassem; Aerts, Stein; Cánovas, José; Olguín, Patricio; Sierralta, Jimena

    2015-09-01

    During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015. PMID:25652545

  20. Cooperative Effect of Monopodal Silica-Supported Niobium Complex Pairs Enhancing Catalytic Cyclic Carbonate Production.

    PubMed

    D'Elia, Valerio; Dong, Hailin; Rossini, Aaron J; Widdifield, Cory M; Vummaleti, Sai V C; Minenkov, Yury; Poater, Albert; Abou-Hamad, Edy; Pelletier, Jérémie D A; Cavallo, Luigi; Emsley, Lyndon; Basset, Jean-Marie

    2015-06-24

    Recent discoveries highlighted the activity and the intriguing mechanistic features of NbCl5 as a molecular catalyst for the cycloaddition of CO2 and epoxides under ambient conditions. This has inspired the preparation of novel silica-supported Nb species by reacting a molecular niobium precursor, [NbCl5·OEt2], with silica dehydroxylated at 700 °C (SiO(2-700)) or at 200 °C (SiO(2-200)) to generate diverse surface complexes. The product of the reaction between SiO(2-700) and [NbCl5·OEt2] was identified as a monopodal supported surface species, [≡SiONbCl4·OEt2] (1a). The reactions of SiO(2-200) with the niobium precursor, according to two different protocols, generated surface complexes 2a and 3a, presenting significant, but different, populations of the monopodal surface complex along with bipodal [(≡SiO)2NbCl3·OEt2]. (93)Nb solid-state NMR spectra of 1a-3a and (31)P solid-state NMR on their PMe3 derivatives 1b-3b led to the unambiguous assignment of 1a as a single-site monopodal Nb species, while 2a and 3a were found to present two distinct surface-supported components, with 2a being mostly monopodal [≡SiONbCl4·OEt2] and 3a being mostly bipodal [(≡SiO)2NbCl3·OEt2]. A double-quantum/single-quantum (31)P NMR correlation experiment carried out on 2b supported the existence of vicinal Nb centers on the silica surface for this species. 1a-3a were active heterogeneous catalysts for the synthesis of propylene carbonate from CO2 and propylene oxide under mild catalytic conditions; the performance of 2a was found to significantly surpass that of 1a and 3a. With the support of a systematic DFT study carried out on model silica surfaces, the observed differences in catalytic efficiency were correlated with an unprecedented cooperative effect between two neighboring Nb centers on the surface of 2a. This is in an excellent agreement with our previous discoveries regarding the mechanism of NbCl5-catalyzed cycloaddition in the homogeneous phase. PMID:25950495

  1. PPARδ Activation Acts Cooperatively with 3-Phosphoinositide-Dependent Protein Kinase-1 to Enhance Mammary Tumorigenesis

    PubMed Central

    Pollock, Claire B.; Yin, Yuzhi; Yuan, Hongyan; Zeng, Xiao; King, Sruthi; Li, Xin; Kopelovich, Levy; Albanese, Chris; Glazer, Robert I.

    2011-01-01

    Peroxisome proliferator-activated receptorδ (PPARδ) is a transcription factor that is associated with metabolic gene regulation and inflammation. It has been implicated in tumor promotion and in the regulation of 3-phosphoinositide-dependent kinase-1 (PDK1). PDK1 is a key regulator of the AGC protein kinase family, which includes the proto-oncogene AKT/PKB implicated in several malignancies, including breast cancer. To assess the role of PDK1 in mammary tumorigenesis and its interaction with PPARδ, transgenic mice were generated in which PDK1 was expressed in mammary epithelium under the control of the MMTV enhancer/promoter region. Transgene expression increased pT308AKT and pS9GSK3β, but did not alter phosphorylation of mTOR, 4EBP1, ribosomal protein S6 and PKCα. The transgenic mammary gland also expressed higher levels of PPARδ and a gene expression profile resembling wild-type mice maintained on a diet containing the PPARδ agonist, GW501516. Both wild-type and transgenic mice treated with GW501516 exhibited accelerated rates of tumor formation that were more pronounced in transgenic animals. GW501516 treatment was accompanied by a distinct metabolic gene expression and metabolomic signature that was not present in untreated animals. GW501516-treated transgenic mice expressed higher levels of fatty acid and phospholipid metabolites than treated wild-type mice, suggesting the involvement of PDK1 in enhancing PPARδ-driven energy metabolism. These results reveal that PPARδ activation elicits a distinct metabolic and metabolomic profile in tumors that is in part related to PDK1 and AKT signaling. PMID:21297860

  2. Plasma Enhanced Atomic Layer Deposition of Cooper Seed Layers at Low Process Temperatures

    NASA Astrophysics Data System (ADS)

    Mao, Jiajun

    In conventional Cu interconnect fabrication, a sputtered copper seed layer is deposited before the electrochemically deposited (ECD) copper plating step. However, as interconnect dimensions scale down, non-conformal seed layer growth and subsequent voiding of metallized structures is becoming a critical issue. With its established excellent thickness controllability and film conformality, atomic layer deposition (ALD) is becoming an attractive deposition approach for the sub-24nm fabrication regime. However, in order to achieve a smooth and continuous seed layer deposition, a low process temperature (below 100°C) is needed, given the tendency of Cu agglomeration at elevated temperature. In this research, plasma enhanced ALD (PEALD) Cu processes at low process temperature are developed using two novel precursors: Cuprum and AbaCus. The volatility and thermal stability of these two precursors are presented. Self-limiting nature of the PEALD processes are demonstrated. Key film properties including purity, resistivity, conformality, adhesion and platability are evaluated using multiple characterization techniques. In addition, film nucleation and growth of PEALD Cu at room temperature on different liner materials are studied. Via structures are employed for the investigation of film continuity on side walls. It is also shown that film conformality and platability can be improved by over saturating the plasma reactions.

  3. A cooperative interaction between NF-kappa B and Sp1 is required for HIV-1 enhancer activation.

    PubMed Central

    Perkins, N D; Edwards, N L; Duckett, C S; Agranoff, A B; Schmid, R M; Nabel, G J

    1993-01-01

    The human immunodeficiency virus (HIV-1) long terminal repeat (LTR) contains two binding sites for NF-kappa B in close proximity to three binding sites for the constitutive transcription factor, Sp1. Previously, stimulation of the HIV enhancer in response to mitogens has been attributed to the binding of NF-kappa B to the viral enhancer. In this report, we show that the binding of NF-kappa B is not by itself sufficient to induce HIV gene expression. Instead, a protein-protein interaction must occur between NF-kappa B and Sp1 bound to an adjacent site. Cooperativity both in DNA binding and in transcriptional activation of NF-kappa B and Sp1 was confirmed by electrophoretic mobility shift gel analysis, DNase footprinting, chemical cross-linking and transfection studies in vivo. With a heterologous promoter, we find that the interaction of NF-kappa B with Sp1 is dependent on orientation and position, and is not observed with other elements, including GATA, CCAAT or octamer. An increase in the spacing between the kappa B and Sp1 elements virtually abolishes this functional interaction, which is not restored when these sites are brought back into the same helical position. Several other promoters regulated by NF-kappa B also contain kappa B in proximity to Sp1 binding sites. These findings suggest that an interaction between NF-kappa B and Sp1 is required for inducible HIV-1 gene expression and may serve as a regulatory mechanism to activate specific viral and cellular genes. Images PMID:8253080

  4. S6K is a morphogenic protein with a mechanism involving Filamin-A phosphorylation and phosphatidic acid binding

    PubMed Central

    Henkels, Karen M.; Mallets, Elizabeth R.; Dennis, Patrick B.; Gomez-Cambronero, Julian

    2015-01-01

    Change of cell shape in vivo plays many roles that are central to life itself, such as embryonic development, inflammation, wound healing, and pathologic processes such as cancer metastasis. Nonetheless, the spatiotemporal mechanisms that control the concerted regulation of cell shape remain understudied. Here, we show that ribosomal S6K, which is normally considered a protein involved in protein translation, is a morphogenic protein. Its presence in cells alters the overall organization of the cell surface and cell circularity [(4π × area)/(perimeter)2] from 0.47 ± 0.06 units in mock-treated cells to 0.09 ± 0.03 units in S6K-overexpressing macrophages causing stellation and arborization of cell shape. This effect was partially reversed in cells expressing a kinase-inactive S6K mutant and was fully reversed in cells silenced with small interference RNA. Equally important is that S6K is itself regulated by phospholipids, specifically phosphatidic acid, whereby 300 nM 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA), but not the control 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), binds directly to S6K and causes an ∼2.9-fold increase in S6K catalytic activity. This was followed by an increase in Filamin A (FLNA) functionality as measured by phospho-FLNA (S2152) expression and by a subsequent elevation of actin nucleation. This reliance of S6K on phosphatidic acid (PA), a curvature-inducing phospholipid, explained the extra-large perimeter of cells that overexpressed S6K. Furthermore, the diversity of the response to S6K in several unrelated cell types (fibroblasts, leukocytes, and invasive cancer cells) that we report here indicates the existence of an underlying common mechanism in mammalian cells. This new signaling set, PA-S6K-FLNA-actin, sheds light for the first time into the morphogenic pathway of cytoskeletal structures that are crucial for adhesion and cell locomotion during inflammation and metastasis.—Henkels, K. M., Mallets, E. R., Dennis, P. B

  5. Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells

    PubMed Central

    Di Donato, Marzia; Bilancio, Antonio; D'Amato, Loredana; Claudiani, Pamela; Oliviero, Maria Antonietta; Barone, Maria Vittoria; Auricchio, Alberto; Appella, Ettore; Migliaccio, Antimo; Auricchio, Ferdinando; Castoria, Gabriella

    2015-01-01

    Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We show that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes with neuritogenesis stimulated by the nonaromatizable synthetic androgen R1881 or NGF. This implies a role for AR not only in androgen signaling, but also in NGF signaling. In turn, a pharmacological TrkA inhibitor interferes with NGF- or androgen-induced neuritogenesis. In addition, androgen or NGF triggers AR association with TrkA, TrkA interaction with PI3-K δ, and downstream activation of PI3-K δ and Rac in PC12 cells. Once associated with AR, filamin A (FlnA) contributes to androgen or NGF neuritogenesis, likely through its interaction with signaling effectors, such as Rac. This study thus identifies a previously unrecognized reciprocal cross-talk between AR and TrkA, which is controlled by β1 integrin. The contribution of FlnA/AR complex and PI3-K δ to neuronal differentiation by androgens and NGF is also novel. This is the first description of AR function in PC12 cells. PMID:26063730

  6. Filamin A Mediates Wound Closure by Promoting Elastic Deformation and Maintenance of Tension in the Collagen Matrix

    PubMed Central

    Mohammadi, Hamid; Pinto, Vanessa I.; Wang, Yongqiang; Hinz, Boris; Janmey, Paul A.; McCulloch, Christopher A.

    2016-01-01

    Cell-mediated remodeling and wound closure are critical for efficient wound healing, but the contribution of actin-binding proteins to contraction of the extracellular matrix is not defined. We examined the role of filamin A (FLNa), an actin filament cross-linking protein, in wound contraction and maintenance of matrix tension. Conditional deletion of FLNa in fibroblasts in mice was associated with ~ 4 day delay of full-thickness skin wound contraction compared with wild-type (WT) mice. We modeled the healing wound matrix using cultured fibroblasts plated on grid-supported collagen gels that create lateral boundaries, which are analogues to wound margins. In contrast to WT cells, FLNa knockdown (KD) cells could not completely maintain tension when matrix compaction was resisted by boundaries, which manifested as relaxed matrix tension. Similarly, WT cells on cross-linked collagen, which requires higher levels of sustained tension, exhibited approximately fivefold larger deformation fields and approximately twofold greater fiber alignment compared with FLNa KD cells. Maintenance of boundary-resisted tension markedly influenced the elongation of cell extensions: in WT cells, the number (~50%) and length (~300%) of cell extensions were greater than FLNa KD cells. We conclude that FLNa is required for wound contraction, in part by enabling elastic deformation and maintenance of tension in the matrix. PMID:26134946

  7. TGFβ and BMP Dependent Cell Fate Changes Due to Loss of Filamin B Produces Disc Degeneration and Progressive Vertebral Fusions.

    PubMed

    Zieba, Jennifer; Forlenza, Kimberly Nicole; Khatra, Jagteshwar Singh; Sarukhanov, Anna; Duran, Ivan; Rigueur, Diana; Lyons, Karen M; Cohn, Daniel H; Merrill, Amy E; Krakow, Deborah

    2016-03-01

    Spondylocarpotarsal synostosis (SCT) is an autosomal recessive disorder characterized by progressive vertebral fusions and caused by loss of function mutations in Filamin B (FLNB). FLNB acts as a signaling scaffold by linking the actin cytoskleteon to signal transduction systems, yet the disease mechanisms for SCT remain unclear. Employing a Flnb knockout mouse, we found morphologic and molecular evidence that the intervertebral discs (IVDs) of Flnb-/-mice undergo rapid and progressive degeneration during postnatal development as a result of abnormal cell fate changes in the IVD, particularly the annulus fibrosus (AF). In Flnb-/-mice, the AF cells lose their typical fibroblast-like characteristics and acquire the molecular and phenotypic signature of hypertrophic chondrocytes. This change is characterized by hallmarks of endochondral-like ossification including alterations in collagen matrix, expression of Collagen X, increased apoptosis, and inappropriate ossification of the disc tissue. We show that conversion of the AF cells into chondrocytes is coincident with upregulated TGFβ signaling via Smad2/3 and BMP induced p38 signaling as well as sustained activation of canonical and noncanonical target genes p21 and Ctgf. These findings indicate that FLNB is involved in attenuation of TGFβ/BMP signaling and influences AF cell fate. Furthermore, we demonstrate that the IVD disruptions in Flnb-/-mice resemble aging degenerative discs and reveal new insights into the molecular causes of vertebral fusions and disc degeneration. PMID:27019229

  8. RACK1 interacts with filamin-A to regulate plasma membrane levels of the cystic fibrosis transmembrane conductance regulator.

    PubMed

    Smith, Laura; Litman, Paul; Kohli, Ekta; Amick, Joseph; Page, Richard C; Misra, Saurav; Liedtke, Carole M

    2013-07-01

    Mutations in cystic fibrosis transmembrane regulator (CFTR), a chloride channel in the apical membranes of secretory epithelial cells, underlie the fatal genetic disorder cystic fibrosis. Certain CFTR mutations, including the common mutation ΔF508-CFTR, result in greatly decreased levels of active CFTR at the apical membrane. Direct interactions between CFTR and the cytoskeletal adaptors filamin-A (FlnA) and Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) stabilize the expression and localization of CFTR at the plasma membrane. The scaffold protein receptor for activated C kinase 1 (RACK1) also stabilizes CFTR surface expression; however, RACK1 does not interact directly with CFTR and its mechanism of action is unknown. In the present study, we report that RACK1 interacts directly with FlnA in vitro and in a Calu-3 airway epithelial cell line. We mapped the interaction between RACK1 and FlnA to the WD4 and WD6 repeats of RACK1 and to a segment of the large rod domain of FlnA, consisting of immunoglobulin-like repeats 8-15. Disruption of the RACK1-FlnA interaction causes a reduction in CFTR surface levels. Our results suggest that a novel RACK1-FlnA interaction is an important regulator of CFTR surface localization. PMID:23636454

  9. Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A.

    PubMed

    Reinstein, Eyal; Frentz, Sophia; Morgan, Tim; García-Miñaúr, Sixto; Leventer, Richard J; McGillivray, George; Pariani, Mitchel; van der Steen, Anthony; Pope, Michael; Holder-Espinasse, Muriel; Scott, Richard; Thompson, Elizabeth M; Robertson, Terry; Coppin, Brian; Siegel, Robert; Bret Zurita, Montserrat; Rodríguez, Jose I; Morales, Carmen; Rodrigues, Yuri; Arcas, Joaquín; Saggar, Anand; Horton, Margaret; Zackai, Elaine; Graham, John M; Rimoin, David L; Robertson, Stephen P

    2013-05-01

    Mutations conferring loss of function at the FLNA (encoding filamin A) locus lead to X-linked periventricular nodular heterotopia (XL-PH), with seizures constituting the most common clinical manifestation of this disorder in female heterozygotes. Vascular dilatation (mainly the aorta), joint hypermobility and variable skin findings are also associated anomalies, with some reports suggesting that this might represents a separate syndrome allelic to XL-PH, termed as Ehlers-Danlos syndrome-periventricular heterotopia variant (EDS-PH). Here, we report a cohort of 11 males and females with both hypomorphic and null mutations in FLNA that manifest a wide spectrum of connective tissue and vascular anomalies. The spectrum of cutaneous defects was broader than previously described and is inconsistent with a specific type of EDS. We also extend the range of vascular anomalies associated with XL-PH to included peripheral arterial dilatation and atresia. Based on these observations, we suggest that there is little molecular or clinical justification for considering EDS-PH as a separate entity from XL-PH, but instead propose that there is a spectrum of vascular and connective tissues anomalies associated with this condition for which all individuals with loss-of-function mutations in FLNA should be evaluated. In addition, since some patients with XL-PH can present primarily with a joint hypermobility syndrome, we propose that screening for cardiovascular manifestations should be offered to those patients when there are associated seizures or an X-linked pattern of inheritance. PMID:23032111

  10. TGFβ and BMP Dependent Cell Fate Changes Due to Loss of Filamin B Produces Disc Degeneration and Progressive Vertebral Fusions

    PubMed Central

    Zieba, Jennifer; Forlenza, Kimberly Nicole; Khatra, Jagteshwar Singh; Sarukhanov, Anna; Duran, Ivan; Rigueur, Diana; Lyons, Karen M.; Cohn, Daniel H.; Merrill, Amy E.; Krakow, Deborah

    2016-01-01

    Spondylocarpotarsal synostosis (SCT) is an autosomal recessive disorder characterized by progressive vertebral fusions and caused by loss of function mutations in Filamin B (FLNB). FLNB acts as a signaling scaffold by linking the actin cytoskleteon to signal transduction systems, yet the disease mechanisms for SCT remain unclear. Employing a Flnb knockout mouse, we found morphologic and molecular evidence that the intervertebral discs (IVDs) of Flnb–/–mice undergo rapid and progressive degeneration during postnatal development as a result of abnormal cell fate changes in the IVD, particularly the annulus fibrosus (AF). In Flnb–/–mice, the AF cells lose their typical fibroblast-like characteristics and acquire the molecular and phenotypic signature of hypertrophic chondrocytes. This change is characterized by hallmarks of endochondral-like ossification including alterations in collagen matrix, expression of Collagen X, increased apoptosis, and inappropriate ossification of the disc tissue. We show that conversion of the AF cells into chondrocytes is coincident with upregulated TGFβ signaling via Smad2/3 and BMP induced p38 signaling as well as sustained activation of canonical and noncanonical target genes p21 and Ctgf. These findings indicate that FLNB is involved in attenuation of TGFβ/BMP signaling and influences AF cell fate. Furthermore, we demonstrate that the IVD disruptions in Flnb–/–mice resemble aging degenerative discs and reveal new insights into the molecular causes of vertebral fusions and disc degeneration. PMID:27019229

  11. Interaction and cooperation of the CCAAT-box enhancer-binding protein β (C/EBPβ) with the homeodomain-interacting protein kinase 2 (Hipk2).

    PubMed

    Steinmann, Simone; Coulibaly, Anna; Ohnheiser, Johanna; Jakobs, Anke; Klempnauer, Karl-Heinz

    2013-08-01

    CCAAT box/enhancer-binding protein β (C/EBPβ) is a bZip transcription factor that plays crucial roles in important cellular processes such as differentiation and proliferation of specific cell types. Previously, we showed that C/EBPβ cooperates with the coactivator p300 through a novel mechanism that involves the C/EBPβ-induced phosphorylation of multiple sites in the carboxyl-terminal domain of p300 by protein kinase Hipk2. We have now examined the interaction and cooperation of C/EBPβ, p300, and Hipk2 in more detail. We show that Hipk2 and C/EBPβ are direct physical binding partners whose interaction is mediated by sequences located in the amino-terminal and central domains of Hipk2 and the amino-terminal part of C/EBPβ. In addition to phosphorylating p300 recruited to C/EBPβ, Hipk2 also phosphorylates C/EBPβ at sites that have previously been shown to plays key roles in the regulation of C/EBPβ activity. Silencing of Hipk2 expression disrupts adipocyte differentiation of 3T3-L1 cells, a physiological C/EBPβ-dependent differentiation process indicating that the cooperation of C/EBPβ and Hipk2 is functionally relevant. Finally, we demonstrate that C/EBPα, a related C/EBP family member whose amino-terminal sequences differ significantly from that of C/EBPβ, is unable to interact and cooperate with Hipk2. Instead, our data suggest that C/EBPα cooperates with the protein kinase Jnk to induce phosphorylation of p300. Overall, our data identify Hipk2 as a novel regulator of C/EBPβ and implicate different protein kinases in the cooperation of p300 with C/EBPβ and C/EBPα. PMID:23782693

  12. The calcium-sensing receptor-dependent regulation of cell-cell adhesion and keratinocyte differentiation requires Rho and filamin A.

    PubMed

    Tu, Chia-Ling; Chang, Wenhan; Bikle, Daniel D

    2011-05-01

    Extracellular Ca(2+) (Ca(2+)(o)) functioning through the calcium-sensing receptor (CaR) induces E-cadherin-mediated cell-cell adhesion and cellular signals mediating cell differentiation in epidermal keratinocytes. Previous studies indicate that CaR regulates cell-cell adhesion through Fyn/Src tyrosine kinases. In this study, we investigate whether Rho GTPase is a part of the CaR-mediated signaling cascade regulating cell adhesion and differentiation. Suppressing endogenous Rho A expression by small interfering RNA (siRNA)-mediated gene silencing blocked the Ca(2+)(o)-induced association of Fyn with E-cadherin and suppressed the Ca(2+)(o)-induced tyrosine phosphorylation of β-, γ-, and p120-catenin and formation of intercellular adherens junctions. Rho A silencing also decreased the Ca(2+)(o)-stimulated expression of terminal differentiation markers. Elevating the Ca(2+)(o) level induced interactions among CaR, Rho A, E-cadherin, and the scaffolding protein filamin A at the cell membrane. Inactivation of CaR expression by adenoviral expression of a CaR antisense complementary DNA inhibited Ca(2+)(o)-induced activation of endogenous Rho. Ca(2+)(o) activation of Rho required a direct interaction between CaR and filamin A. Interference of CaR-filamin interaction inhibited Ca(2+)(o)-induced Rho activation and the formation of cell-cell junctions. These results indicate that Rho is a downstream mediator of CaR in the regulation of Ca(2+)(o)-induced E-cadherin-mediated cell-cell adhesion and keratinocyte differentiation. PMID:21209619

  13. Transcription of Nrdp1 by the androgen receptor is regulated by nuclear filamin A in prostate cancer.

    PubMed

    Savoy, Rosalinda M; Chen, Liqun; Siddiqui, Salma; Melgoza, Frank U; Durbin-Johnson, Blythe; Drake, Christiana; Jathal, Maitreyee K; Bose, Swagata; Steele, Thomas M; Mooso, Benjamin A; D'Abronzo, Leandro S; Fry, William H; Carraway, Kermit L; Mudryj, Maria; Ghosh, Paramita M

    2015-06-01

    Prostate cancer (PCa) progression is regulated by the androgen receptor (AR); however, patients undergoing androgen-deprivation therapy (ADT) for disseminated PCa eventually develop castration-resistant PCa (CRPC). Results of previous studies indicated that AR, a transcription factor, occupies distinct genomic loci in CRPC compared with hormone-naïve PCa; however, the cause of this distinction was unknown. The E3 ubiquitin ligase Nrdp1 is a model AR target modulated by androgens in hormone-naïve PCa but not in CRPC. Using Nrdp1, we investigated how AR switches transcription programs during CRPC progression. The proximal Nrdp1 promoter contains an androgen response element (ARE); we demonstrated AR binding to this ARE in androgen-sensitive PCa. Analysis of hormone-naive human prostatectomy specimens revealed correlation between Nrdp1 and AR expression, supporting AR regulation of NRDP1 levels in androgen-sensitive tissue. However, despite sustained AR levels, AR binding to the Nrdp1 promoter and Nrdp1 expression were suppressed in CRPC. Elucidation of the suppression mechanism demonstrated correlation of NRDP1 levels with nuclear localization of the scaffolding protein filamin A (FLNA) which, as we previously showed, is itself repressed following ADT in many CRPC tumors. Restoration of nuclear FLNA in CRPC stimulated AR binding to Nrdp1 ARE, increased its transcription, and augmented NRDP1 protein expression and responsiveness to ADT, indicating that nuclear FLNA controls AR-mediated androgen-sensitive Nrdp1 transcription. Expression of other AR-regulated genes lost in CRPC was also re-established by nuclear FLNA. Thus, our results indicate that nuclear FLNA promotes androgen-dependent AR-regulated transcription in PCa, while loss of nuclear FLNA in CRPC alters the AR-regulated transcription program. PMID:25759396

  14. Filamin A interacts with the coactivator MKL1 to promote the activity of the transcription factor SRF and cell migration.

    PubMed

    Kircher, Philipp; Hermanns, Constanze; Nossek, Maximilian; Drexler, Maria Katharina; Grosse, Robert; Fischer, Maximilian; Sarikas, Antonio; Penkava, Josef; Lewis, Thera; Prywes, Ron; Gudermann, Thomas; Muehlich, Susanne

    2015-11-10

    Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor (SRF) that promotes the expression of genes associated with cell proliferation, motility, adhesion, and differentiation-processes that also involve dynamic cytoskeletal changes in the cell. MKL1 is inactive when bound to monomeric globular actin (G-actin), but signals that activate the small guanosine triphosphatase RhoA cause actin polymerization and MKL1 dissociation from G-actin. We found a new mechanism of MKL1 activation that is mediated through its binding to filamin A (FLNA), a protein that binds filamentous actin (F-actin). The interaction of FLNA and MKL1 was required for the expression of MKL1 target genes in primary fibroblasts, melanoma, mammary and hepatocellular carcinoma cells. We identified the regions of interaction between MKL1 and FLNA, and cells expressing an MKL1 mutant that was unable to bind FLNA exhibited impaired cell migration and reduced expression of MKL1-SRF target genes. Induction and repression of MKL1-SRF target genes correlated with increased or decreased MKL1-FLNA interaction, respectively. Lysophosphatidic acid-induced RhoA activation in primary human fibroblasts promoted the association of endogenous MKL1 with FLNA, whereas exposure to an actin polymerization inhibitor dissociated MKL1 from FLNA and decreased MKL1-SRF target gene expression in melanoma cells. Thus, FLNA functions as a positive cellular transducer linking actin polymerization to MKL1-SRF activity, counteracting the known repressive complex of MKL1 and monomeric G-actin. PMID:26554816

  15. Enhancing Students' Attitude towards Nigerian Senior Secondary School Physics through the Use of Cooperative, Competitive and Individualistic Learning Strategies

    ERIC Educational Resources Information Center

    Akinbobola, Akinyemi Olufunminiyi

    2009-01-01

    The study was conducted to find out the attitude of students towards the use of cooperative, competitive and individualistic learning strategies in Nigerian senior secondary school physics. The design selected for this study was quasi-experimental. A total of 140 students took part in the study and they were selected by a random sampling…

  16. Enlightening Advantages of Cooperative Learning

    ERIC Educational Resources Information Center

    Faryadi, Qais

    2007-01-01

    This appraisal discusses the notion that cooperative learning enhances learners' emotional and social performance. It also observes the perception that cooperative learning dramatically improves students' academic accomplishment. This review also examines the definition of cooperative learning and attempts to define it through the lens of renowned…

  17. The Effectiveness of an Intervention to Enhance Cooperation Between Sick-Listed Employees and Their Supervisors (COSS).

    PubMed

    Hoefsmit, Nicole; Houkes, Inge; Boumans, Nicolle; Noben, Cindy; Winkens, Bjorn; Nijhuis, Frans J N

    2016-06-01

    Introduction Early return-to-work (RTW) after sick leave is considered to support employees' quality of life. Successful RTW requires adequate cooperation between absent employees and their supervisors. This study assesses the effectiveness of an intervention for COoperation regarding RTW between Sick-listed employees and their Supervisors (COSS; i.e. 'conversation roadmap', monitoring of cooperation and, if necessary, extra occupational physician support). Methods In this field study, employees on sick leave for 2-10 weeks, aged 18 up to and including 60, and performing paid labour for at least 12 h per week were included. Terminally ill were excluded. Multivariate regression (correcting for baseline quality of life) was used to compare 6-months follow up data regarding quality of life between the groups. Using Cox regression analyses, time until first-, full-, and sustainable RTW was compared between groups. Results In total 64 employees received COSS or common practice. No significant group differences were found regarding all study outcomes. The COSS group had a higher chance of work resumption than the common practice group. The hazard ratio was 1.39 for first RTW (95 % CI 0.81-2.37), 1.12 for full RTW (95 % CI 0.65-1.93) and 1.10 for sustainable RTW (95 % CI 0.63-1.95). Conclusions COSS has no significant effects. Yet, the results regarding work resumption show a tendency towards effectiveness. Therefore, COSS can be further developed and applied in practice. Researchers should try to prevent some limitations of the present study in future research, for instance by finding a more common research setting. PMID:26386993

  18. The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis

    PubMed Central

    Liu, Chia-Feng; Lefebvre, Véronique

    2015-01-01

    SOX9 is a transcriptional activator required for chondrogenesis, and SOX5 and SOX6 are closely related DNA-binding proteins that critically enhance its function. We use here genome-wide approaches to gain novel insights into the full spectrum of the target genes and modes of action of this chondrogenic trio. Using the RCS cell line as a faithful model for proliferating/early prehypertrophic growth plate chondrocytes, we uncover that SOX6 and SOX9 bind thousands of genomic sites, frequently and most efficiently near each other. SOX9 recognizes pairs of inverted SOX motifs, whereas SOX6 favors pairs of tandem SOX motifs. The SOX proteins primarily target enhancers. While binding to a small fraction of typical enhancers, they bind multiple sites on almost all super-enhancers (SEs) present in RCS cells. These SEs are predominantly linked to cartilage-specific genes. The SOX proteins effectively work together to activate these SEs and are required for in vivo expression of their associated genes. These genes encode key regulatory factors, including the SOX trio proteins, and all essential cartilage extracellular matrix components. Chst11, Fgfr3, Runx2 and Runx3 are among many other newly identified SOX trio targets. SOX9 and SOX5/SOX6 thus cooperate genome-wide, primarily through SEs, to implement the growth plate chondrocyte differentiation program. PMID:26150426

  19. Novel interactions of ankyrins-G at the costameres: The muscle-specific Obscurin/Titin-Binding-related Domain (OTBD) binds plectin and filamin C

    SciTech Connect

    Maiweilidan, Yimingjiang; Klauza, Izabela; Kordeli, Ekaterini

    2011-04-01

    Ankyrins, the adapters of the spectrin skeleton, are involved in local accumulation and stabilization of integral proteins to the appropriate membrane domains. In striated muscle, tissue-dependent alternative splicing generates unique Ank3 gene products (ankyrins-G); they share the Obscurin/Titin-Binding-related Domain (OTBD), a muscle-specific insert of the C-terminal domain which is highly conserved among ankyrin genes, and binds obscurin and titin to Ank1 gene products. We previously proposed that OTBD sequences constitute a novel domain of protein-protein interactions which confers ankyrins with specific cellular functions in muscle. Here we searched for muscle proteins binding to ankyrin-G OTBD by yeast two hybrid assay, and we found plectin and filamin C, two organizing elements of the cytoskeleton with essential roles in myogenesis, muscle cell cytoarchitecture, and muscle disease. The three proteins coimmunoprecipitate from skeletal muscle extracts and colocalize at costameres in adult muscle fibers. During in vitro myogenesis, muscle ankyrins-G are first expressed in postmitotic myocytes undergoing fusion to myotubes. In western blots of subcellular fractions from C2C12 cells, the majority of muscle ankyrins-G appear associated with membrane compartments. Occasional but not extensive co-localization at nascent costameres suggested that ankyrin-G interactions with plectin and filamin C are not involved in costamere assembly; they would rather reinforce stability and/or modulate molecular interactions in sarcolemma microdomains by establishing novel links between muscle-specific ankyrins-G and the two costameric dystrophin-associated glycoprotein and integrin-based protein complexes. These results report the first protein-protein interactions involving the ankyrin-G OTBD domain and support the hypothesis that OTBD sequences confer ankyrins with a gain of function in vertebrates, bringing further consolidation and resilience of the linkage between sarcomeres

  20. Banana fruit NAC transcription factor MaNAC5 cooperates with MaWRKYs to enhance the expression of pathogenesis-related genes against Colletotrichum musae.

    PubMed

    Shan, Wei; Chen, Jian-Ye; Kuang, Jian-Fei; Lu, Wang-Jin

    2016-04-01

    Plants respond to pathogen attack by the modulation of a large set of genes, which are regulated by different types of transcription factor (TF). NAC (NAM/ATAF/CUC) and WRKY are plant-specific families of TFs, and have received much attention as transcriptional regulators in plant pathogen defence. However, the cooperation between NAC and WRKY TFs in the disease response remains largely unknown. Our previous study has revealed that two banana fruit WRKY TFs, MaWRKY1 and MaWRKY2, are involved in salicylic acid (SA)- and methyl jasmonate (MeJA)-induced resistance against Colletotrichum musae via binding to promoters of pathogenesis-related (PR) genes. Here, we found that MaNAC1, MaNAC2 and MaNAC5 were up-regulated after C. musae infection, and were also significantly enhanced by SA and MeJA treatment. Protein-protein interaction analysis showed that MaNAC5 physically interacted with MaWRKY1 and MaWRKY2. More importantly, dual-luciferase reporter (DLR) assay revealed that MaNAC5, MaWRKY1 and MaWRKY2 were transcriptional activators, and individually or cooperatively activated the transcriptional activities of MaPR1-1, MaPR2, MaPR10c and MaCHIL1 genes. Collectively, our results indicate that MaNAC5 cooperates with MaWRKY1 and MaWRKY2 to regulate the expression of a specific set of PR genes in the disease response, and to contribute at least partially to SA- and MeJA-induced pathogen resistance. PMID:26033522

  1. Cooperative Poetry.

    ERIC Educational Resources Information Center

    McEwen, Pam

    1989-01-01

    Describes "cooperative poetry," a group poetry-writing exercise combining brainstorming, rehearsing, choral reading, assisted reading, memorization, sequencing, and vocabulary development, as well as providing an opportunity for group cooperation. (MM)

  2. Cooperative redox-active additives of anthraquinone-2,7-disulphonate and K4Fe(CN)6 for enhanced performance of active carbon-based capacitors

    NASA Astrophysics Data System (ADS)

    Tian, Ying; Liu, Ming; Che, Ruxing; Xue, Rong; Huang, Liping

    2016-08-01

    Two redox additives of anthraquinone-2,7-disulphonate (AQDS) and K4Fe(CN)6 are introduced into the neutral medium of KNO3 for enhanced performance of active carbon-based (AC) capacitor. The Faradaic redox reactions of AQ/H2AQ and Fe(CN)63-/Fe(CN)64- are diffusion-controlled and occurred on the negative electrode and the positive electrode respectively and simultaneously, resulting in the enhancement of specific capacitance, power density and energy density of 240 F g-1, 527 W kg-1 and 26.3 Wh kg-1, respectively at a current density of 1.0 A g-1 for a symmetric AC capacitor in the electrolyte of 1 M KNO3-0.017 M K4Fe(CN)6-0.017 M AQDS. These values are much higher than those in the controls of either 1 M KNO3-0.017 M K4Fe(CN)6 or 1 M KNO3-0.017 M AQDS with only one pair of redox additives. These results demonstrate the cooperative K4Fe(CN)6 and AQDS for enhanced performance of AC capacitor, and thus provide an alternative approach for efficient capacitors.

  3. Social penalty promotes cooperation in a cooperative society

    PubMed Central

    Ito, Hiromu; Yoshimura, Jin

    2015-01-01

    Why cooperation is well developed in human society is an unsolved question in biological and human sciences. Vast studies in game theory have revealed that in non-cooperative games selfish behavior generally dominates over cooperation and cooperation can be evolved only under very limited conditions. These studies ask the origin of cooperation; whether cooperation can evolve in a group of selfish individuals. In this paper, instead of asking the origin of cooperation, we consider the enhancement of cooperation in a small already cooperative society. We ask whether cooperative behavior is further promoted in a small cooperative society in which social penalty is devised. We analyze hawk-dove game and prisoner’s dilemma introducing social penalty. We then expand it for non-cooperative games in general. The results indicate that cooperation is universally favored if penalty is further imposed. We discuss the current result in terms of the moral, laws, rules and regulations in a society, e.g., criminology and traffic violation. PMID:26238521

  4. Social penalty promotes cooperation in a cooperative society.

    PubMed

    Ito, Hiromu; Yoshimura, Jin

    2015-01-01

    Why cooperation is well developed in human society is an unsolved question in biological and human sciences. Vast studies in game theory have revealed that in non-cooperative games selfish behavior generally dominates over cooperation and cooperation can be evolved only under very limited conditions. These studies ask the origin of cooperation; whether cooperation can evolve in a group of selfish individuals. In this paper, instead of asking the origin of cooperation, we consider the enhancement of cooperation in a small already cooperative society. We ask whether cooperative behavior is further promoted in a small cooperative society in which social penalty is devised. We analyze hawk-dove game and prisoner's dilemma introducing social penalty. We then expand it for non-cooperative games in general. The results indicate that cooperation is universally favored if penalty is further imposed. We discuss the current result in terms of the moral, laws, rules and regulations in a society, e.g., criminology and traffic violation. PMID:26238521

  5. Cooperation of ETV6/RUNX1 and BCL2 enhances immunoglobulin production and accelerates glomerulonephritis in transgenic mice.

    PubMed

    Bauer, Eva; Schlederer, Michaela; Scheicher, Ruth; Horvath, Jaqueline; Aigner, Petra; Schiefer, Ana-Iris; Kain, Renate; Regele, Heinz; Hoermann, Gregor; Steiner, Günter; Kenner, Lukas; Sexl, Veronika; Villunger, Andreas; Moriggl, Richard; Stoiber, Dagmar

    2016-03-15

    The t(12;21) translocation generating the ETV6/RUNX1 fusion gene represents the most frequent chromosomal rearrangement in childhood leukemia. Presence of ETV6/RUNX1 alone is usually not sufficient for leukemia onset, and additional genetic alterations have to occur in ETV6/RUNX1-positive cells to cause transformation. We have previously generated an ETV6/RUNX1 transgenic mouse model where the expression of the fusion gene is restricted to CD19-positive B cells. Since BCL2 family members have been proposed to play a role in leukemogenesis, we investigated combined effects of ETV6/RUNX1 with exogenous expression of the antiapoptotic protein BCL2 by crossing ETV6/RUNX1 transgenic animals with Vav-BCL2 transgenic mice. Strikingly, co-expression of ETV6/RUNX1 and BCL2 resulted in significantly shorter disease latency in mice, indicating oncogene cooperativity. This was associated with faster development of follicular B cell lymphoma and exacerbated immune complex glomerulonephritis. ETV6/RUNX1-BCL2 double transgenic animals displayed increased B cell numbers and immunoglobulin titers compared to Vav-BCL2 transgenic mice. This led to pronounced deposition of immune complexes in glomeruli followed by accelerated development of immune complex glomerulonephritis. Thus, our study reveals a previously unrecognized synergism between ETV6/RUNX1 and BCL2 impacting on malignant disease and autoimmunity. PMID:26919255

  6. Cooperation of ETV6/RUNX1 and BCL2 enhances immunoglobulin production and accelerates glomerulonephritis in transgenic mice

    PubMed Central

    Bauer, Eva; Schlederer, Michaela; Scheicher, Ruth; Horvath, Jaqueline; Aigner, Petra; Schiefer, Ana-Iris; Kain, Renate; Regele, Heinz; Hoermann, Gregor; Steiner, Günter; Kenner, Lukas; Sexl, Veronika; Villunger, Andreas; Moriggl, Richard; Stoiber, Dagmar

    2016-01-01

    The t(12;21) translocation generating the ETV6/RUNX1 fusion gene represents the most frequent chromosomal rearrangement in childhood leukemia. Presence of ETV6/RUNX1 alone is usually not sufficient for leukemia onset, and additional genetic alterations have to occur in ETV6/RUNX1-positive cells to cause transformation. We have previously generated an ETV6/RUNX1 transgenic mouse model where the expression of the fusion gene is restricted to CD19-positive B cells. Since BCL2 family members have been proposed to play a role in leukemogenesis, we investigated combined effects of ETV6/RUNX1 with exogenous expression of the antiapoptotic protein BCL2 by crossing ETV6/RUNX1 transgenic animals with Vav-BCL2 transgenic mice. Strikingly, co-expression of ETV6/RUNX1 and BCL2 resulted in significantly shorter disease latency in mice, indicating oncogene cooperativity. This was associated with faster development of follicular B cell lymphoma and exacerbated immune complex glomerulonephritis. ETV6/RUNX1-BCL2 double transgenic animals displayed increased B cell numbers and immunoglobulin titers compared to Vav-BCL2 transgenic mice. This led to pronounced deposition of immune complexes in glomeruli followed by accelerated development of immune complex glomerulonephritis. Thus, our study reveals a previously unrecognized synergism between ETV6/RUNX1 and BCL2 impacting on malignant disease and autoimmunity. PMID:26919255

  7. Cooperative enhancement versus additivity of two-photon-absorption cross sections in linear and branched squaraine superchromophores.

    PubMed

    Ceymann, Harald; Rosspeintner, Arnulf; Schreck, Maximilian H; Mützel, Carina; Stoy, Andreas; Vauthey, Eric; Lambert, Christoph

    2016-06-28

    The linear and nonlinear optical properties of a series of oligomeric squaraine dyes were investigated by one-photon absorption spectroscopy (1PA) and two-photon absorption (2PA) induced fluorescence spectroscopy. The superchromophores are based on two indolenine squaraine dyes with transoid (SQA) and cisoid configuration (SQB). Using these monomers, linear dimers and trimers as well as star-shaped trimers and hexamers with benzene or triphenylamine cores were synthesised and investigated. The red-shifted and intensified 1PA spectra of all superchromophores could well be explained by exciton coupling theory. In the linear chromophore arrangements we also found superradiance of fluorescence but not in the branched systems. Furthermore, the 2PA showed enhanced cross sections for the linear oligomers but only additivity for the branched systems. This emphasizes that the enhancement of the 2PA cross section in the linear arrangements is probably caused by orbital interactions of higher excited configurations. PMID:27264847

  8. ALK(R1275Q) perturbs extracellular matrix, enhances cell invasion and leads to the development of neuroblastoma in cooperation with MYCN.

    PubMed

    Ueda, T; Nakata, Y; Yamasaki, N; Oda, H; Sentani, K; Kanai, A; Onishi, N; Ikeda, K; Sera, Y; Honda, Z-I; Tanaka, K; Sata, M; Ogawa, S; Yasui, W; Saya, H; Takita, J; Honda, H

    2016-08-25

    Overexpression of MYCN is a hallmark of neuroblastoma (NB). ALK(R1275Q), an activating mutation of ALK (anaplastic lymphoma kinase), has been found in sporadic and familial NB patients. In this report, we demonstrated that ALK(R1275Q) knock-in, MYCN transgenic compound mice developed NB with complete penetrance. Transcriptome analysis revealed that ALK(R1275Q) globally downregulated the expression of extracellular matrix (ECM)- and basement membrane (BM)-associated genes in both primary neuronal cells and NB tumors. Accordingly, ALK(R1275Q)/MYCN tumors exhibited reduced expression of ECM/BM-related proteins as compared with MYCN tumors. In addition, on MYCN transduction, ALK(R1275Q)-expressing neuronal cells exhibited increased migratory and invasive activities. Consistently, enhanced invasion and metastasis were demonstrated in ALK(R1275Q)/MYCN mice. These results collectively indicate that ALK(R1275Q) confers a malignant potential on neuronal cells that overexpress MYCN by impairing normal ECM/BM integrity and enhancing tumor growth and dissemination. Moreover, we found that crizotinib, an ALK inhibitor, almost completely inhibited the growth of ALK(R1275Q)/MYCN tumors in an allograft model. Our findings provided insights into the cooperative mechanism of the mutated ALK and overexpressed MYCN in the pathogenesis of NB and demonstrated the effectiveness of crizotinib on ALK(R1275Q)-positive tumors. PMID:26829053

  9. Declaration of the European Ministers of Vocational Education and Training, and the European Commission, Convened in Copenhagen on 29 and 30 November 2002, on Enhanced European Cooperation in Vocational Education and Training. "The Copenhagen Declaration."

    ERIC Educational Resources Information Center

    European Commission, Brussels (Belgium).

    Enhanced cooperation in vocational education and training (VET) will be an important contribution toward ensuring a successful enlargement of the European Union. The social partners play an indispensable role in development, validation, and recognition of vocational competencies and qualifications at all levels and are partners in promotion of…

  10. Genome Wide Mapping of NR4A Binding Reveals Cooperativity with ETS Factors to Promote Epigenetic Activation of Distal Enhancers in Acute Myeloid Leukemia Cells

    PubMed Central

    Duren, Ryan P.; Boudreaux, Seth P.; Conneely, Orla M.

    2016-01-01

    Members of the NR4A subfamily of orphan nuclear receptors regulate cell fate decisions via both genomic and non-genomic mechanisms in a cell and tissue selective manner. NR4As play a key role in maintenance of hematopoietic stem cell homeostasis and are critical tumor suppressors of acute myeloid leukemia (AML). Expression of NR4As is broadly silenced in leukemia initiating cell enriched populations from human patients relative to normal hematopoietic stem/progenitor cells. Rescue of NR4A expression in human AML cells inhibits proliferation and reprograms AML gene signatures via transcriptional mechanisms that remain to be elucidated. By intersecting an acutely regulated NR4A1 dependent transcriptional profile with genome wide NR4A binding distribution, we now identify an NR4A targetome of 685 genes that are directly regulated by NR4A1. We show that NR4As regulate gene transcription primarily through interaction with distal enhancers that are co-enriched for NR4A1 and ETS transcription factor motifs. Using a subset of NR4A activated genes, we demonstrate that the ETS factors ERG and FLI-1 are required for activation of NR4A bound enhancers and NR4A target gene induction. NR4A1 dependent recruitment of ERG and FLI-1 promotes binding of p300 histone acetyltransferase to epigenetically activate NR4A bound enhancers via acetylation at histone H3K27. These findings disclose novel epigenetic mechanisms by which NR4As and ETS factors cooperate to drive NR4A dependent gene transcription in human AML cells. PMID:26938745

  11. COOPERATION MAINTAINED BY FITNESS ADJUSTMENT

    PubMed Central

    TAYLOR, CHRISTINE; CHEN, JANET; IWASA, YOH

    2008-01-01

    Questions Whether or not cooperation can be enhanced if players with a performance higher than the mean are forced to pay an additional cost in each generation? Mathematical Methods Analysis of replicator dynamics with mutation. The ESS distribution of cooperation level is obtained. Key Assumptions Players engage in cooperative dilemma game, and at the end of each generation, those with higher performance than the mean are forced to pay additional cost. Conclusions Without mutation, the entire population eventually conforms to a single cooperation level determined by the initial composition of the population. With mutation, there is an equilibrium distribution of cooperation level, which has a peak at an intermediate level of cooperation. Whether it is institutionalized such as tax or just a social custom, fitness adjustment based ultimately on people’s emtion of “envy” is able to maintain cooperation. PMID:19079742

  12. Cooperation between catalytic and DNA binding domains enhances thermostability and supports DNA synthesis at higher temperatures by thermostable DNA polymerases.

    PubMed

    Pavlov, Andrey R; Pavlova, Nadejda V; Kozyavkin, Sergei A; Slesarev, Alexei I

    2012-03-13

    We have previously introduced a general kinetic approach for comparative study of processivity, thermostability, and resistance to inhibitors of DNA polymerases [Pavlov, A. R., et al. (2002) Proc. Natl. Acad. Sci. U.S.A.99, 13510-13515]. The proposed method was successfully applied to characterize hybrid DNA polymerases created by fusing catalytic DNA polymerase domains with various sequence-nonspecific DNA binding domains. Here we use the developed kinetic analysis to assess basic parameters of DNA elongation by DNA polymerases and to further study the interdomain interactions in both previously constructed and new chimeric DNA polymerases. We show that connecting helix-hairpin-helix (HhH) domains to catalytic polymerase domains can increase thermostability, not only of DNA polymerases from extremely thermophilic species but also of the enzyme from a faculatative thermophilic bacterium Bacillus stearothermophilus. We also demonstrate that addition of Topo V HhH domains extends efficient DNA synthesis by chimerical polymerases up to 105 °C by maintaining processivity of DNA synthesis at high temperatures. We found that reversible high-temperature structural transitions in DNA polymerases decrease the rates of binding of these enzymes to the templates. Furthermore, activation energies and pre-exponential factors of the Arrhenius equation suggest that the mechanism of electrostatic enhancement of diffusion-controlled association plays a minor role in binding of templates to DNA polymerases. PMID:22320201

  13. Cooperative Enhancement of Second-Harmonic Generation from a Single CdS Nanobelt-Hybrid Plasmonic Structure.

    PubMed

    Liu, Xinfeng; Zhang, Qing; Chong, Wee Kiang; Yip, Jing Ngei; Wen, Xinglin; Li, Zhenpeng; Wei, Fengxia; Yu, Guannan; Xiong, Qihua; Sum, Tze Chien

    2015-05-26

    Semiconductor nanostructures (e.g., nanowires and nanobelts) hold great promise as subwavelength coherent light sources, nonlinear optical frequency converters, and all-optical signal processors for optoelectronic applications. However, at such small scales, optical second-harmonic generation (SHG) is generally inefficient. Herein, we report on a straightforward strategy using a thin Au layer to enhance the SHG from a single CdS nanobelt by 3 orders of magnitude. Through detailed experimental and theoretical analysis, we validate that the augmented SHG originates from the mutual intensification of the local fields induced by the plasmonic nanocavity and by the reflections within the CdS Fabry-Pérot resonant cavity in this hybrid semiconductor-metal system. Polarization-dependent SHG measurements can be employed to determine and distinguish the contributions of SH signals from the CdS nanobelt and gold film, respectively. When the thickness of gold film becomes comparable to the skin depth, SHG from the gold film can be clearly observed. Our work demonstrates a facile approach for tuning the nonlinear optical properties of mesoscopic, nanostructured, and layered semiconductor materials. PMID:25905978

  14. Library Cooperation.

    ERIC Educational Resources Information Center

    Lund, Patricia; And Others

    1993-01-01

    Includes nine articles that discuss cooperative library networking in Illinois. Highlights include library systems as cooperative agencies; PALI (Private Academic Libraries of Illinois); rural school and public library development; systemwide users; regional medical libraries; virtual libraries and the Coalition for Networked Information; a…

  15. Operation Cooperation.

    ERIC Educational Resources Information Center

    Hohl, K. Robert

    The needs of teachers for high-demand and seasonal films have been met by a cooperative effort of the Berks County Educational Television Committee, local school districts, the Berks and Suburban TV cable companies and the Berks County Intermediate Unit in a project called Operation Cooperation. Regionalization of the instructional media services…

  16. Cooperative Education.

    ERIC Educational Resources Information Center

    Office of Education (DHEW), Washington, DC.

    Cooperative education programs, a nontraditional blending of practice and theory, have become an important feature of current higher education. Some educators estimate that by 1984 half of the higher education institutions in the United States will have developed some form of cooperative education. The Federal government's recent involvement in…

  17. Cooperative effect of BI-69A11 and celecoxib enhances radiosensitization by modulating DNA damage repair in colon carcinoma.

    PubMed

    Pal, Ipsita; Dey, Kaushik Kumar; Chaurasia, Madhuri; Parida, Sheetal; Das, Subhayan; Rajesh, Y; Sharma, Kulbhushan; Chowdhury, Tamohan; Mandal, Mahitosh

    2016-05-01

    Amplification of PI3K-Akt pathway promotes radioresistance in various cancers including colorectal carcinoma. Local recurrence in colon cancer causes poor prognosis affecting overall survival of cancer-affected patient population. To avoid local recurrence, pre-operative or post-operative additional radiotherapy is given. However, main concern regarding radiotherapy is to increase the radiosensitivity of malignant cell without hampering the activities of normal cells. In this context, addition of two or more than two chemotherapeutic drugs as a radiosensitizer is a common practice in radiation biology. BI-69A11 earlier showed potential apoptosis-inducing effect in melanoma and colon carcinoma. Celecoxib showed anti-cancer effects in both COX-2 dependent and independent pathways and used to act as a radiosensitizing enhancer. Here, we suggest that the combination of BI-69A11 and celecoxib inhibits the phosphorylation of ataxia telangiectasia mutated (ATM) kinase and DNA-PK responsible for ionizing radiation (IR)-induced double-strand break (DSB) repair. Moreover, the combinatorial effect of BI-69A11 and celecoxib attenuates the IR-induced G2/M cell cycle arrest. Furthermore, this combination also impairs IR-induced activation of Akt and downstream targets of ATM. This might lead to induced activation of apoptotic pathway after triple therapy treatment modulating pro-apoptotic and anti-apoptotic proteins. This activation of apoptotic pathway also showed the interdependence of PUMA and BAD in triple combination-treated colon cancer cells in a p53 independent manner. This study reveals the therapeutic potential of the triple combination therapy in prevention of radioresistance. Besides, it also demonstrates the cytotoxic effects of triple combination therapy in colon cancer. This study shows utility and potential implication on safety of the patients undergoing radiation therapy. PMID:26631035

  18. Cooperative Learning in Elementary Schools.

    ERIC Educational Resources Information Center

    Hadderman, Margaret

    1992-01-01

    Cooperative learning is being recommended as a solution for numerous education problems, from enhancing disadvantaged children's self-esteem to ensuring academic success for all students. Cooperative learning has great potential as a supplement or alternative to traditional teaching methods when students are adequately socialized and motivated.…

  19. Cooperative Learning for Better Performance.

    ERIC Educational Resources Information Center

    Di Natale, John J.; Russell, Gordon

    1995-01-01

    Asserts that linking music ensemble programs and cooperative learning strategies often has been overlooked. Describes the benefits of cooperative learning techniques for music performance preparation. Concludes that the small-group approach can enhance traditional music programs by offering students the chance to make their own decisions. (CFR)

  20. Cooperative processes in image segmentation

    NASA Technical Reports Server (NTRS)

    Davis, L. S.

    1982-01-01

    Research into the role of cooperative, or relaxation, processes in image segmentation is surveyed. Cooperative processes can be employed at several levels of the segmentation process as a preprocessing enhancement step, during supervised or unsupervised pixel classification and, finally, for the interpretation of image segments based on segment properties and relations.

  1. Generation Z, Meet Cooperative Learning

    ERIC Educational Resources Information Center

    Igel, Charles; Urquhart, Vicki

    2012-01-01

    Today's Generation Z teens need to develop teamwork and social learning skills to be successful in the 21st century workplace. Teachers can help students develop these skills and enhance academic achievement by implementing cooperative learning strategies. Three key principles for successful cooperative learning are discussed. (Contains 1 figure.)

  2. Cooperative Education in Outdoor Education

    ERIC Educational Resources Information Center

    Martin, Andy; Flemming, Jenny

    2010-01-01

    Cooperative education is a structured experiential education strategy integrating classroom studies with work place learning. The purpose of this paper is to evaluate how a cooperative education model can be included within an outdoor education undergraduate degree to develop reflective practitioners and to enhance graduate capabilities. Document…

  3. Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells.

    PubMed Central

    Bassuk, A G; Anandappa, R T; Leiden, J M

    1997-01-01

    The transcriptional regulatory elements of many inducible T-cell genes contain adjacent or overlapping binding sites for the Ets and NF-kappaB/NFAT families of transcription factors. Similar arrays of functionally important NF-kappaB/NFAT and Ets binding sites are present in the transcriptional enhancers of human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2), suggesting that this pattern of nuclear protein binding sites reflects an evolutionarily conserved mechanism for regulating inducible T-cell gene expression that has been co-opted during HIV evolution. Despite these findings, the molecular mechanisms by which Ets and NF-kappaB/NFAT proteins cooperatively regulate inducible T-cell gene expression remained unknown. In the studies described in this report, we demonstrated a physical interaction between multiple Ets and NF-kappaB/NFAT proteins both in vitro and in activated normal human T cells. This interaction is mediated by the Ets domain of Ets proteins and the C-terminal region of the Rel homology domains of NF-kappaB/NFAT proteins. In addition, the Ets-NF-kappaB/NFAT interaction requires the presence of DNA binding sites for both proteins, as it is abolished by the DNA intercalating agents propidium iodide and ethidium bromide and enhanced by the presence of synthetic oligonucleotides containing binding sites for Ets and NF-kappaB proteins. A dominant-negative mutant of NF-kappaB p50 that binds DNA but fails to interact with Ets proteins inhibits the synergistic activation of the HIV-1 and HIV-2 enhancers by NF-kappaB (p50 + p65) and Ets-1, suggesting that physical interaction between Ets and NF-kappaB proteins is required for the transcriptional activity of the HIV-1 and HIV-2 enhancers. Taken together, these findings suggest that evolutionarily conserved physical interactions between Ets and NF-kappaB/NFAT proteins are important in regulating the inducible expression of T-cell genes and viruses. These interactions represent a potential target

  4. Cooperative cathode electrode and in situ deposited copper for subsequent enhanced Cd(II) removal and hydrogen evolution in bioelectrochemical systems.

    PubMed

    Wang, Qiang; Huang, Liping; Pan, Yuzhen; Zhou, Peng; Quan, Xie; Logan, Bruce E; Chen, Hongbo

    2016-01-01

    Bioelectrochemical systems (BESs) were first operated in microbial fuel cell mode for recovering Cu(II), and then shifted to microbial electrolysis cells for Cd(II) reduction on the same cathodes of titanium sheet (TS), nickel foam (NF) or carbon cloth (CC). Cu(II) reduction was similar to all materials (4.79-4.88mg/Lh) whereas CC exhibited the best Cd(II) reduction (5.86±0.25mg/Lh) and hydrogen evolution (0.35±0.07m(3)/m(3)d), followed by TS (5.27±0.43mg/Lh and 0.15±0.02m(3)/m(3)d) and NF (4.96±0.48mg/Lh and 0.80±0.07m(3)/m(3)d). These values were higher than no copper controls by factors of 2.0 and 5.0 (TS), 4.2 and 2.0 (NF), and 1.8 and 7.0 (CC). These results demonstrated cooperative cathode electrode and in situ deposited copper for subsequent enhanced Cd(II) reduction and hydrogen production in BESs, providing an alternative approach for efficiently remediating Cu(II) and Cd(II) co-contamination with simultaneous hydrogen production. PMID:26528907

  5. Cooperative self-construction and enhanced optical absorption of nanoplates-assembled hierarchical Bi{sub 2}WO{sub 6} flowers

    SciTech Connect

    Liu Shengwei; Yu Jiaguo

    2008-05-15

    Bi{sub 2}WO{sub 6} hierarchical multilayered flower-like assemblies are fabricated on a large scale by a simple hydrothermal method in the presence of polymeric poly(sodium 4-styrenesulfonate). Such 3D Bi{sub 2}WO{sub 6} assemblies are constructed from orderly arranged 2D layers, which are further composed of a large number of interconnected nanoplates with a mean side length of ca. 50 nm. The bimodal mesopores associated with such hierarchical assembly exhibit peak mesopore size of ca. 4 nm for the voids within a layer, and peak mesopore size of ca. 40 nm corresponding to the interspaces between stacked layers, respectively. The formation process is discussed on the basis of the results of time-dependent experiments, which support a novel 'coupled cooperative assembly and localized ripening' formation mechanism. More interestingly, we have noticed that the collective effect related to such hierarchical assembly induces a significantly enhanced optical absorbance in the UV-visible region. This work may shed some light on the design of complex architectures and exploitation of their potential applications. - Graphical abstract: Bi{sub 2}WO{sub 6} hierarchical multilayered flower-like assemblies are fabricated on a large scale by a simple hydrothermal method in the presence of polymeric poly(sodium 4-styrenesulfonate)

  6. Filamin A-interacting protein (FILIP) is a region-specific modulator of myosin 2b and controls spine morphology and NMDA receptor accumulation.

    PubMed

    Yagi, Hideshi; Nagano, Takashi; Xie, Min-Jue; Ikeda, Hiroshi; Kuroda, Kazuki; Komada, Munekazu; Iguchi, Tokuichi; Tariqur, Rahman M; Morikubo, Soichi; Noguchi, Koichi; Murase, Kazuyuki; Okabe, Masaru; Sato, Makoto

    2014-01-01

    Learning and memory depend on morphological and functional changes to neural spines. Non-muscle myosin 2b regulates actin dynamics downstream of long-term potentiation induction. However, the mechanism by which myosin 2b is regulated in the spine has not been fully elucidated. Here, we show that filamin A-interacting protein (FILIP) is involved in the control of neural spine morphology and is limitedly expressed in the brain. FILIP bound near the ATPase domain of non-muscle myosin heavy chain IIb, an essential component of myosin 2b, and modified the function of myosin 2b by interfering with its actin-binding activity. In addition, FILIP altered the subcellular distribution of myosin 2b in spines. Moreover, subunits of the NMDA receptor were differently distributed in FILIP-expressing neurons, and excitation propagation was altered in FILIP-knockout mice. These results indicate that FILIP is a novel, region-specific modulator of myosin 2b. PMID:25220605

  7. A distinct X-linked syndrome involving joint contractures, keloids, large optic cup-to-disc ratio, and renal stones results from a filamin A (FLNA) mutation.

    PubMed

    Lah, Melissa; Niranjan, Tejasvi; Srikanth, Sujata; Holloway, Lynda; Schwartz, Charles E; Wang, Tao; Weaver, David D

    2016-04-01

    We further evaluated a previously reported family with an apparently undescribed X-linked syndrome involving joint contractures, keloids, an increased optic cup-to-disc ratio, and renal stones to elucidate the genetic cause. To do this, we obtained medical histories and performed physical examination on 14 individuals in the family, five of whom are affected males and three are obligate carrier females. Linkage analysis was performed on all but one individual and chromosome X-exome sequencing was done on two affected males. The analysis localized the putative gene to Xq27-qter and chromosome X-exome sequencing revealed a mutation in exon 28 (c.4726G>A) of the filamin A (FLNA) gene, predicting that a conserved glycine had been replaced by arginine at amino acid 1576 (p.G1576R). Segregation analysis demonstrated that all known carrier females tested were heterozygous (G/A), all affected males were hemizygous for the mutation (A allele) and all normal males were hemizygous for the normal G allele. The data and the bioinformatic analysis indicate that the G1576R mutation in the FLNA gene is very likely pathogenic in this family. The syndrome affecting the family shares phenotypic overlap with other syndromes caused by FLNA mutations, but appears to be a distinct phenotype, likely representing a unique genetic syndrome. © 2016 Wiley Periodicals, Inc. PMID:26804200

  8. Filamin A-interacting protein (FILIP) is a region-specific modulator of myosin 2b and controls spine morphology and NMDA receptor accumulation

    PubMed Central

    Yagi, Hideshi; Nagano, Takashi; Xie, Min-Jue; Ikeda, Hiroshi; Kuroda, Kazuki; Komada, Munekazu; Iguchi, Tokuichi; Tariqur, Rahman M.; Morikubo, Soichi; Noguchi, Koichi; Murase, Kazuyuki; Okabe, Masaru; Sato, Makoto

    2014-01-01

    Learning and memory depend on morphological and functional changes to neural spines. Non-muscle myosin 2b regulates actin dynamics downstream of long-term potentiation induction. However, the mechanism by which myosin 2b is regulated in the spine has not been fully elucidated. Here, we show that filamin A-interacting protein (FILIP) is involved in the control of neural spine morphology and is limitedly expressed in the brain. FILIP bound near the ATPase domain of non-muscle myosin heavy chain IIb, an essential component of myosin 2b, and modified the function of myosin 2b by interfering with its actin-binding activity. In addition, FILIP altered the subcellular distribution of myosin 2b in spines. Moreover, subunits of the NMDA receptor were differently distributed in FILIP-expressing neurons, and excitation propagation was altered in FILIP-knockout mice. These results indicate that FILIP is a novel, region-specific modulator of myosin 2b. PMID:25220605

  9. HCF1 and OCT2 Cooperate with EBNA1 To Enhance OriP-Dependent Transcription and Episome Maintenance of Latent Epstein-Barr Virus

    PubMed Central

    Dheekollu, Jayaraju; Wiedmer, Andreas; Sentana-Lledo, Daniel; Cassel, Joel; Messick, Troy

    2016-01-01

    ABSTRACT Epstein-Barr virus (EBV) establishes latent infections as multicopy episomes with complex patterns of viral gene transcription and chromatin structure. The EBV origin of plasmid replication (OriP) has been implicated as a critical control element for viral transcription, as well as viral DNA replication and episome maintenance. Here, we examine cellular factors that bind OriP and regulate histone modification, transcription regulation, and episome maintenance. We found that OriP is enriched for histone H3 lysine 4 (H3K4) methylation in multiple cell types and latency types. Host cell factor 1 (HCF1), a component of the mixed-lineage leukemia (MLL) histone methyltransferase complex, and transcription factor OCT2 (octamer-binding transcription factor 2) bound cooperatively with EBNA1 (Epstein-Barr virus nuclear antigen 1) at OriP. Depletion of OCT2 or HCF1 deregulated latency transcription and histone modifications at OriP, as well as the OriP-regulated latency type-dependent C promoter (Cp) and Q promoter (Qp). HCF1 depletion led to a loss of histone H3K4me3 (trimethylation of histone H3 at lysine 4) and H3 acetylation at Cp in type III latency and Qp in type I latency, as well as an increase in heterochromatic H3K9me3 at these sites. HCF1 depletion resulted in the loss of EBV episomes from Burkitt's lymphoma cells with type I latency and reactivation from lymphoblastoid cells (LCLs) with type III latency. These findings indicate that HCF1 and OCT2 function at OriP to regulate viral transcription, histone modifications, and episome maintenance. As HCF1 is best known for its function in herpes simplex virus 1 (HSV-1) immediate early gene transcription, our findings suggest that EBV latency transcription shares unexpected features with HSV gene regulation. IMPORTANCE EBV latency is associated with several human cancers. Viral latent cycle gene expression is regulated by the epigenetic control of the OriP enhancer region. Here, we show that cellular factors

  10. FOSTERING MULTI-LATERAL COOPERATION BETWEEN THE GOVERNMENTS OF DOMINICAN REPUBLIC, COLOMBIA, AND THE UNITED STATES TO ENHANCE THE PROTECTION OF HIGH-ACTIVITY RADIOACTIVE SOURCES

    SciTech Connect

    Butler, Nicholas; McCaw, Erica E.; Wright, Kyle A.; Medina, Maximo

    2009-10-06

    The Global Threat Reduction Initiative (GTRI) reduces and protects vulnerable nuclear and radiological material located at civilian sites worldwide from sabotage, theft or diversion. The GTRI has worked successfully with foreign countries to remove and protect nuclear and radioactive materials including high-activity sources used in medical, commercial, and research applications. There are many barriers to successful bilateral cooperation that must be overcome including language, preconceived perceptions, long distances, and different views on the threat and protection requirements. Successful cooperation is often based on relationships and building trusting relationships takes time. In the case of Dominican Republic, the GTRI first received contact in 2008 from the Government of Dominican Republic. They requested cooperation that was similar to the tri-partite cooperation between Colombia, Mexico and the United States. Throughout the region it was widely known that the GTRI’s cooperation with the Government of Colombia was a resounding success resulting in the securing of forty sites; the consolidation of numerous disused/orphan sources at a secure national storage facility; and, the development of a comprehensive approach to security including, inter alia, training and sustainability. The Government of Colombia also showcased this comprehensive approach to thirteen Central American and Caribbean countries at a GTRI regional security conference held in Panama in October 2004. In 2007, Colombia was an integral component of GTRI multi-lateral cooperation initiation in Mexico. As a result, twenty two of Mexico’s largest radioactive sites have been upgraded in the past eighteen months. These two endeavors served as catalysts for cooperation opportunities in the Dominican Republic. Representatives from the Colombian government were aware of GTRI’s interest in initiating cooperation with the Government of Dominican Republic and to facilitate this cooperation, they

  11. FOSTERING MULTI-LATERAL COOPERATION BETWEEN THE GOVERNMENTS OF MEXICO, COLOMBIA, AND THE UNITED STATES TO ENHANCE THE PROTECTION OF HIGH-ACTIVITY RADIOACTIVE SOURCES

    SciTech Connect

    Butler, Nicholas; Watson, Erica E.; Wright, Kyle A.

    2009-10-07

    The Global Threat Reduction Initiative (GTRI) reduces and protects vulnerable nuclear and radiological material located at civilian sites worldwide from sabotage, theft or diversion. The GTRI program has worked successfully with foreign countries to remove and protect nuclear and radioactive materials including high-activity sources used in medical, commercial, and research applications. There are many barriers to successful bilateral cooperation that must be overcome including language, preconceived perceptions, long distances, and different views on the threat and protection requirements. Successful cooperation is often based on relationships and building trusting relationships takes time. In the case of Mexico, GTRI first made contact in 2005. The project then lost momentum and stalled. At the same time, GTRI’s cooperation with the Republic of Colombia was a resounding success resulting in the securing of forty sites; the consolidation of numerous disused/orphan sources at a secure national storage facility; and, the development of a comprehensive approach to security including, inter alia, training and sustainability. The government of Colombia also showcased this comprehensive approach to thirteen Central American and Caribbean countries at a GTRI regional security conference held in Panama in October 2004. Representatives from the Colombian government were aware of GTRI’s interest in initiating cooperation with the Government of Mexico and to facilitate this cooperation, they offered to invite their Mexican counterparts to Colombia to observe its successful cooperation with GTRI. Shortly after that visit, the Government of Mexico agreed to move forward and requested that the cooperative efforts in Mexico be performed in a tripartite manner, leveraging the skills, experience, and resources of the Colombians. As a result, 22 of Mexico’s largest radioactive sites have had security upgrades in place within 18 months of cooperation.

  12. Teacher Cooperatives

    ERIC Educational Resources Information Center

    Hawkins, Beth

    2009-01-01

    Twenty years ago, when the late Albert Shanker endorsed the notion of innovative schools operating outside conventional district bureaucracies, his aim was to put teachers at the helm. Today there are nearly 80 teacher-governed charter schools around the country. Although most are legally constituted as worker cooperatives, they better resemble…

  13. Enhanced deodorization and sludge reduction in situ by a humus soil cooperated anaerobic/anoxic/oxic (A2O) wastewater treatment system.

    PubMed

    Yan, Xing; Li, Biqing; Lei, Fang; Feng, Xin; Pang, Bo

    2016-08-01

    Simultaneous sludge reduction and malodor abatement in humus soil cooperated an anaerobic/anoxic/oxic (A2O) wastewater treatment were investigated in this study. The HSR-A2O was composed of a humus soil reactor (HSR) and a conventional A2O (designated as C-A2O).The results showed that adding HSR did not deteriorate the chemical oxygen demand (COD) removal, while total phosphorus (TP) removal efficiency in HSR-A2O was improved by 18 % in comparison with that in the C-A2O. Both processes had good performance on total nitrogen (TN) removal, and there was no significant difference between them (76.8 and 77.1 %, respectively). However, NH4 (+)-N and NO3 (-)-N were reduced to 0.3 and 6.7 mg/L in HSR-A2O compared to 1.5 and 4.5 mg/L. Moreover, adding HSR induced the sludge reduction, and the sludge production rate was lower than that in the C-A2O. The observed sludge yield was estimated to be 0.32 kg MLSS/day in HSR-A2O, which represent a 33.5 % reduction compared to a C-A2O process. Activated sludge underwent humification and produced more humic acid in HSR-A2O, which is beneficial to sludge reduction. Odor abatement was achieved in HSR-A2O, ammonium (NH3), and sulfuretted hydrogen (H2S) emission decreased from 1.34 and 1.33 to 0.06 mg/m(3), 0.025 mg/m(3) in anaerobic area, with the corresponding reduction efficiency of 95.5 and 98.1 %. Microbial community analysis revealed that the relevant microorganism enrichment explained the reduction effect of humus soil on NH3 and H2S emission. The whole study demonstrated that humus soil enhanced odor abatement and sludge reduction in situ. PMID:27146529

  14. Cooperation and age structure in spatial games

    NASA Astrophysics Data System (ADS)

    Wang, Zhen; Wang, Zhen; Zhu, Xiaodan; Arenzon, Jeferson J.

    2012-01-01

    We study the evolution of cooperation in evolutionary spatial games when the payoff correlates with the increasing age of players (the level of correlation is set through a single parameter, α). The demographic heterogeneous age distribution, directly affecting the outcome of the game, is thus shown to be responsible for enhancing the cooperative behavior in the population. In particular, moderate values of α allow cooperators not only to survive but to outcompete defectors, even when the temptation to defect is large and the ageless, standard α=0 model does not sustain cooperation. The interplay between age structure and noise is also considered, and we obtain the conditions for optimal levels of cooperation.

  15. The Effectiveness of the Consistency Management & Cooperative Discipline (CMCD) Model as a Student Empowerment and Achievement Enhancer: The Experiences of Two K-12 Inner-City School Systems

    ERIC Educational Resources Information Center

    Opuni, Kwame A.

    2006-01-01

    Consistency Management and Cooperative Discipline (CMCD) is a research-based K-12 discipline management program that builds on shared responsibility for learning and classroom organization through the cultivation of democratic and participatory practices that are fair, inclusive, and caring. CMCD seeks to provide a stable and orderly learning…

  16. Assessment in the Cooperative Classroom: Using an Action Research Enhanced Version of the Train the Trainer In-service Model To Impact Teacher Attitudes and Practices.

    ERIC Educational Resources Information Center

    Rolheiser, Carol; Ross, John A.; Hogaboam-Gray, Anne

    This research investigated the impact of combining two approaches to inservice teacher education (action research and train the trainer) on teacher attitudes and practices. The inservice developed assessment approaches aligned with cooperative learning instructional approaches. Teachers were introduced to a model of collaborative assessment aimed…

  17. Investigating the role of filamin C in Belgian patients with frontotemporal dementia linked to GRN deficiency in FTLD-TDP brains.

    PubMed

    Janssens, Jonathan; Philtjens, Stéphanie; Kleinberger, Gernot; Van Mossevelde, Sara; van der Zee, Julie; Cacace, Rita; Engelborghs, Sebastiaan; Sieben, Anne; Banzhaf-Strathmann, Julia; Dillen, Lubina; Merlin, Céline; Cuijt, Ivy; Robberecht, Caroline; Schmid, Bettina; Santens, Patrick; Ivanoiu, Adrian; Vandenbulcke, Mathieu; Vandenberghe, Rik; Cras, Patrick; De Deyn, Peter P; Martin, Jean-Jacques; Maudsley, Stuart; Haass, Christian; Cruts, Marc; Van Broeckhoven, Christine

    2015-01-01

    TAR DNA-binding protein 43 (TDP-43) inclusions are pathological hallmarks of patients with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Loss of TDP-43 in zebrafish engenders a severe muscle and vascular phenotype with a concomitant elevation of filamin C (FLNC) levels, an observation confirmed in the frontal cortex of FTLD-TDP patients. Here, we aimed to further assess the contribution of FLNC to frontotemporal dementia (FTD) etiology. We conducted a mutational screening of FLNC in a cohort of 529 unrelated Belgian FTD and FTD-ALS patients, and a control cohort of 920 unrelated and age-matched individuals. Additionally we performed an in-depth characterization of FLNC expression levels in FTD patients and a murine FTD model.In total 68 missense variants were identified of which 19 (MAF < 1%) were patient-only. Gene burden analysis demonstrated a significant association between the presence of rare variants in FLNC and disease (P = 0.0349, RR = 1.46 [95% CI 1.03-2.07]). Furthermore, elevated FLNC expression levels, observed previously in FTLD-TDP patients, were mainly attributable to FTD patients with the progranulin (GRN) p.0(IVS1 + 5G > C) loss-of-function mutation. Increased FLNC levels were, to a lesser extent, also identified in a FLNC p.V831I variant carrier and in FTD patients with the p.R159H mutation in valosin-containing protein (VCP). The GRN-associated increase of FLNC was confirmed in the frontal cortex of aged Grn knockout mice starting at 16-18 months of age. Combined quantitative proteomic and bioinformatic analyses of the frontal cortex of FTD patients possessing elevated FLNC levels, identified multiple altered protein factors involved in accelerated aging, neurodegeneration and synaptogenesis.Our findings further support the involvement of aberrant FLNC expression levels in FTD pathogenesis. Identification of increased FLNC levels in aged Grn mice and impaired pathways related to aging and

  18. An Overview of the Cooperative Effort between the United States Department of Energy and the China Atomic Energy Authority to Enhance MPC&A Inspections for Civil Nuclear Facilities in China

    SciTech Connect

    Ahern, Keith; Daming, Liu; Hanley, Tim; Livingston, Linwood; McAninch, Connie; McGinnis, Brent R; Ning, Shen; Qun, Yang; Roback, Jason William; Tuttle, Glenn; Xuemei, Gao; Galer, Regina; Peterson, Nancy; Jia, Jinlie

    2011-01-01

    The United States Department of Energy, National Nuclear Security Administration (DOE/NNSA) and the China Atomic Energy Authority (CAEA) are cooperating to enhance the domestic regulatory inspections capacity for special nuclear material protection, control and accounting (MPC&A) requirements for civil nuclear facilities in China. This cooperation is conducted under the auspices of the Agreement between the Department of Energy of the United States of America and the State Development and Planning Commission of the People s Republic of China on Cooperation Concerning Peaceful Uses of Nuclear Technology. This initial successful effort was conducted in three phases. Phase I focused on introducing CAEA personnel to DOE and U. S. Nuclear Regulatory Commission inspection methods for U. S. facilities. This phase was completed in January 2008 during meetings in Beijing. Phase II focused on developing physical protection and material control and accounting inspection exercises that enforced U. S. inspection methods identified during Phase 1. Hands on inspection activities were conducted in the United States over a two week period in July 2009. Simulated deficiencies were integrated into the inspection exercises. The U. S. and Chinese participants actively identified and discussed deficiencies noted during the two week training course. The material control and accounting inspection exercises were conducted at the Paducah Gaseous Diffusion Plant (PGDP) in Paducah, KY. The physical protection inspection exercises were conducted at the Oak Ridge National Laboratory (ORNL) in Oak Ridge, TN. Phase III leveraged information provided under Phase I and experience gained under Phase II to develop a formal inspection guide that incorporates a systematic approach to training for Chinese MPC&A field inspectors. Additional hands on exercises that are applicable to Chinese regulations were incorporated into the Phase III training material. Phase III was completed in May 2010 at the China

  19. 76 FR 78290 - Cooperative Research and Development Agreement: Usage of Biodiesel Fuel Blends Within Marine...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-16

    ... Register (73 FR 3316). Cooperative Research and Development Agreements Cooperative Research and Development... SECURITY Coast Guard Cooperative Research and Development Agreement: Usage of Biodiesel Fuel Blends Within... technology enhancements, performance, costs, and other issues associated with using biodiesel fuel blends...

  20. Co-Operative Education or Co-Operative Placement?

    ERIC Educational Resources Information Center

    Dickson, C. R.

    The Co-operative Education Department at Mohawk College is designed to extend the academic learning process into the workplace through on-the-job learning experiences which enhance the students' vocational maturation and personal development, and are integrated with the learning objectives of the program. The department offers paid, supervised…

  1. Cooperation: the foundation of improvement.

    PubMed

    Clemmer, T P; Spuhler, V J; Berwick, D M; Nolan, T W

    1998-06-15

    Cooperation--working together to produce mutual benefit or attain a common purpose--is almost inseparable from the quest for improvement. Although the case for cooperation can be made on ethical grounds, neither the motivation for nor the effects of cooperation need to be interpreted solely in terms of altruism. Cooperation can be a shrewd and pragmatic strategy for accomplishing personal goals in an interdependent system. Earlier papers in this series have explored the conceptual roots of modern approaches to improvement, which lie in systems theory. To improve systems, we must usually attend first and foremost to interactions. Among humans, "better interaction" is almost synonymous with "better cooperation." Physicians have ample opportunities and, indeed, an obligation to cooperate with other physicians in the same or different specialties, with nurses and other clinical workers, with administrators, and with patients and families. Many intellectual disciplines have made cooperation an object of study. These include anthropology; social psychology; genetics; biology; mathematics; game theory; linguistics; operations research; economics; and, of course, moral and rational philosophy. Scientifically grounded methods to enhance cooperation include developing a shared purpose; creating an open, safe environment; including all who share a common purpose and encouraging diverse viewpoints; negotiating agreement; and insisting on fairness and equity in the application of rules. These methods apply at the organizational level and at the level of the individual physician. This paper describes the application of these methods at the organizational level and focuses on one especially successful example of system-level cooperation in a care delivery site where interactions matter a great deal: the modern intensive care unit. PMID:9625663

  2. Role of Cooperative Learning in Comprehensive Instruction.

    ERIC Educational Resources Information Center

    Reid, D. Kim

    1989-01-01

    Cooperative learning arrangements for students with learning disabilities are discussed. Cooperative learning appears to be as effective as teacher-led instruction because it replicates natural learning contexts, enhances self-efficacy, provides level-appropriate information processing models, and addresses the specific needs of such students.…

  3. Using Cooperative Structures to Promote Deep Learning

    ERIC Educational Resources Information Center

    Millis, Barbara J.

    2014-01-01

    The author explores concrete ways to help students learn more and have fun doing it while they support each other's learning. The article specifically shows the relationships between cooperative learning and deep learning. Readers will become familiar with the tenets of cooperative learning and its power to enhance learning--even more so when…

  4. Cooperative Education. Information Series No. 253.

    ERIC Educational Resources Information Center

    Humbert, Jack T.; Woloszyk, Carl A.

    Cooperative education programs aid students in making the transition from school to work. Other benefits include enhanced employability and earning power. Employers benefit through the ability of cooperative education programs to adapt to labor market needs, through reduced recruitment and training problems, and through the satisfaction gained…

  5. Arsenic Trioxide (ATO) cooperates with All Trans Retinoic Acid (ATRA) to enhance MAPK activation and differentiation in Human Myeloblastic Leukemia (HL-60) cells

    PubMed Central

    Nayak, Satyaprakash; Shen, Miaoqing; Varner, Jeffrey D.; Yen, Andrew

    2016-01-01

    Arsenic trioxide (ATO) synergistically promotes retinoic acid (RA)-induced differentiation of HL-60 myeloblastic leukemia cells, a PML-RARα negative cell line. In PML-RARα positive myeloid leukemia cells, ATO is known to cause degradation of PML-RARα with subsequent induced myeloid differentiation. We find now that ATO by itself does not cause differentiation of the PML-RARα negative HL-60 cells, but enhances RA’s capability to cause differentiation. RA-induced differentiation of HL-60 cells is known to be propelled by an induced hyperactive/persistent MAPK signal. ATO augmented RA induced RAF/MEK/ERK axis signaling and expression of CD11b, an integrin receptor that is a myeloid differentiation marker. p47PHOX, a component of the respiratory burst machinery and inducible oxidative metabolism, functional differentiation marker were also enhanced. However, ATO did not enhance RA-induced CD38 expression, an early cell surface differentiation marker. ATO enhanced RA-induced population growth retardation without evidence of apoptosis or an enhanced G1/0 growth arrest. But compared to RA, ATO plus RA showed reduced pAKT, suggesting that an overall biosynthetic/metabolic retardation was seminal to the apparent enhanced growth retardation due to ATO. In sum, our results indicate that ATO can augment action of RA in causing differentiation of myeloid leukemia cells through promoting MAPK signaling and independent of PML-RARα. PMID:20615082

  6. Hypoxic induction of the human erythropoietin gene: cooperation between the promoter and enhancer, each of which contains steroid receptor response elements.

    PubMed Central

    Blanchard, K L; Acquaviva, A M; Galson, D L; Bunn, H F

    1992-01-01

    Transcription of the human erythropoietin (Epo) gene is stimulated by exposure to hypoxia and/or cobalt in whole animals and in Hep3B cells. We have systematically investigated the promoter and 3' enhancer elements necessary for this induction by transient transfection of Hep3B cells. We define a promoter region of 53 bp and an enhancer region of 43 bp that confer hypoxia and cobalt inducibility. Each element gives rise to a 6- to 10-fold induction alone. In combination they produce a 50-fold induction after stimulation, similar to the 50- to 100-fold induction of the endogenous Epo gene. Two areas of DNA sequence homology are present in these regions. We demonstrate specific DNA-protein interactions in the enhancer and the ability of the promoter element to compete with these interactions in electrophoretic mobility shift assays. DNase I footprinting and methylation interference data further refine the cis-acting element in the 43-bp enhancer to a short region containing a direct repeat of a steroid/thyroid hormone receptor response element half-site separated by a 2-bp gap. Two half-site consensus sequences are also present in the 53-bp promoter. Site-specific mutation of the half-site sequences in the enhancer destroys the functional activity of the enhancer. Images PMID:1448072

  7. A universal cooperative assembly-directed method for coating of mesoporous TiO2 nanoshells with enhanced lithium storage properties

    PubMed Central

    Guan, Bu Yuan; Yu, Le; Li, Ju; Lou, Xiong Wen (David)

    2016-01-01

    TiO2 is exceptionally useful, but it remains a great challenge to develop a universal method to coat TiO2 nanoshells on different functional materials. We report a one-pot, low-temperature, and facile method that can rapidly form mesoporous TiO2 shells on various inorganic, organic, and inorganic-organic composite materials, including silica-based, metal, metal oxide, organic polymer, carbon-based, and metal-organic framework nanomaterials via a cooperative assembly-directed strategy. In constructing hollow, core-shell, and yolk-shell geometries, both amorphous and crystalline TiO2 nanoshells are demonstrated with excellent control. When used as electrode materials for lithium ion batteries, these crystalline TiO2 nanoshells composed of very small nanocrystals exhibit remarkably long-term cycling stability over 1000 cycles. The electrochemical properties demonstrate that these TiO2 nanoshells are promising anode materials. PMID:26973879

  8. A universal cooperative assembly-directed method for coating of mesoporous TiO(2) nanoshells with enhanced lithium storage properties.

    PubMed

    Guan, Bu Yuan; Yu, Le; Li, Ju; Lou, Xiong Wen David

    2016-03-01

    TiO2 is exceptionally useful, but it remains a great challenge to develop a universal method to coat TiO2 nanoshells on different functional materials. We report a one-pot, low-temperature, and facile method that can rapidly form mesoporous TiO2 shells on various inorganic, organic, and inorganic-organic composite materials, including silica-based, metal, metal oxide, organic polymer, carbon-based, and metal-organic framework nanomaterials via a cooperative assembly-directed strategy. In constructing hollow, core-shell, and yolk-shell geometries, both amorphous and crystalline TiO2 nanoshells are demonstrated with excellent control. When used as electrode materials for lithium ion batteries, these crystalline TiO2 nanoshells composed of very small nanocrystals exhibit remarkably long-term cycling stability over 1000 cycles. The electrochemical properties demonstrate that these TiO2 nanoshells are promising anode materials. PMID:26973879

  9. Plant cooperation.

    PubMed

    Dudley, Susan A

    2015-01-01

    The study of plant behaviour will be aided by conceptual approaches and terminology for cooperation, altruism and helping. The plant literature has a rich discussion of helping between species while the animal literature has an extensive and somewhat contentious discussion of within-species helping. Here, I identify and synthesize concepts, terminology and some practical methodology for speaking about helping in plant populations and measuring the costs and benefits. I use Lehmann and Keller's (2006) classification scheme for animal helping and McIntire and Fajardo's (2014) synthesis of facilitation to provide starting points for classifying the mechanisms of how and why organisms help each other. Contextual theory is discussed as a mechanism for understanding and measuring the fitness consequences of helping. I synthesize helping into four categories. The act of helping can be costly to the helper. If the helper gains indirect fitness by helping relatives but loses direct fitness, this is altruism, and it only occurs within species. Helpers can exchange costly help, which is called mutualism when between species, and reciprocation when within a species. The act of helping can directly benefit the helper as well as the recipient, either as an epiphenomenon resulting from behaviours under natural selection for other reasons, or because the helper is creating a mutual benefit, such as satiating predators or supporting a mutualism. Facilitation between species by stress amelioration, creation of novel ecosystems and habitat complexity often meets the definition of epiphenomenon helping. Within species, this kind of helping is called by-product mutualism. If the helping is under selection to create a mutual benefit shared by others, between species this is facilitation with service sharing or access to resources and within species, direct benefits by mutual benefits. These classifications provide a clear starting point for addressing the subject of helping behaviours

  10. Plant cooperation

    PubMed Central

    Dudley, Susan A.

    2015-01-01

    The study of plant behaviour will be aided by conceptual approaches and terminology for cooperation, altruism and helping. The plant literature has a rich discussion of helping between species while the animal literature has an extensive and somewhat contentious discussion of within-species helping. Here, I identify and synthesize concepts, terminology and some practical methodology for speaking about helping in plant populations and measuring the costs and benefits. I use Lehmann and Keller's (2006) classification scheme for animal helping and McIntire and Fajardo's (2014) synthesis of facilitation to provide starting points for classifying the mechanisms of how and why organisms help each other. Contextual theory is discussed as a mechanism for understanding and measuring the fitness consequences of helping. I synthesize helping into four categories. The act of helping can be costly to the helper. If the helper gains indirect fitness by helping relatives but loses direct fitness, this is altruism, and it only occurs within species. Helpers can exchange costly help, which is called mutualism when between species, and reciprocation when within a species. The act of helping can directly benefit the helper as well as the recipient, either as an epiphenomenon resulting from behaviours under natural selection for other reasons, or because the helper is creating a mutual benefit, such as satiating predators or supporting a mutualism. Facilitation between species by stress amelioration, creation of novel ecosystems and habitat complexity often meets the definition of epiphenomenon helping. Within species, this kind of helping is called by-product mutualism. If the helping is under selection to create a mutual benefit shared by others, between species this is facilitation with service sharing or access to resources and within species, direct benefits by mutual benefits. These classifications provide a clear starting point for addressing the subject of helping behaviours

  11. PREFACE: Cooperative dynamics Cooperative dynamics

    NASA Astrophysics Data System (ADS)

    Gov, Nir

    2011-09-01

    The dynamics within living cells are dominated by non-equilibrium processes that consume chemical energy (usually in the form of ATP, adenosine triphosphate) and convert it into mechanical forces and motion. The mechanisms that allow this conversion process are mostly driven by the components of the cytoskeleton: (i) directed (polar) polymerization of filaments (either actin or microtubules) and (ii) molecular motors. The forces and motions produced by these two components of the cytoskeleton give rise to the formation of cellular shapes, and drive the intracellular transport and organization. It is clear that these systems present a multi-scale challenge, from the physics of the molecular processes to the organization of many interacting units. Understanding the physical nature of these systems will have a large impact on many fundamental problems in biology and break new grounds in the field of non-equilibrium physics. This field of research has seen a rapid development over the last ten years. Activities in this area range from theoretical and experimental work on the underlying fundamental (bio)physics at the single-molecule level, to investigations (in vivo and in vitro) of the dynamics and patterns of macroscopic pieces of 'living matter'. In this special issue we have gathered contributions that span the whole spectrum of length- and complexity-scales in this field. Some of the works demonstrate how active forces self-organize within the polymerizing cytoskeleton, on the level of cooperative cargo transport via motors or due to active fluxes at the cell membrane. On a larger scale, it is shown that polar filaments coupled to molecular motors give rise to a huge variety of surprising dynamics and patterns: spontaneously looping rings of gliding microtubules, and emergent phases of self-organized filaments and motors in different geometries. All of these articles share the common feature of being out-of-equilibrium, driven by metabolism. As demonstrated here

  12. Comparison of the Effectiveness of Two Forms of the Enhancing Relationships in School Communities Project for Promoting Cooperative Conflict Resolution Education in Australian Primary Schools

    ERIC Educational Resources Information Center

    Trinder, Margot; Wertheim, Eleanor H.; Freeman, Elizabeth; Sanson, Ann; Richardson, Shanel; Hunt, Sue

    2010-01-01

    This study evaluated the Enhancing Relationships in School Communities (ERIS) Project which aimed to promote constructive conflict resolution (CR) in Australian primary school communities through professional development for core teams of three-five staff (n = 33 teachers). Twelve schools were randomly assigned to a full intervention (FI) group or…

  13. The Globalization of Cooperative Groups.

    PubMed

    Valdivieso, Manuel; Corn, Benjamin W; Dancey, Janet E; Wickerham, D Lawrence; Horvath, L Elise; Perez, Edith A; Urton, Alison; Cronin, Walter M; Field, Erica; Lackey, Evonne; Blanke, Charles D

    2015-10-01

    The National Cancer Institute (NCI)-supported adult cooperative oncology research groups (now officially Network groups) have a longstanding history of participating in international collaborations throughout the world. Most frequently, the US-based cooperative groups work reciprocally with the Canadian national adult cancer clinical trial group, NCIC CTG (previously the National Cancer Institute of Canada Clinical Trials Group). Thus, Canada is the largest contributor to cooperative groups based in the United States, and vice versa. Although international collaborations have many benefits, they are most frequently utilized to enhance patient accrual to large phase III trials originating in the United States or Canada. Within the cooperative group setting, adequate attention has not been given to the study of cancers that are unique to countries outside the United States and Canada, such as those frequently associated with infections in Latin America, Asia, and Africa. Global collaborations are limited by a number of barriers, some of which are unique to the countries involved, while others are related to financial support and to US policies that restrict drug distribution outside the United States. This article serves to detail the cooperative group experience in international research and describe how international collaboration in cancer clinical trials is a promising and important area that requires greater consideration in the future. PMID:26433551

  14. Tubular g-C3 N4 Isotype Heterojunction: Enhanced Visible-Light Photocatalytic Activity through Cooperative Manipulation of Oriented Electron and Hole Transfer.

    PubMed

    Tong, Zhenwei; Yang, Dong; Sun, Yuanyuan; Nan, Yanhu; Jiang, Zhongyi

    2016-08-01

    A tubular g-C3 N4 isotype heterojunction (TCNH) photocatalyst was designed for cooperative manipulation of the oriented transfer of photogenerated electrons and holes to pursue high catalytic performance. The adduct of cyanuric acid and melamine (CA·M) is first hydrothermally treated to assemble into hexagonal prism crystals; then the hybrid precursors of urea and CA·M crystals are calcined to form tubular g-C3 N4 isotype heterojunctions. Upon visible-light irradiation, the photogenerated electrons transfer from g-C3 N4 (CA·M) to g-C3 N4 (urea) driven by the conduction band offset of 0.05 eV, while the photogenerated holes transfer from g-C3 N4 (urea) to g-C3 N4 (CA·M) driven by the valence band offset of 0.18 eV, which renders oriented transfer of the charge carriers across the heterojunction interface. Meanwhile, the tubular structure of TCNH is favorable for oriented electron transfer along the longitudinal dimension, which greatly decreases the chance of charge carrier recombination. Consequently, TCNH exhibits a high hydrogen evolution rate of 63 μmol h(-1) (0.04 g, λ > 420 nm), which is nearly five times of the pristine g-C3 N4 and higher than most of the existing g-C3 N4 photocatalysts. This study demonstrates that isotype heterojunction structure and tubular structure can jointly manipulate the oriented transfer of electrons and holes, thus facilitating the visible-light photocatalysis. PMID:27348710

  15. Telemedical work and cooperation.

    PubMed

    Aas, I H

    2001-01-01

    In telemedicine, cooperation occurs via telecommunication. This represents a new situation for medical cooperation. Whether such cooperation works poorly or well will be important with an increasing volume of telemedicine. When personnel are involved in external cooperation, as in telemedicine, the question of cooperation within one's own organization also arises. To investigate these matters, qualitative interviews were performed with 30 persons working in teledermatology, telepsychiatry, a telepathology frozen-section service and tele-otolaryngology. The results showed that cooperating by telecommunication mainly worked well. The cooperation may be influenced by factors such as personality, knowing each other personally, preparation and experience. Telemedical teamwork may be improved by factors like experience and education. Working with telemedicine did not reduce the personnel's cooperation within their own organizations, but rather improved it, although this effect was slight and most commonly involved improved knowledge of others. In general, the findings concerning cooperation and telemedicine were positive. PMID:11506756

  16. Social Environment Shapes the Speed of Cooperation

    PubMed Central

    Nishi, Akihiro; Christakis, Nicholas A.; Evans, Anthony M.; O’Malley, A. James; Rand, David G.

    2016-01-01

    Are cooperative decisions typically made more quickly or slowly than non-cooperative decisions? While this question has attracted considerable attention in recent years, most research has focused on one-shot interactions. Yet it is repeated interactions that characterize most important real-world social interactions. In repeated interactions, the cooperativeness of one’s interaction partners (the “social environment”) should affect the speed of cooperation. Specifically, we propose that reciprocal decisions (choices that mirror behavior observed in the social environment), rather than cooperative decisions per se, occur more quickly. We test this hypothesis by examining four independent decision time datasets with a total of 2,088 subjects making 55,968 decisions. We show that reciprocal decisions are consistently faster than non-reciprocal decisions: cooperation is faster than defection in cooperative environments, while defection is faster than cooperation in non-cooperative environments. These differences are further enhanced by subjects’ previous behavior – reciprocal decisions are faster when they are consistent with the subject’s previous choices. Finally, mediation analyses of a fifth dataset suggest that the speed of reciprocal decisions is explained, in part, by feelings of conflict – reciprocal decisions are less conflicted than non-reciprocal decisions, and less decision conflict appears to lead to shorter decision times. PMID:27435940

  17. Social Environment Shapes the Speed of Cooperation.

    PubMed

    Nishi, Akihiro; Christakis, Nicholas A; Evans, Anthony M; O'Malley, A James; Rand, David G

    2016-01-01

    Are cooperative decisions typically made more quickly or slowly than non-cooperative decisions? While this question has attracted considerable attention in recent years, most research has focused on one-shot interactions. Yet it is repeated interactions that characterize most important real-world social interactions. In repeated interactions, the cooperativeness of one's interaction partners (the "social environment") should affect the speed of cooperation. Specifically, we propose that reciprocal decisions (choices that mirror behavior observed in the social environment), rather than cooperative decisions per se, occur more quickly. We test this hypothesis by examining four independent decision time datasets with a total of 2,088 subjects making 55,968 decisions. We show that reciprocal decisions are consistently faster than non-reciprocal decisions: cooperation is faster than defection in cooperative environments, while defection is faster than cooperation in non-cooperative environments. These differences are further enhanced by subjects' previous behavior - reciprocal decisions are faster when they are consistent with the subject's previous choices. Finally, mediation analyses of a fifth dataset suggest that the speed of reciprocal decisions is explained, in part, by feelings of conflict - reciprocal decisions are less conflicted than non-reciprocal decisions, and less decision conflict appears to lead to shorter decision times. PMID:27435940

  18. Improving the payoffs of cooperators in three-player cooperative game using weak measurements

    NASA Astrophysics Data System (ADS)

    Liao, Xiang-Ping; Ding, Xiang-Zhuo; Fang, Mao-Fa

    2015-12-01

    In this paper, an efficient method is proposed to improve the payoffs of cooperators in cooperative three-player quantum game under the action of amplitude damping, bit flip and depolarizing channels using weak measurements. It is shown that the payoffs of cooperators can be enhanced to a great extent in the case of amplitude damping channel, and the payoff sudden death can be avoided in the case of bit flip and depolarizing channels. Moreover, the payoffs of cooperators tend to a constant by changing weak measurement strength in spite of sufficiently strong decoherence.

  19. Cooperative Education Coordinator's Handbook.

    ERIC Educational Resources Information Center

    Worley, Tom

    Designed to serve as a guide for teacher-coordinators, counselors, administrators, and the employing community, this handbook is a performance-oriented desk reference that provides a base for cooperative education program operations. Chapter 1 overviews cooperative education, contrasts cooperative training and work experience programs, and…

  20. Learning to Learn Cooperatively

    ERIC Educational Resources Information Center

    Byrd, Anne Hammond

    2009-01-01

    Cooperative learning, put quite simply, is a type of instruction whereby students work together in small groups to achieve a common goal. Cooperative learning has become increasingly popular as a feature of Communicative Language Teaching (CLT) with benefits that include increased student interest due to the quick pace of cooperative tasks,…

  1. Cooperative Learning: Professional's Guide.

    ERIC Educational Resources Information Center

    Grisham, Dana L.; Molinelli, Paul M.

    Noting that since the 1970s cooperative learning has been widely investigated regarding its implementation and efficacy, this booklet is designed to introduce the teaching strategy of cooperative learning to classroom teachers. The booklet first provides an overview and supplies a context for cooperative learning and then defines cooperative…

  2. Cooperative Agreements Study Report.

    ERIC Educational Resources Information Center

    Lawton, R. E.; Magruder, D.

    During the 1983 meeting of the Florida Legislature, action was taken to begin a systematic study of the level of cooperation between the Florida public schools K-12 program and the community and junior colleges. The goals and objectives of the Cooperative Agreements Study were to review and compile a list of the cooperative agreements and identify…

  3. Cooperation of multifunction composite structures and fluorescein for photovoltaic performance-enhanced ZnO-based dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Zhang, Chunyang; Xie, Yahong; Bai, Te; Hu, Jing; Wang, Jide

    2015-11-01

    In this study, ZnO nanoparticles (NPs), ZnO nanorods (NRs) and ZnO nanosheet-based hierarchical structures (NSHSs) were rapidly synthesized using three simple approaches at relatively low temperatures and without any organic surfactants. Based on their structural advantages in light absorption, reflection and electron transfer, an NP/NSHS/NR hybrid structure was fabricated and used as a photoanode in dye-sensitized solar cells (DSSCs). The photoanode was treated in fluorescein acetonitrile solution (down-conversion materials) to enhance the photovoltaic efficiency, as well as in ascorbic acid ethanol solution to inhibit fluorescence quenching, which is caused by the I3-/I- electrolyte. Results showed that the NP/NSHS/NR hybrid structure plus fluorescein treatment was highly effective in improving the light harvesting capacity via an efficient electron transfer path and a down-conversion luminescence process, and the light-to-electric energy conversion efficiency of the DSSCs reached 6.54%, which increased by 34% compared with that of the ZnO NP-based DSSCs.

  4. The Δ14 Mutation of Human Cardiac Troponin T Enhances ATPase Activity and Alters the Cooperative Binding of S1-ADP to Regulated Actin†

    PubMed Central

    Gafurov, Boris; Fredricksen, Scott; Cai, Anmei; Brenner, Bernhard; Chase, P. Bryant; Chalovich, Joseph M.

    2005-01-01

    The complex of tropomyosin and troponin binds to actin and inhibits activation of myosin ATPase activity and force production of striated muscles at low free Ca2+ concentrations. Ca2+ stimulates ATP activity, and at subsaturating actin concentrations, the binding of NEM-modified S1 to actin–tropomyosin–troponin increases the rate of ATP hydrolysis even further. We show here that the Δ14 mutation of troponin T, associated with familial hypertrophic cardiomyopathy, results in an increase in ATPase rate like that seen with wild-type troponin in the presence of NEM-S1. The enhanced ATPase activity was not due to a decreased incorporation of mutant troponin T with troponin I and troponin C to form an active troponin complex. The activating effect was more prominent with a hybrid troponin (skeletal TnI, TnC, and cardiac TnT) than with all cardiac troponin. Thus it appears that changes in the troponin–troponin contacts that result from mutations or from forming hybrids stabilize a more active state of regulated actin. An analysis of the effect of the Δ14 mutation on the equilibrium binding of S1-ADP to actin was consistent with stabilization of an active state of actin. This change in activation may be important in the development of cardiac disease. PMID:15568820

  5. Adjusting learning motivation to promote cooperation

    NASA Astrophysics Data System (ADS)

    Zhang, Haifeng; Small, Michael; Yang, Hanxin; Wang, Binghong

    2010-11-01

    An evolutionary prisoner’s dilemma game with players adjusting their learning motivation is studied. At each time step, each player can adjust his/her learning motivation according to the difference between the current payoff and payoff aspiration. Greater payoff aspiration means stronger learning motivation, and vice versa. We find that the density of cooperation in a spatial prisoner’s dilemma game is enhanced when the learning motivation mechanism is considered. Meanwhile, we show that proper noise can not only induce the highest cooperation level but also can maintain the cooperation phenomenon even though there is more temptation to defect.

  6. Pre-B cell colony enhancing factor (PBEF/NAMPT/Visfatin) and vascular endothelial growth factor (VEGF) cooperate to increase the permeability of the human placental amnion

    PubMed Central

    Astern, J.M.; Collier, A.C.; Kendal-Wright, C.E.

    2012-01-01

    Fluid efflux across the region of the amnion overlying the placenta is an essential component of the intramembranous absorption pathway that maintains amniotic fluid volume homeostasis. Dysregulation of this pathway may result in adverse pregnancy outcomes, however the factors controlling amnion permeability are unknown. Here, we report a novel mechanism that increases placental amnion permeability. Pre-B Cell Colony Enhancing Factor (PBEF) is a stress-responsive cytokine expressed by the human amnion, and is known to induce Vascular Endothelial Growth Factor (VEGF) production by other cell types. Interestingly, VEGF is up-regulated in the ovine amnion when intramembranous absorption is augmented. In this study, we show that PBEF induced VEGF secretion by primary human amniotic epithelial cells (AEC) derived from the placental amnion, as well as from the reflected amnion that lines the remainder of the gestational sac. Further, PBEF treatment led to the increased expression of VEGFR2 in placental AEC, but not reflected AEC. To test the hypothesis that PBEF and VEGF increase placental amnion permeability, we monitored the transfer of 2′,7′-dichlorofluorescein (DCF) from the fetal to the maternal side of human amnion explants. A treatment regimen including both PBEF and VEGF increased the rate of DCF transfer across the placental amnion, but not the reflected amnion. In summary, our results suggest that by augmenting VEGFR2 expression in the placental amnion, PBEF primes the tissue for a VEGF-mediated increase in permeability. This mechanism may have important implications in amniotic fluid volume control throughout gestation. PMID:23151382

  7. Cooperative surmounting of bottlenecks

    NASA Astrophysics Data System (ADS)

    Hennig, D.; Mulhern, C.; Schimansky-Geier, L.; Tsironis, G. P.; Hänggi, P.

    2015-07-01

    The physics of activated escape of objects out of a metastable state plays a key role in diverse scientific areas involving chemical kinetics, diffusion and dislocation motion in solids, nucleation, electrical transport, motion of flux lines superconductors, charge density waves, and transport processes of macromolecules and astrophysics, to name but a few. The underlying activated processes present the multidimensional extension of the Kramers problem of a single Brownian particle. In comparison to the latter case, however, the dynamics ensuing from the interactions of many coupled units can lead to intriguing novel phenomena that are not present when only a single degree of freedom is involved. In this review we report on a variety of such phenomena that are exhibited by systems consisting of chains of interacting units in the presence of potential barriers. In the first part we consider recent developments in the case of a deterministic dynamics driving cooperative escape processes of coupled nonlinear units out of metastable states. The ability of chains of coupled units to undergo spontaneous conformational transitions can lead to a self-organised escape. The mechanism at work is that the energies of the units become re-arranged, while keeping the total energy conserved, in forming localised energy modes that in turn trigger the cooperative escape. We present scenarios of significantly enhanced noise-free escape rates if compared to the noise-assisted case. The second part of the review deals with the collective directed transport of systems of interacting particles overcoming energetic barriers in periodic potential landscapes. Escape processes in both time-homogeneous and time-dependent driven systems are considered for the emergence of directed motion. It is shown that ballistic channels immersed in the associated mixed high-dimensional phase space are at the source for the directed long-range transport. Open problems and future directions are discussed in

  8. Genetic information transfer promotes cooperation in bacteria.

    PubMed

    Dimitriu, Tatiana; Lotton, Chantal; Bénard-Capelle, Julien; Misevic, Dusan; Brown, Sam P; Lindner, Ariel B; Taddei, François

    2014-07-29

    Many bacterial species are social, producing costly secreted "public good" molecules that enhance the growth of neighboring cells. The genes coding for these cooperative traits are often propagated via mobile genetic elements and can be virulence factors from a biomedical perspective. Here, we present an experimental framework that links genetic information exchange and the selection of cooperative traits. Using simulations and experiments based on a synthetic bacterial system to control public good secretion and plasmid conjugation, we demonstrate that horizontal gene transfer can favor cooperation. In a well-mixed environment, horizontal transfer brings a direct infectious advantage to any gene, regardless of its cooperation properties. However, in a structured population transfer selects specifically for cooperation by increasing the assortment among cooperative alleles. Conjugation allows cooperative alleles to overcome rarity thresholds and invade bacterial populations structured purely by stochastic dilution effects. Our results provide an explanation for the prevalence of cooperative genes on mobile elements, and suggest a previously unidentified benefit of horizontal gene transfer for bacteria. PMID:25024219

  9. Genetic information transfer promotes cooperation in bacteria

    PubMed Central

    Dimitriu, Tatiana; Lotton, Chantal; Bénard-Capelle, Julien; Misevic, Dusan; Brown, Sam P.; Lindner, Ariel B.; Taddei, François

    2014-01-01

    Many bacterial species are social, producing costly secreted “public good” molecules that enhance the growth of neighboring cells. The genes coding for these cooperative traits are often propagated via mobile genetic elements and can be virulence factors from a biomedical perspective. Here, we present an experimental framework that links genetic information exchange and the selection of cooperative traits. Using simulations and experiments based on a synthetic bacterial system to control public good secretion and plasmid conjugation, we demonstrate that horizontal gene transfer can favor cooperation. In a well-mixed environment, horizontal transfer brings a direct infectious advantage to any gene, regardless of its cooperation properties. However, in a structured population transfer selects specifically for cooperation by increasing the assortment among cooperative alleles. Conjugation allows cooperative alleles to overcome rarity thresholds and invade bacterial populations structured purely by stochastic dilution effects. Our results provide an explanation for the prevalence of cooperative genes on mobile elements, and suggest a previously unidentified benefit of horizontal gene transfer for bacteria. PMID:25024219

  10. Cooperativity: over the Hill.

    PubMed

    Forsén, S; Linse, S

    1995-12-01

    Cooperativity, the ability of ligand binding at one site on a macromolecule to influence ligand binding at a different site on the same macromolecule, is a fascinating biological property that is often poorly explained in textbooks. The Hill coefficient is commonly used in biophysical studies of cooperative systems although it is not a quantitative measure of cooperativity. The free energy of interaction between binding sites (delta delta G) is a more stringent definition of cooperativity and provides a direct quantitative measure of how the binding of ligand at one site affects the ligand affinity of another site. PMID:8571449