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Sample records for filamin cooperatively enhance

  1. Enhancing the effectiveness of androgen deprivation in prostate cancer by inducing Filamin A nuclear localization

    PubMed Central

    Mooso, Benjamin A.; Vinall, Ruth L.; Tepper, Clifford G.; Savoy, Rosalinda M.; Cheung, Jean P.; Singh, Sheetal; Siddiqui, Salma; Wang, Yu; Bedolla, Roble G.; Martinez, Anthony; Mudryj, Maria; Kung, Hsing-Jien; deVere White, Ralph W.; Ghosh, Paramita M.

    2013-01-01

    Since prostate cancer (CaP) is regulated by androgen receptor (AR) activity, metastatic CaP is treated with androgen deprivation therapy (ADT). Despite initial response, patients on ADT eventually progress to castration-resistant CaP (CRPC), which is currently incurable. We previously showed that cleavage of the 280kDa structural protein Filamin A (FlnA) to a 90kDa fragment, and nuclear localization of the cleaved product, sensitized CRPC cells to ADT. Hence, treatment promoting FlnA nuclear localization would enhance androgen responsiveness. Here, we show that FlnA nuclear localization induced apoptosis in CRPC cells during ADT, identifying it as a treatment tool in advanced CaP. Significantly, the natural product genistein-combined-polysaccharide (GCP) had a similar effect. Investigation of the mechanism of GCP-induced apoptosis showed that GCP induced FlnA cleavage and nuclear localization, and that apoptosis resulting from GCP treatment was mediated by FlnA nuclear localization. Two main components of GCP are genistein and daidzein: the ability of GCP to induce G2 arrest was due to genistein whereas sensitivity to ADT stemmed from daidzein; hence both were needed to mediate GCP's effects. FlnA cleavage is regulated by its phosphorylation; we show that ADT enhanced FlnA phosphorylation, which prevented its cleavage, whereas GCP inhibited FlnA phosphorylation, thereby sensitizing CaP cells to ADT. In a mouse model of CaP recurrence, GCP, but not vehicle, impeded relapse following castration; indicating that GCP, when administered with ADT, interrupted the development of CRPC. These results demonstrate the efficacy of GCP in promoting FlnA nuclear localization and enhancing androgen responsiveness in CaP. PMID:22993077

  2. Enhancing the effectiveness of androgen deprivation in prostate cancer by inducing Filamin A nuclear localization.

    PubMed

    Mooso, Benjamin A; Vinall, Ruth L; Tepper, Clifford G; Savoy, Rosalinda M; Cheung, Jean P; Singh, Sheetal; Siddiqui, Salma; Wang, Yu; Bedolla, Roble G; Martinez, Anthony; Mudryj, Maria; Kung, Hsing-Jien; Devere White, Ralph W; Ghosh, Paramita M

    2012-12-01

    As prostate cancer (CaP) is regulated by androgen receptor (AR) activity, metastatic CaP is treated with androgen deprivation therapy (ADT). Despite initial response, patients on ADT eventually progress to castration-resistant CaP (CRPC), which is currently incurable. We previously showed that cleavage of the 280 kDa structural protein Filamin A (FlnA) to a 90 kDa fragment, and nuclear localization of the cleaved product, sensitized CRPC cells to ADT. Hence, treatment promoting FlnA nuclear localization would enhance androgen responsiveness. Here, we show that FlnA nuclear localization induced apoptosis in CRPC cells during ADT, identifying it as a treatment tool in advanced CaP. Significantly, the natural product genistein combined polysaccharide (GCP) had a similar effect. Investigation of the mechanism of GCP-induced apoptosis showed that GCP induced FlnA cleavage and nuclear localization and that apoptosis resulting from GCP treatment was mediated by FlnA nuclear localization. Two main components of GCP are genistein and daidzein: the ability of GCP to induce G2 arrest was due to genistein whereas sensitivity to ADT stemmed from daidzein; hence, both were needed to mediate GCP's effects. FlnA cleavage is regulated by its phosphorylation; we show that ADT enhanced FlnA phosphorylation, which prevented its cleavage, whereas GCP inhibited FlnA phosphorylation, thereby sensitizing CaP cells to ADT. In a mouse model of CaP recurrence, GCP, but not vehicle, impeded relapse following castration, indicating that GCP, when administered with ADT, interrupted the development of CRPC. These results demonstrate the efficacy of GCP in promoting FlnA nuclear localization and enhancing androgen responsiveness in CaP.

  3. Prognostic values of filamin-A status for topoisomerase II poison chemotherapy.

    PubMed

    Yue, Jingyin; Lan, Shijie; Yuan, Changji; Shen, Zhiyuan

    2012-01-01

    Filamin-A, also called Actin Binding Protein-280, is not only an essential component of the cytoskeleton networks, but also serves as the scaffold in various signaling networks. It has been shown that filamin-A facilitates DNA repair and filamin-A proficient cells are more resistant to ionizing radiation, bleomycin, and cisplatin. In this study, we assessed the role of filamin-A in modulating cancer cell sensitivity to Topo II poisons, including etoposide and doxorubicin. Intriguingly, we found that cells with filamin-A expression are more sensitive to Topo II poisons than those with defective filamin-A, and filamin-A proficient xenograft melanomas have better response to etoposide treatment than the filamin-A deficient tumors. This is associated with more potent induction of DNA double strand breaks (DSBs) by Topo II poisons in filamin-A proficient cells than the deficient cells. Although the expression of filamin-A enables cells a slightly stronger capability to repair DSB, the net outcome is that filamin-A proficient cells bear more DSBs due to the significantly enhanced DSB induction by Topo II poisons in these cells. We further found that filamin-A proficient cells have increased drug influx and decreased drug efflux, suggesting that filamin-A modulates the intra-cellular drug kinetics of Topo II poisons to facilitate the generation of DSB after Topo II poison exposure. These data suggest a novel function of filamin-A in regulating the pharmacokinetics of Topo II poisons, and that the status of filamin-A may be used as a prognostic marker for Topo II poisons based cancer treatments.

  4. Filamin 2 (Fln2)

    PubMed Central

    Thompson, Terri G.; Chan, Yiu-Mo; Hack, Andrew A.; Brosius, Melissa; Rajala, Michael; Lidov, Hart G.W.; McNally, Elizabeth M.; Watkins, Simon; Kunkel, Louis M.

    2000-01-01

    Mutations in genes encoding for the sarcoglycans, a subset of proteins within the dystrophin–glycoprotein complex, produce a limb-girdle muscular dystrophy phenotype; however, the precise role of this group of proteins in the skeletal muscle is not known. To understand the role of the sarcoglycan complex, we looked for sarcoglycan interacting proteins with the hope of finding novel members of the dystrophin–glycoprotein complex. Using the yeast two-hybrid method, we have identified a skeletal muscle-specific form of filamin, which we term filamin 2 (FLN2), as a γ- and δ-sarcoglycan interacting protein. In addition, we demonstrate that FLN2 protein localization in limb-girdle muscular dystrophy and Duchenne muscular dystrophy patients and mice is altered when compared with unaffected individuals. Previous studies of filamin family members have determined that these proteins are involved in actin reorganization and signal transduction cascades associated with cell migration, adhesion, differentiation, force transduction, and survival. Specifically, filamin proteins have been found essential in maintaining membrane integrity during force application. The finding that FLN2 interacts with the sarcoglycans introduces new implications for the pathogenesis of muscular dystrophy. PMID:10629222

  5. Filamin A controls matrix metalloproteinase activity and regulates cell invasion in human fibrosarcoma cells

    PubMed Central

    Baldassarre, Massimiliano; Razinia, Ziba; N. Brahme, Nina; Buccione, Roberto; Calderwood, David A.

    2012-01-01

    Summary Filamins are an important family of actin-binding proteins that, in addition to bundling actin filaments, link cell surface adhesion proteins, signaling receptors and channels to the actin cytoskeleton, and serve as scaffolds for an array of intracellular signaling proteins. Filamins are known to regulate the actin cytoskeleton, act as mechanosensors that modulate tissue responses to matrix density, control cell motility and inhibit activation of integrin adhesion receptors. In this study, we extend the repertoire of filamin activities to include control of extracellular matrix (ECM) degradation. We show that knockdown of filamin increases matrix metalloproteinase (MMP) activity and induces MMP2 activation, enhancing the ability of cells to remodel the ECM and increasing their invasive potential, without significantly altering two-dimensional random cell migration. We further show that within filamin A, the actin-binding domain is necessary, but not sufficient, to suppress the ECM degradation seen in filamin-A-knockdown cells and that dimerization and integrin binding are not required. Filamin mutations are associated with neuronal migration disorders and a range of congenital malformations characterized by skeletal dysplasia and various combinations of cardiac, craniofacial and intestinal anomalies. Furthermore, in breast cancers loss of filamin A has been correlated with increased metastatic potential. Our data suggest that effects on ECM remodeling and cell invasion should be considered when attempting to provide cellular explanations for the physiological and pathological effects of altered filamin expression or filamin mutations. PMID:22595522

  6. Filamin C, a dysregulated protein in cancer revealed by label-free quantitative proteomic analyses of human gastric cancer cells.

    PubMed

    Qiao, Jie; Cui, Shu-Jian; Xu, Lei-Lei; Chen, Si-Jie; Yao, Jun; Jiang, Ying-Hua; Peng, Gang; Fang, Cai-Yun; Yang, Peng-Yuan; Liu, Feng

    2015-01-20

    Gastric cancer (GC) is the fourth and fifth most common cancer in men and women, respectively. We identified 2,750 proteins at false discovery rates of 1.3% (protein) and 0.03% (spectrum) by comparing the proteomic profiles of three GC and a normal gastric cell lines. Nine proteins were significantly dysregulated in all three GC cell lines, including filamin C, a muscle-specific filamin and a large actin-cross-linking protein. Downregulation of filamin C in GC cell lines and tissues were verified using quantitative PCR and immunohistochemistry. Data-mining using public microarray datasets shown that filamin C was significantly reduced in many human primary and metastasis cancers. Transient expression or silencing of filamin C affected the proliferation and colony formation of cancer cells. Silencing of endogenous filamin C enhanced cancer cell migration and invasion, whereas ectopic expression of filamin C had opposing effects. Silencing of filamin C increased the expression of matrix metallopeptidase 2 and improved the metastasis of prostate cancer in a zebrafish model. High filamin C associated with better prognosis of prostate cancer, leukemia and breast cancer patients. These findings establish a functional role of filamin C in human cancers and these data will be valuable for further study of its mechanisms.

  7. 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

  8. 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),…

  9. 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),…

  10. Switching of filamin polypeptides during myogenesis in vitro

    PubMed Central

    1983-01-01

    During chicken skeletal myogenesis in vitro, the actin-binding protein filamin is present at first in association with actin filament bundles both in myoblasts and in myotubes early after fusion. Later in mature myotubes it is found in association with myofibril Z disks. These two associations of filamin are separated by a period of several days, during which the protein is absent from the cytoplasm of differentiating myotubes (Gomer, R., and E. Lazarides, 1981, Cell, 23:524-532). To characterize the two classes of filamin polypeptides we have compared, by two-dimensional peptide mapping, 125I-labeled filamin immunoprecipitated from myoblasts and fibroblasts to filamin immunoprecipitated from mature myotubes and adult skeletal myofibrils. Myoblast filamin is highly homologous to fibroblast and purified chicken gizzard filamins. Mature myotube and adult myofibril filamins are highly homologous but exhibit extensive peptide differences with respect to the other three classes of filamin. Comparison of peptide maps from immunoprecipitated 35S-methionine-labeled filamins also shows that fibroblast and myoblast filamins are highly homologous but show substantial peptide differences with respect to mature myotube filamin. Filamins from both mature myotubes and skeletal myofibrils exhibit a slightly higher electrophoretic mobility than gizzard, fibroblast, and myoblast filamins. Short pulse-labeling studies show that mature myotube filamin is synthesized as a lower molecular weight variant and is not derived from a higher molecular weight precursor. These results suggest that myoblast and mature myotube filamins are distinct gene products and that during skeletal myogenesis in vitro one class of filamin polypeptides is replaced by a new class of filamin polypeptides, and that the latter is maintained into adulthood. PMID:6833359

  11. Loss Of Klotho During Melanoma Progression Leads To Increased Filamin Cleavage, Increased Wnt5A Expression and Enhanced Melanoma Cell Motility

    PubMed Central

    Camilli, Tura C.; Xu, Mai; O'Connell, Michael P.; Chien, Bonnie; Frank, Brittany P.; Subaran, Sarah; Indig, Fred E.; Morin, Patrice J.; Hewitt, Stephen M.; Weeraratna, Ashani T.

    2010-01-01

    Summary We have previously shown that Wnt5A-mediated signaling can promote melanoma metastasis. It has been shown that Wnt signaling is antagonized by the protein Klotho, which has been implicated in aging. We show here that in melanoma cells, expressions of Wnt5A and Klotho are inversely correlated. In the presence of recombinant Klotho (rKlotho) we show that Wnt5A internalization and signaling is decreased in high Wnt5A expressing cells. Moreover, in the presence of rKlotho, we observe an increase in Wnt5A remaining in the medium, coincident with an increase in sialidase activity and decrease in syndecan expression. These effects can be inhibited using a sialidase inhibitor. In addition to its effects on Wnt5A internalization, we also demonstrate that Klotho decreases melanoma cell invasive potential by a second mechanism, that involves the inhibition of calpain and a resultant decrease in filamin cleavage, which we demonstrate is critical for melanoma cell motility. PMID:20955350

  12. Optimal Cooperation Enhancement on Spatial Networks

    NASA Astrophysics Data System (ADS)

    Tao, Shui-Yuan; Cui, Ming-Zhu; Dai, Qiong-Lin; Yang, Jun-Zhong

    2014-11-01

    We investigate the evolutionary Prisoner's dilemma game on the simplest spatial networks constructed as geometrical graphs. The optimal cooperation enhancement against the topology randomness is found. It is proposed that the optimal behavior of the cooperation results from the competition between individuals with high degrees and with low degrees: the former assists the formation of cooperator clusters and the latter tends to prevent the formation of such clusters.

  13. Inhibition of Filamin-A Reduces Cancer Metastatic Potential

    PubMed Central

    Jiang, Xi; Yue, Jingyin; Lu, Huimei; Campbell, Neil; Yang, Qifeng; Lan, Shijie; Haffty, Bruce G.; Yuan, Changji; Shen, Zhiyuan

    2013-01-01

    Filamin-A cross-links actin filaments into dynamic orthogonal networks, and interacts with an array of proteins of diverse cellular functions. Because several filamin-A interaction partners are implicated in signaling of cell mobility regulation, we tested the hypothesis that filamin-A plays a role in cancer metastasis. Using four pairs of filamin-A proficient and deficient isogenic cell lines, we found that filamin-A deficiency in cancer cells significantly reduces their migration and invasion. Using a xenograft tumor model with subcutaneous and intracardiac injections of tumor cells, we found that the filamin-A deficiency causes significant reduction of lung, splenic and systemic metastasis in nude mice. We evaluated the expression of filamin-A in breast cancer tissues by immunohistochemical staining, and found that low levels of filamin-A expression in cancer cells of the tumor tissues are associated with a better distant metastasis-free survival than those with normal levels of filamin-A. These data not only validate filamin-A as a prognostic marker for cancer metastasis, but also suggest that inhibition of filamin-A in cancer cells may reduce metastasis and that filamin-A can be used as a therapeutic target for filamin-A positive cancer. PMID:23289018

  14. PTI-609: a novel analgesic that binds filamin A to control opioid signaling.

    PubMed

    Burns, Lindsay H; Wang, Hoau-Yan

    2010-11-01

    Binding a critical pentapeptide region on the scaffolding protein filamin A regulates signaling of mu opioid receptors (MORs) so that their activation should not result in the opioid tolerance, dependence and addiction associated with current opioid painkillers. Additionally, we show that compounds that bind this site on filamin A reduce release of inflammatory cytokines. PTI-609 is a new chemical entity that binds filamin A with picomolar affinity and also activates opioid receptors via a novel binding domain. PTI-609 and analogs have similar analgesic efficacy to morphine by oral administration in mice, provide some anti-inflammatory activity in the rat collagen-induced arthritis model, and show no conditioned place preference at analgesic doses, suggesting no potential for abuse and addiction. PTI-609 was designed after discovering filamin A as the high-affinity target of naltrexone or naloxone. Combined with opiates, ultra-low-dose naloxone or naltrexone can enhance and prolong the analgesia of the opiate alone and prevent or attenuate opioid tolerance, dependence and addictive properties. We will review here the mechanism of action of ultra-low-dose naltrexone and naloxone, the discovery of filamin A as their high-affinity target, and the rationale as to why the current, dualfunction new chemical entity should not only be easier to develop but also more consistently efficacious than opioids combined with ultra-low-dose naltrexone. This new class of compounds, as well as the concept, screening assay and pharmacophore model, are covered in a family of recent patent applications.

  15. 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

  16. 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.

  17. RNase L interacts with Filamin A to regulate actin dynamics and barrier function for viral entry.

    PubMed

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

    2014-10-28

    infections. The molecular mechanisms that link virus-induced physical perturbations to host defense pathways remain unclear. Our studies identified a novel interaction between the antiviral endoribonuclease RNase L and the actin-binding protein Filamin A that enhances host defense by preventing viral entry into naive cells. This role for RNase L is independent of its enzymatic function. Virus infection alters actin dynamics, disrupts the RNase L-Filamin A complex, and releases RNase L to mediate antiviral signaling and effector functions via its established nucleolytic activities. These dual roles for RNase L provide an efficient strategy to protect cells from infection and rapidly respond upon pathogen exposure. Copyright © 2014 Malathi et al.

  18. Filamin repeat segments required for photosensory signalling in Dictyostelium discoideum

    PubMed Central

    Annesley, Sarah J; Bandala-Sanchez, Esther; Ahmed, Afsar U; Fisher, Paul R

    2007-01-01

    Background Filamin is an actin binding protein which is ubiquitous in eukaryotes and its basic structure is well conserved – an N-terminal actin binding domain followed by a series of repeated segments which vary in number in different organisms. D. discoideum is a well established model organism for the study of signalling pathways and the actin cytoskeleton and as such makes an excellent organism in which to study filamin. Ddfilamin plays a putative role as a scaffolding protein in a photosensory signalling pathway and this role is thought to be mediated by the unusual repeat segments in the rod domain. Results To study the role of filamin in phototaxis, a filamin null mutant, HG1264, was transformed with constructs each of which expressed wild type filamin or a mutant filamin with a deletion of one of the repeat segments. Transformants expressing the full length filamin to wild type levels completely rescued the phototaxis defect in HG1264, however if filamin was expressed at lower than wild type levels the phototaxis defect was not restored. The transformants lacking any one of the repeat segments 2–6 retained defective phototaxis and thermotaxis phenotypes, whereas transformants expressing filaminΔ1 exhibited a range of partial complementation of the phototaxis phenotype which was related to expression levels. Immunofluorescence microscopy showed that filamin lacking any of the repeat segments still localised to the same actin rich areas as wild type filamin. Ddfilamin interacts with RasD and IP experiments demonstrated that this interaction did not rely upon any single repeat segment or the actin binding domain. Conclusion This paper demonstrates that wild type levels of filamin expression are essential for the formation of functional photosensory signalling complexes and that each of the repeat segments 2–6 are essential for filamins role in phototaxis. By contrast, repeat segment 1 is not essential provided the mutated filamin lacking repeat segment

  19. R-Ras Regulates Migration through an Interaction with Filamin A in Melanoma Cells

    PubMed Central

    Gawecka, Joanna E.; Griffiths, Genevieve S.; Ek-Rylander, Barbro; Ramos, Joe W.; Matter, Michelle L.

    2010-01-01

    Background Changes in cell adhesion and migration in the tumor microenvironment are key in the initiation and progression of metastasis. R-Ras is one of several small GTPases that regulate cell adhesion and migration on the extracellular matrix, however the mechanism has not been completely elucidated. Using a yeast two-hybrid approach we sought to identify novel R-Ras binding proteins that might mediate its effects on integrins. Methods and Findings We identified Filamin A (FLNa) as a candidate interacting protein. FLNa is an actin-binding scaffold protein that also binds to integrin β1, β2 and β7 tails and is associated with diverse cell processes including cell migration. Indeed, M2 melanoma cells require FLNa for motility. We further show that R-Ras and FLNa interact in co-immunoprecipitations and pull-down assays. Deletion of FLNa repeat 3 (FLNaΔ3) abrogated this interaction. In M2 melanoma cells active R-Ras co-localized with FLNa but did not co-localize with FLNa lacking repeat 3. Thus, activated R-Ras binds repeat 3 of FLNa. The functional consequence of this interaction was that active R-Ras and FLNa coordinately increased cell migration. In contrast, co-expression of R-Ras and FLNaΔ3 had a significantly reduced effect on migration. While there was enhancement of integrin activation and fibronectin matrix assembly, cell adhesion was not altered. Finally, siRNA knockdown of endogenous R-Ras impaired FLNa-dependent fibronectin matrix assembly. Conclusions These data support a model in which R-Ras functionally associates with FLNa and thereby regulates integrin-dependent migration. Thus in melanoma cells R-Ras and FLNa may cooperatively promote metastasis by enhancing cell migration. PMID:20585650

  20. The evolution of filamin-a protein domain repeat perspective.

    PubMed

    Light, Sara; Sagit, Rauan; Ithychanda, Sujay S; Qin, Jun; Elofsson, Arne

    2012-09-01

    Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. The evolution of filamin – A protein domain repeat perspective

    PubMed Central

    Light, Sara; Sagit, Rauan; Ithychanda, Sujay S.; Qin, Jun; Elofsson, Arne

    2013-01-01

    Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. PMID:22414427

  2. A meckelin–filamin A interaction mediates ciliogenesis

    PubMed Central

    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.

    2012-01-01

    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 FlnaDilp2 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

  3. Cooperative Learning Principles Enhance Online Interaction

    ERIC Educational Resources Information Center

    Jacobs, George; Seow, Peter

    2014-01-01

    This paper describes eight principles that can be used to promote cooperative interactions among students working in online environments. The principles derive from a well-established approach to education, known variously as cooperative learning and collaborative learning. Each principle is explained as to what it means, why it is important and…

  4. Enhancing mobility via cooperation: analysis and design

    NASA Astrophysics Data System (ADS)

    Deshpande, Ashish D.; Luntz, Jonathan E.

    2003-09-01

    A team of small, low cost robots instead of one large, complex robot is useful in operations such as search and rescue, urban exploration etc. However, the performance of such a team is limited due to restricted mobility of the team members. We propose to overcome the mobility restrictions by physical cooperation among the team members. We carry out a feasibility analysis of a particular behavior of two robots cooperating to cross a gap and also consider the effect of the scaling of the robot dimensions. We simulate the dynamic equations describing the motion which leads to the relaxation the requirements derived from the static analysis. A decentralized control architecture is designed which avoids continuous communication between the robots thus rendering the cooperation to be simple and low cost.

  5. 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.

  6. 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.

  7. Filamin A mutation is one cause of FG syndrome.

    PubMed

    Unger, Sheila; Mainberger, Anita; Spitz, Christian; Bähr, Anna; Zeschnigk, Christine; Zabel, Bernhard; Superti-Furga, Andrea; Morris-Rosendahl, Deborah J

    2007-08-15

    FG syndrome was originally described as a rare syndromic cause of X-linked mental retardation associated with congenital heart disease, anal atresia, inguinal hernia, cryptorchidism, and other anomalies. However, recent reports have highlighted the more common milder presentation which has for cardinal features developmental delay, particularly in speech, neonatal hypotonia, relative macrocephaly, dysmorphic facial features, severe constipation, and few if any congenital malformations. Thus far, five separate loci have been identified on the X chromosome but attempts at finding the responsible gene have not yet been successful. Given that one putative FG locus (FGS2) is situated at Xq28, which is the location of the Filamin A gene (FLNA), and that a Filamin A mutation was reported in a boy with facial dysmorphism and constipation, it was hypothesized that Filamin A mutations could be one cause of FG syndrome. Indeed, a previously unreported FLNA missense mutation (P1291L) was detected in our patient with FG syndrome, thus supporting this hypothesis and indicating that FG syndrome could now be added to the list of Filamin A-related disorders. Filamin A studies in other children with FG syndrome would help to confirm this association. (c) 2007 Wiley-Liss, Inc.

  8. 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…

  9. 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…

  10. Cell mechanics: filaminA leads the way.

    PubMed

    McGrath, James L

    2006-05-09

    Actin filaments are thought to be the major structural components of most eukaryotic cells, but reconstituted actin networks have yet to account for the remarkable strength exhibited by cellular networks. A new study has found that reconstituted networks that include the cross-linker filaminA can replicate many of the mechanical properties of cells if they are stressed prior to mechanical measurement.

  11. Reputation can enhance or suppress cooperation through positive feedback.

    PubMed

    McNamara, John M; Doodson, Polly

    2015-01-20

    One possible explanation for the widespread existence of cooperation in nature is that individuals cooperate to establish reputations and so benefit in future interactions with others. We consider a class of games in which individuals contribute to a common good at a cost to themselves. Population members vary in type, that is, in the cost paid for a given level of contribution. We consider a form of indirect reciprocity in which the contribution of an individual depends on their partner's reputation and their own type. Here we show that for such games, reputation destabilizes the selfish equilibrium through a novel and robust feedback mechanism. For those games in which the selfish optimal contribution to the common good increases as the contribution of the partner increases, the feedback mechanism enhances cooperation levels. In contrast, when the optimal contribution decreases as partner's contribution increases, cooperation levels are reduced still further.

  12. Regulation of the Actin Cytoskeleton by an Interaction of IQGAP Related Protein GAPA with Filamin and Cortexillin I

    PubMed Central

    Rieger, Daniela; Müller, Rolf; Rivero, Francisco; Faix, Jan; Schleicher, Michael; Noegel, Angelika A.

    2010-01-01

    Filamin and Cortexillin are F-actin crosslinking proteins in Dictyostelium discoideum allowing actin filaments to form three-dimensional networks. GAPA, an IQGAP related protein, is required for cytokinesis and localizes to the cleavage furrow during cytokinesis. Here we describe a novel interaction with Filamin which is required for cytokinesis and regulation of the F-actin content. The interaction occurs through the actin binding domain of Filamin and the GRD domain of GAPA. A similar interaction takes place with Cortexillin I. We further report that Filamin associates with Rac1a implying that filamin might act as a scaffold for small GTPases. Filamin and activated Rac associate with GAPA to regulate actin remodelling. Overexpression of filamin and GAPA in the various strains suggests that GAPA regulates the actin cytoskeleton through interaction with Filamin and that it controls cytokinesis through association with Filamin and Cortexillin. PMID:21085675

  13. 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.…

  14. 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.…

  15. Filamin acts as a key regulator in epithelial defence against transformed cells.

    PubMed

    Kajita, Mihoko; Sugimura, Kaoru; Ohoka, Atsuko; Burden, Jemima; Suganuma, Hitomi; Ikegawa, Masaya; Shimada, Takashi; Kitamura, Tetsuya; Shindoh, Masanobu; Ishikawa, Susumu; Yamamoto, Sayaka; Saitoh, Sayaka; Yako, Yuta; Takahashi, Ryosuke; Okajima, Takaharu; Kikuta, Junichi; Maijima, Yumiko; Ishii, Masaru; Tada, Masazumi; Fujita, Yasuyuki

    2014-07-31

    Recent studies have shown that certain types of transformed cells are extruded from an epithelial monolayer. However, it is not known whether and how neighbouring normal cells play an active role in this process. In this study, we demonstrate that filamin A and vimentin accumulate in normal cells specifically at the interface with Src- or RasV12-transformed cells. Knockdown of filamin A or vimentin in normal cells profoundly suppresses apical extrusion of the neighbouring transformed cells. In addition, we show in zebrafish embryos that filamin plays a positive role in the elimination of the transformed cells. Furthermore, the Rho/Rho kinase pathway regulates filamin accumulation and filamin acts upstream of vimentin in the apical extrusion. This is the first report demonstrating that normal epithelial cells recognize and actively eliminate neighbouring transformed cells and that filamin is a key mediator in the interaction between normal and transformed epithelial cells.

  16. 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.

  17. Filamin A phosphorylation by Akt promotes cell migration in response to arsenic

    PubMed Central

    Li, Lingzhi; Lu, Yongju; Stemmer, Paul M.; Chen, Fei

    2015-01-01

    We had previously reported that trivalent arsenic (As3+), a well-known environmental carcinogen, induces phosphorylation of several putative Akt substrates. In the present report, we characterized one of these substrates by immunoprecipitation and proteomics analysis. The results indicate that a cytoskeleton remodeling protein, filamin A, with a molecular weight around 280 kDa, is phosphorylated by Akt in HEK-293 cells treated with As3+, which was also confirmed in human bronchial epithelial cell line, BEAS-2B cells. Additional biochemical and biological studies revealed that serine 2152 (S2152) of filamin A is phosphorylated by activated Akt in the cells treated with As3+. To further confirm the importance of Akt-dependent filamin A S2152 phosphorylation in As3+-induced cell migration, we over-expressed either wild type filamin A or the mutated filamin A in which the S2152 was substituted with alanine (S2152A). The capability of cell migration was reduced significantly in the cells expressing the mutated filamin A (S2152A). Clinically, we found that increased expression of filamin A predicts poorer overall survival of the lung cancer patients with adenocarcinoma. Thus, these data suggest that Akt dependent filamin A phosphorylation is one of the key events in mediating As3+-induced carcinogenesis. Antagonizing Akt signaling can ameliorate As3+-induced filamin A phosphorylation and cell migration, which may serve as a molecular targeting strategy for malignancies associated with environmental As3+ exposure. PMID:25944616

  18. Filamin A phosphorylation by Akt promotes cell migration in response to arsenic.

    PubMed

    Li, Lingzhi; Lu, Yongju; Stemmer, Paul M; Chen, Fei

    2015-05-20

    We had previously reported that trivalent arsenic (As(3+)), a well-known environmental carcinogen, induces phosphorylation of several putative Akt substrates. In the present report, we characterized one of these substrates by immunoprecipitation and proteomics analysis. The results indicate that a cytoskeleton remodeling protein, filamin A, with a molecular weight around 280 kDa, is phosphorylated by Akt in HEK-293 cells treated with As(3+), which was also confirmed in human bronchial epithelial cell line, BEAS-2B cells. Additional biochemical and biological studies revealed that serine 2152 (S2152) of filamin A is phosphorylated by activated Akt in the cells treated with As(3+). To further confirm the importance of Akt-dependent filamin A S2152 phosphorylation in As(3+)-induced cell migration, we over-expressed either wild type filamin A or the mutated filamin A in which the S2152 was substituted with alanine (S2152A). The capability of cell migration was reduced significantly in the cells expressing the mutated filamin A (S2152A). Clinically, we found that increased expression of filamin A predicts poorer overall survival of the lung cancer patients with adenocarcinoma. Thus, these data suggest that Akt dependent filamin A phosphorylation is one of the key events in mediating As(3+)-induced carcinogenesis. Antagonizing Akt signaling can ameliorate As(3+)-induced filamin A phosphorylation and cell migration, which may serve as a molecular targeting strategy for malignancies associated with environmental As(3+) exposure.

  19. The ASEAN Political-Security Community: Enhancing Defense Cooperation

    DTIC Science & Technology

    2015-12-01

    meeting that year, they agreed to a broader goal of creating an ASEAN Community, which would have three pillars . One of these would be the ASEAN... pillars . Under APSC, endorsing and enhancing defense cooperation through military engagement is evidence to support the argument that ASEAN has changed...economy. A similar case happened to the West Papua, where its natural resources— copper and gold—had been exploited with little compensation and

  20. Filamin A is required in injured axons for HDAC5 activity and axon regeneration.

    PubMed

    Cho, Yongcheol; Park, Dongeun; Cavalli, Valeria

    2015-09-11

    Microtubule dynamics are important for axon growth during development as well as axon regeneration after injury. We have previously identified HDAC5 as an injury-regulated tubulin deacetylase that functions at the injury site to promote axon regeneration. However, the mechanisms involved in the spatial control of HDAC5 activity remain poorly understood. Here we reveal that HDAC5 interacts with the actin binding protein filamin A via its C-terminal domain. Filamin A plays critical roles in HDAC5-dependent tubulin deacetylation because, in cells lacking filamin A, the levels of acetylated tubulin are elevated markedly. We found that nerve injury increases filamin A axonal expression in a protein synthesis-dependent manner. Reducing filamin A levels or interfering with the interaction between HDAC5 and filamin A prevents injury-induced tubulin deacetylation as well as HDAC5 localization at the injured axon tips. In addition, neurons lacking filamin A display reduced axon regeneration. Our findings suggest a model in which filamin A local translation following axon injury controls localized HDAC5 activity to promote axon regeneration.

  1. Filamin A Is Required in Injured Axons for HDAC5 Activity and Axon Regeneration*

    PubMed Central

    Cho, Yongcheol; Park, Dongeun; Cavalli, Valeria

    2015-01-01

    Microtubule dynamics are important for axon growth during development as well as axon regeneration after injury. We have previously identified HDAC5 as an injury-regulated tubulin deacetylase that functions at the injury site to promote axon regeneration. However, the mechanisms involved in the spatial control of HDAC5 activity remain poorly understood. Here we reveal that HDAC5 interacts with the actin binding protein filamin A via its C-terminal domain. Filamin A plays critical roles in HDAC5-dependent tubulin deacetylation because, in cells lacking filamin A, the levels of acetylated tubulin are elevated markedly. We found that nerve injury increases filamin A axonal expression in a protein synthesis-dependent manner. Reducing filamin A levels or interfering with the interaction between HDAC5 and filamin A prevents injury-induced tubulin deacetylation as well as HDAC5 localization at the injured axon tips. In addition, neurons lacking filamin A display reduced axon regeneration. Our findings suggest a model in which filamin A local translation following axon injury controls localized HDAC5 activity to promote axon regeneration. PMID:26157139

  2. 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.

  3. Complex roles of filamin-A mediated cytoskeleton network in cancer progression

    PubMed Central

    2013-01-01

    Filamin-A (FLNA), also called actin-binding protein 280 (ABP-280), was originally identified as a non-muscle actin binding protein, which organizes filamentous actin into orthogonal networks and stress fibers. Filamin-A also anchors various transmembrane proteins to the actin cytoskeleton and provides a scaffold for a wide range of cytoplasmic and nuclear signaling proteins. Intriguingly, several studies have revealed that filamin-A associates with multiple non-cytoskeletal proteins of diverse function and is involved in several unrelated pathways. Mutations and aberrant expression of filamin-A have been reported in human genetic diseases and several types of cancer. In this review, we discuss the implications of filamin-A in cancer progression, including metastasis and DNA damage response. PMID:23388158

  4. Filamin B Regulates Chondrocyte Proliferation and Differentiation through Cdk1 Signaling

    PubMed Central

    Lian, Gewei; Zhang, Jingping; Hecht, Jonathan L.; Sheen, Volney L.

    2014-01-01

    Humans who harbor loss of function mutations in the actin-associated filamin B (FLNB) gene develop spondylocarpotarsal syndrome (SCT), a disorder characterized by dwarfism (delayed bone formation) and premature fusion of the vertebral, carpal and tarsal bones (premature differentiation). To better understand the cellular and molecular mechanisms governing these seemingly divergent processes, we generated and characterized FlnB knockdown ATDC5 cell lines. We found that FlnB knockdown led to reduced proliferation and enhanced differentiation in chondrocytes. Within the shortened growth plate of postnatal FlnB−/− mice long bone, we observed a similarly progressive decline in the number of rapidly proliferating chondrocytes and premature differentiation characterized by an enlarged prehypertrophic zone, a widened Col2a1+/Col10a1+ overlapping region, but relatively reduced hypertrophic zone length. The reduced chondrocyte proliferation and premature differentiation were, in part, attributable to enhanced G2/M phase progression, where fewer FlnB deficient ATDC5 chondrocytes resided in the G2/M phase of the cell cycle. FlnB loss reduced Cdk1 phosphorylation (an inhibitor of G2/M phase progression) and Cdk1 inhibition in chondrocytes mimicked the null FlnB, premature differentiation phenotype, through a β1-integrin receptor- Pi3k/Akt (a key regulator of chondrocyte differentiation) mediated pathway. In this context, the early prehypertrophic differentiation provides an explanation for the premature differentiation seen in this disorder, whereas the progressive decline in proliferating chondrocytes would ultimately lead to reduced chondrocyte production and shortened bone length. These findings begin to define a role for filamin proteins in directing both cell proliferation and differentiation through indirect regulation of cell cycle associated proteins. PMID:24551245

  5. Spatial structure enhanced cooperation in dissatisfied adaptive snowdrift game

    NASA Astrophysics Data System (ADS)

    Zhang, Wen; Xu, Chen; Hui, Pak Ming

    2013-05-01

    The dissatisfied adaptive snowdrift game (DASG) describes the adaptive actions driven by the level of dissatisfaction when two connected agents interact. We study the DASG in static networks both numerically and analytically. In a random network of uniform degree k, the system evolves into a homogeneous state consisting only of cooperators when the cost-to-benefit ratio r < r 0 and a mixed phase with the coexistence of cooperators and defectors when r > r 0, where r 0 is a threshold. For an infinite population, the large k limit corresponding to the well-mixed case is solved analytically. A theory is developed based on the pair approximation. It gives the frequency of cooperation f c and the densities of different pairs that are in good agreement with simulation results. The results revealed that f c is enhanced in networked populations with a finite k, when compared with the well-mixed case. The reasons that the theory works well for the present model are traced back to the weak spatial correlation implied by the random network and the fact that the adaptive actions in DASG are driven only by the strategy pairs. The results shed light on the class of models that the pair approximation is applicable.

  6. Perfect Problems and Homogeneous Groups Enhance Cooperative Learning in Abstract Algebra.

    ERIC Educational Resources Information Center

    Weld, Kathryn

    1999-01-01

    Cooperative student work often fails to generate individual understanding of abstract algebra materials. Suggests techniques that enable abstract algebra students to master proofs and enhance cooperative work. (Author/ASK)

  7. GPIbα regulates platelet size by controlling the subcellular localization of filamin

    PubMed Central

    Ware, Jerry; Okamura, Takashi; Newman, Peter J.

    2012-01-01

    Interaction between the cytoplasmic domain of GPIbα with its cytoskeletal binding partner, filamin, is a major determinant of platelet size, and deficiency of either protein results in macrothrombocytopenia. To clarify the mechanism by which GPIbα-filamin interactions regulate platelet production, we manipulated the expression levels of filamin and GPIb in cultured embryonic stem cells (ESCs) that were subsequently differentiated into platelets. Knocking down filamins A and B resulted in the production of ESC-derived proplatelets with abnormally large swellings and proplatelet shafts that generated giant platelets in culture. Large platelets could also be generated by overexpressing GPIbα in ESCs, or by overexpressing in vivo a transgene encoding a chimeric protein containing the cytoplasmic domain of GPIbα. To identify the mechanism by which the GPIb:filamin ratio regulates platelet size, we manipulated filamin and GPIbα levels in HEK293T cells and examined the effects of overexpressing either protein on their ability to traffic to the cell periphery. Accumulation of either protein within the endoplasmic reticulum resulted in trapping of the other. Taken together, these data demonstrate that coordinated expression of GPIbα and filamin is required for efficient trafficking of either protein to the cell surface, and for production of normal-sized platelets. PMID:22174152

  8. Filamin-regulated F-actin assembly is essential for morphogenesis and controls phototaxis in Dictyostelium.

    PubMed

    Khaire, Nandkumar; Müller, Rolf; Blau-Wasser, Rosemarie; Eichinger, Ludwig; Schleicher, Michael; Rief, Matthias; Holak, Tad A; Noegel, Angelika A

    2007-01-19

    Dictyostelium strains lacking the F-actin cross-linking protein filamin (ddFLN) have a severe phototaxis defect at the multicellular slug stage. Filamins are rod-shaped homodimers that cross-link the actin cytoskeleton into highly viscous, orthogonal networks. Each monomer chain of filamin is comprised of an F-actin-binding domain and a rod domain. In rescue experiments only intact filamin re-established correct phototaxis in filamin minus mutants, whereas C-terminally truncated filamin proteins that had lost the dimerization domain and molecules lacking internal repeats but retaining the dimerization domain did not rescue the phototaxis defect. Deletion of individual rod repeats also changed their subcellular localization, and mutant filamins in general were less enriched at the cell cortex as compared with the full-length protein and were increasingly present in the cytoplasm. For correct phototaxis ddFLN is only required at the tip of the slug because expression under control of the cell type-specific extracellular-matrix protein A (ecmA) promoter and mixing experiments with wild type cells supported phototactic orientation. Likewise, in chimeric slugs wild type cells were primarily found at the tip of the slug, which acts as an organizer in Dictyostelium morphogenesis.

  9. Cooperation.

    ERIC Educational Resources Information Center

    Online-Offline, 1997

    1997-01-01

    The theme of this month's issue is "cooperation"--related to animal, personal, national, and global cooperation; rules and regulations; and team efforts. K-8 resources on the theme include World Wide Web sites, CD-ROM, software, videos, books, and others. Features include cooperative living, alliances of nations, songs of cooperation, and animals…

  10. 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

  11. Filamin A protects cells against force-induced apoptosis by stabilizing talin- and vinculin-containing cell adhesions.

    PubMed

    Pinto, Vanessa I; Senini, Vincent W; Wang, Yongqiang; Kazembe, Mwayi P; McCulloch, Christopher A

    2014-01-01

    In mechanically loaded tissues such as weight-bearing joints, myocardium, and periodontal ligament, pathophysiological forces can disrupt cell-matrix contacts, which can induce cell death, leading to tissue and organ dysfunction. Protection against force-induced cell death may be mediated by filamin A (FLNa), an actin-binding protein that regulates β1 integrin-mediated cell adhesion. We examined the affect of filamin expression on collagen distribution and cell death in the periodontal ligament, a force-loaded tissue. Conditional deletion of FLNa in fibroblasts was associated with 2-fold increase of acellular areas in periodontal ligament and 7-fold higher proportions of apoptotic cells. In cultured fibroblasts with FLNa knockdown, we examined the affect of supraphysiological forces (1 pN/μm(2) cell area; applied through the β1 integrin) on recruitment of talin and vinculin to focal adhesions and on apoptosis. Compared with the wild type, FLNa-knockdown cells exhibited 3-fold increases in floating cells after overnight force application and a 2-fold increase in cell detachment. Force induced time-dependent reductions (P<0.05) in the numbers of activated β1 integrin-, talin-, and vinculin-stained adhesions in FLNa-knockdown compared with those in wild-type cells. We conclude that FLNa protects against apoptosis in force-loaded cells, and this protection is mediated by enhanced formation and maturation of matrix adhesions.

  12. Filamin actin-binding and titin-binding fulfill distinct functions in Z-disc cohesion

    PubMed Central

    González-Morales, Nicanor

    2017-01-01

    Many proteins contribute to the contractile properties of muscles, most notably myosin thick filaments, which are anchored at the M-line, and actin thin filaments, which are anchored at the Z-discs that border each sarcomere. In humans, mutations in the actin-binding protein Filamin-C result in myopathies, but the underlying molecular function is not well understood. Here we show using Drosophila indirect flight muscle that the filamin ortholog Cheerio in conjunction with the giant elastic protein titin plays a crucial role in keeping thin filaments stably anchored at the Z-disc. We identify the filamin domains required for interaction with the titin ortholog Sallimus, and we demonstrate a genetic interaction of filamin with titin and actin. Filamin mutants disrupting the actin- or the titin-binding domain display distinct phenotypes, with Z-discs breaking up in parallel or perpendicularly to the myofibril, respectively. Thus, Z-discs require filamin to withstand the strong contractile forces acting on them. PMID:28732005

  13. Disruption of TACE-filamin interaction can inhibit TACE-mediated ectodomain shedding.

    PubMed

    Cho, Yongcheol; Park, Dongeun; Kim, Chungho

    2017-08-26

    Ectodomain shedding regulates functions of many membrane proteins through the cleavage of their juxtamembrane region mainly by a disintegrin and metalloproteinase family proteinases. Tumor necrosis factor-alpha converting enzyme (TACE) is known to be responsible for phorbol myristate acetate (PMA)-induced shedding of various membrane proteins. How PMA regulates TACE-dependent shedding and how TACE exhibits substrate specificity without proteolysis of other membrane proteins are questionable. Here, we show that TACE can interact with an actin-binding protein, filamin, through 20th filamin repeat. We found that the interaction between TACE and filamin was increased by PMA treatment. In addition, loss of filamin or specific disruption of TACE-filamin interaction inhibited ectodomain shedding of representative TACE substrates, CD44 and amyloid protein precursor. From these data, we suggest that filamin may work as a scaffold that can recruit TACE and its substrates in a PMA-dependent manner to achieve substrate specificity for TACE. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 75 FR 9380 - Cooperative Conservation Partners Initiative; Wetlands Reserve Enhancement Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-02

    ...; ] DEPARTMENT OF AGRICULTURE Commodity Credit Corporation Cooperative Conservation Partners Initiative; Wetlands... Partnership Initiative (CCPI) and $25 million in the Wetlands Reserve Enhancement Program (WREP) through the... runoff; protect, restore, and enhance wetlands; maintain agricultural productivity; ] improve...

  15. 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-…

  16. Adoption of simultaneous different strategies against different opponents enhances cooperation

    NASA Astrophysics Data System (ADS)

    Wardil, Lucas; K. L. da Silva, Jafferson

    2009-05-01

    The emergence of cooperation has been widely studied in the context of game theory on structured populations. Usually the individuals adopt one strategy against all their neighbors. The structure can provide reproductive success for the cooperative strategy, at least for low values of defection tendency. Other mechanisms, such as punishment, can also be responsible for cooperation emergence. But what happens if the players adopt simultaneously different strategies against each one of their opponents, not just a single one? Here we study this question in the prisoner dilemma scenario structured on a square lattice and on a ring. We show that if an update rule is defined in which the players replace the strategy that furnishes the smallest payoff, a punishment response mechanism against defectors without imputing cost to the punishers appears, cooperation dominates and, even if the tendency of defection is huge, cooperation still remains alive.

  17. Enhancing Military Cooperation Among ’ASEAN’ Countries.

    DTIC Science & Technology

    1988-04-15

    extension of military cooperation among the ASEAN members. It is an attempt to convince political and military leaders in ASEAN countries that such proper...It is an attempt to convince political and military leaders in ASEAN countries that such proper application of military cooperation should be fostered...serious political disputes among its three members that ruined this fragile organization. ASEAN’s declared objectives, set out in its founding charter

  18. Upregulation of neurovascular communication through filamin abrogation promotes ectopic periventricular neurogenesis

    PubMed Central

    Houlihan, Shauna L; Lanctot, Alison A; Guo, Yan; Feng, Yuanyi

    2016-01-01

    Neuronal fate-restricted intermediate progenitors (IPs) are derived from the multipotent radial glia (RGs) and serve as the direct precursors for cerebral cortical neurons, but factors that control their neurogenic plasticity remain elusive. Here we report that IPs’ neuron production is enhanced by abrogating filamin function, leading to the generation of periventricular neurons independent of normal neocortical neurogenesis and neuronal migration. Loss of Flna in neural progenitor cells (NPCs) led RGs to undergo changes resembling epithelial-mesenchymal transition (EMT) along with exuberant angiogenesis that together changed the microenvironment and increased neurogenesis of IPs. We show that by collaborating with β-arrestin, Flna maintains the homeostatic signaling between the vasculature and NPCs, and loss of this function results in escalated Vegfa and Igf2 signaling, which exacerbates both EMT and angiogenesis to further potentiate IPs’ neurogenesis. These results suggest that the neurogenic potential of IPs may be boosted in vivo by manipulating Flna-mediated neurovascular communication. DOI: http://dx.doi.org/10.7554/eLife.17823.001 PMID:27664421

  19. A novel partner for Dictyostelium filamin is an alpha-helical developmentally regulated protein.

    PubMed

    Knuth, Monika; Khaire, Nandkumar; Kuspa, Adam; Lu, Si Jie; Schleicher, Michael; Noegel, Angelika A

    2004-10-01

    The filamins are a family of highly homologous actin-crosslinking proteins that stabilize three-dimensional actin networks, link them to membrane proteins and direct intracellular signaling reactions to the actin scaffold through interaction with various binding partners. Here, we describe the first Dictyostelium filamin-interacting protein to be isolated--FIP, a 229.8 kDa protein with two alpha-helical coiled coil domains. FIP was identified in a yeast two-hybrid screen using the rod domain of filamin as bait. FIP can also be coimmunoprecipitated with filamin from cellular extracts. Deletion analysis located the interaction domain of FIP to a C-terminal region; by contrast, in filamin rods, repeats 2-4 interacted with the recombinant FIP protein. The 7 kb transcript of FIP is upregulated during early development. Monoclonal antibodies raised against a bacterially expressed FIP polypeptide recognize a 230 kDa developmentally regulated protein in western blots. Immunofluorescence analysis shows a punctate staining pattern in the cytosol and, in cell fractionation experiments, FIP is mainly found in the cytosolic fraction. A fusion protein composed of GFP and the C-terminal part localizes to the plasma membrane and is associated with the cytoskeleton. Expression of the fusion protein affects development and influences the size of the multicellular aggregates and the phototactic behavior of slugs. Thus, FIP might provide a candidate link between the dynamic actin cytoskeleton and signal transduction events during the multicellular stages of Dictyostelium amoebae.

  20. Filamin, a synaptic organizer in Drosophila, determines glutamate receptor composition and membrane growth

    PubMed Central

    Lee, GaYoung; Schwarz, Thomas L

    2016-01-01

    Filamin is a scaffolding protein that functions in many cells as an actin-crosslinker. FLN90, an isoform of the Drosophila ortholog Filamin/cheerio that lacks the actin-binding domain, is here shown to govern the growth of postsynaptic membrane folds and the composition of glutamate receptor clusters at the larval neuromuscular junction. Genetic and biochemical analyses revealed that FLN90 is present surrounding synaptic boutons. FLN90 is required in the muscle for localization of the kinase dPak and, downstream of dPak, for localization of the GTPase Ral and the exocyst complex to this region. Consequently, Filamin is needed for growth of the subsynaptic reticulum. In addition, in the absence of filamin, type-A glutamate receptor subunits are lacking at the postsynapse, while type-B subunits cluster correctly. Receptor composition is dependent on dPak, but independent of the Ral pathway. Thus two major aspects of synapse formation, morphological plasticity and subtype-specific receptor clustering, require postsynaptic Filamin. DOI: http://dx.doi.org/10.7554/eLife.19991.001 PMID:27914199

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. Cross-sector cooperation in health-enhancing physical activity policymaking: more potential than achievements?

    PubMed

    Hämäläinen, Riitta-Maija; Aro, Arja R; Lau, Cathrine Juel; Rus, Diana; Cori, Liliana; Syed, Ahmed M

    2016-04-29

    The cooperation of actors across policy fields and the need for cross-sector cooperation as well as recommendations on how to implement cross-sector cooperation have been addressed in many national and international policies that seek to solve complex issues within societies. For such a purpose, the relevant governance structure between policy sectors is cross-sector cooperation. Therefore, cross-sector cooperation and its structures need to be better understood for improved implementation. This article reports on the governance structures and processes of cross-sector cooperation in health-enhancing physical activity (HEPA) policies in six European Union (EU) member states. Qualitative content analysis of HEPA policies and semi-structured interviews with key policymakers in six European countries. Cross-sector cooperation varied between EU member states within HEPA policies. The main issues of the cross-sector policy process can be divided into stakeholder involvement, governance structures and coordination structures and processes. Stakeholder involvement included citizen hearings and gatherings of stakeholders from various non-governmental organisations and citizen groups. Governance structures with policy and political discussions included committees, working groups and consultations for HEPA policymaking. Coordination structures and processes included administrative processes with various stakeholders, such as ministerial departments, research institutes and private actors for HEPA policymaking. Successful cross-sector cooperation required joint planning and evaluation, financial frameworks, mandates based on laws or agreed methods of work, communication lines, and valued processes of cross-sector cooperation. Cross-sector cooperation required participation with the co-production of goals and sharing of resources between stakeholders, which could, for example, provide mechanisms for collaborative decision-making through citizen hearing. Clearly stated

  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

    2016-03-08

    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.

  7. MEKK4 Signaling Regulates Filamin Expression and Neuronal Migration

    PubMed Central

    Sarkisian, Matthew R.; Bartley, Christopher M.; Chi, Hongbo; Nakamura, Fumihiko; Hashimoto-Torii, Kazue; Torii, Masaaki; Flavell, Richard A.; Rakic, Pasko

    2007-01-01

    Summary Periventricular heterotopia (PVH) is a congenital malformation of human cerebral cortex frequently associated with Filamin-A (FLN-A) mutations but the pathogenetic mechanisms remain unclear. Here we show that the MEKK4 (MAP3K4) pathway is involved in Fln-A regulation and PVH formation. MEKK4−/− mice developed PVH associated with breaches in the neuroependymal lining which were largely comprised of neurons that failed to reach the cortical plate. RNA interference (RNAi) targeting MEKK4 also impaired neuronal migration. Expression of Fln was elevated in MEKK4−/− forebrain, most notably near sites of failed neuronal migration. Importantly, recombinant-MKK4 protein precipitated a complex containing MEKK4 and Fln-A, and MKK4 mediated signaling between MEKK4 and Fln-A, suggesting that MKK4 may bridge these molecules during development. Finally, we showed that wild-type FLN-A over-expression inhibited neuronal migration. Collectively, our results demonstrate a link between MEKK4 and Fln-A that impacts neuronal migration-initiation and provides insight into the pathogenesis of human PVH. PMID:17145501

  8. Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling.

    PubMed

    Pons, Mònica; Izquierdo, Ismael; Andreu-Carbó, Mireia; Garrido, Georgina; Planagumà, Jesús; Muriel, Olivia; Del Pozo, Miguel A; Geli, M Isabel; Aragay, Anna M

    2017-01-15

    Proper endosomal trafficking of ligand-activated G-protein-coupled receptors (GPCRs) is essential to spatiotemporally tune their physiological responses. For the monocyte chemoattractant receptor 2 (CCR2B; one of two isoforms encoded by CCR2), endocytic recycling is important to sustain monocyte migration, whereas filamin A (FLNa) is essential for CCL2-induced monocyte migration. Here, we analyze the role of FLNa in the trafficking of CCR2B along the endocytic pathway. In FLNa-knockdown cells, activated CCR2B accumulated in enlarged EEA-1-positive endosomes, which exhibited slow movement and fast fluorescence recovery, suggesting an imbalance between receptor entry and exit rates. Utilizing super-resolution microscopy, we observed that FLNa-GFP, CCR2B and β2-adrenergic receptor (β2AR) were present in actin-enriched endosomal microdomains. Depletion of FLNa decreased CCR2B association with these microdomains and concomitantly delayed CCR2B endosomal traffic, without apparently affecting the number of microdomains. Interestingly, CCR2B and β2AR signaling induced phosphorylation of FLNa at residue S2152, and this phosphorylation event was contributes to sustain receptor recycling. Thus, our data strongly suggest that CCR2B and β2AR signals to FLNa to stimulate its endocytosis and recycling to the plasma membrane. © 2017. Published by The Company of Biologists Ltd.

  9. Phosphorylated filamin A regulates actin-linked caveolae dynamics.

    PubMed

    Muriel, Olivia; Echarri, Asier; Hellriegel, Christian; Pavón, Dácil M; Beccari, Leonardo; Del Pozo, Miguel A

    2011-08-15

    Caveolae are relatively stable membrane invaginations that compartmentalize signaling, regulate lipid metabolism and mediate viral entry. Caveolae are closely associated with actin fibers and internalize in response to diverse stimuli. Loss of cell adhesion is known to induce rapid and robust caveolae internalization and trafficking toward a Rab11-positive recycling endosome; however, pathways governing this process are poorly understood. Here, we report that filamin A is required to maintain the F-actin-dependent linear distribution of caveolin-1. High spatiotemporal resolution particle tracking of caveolin-1-GFP vesicles by total internal reflection fluorescence (TIRF) microscopy revealed that FLNa is required for the F-actin-dependent arrest of caveolin-1 vesicles in a confined area and their stable anchorage to the plasma membrane. The linear distribution and anchorage of caveolin-1 vesicles are both required for proper caveolin-1 inwards trafficking. De-adhesion-triggered caveolae inward trafficking towards a recycling endosome is impaired in FLNa-depleted HeLa and FLNa-deficient M2-melanoma cells. Inwards trafficking of caveolin-1 requires both the ability of FLNa to bind actin and cycling PKCα-dependent phosphorylation of FLNa on Ser2152 after cell detachment. © 2011. Published by The Company of Biologists Ltd

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. Filamin C-related myopathies: pathology and mechanisms

    PubMed Central

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

    2016-01-01

    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

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

    NASA Astrophysics Data System (ADS)

    Dougherty, R. C.; Bowen, C. W.; Berger, T.; Rees, W.; Mellon, E. K.; Pulliam, E.

    1995-09-01

    This report discusses the retention and performance of three sections of general chemistry that utilized different levels of cooperative learning and enhanced communication. The structured cooperative section (S-coop) required that students belonged to study groups, had group homework and group quizzes and had course credit driven electronic mail. The unstructured cooperative section (U-coop) encouraged students to form optional informal groups and provided for optional enhanced communication by paper mail. The control section used a standard lecture format without any cooperative learning or enhanced communication options. The student retention (C or better) was S-coop 85 %, U-coop 76 %, and Control 59 % (all differences were statistically significant). On the final exam the percent correct for common questions was S-coop 58%, U-coop 60%, and Control 55%. Adjusted for the difference in retention there was no significant difference between the two cooperative sections. The results of the Student Instructional Rating System for the three sections had the following percentage of students agreeing that the instructor was an effective teacher: S-coop 74%; U-coop 99%; and Control 80%. In all cases the differences were statistically significant. We conclude that a structured cooperative learning environment with enhanced communication can improve overall student retention and performance in general chemistry.

  16. Calpain 1-gamma filamin interaction in muscle cells: a possible in situ regulation by PKC-alpha.

    PubMed

    Raynaud, Fabrice; Fabrice, Raynaud; Jond-Necand, Carole; Carole, Jond-Necand; Marcilhac, Anne; Anne, Marcilhac; Fürst, Dieter; Dieter, Fürst; Benyamin, Yves; Yves, Benyamin

    2006-03-01

    Calpains are a family of calcium-dependent cysteine-proteases involved in cytoskeleton remodelling and muscle differentiation. In a recent study, we observed the presence of calpain 1 in the muscle contractile apparatus and specifically in the N1- and N2-lines. This calpain isoform was found to be involved in the degradation of muscle fibres via proteolysis of key proteins in Z-disk and costameric junctions. The goal of this study was to determine whether gamma-filamin--a specific muscle isoform of the filamin family--is a calpain 1 substrate and to characterise this interaction. Gamma-filamin is a major muscle architectural protein located in the Z-line and under the sarcolemmal membrane. This protein is a component of the chain binding the sarcolemma to the sarcomeric structure. In this study, we found that gamma-filamin formed a stable complex in vitro and in cells with calpain 1 in the absence of calcium stimulation. We also located the binding domains in the C-terminus of gamma-filamin with a cleavage site between serine 2626 and serine 2627 in the hinge 2 region. The catalytic (80 kDa) and regulatory (28 kDa) subunits of calpain 1 are both involved in high affinity binding at gamma-filamin. Moreover, we showed that phosphorylation of the filamin C-terminus domain by PKC alpha protected gamma-filamin against proteolysis by calpain 1 in COS cells. Stimulation of PKC activity in myotubes, prevented gamma-filamin proteolysis by calpain and resulted in an increase in myotube adhesion.

  17. Direct interaction with filamins modulates the stability and plasma membrane expression of CFTR

    PubMed Central

    Thelin, William R.; Chen, Yun; Gentzsch, Martina; Kreda, Silvia M.; Sallee, Jennifer L.; Scarlett, Cameron O.; Borchers, Christoph H.; Jacobson, Ken; Stutts, M. Jackson; Milgram, Sharon L.

    2007-01-01

    The role of the cystic fibrosis transmembrane conductance regulator (CFTR) as a cAMP-dependent chloride channel on the apical membrane of epithelia is well established. However, the processes by which CFTR is regulated on the cell surface are not clear. Here we report the identification of a protein-protein interaction between CFTR and the cytoskeletal filamin proteins. Using proteomic approaches, we identified filamins as proteins that associate with the extreme CFTR N terminus. Furthermore, we identified a disease-causing missense mutation in CFTR, serine 13 to phenylalanine (S13F), which disrupted this interaction. In cells, filamins tethered plasma membrane CFTR to the underlying actin network. This interaction stabilized CFTR at the cell surface and regulated the plasma membrane dynamics and confinement of the channel. In the absence of filamin binding, CFTR was internalized from the cell surface, where it prematurely accumulated in lysosomes and was ultimately degraded. Our data demonstrate what we believe to be a previously unrecognized role for the CFTR N terminus in the regulation of the plasma membrane stability and metabolic stability of CFTR. In addition, we elucidate the molecular defect associated with the S13F mutation. PMID:17235394

  18. Cooperatively enhanced dipole forces from artificial atoms in trapped nanodiamonds

    NASA Astrophysics Data System (ADS)

    Juan, Mathieu L.; Bradac, Carlo; Besga, Benjamin; Johnsson, Mattias; Brennen, Gavin; Molina-Terriza, Gabriel; Volz, Thomas

    2017-03-01

    Optical trapping is a powerful tool to manipulate small particles, from micrometre-size beads in liquid environments to single atoms in vacuum. The trapping mechanism relies on the interaction between a dipole and the electric field of laser light. In atom trapping, the dominant contribution to the associated force typically comes from the allowed optical transition closest to the laser wavelength, whereas for mesoscopic particles it is given by the polarizability of the bulk material. Here, we show that for nanoscale diamond crystals containing a large number of artificial atoms, nitrogen-vacancy colour centres, the contributions from both the nanodiamond and the colour centres to the optical trapping strength can be simultaneously observed in a noisy liquid environment. For wavelengths around the zero-phonon line transition of the colour centres, we observe a 10% increase of overall trapping strength. The magnitude of this effect suggests that due to the large density of centres, cooperative effects between the artificial atoms contribute to the observed modification of the trapping strength. Our approach may enable the study of cooperativity in nanoscale solid-state systems and the use of atomic physics techniques in the field of nano-manipulation.

  19. 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.

  20. 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.

  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. Third-Party Cooperation: How Reducing Material Involvement Enhances Contributions to the Public Good.

    PubMed

    Losecaat Vermeer, Annabel B; Heerema, Roeland L; Sanfey, Alan G

    2016-03-01

    Decisions to cooperate are often delegated to a third party. We examined whether cooperation differs when decisions are made for a third party compared with ourselves and specified which motives are important for third-party cooperation. Participants played multiple rounds of a public goods game (PGG). In Study 1, we varied personal involvement from high to low; participants played for themselves (Self), for themselves and a third party (Shared), and solely for a third party (Third Party). Participants contributed most when personal involvement was lowest (i.e., Third Party) and least when personal involvement was high (i.e., Self). Study 2 explored if social motives underlie third-party cooperation by comparing cooperation with social (human) and non-social (computer) group members. Reducing personal involvement in the PGG (i.e., Third Party) increased cooperation in social contexts compared with non-social contexts, indicating enhanced collective interest. Increased cooperation for a third party may result from taking the other's perspective, thereby increasing social norm preferences.

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

    PubMed

    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.

  4. Enhanced Cooperativity in Supported Spin-Crossover Metal-Organic Frameworks.

    PubMed

    Groizard, Thomas; Papior, Nick; Le Guennic, Boris; Robert, Vincent; Kepenekian, Mikaël

    2017-07-20

    The impact of surface deposition on cooperativity is explored in Au(111)-supported self-assembled metal-organic frameworks (MOFs) based on Fe(II) ions. Using a thermodynamic model, we first demonstrate that dimensionality reduction combined with deposition on a metal surface is likely to deeply enhance the spin-crossover cooperativity, going from γ3D = 16 K for the bulk material to γ2D(supp) = 386 K for its 2D supported derivative. On the basis of density functional theory, we then elucidate the electronic structure of a promising Fe-based MOF. A chemical strategy is proposed to turn a weakly interacting magnetic system into a strongly cooperative spin-crossover monolayer with γMOF(Au(111)) = 83 K. These results open a promising route to the fabrication of cooperative materials based on SCO Fe(II) platforms.

  5. 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. © 2012 American Chemical Society

  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. 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…

  8. 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…

  9. 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…

  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. Cooperation enhanced by indirect reciprocity in spatial prisoner's dilemma games for social P2P systems

    NASA Astrophysics Data System (ADS)

    Tian, Lin-Lin; Li, Ming-Chu; Wang, Zhen

    2016-11-01

    With the growing interest in social Peer-to-Peer (P2P) applications, relationships of individuals are further exploited to improve the performances of reputation systems. It is an on-going challenge to investigate how spatial reciprocity aids indirect reciprocity in sustaining cooperation in practical P2P environments. This paper describes the construction of an extended prisoner's dilemma game on square lattice networks with three strategies, i.e., defection, unconditional cooperation, and reciprocal cooperation. Reciprocators discriminate partners according to their reputations based on image scoring, where mistakes in judgment of reputations may occur. The independent structures of interaction and learning neighborhood are discussed, with respect to the situation in which learning environments differ from interaction networks. The simulation results have indicated that the incentive mechanism enhances cooperation better in structured peers than among a well-mixed population. Given the realistic condition of inaccurate reputation scores, defection is still successfully held down when the players interact and learn within the unified neighborhoods. Extensive simulations have further confirmed the positive impact of spatial structure on cooperation with different sizes of lattice neighborhoods. And similar conclusions can also be drawn on regular random networks and scale-free networks. Moreover, for the separated structures of the neighborhoods, the interaction network has a critical effect on the evolution dynamics of cooperation and learning environments only have weaker impacts on the process. Our findings further provide some insights concerning the evolution of collective behaviors in social systems.

  12. Synaptic amplification by dendritic spines enhances input cooperativity.

    PubMed

    Harnett, Mark T; Makara, Judit K; Spruston, Nelson; Kath, William L; Magee, Jeffrey C

    2012-11-22

    Dendritic spines are the nearly ubiquitous site of excitatory synaptic input onto neurons and as such are critically positioned to influence diverse aspects of neuronal signalling. Decades of theoretical studies have proposed that spines may function as highly effective and modifiable chemical and electrical compartments that regulate synaptic efficacy, integration and plasticity. Experimental studies have confirmed activity-dependent structural dynamics and biochemical compartmentalization by spines. However, there is a longstanding debate over the influence of spines on the electrical aspects of synaptic transmission and dendritic operation. Here we measure the amplitude ratio of spine head to parent dendrite voltage across a range of dendritic compartments and calculate the associated spine neck resistance (R(neck)) for spines at apical trunk dendrites in rat hippocampal CA1 pyramidal neurons. We find that R(neck) is large enough (~500 MΩ) to amplify substantially the spine head depolarization associated with a unitary synaptic input by ~1.5- to ~45-fold, depending on parent dendritic impedance. A morphologically realistic compartmental model capable of reproducing the observed spatial profile of the amplitude ratio indicates that spines provide a consistently high-impedance input structure throughout the dendritic arborization. Finally, we demonstrate that the amplification produced by spines encourages electrical interaction among coactive inputs through an R(neck)-dependent increase in spine head voltage-gated conductance activation. We conclude that the electrical properties of spines promote nonlinear dendritic processing and associated forms of plasticity and storage, thus fundamentally enhancing the computational capabilities of neurons.

  13. 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

  14. Identification of Filamin-A and -B as potential biomarkers for prostate cancer

    PubMed Central

    Narain, Niven R; Diers, Anne R; Lee, Arleide; Lao, Socheata; Chan, Joyce Y; Schofield, Sally; Andreazi, Joe; Ouro-Djobo, Rakibou; Jimenez, Joaquin J; Friss, Tracey; Tanna, Nikunj; Dalvi, Aditee; Wang, Sihe; Bunch, Dustin; Sun, Yezhou; Wu, Wenfang; Thapa, Khampaseuth; Gesta, Stephane; Rodrigues, Leonardo O; Akmaev, Viatcheslav R; Vishnudas, Vivek K; Sarangarajan, Rangaprasad

    2017-01-01

    Aim: A novel strategy for prostate cancer (PrCa) biomarker discovery is described. Materials & methods: In vitro perturbation biology, proteomics and Bayesian causal analysis identified biomarkers that were validated in in vitro models and clinical specimens. Results: Filamin-B (FLNB) and Keratin-19 were identified as biomarkers. Filamin-A (FLNA) was found to be causally linked to FLNB. Characterization of the biomarkers in a panel of cells revealed differential mRNA expression and regulation. Moreover, FLNA and FLNB were detected in the conditioned media of cells. Last, in patients without PrCa, FLNA and FLNB blood levels were positively correlated, while in patients with adenocarcinoma the relationship is dysregulated. Conclusion: These data support the strategy and the potential use of the biomarkers for PrCa. PMID:28344825

  15. Synaptic amplification by dendritic spines enhances input cooperativity

    PubMed Central

    Harnett, Mark T.; Makara, Judit K.; Spruston, Nelson; Kath, William L.; Magee, Jeffrey C.

    2012-01-01

    Dendritic spines are the nearly ubiquitous site of excitatory synaptic input onto neurons1–2 and as such are critically positioned to influence diverse aspects of neuronal signaling. Decades of theoretical studies have proposed that spines may function as highly effective and modifiable chemical and electrical compartments that regulate synaptic efficacy, integration, and plasticity3–8. Experimental studies have confirmed activity-dependent structural dynamics and biochemical compartmentalization by spines9–12. However, a longstanding debate remains over the influence of spines on the electrical aspects of synaptic transmission and dendritic operation3–8,13–18. Here, we measured the amplitude ratio (AR) of spine head to parent dendrite voltage across a range of dendritic compartments and calculated the associated Rneck for spines at apical trunk dendrites in hippocampal CA1 pyramidal neurons. We found that Rneck is large enough (~500 MΩ) to substantially amplify the spine head depolarization associated with a unitary synaptic input by ~1.5- to ~45-fold depending on parent dendritic impedance. A morphologically realistic compartmental model capable of reproducing the observed spatial profile of AR indicates that spines provide a consistently high impedance input structure throughout the dendritic arbor. Finally, we demonstrate that the amplification produced by spines encourages electrical interaction among coactive inputs through an Rneck-dependent increase in spine head voltage- dependent conductance activation. We conclude that the electrical properties of spines promote nonlinear dendritic processing and associated forms of plasticity and storage, thus fundamentally enhancing the computational capabilities of neurons19–21. PMID:23103868

  16. Cooperative plasmonic effect of Ag and Au nanoparticles on enhancing performance of polymer solar cells.

    PubMed

    Lu, Luyao; Luo, Zhiqiang; Xu, Tao; Yu, Luping

    2013-01-09

    This article describes a cooperative plasmonic effect on improving the performance of polymer bulk heterojunction solar cells. When mixed Ag and Au nanoparticles are incorporated into the anode buffer layer, dual nanoparticles show superior behavior on enhancing light absorption in comparison with single nanoparticles, which led to the realization of a polymer solar cell with a power conversion efficiency of 8.67%, accounting for a 20% enhancement. The cooperative plasmonic effect aroused from dual resonance enhancement of two different nanoparticles. The idea was further unraveled by comparing Au nanorods with Au nanoparticles for solar cell application. Detailed studies shed light into the influence of plasmonic nanostructures on exciton generation, dissociation, and charge recombination and transport inside thin film devices.

  17. IKAP localizes to membrane ruffles with filamin A and regulates actin cytoskeleton organization and cell migration.

    PubMed

    Johansen, Lars Dan; Naumanen, Tiina; Knudsen, Astrid; Westerlund, Nina; Gromova, Irina; Junttila, Melissa; Nielsen, Christina; Bøttzauw, Trine; Tolkovsky, Aviva; Westermarck, Jukka; Coffey, Eleanor T; Jäättelä, Marja; Kallunki, Tuula

    2008-03-15

    Loss-of-function mutations in the IKBKAP gene, which encodes IKAP (ELP1), cause familial dysautonomia (FD), with defective neuronal development and maintenance. Molecular mechanisms leading to FD are poorly understood. We demonstrate that various RNA-interference-based depletions of IKAP lead to defective adhesion and migration in several cell types, including rat primary neurons. The defects could be rescued by reintroduction of wild-type IKAP but not by FD-IKAP, a truncated form of IKAP constructed according to the mutation found in the majority of FD patients. Cytosolic IKAP co-purified with proteins involved in cell migration, including filamin A, which is also involved in neuronal migration. Immunostaining of IKAP and filamin A revealed a distinct co-localization of these two proteins in membrane ruffles. Depletion of IKAP resulted in a significant decrease in filamin A localization in membrane ruffles and defective actin cytoskeleton organization, which both could be rescued by the expression of wild-type IKAP but not by FD-IKAP. No downregulation in the protein levels of paxillin or beclin 1, which were recently described as specific transcriptional targets of IKAP, was detected. These results provide evidence for the role of the cytosolic interactions of IKAP in cell adhesion and migration, and support the notion that cell-motility deficiencies could contribute to FD.

  18. Interaction of TIF-90 and filamin A in the regulation of rRNA synthesis in leukemic cells.

    PubMed

    Nguyen, Le Xuan Truong; Chan, Steven M; Ngo, Tri Duc; Raval, Aparna; Kim, Kyeong Kyu; Majeti, Ravindra; Mitchell, Beverly S

    2014-07-24

    The transcription initiation factor I (TIF-IA) is an important regulator of the synthesis of ribosomal RNA (rRNA) through its facilitation of the recruitment of RNA polymerase I (Pol I) to the ribosomal DNA promoter. Activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, which occurs commonly in acute myelogenous leukemia, enhances rRNA synthesis through TIF-IA stabilization and phosphorylation. We have discovered that TIF-IA coexists with a splicing isoform, TIF-90, which is expressed preferentially in the nucleolus and at higher levels in proliferating and transformed hematopoietic cells. TIF-90 interacts directly with Pol I to increase rRNA synthesis as a consequence of Akt activation. Furthermore, TIF-90 binds preferentially to a 90-kDa cleavage product of the actin binding protein filamin A (FLNA) that inhibits rRNA synthesis. Increased expression of TIF-90 overcomes the inhibitory effect of this cleavage product and stimulates rRNA synthesis. Because activated Akt also reduces FLNA cleavage, these results indicate that activated Akt and TIF-90 function in parallel to increase rRNA synthesis and, as a consequence, cell proliferation in leukemic cells. These results provide evidence that the direct targeting of Akt would be an effective therapy in acute leukemias in which Akt is activated. © 2014 by The American Society of Hematology.

  19. 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.

  20. Spatio-temporal profiling of Filamin A RNA-editing reveals ADAR preferences and high editing levels outside neuronal tissues

    PubMed Central

    Stulić, Maja; Jantsch, Michael F

    2013-01-01

    RNA editing by ADARs can change the coding potential of protein-coding mRNAs. So far, this type of RNA editing has mainly been shown to affect RNAs expressed in the nervous system with much lower editing levels being observed in other tissues. The actin crosslinking proteins filamin α and filamin β are widely expressed in most tissues. The mRNAs encoding either protein are edited at the same position leading to a conserved Q to R exchange in both proteins. Using bar-coded next generation sequencing, we show that editing of filamin α is most abundant in the gastrointestinal tract and only to a lesser extent in the nervous system. Using knockout mice, we show that ADARB1 (ADAR2) is responsible for the majority of FLNA editing, while ADAR1 can edit filamin α mRNA in some tissues quite efficiently. Interestingly, editing levels of filamin α and β do not follow the same trend across tissues, suggesting a substrate-specific regulation of editing. PMID:24025532

  1. Cooperative enhancement of deoxyribozyme activity by chemical modification and added cationic copolymer

    PubMed Central

    Saito, Ken; Shimada, Naohiko; Maruyama, Atushi

    2016-01-01

    Abstract Deoxyribozymes (DNAzymes) having RNA-cleaving activity have widely been explored as tools for therapeutic and diagnostic purposes. Both the chemical cleaving step and the turnover step should be improved for enhancing overall activity of DNAzymes. We have shown that cationic copolymer enhanced DNAzyme activity by increasing turnover efficacy. In this paper, effects of the copolymer on DNAzymes modified with locked nucleic acids (LNA) or 2′-O-methylated (2′-OMe) nucleic acids were studied. The copolymer increased activity of these chemically modified DNAzymes. More than 30-fold enhancement in multiple-turnover catalytic activity was observed with 2′-OMe-modified DNAzyme in the presence of the copolymer. DNAzyme catalytic activity was successfully enhanced by cooperation of the added copolymer and chemical modification of DNAzyme. PMID:27877894

  2. Cell type-specific filamin complex regulation by a novel class of HECT ubiquitin ligase is required for normal cell motility and patterning

    PubMed Central

    Blagg, Simone L.; Battom, Suzanne E.; Annesley, Sarah J.; Keller, Thomas; Parkinson, Katie; Wu, Jasmine M. F.; Fisher, Paul R.; Thompson, Christopher R. L.

    2011-01-01

    Differential cell motility, which plays a key role in many developmental processes, is perhaps most evident in examples of pattern formation in which the different cell types arise intermingled before sorting out into discrete tissues. This is thought to require heterogeneities in responsiveness to differentiation-inducing signals that result in the activation of cell type-specific genes and ‘salt and pepper’ patterning. How differential gene expression results in cell sorting is poorly defined. Here we describe a novel gene (hfnA) that provides the first mechanistic link between cell signalling, differential gene expression and cell type-specific sorting in Dictyostelium. HfnA defines a novel group of evolutionarily conserved HECT ubiquitin ligases with an N-terminal filamin domain (HFNs). HfnA expression is induced by the stalk differentiation-inducing factor DIF-1 and is restricted to a subset of prestalk cells (pstO). hfnA− pstO cells differentiate but their sorting out is delayed. Genetic interactions suggest that this is due to misregulation of filamin complex activity. Overexpression of filamin complex members phenocopies the hfnA− pstO cell sorting defect, whereas disruption of filamin complex function in a wild-type background results in pstO cells sorting more strongly. Filamin disruption in an hfnA− background rescues pstO cell localisation. hfnA− cells exhibit altered slug phototaxis phenotypes consistent with filamin complex hyperactivity. We propose that HfnA regulates filamin complex activity and cell type-specific motility through the breakdown of filamin complexes. These findings provide a novel mechanism for filamin regulation and demonstrate that filamin is a crucial mechanistic link between responses to differentiation signals and cell movement in patterning based on ‘salt and pepper’ differentiation and sorting out. PMID:21389049

  3. 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.

  4. Rac1 is deactivated at integrin activation sites through an IQGAP1–filamin-A–RacGAP1 pathway

    PubMed Central

    Jacquemet, Guillaume; Morgan, Mark R.; Byron, Adam; Humphries, Jonathan D.; Choi, Colin K.; Chen, Christopher S.; Caswell, Patrick T.; Humphries, Martin J.

    2013-01-01

    Summary Cell migration makes a fundamental contribution to both normal physiology and disease pathogenesis. Integrin engagement with extracellular ligands spatially controls, via the cyclical activation and deactivation of the small GTPase Rac1, the dynamic membrane protrusion and cytoskeletal reorganization events that are required for directional migration. Although the pathways that control integrin-mediated Rac1 activation are reasonably well defined, the mechanisms that are responsible for switching off activity are poorly understood. Here, proteomic analysis of activated integrin-associated complexes suggests filamin-A and IQ-motif-containing GTPase-activating protein 1 (IQGAP1) as candidates that link β1 integrin to Rac1. siRNA-mediated knockdown of either filamin-A or IQGAP1 induced high, dysregulated Rac1 activity during cell spreading on fibronectin. Using immunoprecipitation and immunocytochemistry, filamin-A and IQGAP1 were shown to be part of a complex that is recruited to active β1 integrin. Mass spectrometric analysis of individual filamin-A, IQGAP1 and Rac1 pull-downs and biochemical analysis, identified RacGAP1 as a novel IQGAP1 binding partner. Further immunoprecipitation and immunocytochemistry analyses demonstrated that RacGAP1 is recruited to IQGAP1 and active β1 integrin, and that suppression of RacGAP1 expression triggered elevated Rac1 activity during spreading on fibronectin. Consistent with these findings, reduced expression of filamin-A, IQGAP1 or RacGAP1 triggered unconstrained membrane protrusion and disrupted directional cell migration on fibrillar extracellular matrices. These findings suggest a model whereby integrin engagement, followed by filamin-A, IQGAP1 and RacGAP1 recruitment, deactivates Rac1 to constrain its activity spatially and thereby coordinate directional cell migration. PMID:23843620

  5. Cooperative enhancement of the nonlinear optical response in conjugated energetic materials: A TD-DFT study.

    PubMed

    Sifain, Andrew E; Tadesse, Loza F; Bjorgaard, Josiah A; Chavez, David E; Prezhdo, Oleg V; Scharff, R Jason; Tretiak, Sergei

    2017-03-21

    Conjugated energetic molecules (CEMs) are a class of explosives with high nitrogen content that posses both enhanced safety and energetic performance properties and are ideal for direct optical initiation. As isolated molecules, they absorb within the range of conventional lasers. Crystalline CEMs are used in practice, however, and their properties can differ due to intermolecular interaction. Herein, time-dependent density functional theory was used to investigate one-photon absorption (OPA) and two-photon absorption (TPA) of monomers and dimers obtained from experimentally determined crystal structures of CEMs. OPA scales linearly with the number of chromophore units, while TPA scales nonlinearly, where a more than 3-fold enhancement in peak intensity, per chromophore unit, is calculated. Cooperative enhancement depends on electronic delocalization spanning both chromophore units. An increase in sensitivity to nonlinear laser initiation makes these materials suitable for practical use. This is the first study predicting a cooperative enhancement of the nonlinear optical response in energetic materials composed of relatively small molecules. The proposed model quantum chemistry is validated by comparison to crystal structure geometries and the optical absorption of these materials dissolved in solution.

  6. Cooperative enhancement of the nonlinear optical response in conjugated energetic materials: A TD-DFT study

    DOE PAGES

    Sifain, Andrew E.; Tadesse, Loza F.; Bjorgaard, Josiah August; ...

    2017-03-21

    Conjugated energetic molecules (CEMs) are a class of explosives with high nitrogen content that posses both enhanced safety and energetic performance properties and are ideal for direct optical initiation. As isolated molecules, they absorb within the range of conventional lasers. Crystalline CEMs are used in practice, however, and their properties can differ due to intermolecular interaction. Herein, time-dependent density functional theory was used to investigate one-photon absorption (OPA) and two-photon absorption (TPA) of monomers and dimers obtained from experimentally determined crystal structures of CEMs. OPA scales linearly with the number of chromophore units, while TPA scales nonlinearly, where a moremore » than 3-fold enhancement in peak intensity, per chromophore unit, is calculated. Cooperative enhancement depends on electronic delocalization spanning both chromophore units. An increase in sensitivity to nonlinear laser initiation makes these materials suitable for practical use. This is the first study predicting a cooperative enhancement of the nonlinear optical response in energetic materials composed of relatively small molecules. Finally, the proposed model quantum chemistry is validated by comparison to crystal structure geometries and the optical absorption of these materials dissolved in solution.« less

  7. Cooperative enhancement of the nonlinear optical response in conjugated energetic materials: A TD-DFT study

    NASA Astrophysics Data System (ADS)

    Sifain, Andrew E.; Tadesse, Loza F.; Bjorgaard, Josiah A.; Chavez, David E.; Prezhdo, Oleg V.; Scharff, R. Jason; Tretiak, Sergei

    2017-03-01

    Conjugated energetic molecules (CEMs) are a class of explosives with high nitrogen content that posses both enhanced safety and energetic performance properties and are ideal for direct optical initiation. As isolated molecules, they absorb within the range of conventional lasers. Crystalline CEMs are used in practice, however, and their properties can differ due to intermolecular interaction. Herein, time-dependent density functional theory was used to investigate one-photon absorption (OPA) and two-photon absorption (TPA) of monomers and dimers obtained from experimentally determined crystal structures of CEMs. OPA scales linearly with the number of chromophore units, while TPA scales nonlinearly, where a more than 3-fold enhancement in peak intensity, per chromophore unit, is calculated. Cooperative enhancement depends on electronic delocalization spanning both chromophore units. An increase in sensitivity to nonlinear laser initiation makes these materials suitable for practical use. This is the first study predicting a cooperative enhancement of the nonlinear optical response in energetic materials composed of relatively small molecules. The proposed model quantum chemistry is validated by comparison to crystal structure geometries and the optical absorption of these materials dissolved in solution.

  8. Circulating anti-filamin C autoantibody as a potential serum biomarker for low-grade gliomas

    PubMed Central

    2014-01-01

    Background Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable due to its invasive nature. Establishment of serum biomarkers for glioma would be beneficial both for early diagnosis and adequate therapeutic intervention. Filamins are an actin cross-linker and filamin C (FLNC), normally restricted in muscle tissues, offers many signaling molecules an essential communication fields. Recently, filamins have been considered important for tumorigenesis in cancers. Methods We searched for novel glioma-associated antigens by serological identification of antigens utilizing recombinant cDNA expression cloning (SEREX), and found FLNC as a candidate protein. Tissue expressions of FLNC (both in normal and tumor tissues) were examined by immunohistochemistry and quantitative RT-PCR analyses. Serum anti-FLNC autoantibody level was measured by ELISA in normal volunteers and in the patients with various grade gliomas. Results FLNC was expressed in glioma tissues and its level got higher as tumor grade advanced. Anti-FLNC autoantibody was also detected in the serum of glioma patients, but its levels were inversely correlated with the tissue expression. Serum anti-FLNC autoantibody level was significantly higher in low-grade glioma patients than in high-grade glioma patients or in normal volunteers, which was confirmed in an independent validation set of patients’ sera. The autoantibody levels in the patients with meningioma or cerebral infarction were at the same level of normal volunteers, and they were significantly lower than that of low-grade gliomas. Total IgG and anti-glutatione S-transferase (GST) antibody level were not altered among the patient groups, which suggest that the autoantibody response was specific for FLNC. Conclusions The present results suggest that serum anti-FLNC autoantibody can be a potential serum biomarker for early diagnosis of low-grade gliomas while it needs a large-scale clinical study

  9. Structure of filamin A immunoglobulin-like repeat 10 from Homo sapiens.

    PubMed

    Page, Richard C; Clark, Jeffrey G; Misra, Saurav

    2011-08-01

    Filamin A (FlnA) plays a critical role in cytoskeletal organization, cell motility and cellular signaling. FlnA utilizes different binding sites on a series of 24 immunoglobulin-like domains (Ig repeats) to interact with diverse cytosolic proteins and with cytoplasmic portions of membrane proteins. Mutations in a specific domain, Ig10 (FlnA-Ig10), are correlated with two severe forms of the otopalatodigital syndrome spectrum disorders Melnick-Needles syndrome and frontometaphyseal dysplasia. The crystal structure of FlnA-Ig10 determined at 2.44 Å resolution provides insight into the perturbations caused by these mutations.

  10. 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

  11. Natural discharge after pulse and cooperative electrodes to enhance droplet velocity in digital microfluidics

    SciTech Connect

    Chen, Tianlan; Dong, Cheng; Gao, Jie; Jia, Yanwei; Mak, Pui-In Vai, Mang-I; Martins, Rui P.

    2014-04-15

    Digital Microfluidics (DMF) is a promising technology for biological/chemical micro-reactions due to its distinct droplet manageability via electronic automation, but the limited velocity of droplet transportation has hindered DMF from utilization in high throughput applications. In this paper, by adaptively fitting the actuation voltages to the dynamic motions of droplet movement under real-time feedback monitoring, two control-engaged electrode-driving techniques: Natural Discharge after Pulse (NDAP) and Cooperative Electrodes (CE) are proposed. They together lead to, for the first time, enhanced droplet velocity with lower root mean square voltage value.

  12. 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

  13. Identification of Filamin as a Novel Ligand for Caveolin-1: Evidence for the Organization of Caveolin-1–associated Membrane Domains by the Actin Cytoskeleton

    PubMed Central

    Stahlhut, Martin; van Deurs, Bo

    2000-01-01

    Reports on the ultrastructure of cells as well as biochemical data have, for several years, been indicating a connection between caveolae and the actin cytoskeleton. Here, using a yeast two-hybrid approach, we have identified the F-actin cross-linking protein filamin as a ligand for the caveolae-associated protein caveolin-1. Binding of caveolin-1 to filamin involved the N-terminal region of caveolin-1 and the C terminus of filamin close to the filamin-dimerization domain. In in vitro binding assays, recombinant caveolin-1 bound to both nonmuscle and muscle filamin, indicating that the interaction might not be cell type specific. With the use of confocal microscopy, colocalization of caveolin-1 and filamin was observed in elongated patches at the plasma membrane. Remarkably, when stress fiber formation was induced with Rho-stimulating Escherichia coli cytotoxic necrotizing factor 1, the caveolin-1–positive structures became coaligned with stress fibers, indicating that there was a physical link connecting them. Immunogold double-labeling electron microscopy confirmed that caveolin-1–labeled racemose caveolae clusters were positive for filamin. The actin network, therefore, seems to be directly involved in the spatial organization of caveolin-1–associated membrane domains. PMID:10637311

  14. Tead proteins activate the Foxa2 enhancer in the node in cooperation with a second factor.

    PubMed

    Sawada, Atsushi; Nishizaki, Yuriko; Sato, Hiroko; Yada, Yukari; Nakayama, Rika; Yamamoto, Shinji; Nishioka, Noriyuki; Kondoh, Hisato; Sasaki, Hiroshi

    2005-11-01

    The cell population and the activity of the organizer change during the course of development. We addressed the mechanism of mouse node development via an analysis of the node/notochord enhancer (NE) of Foxa2. We first identified the core element (CE) of the enhancer, which in multimeric form drives gene expression in the node. The CE was activated in Wnt/beta-catenin-treated P19 cells with a time lag, and this activation was dependent on two separate sequence motifs within the CE. These same motifs were also required for enhancer activity in transgenic embryos. We identified the Tead family of transcription factors as binding proteins for the 3' motif. Teads and their co-factor YAP65 activated the CE in P19 cells, and binding of Tead to CE was essential for enhancer activity. Inhibition of Tead activity by repressor-modified Tead compromised NE enhancer activation and notochord development in transgenic mouse embryos. Furthermore, manipulation of Tead activity in zebrafish embryos led to altered expression of foxa2 in the embryonic shield. These results suggest that Tead activates the Foxa2 enhancer core element in the mouse node in cooperation with a second factor that binds to the 5' element, and that a similar mechanism also operates in the zebrafish shield.

  15. Dependence of evolutionary cooperation on the additive noise to the enhancement level in the spatial public goods game

    NASA Astrophysics Data System (ADS)

    Jia, Chun-Xiao; Liu, Run-Ran; Rong, Zhihai

    2017-03-01

    Either in societies or economic cycles, the benefits of a group can be affected by various unpredictable factors. We study effects of additive spatiotemporal random variations on the evolution of cooperation by introducing them to the enhancement level of the spatial public goods game. Players are located on the sites of a two-dimensional lattice and gain their payoffs from games with their neighbors by choosing cooperation or defection. We observe that a moderate intensity of variations can best favor cooperation at low enhancement levels, which resembles classical coherence resonance. Whereas for high enhancement levels, we find that the random variations cannot increase the cooperation level, but hamper cooperation instead. This discrepancy is attributed to the different roles the additive variations played in the early and late stages of evolution. In the early stage of evolution, the additive variations increase the survival probability of the players with lower average payoffs. However, in the late stage of evolution, the additive variations can promote defectors to destroy the cooperative clusters that have been formed. Our results indicate that additive spatiotemporal noise may not be as universally beneficial for cooperation as the spatial prisoner's dilemma game.

  16. Differential expression of filamin B splice variants in giant cell tumor cells

    PubMed Central

    Tsui, Joseph Chi-Ching; Lau, Carol Po-Ying; Cheung, Alex Chun; Wong, Kwok-Chuen; Huang, Lin; Tsui, Stephen Kwok-Wing; Kumta, Shekhar Madhukar

    2016-01-01

    Giant cell tumor of bone (GCT) is the most commonly reported non-malignant bone tumor in Hong Kong. This kind of tumor usually affects people aged 20–40 years. Also, it is well known for recurrence locally, especially when the tumor cannot be removed completely. Filamins are actin-binding proteins which contain three family members, filamin A, B and C. They are the products of three different genes, FLNA, FLNB and FLNC, which can generate various transcript variants in different cell types. In this study, we focused on the effects of FLNBv2 and FLNBv4 toward GCT cells. The only difference between FLNBv2 and FLNBv4 is that FLNBv4 does not contain hinge 1 region. We found that the relative abundance of FLNBv4 varies among different GCT cell lines while the expression level of FLNBv4 in normal osteoblasts was only marginally detectable. In the functional aspect, overexpression of FLNBv4 led to upregulation of RANKL, OCN, OPG and RUNX2, which are closely related to GCT cell survival and differentiation. Moreover, FLNBv4 can have a negative effect on cell viability of GCT cells when compare with FLNBv2. In conclusion, splicing variants of FLNB are differentially expressed in GCT cells and may play a role in the proliferation and differentiation of tumor cells. PMID:27779699

  17. Actin binding domain of filamin distinguishes posterior from anterior actin filaments in migrating Dictyostelium cells

    PubMed Central

    Shibata, Keitaro; Nagasaki, Akira; Adachi, Hiroyuki; Uyeda, Taro Q. P.

    2016-01-01

    Actin filaments in different parts of a cell interact with specific actin binding proteins (ABPs) and perform different functions in a spatially regulated manner. However, the mechanisms of those spatially-defined interactions have not been fully elucidated. If the structures of actin filaments differ in different parts of a cell, as suggested by previous in vitro structural studies, ABPs may distinguish these structural differences and interact with specific actin filaments in the cell. To test this hypothesis, we followed the translocation of the actin binding domain of filamin (ABDFLN) fused with photoswitchable fluorescent protein (mKikGR) in polarized Dictyostelium cells. When ABDFLN-mKikGR was photoswitched in the middle of a polarized cell, photoswitched ABDFLN-mKikGR rapidly translocated to the rear of the cell, even though actin filaments were abundant in the front. The speed of translocation (>3 μm/s) was much faster than that of the retrograde flow of cortical actin filaments. Rapid translocation of ABDFLN-mKikGR to the rear occurred normally in cells lacking GAPA, the only protein, other than actin, known to bind ABDFLN. We suggest that ABDFLN recognizes a certain feature of actin filaments in the rear of the cell and selectively binds to them, contributing to the posterior localization of filamin. PMID:28409084

  18. Motion depending on the strategies of players enhances cooperation in a co-evolutionary prisoner's dilemma game

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

    In the evolution of cooperation, the motion of players plays an important role. In this paper, we incorporate, into an evolutionary prisoner dilemma's game on networks, a new factor that cooperators and defectors move with different probabilities. By investigating the dependence of the cooperator frequency on the moving probabilities of cooperators and defectors, μc and μd, we find that cooperation is greatly enhanced in the parameter regime of μc<μd. The snapshots of strategy pattern and the evolutions of cooperator clusters and defector clusters reveal that either the fast motion of defectors or the slow motion of cooperators always favors the formation of large cooperator clusters. The model is investigated on different types of networks such as square lattices, Erdös-Rényi networks and scale-free networks and with different types of strategy-updating rules such as the richest-following rule and the Fermi rule. The numerical results show that the observed phenomena are robust to different networks and to different strategy-updating rules.

  19. 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.

  20. 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.

  1. 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.

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

    PubMed

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

    2015-09-09

    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.

  3. Cooperative translocation enhances the unwinding of duplex DNA by SARS coronavirus helicase nsP13.

    PubMed

    Lee, Na-Ra; Kwon, Hyun-Mi; Park, Kkothanahreum; Oh, Sangtaek; Jeong, Yong-Joo; Kim, Dong-Eun

    2010-11-01

    SARS coronavirus encodes non-structural protein 13 (nsP13), a nucleic acid helicase/NTPase belonging to superfamily 1 helicase, which efficiently unwinds both partial-duplex RNA and DNA. In this study, unwinding of DNA substrates that had different duplex lengths and 5'-overhangs was examined under single-turnover reaction conditions in the presence of excess enzyme. The amount of DNA unwound decreased significantly as the length of the duplex increased, indicating a poor in vitro processivity. However, the quantity of duplex DNA unwound increased as the length of the single-stranded 5'-tail increased for the 50-bp duplex. This enhanced processivity was also observed for duplex DNA that had a longer single-stranded gap in between. These results demonstrate that nsP13 requires the presence of a long 5'-overhang to unwind longer DNA duplexes. In addition, enhanced DNA unwinding was observed for gapped DNA substrates that had a 5'-overhang, indicating that the translocated nsP13 molecules pile up and the preceding helicase facilitate DNA unwinding. Together with the propensity of oligomer formation of nsP13 molecules, we propose that the cooperative translocation by the functionally interacting oligomers of the helicase molecules loaded onto the 5'-overhang account for the observed enhanced processivity of DNA unwinding.

  4. 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

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

    SciTech Connect

    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. - Highlights: • RhoGDI2 is identified as a potential filamin A (FLNA)-binding partner. • Phosphomimetic mutant, RhoGDI2(Tyr153Glu) interacts with FLNA. • RhoGDI2 phosphorylated (Tyr153) by src kinase does not interact with FLNA. • Mutation of Tyr-153 to Glu of RhoGDI2 does not mimic phosphorylation. • RhoGDI2(Tyr153Glu) provokes an adventitious interaction with FLNA.

  6. Metformin enhances glucagon-like peptide 1 via cooperation between insulin and Wnt signaling.

    PubMed

    Kim, Mi-Hyun; Jee, Jae-Hwan; Park, Sunyoung; Lee, Myung-Shik; Kim, Kwang-Won; Lee, Moon-Kyu

    2014-02-01

    One aspect of the effects of metformin on glucagon-like peptide (GLP)-1 might be associated with the mechanism by which the cross talk between insulin and Wnt signaling enhances GLP1 secretion, due to the action of metformin as an insulin sensitizer. However, this remains completely unknown. In this study, we have investigated the mechanisms of the action of metformin on cross talk between insulin and Wnt signaling. GLP1 enhancement by meformin was determined in human NCI-H716 intestinal L-cells and hyperglycemic db/db mice treated with metformin (0.25 and 0.5 mM and/or 12.5 mg/kg body weight) for 24 h and 2 months. Metformin increased GLP1 secretion in L-cells and db/db mice. Metformin stimulated the nuclear translocation of β-catenin and TOPflash reporter activity, and gene depletion of β-catenin or enhancement of mutation of transcription factor 7-like 2 binding site offset GLP1. In addition, insulin receptor substrate 2 gene depletion blocked metformin-enhanced β-catenin translocation. These effects were preceded by an increase in glucose utilization and calcium influx, the activation of calcium-dependent protein kinase, and, in turn, the activation of insulin signaling, and the inhibition of glycogen synthase kinase 3β, a potent inhibitor of β-catenin. Furthermore, high blood glucose levels were controlled via GLP1 receptor-dependent insulinotropic pathways in db/db mice, which were evidenced by the increase in GLP1 and insulin levels at 30 min after oral glucose loading and pancreatic insulinotropic gene expression. Our findings indicate that the cooperation between Wnt and its upstream insulin signaling pathways might be a novel and important mechanism underlying the effects of metformin on GLP1 production.

  7. Organic nanoclusters for nonlinear optics: from model systems to cooperative nanoassemblies with enhanced NLO responses

    NASA Astrophysics Data System (ADS)

    Terenziani, Francesca; Parthasarathy, Venkatakrishnan; Ghosh, Sampa; Pandey, Ravindra; Das, Puspendu K.; Blanchard-Desce, Mireille

    2009-08-01

    While structure-properties relationships are quite actively and successfully investigated at the molecular level of engineering of optical nonlinear responses, supramolecular structure-property relationships are an appealing field. The realization that interchromophoric interactions between strongly polar/polarizable NLO chromophores can significantly affect the NLO response of each chromophoric unit as well as promote associations has opened new dimensions for molecular design. Several elegant routes have been implemented to hinder or counterbalance dipole-dipole interactions between dipolar NLO chromophores for the elaboration of second-order materials (for SHG or electro-optical modulation). At opposite, we have implemented a reverse strategy by confining discrete numbers of NLO push-pull chromophores in close proximity within covalent organic nanoclusters with the aim to exploit interchromophoric interactions in order to achieve enhanced NLO responses. As a proof of concept, we present here the investigation of two-series of multichromophoric covalent assemblies built from NLO push-pull chromophores showing that cooperative enhancement can be achieved both for second-order optical responses (first hyperpolarizabilities) or third-order responses (two-photon absorption cross-sections).

  8. Plasmon-enhanced molecular electroluminescence: Effects of nonlinear excitation and molecular cooperativity

    NASA Astrophysics Data System (ADS)

    Zhang, Yuan; May, Volkhard

    2014-06-01

    Plasmon enhanced electroluminescence of a single as well as a couple of molecules is discussed theoretically. The considered system is formed by a metal nanoparticle (MNP) placed in the proximity of a junction with molecules sandwiched between a left and a right lead. In continuing recent work on a junction with a single molecule [Phys. Rev. B 88, 155426 (2013), 10.1103/PhysRevB.88.155426] the case of strong charge injection and resulting further enhanced electroluminescence is investigated. Photoemission and plasmon excitation saturate if the molecule-lead coupling enters a range of about 50 meV. This saturation appears long before the molecule-lead coupling approaches the limit at which the considered sequential type of charge transfer becomes invalid. Turning to junctions with up to five molecules stronger plasmon excitation is achieved and a noticeable population of the second and third excited dipole plasmon level appears. This goes along with a nonlinear increase of the photoemission intensity and a decrease of the emission linewidth displaying the onset of cooperative molecule-MNP coupling.

  9. 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

  10. 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…

  11. 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…

  12. 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.

  13. 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

  14. Enhancement of cooperation in the spatial prisoner's dilemma with a coherence-resonance effect through annealed randomness at a cooperator-defector boundary; comparison of two variant models

    NASA Astrophysics Data System (ADS)

    Tanimoto, Jun

    2016-11-01

    Inspired by the commonly observed real-world fact that people tend to behave in a somewhat random manner after facing interim equilibrium to break a stalemate situation whilst seeking a higher output, we established two models of the spatial prisoner's dilemma. One presumes that an agent commits action errors, while the other assumes that an agent refers to a payoff matrix with an added random noise instead of an original payoff matrix. A numerical simulation revealed that mechanisms based on the annealing of randomness due to either the action error or the payoff noise could significantly enhance the cooperation fraction. In this study, we explain the detailed enhancement mechanism behind the two models by referring to the concepts that we previously presented with respect to evolutionary dynamic processes under the names of enduring and expanding periods.

  15. Cooperative enhancement of TPA in cruciform double-chain DSB derivation: a femtosecond transient absorption spectra study

    NASA Astrophysics Data System (ADS)

    He, X.; Wang, Y.; Yang, Z.; Ma, Y.; Yang, Y.

    2010-09-01

    Femtosecond time-resolved transient absorption (TA) spectra study was adopted to study the mechanism of the cooperative enhancement of two-photon absorption (TPA) cross section from the linear structure 1,4-di(4'-N,N-diphenylaminostyryl)benzene (DPA-DSB) to its cruciform double-chain dimer DPA-TSB. The results suggested that a non-emissive intramolecular charge-transfer (ICT) state, ICT’, was present upon excitation in the dimer, which was absent in the monomer. The existence of this non-emissive state, indicating the enhancement of the intramolecular charge-transfer of the dimer, should be the reason for the cooperative enhancement of the TPA cross section of the dimer compared to the monomer.

  16. Cooperatively enhanced ionic hydrogen bonds in Cl-(CH3OH)(1-3)Ar clusters.

    PubMed

    Beck, Jordan P; Lisy, James M

    2010-09-23

    Infrared predissociation (IRPD) spectra of Cl−(CH3OH)1-3Ar and Cl-(CH3OD)1-3Ar were obtained in the OH and CH stretching regions. The use of methanol-d1 was necessary to distinguish between CH stretches and hydrogen-bonded OH features. The spectra of Cl-(CH3OH)2-3Ar show intense features at frequencies lower than the CH stretches, indicating structures with very strong hydrogen bonds. These strong hydrogen bonds arise from structures in which a Cl-···methanol ionic hydrogen bond is cooperatively enhanced by the presence of a second shell and, in the case of Cl-(CH3OH)3Ar, a third shell methanol. The strongest hydrogen bond is observed in the Cl-(CH3OH)3Ar spectrum at 2733 cm-1, shifted a remarkable -948 cm-1 from the neutral, gas-phase methanol value. Harmonic, ab initio frequency calculations are not adequate in describing these strong hydrogen bonds. Therefore, we describe a simple computational approach to better approximate the hydrogen bond frequencies. Overall, the results of this study indicate that high-energy isomers are very efficiently trapped using our experimental method of introducing Cl- into neutral, cold methanol-argon clusters.

  17. 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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. All-fiber transparent piezoelectric harvester with a cooperatively enhanced structure

    NASA Astrophysics Data System (ADS)

    Fuh, Yiin-Kuen; Ho, Hsi-Chun; Wang, Bo-Sheng; Li, Shan-Chien

    2016-10-01

    In this paper, we demonstrated a highly-flexible all-fiber based transparent piezoelectric harvester (ATPH) by using the direct-write, near-field electrospinning (NFES) technique and polyvinylidene fluoride (PVDF) micro/nano fibers (MNFs) as source materials. Here, we comprehensively show that transferred high performance transparent electrodes with Au-coated nanowire (NW) electrodes can be obtained using a facile and scalable combined fabrication route of both electrospinning and sputtering processes. Au-coated MNFs of a.c. 110 nm thick can significantly reduce junction resistance, which results in high transmittance (90%) at low sheet resistance (175 Ω sq-1). The Au-coated MNFs electrodes also show great flexibility and stretchability, which easily surpass the brittleness of indium tin oxide (ITO) films. Further improvement in ATPH performance was realized by rolling the device into a cylindrical shape, resulting in an increase in power output due to the cooperatively enhanced effect. The rolled ATPH with 0.34 cm diameter produces a high output voltage of ˜4.1 V, current ˜295 nA at a strain of 0.5% and 5 hz. This can efficiently run commercially available electronic components in a self-powered mode without any external electrical supply.

  19. All-fiber transparent piezoelectric harvester with a cooperatively enhanced structure.

    PubMed

    Fuh, Yiin-Kuen; Ho, Hsi-Chun; Wang, Bo-Sheng; Li, Shan-Chien

    2016-10-28

    In this paper, we demonstrated a highly-flexible all-fiber based transparent piezoelectric harvester (ATPH) by using the direct-write, near-field electrospinning (NFES) technique and polyvinylidene fluoride (PVDF) micro/nano fibers (MNFs) as source materials. Here, we comprehensively show that transferred high performance transparent electrodes with Au-coated nanowire (NW) electrodes can be obtained using a facile and scalable combined fabrication route of both electrospinning and sputtering processes. Au-coated MNFs of a.c. 110 nm thick can significantly reduce junction resistance, which results in high transmittance (90%) at low sheet resistance (175 Ω sq(-1)). The Au-coated MNFs electrodes also show great flexibility and stretchability, which easily surpass the brittleness of indium tin oxide (ITO) films. Further improvement in ATPH performance was realized by rolling the device into a cylindrical shape, resulting in an increase in power output due to the cooperatively enhanced effect. The rolled ATPH with 0.34 cm diameter produces a high output voltage of ∼4.1 V, current ∼295 nA at a strain of 0.5% and 5 hz. This can efficiently run commercially available electronic components in a self-powered mode without any external electrical supply.

  20. 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.

  1. 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 using…

  2. 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 using…

  3. 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…

  4. 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…

  5. 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…

  6. Filamin A-Bound PEBP2β/CBFβ Is Retained in the Cytoplasm and Prevented from Functioning as a Partner of the Runx1 Transcription Factor

    PubMed Central

    Yoshida, Naomi; Ogata, Takehiro; Tanabe, Kenji; Li, Songhua; Nakazato, Megumi; Kohu, Kazuyoshi; Takafuta, Toshiro; Shapiro, Sandor; Ohta, Yasutaka; Satake, Masanobu; Watanabe, Toshio

    2005-01-01

    The heterodimeric transcription factor PEBP2/CBF is composed of a DNA-binding subunit, called Runx1, and a non-DNA-binding subunit, called PEBP2β/CBFβ. The Runx1 protein is detected exclusively in the nuclei of most cells and tissues, whereas PEBP2β is located in the cytoplasm. We addressed the mechanism by which PEBP2β localizes to the cytoplasm and found that it is associated with filamin A, an actin-binding protein. Filamin A retains PEBP2β in the cytoplasm, thereby hindering its engagement as a Runx1 partner. The interaction with filamin A is mediated by a region within PEBP2β that includes amino acid residues 68 to 93. The deletion of this region or the repression of filamin A enables PEBP2β to translocate to the nucleus. Based on these observations, we propose that PEBP2β has two distinct domains, a newly defined regulatory domain that interacts with filamin A and the previously identified Runx1-binding domain. PMID:15657428

  7. 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

  8. Enhanced old-new recognition and source memory for faces of cooperators and defectors in a social-dilemma game.

    PubMed

    Bell, Raoul; Buchner, Axel; Musch, Jochen

    2010-12-01

    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 interaction took place. In a surprise memory test, old-new recognition for faces and source memory for the associated cooperative or non-cooperative behavior were assessed. A multinomial model was used to measure old-new discrimination, source memory, and guessing biases separately. Inconsistent with the assumption of a memory mechanism that focuses exclusively on cheating, the present study showed enhanced old-new discrimination and source memory for both cooperators and defectors. Rarity of the behavior strategies within the experiment modulated source memory, but only when the differences in base rates were extreme. The findings can be attributed to a mechanism that focuses on exchange-relevant information and flexibly adapts to take into account the relative significance of this information in the encoding context, which may be more beneficial than focusing exclusively on cheaters. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Molecular mechanisms of cooperative binding of transcription factors Runx1-CBFβ-Ets1 on the TCRα gene enhancer.

    PubMed

    Kasahara, Kota; Shiina, Masaaki; Fukuda, Ikuo; Ogata, Kazuhiro; Nakamura, Haruki

    2017-01-01

    Ets1 is an essential transcription factor (TF) for several important physiological processes, including cell proliferation and differentiation. Its recognition of the enhancer region of the TCRα gene is enhanced by the cooperative binding of the Runx1-CBFβ heterodimer, with the cancelation of phosphorylation-dependent autoinhibition. The detailed mechanism of this interesting cooperativity between Ets1 and the Runx1-CBFβ heterodimer is still largely unclear. Here, we investigated the molecular mechanisms of this cooperativity, by using molecular dynamics simulations. Consequently, we detected high flexibility of the loop region between the HI2 and H1 helices of Ets1. Upon Runx1-CBFβ heterodimer binding, this loop transiently adopts various sub-stable conformations in its interactions with the DNA. In addition, a network analysis suggested an allosteric pathway in the molecular assembly and identified some key residues that coincide with previous experimental studies. Our simulations suggest that the cooperative binding of Ets1 and the Runx1-CBFβ heterodimer alters the DNA conformation and induces sub-stable conformations of the HI2-H1 loop of Ets1. This phenomenon increases the flexibility of the regulatory module, including the HI2 helix, and destabilizes the inhibitory form of this module. Thus, we hypothesize that this effect facilitates Ets1-DNA binding and prevents the phosphorylation-dependent DNA binding autoinhibition.

  10. [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.

  11. Using cooperative learning to enhance the academic and social experiences of freshman student athletes.

    PubMed

    Dudley, B S; Johnson, D W; Johnson, R T

    1997-08-01

    One hundred seven freshman student athletes in 17 different women's and men's intercollegiate sports were required to attend evening study sessions. The student athletes completed academic assignments and studied for tests primarily in cooperative learning groups. As gauges of the program's impact on the participants, 3 questionnaires were administered to a sample of 50 (25 women and 25 men). The respondents reported that (a) they worked cooperatively on academic assignments, (b) the program staff provided both academic and personal support while structuring and facilitating cooperative learning groups, and (c) they themselves were highly task oriented, confident of their academic ability, and involved in positive and supportive relationships with their fellow participants.

  12. 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.

  13. Triosephosphate Isomerase and Filamin C Share Common Epitopes as Novel Allergens of Procambarus clarkii.

    PubMed

    Yang, Yang; Zhang, Yong-Xia; Liu, Meng; Maleki, Soheila J; Zhang, Ming-Li; Liu, Qing-Mei; Cao, Min-Jie; Su, Wen-Jin; Liu, Guang-Ming

    2017-02-01

    Triosephosphate isomerase (TIM) is a key enzyme in glycolysis and has been identified as an allergen in saltwater products. In this study, TIM with a molecular mass of 28 kDa was purified from the freshwater crayfish (Procambarus clarkii) muscle. A 90-kDa protein that showed IgG/IgE cross-reactivity with TIM was purified and identified as filamin C (FLN c), which is an actin-binding protein. TIM showed similar thermal and pH stability with better digestion resistance compared with FLN c. The result of the surface plasmon resonance (SPR) experiment demonstrated the infinity of anti-TIM polyclonal antibody (pAb) to both TIM and FLN c. Five linear and 3 conformational epitopes of TIM, as well as 9 linear and 10 conformational epitopes of FLN c, were mapped by phage display. Epitopes of TIM and FLN c demonstrated the sharing of certain residues; the occurrence of common epitopes in the two allergens accounts for their cross-reactivity.

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

    PubMed Central

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

    2011-01-01

    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

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

    PubMed Central

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

    2012-01-01

    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

  16. Domain-domain interactions in filamin A (16-23) impose a hierarchy of unfolding forces.

    PubMed

    Xu, Tianyou; Lannon, Herbert; Wolf, Sébastein; Nakamura, Fumihiko; Brujic, Jasna

    2013-05-07

    The quaternary structure of Filamin A (FLNa) 16-23 was recently shown to exhibit multiple domain-domain interactions that lead to a propeller-like construction. Here we present single-molecule force spectroscopy experiments to show a wide variety of mechanical responses of this molecule and compare it with its linear counterpart FLNa 1-8. The compact structure of FLNa 16-23 leads to a broad distribution of rupture forces and end-to-end lengths in the force-extension mode and multiple unraveling timescales in the force-clamp mode. Moreover, a subset of force-extension trajectories reveals a mechanical hierarchy in which the rupture of domain-domain interactions at high forces (>200 pN) liberates the unfolding of individual domains at low forces (∼100 pN). This mechanism may also explain the order-of-magnitude difference in the rates of the biexponential fits to the distribution of unfolding dwell times under force-clamp. Overall, FLNa 16-23 under a force of 100 pN is more compliant than the linear FLNa 1-8. Because a physiological role of FLNa is to crosslink actin filaments, this range of responses allows it to accommodate a broad spectrum of forces exerted by the cell and its environment. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. Punish and Voice: Punishment Enhances Cooperation when Combined with Norm-Signalling

    PubMed Central

    Andrighetto, Giulia; Brandts, Jordi; Conte, Rosaria; Sabater-Mir, Jordi; Solaz, Hector; Villatoro, Daniel

    2013-01-01

    Material punishment has been suggested to play a key role in sustaining human cooperation. Experimental findings, however, show that inflicting mere material costs does not always increase cooperation and may even have detrimental effects. Indeed, ethnographic evidence suggests that the most typical punishing strategies in human ecologies (e.g., gossip, derision, blame and criticism) naturally combine normative information with material punishment. Using laboratory experiments with humans, we show that the interaction of norm communication and material punishment leads to higher and more stable cooperation at a lower cost for the group than when used separately. In this work, we argue and provide experimental evidence that successful human cooperation is the outcome of the interaction between instrumental decision-making and the norm psychology humans are provided with. Norm psychology is a cognitive machinery to detect and reason upon norms that is characterized by a salience mechanism devoted to track how much a norm is prominent within a group. We test our hypothesis both in the laboratory and with an agent-based model. The agent-based model incorporates fundamental aspects of norm psychology absent from previous work. The combination of these methods allows us to provide an explanation for the proximate mechanisms behind the observed cooperative behaviour. The consistency between the two sources of data supports our hypothesis that cooperation is a product of norm psychology solicited by norm-signalling and coercive devices. PMID:23776441

  18. Punish and voice: punishment enhances cooperation when combined with norm-signalling.

    PubMed

    Andrighetto, Giulia; Brandts, Jordi; Conte, Rosaria; Sabater-Mir, Jordi; Solaz, Hector; Villatoro, Daniel

    2013-01-01

    Material punishment has been suggested to play a key role in sustaining human cooperation. Experimental findings, however, show that inflicting mere material costs does not always increase cooperation and may even have detrimental effects. Indeed, ethnographic evidence suggests that the most typical punishing strategies in human ecologies (e.g., gossip, derision, blame and criticism) naturally combine normative information with material punishment. Using laboratory experiments with humans, we show that the interaction of norm communication and material punishment leads to higher and more stable cooperation at a lower cost for the group than when used separately. In this work, we argue and provide experimental evidence that successful human cooperation is the outcome of the interaction between instrumental decision-making and the norm psychology humans are provided with. Norm psychology is a cognitive machinery to detect and reason upon norms that is characterized by a salience mechanism devoted to track how much a norm is prominent within a group. We test our hypothesis both in the laboratory and with an agent-based model. The agent-based model incorporates fundamental aspects of norm psychology absent from previous work. The combination of these methods allows us to provide an explanation for the proximate mechanisms behind the observed cooperative behaviour. The consistency between the two sources of data supports our hypothesis that cooperation is a product of norm psychology solicited by norm-signalling and coercive devices.

  19. Facial Likability and Smiling Enhance Cooperation, but Have No Direct Effect on Moralistic Punishment.

    PubMed

    Mieth, Laura; Bell, Raoul; Buchner, Axel

    2016-09-01

    The present study serves to test how positive and negative appearance-based expectations affect cooperation and punishment. Participants played a prisoner's dilemma game with partners who either cooperated or defected. Then they were given a costly punishment option: They could spend money to decrease the payoffs of their partners. Aggregated over trials, participants spent more money for punishing the defection of likable-looking and smiling partners compared to punishing the defection of unlikable-looking and nonsmiling partners, but only because participants were more likely to cooperate with likable-looking and smiling partners, which provided the participants with more opportunities for moralistic punishment. When expressed as a conditional probability, moralistic punishment did not differ as a function of the partners' facial likability. Smiling had no effect on the probability of moralistic punishment, but punishment was milder for smiling in comparison to nonsmiling partners.

  20. Enhancer cooperativity as a novel mechanism underlying the transcriptional regulation of E-cadherin during mesenchymal to epithelial transition.

    PubMed

    Alotaibi, Hani; Basilicata, M Felicia; Shehwana, Huma; Kosowan, Tyler; Schreck, Ilona; Braeutigam, Christien; Konu, Ozlen; Brabletz, Thomas; Stemmler, Marc P

    2015-06-01

    Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) highlight crucial steps during embryogenesis and tumorigenesis. Induction of dramatic changes in gene expression and cell features is reflected by modulation of Cdh1 (E-cadherin) expression. We show that Cdh1 activity during MET is governed by two enhancers at +7.8 kb and at +11.5 kb within intron 2 that are activated by binding of Grhl3 and Hnf4α, respectively. Recruitment of Grhl3 and Hnf4α to the enhancers is crucial for activating Cdh1 and accomplishing MET in non-tumorigenic mouse mammary gland cells (NMuMG). Moreover, the two enhancers cooperate via Grhl3 and Hnf4α binding, induction of DNA-looping and clustering at the promoter to orchestrate E-cadherin re-expression. Our results provide novel insights into the cellular mechanisms whereby cells respond to MET signals and re-establish an epithelial phenotype by enhancer cooperativity. A general importance of our findings including MET-mediated colonization of metastasizing tumor cells is suggested. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. 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.

  2. 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

  3. Filamin A is reduced and contributes to the CASR sensitivity in human parathyroid tumors.

    PubMed

    Mingione, Alessandra; Verdelli, Chiara; Ferrero, Stefano; Vaira, Valentina; Guarnieri, Vito; Scillitani, Alfredo; Vicentini, Leonardo; Balza, Gianni; Beretta, Edoardo; Terranegra, Annalisa; Vezzoli, Giuseppe; Soldati, Laura; Corbetta, Sabrina

    2017-02-01

    Parathyroid tumors display reduced sensitivity to extracellular calcium ([Ca(2+)]o). [Ca(2+)]o activates calcium-sensing receptor (CASR), which interacts with the scaffold protein filamin A (FLNA). The study aimed to investigate: (1) the FLNA expression in human parathyroid tumors, (2) its effects on the CASR mRNA and protein expression, and (3) on ERK signaling activation, (4) the effect of the carboxy-terminal CASR variants and (5) of the treatment with the CASR agonist R568 on FLNA-mediated ERK phosphorylation in HEK293 cells. Full-length FLNA immunostaining was variably reduced in parathyroid tumors. Immunofluorescence showed that FLNA localized in membrane and cytoplasm and co-localized with CASR in parathyroid adenomas (PAds)-derived cells. Cleaved C-terminus FLNA fragment could also be detected in PAds nuclear protein fractions. In HEK293 cells transfected with 990R-CASR or 990G-CASR variants, silencing of endogenous FLNA reduced CASR mRNA levels and total and membrane-associated CASR proteins. In agreement, FLNA mRNA levels positively correlated with CASR expression in a series of 74 PAds; however, any significant correlation with primary hyperparathyroidism severity could be detected and FLNA transcript levels did not differ between PAds harboring 990R or 990G CASR variants. R568 treatment was efficient in restoring 990R-CASR and 990G-CASR sensitivity to [Ca(2+)]o in the absence of FLNA. In conclusion, FLNA is downregulated in parathyroid tumors and parallels the CASR expression levels. Loss of FLNA reduces CASR mRNA and protein expression levels and the CASR-induced ERK phosphorylation. FLNA is involved in receptor expression, membrane localization and ERK signaling activation of both 990R and 990G CASR variants.

  4. Androgen-Induced Cell Migration: Role of Androgen Receptor/Filamin A Association

    PubMed Central

    Castoria, Gabriella; D'Amato, Loredana; Ciociola, Alessandra; Giovannelli, Pia; Giraldi, Tiziana; Sepe, Leandra; Paolella, Giovanni; Barone, Maria Vittoria; Migliaccio, Antimo; Auricchio, Ferdinando

    2011-01-01

    Background Androgen receptor (AR) controls male morphogenesis, gametogenesis and prostate growth as well as development of prostate cancer. These findings support a role for AR in cell migration and invasiveness. However, the molecular mechanism involved in AR-mediated cell migration still remains elusive. Methodology/Principal Findings Mouse embryo NIH3T3 fibroblasts and highly metastatic human fibrosarcoma HT1080 cells harbor low levels of transcriptionally incompetent AR. We now report that, through extra nuclear action, AR triggers migration of both cell types upon stimulation with physiological concentrations of the androgen R1881. We analyzed the initial events leading to androgen-induced cell migration and observed that challenging NIH3T3 cells with 10 nM R1881 rapidly induces interaction of AR with filamin A (FlnA) at cytoskeleton. AR/FlnA complex recruits integrin beta 1, thus activating its dependent cascade. Silencing of AR, FlnA and integrin beta 1 shows that this ternary complex controls focal adhesion kinase (FAK), paxillin and Rac, thereby driving cell migration. FAK-null fibroblasts migrate poorly and Rac inhibition by EHT impairs motility of androgen-treated NIH3T3 cells. Interestingly, FAK and Rac activation by androgens are independent of each other. Findings in human fibrosarcoma HT1080 cells strengthen the role of Rac in androgen signaling. The Rac inhibitor significantly impairs androgen-induced migration in these cells. A mutant AR, deleted of the sequence interacting with FlnA, fails to mediate FAK activation and paxillin tyrosine phosphorylation in androgen-stimulated cells, further reinforcing the role of AR/FlnA interaction in androgen-mediated motility. Conclusions/Significance The present report, for the first time, indicates that the extra nuclear AR/FlnA/integrin beta 1 complex is the key by which androgen activates signaling leading to cell migration. Assembly of this ternary complex may control organ development and prostate cancer

  5. 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

  6. 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.

  7. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE... Justice. ACTION: Solicitation for a Cooperative Agreement. SUMMARY: The National Institute of Corrections... will be based on research and theory and are meant to provide a medium to inform NIC initiatives as...

  8. 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…

  9. The Collaboration of Cooperative Learning and Conceptual Change: Enhancing the Students' Understanding of Chemical Bonding Concepts

    ERIC Educational Resources Information Center

    Eymur, Gülüzar; Geban, Ömer

    2017-01-01

    The main purpose of this study was to investigate the effects of cooperative learning based on conceptual change approach instruction on ninth-grade students' understanding in chemical bonding concepts compared to traditional instruction. Seventy-two ninth-grade students from two intact chemistry classes taught by the same teacher in a public high…

  10. 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…

  11. 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…

  12. 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…

  13. [Councelling regarding prenatal diagnostic: a model project to enhance cooperation between medical and psychosocial consultants].

    PubMed

    Kuhn, Rita; Schmidt, Ulrike; Ottomar, Bahrs; Riehl-Emde, Astrid

    2007-01-01

    Although according to section 2 of the Pregnancy Conflicts Law, there is a legal claim to psychosocial counselling and although its benefit has been proven empirically, pregnant women rarely draw upon it in the context of prenatal diagnostics (PND). One of the reasons is probably that physicians are not sufficiently aware of this counselling offer. By means of the model project "Interprofessional quality circles in prenatal diagnostics" an attempt was made to counteract this deficit. For this purpose, interprofessional quality circles have been established in six different places in Germany in order to motivate medical and psychosocial consultants to an increased cooperation. The effects and realization of the quality circle efforts have been evaluated. For this purpose, structural characteristics such as cooperation practice and utilization of psychosocial counselling have been assessed using a questionnaire before and after the introduction of the quality circles. All sessions have been documented; in addition, they have been evaluated by the participants using another shorter questionnaire. The results show that the quality circles led to an improved cooperation between the different professional groups and an increased utilization of psychosocial counselling. The work of the quality circles has been evaluated positively. It was regarded as conductive to cooperation, emotionally exonerative and extremely helpful with respect to the daily counselling work. Most of all, its practicality and case management were appraised. Thus, interprofessional quality circles prove to be an adequate instrument to advance the interprofessional and aim-oriented cooperation in such a way as demanded emphatically by the German Expert Advisory Board of Community Health in its recent experts report.

  14. Hypoxia-induced expression of VE-cadherin and Filamin B in gliomacell cultures and pseudopalisade structures

    PubMed Central

    Nissou, Marie-France; Elatifi, Michèle; Guttin, Audrey; Godfraind, Catherine; Salon, Caroline; Garcion, Emmanuel; Van Der Sanden, Boudewijn; Issartel, Jean-Paul; Berger, François; Wion, Didier

    2013-01-01

    Most of our knowledge regarding glioma cell biology comes from cell culture experiments. For many years the standards for glioma cell culture were the use of cell lines cultured in the presence of serum and 20% O2. However, in vivo, normoxia in many brain areas is in close to 3% O2. Hence, in cell culture, the experimental value referred as the norm is hyperoxic compared to any brain physiological value. Likewise, cells in vivo are not usually exposed to serum, and low-passaged gliomaneurosphere cultures maintained in serum-free medium is emerging as a new standard. A consequence of changing the experimental normoxic standard from 20% O2 to the more brain physiological value of 3% O2, is that a 3% O2 normoxic reference point enabled a more rigorous characterization of the level of regulation of genes by hypoxia. Among the glioma hypoxia-regulated genes characterized using this approach we found VE-cadherin that is required for blood vessel formation, and Filamin B a gene involved in endothelial cell motility. Both VE-Cadherin and Filamin B were found expressed in pseudopalisades, a glioblastoma pathognomonic structure made of hypoxic migrating cancer cells. These results provide additional clues on the role played by hypoxia in the acquisition of endothelial traits by glioma cells and on the functional links existing between pseudopalisades, hypoxia, and tumor progression. PMID:23543272

  15. Cooperative and substitution effects in enhancing strengths of halogen bonds in FCl⋯CNX complexes

    NASA Astrophysics Data System (ADS)

    Li, Qingzhong; Ma, Shumin; Liu, Xiaofeng; Li, Wenzuo; Cheng, Jianbo

    2012-08-01

    In this paper, the cooperative effect of halogen bond with hydrogen bond has been used to make a halogen bond in FCl-CNH dimer vary from a chlorine-shared one to an ion-pair one. The halogen bond is strengthened in FCl-CNH-CNH trimer and its maximal interaction energy equals to -76 kJ/mol when the number of CNH in FCl-CNH-(CNH)n polymer approaches infinity. Once the free H atom in FCl-CNH-CNH trimer is replaced with alkali metals, the halogen bond becomes strong enough to be an ion-pair one in FCl-CNH-CNLi and FCl-CNH-CNNa trimers. An introduction of a Lewis acid in FCl-CNH dimer has a more prominent effect on the type of halogen bond. A prominent cooperative effect is found for the halogen bond and hydrogen bond in the trimers. FH-FCl-CNH-CNH and FH-FCl-CNH-CNLi tetramers have also been studied and the interaction energy of halogen bonding in FH-FCl-CNH-CNLi tetramer is about 12 times as much as that in the FCl-CNH dimer. The atoms in molecules and natural bond orbital analyses have been carried out for these complexes to understand the nature of halogen bond and the origin of the cooperativity.

  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. Nuclear vs Cytoplasmic localization of Filamin A in Prostate Cancer: Immunohistochemical Correlation with Metastases

    PubMed Central

    Bedolla, Roble G.; Wang, Yu; Asuncion, Alfredo; Chamie, Karim; Siddiqui, Salma; Mudryj, Maria M.; Prihoda, Thomas J.; Siddiqui, Javed; Chinnaiyan, Arul M.; Mehra, Rohit; deVereWhite, Ralph W.; Ghosh, Paramita M.

    2009-01-01

    Purpose We previously showed that nuclear localization of the actin-binding protein FilaminA (FlnA) corresponded to hormone-dependence in prostate cancer (Oncogene, 2007, 26:6061-6070). Intact FlnA (280kDa, cytoplasmic) cleaved to a 90kDa fragment which translocated to the nucleus in hormone-naïve cells, whereas in hormone-refractory cells, FlnA was phosphorylated, preventing its cleavage and nuclear translocation. We now examined whether FlnA localization determines a propensity to metastasis in advanced androgen independent prostate cancer. Experimental Design We examined, by immunohistochemistry, FlnA localization in paraffin-embedded human prostate tissue representing different stages of progression. Results were correlated with in vitro studies in a cell model of prostate cancer. Results Nuclear FlnA was significantly higher in benign prostate (0.6612±0.5888), PIN (0.6024±0.4620) and clinically localized cancers (0.69134±0.5686), compared to metastatic prostate cancers (0.3719±0.4992, p=0.0007). Cytoplasmic FlnA increased from benign prostate (0.0833±0.2677), PIN (0.1409±0.2293), localized cancers (0.3008±0.3762, p=0.0150), to metastases (0.7632±0.4414, p<0.00001). Logistic regression of metastatic vs non-metastatic tissue yielded the area-under-ROC curve as 0.67 for nuclear-FlnA, 0.79 for cytoplasmic-FlnA and 0.82 for both, indicating that metastasis correlates with cytoplasmic-to-nuclear translocation. In vitro studies showed that cytoplasmic localization of FlnA induced cell invasion whereas nuclear translocation of the protein inhibited it. FlnA dephosphorylation with the PKA inhibitor H-89 facilitated FlnA nuclear translocation, resulting in decreased invasiveness and AR transcriptional activity, and induced sensitivity to androgen withdrawal in hormone-refractory cells. Conclusions The data presented in this study indicate that in prostate cancer, metastasis correlates with cytoplasmic localization of FlnA and may be prevented by cleavage and

  18. Nuclear versus cytoplasmic localization of filamin A in prostate cancer: immunohistochemical correlation with metastases.

    PubMed

    Bedolla, Roble G; Wang, Yu; Asuncion, Alfredo; Chamie, Karim; Siddiqui, Salma; Mudryj, Maria M; Prihoda, Thomas J; Siddiqui, Javed; Chinnaiyan, Arul M; Mehra, Rohit; de Vere White, Ralph W; Ghosh, Paramita M

    2009-02-01

    We previously showed that nuclear localization of the actin-binding protein, filamin A (FlnA), corresponded to hormone-dependence in prostate cancer. Intact FlnA (280 kDa, cytoplasmic) cleaved to a 90 kDa fragment which translocated to the nucleus in hormone-naïve cells, whereas in hormone-refractory cells, FlnA was phosphorylated, preventing its cleavage and nuclear translocation. We have examined whether FlnA localization determines a propensity to metastasis in advanced androgen-independent prostate cancer. We examined, by immunohistochemistry, FlnA localization in paraffin-embedded human prostate tissue representing different stages of progression. Results were correlated with in vitro studies in a cell model of prostate cancer. Nuclear FlnA was significantly higher in benign prostate (0.6612 +/- 0.5888), prostatic intraepithelial neoplasia (PIN; 0.6024 +/- 0.4620), and clinically localized cancers (0.69134 +/- 0.5686) compared with metastatic prostate cancers (0.3719 +/- 0.4992, P = 0.0007). Cytoplasmic FlnA increased from benign prostate (0.0833 +/- 0.2677), PIN (0.1409 +/- 0.2293), localized cancers (0.3008 +/- 0.3762, P = 0.0150), to metastases (0.7632 +/- 0.4414, P < 0.00001). Logistic regression of metastatic versus nonmetastatic tissue yielded the area under the receiver operating curve as 0.67 for nuclear-FlnA, 0.79 for cytoplasmic-FlnA, and 0.82 for both, indicating that metastasis correlates with cytoplasmic to nuclear translocation. In vitro studies showed that cytoplasmic localization of FlnA induced cell invasion whereas nuclear translocation of the protein inhibited it. FlnA dephosphorylation with the protein kinase A inhibitor H-89 facilitated FlnA nuclear translocation, resulting in decreased invasiveness and AR transcriptional activity, and induced sensitivity to androgen withdrawal in hormone-refractory cells. The data presented in this study indicate that in prostate cancer, metastasis correlates with cytoplasmic localization of FlnA and may

  19. 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.

  20. 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

  1. 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

  2. The upside of downsizing: asymmetric trifunctional organocatalysts as small enzyme mimics for cooperative enhancement of both rate and enantioselectivity with regulation.

    PubMed

    Liu, Fei

    2013-11-01

    Small molecule organic catalysts (organocatalysts) are widely used in asymmetric catalysis and synthesis. Compared to their enzymatic and transition-metal counterparts, organocatalysts have advantages in catalytic scope and efficiency but are more limited in proficiency. Chiral trifunctional organocatalysts, in which multiple catalytic motifs act cooperatively on a chiral scaffold, are an emerging class of organocatalysts with improved proficiency. Cooperativity design that enables both enantioselectivity and rate enhancement is essential to developing future generations of organocatalysts in biomimetic asymmetric catalysis.

  3. Brief, cooperative peer-instruction sessions during lectures enhance student recall and comprehension*

    PubMed Central

    Zhang, Niu; Henderson, Charles N.R.

    2016-01-01

    Objective: The objective of this study was to evaluate the academic impact of cooperative peer instruction during lecture pauses in an immunology/endocrinology course. Methods: Third-quarter students participated across iterations of the course. Each class offered 20 lectures of 50 minutes each. Classes were divided into a peer-instruction group incorporating cooperative peer instruction and a control group receiving traditional lectures. Peer-instruction group lectures were divided into 2–3 short presentations followed by a multiple-choice question (MCQ). Students recorded an initial answer and then had 1 minute to discuss answers with group peers. Following this, students could submit a revised answer. The control group received the same lecture material, but without MCQs or peer discussions. Final-exam scores were compared across study groups. A mixed-design analysis of covariance was used to analyze the data. Results: There was a statistically significant main effect for the peer-instruction activity (F(1, 93) = 6.573, p = .012, r = .257), with recall scores higher for MCQs asked after peer-instruction activities than for those asked before peer instruction. Final-exam scores at the end of term were greater in the peer-instruction group than the control group (F(1, 193) = 9.264, p = .003, r = .214; question type, F(1, 193) = 26.671, p = .000, r = .348). Conclusion: Lectures with peer-instruction pauses increase student recall and comprehension compared with traditional lectures. PMID:26967766

  4. Brief, cooperative peer-instruction sessions during lectures enhance student recall and comprehension.

    PubMed

    Zhang, Niu; Henderson, Charles N R

    2016-10-01

    The objective of this study was to evaluate the academic impact of cooperative peer instruction during lecture pauses in an immunology/endocrinology course. Third-quarter students participated across iterations of the course. Each class offered 20 lectures of 50 minutes each. Classes were divided into a peer-instruction group incorporating cooperative peer instruction and a control group receiving traditional lectures. Peer-instruction group lectures were divided into 2-3 short presentations followed by a multiple-choice question (MCQ). Students recorded an initial answer and then had 1 minute to discuss answers with group peers. Following this, students could submit a revised answer. The control group received the same lecture material, but without MCQs or peer discussions. Final-exam scores were compared across study groups. A mixed-design analysis of covariance was used to analyze the data. There was a statistically significant main effect for the peer-instruction activity (F(1, 93) = 6.573, p = .012, r = .257), with recall scores higher for MCQs asked after peer-instruction activities than for those asked before peer instruction. Final-exam scores at the end of term were greater in the peer-instruction group than the control group (F(1, 193) = 9.264, p = .003, r = .214; question type, F(1, 193) = 26.671, p = .000, r = .348). Lectures with peer-instruction pauses increase student recall and comprehension compared with traditional lectures.

  5. Nicotine and ethanol cooperate to enhance ventral tegmental area AMPA receptor function via α6-containing nicotinic receptors.

    PubMed

    Engle, Staci E; McIntosh, J Michael; Drenan, Ryan M

    2015-04-01

    Nicotine + ethanol co-exposure results in additive and/or synergistic effects in the ventral tegmental area (VTA) to nucleus accumbens (NAc) dopamine (DA) pathway, but the mechanisms supporting this are unclear. We tested the hypothesis that nAChRs containing α6 subunits (α6* nAChRs) are involved in the response to nicotine + ethanol co-exposure. Exposing VTA slices from C57BL/6 WT animals to drinking-relevant concentrations of ethanol causes a marked enhancement of α-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA) receptor (AMPAR) function in VTA neurons. This effect was sensitive to α-conotoxin MII (an α6β2* nAChR antagonist), suggesting that α6* nAChR function is required. In mice expressing hypersensitive α6* nAChRs (α6L9S mice), we found that lower concentrations (relative to C57BL/6 WT) of ethanol were sufficient to enhance AMPAR function in VTA neurons. Exposure of live C57BL/6 WT mice to ethanol also produced AMPAR functional enhancement in VTA neurons, and studies in α6L9S mice strongly suggest a role for α6* nAChRs in this response. We then asked whether nicotine and ethanol cooperate to enhance VTA AMPAR function. We identified low concentrations of nicotine and ethanol that were capable of strongly enhancing VTA AMPAR function when co-applied to slices, but that did not enhance AMPAR function when applied alone. This effect was sensitive to both varenicline (an α4β2* and α6β2* nAChR partial agonist) and α-conotoxin MII. Finally, nicotine + ethanol co-exposure also enhanced AMPAR function in VTA neurons from α6L9S mice. Together, these data identify α6* nAChRs as important players in the response to nicotine + ethanol co-exposure in VTA neurons.

  6. 77 FR 73 - Cooperative Conservation Partnership Initiative and Wetlands Reserve Enhancement Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-03

    ... Conservation Partnership Initiative and Wetlands Reserve Enhancement Program AGENCY: Natural Resources... Partnership Initiative (CCPI) and up to $25 million in the Wetlands Reserve Enhancement Program (WREP) through... wetlands. The designated 8-digit HUC focus areas are listed below. A complete list of the smaller-scale,...

  7. Evaluation of sarcoglycans, vinculin-talin-integrin system and filamin2 in alpha- and gamma-sarcoglycanopathy: an immunohistochemical study.

    PubMed

    Anastasi, Giuseppe; Cutroneo, Giuseppina; Trimarchi, Fabio; Santoro, Giuseppe; Bruschetta, Daniele; Bramanti, Placido; Pisani, Antonina; Favaloro, Angelo

    2004-12-01

    The sarcoglycan subcomplex (SGC) is a well-known system of interaction between extracellular matrix and sarcolemma-associated cytoskeleton in skeletal and cardiac muscle. The SGC is included in the DGC made up of sarcoplasmic subcomplex and a dystroglycan subcomplex. Recent developments in molecular genetics have demonstrated that the mutation of each single sarcoglycan gene, causes a series of recessive autosomal muscular dystrophies, dystrophin-positive, called sarcoglycanopathies or limb girdle muscular dystrophies. Our recent studies have demonstrated that costameres are a proteic machinery made up of DGC and vinculin-talin-integrin system, also revealing the colocalization of sarcoglycans and integrins in adult human skeletal muscle. These results may support the hypothesis of the existence of a bidirectional signalling between sarcoglycans and integrins in cultured L6 myocytes. The hypothesis of bidirectional signalling between sarcoglycans and integrins could be supported by the identification of a skeletal and cardiac muscle filamin2 as a gamma-sarcoglycan, delta-sarcoglycan and, hypothetically, beta1 integrin interacting protein. Our results, acquired with an immunofluorescence study on adult human skeletal muscle affected by LGMD type 2D and 2C, showed that in LGMD2D: a) alpha-sarcoglycan staining is severely reduced; b) the beta-gamma-delta-sarcoglycan subunit and all tested integrins staining are clearly detectable; c) filamin2 is normal and shows a costameric distribution. In LGMD2C: a) alpha-sarcoglycan staining is preserved; b) the beta-gamma-delta-sarcoglycan subunit staining is severely reduced; c) the alpha7B-integrin is slightly reduced and beta1D-integrin is severely reduced; d) filamin2 is severely reduced. Other tested proteins of the two systems show a normal staining pattern in both sarcoglycanopathies. Our study seems to confirm, for the first time on adult human skeletal muscle of subjects affected by LGMDs, the hypo-theses of: a) the

  8. ETS-Mediated Cooperation between Basic Helix-Loop-Helix Motifs of the Immunoglobulin μ Heavy-Chain Gene Enhancer

    PubMed Central

    Dang, Wei; Sun, Xiao-hong; Sen, Ranjan

    1998-01-01

    The μE motifs of the immunoglobulin μ heavy-chain gene enhancer bind ubiquitously expressed proteins of the basic helix-loop-helix (bHLH) family. These elements work together with other, more tissue-restricted elements to produce B-cell-specific enhancer activity by presently undefined combinatorial mechanisms. We found that μE2 contributed to transcription activation in B cells only when the μE3 site was intact, providing the first evidence for functional interactions between bHLH proteins. In vitro assays showed that bHLH zipper proteins binding to μE3 enhanced Ets-1 binding to μA. One of the consequences of this protein-protein interaction was to facilitate binding of a second bHLH protein, E47, to the μE2 site, thereby generating a three-protein–DNA complex. Furthermore, transcriptional synergy between bHLH and bHLH zipper factors also required an intermediate ETS protein, which may bridge the transcription activation domains of the bHLH factors. Our observations define an unusual form of cooperation between bHLH and ETS proteins and suggest mechanisms by which tissue-restricted and ubiquitous factors combine to generate tissue-specific enhancer activity. PMID:9488464

  9. 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

  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.

  11. Caffeinated coffee enhances co-operative behavior in the Mixed Motive Game in healthy volunteers.

    PubMed

    Tse, Wai S; Chan, Chi Choi S; Shiu, Shun Yan K; Chung, Pik Yee A; Cheng, Shuk Han

    2009-02-01

    Caffeinated drinks are commonly consumed in social gatherings. However, their effects on social behavior remain unclear. The present study examined the effects of caffeinated coffee on antidepressant-related co-operative behavior. Seventy-seven low-caffeine users took part in a randomized, double-blind, cross-over study of single dose of caffeinated coffee (150 mg caffeine) and decaffeinated coffee (9 mg caffeine) with at least a 3-day washout period. In each session, participants were asked to imagine a fictitious person and play the Mixed Motive Game with that person 45 min after coffee consumption. Heart rate, blood pressure, and state moods were measured at baseline and at 45 min post-coffee consumption. After caffeinated coffee, participants exhibited significantly higher blood pressure. They also allocated significantly fewer scores to themselves and sent significantly more sadness message during the game. These results suggest that caffeinated coffee may help to improve social support and depressive symptoms.

  12. Material protection, control, and accounting enhancements through the Russian/US cooperative MPC & A program

    SciTech Connect

    Scott, S.C.; Sude, S.; Buckley, W.M.

    1997-11-01

    The cooperative Russian/US Mining and Chemical Combine (Gorno-Khimichesky Kombinat, GKhK, also referred to as Krasnoyarsk-26) Materials Protection, Control, and Accounting (MPC & A) project was initiated in June 1996. Since then, the GKhK has collaborated with Brookhaven, Lawrence Livermore, Los Alamos, Oak Ridge, Pacific Northwest, and Sandia National Laboratories to test, evaluate, and implement MPC & A elements including bar codes, computerized nuclear material accounting software, nondestructive assay technologies, bulk measurement systems, seals, video surveillance systems, radio communication systems, metal detectors, vulnerability assessment tools, personnel access control systems, and pedestrian nuclear material portal monitors. This paper describes the strategy for implementation of these elements at the GKhK and the status of the collaborative efforts. 8 refs., 7 figs., 1 tab.

  13. 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.

  14. The enhancement of X-H⋯π hydrogen bond by cooperativity effects - Ab initio and QTAIM calculations

    NASA Astrophysics Data System (ADS)

    Grabowski, Sławomir J.; Leszczynski, Jerzy

    2009-01-01

    The cooperativity effects for C 2H 2⋯(HF) n and C 2H 4⋯(HF) n ( n = 1-4) complexes are analyzed using the results of MP2/6-311++G(d,p) calculations. It has been revealed that F-H⋯π and F-H⋯F hydrogen bonds exist for these complexes and those interactions are enhanced if the number of HF molecules increases. It is shown that cooperativity effect causes the shortening of H⋯F and H⋯π distances, simultaneously the electron density and its Laplacian at the corresponding bond critical point (BCP) increase. There is also the greater charge transfer corresponding to π(C dbnd C) → σ ∗(F-H), π(C tbnd C) → σ ∗(F-H) and n(F) → σ ∗(F-H) interactions. One notices the greater elongation of H-F bonds within complexes if the number of HF molecules increases. The various correlations were found between geometrical, energetic and topological parameters. There are unique bond paths of the complexes analyzed that connect the hydrogen attractors with the BCPs of C dbnd C and C tbnd C bonds of Lewis base sub-systems.

  15. Ultrastructural localization of alpha-actinin and filamin in cultured cells with the immunogold staining (IGS) method

    PubMed Central

    1984-01-01

    Monospecific antibodies to chicken gizzard actin, alpha-actinin, and filamin have been used to localize these proteins at the ultrastructural level: secondary cultures of 14-d-old chicken embryo lung epithelial cells and chicken heart fibroblasts were briefly lysed with either a 0.5% Triton X-100/0.25% glutaraldehyde mixture, or 0.1% Triton X-100, fixed with 0.5% glutaraldehyde, and further permeabilized with 0.5% Triton X-100, to allow penetration of the gold-conjugated antibodies. After immunogold staining (De Mey, J., M. Moeremans, G. Geuens, R. Nuydens, and M. De Brabander, 1981, Cell Biol. Int. Rep. 5:889-899), the cells were postfixed in glutaraldehyde-tannic acid and further processed for embedding and thin sectioning. This approach enabled us to document the distribution of alpha-actinin and filamin either on the delicate cortical networks of the cell periphery or in the densely bundled stress fibers and polygonal nets. By using antiactin immunogold staining as a control, we were able to demonstrate the applicability of the method to the microfilament system: the label was distributed homogeneously over all areas containing recognizable microfilaments, except within very thick stress fibers, where the marker did not penetrate completely. Although alpha-actinin specific staining was homogeneously localized along loosely-organized microfilaments, it was concentrated in the dense bodies of stress fibers. The antifilamin-specific staining showed a typically spotty or patchy pattern associated with the fine cortical networks and stress fibers. This pattern occurred along all actin filaments, including the dense bodies also marked by anti-alpha-actinin antibodies. The results confirm and extend the data from light microscopic investigations and provide more information on the structural basis of the microfilament system. PMID:6207180

  16. High temperatures enhance cooperative motions between CBM and catalytic domains of a thermostable cellulase: mechanism insights from essential dynamics.

    PubMed

    Batista, Paulo Ricardo; Costa, Mauricio Garcia de Souza; Pascutti, Pedro Geraldo; Bisch, Paulo Mascarello; de Souza, Wanderley

    2011-08-14

    Cellulases from thermophiles are capable of cleaving sugar chains from cellulose efficiently at high temperatures. The thermo-resistant Cel9A-68 cellulase possesses two important domains: CBM and a catalytic domain connected by a Pro/Ser/Thr rich linker. These domains act cooperatively to allow efficient catalysis. Despite exhaustive efforts to characterize cellulase binding and mechanism of action, a detailed description of the cellulose intrinsic flexibility is still lacking. From computational simulations we studied the temperature influence on the enzyme plasticity, prior to substrate binding. Interestingly, we observed an enhancement of collective motions at high temperatures. These motions are the most representative and describe an intrinsic hinge bending transition. A detailed analysis of these motions revealed an interdomain approximation where D459 and G460, located at the linker region, are the hinge residues. Therefore, we propose a new putative site for mutagenesis targeting the modulation of such conformational transition that may be crucial for activity.

  17. 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.

  18. Lineage-specific dynamic and pre-established enhancer-promoter contacts cooperate in terminal differentiation.

    PubMed

    Rubin, Adam J; Barajas, Brook C; Furlan-Magaril, Mayra; Lopez-Pajares, Vanessa; Mumbach, Maxwell R; Howard, Imani; Kim, Daniel S; Boxer, Lisa D; Cairns, Jonathan; Spivakov, Mikhail; Wingett, Steven W; Shi, Minyi; Zhao, Zhixin; Greenleaf, William J; Kundaje, Anshul; Snyder, Michael; Chang, Howard Y; Fraser, Peter; Khavari, Paul A

    2017-10-01

    Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer-promoter contact remodeling during cellular differentiation remains poorly understood. To address this, genome-wide promoter capture Hi-C (CHi-C) was performed during epidermal differentiation. Two classes of enhancer-promoter contacts associated with differentiation-induced genes were identified. The first class ('gained') increased in contact strength during differentiation in concert with enhancer acquisition of the H3K27ac activation mark. The second class ('stable') were pre-established in undifferentiated cells, with enhancers constitutively marked by H3K27ac. The stable class was associated with the canonical conformation regulator cohesin, whereas the gained class was not, implying distinct mechanisms of contact formation and regulation. Analysis of stable enhancers identified a new, essential role for a constitutively expressed, lineage-restricted ETS-family transcription factor, EHF, in epidermal differentiation. Furthermore, neither class of contacts was observed in pluripotent cells, suggesting that lineage-specific chromatin structure is established in tissue progenitor cells and is further remodeled in terminal differentiation.

  19. TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activation.

    PubMed

    Vanden Bush, Tony J; Bishop, Gail A

    2008-02-01

    During vaccination or infection, adaptive and innate immune receptors of B cells are engaged by microbial antigens/ligands. A better understanding of how innate and adaptive signaling pathways interact could enlighten B lymphocyte biology as well as aid immunotherapy strategies and vaccine design. To address this goal, we examined the effects of TLR stimulation on BCR and CD40-induced B cell activation. Synergistic production of IL-6 was observed in both human and mouse primary B cells stimulated through B cell antigen receptors, CD40 and TLR7, and these two receptors also cooperated independently of BCR signals. The enhanced IL-6 production was dependent upon the activity of c-Jun kinase (JNK) and cFos. Dual stimulation through CD40 and TLR7 markedly enhanced JNK activity. The increased level of active JNK in dual-stimulated cells was accompanied by an increase in the level of active AP-1 monomers cJun and cFos. The stimulation of B cells through both CD40 and TLR7 therefore enhanced the production of cytokines through increased JNK signaling and AP-1 activity. In addition, the dual stimulation increased cFos/AP-1 species in stimulated cells, effectively expanding the repertoire of AP-1 dimers as compared to singly stimulated B cells.

  20. The Importance of Building and Enhancing Worldwide Industry Cooperation in the Areas of Radiological Protection, Waste Management and Decommissioning

    SciTech Connect

    Saint-Pierre, S.

    2006-07-01

    The slow or stagnant rate of nuclear power generation development in many developed countries over the last two decades has resulted in a significant shortage in the population of mid-career nuclear industry professionals. This shortage is even more pronounced in some specific areas of expertise such as radiological protection, waste management and decommissioning. This situation has occurred at a time when the renaissance of nuclear power and the globalization of the nuclear industry are steadily gaining momentum and when the industry's involvement in international and national debates in these three fields of expertise (and the industry's impact on these debates) is of vital importance. This paper presents the World Nuclear Association (WNA) approach to building and enhancing worldwide industry cooperation in radiological protection, waste management and decommissioning, which is manifested through the activities of the two WNA working groups on radiological protection (RPWG) and on waste management and decommissioning (WM and DWG). This paper also briefly describes the WNA's participatory role, as of summer 2005, in the International Atomic Energy Agency (IAEA) standard development committees on radiation safety (RASSC), waste safety (WASSC) and nuclear safety (NUSSC). This participation provides the worldwide nuclear industry with an opportunity to be part of IAEA's discussions on shaping changes to the control regime of IAEA safety standards. The review (and the prospect of a revision) of IAEA safety standards, which began in October 2005, makes this WNA participation and the industry ' s involvement at the national level timely and important. All of this excellent industry cooperation and team effort is done through 'collegial' exchanges between key industry experts, which help tackle important issues more effectively. The WNA is continuously looking to enhance its worldwide industry representation in these fields of expertise through the RPWG and WM and DWG

  1. Cytoadhesion of Plasmodium falciparum–infected erythrocytes to chondroitin-4-sulfate is cooperative and shear enhanced

    PubMed Central

    Rieger, Harden; Yoshikawa, Hiroshi Y.; Quadt, Katharina; Nielsen, Morten A.; Sanchez, Cecilia P.; Salanti, Ali

    2015-01-01

    Infections with the human malaria parasite Plasmodium falciparum during pregnancy can lead to severe complications for both mother and child, resulting from the cytoadhesion of parasitized erythrocytes in the intervillous space of the placenta. Cytoadherence is conferred by the specific interaction of the parasite-encoded adhesin VAR2CSA with chondroitin-4-sulfate (CSA) present on placental proteoglycans. CSA presented elsewhere in the microvasculature does not afford VAR2CSA-mediated cytoadhesion of parasitized erythrocytes. To address the placenta-specific binding tropism, we investigated the effect of the receptor/ligand arrangement on cytoadhesion, using artificial membranes with different CSA spacing intervals. We found that cytoadhesion is strongly dependent on the CSA distance, with half-maximal adhesion occurring at a CSA distance of 9 ± 1 nm at all hydrodynamic conditions. Moreover, binding to CSA was cooperative and shear stress induced. These findings suggest that the CSA density, together with allosteric effects in VAR2CSA, aid in discriminating between different CSA milieus. PMID:25352129

  2. Application of a Cooperative University/Middle School Model to Enhance Science Education Accountability.

    ERIC Educational Resources Information Center

    Zigler, John T.; And Others

    This study concerned whether a model designed to enchance educational accountability developed by university science educators could be used to enhance science educational accountability in a public middle school. Participants in the study were 39 teachers who attended a combined summer/inservice institute in the summer of 1973 at Ball State…

  3. DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors

    PubMed Central

    Narasimhan, Kamesh; Pillay, Shubhadra; Huang, Yong-Heng; Jayabal, Sriram; Udayasuryan, Barath; Veerapandian, Veeramohan; Kolatkar, Prasanna; Cojocaru, Vlad; Pervushin, Konstantin; Jauch, Ralf

    2015-01-01

    Sox2 and Pax6 are transcription factors that direct cell fate decision during neurogenesis, yet the mechanism behind how they cooperate on enhancer DNA elements and regulate gene expression is unclear. By systematically interrogating Sox2 and Pax6 interaction on minimal enhancer elements, we found that cooperative DNA recognition relies on combinatorial nucleotide switches and precisely spaced, but cryptic composite DNA motifs. Surprisingly, all tested Sox and Pax paralogs have the capacity to cooperate on such enhancer elements. NMR and molecular modeling reveal very few direct protein–protein interactions between Sox2 and Pax6, suggesting that cooperative binding is mediated by allosteric interactions propagating through DNA structure. Furthermore, we detected and validated several novel sites in the human genome targeted cooperatively by Sox2 and Pax6. Collectively, we demonstrate that Sox–Pax partnerships have the potential to substantially alter DNA target specificities and likely enable the pleiotropic and context-specific action of these cell-lineage specifiers. PMID:25578969

  4. 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

  5. Filamin C promotes lymphatic invasion and lymphatic metastasis and increases cell motility by regulating Rho GTPase in esophageal squamous cell carcinoma

    PubMed Central

    Furukawa, Tatsuhiko; Kita, Yoshiaki; Hatanaka, Kazuhito; Minami, Kentaro; Kawahara, Kohichi; Yamamoto, Masatatsu; Baba, Kenji; Mori, Shinichiro; Uchikado, Yasuto; Maemura, Kosei; Tanimoto, Akihide; Natsugoe, Shoji

    2017-01-01

    To establish treatments to improve the prognosis of cancer patients, it is necessary to find new targets to control metastasis. We found that expression of FilaminC (FLNC), a member of the actin binding and cross-linking filamin protein family is correlated with lymphatic invasion and lymphatic metastasis in esophageal squamous cell carcinoma (ESCC) by increasing cell motility through activation of Rho GTPase. Immunohistochemistry analysis showed that FLNC expression in ESCC is associated with lymphatic invasion, metastasis, and prognosis. FLNC knockdown in esophageal cancer cell lines decreased cell migration in wound healing and transwell migration assays, and invasion in transwell migration assays. Furthermore, FLNC knockdown reduced the amount of activated Rac-1 (GTP-Rac1) and activated Cdc42 (GTP-Cdc42). Our results suggest that FLNC expression is a useful biomarker of ESCC metastatic tendency and that inhibiting FLNC function may be useful to control the metastasis of ESCC. PMID:28031525

  6. 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…

  7. 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.

  8. Enhancing clinical effectiveness of pre-radiotherapy workflow by using multidisciplinary-cooperating e-control and e-alerts

    PubMed Central

    Lin, Yung-Hsiang; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Lai, Chun-Liang; Shih, Yi-Ting; Yeh, Pei-Han; Lin, Yi-An; Tsai, Wei-Ta; Hsieh, Hui-Ling; Chen, Liang-Cheng; Huang, Li-Wen; Lin, Po-Hao; Liu, Dai-Wei; Hsu, Feng-Chun; Tsai, Shiang-Jiun; Liu, Jia-Chi; Chung, En-Seu; Lin, Hon-Yi

    2017-01-01

    Abstract Radiotherapy (RT) is useful in managing cancer diseases. In clinical practice, early initiation of RT is crucial for enhancing tumor control. But, delivering precise RT requires a series of pre-RT working processes in a tight staff-cooperation manner. In this regard, using information system to conduct e-control and e-alerts has been suggested to improve practice effectiveness; however, this effect is not well defined in a real-world RT setting. We designed an information system to perform e-control and e-alerts for the whole process of pre-RT workflow to shorten processing time, to improve overall staff satisfaction, and to enhance working confidence. A quality-improving study conducted in a large RT center. Externally validated data were retrospectively analyzed for comparison before (from Sep. 2012 to Dec. 2012, n = 223) and after (from Sep. 2013 to Dec. 2013, n = 240) implementation of pre-RT e-control and e-alerts. Applying the e-control with delay-working e-alerts in pre-RT workflow was the main intervention. Nine workstations were identified in pre-RT workflow. The primary outcome measure was the processing time in each pre-RT workstations before and after implementing the e-control and e-alerts. Secondary measures were staff-working confidence and near-missing cases during the process of pre-RT workflow. After implementing e-control, overall processing time of pre-RT workflow was shortened from 12.2 days to 8.9 days (P < .001). Follow-up data (till Jul. 2016) showed a durable effect of 9.2 days, being still below the predefined threshold of <10 days. Using a multidisciplinary-cooperating information system is useful to conduct e-control and e-alerts in the whole process of pre-RT workflow. Clinical effectiveness, staff satisfaction, and working confidence are able to be enhanced obviously. PMID:28614257

  9. 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

    2016-06-08

    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.

  10. Surface mediated cooperative interactions of drugs enhance mechanical forces for antibiotic action.

    PubMed

    Ndieyira, Joseph W; Bailey, Joe; Patil, Samadhan B; Vögtli, Manuel; Cooper, Matthew A; Abell, Chris; McKendry, Rachel A; Aeppli, Gabriel

    2017-02-03

    The alarming increase of pathogenic bacteria that are resistant to multiple antibiotics is now recognized as a major health issue fuelling demand for new drugs. Bacterial resistance is often caused by molecular changes at the bacterial surface, which alter the nature of specific drug-target interactions. Here, we identify a novel mechanism by which drug-target interactions in resistant bacteria can be enhanced. We examined the surface forces generated by four antibiotics; vancomycin, ristomycin, chloroeremomycin and oritavancin against drug-susceptible and drug-resistant targets on a cantilever and demonstrated significant differences in mechanical response when drug-resistant targets are challenged with different antibiotics although no significant differences were observed when using susceptible targets. Remarkably, the binding affinity for oritavancin against drug-resistant targets (70 nM) was found to be 11,000 times stronger than for vancomycin (800 μM), a powerful antibiotic used as the last resort treatment for streptococcal and staphylococcal bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Using an exactly solvable model, which takes into account the solvent and membrane effects, we demonstrate that drug-target interactions are strengthened by pronounced polyvalent interactions catalyzed by the surface itself. These findings further enhance our understanding of antibiotic mode of action and will enable development of more effective therapies.

  11. Surface mediated cooperative interactions of drugs enhance mechanical forces for antibiotic action

    NASA Astrophysics Data System (ADS)

    Ndieyira, Joseph W.; Bailey, Joe; Patil, Samadhan B.; Vögtli, Manuel; Cooper, Matthew A.; Abell, Chris; McKendry, Rachel A.; Aeppli, Gabriel

    2017-02-01

    The alarming increase of pathogenic bacteria that are resistant to multiple antibiotics is now recognized as a major health issue fuelling demand for new drugs. Bacterial resistance is often caused by molecular changes at the bacterial surface, which alter the nature of specific drug-target interactions. Here, we identify a novel mechanism by which drug-target interactions in resistant bacteria can be enhanced. We examined the surface forces generated by four antibiotics; vancomycin, ristomycin, chloroeremomycin and oritavancin against drug-susceptible and drug-resistant targets on a cantilever and demonstrated significant differences in mechanical response when drug-resistant targets are challenged with different antibiotics although no significant differences were observed when using susceptible targets. Remarkably, the binding affinity for oritavancin against drug-resistant targets (70 nM) was found to be 11,000 times stronger than for vancomycin (800 μM), a powerful antibiotic used as the last resort treatment for streptococcal and staphylococcal bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Using an exactly solvable model, which takes into account the solvent and membrane effects, we demonstrate that drug-target interactions are strengthened by pronounced polyvalent interactions catalyzed by the surface itself. These findings further enhance our understanding of antibiotic mode of action and will enable development of more effective therapies.

  12. Surface mediated cooperative interactions of drugs enhance mechanical forces for antibiotic action

    PubMed Central

    Ndieyira, Joseph W.; Bailey, Joe; Patil, Samadhan B.; Vögtli, Manuel; Cooper, Matthew A.; Abell, Chris; McKendry, Rachel A.; Aeppli, Gabriel

    2017-01-01

    The alarming increase of pathogenic bacteria that are resistant to multiple antibiotics is now recognized as a major health issue fuelling demand for new drugs. Bacterial resistance is often caused by molecular changes at the bacterial surface, which alter the nature of specific drug-target interactions. Here, we identify a novel mechanism by which drug-target interactions in resistant bacteria can be enhanced. We examined the surface forces generated by four antibiotics; vancomycin, ristomycin, chloroeremomycin and oritavancin against drug-susceptible and drug-resistant targets on a cantilever and demonstrated significant differences in mechanical response when drug-resistant targets are challenged with different antibiotics although no significant differences were observed when using susceptible targets. Remarkably, the binding affinity for oritavancin against drug-resistant targets (70 nM) was found to be 11,000 times stronger than for vancomycin (800 μM), a powerful antibiotic used as the last resort treatment for streptococcal and staphylococcal bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Using an exactly solvable model, which takes into account the solvent and membrane effects, we demonstrate that drug-target interactions are strengthened by pronounced polyvalent interactions catalyzed by the surface itself. These findings further enhance our understanding of antibiotic mode of action and will enable development of more effective therapies. PMID:28155918

  13. Strong cooperativity and loose geometry between CUB domains are the basis for procollagen c-proteinase enhancer activity.

    PubMed

    Kronenberg, Daniel; Vadon-Le Goff, Sandrine; Bourhis, Jean-Marie; Font, Bernard; Eichenberger, Denise; Hulmes, David J S; Moali, Catherine

    2009-11-27

    Procollagen C-proteinase enhancers (PCPE-1 and -2) specifically activate bone morphogenetic protein-1 (BMP-1) and other members of the tolloid proteinase family during C-terminal processing of fibrillar collagen precursors. PCPEs consist of two CUB domains (CUB1 and CUB2) and one NTR domain separated by one short and one long linker. It was previously shown that PCPEs can strongly interact with procollagen molecules, but the exact mechanism by which they enhance BMP-1 activity remains largely unknown. Here, we used a series of deletion mutants of PCPE-1 and two chimeric constructs with repetitions of the same CUB domain to study the role of each domain and linker. Out of all the forms tested, only those containing both CUB1 and CUB2 were capable of enhancing BMP-1 activity and binding to a mini-procollagen substrate with nanomolar affinity. Both these properties were lost by individual CUB domains, which had dissociation constants at least three orders of magnitude higher. In addition, none of the constructs tested could inhibit PCPE activity, although CUB2CUB2NTR was found to modulate BMP-1 activity through direct complex formation with the enzyme, resulting in a decreased rate of substrate processing. Finally, increasing the length of the short linker between CUB1 and CUB2 was without detrimental effect on both activity and substrate binding. These data support the conclusion that CUB1 and CUB2 bind to the procollagen substrate in a cooperative manner, involving the short linker that provides a flexible tether linking the two binding regions.

  14. Cooperative plasminogen recruitment to the surface of Streptococcus canis via M protein and enolase enhances bacterial survival.

    PubMed

    Fulde, Marcus; Rohde, Manfred; Polok, Andy; Preissner, Klaus T; Chhatwal, Gursharan Singh; Bergmann, Simone

    2013-03-12

    Streptococcus canis is a zoonotic pathogen capable of causing serious invasive diseases in domestic animals and humans. Surface-exposed M proteins and metabolic enzymes have been characterized as major virulence determinants in various streptococcal species. Recently, we have identified SCM, the M-like protein of S. canis, as the major receptor for miniplasminogen localized on the bacterial surface. The present study now characterizes the glycolytic enzyme enolase as an additional surface-exposed plasminogen-binding protein. According to its zoonotic properties, purified S. canis enolase binds to both human and canine plasminogen and facilitates degradation of aggregated fibrin matrices after activation with host-derived urokinase-type plasminogen activator (uPA). Unlike SCM, which binds to the C terminus of human plasminogen, the S. canis enolase interacts N terminally with the first four kringle domains of plasminogen, representing angiostatin. Radioactive binding analyses confirmed cooperative plasminogen recruitment to both surface-exposed enolase and SCM. Furthermore, despite the lack of surface protease activity via SpeB in S. canis, SCM is released and reassociated homophilically to surface-anchored SCM and heterophilically to surface-bound plasminogen. In addition to plasminogen-mediated antiphagocytic activity, reassociation of SCM to the bacterial surface significantly enhanced bacterial survival in phagocytosis analyses using human neutrophils. Streptococcal infections are a major issue in medical microbiology due to the increasing spread of antibiotic resistances and the limited availability of efficient vaccines. Surface-exposed glycolytic enzymes and M proteins have been characterized as major virulence factors mediating pathogen-host interaction. Since streptococcal infection mechanisms exert a subset of multicombinatorial processes, the investigation of synergistic activities mediated via different virulence factors has become a high priority. Our

  15. A novel cooperative localization algorithm using enhanced particle filter technique in maritime search and rescue wireless sensor network.

    PubMed

    Wu, Huafeng; Mei, Xiaojun; Chen, Xinqiang; Li, Junjun; Wang, Jun; Mohapatra, Prasant

    2017-09-29

    Maritime search and rescue (MSR) play a significant role in Safety of Life at Sea (SOLAS). However, it suffers from scenarios that the measurement information is inaccurate due to wave shadow effect when utilizing wireless Sensor Network (WSN) technology in MSR. In this paper, we develop a Novel Cooperative Localization Algorithm (NCLA) in MSR by using an enhanced particle filter method to reduce measurement errors on observation model caused by wave shadow effect. First, we take into account the mobility of nodes at sea to develop a motion model-Lagrangian model. Furthermore, we introduce both state model and observation model to constitute a system model for particle filter (PF). To address the impact of the wave shadow effect on the observation model, we develop an optimal parameter derived by Kullback-Leibler divergence (KLD) to mitigate the error. After the optimal parameter is acquired, an improved likelihood function is presented. Finally, the estimated position is acquired. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  16. Interleukin (IL)-18, cooperatively with IL-23, induces prominent inflammation and enhances psoriasis-like epidermal hyperplasia.

    PubMed

    Shimoura, Noriko; Nagai, Hiroshi; Fujiwara, Susumu; Jimbo, Haruki; Yoshimoto, Takayuki; Nishigori, Chikako

    2017-05-01

    The interleukin (IL)-23/IL-17 axis is strongly implicated in the pathogenesis of psoriasis. Previous studies showed that IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index. However, the mechanism whereby IL-18 affects disease severity remains unknown. In this study, we investigated the effects of IL-18 on a psoriasis-like skin inflammation model induced by recombinant mouse IL-23. We found that IL-18, cooperatively with IL-23, induced prominent inflammation and enhanced psoriasis-like epidermal hyperplasia. In the skin of mice treated with IL-23 plus IL-18, the expression of interferon-γ was significantly upregulated and that of chemokine (C-X-C motif) ligand 9 (CXCL9) was synergistically increased. Histologically, strong positive signals of CXCL9 were observed around the infiltrating inflammatory cells. The current results suggest that IL-18 might synergize with IL-23 to induce a T helper 1 immune reaction, without inhibiting the IL-23/IL-17 axis, and thus may aggravate psoriatic inflammation.

  17. NOD1 Cooperates with TLR2 to Enhance T Cell Receptor-Mediated Activation in CD8 T Cells

    PubMed Central

    Mercier, Blandine C.; Debaud, Anne-Laure; Tomkowiak, Martine; Marvel, Jacqueline; Bonnefoy, Nathalie

    2012-01-01

    Pattern recognition receptors (PRR), like Toll-like receptors (TLR) and NOD-like receptors (NLR), are involved in the detection of microbial infections and tissue damage by cells of the innate immune system. Recently, we and others have demonstrated that TLR2 can additionally function as a costimulatory receptor on CD8 T cells. Here, we establish that the intracytosolic receptor NOD1 is expressed and functional in CD8 T cells. We show that C12-iEDAP, a synthetic ligand for NOD1, has a direct impact on both murine and human CD8 T cells, increasing proliferation and effector functions of cells activated via their T cell receptor (TCR). This effect is dependent on the adaptor molecule RIP2 and is associated with an increased activation of the NF-κB, JNK and p38 signaling pathways. Furthermore, we demonstrate that NOD1 stimulation can cooperate with TLR2 engagement on CD8 T cells to enhance TCR-mediated activation. Altogether our results indicate that NOD1 might function as an alternative costimulatory receptor in CD8 T cells. Our study provides new insights into the function of NLR in T cells and extends to NOD1 the recent concept that PRR stimulation can directly control T cell functions. PMID:22848741

  18. Cooperative Plasminogen Recruitment to the Surface of Streptococcus canis via M Protein and Enolase Enhances Bacterial Survival

    PubMed Central

    Fulde, Marcus; Rohde, Manfred; Polok, Andy; Preissner, Klaus T.; Chhatwal, Gursharan Singh; Bergmann, Simone

    2013-01-01

    ABSTRACT Streptococcus canis is a zoonotic pathogen capable of causing serious invasive diseases in domestic animals and humans. Surface-exposed M proteins and metabolic enzymes have been characterized as major virulence determinants in various streptococcal species. Recently, we have identified SCM, the M-like protein of S. canis, as the major receptor for miniplasminogen localized on the bacterial surface. The present study now characterizes the glycolytic enzyme enolase as an additional surface-exposed plasminogen-binding protein. According to its zoonotic properties, purified S. canis enolase binds to both human and canine plasminogen and facilitates degradation of aggregated fibrin matrices after activation with host-derived urokinase-type plasminogen activator (uPA). Unlike SCM, which binds to the C terminus of human plasminogen, the S. canis enolase interacts N terminally with the first four kringle domains of plasminogen, representing angiostatin. Radioactive binding analyses confirmed cooperative plasminogen recruitment to both surface-exposed enolase and SCM. Furthermore, despite the lack of surface protease activity via SpeB in S. canis, SCM is released and reassociated homophilically to surface-anchored SCM and heterophilically to surface-bound plasminogen. In addition to plasminogen-mediated antiphagocytic activity, reassociation of SCM to the bacterial surface significantly enhanced bacterial survival in phagocytosis analyses using human neutrophils. PMID:23481605

  19. Cooperative self-construction and enhanced optical absorption of nanoplates-assembled hierarchical Bi 2WO 6 flowers

    NASA Astrophysics Data System (ADS)

    Liu, Shengwei; Yu, Jiaguo

    2008-05-01

    Bi 2WO 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 2WO 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.

  20. RefilinB (FAM101B) targets FilaminA to organize perinuclear actin networks and regulates nuclear shape

    PubMed Central

    Gay, Olivia; Gilquin, Benoît; Nakamura, Fumihiko; Jenkins, Zandra A.; McCartney, Rosannah; Krakow, Deborah; Deshiere, Alexandre; Assard, Nicole; Hartwig, John H.; Robertson, Stephen P.; Baudier, Jacques

    2011-01-01

    The intracellular localization and shape of the nucleus plays a central role in cellular and developmental processes. In fibroblasts, nuclear movement and shape are controlled by a specific perinuclear actin network made of contractile actin filament bundles called transmembrane actin-associated nuclear (TAN) lines that form a structure called the actin cap. The identification of regulatory proteins associated with this specific actin cytoskeletal dynamic is a priority for understanding actin-based changes in nuclear shape and position in normal and pathological situations. Here, we first identify a unique family of actin regulators, the refilin proteins (RefilinA and RefilinB), that stabilize specifically perinuclear actin filament bundles. We next identify the actin-binding filamin A (FLNA) protein as the downstream effector of refilins. Refilins act as molecular switches to convert FLNA from an actin branching protein into one that bundles. In NIH 3T3 fibroblasts, the RefilinB/FLNA complex organizes the perinuclear actin filament bundles forming the actin cap. Finally, we demonstrate that in epithelial normal murine mammary gland (NmuMG) cells, the RefilinB/FLNA complex controls formation of a new perinuclear actin network that accompanies nuclear shape changes during the epithelial–mesenchymal transition (EMT). Our studies open perspectives for further functional analyses of this unique actin-based network and shed light on FLNA function during development and in human syndromes associated with FLNA mutations. PMID:21709252

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

    PubMed Central

    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

    2013-01-01

    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

  2. Filamin A (FLNA) mutation-A newcomer to the childhood interstitial lung disease (ChILD) classification.

    PubMed

    Shelmerdine, Susan C; Semple, Thomas; Wallis, Colin; Aurora, Paul; Moledina, Shahin; Ashworth, Michael T; Owens, Catherine M

    2017-10-01

    Interstitial lung disease (ILD) in infants represents a rare and heterogenous group of disorders, distinct from those occurring in adults. In recent years a new entity within this category is being recognized, namely filamin A (FLNA) mutation related lung disease. Our aims are to describe the clinical and radiological course of patients with this disease entity to aid clinicians in the prognostic counseling and management of similar patients they may encounter. A retrospective case note review was conducted of all patients treated at our institution (a specialist tertiary referral childrens' center) for genetically confirmed FLNA mutation related lung disease. The clinical presentation, evolution, management and radiological features were recorded and a medical literature review of Medline indexed articles was conducted. We present a case series of four patients with interstitial lung disease and genetically confirmed abnormalities within the FLNA gene. Their imaging findings all reveal a pattern of predominantly upper lobe overinflation, coarse pulmonary lobular septal thickening and diffuse patchy atelectasis. The clinical outcomes of our patients have been variable ranging from infant death, lobar resection and need for supplemental oxygen and bronchodilators. The progressive nature of the pulmonary aspect of this disorder and need for early aggressive supportive treatment make identification crucial to patient management and prognostic counseling. © 2017 Wiley Periodicals, Inc.

  3. 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

  4. Molecular mechanisms of cooperative binding of transcription factors Runx1–CBFβ–Ets1 on the TCRα gene enhancer

    PubMed Central

    Kasahara, Kota; Shiina, Masaaki; Fukuda, Ikuo; Ogata, Kazuhiro; Nakamura, Haruki

    2017-01-01

    Ets1 is an essential transcription factor (TF) for several important physiological processes, including cell proliferation and differentiation. Its recognition of the enhancer region of the TCRα gene is enhanced by the cooperative binding of the Runx1–CBFβ heterodimer, with the cancelation of phosphorylation-dependent autoinhibition. The detailed mechanism of this interesting cooperativity between Ets1 and the Runx1–CBFβ heterodimer is still largely unclear. Here, we investigated the molecular mechanisms of this cooperativity, by using molecular dynamics simulations. Consequently, we detected high flexibility of the loop region between the HI2 and H1 helices of Ets1. Upon Runx1–CBFβ heterodimer binding, this loop transiently adopts various sub-stable conformations in its interactions with the DNA. In addition, a network analysis suggested an allosteric pathway in the molecular assembly and identified some key residues that coincide with previous experimental studies. Our simulations suggest that the cooperative binding of Ets1 and the Runx1–CBFβ heterodimer alters the DNA conformation and induces sub-stable conformations of the HI2–H1 loop of Ets1. This phenomenon increases the flexibility of the regulatory module, including the HI2 helix, and destabilizes the inhibitory form of this module. Thus, we hypothesize that this effect facilitates Ets1–DNA binding and prevents the phosphorylation-dependent DNA binding autoinhibition. PMID:28231333

  5. Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase.

    PubMed

    Hjälm, G; MacLeod, R J; Kifor, O; Chattopadhyay, N; Brown, E M

    2001-09-14

    The G protein-coupled, extracellular calcium-sensing receptor (CaR) regulates parathyroid hormone secretion and parathyroid cellular proliferation as well as the functions of diverse other cell types. The CaR resides in caveolae-plasma membrane microdomains containing receptors and associated signaling molecules that are thought to serve as cellular "message centers." An additional mechanism for coordinating cellular signaling is the presence of scaffold proteins that bind and organize components of signal transduction cascades. With the use of the yeast two-hybrid system, we identified filamin-A (an actin-cross-linking, putative scaffold protein that binds mitogen-activated protein kinase (MAPK) components activated by the CaR) as an intracellular binding partner of the CaR's carboxyl (COOH)-terminal tail. A direct interaction of the two proteins was confirmed by an in vitro binding assay. Moreover, confocal microscopy combined with two color immunofluorescence showed co-localization of the CaR and filamin-A within parathyroid cells as well as HEK-293 cells stably transfected with the CaR. Deletion mapping localized the sites of interaction between the two proteins to a stretch of 60 amino acid residues within the distal portion of the CaR's COOH-terminal tail and domains 14 and 15 in filamin-A, respectively. Finally, introducing the portion of filamin-A interacting with the CaR into CaR-transfected HEK-293 cells using protein transduction with a His-tagged, Tat-filamin-A fusion protein nearly abolished CaR-mediated activation of ERK1/2 MAPK but had no effect on ERK1/2 activity stimulated by ADP. Therefore, the binding of the CaR's COOH-terminal tail to filamin-A may contribute to its localization in caveolae, link it to the actin-based cytoskeleton, and participate in CaR-mediated activation of MAPK.

  6. 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.

  7. Expression of distinct classes of titin isoforms in striated and smooth muscles by alternative splicing, and their conserved interaction with filamins.

    PubMed

    Labeit, Siegfried; Lahmers, Sunshine; Burkart, Christoph; Fong, Chi; McNabb, Mark; Witt, Stephanie; Witt, Christian; Labeit, Dietmar; Granzier, Henk

    2006-09-29

    While the role of titin as a sarcomeric protein is well established, its potential functional role(s) in smooth muscles and non-muscle tissues are controversial. We used a titin exon array to search for which part(s) of the human titin transcriptional unit encompassing 363 exons is(are) expressed in non-striated muscle tissues. Expression profiling of adult smooth muscle tissues (aorta, bladder, carotid, stomach) identified alternatively spliced titin isoforms, encompassing 80 to about 100 exons. These exons code for parts of the titin Z-disk, I-band and A-band regions, allowing the truncated smooth muscle titin isoform to link Z-disks/dense bodies together with thick filaments. Consistent with the array data, Western blot studies detected the expression of approximately 1 MDa smooth muscle titin in adult smooth muscles, reacting with selected Z-disc, I-band, and A-band titin antibodies. Immunofluorescence with these antibodies located smooth muscle titin in the cytoplasm of cultured human aortic smooth muscle cells and in the tunica media of intact adult bovine aorta. Real time PCR studies suggested that smooth muscle titins are expressed from a promoter located 35 kb or more upstream of the transcription initiation site used for striated muscle titin, driving expression of a bi-cistronic mRNA, coding 5' for the anonymous gene FL39502, followed 3' by titin, respectively. Our work showed that smooth muscle and striated muscle titins share in their conserved amino-terminal regions binding sites for alpha-actinin and filamins: Yeast two-hybrid screens using Z2-Zis1 titin baits identified prey clones coding for alpha-actinin-1 and filamin-A from smooth muscle, and alpha-actinin-2/3, filamin-C, and nebulin from skeletal muscle cDNA libraries, respectively. This suggests that the titin Z2-Zis1 domain can link filamins and alpha-actinin together in the periphery of the Z-line/dense bodies in a fashion that is conserved in smooth and striated muscles.

  8. Naloxone's pentapeptide binding site on filamin A blocks Mu opioid receptor-Gs coupling and CREB activation of acute morphine.

    PubMed

    Wang, Hoau-Yan; Burns, Lindsay H

    2009-01-01

    Chronic morphine causes the mu opioid receptor (MOR) to switch its coupling from Gi/o to Gs, resulting in excitatory signaling via both Galphas and its Gbetagamma dimer. Ultra-low-dose naloxone (NLX) prevents this switch and attenuates opioid tolerance and dependence. This protective effect is mediated via a high-affinity interaction of NLX to a pentapeptide region in c-terminal filamin A (FLNA), a scaffolding protein interacting with MOR. In organotypic striatal slice cultures, we now show that acute morphine induces a dose-dependent Go-to-Gs coupling switch at 5 and 15 min that resolves by 1 hr. The acute Gs coupling induced by 100 microM morphine was completely prevented by co-treatment with 100 pM NLX, (+)NLX, or naltrexone (NTX), or their pentapeptide binding site (FLNA(2561-2565)), which we show can act as a decoy for MOR or bind to FLNA itself. All of these co-treatments presumably prevent the MOR-FLNA interaction. Since ultra-low-dose NTX also attenuates the addictive properties of opioids, we assessed striatal cAMP production and CREB phosphorylation at S(133). Correlating with the Gs coupling, acute morphine induced elevated cAMP levels and a several-fold increase in pS(133)CREB that were also completely blocked by NLX, NTX or the FLNA pentapeptide. We propose that acute, robust stimulation of MOR causes an interaction with FLNA that allows an initially transient MOR-Gs coupling, which recovers with receptor recycling but persists when MOR stimulation is repeated or prolonged. The complete prevention of this acute, morphine-induced MOR-Gs coupling by 100 pM NLX/NTX or 10 microM pentapeptide segment of FLNA further elucidates both MOR signaling and the mechanism of action of ultra-low-dose NLX or NTX in attenuating opioid tolerance, dependence and addictive potential.

  9. Skeletal dysplasias due to filamin A mutations result from a gain-of-function mechanism distinct from allelic neurological disorders.

    PubMed

    Clark, Alice R; Sawyer, Gregory M; Robertson, Stephen P; Sutherland-Smith, Andrew J

    2009-12-15

    Filamin A (FLNA) crosslinks F-actin and binds proteins consistent with roles integrating cell signalling and the cytoskeleton. FLNA missense mutations are associated with the otopalatodigital syndrome (OPD) spectrum of skeletal disorders, clustering in discrete domains. One cluster is found in the second calponin homology domain of the FLNA actin-binding domain (ABD), implicating this region as essential for mediating correct function. Here we show that OPD (FLNA E254K) fibroblast lysates have equivalent concentrations of FLNA compared with controls and that recombinant FLNA E254K ABD has increased in vitro F-actin binding (K(d) 13 microm) compared with wild type (WT; K(d) 48 microm). These observations are consistent with a gain-of-function mechanism for OPD. We have determined the crystal structures of the WT and E254K FLNA ABDs at 2.3 A resolution, revealing that they adopt similar closed conformations. The E254K mutation removes a conserved salt bridge but does not disrupt the ABD structure. The solution structures are also equivalent as determined by circular dichroism spectroscopy, but differential scanning fluorimetry denaturation showed reduced stability (decreased T(m) of 5.6 degrees C) for E254K relative to WT. Ex vivo characterization of E254K OPD patient fibroblasts revealed they have similar motility and adhesion as control cells, implying that many core functions mediated by FLNA are unaffected, consistent with OPD only affecting specific tissues despite FLNA being widely expressed. These data provide the first biochemical evidence for a gain-of-function mechanism for the OPD disorders, and mechanistically distinguishes them from the loss-of-function phenotypes that manifest as disorders of neuronal migration.

  10. Nephrocystin-conserved domains involved in targeting to epithelial cell-cell junctions, interaction with filamins, and establishing cell polarity.

    PubMed

    Donaldson, John C; Dise, Rebecca S; Ritchie, Marylyn D; Hanks, Steven K

    2002-08-09

    Nephrocystin is the protein product of the gene mutated in juvenile nephronophthisis, an autosomal recessive cystic kidney disease afflicting children and young adults. Because the normal cellular function of nephrocystin is largely unknown, the molecular defects underlying disease pathogenesis remain obscure. Analysis of nephrocystin amino acid sequences from human and other species revealed three distinct conserved domains including Src homology 3 and coil-coil domains in the N-terminal region, as well as a large highly conserved C-terminal region bearing no obvious homology to other proteins and hence referred to as the "nephrocystin homology domain" (NHD). The objective of this study was to gain insight into nephrocystin function by defining functional properties of the conserved domains. We analyzed a series of nephrocystin deletion mutants expressed in Madin-Darby canine kidney and COS-7 cells. This analysis revealed previously unrecognized functional attributes of the NHD, including abilities to promote both self-association and epithelial cell-cell junctional targeting. We further observed that Madin-Darby canine kidney cell lines stably expressing a nephrocystin mutant with a deletion of the Src homology 3 domain have reduced ability to establish tight junctions as measured by transepithelial electrical resistance. Finally, from a two-hybrid screen and coimmunoprecipitation studies we identified members of the filamin family of actin-binding proteins as having the capacity to interact with the NHD. These findings support a functional role for nephrocystin as a docking protein involved in organizing a protein complex to regulate the actin cytoskeleton at sites of epithelial cell-cell adhesion and further suggest that these properties are important for establishing epithelial cell polarity.

  11. Formin 1 and Filamin B physically interact to coordinate chondrocyte proliferation and differentiation in the growth plate

    PubMed Central

    Hu, Jianjun; Lu, Jie; Lian, Gewei; Ferland, Russell J.; Dettenhofer, Markus; Sheen, Volney L.

    2014-01-01

    Filamin B (FlnB) is an actin-binding protein thought to transduce signals from various membrane receptors and intracellular proteins onto the actin cytoskeleton. Formin1 (Fmn1) is an actin-nucleating protein, implicated in actin assembly and intracellular signaling. Human mutations in FLNB cause several skeletal disorders associated with dwarfism and early bone fusion. Mouse mutations in Fmn1 cause aberrant fusion of carpal digits. We report here that FlnB and Fmn1 physically interact, are co-expressed in chondrocytes in the growth plate and share overlapping expression in the cell cytoplasm and nucleus. Loss of FlnB leads to a dramatic decrease in Fmn1 expression at the hypertrophic-to-ossification border. Loss of Fmn1-FlnB in mice leads to a more severe reduction in body size, weight and growth plate length, than observed in mice following knockout of either gene alone. Shortening of the long bone is associated with a decrease in chondrocyte proliferation and an overall delay in ossification in the double-knockout mice. In contrast to FlnB null, Fmn1 loss results in a decrease in the width of the prehypertrophic zone. Loss of both proteins, however, causes an overall decrease in the width of the proliferation zone and an increase in the differentiated hypertrophic zone. The current findings suggest that Fmn1 and FlnB have shared and independent functions. FlnB loss promotes prehypertrophic differentiation whereas Fmn1 leads to a delay. Both proteins, however, regulate chondrocyte proliferation, and FlnB may regulate Fmn1 function at the hypertrophic-to-ossification border, thereby explaining the overall delay in ossification. PMID:24760772

  12. Transcription of Nrdp1 by the androgen receptor is regulated by nuclear Filamin A in prostate cancer

    PubMed Central

    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.

    2015-01-01

    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). Studies showed that AR, a transcription factor, occupies distinct genomic loci in CRPC compared to hormone-naïve PCa; however, the cause for 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. Expressions of other AR-regulated genes lost in CRPC were also re-established by nuclear FlnA. Thus our data demonstrate 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

  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. © 2015 Society for Endocrinology.

  14. A case of boomerang dysplasia with a novel causative mutation in filamin B: identification of typical imaging findings on ultrasonography and 3D-CT imaging.

    PubMed

    Tsutsumi, Seiji; Maekawa, Ayako; Obata, Miyuki; Morgan, Timothy; Robertson, Stephen P; Kurachi, Hirohisa

    2012-01-01

    Boomerang dysplasia is a rare lethal osteochondrodysplasia characterized by disorganized mineralization of the skeleton, leading to complete nonossification of some limb bones and vertebral elements, and a boomerang-like aspect to some of the long tubular bones. Like many short-limbed skeletal dysplasias with accompanying thoracic hypoplasia, the potential lethality of the phenotype can be difficult to ascertain prenatally. We report a case of boomerang dysplasia prenatally diagnosed by use of ultrasonography and 3D-CT imaging, and identified a novel mutation in the gene encoding the cytoskeletal protein filamin B (FLNB) postmortem. Findings that aided the radiological diagnosis of this condition in utero included absent ossification of two out of three long bones in each limb and elements of the vertebrae and a boomerang-like shape to the ulnae. The identified mutation is the third described for this disorder and is predicted to lead to amino acid substitution in the actin-binding domain of the filamin B molecule. Copyright © 2012 S. Karger AG, Basel.

  15. Cooperative enhancement of water binding to crownophane by multiple hydrogen bonds: analysis by high level ab initio calculations.

    PubMed

    Tsuzuki, S; Houjou, H; Nagawa, Y; Goto, M; Hiratani, K

    2001-05-09

    The intermolecular interaction energy of the model system of the water-crownophane complex was analyzed. The water molecule has four hydrogen bonds, with the two hydrogen-donating phenolic hydroxy groups and two hydrogen-accepting oxygen atoms of the poly-oxyethylene chain of the crownophane in the complex. The MP2/6-311G(2d,2p) level calculations of the model system of the complex (hydrogen donating unit + hydrogen accepting unit + water) indicate that the binding energy of the water is 21.85 kcal/mol and that the hydrogen bond cooperativity increases the binding energy as much as 3.67 kcal/mol. The calculated interaction energies depend on the basis set, while the basis set dependence of the cooperative increment is negligible. Most of the cooperative increment is covered by the HF level calculation, which suggests that the major source of the hydrogen bond cooperativity in this system has its origin in induction. The BLYP/6-311G** and PW91/6-311G** level interaction energies of the model system are close to the MP2/6-311G** interaction energies, which suggests that the DFT calculations with these functionals are useful methods to evaluated the interactions of hydrogen bonded systems.

  16. Enhancing the Security Cooperation Marine Air Ground Task Force to Satisfy the Needs of the Uncertain Global Security Environment

    DTIC Science & Technology

    2009-06-12

    operations” ( Hamblet 2000, 95). As a response, the National Foreign Affairs Training Center and National Defense University have joined the service...MacMillan and Co., Limited. Hamblet , William P., and Jerry G. Kline. 200. "Interagency Cooperation: PDD 56 and Complex Contingency Operations." Joint

  17. 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…

  18. 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…

  19. Binding of the P2Y2 Nucleotide Receptor to Filamin A Regulates Migration of Vascular Smooth Muscle Cells

    PubMed Central

    Yu, Ningpu; Erb, Laurie; Shivaji, Rikka; Weisman, Gary A.; Seye, Cheikh I.

    2013-01-01

    The functional expression of the G protein– coupled P2Y2 nucleotide receptor (P2Y2R) has been associated with proliferation and migration of vascular smooth muscle cells (SMCs), 2 processes involved in atherosclerosis and restenosis. Activation of the P2Y2R causes dynamic reorganization of the actin cytoskeleton, which transmits biochemical signals and forces necessary for cell locomotion, suggesting that P2Y2Rs may be linked to the actin cytoskeleton. Here, we identified filamin A (FLNa) as a P2Y2R-interacting protein using a yeast 2-hybrid system screen with the C-terminal region of the P2Y2R as bait. The FLNa binding site in the P2Y2R is localized between amino acids 322 and 333. Deletion of this region led to selective loss of FLNa binding to the P2Y2R and abolished Tyr phosphorylation of FLNa induced by the P2Y2R agonist UTP. Using both time-lapse microscopy and the Transwell cell migration assay, we showed that UTP significantly increased SMC spreading on collagen I (6.8 fold; P≤0.01) and migration (3.6 fold; P≤0.01) of aortic SMCs isolated from wild-type mice, as compared with unstimulated SMCs. UTP-induced spreading and migration of aortic SMCs did not occur with cells isolated from P2Y2R knockout mice. Expression of the full-length P2Y2R in SMCs isolated from P2Y2R knockout mice restored both UTP-induced spreading and migration. In contrast, UTP-induced spreading and migration did not occur in SMCs isolated from P2Y2R knockout mice transfected with a mutant P2Y2R that does not bind FLNa. Furthermore, ex vivo studies showed that both ATP and UTP (10 µmol/L) promoted migration of SMCs out of aortic explants isolated from wild-type but not P2Y2R knockout mice. Thus, this study demonstrates that P2Y2R/FLNa interaction selectively regulates spreading and migration of vascular SMCs. PMID:18202316

  20. Comparison of technology-based cooperative learning with technology-based individual learning in enhancing fundamental nursing proficiency.

    PubMed

    Lin, Zu-Chun

    2013-05-01

    The aim of nursing education is to prepare students with critical thinking, high interests in profession and high proficiency in patient care. Cooperative learning promotes team work and encourages knowledge building upon discussion. It has been viewed as one of the most powerful learning methods. Technology has been considered an influential tool in teaching and learning. It assists students in gathering more information to solve the problems and master skills better. The purpose of this study was to compare the effect of technology-based cooperative learning with technology-based individual learning in nursing students' critical thinking in catheterization knowledge gaining, error discovering, skill acquisitions, and overall scores. This study used a pretest-posttest experimental design. Ninety-eight students were assigned randomly to one of two groups. Questionnaires and tests were collected at baseline and after completion of intervention. The results of this study showed that there was no significant difference in related catheterization skill performance. However, the remaining variables differed greatly between the two groups. CONCLUSIONS AND APPLICATIONS: This study's findings guide the researchers and instructors to use technology-based cooperative learning more appropriately. Future research should address the design of the course module and the availability of mobile devices to reach student-centered and learn on the move goals. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Cooperation of Adenosine with Macrophage Toll-4 Receptor Agonists Leads to Increased Glycolytic Flux through the Enhanced Expression of PFKFB3 Gene*

    PubMed Central

    Ruiz-García, Almudena; Monsalve, Eva; Novellasdemunt, Laura; Navarro-Sabaté, Àurea; Manzano, Anna; Rivero, Samuel; Castrillo, Antonio; Casado, Marta; Laborda, Jorge; Bartrons, Ramón; Díaz-Guerra, María José M.

    2011-01-01

    Macrophages activated through Toll receptor triggering increase the expression of the A2A and A2B adenosine receptors. In this study, we show that adenosine receptor activation enhances LPS-induced pfkfb3 expression, resulting in an increase of the key glycolytic allosteric regulator fructose 2,6-bisphosphate and the glycolytic flux. Using shRNA and differential expression of A2A and A2B receptors, we demonstrate that the A2A receptor mediates, in part, the induction of pfkfb3 by LPS, whereas the A2B receptor, with lower adenosine affinity, cooperates when high adenosine levels are present. pfkfb3 promoter sequence deletion analysis, site-directed mutagenesis, and inhibition by shRNAs demonstrated that HIF1α is a key transcription factor driving pfkfb3 expression following macrophage activation by LPS, whereas synergic induction of pfkfb3 expression observed with the A2 receptor agonists seems to depend on Sp1 activity. Furthermore, levels of phospho-AMP kinase also increase, arguing for increased PFKFB3 activity by phosphorylation in long term LPS-activated macrophages. Taken together, our results show that, in macrophages, endogenously generated adenosine cooperates with bacterial components to increase PFKFB3 isozyme activity, resulting in greater fructose 2,6-bisphosphate accumulation. This process enhances the glycolytic flux and favors ATP generation helping to develop and maintain the long term defensive and reparative functions of the macrophages. PMID:21464136

  2. Effective Blocking of the White Enhancer Requires Cooperation between Two Main Mechanisms Suggested for the Insulator Function

    PubMed Central

    Stakhov, Viacheslav; Ivlieva, Tatyana; Parshikov, Alexander; Studitsky, Vasily M.; Georgiev, Pavel

    2013-01-01

    Chromatin insulators block the action of transcriptional enhancers when interposed between an enhancer and a promoter. In this study, we examined the role of chromatin loops formed by two unrelated insulators, gypsy and Fab-7, in their enhancer-blocking activity. To test for this activity, we selected the white reporter gene that is activated by the eye-specific enhancer. The results showed that one copy of the gypsy or Fab-7 insulator failed to block the eye enhancer in most of genomic sites, whereas a chromatin loop formed by two gypsy insulators flanking either the eye enhancer or the reporter completely blocked white stimulation by the enhancer. However, strong enhancer blocking was achieved due not only to chromatin loop formation but also to the direct interaction of the gypsy insulator with the eye enhancer, which was confirmed by the 3C assay. In particular, it was observed that Mod(mdg4)-67.2, a component of the gypsy insulator, interacted with the Zeste protein, which is critical for the eye enhancer–white promoter communication. These results suggest that efficient enhancer blocking depends on the combination of two factors: chromatin loop formation by paired insulators, which generates physical constraints for enhancer–promoter communication, and the direct interaction of proteins recruited to an insulator and to the enhancer–promoter pair. PMID:23861668

  3. Cooperative Teaching Designed To Enhance Cooperative Learning.

    ERIC Educational Resources Information Center

    Cromwell, Ronald; Dunlap, Linda

    Despite institutional reluctance to move away from a traditional lecture format for content presentation and written exams and term papers for evaluation, a team-taught course entitled "Integration of Learning Theory and Teaching Methodology" has been taught at Marist College, a small liberal arts college in New York. Rather than…

  4. Social penalty promotes cooperation in a cooperative society.

    PubMed

    Ito, Hiromu; Yoshimura, Jin

    2015-08-04

    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.

  5. 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

  6. Effects of lentivirus-mediated CREB expression in the dorsolateral striatum: memory enhancement and evidence for competitive and cooperative interactions with the hippocampus.

    PubMed

    Kathirvelu, Balachandar; Colombo, Paul J

    2013-11-01

    Neural systems specialized for memory may interact during memory formation or recall, and the results of interactions are important determinants of how systems control behavioral output. In two experiments, we used lentivirus-mediated expression of the transcription factor CREB (LV-CREB) to test if localized manipulations of cellular plasticity influence interactions between the hippocampus and dorsolateral striatum. In Experiment 1, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for response learning, and impairs memory for place learning. LV-CREB in the dorsolateral striatum had no effect on response learning, but impaired place memory; a finding consistent with competition between the striatum and hippocampus. In Experiment 2, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for cue learning, and impairs memory for contextual fear conditioning. LV-CREB in the dorsolateral striatum enhanced memory for cue learning and, in contrast to our prediction, also enhanced memory for contextual fear conditioning, consistent with a cooperative interaction between the striatum and hippocampus. Overall, the current experiments demonstrate that infusion of LV-CREB in the dorsolateral striatum (1) increases levels of CREB protein locally, (2) does not alter acquisition of place, response, cue, or contextual fear conditioning, (3) facilitates memory for cue learning and contextual fear conditioning, and (4) impairs memory for place learning. Taken together, the present results provide evidence that LV-CREB in the dorsolateral striatum can enhance memory formation and cause both competitive and cooperative interactions with the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

  7. 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

  8. Bilateral periventricular nodular heterotopia due to filamin 1 gene mutation: widespread glomeruloid microvascular anomaly and dysplastic cytoarchitecture in the cerebral cortex.

    PubMed

    Kakita, Akiyoshi; Hayashi, Shintaro; Moro, Francesca; Guerrini, Renzo; Ozawa, Tsunenori; Ono, Koji; Kameyama, Shigeki; Walsh, Christopher A; Takahashi, Hitoshi

    2002-12-01

    Bilateral periventricular nodular heterotopia (BPNH) is a neuronal migration disorder that is characterized by subependymal nodules of gray matter. Recently, a causative gene for BPNH, filamin 1, has been identified, and possible roles of the translated protein in cell migration and blood vessel development have been proposed. We report here the histopathological features of an autopsy case of BPNH with widespread glomeruloid microvascular anomaly and dysplastic cytoarchitecture in the cerebral cortex, in whom we found a novel exon 11 (Val528Met) filamin 1 mutation. Within the periventricular nodules, well-differentiated pyramidal neurons were randomly oriented. A small proportion of neurons were immunolabeled with antibodies raised against calbindin D-28k, parvalbumin, or calretinin. We used a carbocyanine dye (DiI) tracing technique to investigate the extent of fiber projections within and outside the nodules. The labeled fibers formed bundles that extended into the surrounding white matter. Connections between adjacent nodules were evident. Connections between the nodules and the cerebral cortex were also seen, with a small number of labeled fibers reaching the cortex. In the cerebral cortex, small closely packed vessels ran in a parallel fashion throughout all of the layers. Immunohistochemically, the inner rim of individual vessel lumina was labeled by an antibody against factor VIII, and the vessel walls were labeled by antibodies against actin and laminin. Astrocyte processes, labeled with an antibody to glial fibrillary acidic protein, invaded these vascular channels. Ultrastructurally, a network of basal lamina-like materials lined with endothelial cells was evident. The cytoarchitecture of the cerebral cortex was disturbed, in that the columnar neuronal arrangement was distorted around the malformed vessels. This case appears to represent an example of BPNH manifesting widespread developmental anomalies within the blood vessels and the cortical

  9. Inclusion of many-body effects in the additive CHARMM protein CMAP potential results in enhanced cooperativity of α-helix and β-hairpin formation.

    PubMed

    Best, Robert B; Mittal, Jeetain; Feig, Michael; MacKerell, Alexander D

    2012-09-05

    Folding simulations on peptides and proteins using empirical force fields have demonstrated the sensitivity of the results to details of the backbone potential. A recently revised version of the additive CHARMM protein force field, which includes optimization of the backbone CMAP potential to achieve good balance between different types of secondary structure, correcting the α-helical bias present in the former CHARMM22/CMAP energy function, is shown to result in improved cooperativity for the helix-coil transition. This is due to retention of the empirical corrections introduced in the original CMAP to reproduce folded protein structures-corrections that capture many-body effects missing from an energy surface fitted to gas phase calculations on dipeptides. The experimental temperature dependence of helix formation in (AAQAA)(3) and parameters for helix nucleation and elongation are in much better agreement with experiment than those obtained with other recent force fields. In contrast, CMAP parameters derived by fitting to a vacuum quantum mechanical surface for the alanine dipeptide do not reproduce the enhanced cooperativity, showing that the empirical backbone corrections, and not some other feature of the force field, are responsible. We also find that the cooperativity of β-hairpin formation is much improved relative to other force fields we have studied. Comparison with (ϕ,ψ) distributions from the Protein Data Bank further justifies the inclusion of many-body effects in the CMAP. These results suggest that the revised energy function will be suitable for both simulations of unfolded or intrinsically disordered proteins and for investigating protein-folding mechanisms. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  10. Cooperative binding of estrogen receptor to imperfect estrogen-responsive DNA elements correlates with their synergistic hormone-dependent enhancer activity.

    PubMed

    Martinez, E; Wahli, W

    1989-12-01

    The Xenopus vitellogenin (vit) gene B1 estrogen-inducible enhancer is formed by two closely adjacent 13 bp imperfect palindromic estrogen-responsive elements (EREs), i.e. ERE-2 and ERE-1, having one and two base substitutions respectively, when compared to the perfect palindromic consensus ERE (GGTCANNNTGACC). Gene transfer experiments indicate that these degenerated elements, on their own, have a low or no regulatory capacity at all, but in vivo act together synergistically to confer high receptor- and hormone-dependent transcription activation to the heterologous HSV thymidine kinase promoter. Thus, the DNA region upstream of the vitB1 gene comprising these two imperfect EREs separated by 7 bp, was called the vitB1 estrogen-responsive unit (vitB1 ERU). Using in vitro protein-DNA interaction techniques, we demonstrate that estrogen receptor dimers bind cooperatively to the imperfect EREs of the vitB1 ERU. Binding of a first receptor dimer to the more conserved ERE-2 increases approximately 4- to 8-fold the binding affinity of the receptor to the adjacent less conserved ERE-1. Thus, we suggest that the observed synergistic estrogen-dependent transcription activation conferred by the pair of hormone-responsive DNA elements of the vit B1 ERU is the result of cooperative binding of two estrogen receptor dimers to these two adjacent imperfect EREs.

  11. Cooperative binding of estrogen receptor to imperfect estrogen-responsive DNA elements correlates with their synergistic hormone-dependent enhancer activity.

    PubMed Central

    Martinez, E; Wahli, W

    1989-01-01

    The Xenopus vitellogenin (vit) gene B1 estrogen-inducible enhancer is formed by two closely adjacent 13 bp imperfect palindromic estrogen-responsive elements (EREs), i.e. ERE-2 and ERE-1, having one and two base substitutions respectively, when compared to the perfect palindromic consensus ERE (GGTCANNNTGACC). Gene transfer experiments indicate that these degenerated elements, on their own, have a low or no regulatory capacity at all, but in vivo act together synergistically to confer high receptor- and hormone-dependent transcription activation to the heterologous HSV thymidine kinase promoter. Thus, the DNA region upstream of the vitB1 gene comprising these two imperfect EREs separated by 7 bp, was called the vitB1 estrogen-responsive unit (vitB1 ERU). Using in vitro protein-DNA interaction techniques, we demonstrate that estrogen receptor dimers bind cooperatively to the imperfect EREs of the vitB1 ERU. Binding of a first receptor dimer to the more conserved ERE-2 increases approximately 4- to 8-fold the binding affinity of the receptor to the adjacent less conserved ERE-1. Thus, we suggest that the observed synergistic estrogen-dependent transcription activation conferred by the pair of hormone-responsive DNA elements of the vit B1 ERU is the result of cooperative binding of two estrogen receptor dimers to these two adjacent imperfect EREs. Images PMID:2583118

  12. Implementing web-based ping-pong-type e-communication to enhance staff satisfaction, multidisciplinary cooperation, and clinical effectiveness

    PubMed Central

    Yeh, Pei-Han; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Lai, Chun-Liang; Tsai, Wei-Ta; Hsieh, Hui-Ling; Shih, Yi-Ting; Chen, Liang-Cheng; Huang, Li-Wen; Lin, Yi-An; Lin, Po-Hao; Lin, Yung-Hsiang; Liu, Dai-Wei; Hsu, Feng-Chun; Tsai, Shiang-Jiun; Liu, Jia-Chi; Chung, En-Seu; Lin, Hon-Yi

    2016-01-01

    Abstract Background: Frequent multidisciplinary communication is essential in conducting daily radiotherapy (RT) practice. However, traditional oral or paper-based communication has limitations. E-communication has been suggested, but its effects are still not well demarcated in the field of radiation oncology. Objects: In our web-based integrated information platform, we constructed a ping-pong-type e-communication function to transfer specific notations among multidisciplinary RT staffs. The purpose was to test whether applying this e-communication can increase effectiveness of multidisciplinary cooperation when compared with oral or paper-based practice. Staff satisfaction and clinical benefits were also demonstrated. Design and setting: A real-world quality-improving study was conducted in a large center of radiation oncology. Participants and dataset used: Before and after applying multidisciplinary e-communication (from 2014 to 2015), clinical RT staffs were surveyed for their user experience and satisfaction (n = 23). For measuring clinical effectiveness, a secondary database of irradiated head and neck cancer patients was re-analyzed for comparing RT toxicities (n = 402). Interventions: Applying ping-pong-type multidisciplinary reflective e-communication was the main intervention. Outcome measures: For measuring staff satisfaction, eight domains were surveyed, such as timeliness, convenience, and completeness. For measuring clinical effectiveness of multidisciplinary cooperation, event rates of severe (i.e., grade 3–4) RT mucositis and dermatitis were recorded. Results: Overall, when compared with oral communication only, e-communication demonstrated multiple benefits, particularly on notation-review convenience (2.00 ± 1.76 vs 9.19 ± 0.81; P < 0.0001). When compared with paper-based practice, e-communication showed statistically significant benefits on all eight domains, especially on notation-review convenience (5.05 ± 2.11 vs

  13. 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.

  14. Enhancing Graduate Education and Research in Ocean Sciences at the Universidad de Concepcion (UDEC) and in Chile: Cooperation Between UDEC and Woods Hole Oceanographic Institution.

    NASA Astrophysics Data System (ADS)

    Farrington, J.; Pantoja, S.

    2007-05-01

    The Woods Hole Oceanographic Institution, USA (WHOI) and the University of Concepcion, Chile (UDEC) entered into an MOU to enhance graduate education and research in ocean sciences in Chile and enhance research for understanding the Southeastern Pacific Ocean. The MOU was drafted and signed after exchange visits of faculty. The formulation of a five year program of activities included: exchange of faculty for purposes of enhancing research, teaching and advising; visits of Chilean graduate students to WHOI for several months of supplemental study and research in the area of their thesis research; participation of Chilean faculty and graduate students in WHOI faculty led cruises off Chile and Peru (with Peruvian colleagues); a postdoctoral fellowship program for Chilean ocean scientists at WHOI; and the establishment of an Austral Summer Institute of advanced undergraduate and graduate level intensive two to three week courses on diverse topics at the cutting edge of ocean science research co-sponsored by WHOI and UDEC for Chilean and South American students with faculty drawn from WHOI and other U.S. universities with ocean sciences graduate schools and departments, e.g. Scripps Institution of Oceanography, University of Delaware. The program has been evaluated by external review and received excellent comments. The success of the program has been due mainly to: (1) the cooperative attitude and enthusiasm of the faculty colleagues of both Chilean Universities (especially UDEC) and WHOI, students and postdoctoral fellows, and (2) a generous grant from the Fundacion Andes- Chile enabling these activities.

  15. SIRT1 induces EMT by cooperating with EMT transcription factors and enhances prostate cancer cell migration and metastasis.

    PubMed

    Byles, V; Zhu, L; Lovaas, J D; Chmilewski, L K; Wang, J; Faller, D V; Dai, Y

    2012-10-25

    The epithelial-to-mesenchymal transition (EMT) is a crucial program for the invasion and metastasis of epithelial tumors that involves loss of cell-cell adhesion and increased cell mobility; however, mechanisms underlying this transition are not fully elucidated. Here, we propose a novel mechanism through which the nicotinamide adenine dinucleotide-dependent histone deacetylase SIRT1 regulates EMT in prostate cancer cells through cooperation with the EMT inducing transcription factor ZEB1. We found that forced expression of SIRT1 in non-transformed PZ-HPV-7 prostate epithelial cells disrupts the epithelial morphology concomitant with decreased expression of the epithelial marker, E-cadherin, and increased expression of mesenchymal markers. In contrast, silencing SIRT1 in metastatic prostate tumor cells restores cell-cell adhesion and induces a shift toward an epithelial morphology concomitant with increased expression of E-cadherin and decreased expression of mesenchymal markers. We also found that SIRT1 has a physiologically relevant role in endogenous EMT induced by EGF signaling in prostate cancer cells. We propose that the regulation of EMT by SIRT1 involves modulation of, and cooperation with, the EMT inducing transcription factor ZEB1. Specifically, we show that SIRT1 silencing reduces expression of ZEB1 and that SIRT1 is recruited to the E-cadherin proximal promoter by ZEB1 to deacetylate histone H3 and to reduce binding of RNA polymerase II, ultimately suppressing E-cadherin transcription. We thus identify a necessary role for ZEB1 in SIRT1-mediated EMT. Finally, we show that reduction of SIRT1 decreases prostate cancer cell migration in vitro and metastasis in vivo in immunodeficient mice, which is largely independent of any general effects of SIRT1 on prostate cancer growth and survival. We therefore identify SIRT1 as a positive regulator of EMT and metastatic growth of prostate cancer cells and our findings implicate overexpressed SIRT1 as a potential

  16. 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

  17. 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.

  18. Glucocorticoid receptor-mediated suppression of the interleukin 2 gene expression through impairment of the cooperativity between nuclear factor of activated T cells and AP-1 enhancer elements

    PubMed Central

    1992-01-01

    The immunosuppressant hormone dexamethasone (Dex) interferes with T cell-specific signals activating the enhancer sequences directing interleukin 2 (IL-2) transcription. We report that the Dex-dependent downregulation of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and calcium ionophore-induced activity of the IL-2 enhancer are mediated by glucocorticoid receptor (GR) via a process that requires intact NH2- and COOH-terminal and DNA-binding domains. Functional analysis of chloramphenicol acetyltransferase (CAT) vectors containing internal deletions of the -317 to +47 bp IL-2 enhancer showed that the GR- responsive elements mapped to regions containing nuclear factor of activated T cells protein (NFAT) (-279 to -263 bp) and AP-1 (-160 to - 150 bp) motifs. The AP-1 motif binds TPA and calcium ionophore-induced nuclear factor(s) containing fos protein. TPA and calcium ionophore- induced transcriptional activation of homo-oligomers of the NFAT element were not inhibited by Dex, while AP-1 motif concatemers were not stimulated by TPA and calcium ionophore. When combined, NFAT and AP- 1 motifs significantly synergized in directing CAT transcription. Such a synergism was impaired by specific mutations affecting the trans- acting factor binding to either NFAT or AP-1 motifs. In spite of the lack of hormone regulation of isolated cis elements, TPA/calcium ionophore-mediated activation of CAT vectors containing a combination of the NFAT and the AP-1 motifs became suppressible by Dex. Our results show that the IL-2-AP-1 motif confers GR sensitivity to a flanking region containing a NFAT element and suggest that synergistic cooperativity between the NFAT and AP-1 sites allows GR to mediate the Dex inhibition of IL-2 gene transcription. Therefore, a Dex-modulated second level of IL-2 enhancer regulation, based on a combinatorial modular interplay, appears to be present. PMID:1740658

  19. Enhancing clinical effectiveness of pre-radiotherapy workflow by using multidisciplinary-cooperating e-control and e-alerts: A SQUIRE-compliant quality-improving study.

    PubMed

    Lin, Yung-Hsiang; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Lai, Chun-Liang; Shih, Yi-Ting; Yeh, Pei-Han; Lin, Yi-An; Tsai, Wei-Ta; Hsieh, Hui-Ling; Chen, Liang-Cheng; Huang, Li-Wen; Lin, Po-Hao; Liu, Dai-Wei; Hsu, Feng-Chun; Tsai, Shiang-Jiun; Liu, Jia-Chi; Chung, En-Seu; Lin, Hon-Yi

    2017-06-01

    Radiotherapy (RT) is useful in managing cancer diseases. In clinical practice, early initiation of RT is crucial for enhancing tumor control. But, delivering precise RT requires a series of pre-RT working processes in a tight staff-cooperation manner. In this regard, using information system to conduct e-control and e-alerts has been suggested to improve practice effectiveness; however, this effect is not well defined in a real-world RT setting.We designed an information system to perform e-control and e-alerts for the whole process of pre-RT workflow to shorten processing time, to improve overall staff satisfaction, and to enhance working confidence.A quality-improving study conducted in a large RT center.Externally validated data were retrospectively analyzed for comparison before (from Sep. 2012 to Dec. 2012, n = 223) and after (from Sep. 2013 to Dec. 2013, n = 240) implementation of pre-RT e-control and e-alerts.Applying the e-control with delay-working e-alerts in pre-RT workflow was the main intervention.Nine workstations were identified in pre-RT workflow. The primary outcome measure was the processing time in each pre-RT workstations before and after implementing the e-control and e-alerts. Secondary measures were staff-working confidence and near-missing cases during the process of pre-RT workflow.After implementing e-control, overall processing time of pre-RT workflow was shortened from 12.2 days to 8.9 days (P < .001). Follow-up data (till Jul. 2016) showed a durable effect of 9.2 days, being still below the predefined threshold of <10 days.Using a multidisciplinary-cooperating information system is useful to conduct e-control and e-alerts in the whole process of pre-RT workflow. Clinical effectiveness, staff satisfaction, and working confidence are able to be enhanced obviously.

  20. Enhanced Electronic Communication and Electrochemical Sensitivity Benefiting from the Cooperation of Quadruple Hydrogen Bonding and π-π Interactions in Graphene/Multi-Walled Carbon Nanotube Hybrids.

    PubMed

    Wang, Qiguan; Wang, Sumin; Shang, Jiayin; Qiu, Shenbao; Zhang, Wenzhi; Wu, Xinming; Li, Jinhua; Chen, Weixing; Wang, Xinhai

    2017-02-22

    By designing a molecule labeled as UPPY with both ureidopyrimidinone (UP) and pyrene (PY) units, the supramolecular self-assembly of multiwalled carbon nanotube (MWNT) and reduced graphene oxide (rGO) was driven by the UP quadruple hydrogen-bonding and PY-based π-π interactions to form a novel hybrid of rGO-UPPY-MWNT in which the morphology of rGO-wrapped MWNT was found. Bridged by the two kinds of noncovalent bonding, enhanced electronic communication occurred in rGO-UPPY-MWNT. Also, under the cooperation of UP quadruple hydrogen-bonding and PY-based π-π interactions, higher electrical conductivity and better charge transfer were observed for rGO-UPPY-MWNT, compared with the rGO-MWNT composite without such noncovalent bonds, and that with just single PY-based π-π interaction (rGO-PY-MWNT) or UP quadruple hydrogen bond (rGO-UP-MWNT). Specifically, the electrical conductivity of rGO-PY-MWNT hybrids was increased approximately sevenfold, and the interfacial charge transfer resistance was nearly decreased by 1 order of magnitude compared with rGO-MWNT, rGO-UP-MWNT, and rGO-PY-MWNT. Resulting from its excellent electrical conductivity and charge transfer properties, the rGO-UPPY-MWNT modified electrode exhibited enhanced electrochemical activity toward dopamine with detection limit as low as 20 nM.

  1. THE ENDOCANNABINOID 2-ARACHIDONOYLGLYCEROL MEDIATES D1 AND D2 RECEPTOR COOPERATIVE ENHANCEMENT OF RAT NUCLEUS ACCUMBENS CORE NEURON FIRING

    PubMed Central

    Seif, T.; Makriyannis, A.; Kunos, G.; Bonci, A.; Hopf, F. W.

    2011-01-01

    Many motivated and addiction-related behaviors are sustained by activity of both dopamine D1- and D2-type receptors (D1Rs and D2Rs) as well as CB1 receptors (CB1Rs) in the nucleus accumbens (NAc). Here, we use in vitro whole-cell patch-clamp electrophysiology to describe an endocannabinoid (eCB)–dopamine receptor interaction in adult rat NAc core neurons. D1R and D2R agonists in combination enhanced firing, with no effect of a D1R or D2R agonist alone. This D1R+D2R-mediated firing increase required CB1Rs, since it was prevented by the CB1R antagonists AM251 and Rimonabant. The D1R+D2R firing increase also required phospholipase C (PLC), the major synthesis pathway for the eCB 2-arachidonoylglycerol (2-AG) and one of several pathways for anandamide. Further, inhibition of 2-AG hydrolysis with the monoglyceride lipase (MGL) inhibitor JZL184 allowed subthreshold levels of D1R+D2R receptor agonists to enhance firing, while inhibition of anandamide hydrolysis with the fatty acid amide hydrolase (FAAH) inhibitors URB597 or AM3506 did not. Filling the postsynaptic neuron with 2-AG enabled subthreshold D1R+D2R agonists to increase firing, and the 2AG+D1R+D2R increase in firing was prevented by a CB1R antagonist. Also, the metabotropic glutamate receptor 5 (mGluR5) blocker MPEP prevented the ability of JZL184 to promote subthreshold D1R+D2R enhancement of firing, while the 2-AG+D1R+D2R increase in firing was not prevented by the mGluR5 blocker, suggesting that mGluR5s acted upstream of 2-AG production. Thus, our results taken together are consistent with the hypothesis that NAc core eCBs mediate dopamine receptor (DAR) enhancement of firing, perhaps providing a cellular mechanism underlying the central role of NAc core D1Rs, D2Rs, CB1Rs, and mGluR5s during many drug-seeking behaviors. PMID:21821098

  2. 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…

  3. Cooperative Strategies for Enhancing Performance of Photothermal Therapy (PTT) Agent: Optimizing Its Photothermal Conversion and Cell Internalization Ability.

    PubMed

    Du, Baoji; Ma, Chongbo; Ding, Guanyu; Han, Xu; Li, Dan; Wang, Erkang; Wang, Jin

    2017-01-23

    Photothermal conversion ability (PCA) and cell internalization ability (CIA) are two key factors for determining the performance of photothermal agents. The previous studies mostly focus on improving the PCA by exploring new photothermal nanomaterials. Herein, the authors take the hybrids of graphene and gold nanostar (GGN) as an example to investigate the gradually enhanced phototherapy effect by changing the PCA and CIA of photothermal therapy (PTT) agent simultaneously. Based on the GGN, the GGN and the reduced GGN protected by bovine serum albumin (BSA) or BSA-FA (folic acid) are prepared, which are named as GGNB, rGGNB, and rGGNB-FA, respectively. The rGGNB showed an enhanced PCA compared to GGNB, leading to strong cell ablation. On the other hand, the 1,2-dioleoyl-3-trimethylammoniumpropan (DOTAP) can activate the endocytosis and promote the CIA of rGGNB, further help rGGNB to be more internalized into the cells. Finally, rGGNB-FA with the target ability can make itself further internalized into the cells with the aid of DOTAP, which can significantly destroy the cancer cells even at the low laser density of 0.3 W cm(-2) . Therefore, a new angle of view is brought out for researching the PTT agents of high performance.

  4. 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.

  5. 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.)

  6. 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.…

  7. 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.

  8. 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.)

  9. 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

  10. Activated CD4+ T cells enhance radiation effect through the cooperation of interferon-γ and TNF-α

    PubMed Central

    2010-01-01

    Background Approaches that enhance radiation effect may lead to improved clinical outcome and decrease toxicity. Here we investigated whether activated CD4+ T cells (aCD4) can serve as an effective radiosensitizer. Methods CD4+ T cells were activated with anti-CD3 and anti-CD28 mAbs. Hela cells were presensitized with aCD4 or conditioned supernatant (aCD4S) or recombinant cytokines for 2 days, followed γ-irradiation. The treated cells were cultured for an additional 2 to 5 days for cell proliferation, cell cycle, and western blot assays. For confirmation, other cancer cell lines were also used. Results Presensitization of tumor cells with aCD4 greatly increased tumor cell growth inhibition. Soluble factors secreted from activated CD4+ T cells were primarily responsible for the observed effect. IFN-γ seemed to play a major role. TNF-α, though inactive by itself, significantly augmented the radiosensitizing activity of IFN-γ. aCD4S, but not IFN-γ or IFN-γ/TNF-α combination, was found to enhance the γ-irradiation-induced G2/M phase arrest. Bax expression was highly upregulated in Hela cells presensitized with aCD4S followed by γ-irradiation. The radio-sensitizing activity of aCD4 is not uniquely observed with Hela cell line, but also seen with other cancer cell lines of various histology. Conclusions Our findings suggest possible molecular and cellular mechanisms that may help explain the radio-sensitization effect of activated lymphocytes, and may provide an improved strategy in the treatment of cancer with radiotherapy. PMID:20178622

  11. Cooperative Learning and Critical Thinking.

    ERIC Educational Resources Information Center

    Cooper, James L.

    1995-01-01

    Contends that, in many ways, college teaching has remained largely unchanged since the days of the medieval university. Discusses the role of cooperative learning in higher education and maintains that the technique can enhance critical thinking skills. (CFR)

  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.

  13. 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.

  14. Cooperative Networks

    DTIC Science & Technology

    2009-02-23

    than the traditional direct transmission and full cooperation schemes. B. OFDM-Based Cooperation Relay and Subchannel Assignment and Combining We... subchannel assignment and combining schemes. Based on the amount of CSI, resources, such as subchannels , can be allocated to relays to improve the end-to-end...relay node uses the same subchannel to relay the information transmitted by the source node. To further improve the performance gain, subchannel

  15. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. IFN-γ and CCL2 cooperate to redirect tumor-infiltrating monocytes to degrade fibrosis and enhance chemotherapy efficacy in pancreatic carcinoma

    PubMed Central

    Tooker, Graham M.; Graham, Kathleen; Fraietta, Joseph A.; Beatty, Gregory L.

    2016-01-01

    Dense fibrosis and a robust macrophage infiltrate are key therapeutic barriers in pancreatic ductal adenocarcinoma (PDAC). CD40 activation can circumvent these barriers by inducing macrophages, originating from peripheral blood monocytes, to deplete fibrosis. The precise mechanism and therapeutic implications of this anti-fibrotic activity, though, remain unclear. Here, we report that IFN-γ and CCL2 released systemically in response to a CD40 agonist cooperate to redirect a subset of Ly6C+CCR2+ monocytes/macrophages to infiltrate tumors and deplete fibrosis. Whereas CCL2 is required for Ly6C+ monocyte/macrophage infiltration, IFN-γ is necessary for tumor-infiltrating monocytes/macrophages to shift the profile of matrix metalloproteinases (MMPs) in tumors leading to MMP-dependent fibrosis degradation. In addition, MMP13-dependent loss of extracellular matrix components induced by a CD40 agonist increased PDAC sensitivity to chemotherapy. Our findings demonstrate that fibrosis in PDAC is a bidirectional process that can be rapidly altered by manipulating a subset of tumor-infiltrating monocytes leading to enhanced chemotherapy efficacy. PMID:26896096

  17. Interspecific cooperation: enhanced growth, attachment and strain-specific distribution in biofilms through Azospirillum brasilense-Pseudomonas protegens co-cultivation.

    PubMed

    Pagnussat, Luciana A; Salcedo, Florencia; Maroniche, Guillermo; Keel, Christoph; Valverde, Claudio; Creus, Cecilia M

    2016-10-01

    Plant-growth-promoting bacteria belonging to Azospirillum and Pseudomonas genera are major inhabitants of the rhizosphere. Both are increasingly commercialized as crops inoculants. Interspecific interaction in the rhizosphere is critical for inoculants aptness. The objective of this work was to evaluate Azospirillum and Pseudomonas interaction in mixed biofilms by co-cultivation of the model strains Azospirillum brasilense Sp245 and Pseudomonas protegens CHA0. The results revealed enhanced growth of both strains when co-cultured in static conditions. Moreover, Sp245 biofilm formed in plastic surfaces was increased 2-fold in the presence of CHA0. Confocal microscopy revealed highly structured mixed biofilms showing Sp245 mainly on the bottom and CHA0 towards the biofilm surface. In addition, A. brasilense biofilm was thicker and denser when co-cultured with P. protegens. In a colony-colony interaction assay, Sp245 changed nearby CHA0 producing small colony phenotype, which accounts for a diffusible metabolite mediator; though CHA0 spent medium did not affect Sp245 colony phenotype. Altogether, these results point to a cooperative interaction between A. brasilense Sp245 and P. protegens CHA0 in which both strains increase their static growth and produce structured mixed biofilms with a strain-specific distribution. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. 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.

  19. Filamin B Plays a Key Role in Vascular Endothelial Growth Factor-induced Endothelial Cell Motility through Its Interaction with Rac-1 and Vav-2*

    PubMed Central

    del Valle-Pérez, Beatriz; Martínez, Vanesa Gabriela; Lacasa-Salavert, Cristina; Figueras, Agnès; Shapiro, Sandor S.; Takafuta, Toshiro; Casanovas, Oriol; Capellà, Gabriel; Ventura, Francesc; Viñals, Francesc

    2010-01-01

    Actin-binding proteins filamin A (FLNA) and B (FLNB) are expressed in endothelial cells and play an essential role during vascular development. In order to investigate their role in adult endothelial cell function, we initially confirmed their expression pattern in different adult mouse tissues and cultured cell lines and found that FLNB expression is concentrated mainly in endothelial cells, whereas FLNA is more ubiquitously expressed. Functionally, small interfering RNA knockdown of endogenous FLNB in human umbilical vein endothelial cells inhibited vascular endothelial growth factor (VEGF)-induced in vitro angiogenesis by decreasing endothelial cell migration capacity, whereas FLNA ablation did not alter these parameters. Moreover, FLNB-depleted cells increased their substrate adhesion with more focal adhesions. The molecular mechanism underlying this effect implicates modulation of small GTP-binding protein Rac-1 localization and activity, with altered activation of its downstream effectors p21 protein Cdc42/Rac-activated kinase (PAK)-4/5/6 and its activating guanine nucleotide exchange factor Vav-2. Moreover, our results suggest the existence of a signaling complex, including FLNB, Rac-1, and Vav-2, under basal conditions that would further interact with VEGFR2 and integrin αvβ5 after VEGF stimulation. In conclusion, our results reveal a crucial role for FLNB in endothelial cell migration and in the angiogenic process in adult endothelial cells. PMID:20110358

  20. The ER Stress Sensor PERK Coordinates ER-Plasma Membrane Contact Site Formation through Interaction with Filamin-A and F-Actin Remodeling.

    PubMed

    van Vliet, Alexander R; Giordano, Francesca; Gerlo, Sarah; Segura, Inmaculada; Van Eygen, Sofie; Molenberghs, Geert; Rocha, Susana; Houcine, Audrey; Derua, Rita; Verfaillie, Tom; Vangindertael, Jeroen; De Keersmaecker, Herlinde; Waelkens, Etienne; Tavernier, Jan; Hofkens, Johan; Annaert, Wim; Carmeliet, Peter; Samali, Afshin; Mizuno, Hideaki; Agostinis, Patrizia

    2017-03-02

    Loss of ER Ca(2+) homeostasis triggers endoplasmic reticulum (ER) stress and drives ER-PM contact sites formation in order to refill ER-luminal Ca(2+). Recent studies suggest that the ER stress sensor and mediator of the unfolded protein response (UPR) PERK regulates intracellular Ca(2+) fluxes, but the mechanisms remain elusive. Here, using proximity-dependent biotin identification (BioID), we identified the actin-binding protein Filamin A (FLNA) as a key PERK interactor. Cells lacking PERK accumulate F-actin at the cell edges and display reduced ER-PM contacts. Following ER-Ca(2+) store depletion, the PERK-FLNA interaction drives the expansion of ER-PM juxtapositions by regulating F-actin-assisted relocation of the ER-associated tethering proteins Stromal Interaction Molecule 1 (STIM1) and Extended Synaptotagmin-1 (E-Syt1) to the PM. Cytosolic Ca(2+) elevation elicits rapid and UPR-independent PERK dimerization, which enforces PERK-FLNA-mediated ER-PM juxtapositions. Collectively, our data unravel an unprecedented role of PERK in the regulation of ER-PM appositions through the modulation of the actin cytoskeleton.

  1. 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

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

    PubMed

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

    2016-06-01

    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. 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 OCT2 and HCF1 bind Ori

  3. Cooperative enhancement of translation by two adjacent microRNA-122/Argonaute 2 complexes binding to the 5' untranslated region of hepatitis C virus RNA.

    PubMed

    Nieder-Röhrmann, Anika; Dünnes, Nadia; Gerresheim, Gesche K; Shalamova, Lyudmila A; Herchenröther, Andreas; Niepmann, Michael

    2017-02-01

    The liver-specific microRNA-122 (miR-122) binds to two conserved binding sites in the 5' UTR of hepatitis C virus (HCV) RNA. This binding was reported to enhance HCV RNA replication, translation and stability. We have analysed binding of miR-122/Argonaute 2 (Ago2) complexes to these sites using anti-Ago2 co-immunoprecipitation of radioactively labelled HCV RNAs along with ectopic miR-122 in HeLa cells. Our results show that the miR-122 target sites can be addressed separately. When both target sites were addressed simultaneously, we observed a synergistic binding of both miR/Ago2 complexes. Consistently, simultaneous binding of both miR-122/Ago2 complexes results in cooperative translation stimulation. In the binding assays as well as in the translation assays, binding site 1 has a stronger effect than binding site 2. We also analysed the overall RNA stability as well as the 5' end integrity of these HCV RNAs in the presence of miR-122. Surprisingly, using short HCV reporter RNAs, we did not find effects of miR-122 binding on overall RNA stability or 5' end integrity over up to 36 h. In contrast, using full-length HCV genomes that are incapable of replication, we found a positive influence of miR-122 on RNA stability, indicating that features of the full-length HCV genome that do not reside in the 5' and 3' UTRs may render HCV RNA genome stability miR-122 dependent.

  4. 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

  5. Making Cooperative Learning Work.

    ERIC Educational Resources Information Center

    Johnson, David W.; Johnson, Roger T.

    1999-01-01

    Discusses the importance of cooperative learning, focusing on what is and is not a cooperative effort; types of cooperative learning; an example of integrated use of cooperative learning; cooperative schools; basic elements of cooperation; and what is known about cooperative efforts (related to achievement, interpersonal relationship, and…

  6. 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…

  7. 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…

  8. Cooperative Education.

    ERIC Educational Resources Information Center

    Brown, Robert L.

    Cooperative education involves on-campus instruction and off-campus work experience. These programs can be referred to as work study, field work, or work experience. The student has the advantage of applying his knowledge in a work situation; the college gains financial benefits; and the employer has the opportunity to influence the student to…

  9. 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.

  10. Filamin A interaction with the CXCR4 third intracellular loop regulates endocytosis and signaling of WT and WHIM-like receptors

    PubMed Central

    Gómez-Moutón, Concepción; Fischer, Thierry; Peregil, Rosa M.; Jiménez-Baranda, Sonia; Stossel, Thomas P.; Nakamura, Fumihiko

    2015-01-01

    Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare congenital immunodeficiency often caused by mutations in the last 10 to 19 C-terminal amino acids of CXCR4. These mutations impair CXCR4 internalization and increase responsiveness to CXCL12. The CXCR4 C-terminal domain (C-tail) also has a binding site for the actin-binding protein filamin A (FLNA); it is not known whether FLNA binds to WHIM CXCR4 mutants or whether this interaction is implicated in the hyperfunction of these receptors. Here we show that, in addition to interacting with the CXCR4 C-tail, FLNA interacted with a region in the receptor third intracellular loop (ICL3) spanning amino acids 238 to 246. This interaction involved specific FLNA repeats and was sensitive to Rho kinase inhibition. Deletion of the 238-246 motif accelerated CXCL12-induced wild-type (WT) receptor endocytosis but enabled CXCL12-mediated endocytosis and normalized signaling by the WHIM-associated receptor CXCR4R334X. CXCL12 stimulation triggered CXCR4R334X internalization in FLNA-deficient M2 cells but not in the FLNA-expressing M2 subclone A7; this suggests a role for FLNA in stabilization of WHIM-like CXCR4 at the cell surface. FLNA increased β-arrestin2 binding to CXCR4R334X in vivo, which provides a molecular basis for FLNA-mediated hyperactivation of WHIM receptor signaling. We propose that FLNA interaction with ICL3 is central for endocytosis and signaling of WT and WHIM-like CXCR4 receptors. PMID:25355818

  11. The dual role of filamin A in cancer: can’t live with (too much of) it, can’t live without it

    PubMed Central

    Savoy, Rosalinda M; Ghosh, Paramita M

    2015-01-01

    Filamin A (FlnA) has been associated with actin as cytoskeleton regulator. Recently its role in the cell has come under scrutiny for FlnA’s involvement in cancer development. FlnA was originally revealed as a cancer-promoting protein, involved in invasion and metastasis. However, recent studies have also found that under certain conditions, it prevented tumor formation or progression, confusing the precise function of FlnA in cancer development. Here, we try to decipher the role of FlnA in cancer and the implications for its dual role. We propose that differences in subcellular localization of FlnA dictate its role in cancer development. In the cytoplasm, FlnA functions in various growth signaling pathways, such as vascular endothelial growth factor, in addition to being involved in cell migration and adhesion pathways, such as R-Ras and integrin signaling. Involvement in these pathways and various others has shown a correlation between high cytoplasmic FlnA levels and invasive cancers. However, an active cleaved form of FlnA can localize to the nucleus rather than the cytoplasm and its interaction with transcription factors has been linked to a decrease in invasiveness of cancers. Therefore, overexpression of FlnA has a tumor-promoting effect, only when it is localized to the cytoplasm, whereas if FlnA undergoes proteolysis and the resulting C-terminal fragment localizes to the nucleus, it acts to suppress tumor growth and inhibit metastasis. Development of drugs to target FlnA and cause cleavage and subsequent localization to the nucleus could be a new and potent field of research in treating cancer. PMID:24108109

  12. Filamin A interaction with the CXCR4 third intracellular loop regulates endocytosis and signaling of WT and WHIM-like receptors.

    PubMed

    Gómez-Moutón, Concepción; Fischer, Thierry; Peregil, Rosa M; Jiménez-Baranda, Sonia; Stossel, Thomas P; Nakamura, Fumihiko; Mañes, Santos

    2015-02-12

    Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare congenital immunodeficiency often caused by mutations in the last 10 to 19 C-terminal amino acids of CXCR4. These mutations impair CXCR4 internalization and increase responsiveness to CXCL12. The CXCR4 C-terminal domain (C-tail) also has a binding site for the actin-binding protein filamin A (FLNA); it is not known whether FLNA binds to WHIM CXCR4 mutants or whether this interaction is implicated in the hyperfunction of these receptors. Here we show that, in addition to interacting with the CXCR4 C-tail, FLNA interacted with a region in the receptor third intracellular loop (ICL3) spanning amino acids 238 to 246. This interaction involved specific FLNA repeats and was sensitive to Rho kinase inhibition. Deletion of the 238-246 motif accelerated CXCL12-induced wild-type (WT) receptor endocytosis but enabled CXCL12-mediated endocytosis and normalized signaling by the WHIM-associated receptor CXCR4(R334X). CXCL12 stimulation triggered CXCR4(R334X) internalization in FLNA-deficient M2 cells but not in the FLNA-expressing M2 subclone A7; this suggests a role for FLNA in stabilization of WHIM-like CXCR4 at the cell surface. FLNA increased β-arrestin2 binding to CXCR4(R334X) in vivo, which provides a molecular basis for FLNA-mediated hyperactivation of WHIM receptor signaling. We propose that FLNA interaction with ICL3 is central for endocytosis and signaling of WT and WHIM-like CXCR4 receptors.

  13. Evolution of cooperation among mobile agents

    NASA Astrophysics Data System (ADS)

    Chen, Zhuo; Gao, Jianxi; Cai, Yunze; Xu, Xiaoming

    2011-05-01

    We study the effects of mobility on the evolution of cooperation among mobile players, which imitate collective motion of biological flocks and interact with neighbors within a prescribed radius R. Adopting the the prisoner’s dilemma game and the snowdrift game as metaphors, we find that cooperation can be maintained and even enhanced for low velocities and small payoff parameters, when compared with the case that all agents do not move. But such enhancement of cooperation is largely determined by the value of R, and for modest values of R, there is an optimal value of velocity to induce the maximum cooperation level. Besides, we find that intermediate values of R or initial population densities are most favorable for cooperation, when the velocity is fixed. Depending on the payoff parameters, the system can reach an absorbing state of cooperation when the snowdrift game is played. Our findings may help understanding the relations between individual mobility and cooperative behavior in social systems.

  14. Inactive sites and the evolution of cooperation

    NASA Astrophysics Data System (ADS)

    da Silva Júnior, E. J.; Wardil, L. L.; da Silva, J. K. L.

    2016-10-01

    Cooperation is often conditioned on environmental factors. Behaviors may be inactive due to external factors, and yet the trait itself may not change. We study the evolution of cooperation with active and inactive sites. In inactive sites cooperators behave as defectors, receiving but not providing benefits. This unintentional mimicry provides local advantage to cooperation, but also prevents the mutual reinforcement provided by clusters of active cooperators. In general, we found that cooperation is enhanced by inactivity. In particular, if most sites are inactive, cooperation survives even if the temptation to defect is very large. Interestingly, in the square lattice with pairwise comparison rule we found that cooperation is enforced by inactive sites only up to a certain limit.

  15. Recovery- Cooper

    NASA Image and Video Library

    1963-05-16

    S63-07853 (16 May 1963) --- Astronaut L. Gordon Cooper Jr., pilot of the Mercury-Atlas 9 (MA-9) mission, stands supported by strong hands after climbing out of his spacecraft "Faith 7" after a 600,000-mile, 22-orbit journey around Earth. He elected to remain in the spacecraft until it was hoisted to the deck of the USS Kearsarge, as did astronaut Walter Schirra during the previous mission. Photo credit: NASA

  16. 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.

  17. Enhancing Trilateral Disaster Preparedness and Relief Cooperation between Japan, U.S. and Australia: Approaches from Various Civil-Military Perspectives

    DTIC Science & Technology

    2013-07-01

    Disaster Management and Emergency Response ACDM The ASEAN Committee On Disaster Management ACJUA Association for Cooperation between Japan, U.S., and... disaster reconstruction and rehabilitation. Natural disasters generate complex emergencies that require urgent and coordinated responses from a broad...mitigation, relief and assistance.5 Accordingly, ASEAN initiated the annual Regional Disaster Emergency Response Simulation Exercise in 2005, to

  18. 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…

  19. 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…

  20. 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

  1. 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…

  2. 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…

  3. Evolutionary explanations for cooperation.

    PubMed

    West, Stuart A; Griffin, Ashleigh S; Gardner, Andy

    2007-08-21

    Natural selection favours genes that increase an organism's ability to survive and reproduce. This would appear to lead to a world dominated by selfish behaviour. However, cooperation can be found at all levels of biological organisation: genes cooperate in genomes, organelles cooperate to form eukaryotic cells, cells cooperate to make multicellular organisms, bacterial parasites cooperate to overcome host defences, animals breed cooperatively, and humans and insects cooperate to build societies. Over the last 40 years, biologists have developed a theoretical framework that can explain cooperation at all these levels. Here, we summarise this theory, illustrate how it may be applied to real organisms and discuss future directions.

  4. A gene-type-specific enhancer regulates the carbamyl phosphate synthetase I promoter by cooperating with the proximal GAG activating element.

    PubMed Central

    Goping, I S; Lamontagne, S; Shore, G C; Nguyen, M

    1995-01-01

    The rat carbamyl phosphate synthetase I gene is expressed in two cell types: hepatocytes and epithelial cells of the intestinal mucosa. The proximal promoter contains a single activating element, GAG, two repressor elements (sites I and III) and an anti-repressor element (site II). Although these elements together exhibit the potential for complex regulation, they are unable to confer tissue-specific promoter activity. Here we have identified a cell-type-specific enhancer that lies 10 kilobases upstream of the promoter. Unexpectedly, the enhancer also functioned in a gene-type-specific manner. The enhancer stimulated promoter activity exclusively through the proximal GAG element. Abrogation of GAG, either directly by mutation of GAG or indirectly by sites I and III repressors, abolished enhancer activation. Conversely, activation of the heterologous thymidine kinase promoter by the enhancer required the introduction of GAG. The requirement for GAG, therefore, functions to constrain the enhancer to a specific target promoter. PMID:7784176

  5. Plant cooperation.

    PubMed

    Dudley, Susan A

    2015-09-25

    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.

  6. 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

  7. Evolution of cooperation on spatially embedded networks

    NASA Astrophysics Data System (ADS)

    Buesser, Pierre; Tomassini, Marco

    2012-12-01

    In this work we study the behavior of classical two-person, two-strategies evolutionary games on networks embedded in a Euclidean two-dimensional space with different kinds of degree distributions and topologies going from regular to random and to scale-free ones. Using several imitative microscopic dynamics, we study the evolution of global cooperation on the above network classes and find that specific topologies having a hierarchical structure and an inhomogeneous degree distribution, such as Apollonian and grid-based networks, are very conducive to cooperation. Spatial scale-free networks are still good for cooperation but to a lesser degree. Both classes of networks enhance average cooperation in all games with respect to standard random geometric graphs and regular grids by shifting the boundaries between cooperative and defective regions. These findings might be useful in the design of interaction structures that maintain cooperation when the agents are constrained to live in physical two-dimensional space.

  8. 3 CFR - Certifications Pursuant to Section 104 of the United States-India Nuclear Cooperation Approval...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... States-India Nuclear Cooperation Approval and Nonproliferation Enhancement Act Regarding the Safeguards Agreement Between India and the International Atomic Energy Agency Presidential Documents Other Presidential... of the United States-India Nuclear Cooperation Approval and Nonproliferation Enhancement...

  9. The Evolution of Cooperation.

    ERIC Educational Resources Information Center

    Dugatkin, Lee Alan

    1997-01-01

    Outlines the four paths to the evolution and maintenance of cooperative behavior and provides two stories highlighting each path. Discusses reciprocity, byproduct mutualism, kin-selected cooperation, and group-selected cooperation. Presents some thoughts on where the study of animal cooperation might head in the future. Contains 67 references.…

  10. Concerning two-metal cooperativity in model phosphate hydrolysis.

    PubMed

    Leivers, M; Breslow, R

    2001-12-01

    Three series of bimetallic ligands were tested for cooperativity in the hydrolysis of phosphate esters. It was shown that rate enhancements were in part contributed by binding to the hydrophobic linkers when the substrates were also hydrophobic, and two metal cooperativity was not found to be present. Kinetic order tests were performed and shown to be superior to previous methods for analyzing cooperativity.

  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. Sequential Assessments of the Eastern Cooperative Oncology Group Performance Scale Enhance Prognostic Value in Patients With Terminally Ill Cancer Receiving Palliative Care.

    PubMed

    Peng, Meng-Ting; Liu, Chien-Ting; Hung, Yu-Shin; Kao, Chen-Yi; Chang, Pei-Hung; Yeh, Kun-Yun; Wang, Hung-Ming; Lin, Yung-Chang; Chou, Wen-Chi

    2016-06-01

    This study aimed to assess the utility of the Eastern Cooperative Oncology Group (ECOG) performance scale assessments on days 1 and 8 of palliative care, as well as scale change between these assessments, as prognostic tools for patients with terminally ill cancer. A total of 2392 patients with terminally ill cancer who received palliative care between January 2006 and December 2011 at a single medical center were analyzed. Our study showed that the ECOG scale is a useful prognostic tool to predict life expectancy in patients with terminally ill cancer. The ECOG scale assessments at different time points under palliative care were independent predictors for overall survival. The combined ECOG scale assessments on days 1 and 8 predicted survival more precisely than using day 1 ECOG scale assessment alone.

  13. 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

  14. 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

  15. 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.

  16. The Globalization of Cooperative Groups

    PubMed Central

    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.

    2015-01-01

    The National Cancer Institute-supported adult cooperative oncology research groups (now officially Network groups) have a long-standing history of participating in international collaborations throughout the world. Most frequently, the U.S. 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 U.S., 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 U.S. 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 U.S. 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 U.S. policies that restrict drug distribution outside the U.S. This manuscript 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

  17. Implementing web-based ping-pong-type e-communication to enhance staff satisfaction, multidisciplinary cooperation, and clinical effectiveness: A SQUIRE-compliant quality-improving study.

    PubMed

    Yeh, Pei-Han; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Lai, Chun-Liang; Tsai, Wei-Ta; Hsieh, Hui-Ling; Shih, Yi-Ting; Chen, Liang-Cheng; Huang, Li-Wen; Lin, Yi-An; Lin, Po-Hao; Lin, Yung-Hsiang; Liu, Dai-Wei; Hsu, Feng-Chun; Tsai, Shiang-Jiun; Liu, Jia-Chi; Chung, En-Seu; Lin, Hon-Yi

    2016-11-01

    Frequent multidisciplinary communication is essential in conducting daily radiotherapy (RT) practice. However, traditional oral or paper-based communication has limitations. E-communication has been suggested, but its effects are still not well demarcated in the field of radiation oncology. In our web-based integrated information platform, we constructed a ping-pong-type e-communication function to transfer specific notations among multidisciplinary RT staffs. The purpose was to test whether applying this e-communication can increase effectiveness of multidisciplinary cooperation when compared with oral or paper-based practice. Staff satisfaction and clinical benefits were also demonstrated. A real-world quality-improving study was conducted in a large center of radiation oncology. Before and after applying multidisciplinary e-communication (from 2014 to 2015), clinical RT staffs were surveyed for their user experience and satisfaction (n = 23). For measuring clinical effectiveness, a secondary database of irradiated head and neck cancer patients was re-analyzed for comparing RT toxicities (n = 402). Applying ping-pong-type multidisciplinary reflective e-communication was the main intervention. For measuring staff satisfaction, eight domains were surveyed, such as timeliness, convenience, and completeness. For measuring clinical effectiveness of multidisciplinary cooperation, event rates of severe (i.e., grade 3-4) RT mucositis and dermatitis were recorded. Overall, when compared with oral communication only, e-communication demonstrated multiple benefits, particularly on notation-review convenience (2.00 ± 1.76 vs 9.19 ± 0.81; P < 0.0001).When compared with paper-based practice, e-communication showed statistically significant benefits on all eight domains, especially on notation-review convenience (5.05 ± 2.11 vs 9.19 ± 0.81; P < 0.0001) and convenience of feedback notation (4.81 ± 1.72 vs 8.76 ± 1.09; P < 0

  18. Determinants of public cooperation in multiplex networks

    NASA Astrophysics Data System (ADS)

    Battiston, Federico; Perc, Matjaž; Latora, Vito

    2017-07-01

    Synergies between evolutionary game theory and statistical physics have significantly improved our understanding of public cooperation in structured populations. Multiplex networks, in particular, provide the theoretical framework within network science that allows us to mathematically describe the rich structure of interactions characterizing human societies. While research has shown that multiplex networks may enhance the resilience of cooperation, the interplay between the overlap in the structure of the layers and the control parameters of the corresponding games has not yet been investigated. With this aim, we consider here the public goods game on a multiplex network, and we unveil the role of the number of layers and the overlap of links, as well as the impact of different synergy factors in different layers, on the onset of cooperation. We show that enhanced public cooperation emerges only when a significant edge overlap is combined with at least one layer being able to sustain some cooperation by means of a sufficiently high synergy factor. In the absence of either of these conditions, the evolution of cooperation in multiplex networks is determined by the bounds of traditional network reciprocity with no enhanced resilience. These results caution against overly optimistic predictions that the presence of multiple social domains may in itself promote cooperation, and they help us better understand the complexity behind prosocial behavior in layered social systems.

  19. 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

  20. Repetitive elements and enforced transcriptional repression co-operate to enhance DNA methylation spreading into a promoter CpG-island

    PubMed Central

    Zhang, Yan; Shu, Jingmin; Si, Jiali; Shen, Lanlan; Estecio, Marcos R.H.; Issa, Jean-Pierre J.

    2012-01-01

    Repression of many tumor suppressor genes in cancer is concurrent with aberrantly increased DNA methylation levels at promoter CpG islands (CGIs). About one-fourth of empirically defined human promoters are surrounded by or contain clustered repetitive elements. It was previously observed that a sharp transition of methylation exists between highly methylated repetitive elements and unmethylated promoter-CGIs in normal tissues. The factors that lead to aberrant CGI hypermethylation in cancer remain poorly understood. Here, we established a site-specific integration system with enforced local transcriptional repression in colorectal cancer cells and monitored the occurrence of initial de novo methylation at specific CG sites adjacent to the CGI of the INSL6 promoter, which could be accelerated by binding a KRAB-containing transcriptional factor. Additional repetitive elements from P16 and RIL (PDLIM4), if situated adjacent to the promoter of INSL6, could confer DNA methylation spreading into the CGI particularly in the setting of KRAB-factor binding. However, a repressive chromatin alone was not sufficient to initiate DNA methylation, which required specific DNA sequences and was integration-site (and/or cell-line) specific. Overall, these results demonstrate a requirement for specific DNA sequences to trigger de novo DNA methylation, and repetitive elements as cis-regulatory factors to cooperate with advanced transcriptional repression in promoting methylation spreading. PMID:22600741

  1. 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…

  2. Cooperative effects of immune enhancer TPPPS and different adjuvants on antibody responses induced by recombinant ALV-J gp85 subunit vaccines in SPF chickens.

    PubMed

    Li, Yang; Meng, Fanfeng; Cui, Shuai; Fu, Jiayuan; Wang, Yixin; Cui, Zhizhong; Chang, Shuang; Zhao, Peng

    2017-03-14

    To explore the antibody responses and protective effects induced by subgroup J avian leukosis virus (ALV-J) gp85 protein vaccine plus different adjuvants (CpG and white oil adjuvant YF01) combined with the immune enhancer Taishan Pinus massoniana pollen polysaccharide (TPPPS), we immunized SPF chickens with the recombinant ALV-J gp85 protein, along with different adjuvants and immune enhancer, which protected the chickens by inducing different levels of protective antibodies. Results showed that a single injection of gp85 recombinant protein could only produce low-titre antibodies that were maintained over a short time in few chickens. When combined with YF01 or CpG adjuvants, the recombinant protein could induce high-titre antibodies in most of the immunized chickens. Moreover, when the immune enhancer TPPPS was used with the two adjuvants, it further elevated the antibody levels for a longer duration. The eggs from four groups with the highest levels of ALV-J antibodies were collected, hatched, and examined for maternal antibodies. The protection by the maternal antibodies against ALV-J infection in the TPPPS-immunized group was higher than that in the group without TPPPS, which was consistent with the observations in the parents. This study shows that the immune enhancer TPPPS, combined with YF01 or CpG adjuvants, can enhance the immunogenicity of gp85 recombinant proteins, and provide a better immuno-protection. It provides a powerful experimental basis for the development of ALV-J subunit vaccine. Efficient subunit vaccine development will also accelerate the process of purification of ALV-J.

  3. 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.

  4. DNA methyltransferase inhibitor RG108 and histone deacetylase inhibitors cooperate to enhance NB4 cell differentiation and E-cadherin re-expression by chromatin remodelling.

    PubMed

    Savickiene, Jurate; Treigyte, Grazina; Jazdauskaite, Arune; Borutinskaite, Veronika-Viktorija; Navakauskiene, Ruta

    2012-11-01

    Epigenetic silencing of cancer-related genes by abnormal methylation and the reversal of this process by DNA methylation inhibitors represents a promising strategy in cancer therapy. As DNA methylation affects gene expression and chromatin structure, we investigated the effects of novel DNMT (DNA methyltransferase) inhibitor, RG108, alone and in its combinations with structurally several HDAC (histone deacetylase) inhibitors [sodium PB (phenyl butyrate) or BML-210 (N-(2-aminophenyl)-N'phenyloctanol diamine), and all-trans RA (retinoic acid)] in the human PML (promyelocytic leukaemia) NB4 cells. RG108 at different doses from 20 to 100 μM caused time-, but not a dose-dependent inhibition of NB4 cell proliferation without cytotoxicity. Temporal pretreatment with RG108 before RA resulted in a dose-dependent cell growth inhibition and remarkable acceleration of granulocytic differentiation. Prolonged treatments with RG108 and RA in the presence of HDAC inhibitors significantly increased differentiation. RG108 caused time-dependent re-expression of methylation-silenced E-cadherin, with increase after temporal or continuous treatments with RG108 and RA, or RA together with PB in parallel, in cell maturation, suggesting the role of E-cadherin as a possible therapeutic marker. These processes required both PB-induced hyperacetylation of histone H4 and trimethylation of histone H3 at lysine 4, indicating the cooperative action of histone modifications and DNA methylation/demethylation in derepression of E-cadherin. This work provides novel experimental evidence of the beneficial role of the DNMT inhibitor RG108 in combinations with RA and HDACIs in the effective differentiation of human PML based on epigenetics.

  5. Choosing the cooperative option

    SciTech Connect

    English, G. )

    1999-06-01

    Cooperatives do not ask to be exempted from the law. They do ask that laws and regulations be designed to allow them to meet the needs of their consumer-owners in accordance with cooperative principles, at a time that the marginal consumers being abandoned by for-profit utilities may be ready to gravitate toward cooperatives. The cooperative principles are worth reviewing because they explain the focus on the consumer and the cooperative concept of service: cooperatives are voluntary organizations, open to all persons able to use their services and willing to accept the responsibilities of membership; cooperatives are democratic organizations controlled by their members, who actively participate in setting policies and making decisions, the elected representatives are accountable to the membership; members contribute equitably to, and democratically control, the capital of their cooperative; cooperatives are autonomous, self-help organizations controlled by their members, if they enter into agreements with other organizations, including governments, they do so on terms that ensure democratic control by their members and maintain their cooperative autonomy; cooperatives provide education and training for their members, elected representatives, managers, and employees so they can contribute effectively to the development of their cooperatives, they inform the general public, particularly young people and opinion leaders, about the nature and benefits of cooperation; cooperatives serve their members most effectively and strength the cooperative movement by working together through local, national, regional, and international structures; and while focusing on member needs, cooperatives work for the sustainable development of their communities through policies accepted by their members.

  6. What is a cooperative?

    Treesearch

    Kimberly Zeuli

    2006-01-01

    Groups of individuals throughout time have worked together in pursuit of common goals. The earliest forms of hunting and agriculture required a great deal of cooperation among humans. Although the word "cooperative" can be applied to many different types of group activities, in this publication it refers to a formal business model. Cooperative businesses are...

  7. 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…

  8. 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,…

  9. Advising People about Cooperatives.

    ERIC Educational Resources Information Center

    Kirkman, C. H., Jr.; Mohn, Paul O.

    This document provides background and references for educational programs on cooperatives. Seven major topics are covered: Cooperatives Are Distinctive Business Corporations, Types of Cooperatives (such as agricultural, credit, housing, crafts, health, memorial association, fishing, forestry, recreation, labor, buying clubs, consumer, student, and…

  10. Interlibrary Cooperation. Final Report.

    ERIC Educational Resources Information Center

    Olson, Edwin E.

    The major dimensions of interlibrary cooperation which have implications for manpower development in librarianship are identified, categorized and described. These dimensions include: (1) the "power budget" of a cooperative; that is, the capability of a cooperative as represented by its structure, resources, and decision-making processes to…

  11. Cooperation Among State Agencies

    ERIC Educational Resources Information Center

    Wattenbarger, James L.; Hansen, Dean M.

    1975-01-01

    Most states have separate agencies to deal with vocational education, adult education, and community colleges. Because current procedures for interagency cooperation are inadequate and often nonproductive, there is a need for a national or extra-state catalyst to encourage cooperation in a positive way. Five strategies for cooperation are…

  12. CCAAT/Enhancer-binding Protein α (C/EBPα) and Hepatocyte Nuclear Factor 4α (HNF4α) Synergistically Cooperate with Constitutive Androstane Receptor to Transactivate the Human Cytochrome P450 2B6 (CYP2B6) Gene

    PubMed Central

    Benet, Marta; Lahoz, Agustín; Guzmán, Carla; Castell, José V.; Jover, Ramiro

    2010-01-01

    The transcription of tissue-specific and inducible genes is usually subject to the dynamic control of multiple activators. Dedifferentiated hepatic cell lines lose the expression of tissue-specific activators and many characteristic hepatic genes, such as drug-metabolizing cytochrome P450. Here we demonstrate that by combining adenoviral vectors for CCAAT/enhancer-binding protein α (C/EBPα), hepatocyte nuclear factor 4α (HNF4α), and constitutive androstane receptor, the CYP2B6 expression and inducibility by CITCO are restored in human hepatoma HepG2 cells at levels similar to those in cultured human hepatocytes. Moreover, several other phase I and II genes are simultaneously activated, which suggests that this is an effective approach to endow dedifferentiated human hepatoma cells with a particular metabolic competence and response to inducers. In order to gain insight into the molecular mechanism, we examined the cooperation of these three transcription factors on the CYP2B6 5′-flanking region. We show new CYP2B6-responsive sequences for C/EBPα and HNF4α and a novel synergistic regulatory mechanism whereby C/EBPα, HNF4α, and constitutive androstane receptor bind and cooperate through proximal and distal response elements to confer a maximal level of expression. The results obtained from human liver also suggest that important differences in the expression and binding of C/EBPα and HNF4α could account for the large interindividual variability of the hepatic CYP2B6 enzyme, which metabolizes commonly used drugs. PMID:20622021

  13. Toll-Like Receptor 7/8 (TLR7/8) and TLR9 Agonists Cooperate To Enhance HIV-1 Envelope Antibody Responses in Rhesus Macaques

    PubMed Central

    Santra, Sampa; Vandergrift, Nathan A.; Sutherland, Laura L.; Gurley, Thaddeus C.; Drinker, Mark S.; Allen, Ashley A.; Xia, Shi-Mao; Meyerhoff, R. Ryan; Parks, Robert; Lloyd, Krissey E.; Easterhoff, David; Alam, S. Munir; Liao, Hua-Xin; Ward, Brandy M.; Ferrari, Guido; Montefiori, David C.; Tomaras, Georgia D.; Seder, Robert A.; Letvin, Norman L.; Haynes, Barton F.

    2014-01-01

    ABSTRACT The development of a vaccine that can induce high titers of functional antibodies against HIV-1 remains a high priority. We have developed an adjuvant based on an oil-in-water emulsion that incorporates Toll-like receptor (TLR) ligands to test whether triggering multiple pathogen-associated molecular pattern receptors could enhance immunogenicity. Compared to single TLR agonists or other pairwise combinations, TLR7/8 and TLR9 agonists combined were able to elicit the highest titers of binding, neutralizing, and antibody-dependent cellular cytotoxicity-mediating antibodies against the protein immunogen, transmitted/founder HIV-1 envelope gp140 (B.63521). We further found that the combination of TLR7/8 and TLR9 agonists was associated with the release of CXCL10 (IP-10), suggesting that this adjuvant formulation may have optimally stimulated innate and adaptive immunity to elicit high titers of antibodies. IMPORTANCE Combining TLR agonists in an adjuvant formulation resulted in higher antibody levels compared to an adjuvant without TLR agonists. Adjuvants that combine TLR agonists may be useful for enhancing antibody responses to HIV-1 vaccines. PMID:24390332

  14. 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

  15. Dilemmas of partial cooperation.

    PubMed

    Stark, Hans-Ulrich

    2010-08-01

    Related to the often applied cooperation models of social dilemmas, we deal with scenarios in which defection dominates cooperation, but an intermediate fraction of cooperators, that is, "partial cooperation," would maximize the overall performance of a group of individuals. Of course, such a solution comes at the expense of cooperators that do not profit from the overall maximum. However, because there are mechanisms accounting for mutual benefits after repeated interactions or through evolutionary mechanisms, such situations can constitute "dilemmas" of partial cooperation. Among the 12 ordinally distinct, symmetrical 2 x 2 games, three (barely considered) variants are correspondents of such dilemmas. Whereas some previous studies investigated particular instances of such games, we here provide the unifying framework and concisely relate it to the broad literature on cooperation in social dilemmas. Complementing our argumentation, we study the evolution of partial cooperation by deriving the respective conditions under which coexistence of cooperators and defectors, that is, partial cooperation, can be a stable outcome of evolutionary dynamics in these scenarios. Finally, we discuss the relevance of such models for research on the large biodiversity and variation in cooperative efforts both in biological and social systems.

  16. Novel Mucosal DNA-MVA HIV Vaccination in Which DNA-IL-12 Plus Cholera Toxin B Subunit (CTB) Cooperates to Enhance Cellular Systemic and Mucosal Genital Tract Immunity

    PubMed Central

    Holgado, María Pía; Falivene, Juliana; Gherardi, María Magdalena

    2014-01-01

    Induction of local antiviral immune responses at the mucosal portal surfaces where HIV-1 and other viral pathogens are usually first encountered remains a primary goal for most vaccines against mucosally acquired viral infections. Exploring mucosal immunization regimes in order to find optimal vector combinations and also appropriate mucosal adjuvants in the HIV vaccine development is decisive. In this study we analyzed the interaction of DNA-IL-12 and cholera toxin B subunit (CTB) after their mucosal administration in DNA prime/MVA boost intranasal regimes, defining the cooperation of both adjuvants to enhance immune responses against the HIV-1 Env antigen. Our results demonstrated that nasal mucosal DNA/MVA immunization schemes can be effectively improved by the co-delivery of DNA-IL-12 plus CTB inducing elevated HIV-specific CD8 responses in spleen and more importantly in genital tract and genito-rectal draining lymph nodes. Remarkably, these CTL responses were of superior quality showing higher avidity, polyfunctionality and a broader cytokine profile. After IL-12+CTB co-delivery, the cellular responses induced showed an enhanced breadth recognizing with higher efficiency Env peptides from different subtypes. Even more, an in vivo CTL cytolytic assay demonstrated the higher specific CD8 T-cell performance after the IL-12+CTB immunization showing in an indirect manner its potential protective capacity. Improvements observed were maintained during the memory phase where we found higher proportions of specific central memory and T memory stem-like cells T-cell subpopulations. Together, our data show that DNA-IL-12 plus CTB can be effectively employed acting as mucosal adjuvants during DNA prime/MVA boost intranasal vaccinations, enhancing magnitude and quality of HIV-specific systemic and mucosal immune responses. PMID:25215887

  17. Genetic Enhancer Analysis Reveals that FLORAL ORGAN NUMBER2 and OsMADS3 Cooperatively Regulate Maintenance and Determinacy of the Flower Meristem in Rice.

    PubMed

    Yasui, Yukiko; Tanaka, Wakana; Sakamoto, Tomoaki; Kurata, Tetsuya; Hirano, Hiro-Yuki

    2017-03-22

    Meristems such as the shoot apical meristem and flower meristem (FM) act as a reservoir of stem cells, which reproduce themselves and supply daughter cells for the differentiation of lateral organs. In Oryza sativa (rice), FLORAL ORGAN NUMBER2 (FON2) gene, which is similar to Arabidopsis CLAVATA3, is involved in meristem maintenance. In fon2 mutants, the numbers of floral organs are increased due to an enlargement of the FM. To identify new factors regulating meristem maintenance in rice, we performed a genetic screening of mutants that enhanced the fon2 mutation, and found a mutant line (2B-424) in which pistil number was dramatically increased. By using a map-based approach and next-generation sequencing, we found that the line 2B-424 had a complete loss-of-function mutation (a large deletion) in OsMADS3, a class C MADS-box gene that is known to be involved in stamen specification. Disruption of OsMADS3 in the fon2 mutant by CRISPR-Cas9 technology caused a flower phenotype similar to that of 2B-424, confirming that the gene responsible for enhancement of fon2 was OsMADS3. Morphological analysis showed that the fon2 and osmads3 mutations synergistically affected pistil development and FM determinacy. We also found that whorl 3 was duplicated in mature flowers and the FM was enlarged at an early developmental stage in severe osmads3 single mutants. These findings suggest that OsMADS3 is involved not only in FM determinacy in late flower development but also in FM activity in early flower development.

  18. Cooperative Catalytic Effect of ZrO2 and α-Fe2 O3 Nanoparticles on BiVO4 Photoanodes for Enhanced Photoelectrochemical Water Splitting.

    PubMed

    Shaddad, Maged N; Ghanem, Mohamed A; Al-Mayouf, Abdullah M; Gimenez, Sixto; Bisquert, Juan; Herraiz-Cardona, Isaac

    2016-10-06

    Photoelectrochemical water splitting with metal oxide semiconductors offers a cost-competitive alternative for the generation of solar fuels. Most of the materials studied so far suffer from poor charge-transfer kinetics at the semiconductor/liquid interface, making compulsory the use of catalytic layers to overcome the large overpotentials required for the water oxidation reaction. Herein, we report a very soft electrolytic synthesis deposition method, which allows remarkably enhanced water oxidation kinetics of BiVO4 photoanodes by the sequential addition of Zr and Fe precursors. Upon a heat treatment cycle, these precursors are converted into monoclinic ZrO2 and α-Fe2 O3 nanoparticles, which mainly act as catalysts, leading to a five-fold increase of the water oxidation photocurrent of BiVO4 . This method provides a versatile platform that is easy to apply to different semiconductor materials, fully reproducible, and facile to scale-up on large area conductive substrates with attractive implications for technological deployment. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Cooperation between Catalytic and DNA-binding Domains Enhances Thermostability and Supports DNA Synthesis at Higher Temperatures by Thermostable DNA Polymerases

    PubMed Central

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

    2012-01-01

    We have previously introduced a general kinetic approach for comparative study of processivity, thermostability, and resistance to inhibitors of DNA polymerases (Pavlov et. al., (2002) Proc. Natl. Acad. Sci. USA 99, 13510–13515). The proposed method was successfully applied to characterize hybrid DNA polymerases created by fusing catalytic DNA polymerase domains with various non-specific 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 TopoV HhH domains extends efficient DNA synthesis by chimerical polymerases up to 105°C by maintaining processivity of DNA synthesis at high temperatures. We also 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 templates to DNA polymerases. PMID:22320201

  20. IL-2 and IL-6 cooperate to enhance the generation of influenza-specific CD8 T cells responding to live influenza virus in aged mice and humans

    PubMed Central

    Zhou, Xin; Hopkins, Jacob W.; Wang, Chongkai; Brahmakshatriya, Vinayak; Swain, Susan L.; Kuchel, George A.; Haynes, Laura; McElhaney, Janet E.

    2016-01-01

    An age-related decline in cytolytic activity has been described in CD8+ T cells and we have previously shown that the poor CD8+ effector T cell responses to influenza A/H3N2 challenge result from a decline in the proportion and function of these cytolytic T lymphocytes (CTL). Here, we describe that addition of exogenous cytokines to influenza-stimulated PBMC from both aged mice and humans, enhances the generation of influenza specific CD8 CTL by increasing their proliferation and survival. Our data show that the addition of IL-2 and IL-6 to splenocytes from mice previously infected with influenza virus restores the aged CD8+ T cell response to that observed in young mice. In humans, IL-2 plus IL-6 also reduces the proportion of apoptotic effector CD8+ T cells to levels resembling those of younger adults. In HLA-A2+ donors, MHC Class I tetramer staining showed that adding both exogenous IL-2 and IL-6 resulted in greater differentiation into influenza-specific effector CD8+ T cells. Since this effect of IL-2/IL-6 supplementation can be reproduced with the addition of Toll-like receptor agonists, it may be possible to exploit this mechanism and design new vaccines to improve the CD8 T cell response to influenza vaccination in older adults. PMID:27322555

  1. The performance of cooperative processes

    NASA Astrophysics Data System (ADS)

    Huberman, Bernardo A.

    1990-06-01

    Computational processes in distributed networks without global controls resemble a community of concurrent agents which, in their interactions, strategies, and competition, for resources behave like whole ecologies. This brings to mind the spontaneous appearance of organized behavior in biological and social systems, where agents can engage in cooperative strategies while working on the solution of particular problems. This paper analyzes the performance characteristics of interacting processes engaged in cooperative problem solving. It shows that for a wide class of problems, there is a highly nonlinear and universal increase in performance due to the interactions between agents. In some cases this is further enhanced by sharp phase transitions in the topological structure of the problem. These results are illustrated in the context of three prototypical search examples.

  2. A zinc-dependent DNA-binding activity co-operates with cAMP-responsive-element-binding protein to activate the human thyroglobulin enhancer.

    PubMed Central

    Berg, V; Vassart, G; Christophe, D

    1997-01-01

    Footprinting experiments involving the human thyroglobulin gene enhancer and thyroid nuclear extracts revealed a protected region called X2, containing an incomplete cAMP-responsive element (CRE). Band-shift experiments identified two binding activities recognizing the X2 element: a CRE-binding protein (CREB)/activating transcription factor (ATF) relative that binds the half CRE motif and a second factor that interacts with a G-rich motif located just upstream from the CRE. The first factor appears to be CREB itself, as indicated by the supershifting when using an antibody directed against CREB, and the second DNA-binding activity involved was shown to be zinc-dependent and exhibited an apparent molecular mass of 42-44 kDa in South-Western blotting experiments. This factor may represent a novel entity, which we named CAF, for 'CREB Associated Factor'. Three copies of X2 sequence conferred a strong cAMP-dependent transcriptional activation to a heterologous promoter in transient transfection assay in cAMP-stimulated primary thyrocytes and HeLa cells. Transfection experiments of constructs containing the X2 element mutated in either the CRE or the G-rich site showed that both motifs were required for this transcription activating function. Moreover, the combination of several individual X2 elements mutated in either the CRE or the G-rich motif did not exhibit full transcriptional activity. This suggests that, in the context of the X2 element, CREB requires a close interaction with CAF to achieve both basal and cAMP-dependent transcriptional activation. PMID:9163323

  3. 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

  4. TOK-1, a novel p21Cip1-binding protein that cooperatively enhances p21-dependent inhibitory activity toward CDK2 kinase.

    PubMed

    Ono, T; Kitaura, H; Ugai, H; Murata, T; Yokoyama, K K; Iguchi-Ariga, S M; Ariga, H

    2000-10-06

    A p21(Cip1/Waf1/Sdi1) is known to act as a negative cell-cycle regulator by inhibiting kinase activity of a variety of cyclin-dependent kinases. In addition to binding of the cyclin-dependent kinase to the N-terminal region of p21, p21 is also bound at its C-terminal region by proliferating cell nuclear antigen (PCNA), SET/TAF1, and calmodulin, indicating the versatile function of p21. In this study, we cloned cDNA encoding a novel protein named TOK-1 as a p21 C-terminal-binding protein by a two-hybrid system. Two splicing isoforms of TOK-1, TOK-1alpha and TOK-1beta, comprising 322 and 314 amino acids, respectively, were co-localized with p21 in nuclei and showed a similar expression profile to that of p21 in human tissues. TOK-1alpha, but not TOK-1beta, directly bound to the C-terminal proximal region of p21, and both were expressed at the G(1)/S boundary of the cell cycle. TOK-1alpha also preferentially bound to an active form of cyclin-dependent kinase 2 (CDK2) via p21, and these made a ternary complex in human cells. Furthermore, the results of three different types of experiments showed that TOK-1alpha enhanced the inhibitory activity of p21 toward histone H1 kinase activity of CDK2. TOK-1alpha is thus thought to be a new type of CDK2 modulator.

  5. The Cooperative Groups: past and future.

    PubMed

    Comis, R L

    1998-01-01

    conducting trials can be established; to enhance international cooperation in clinical trials; to encourage greater involvement of third-party payers in clinical trials; to build on the scientific breadth of the members; to identify the most appropriate therapies to consider for reimbursement; to establish a framework which builds on the strengths of each of the members; and to integrate health outcomes and economic measures into the protocol activities. The Cooperative Groups are making changes to ensure they remain the leaders in cancer clinical trials well into the 21st century. The benefits of these adjustments will be realized not only by patients, but also by health professionals and the healthcare industry.

  6. Synthetic Yeast Cooperation

    NASA Astrophysics Data System (ADS)

    Shou, Wenying; Burton, Justin

    2010-03-01

    Cooperation is wide-spread and has been postulated to drive major transitions in evolution. However, Darwinian selection favors ``cheaters'' that consume benefits without paying a fair cost. How did cooperation evolve against the threat of cheaters? To investigate the evolutionary trajectories of cooperation, we created a genetically tractable system that can be observed as it evolves from inception. The system consists of two engineered yeast strains -- a red-fluorescent strain that requires adenine and releases lysine and a yellow-fluorescent strain that requires lysine and releases adenine. Cells that consume but not supply metabolites would be cheaters. From the properties of two cooperating strains, we calculated and experimentally verified the minimal initial cell densities required for the viability of the cooperative system in the absence of exogenously added adenine and lysine. Strikingly, evolved cooperative systems were viable at 100-fold lower initial cell densities than their ancestors. We are investigating the nature and diversity of pro-cooperation changes, the dynamics of cooperator-cheater cocultures, and the effects of spatial environment on cooperation and cheating.

  7. Futures for energy cooperatives

    SciTech Connect

    1981-01-01

    A listing of Federal agencies and programs with potential funding for community-scale cooperatives using conservation measures and solar technologies is presented in Section 1. Section 2 presents profiles of existing community energy cooperatives describing their location, history, membership, services, sources of finance and technical assistance. A condensed summary from a recent conference on Energy Cooperatives featuring notes on co-op members' experiences, problems, and opportunities is presented in Section 3. Section 4 lists contacts for additional information. A National Consumer Cooperative Bank Load Application is shown in the appendix.

  8. 76 FR 57056 - International Cooperation on Harmonisation of Technical Requirements for Registration of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-15

    ... HUMAN SERVICES Food and Drug Administration International Cooperation on Harmonisation of Technical... veterinary use by the International Cooperation on Harmonisation of Technical Requirements for Registration... international harmonization of regulatory requirements. FDA has participated in efforts to enhance harmonization...

  9. 75 FR 18504 - International Cooperation on Harmonisation of Technical Requirements for Registration of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-12

    ... HUMAN SERVICES Food and Drug Administration International Cooperation on Harmonisation of Technical... developed for veterinary use by the International Cooperation on Harmonisation of Technical Requirements for... international harmonization of regulatory requirements. FDA has participated in efforts to enhance harmonization...

  10. Population bottlenecks promote cooperation in bacterial biofilms.

    PubMed

    Brockhurst, Michael A

    2007-07-25

    Population bottlenecks are assumed to play a key role in the maintenance of social traits in microbes. Ecological parameters such as colonisation or disturbances can favour cooperation through causing population bottlenecks that enhance genetic structuring (relatedness). However, the size of the population bottleneck is likely to play a crucial role in determining the success of cooperation. Relatedness is likely to increase with decreasing bottleneck size thus favouring the evolution of cooperation. I used an experimental evolution approach to test this prediction with biofilm formation by the bacterium Pseudomonas fluorescens as the cooperative trait. Replicate populations were exposed to disturbance events every four days under one of six population bottleneck treatments (from 10(3) to 10(8) bacterial cells). In line with predictions, the frequency of evolved cheats within the populations increased with increasing bottleneck size. This result highlights the importance of ecologically mediated population bottlenecks in the maintenance of social traits in microbes.

  11. Costly Advertising and the Evolution of Cooperation

    PubMed Central

    Brede, Markus

    2013-01-01

    In this paper, I investigate the co-evolution of fast and slow strategy spread and game strategies in populations of spatially distributed agents engaged in a one off evolutionary dilemma game. Agents are characterized by a pair of traits, a game strategy (cooperate or defect) and a binary ‘advertising’ strategy (advertise or don’t advertise). Advertising, which comes at a cost , allows investment into faster propagation of the agents’ traits to adjacent individuals. Importantly, game strategy and advertising strategy are subject to the same evolutionary mechanism. Via analytical reasoning and numerical simulations I demonstrate that a range of advertising costs exists, such that the prevalence of cooperation is significantly enhanced through co-evolution. Linking costly replication to the success of cooperators exposes a novel co-evolutionary mechanism that might contribute towards a better understanding of the origins of cooperation-supporting heterogeneity in agent populations. PMID:23861752

  12. Costly advertising and the evolution of cooperation.

    PubMed

    Brede, Markus

    2013-01-01

    In this paper, I investigate the co-evolution of fast and slow strategy spread and game strategies in populations of spatially distributed agents engaged in a one off evolutionary dilemma game. Agents are characterized by a pair of traits, a game strategy (cooperate or defect) and a binary 'advertising' strategy (advertise or don't advertise). Advertising, which comes at a cost [Formula: see text], allows investment into faster propagation of the agents' traits to adjacent individuals. Importantly, game strategy and advertising strategy are subject to the same evolutionary mechanism. Via analytical reasoning and numerical simulations I demonstrate that a range of advertising costs exists, such that the prevalence of cooperation is significantly enhanced through co-evolution. Linking costly replication to the success of cooperators exposes a novel co-evolutionary mechanism that might contribute towards a better understanding of the origins of cooperation-supporting heterogeneity in agent populations.

  13. Persistence paves the way for cooperation in evolutionary games

    NASA Astrophysics Data System (ADS)

    Huang, Chang-Wei; Dai, Qiong-Lin

    2017-04-01

    Cooperation is an effective way to maximize collective benefits, especially in modern human society. The issues on the emergence and maintenance of cooperation have attracted much attention in recent years. Here, we introduce the persistence parameter τ to characterize the time duration of choices held by individuals and consider the effects of τ on cooperation. We find that persistence could promote cooperation in a population no matter what the network structure is. Furthermore, the results on heterogeneous networks show that individuals with larger τ are more inclined to cooperate than those with smaller τ. Moreover, we investigate the effects of correlations between degree and persistence in scale-free networks and find that assortative matching could remarkably enhance cooperation whereas disassortative matching has adverse impacts on the evolution of cooperation.

  14. Cellular cooperation: insights from microbes.

    PubMed

    Celiker, Hasan; Gore, Jeff

    2013-01-01

    Cooperation between cells is a widespread phenomenon in nature, found across diverse systems ranging from microbial populations to multicellular organisms. For cooperation to evolve and be maintained within a population of cells, costs due to competition have to be outweighed by the benefits gained through cooperative actions. Because cooperation generally confers a cost to the cooperating cells, defector cells that do not cooperate but reap the benefits of cooperation can thrive and eventually drive the cooperating phenotypes to extinction. Here we summarize recent advances made in understanding how cooperation and multicellularity can evolve in microbial populations in the face of such conflicts and discuss parallels with cell populations within multicellular organisms.

  15. It is the Cooperation, Stupid!

    PubMed Central

    Gupta, Somesh

    2016-01-01

    The rise of aesthetics in medicine has resulted from society's acknowledgement of the importance of physical beauty. This has led to an emerging conflict between allied specialties. The author introduces the concept of “Aesthetic Socialism” according to which everyone should have an opportunity to enhance or restore the beauty where it is missing or when it is lost due to disease, trauma or ageing. However, there are multiple aspects of aesthetics, which can not be addressed by a single specialty, therefore author recommends interdisciplinary cooperation rather than conflict to achieve aesthetic socialism. PMID:28163463

  16. Cooperative Learning Strategies.

    ERIC Educational Resources Information Center

    Barnes, Buckley; O'Farrell, Gail

    1990-01-01

    Presents essential characteristics and types of cooperative learning strategies for use in elementary social studies. Outlines exercises for forming teams and building team spirit. Points out such methods promote group interdependence and student responsibility for learning and teaching others. Highlights two cooperative group strategies, Jigsaw…

  17. Helping Children Cooperate

    ERIC Educational Resources Information Center

    Pica, Rae

    2011-01-01

    There are occasions in life when the competitive process is appropriate. But when people consider the relationships in their lives--with friends, family members, coworkers, and the larger community--they realize the value of cooperation. When adults give children the chance to cooperate, to work together toward a solution or a common goal like…

  18. Educational Cooperatives. PREP-23

    ERIC Educational Resources Information Center

    National Center for Educational Communication (DHEW/OE), Washington, DC.

    Dr. Larry W. Hughes and Dr. C. M. Achilles of the University of Tennessee, Knoxville, conducted a national survey for the Office of Education on educational cooperatives--studying and reporting on the nature and kind of cooperative endeavors, their organization, governance, financial arrangements, services, and personnel. Their study focused upon…

  19. Cooperative Learning and Technology.

    ERIC Educational Resources Information Center

    Denning, Rebecca; Smith, Philip J.

    1997-01-01

    Cooperative learning has been used as an educational technique for some time, and recently researchers have been exploring technology as a mechanism to further this educational method. Presents several examples of the use of technology to support cooperative learning episodes and examines the underlying design concepts and principles embedded in…

  20. Testimony: Writing Cooperatively.

    ERIC Educational Resources Information Center

    Sasser, Linda; Cromwell, Carole

    A lesson plan and supportive materials for an exercise in reading comprehension and cooperative writing are presented. The exercise is based on a story entitled "Testimony," in which a writer expresses feelings about a boxing match. The lesson plan outlines procedures for presentation of the exercise to the class, for the cooperative teams to…

  1. Achieving cooperative success

    Treesearch

    Kimberly Zeuli

    2006-01-01

    Success of a cooperative depends on the foundation built during its organization. Successful businesses are not started overnight. Careful and deliberate planning must be started long before the co-op opens its doors. This chapter begins with an outline of six fundamental steps that should be followed when organizing any cooperative. From initial concept to the start...

  2. Making Cooperative Learning Powerful

    ERIC Educational Resources Information Center

    Slavin, Robert E.

    2014-01-01

    Just about everyone loves the "idea" of cooperative learning, children working productively and excitedly in groups, everyone getting along and enthusiastically helping one another learn. This article presents five strategies that teachers can use to get the greatest benefit possible from cooperative learning and ensure that…

  3. Cooperative Learning Strategies.

    ERIC Educational Resources Information Center

    Barnes, Buckley; O'Farrell, Gail

    1990-01-01

    Presents essential characteristics and types of cooperative learning strategies for use in elementary social studies. Outlines exercises for forming teams and building team spirit. Points out such methods promote group interdependence and student responsibility for learning and teaching others. Highlights two cooperative group strategies, Jigsaw…

  4. Cooperative Vocational Education Programs.

    ERIC Educational Resources Information Center

    Bureau of Adult, Vocational, and Technical Education (DHEW/OE), Washington, DC. Div. of Vocational and Technical Education.

    Cooperative education, said to be a "sleeping giant" in vocational education, received special authorization in Public Law 90 576 and was made a priority in vocational education. This publication summarizes information to assist the states in planning development of cooperative vocational education: definitions, funding sources, program…

  5. Montana Cooperative Education Handbook.

    ERIC Educational Resources Information Center

    Harris, Ron, Ed.

    This revised handbook was developed to help teachers and administrators in Montana conduct cooperative education programs. The handbook is organized in 13 sections. In narrative style, the first 11 sections cover the following topics: introduction to cooperative education, advisory committees, related instruction, coordination of activities,…

  6. Cooperative Science Lesson Plans.

    ERIC Educational Resources Information Center

    Cooperative Learning, 1991

    1991-01-01

    Offers several elementary level cooperative science lesson plans. The article includes a recipe for cooperative class learning, instructions for making a compost pile, directions for finding evidence of energy, experiments in math and science using oranges to test density, and discussions of buoyancy using eggs. (SM)

  7. Distinguished Cooperating Teacher Program.

    ERIC Educational Resources Information Center

    Chicago State Univ., IL.

    The Distinguished Cooperating Teacher Program at Chicago State University was developed to train cooperating teachers to supervise student teachers. The program departs from traditional practice by changing the roles of the classroom teacher and the university field supervisor. The supervisor's role becomes that of coordinator while the teacher…

  8. Cooperative Science Lesson Plans.

    ERIC Educational Resources Information Center

    Cooperative Learning, 1991

    1991-01-01

    Offers several elementary level cooperative science lesson plans. The article includes a recipe for cooperative class learning, instructions for making a compost pile, directions for finding evidence of energy, experiments in math and science using oranges to test density, and discussions of buoyancy using eggs. (SM)

  9. Making Cooperative Learning Powerful

    ERIC Educational Resources Information Center

    Slavin, Robert E.

    2014-01-01

    Just about everyone loves the "idea" of cooperative learning, children working productively and excitedly in groups, everyone getting along and enthusiastically helping one another learn. This article presents five strategies that teachers can use to get the greatest benefit possible from cooperative learning and ensure that…

  10. Culture and cooperation.

    PubMed

    Gächter, Simon; Herrmann, Benedikt; Thöni, Christian

    2010-09-12

    Does the cultural background influence the success with which genetically unrelated individuals cooperate in social dilemma situations? In this paper, we provide an answer by analysing the data of Herrmann et al. (2008a), who studied cooperation and punishment in 16 subject pools from six different world cultures (as classified by Inglehart & Baker (2000)). We use analysis of variance to disentangle the importance of cultural background relative to individual heterogeneity and group-level differences in cooperation. We find that culture has a substantial influence on the extent of cooperation, in addition to individual heterogeneity and group-level differences identified by previous research. The significance of this result is that cultural background has a substantial influence on cooperation in otherwise identical environments. This is particularly true in the presence of punishment opportunities.

  11. Culture and cooperation

    PubMed Central

    Gächter, Simon; Herrmann, Benedikt; Thöni, Christian

    2010-01-01

    Does the cultural background influence the success with which genetically unrelated individuals cooperate in social dilemma situations? In this paper, we provide an answer by analysing the data of Herrmann et al. (2008a), who studied cooperation and punishment in 16 subject pools from six different world cultures (as classified by Inglehart & Baker (2000)). We use analysis of variance to disentangle the importance of cultural background relative to individual heterogeneity and group-level differences in cooperation. We find that culture has a substantial influence on the extent of cooperation, in addition to individual heterogeneity and group-level differences identified by previous research. The significance of this result is that cultural background has a substantial influence on cooperation in otherwise identical environments. This is particularly true in the presence of punishment opportunities. PMID:20679109

  12. The Essential Elements of Cooperative Learning.

    ERIC Educational Resources Information Center

    Watson, Scott B.

    1992-01-01

    Discusses four elements of cooperative learning in science classrooms: cooperative task structures; cooperative incentive structures; individual accountability; and heterogeneous grouping. Presents and describes seven cooperative learning methods. (MDH)

  13. An Investigative, Cooperative Learning Approach to the General Microbiology Laboratory

    ERIC Educational Resources Information Center

    Seifert, Kyle; Fenster, Amy; Dilts, Judith A.; Temple, Louise

    2009-01-01

    Investigative- and cooperative-based learning strategies have been used effectively in a variety of classrooms to enhance student learning and engagement. In the General Microbiology laboratory for juniors and seniors at James Madison University, these strategies were combined to make a semester-long, investigative, cooperative learning experience…

  14. Social Networks-Based Adaptive Pairing Strategy for Cooperative Learning

    ERIC Educational Resources Information Center

    Chuang, Po-Jen; Chiang, Ming-Chao; Yang, Chu-Sing; Tsai, Chun-Wei

    2012-01-01

    In this paper, we propose a grouping strategy to enhance the learning and testing results of students, called Pairing Strategy (PS). The proposed method stems from the need of interactivity and the desire of cooperation in cooperative learning. Based on the social networks of students, PS provides members of the groups to learn from or mimic…

  15. Cooperative Learning in Vocational Education. Trends and Issues Alerts.

    ERIC Educational Resources Information Center

    Lankard, Bettina A.

    Cooperative learning is gaining the attention of vocational educators who must prepare students for employment in a workplace increasingly focused on teamwork. It is a model that provides opportunities for students to explore concepts and develop interpersonal skills that enhance their learning. Research shows that cooperative learning promotes…

  16. A Computer-Assisted Approach to Conducting Cooperative Learning Process

    ERIC Educational Resources Information Center

    Tsai, Pei-Jin; Hwang, Gwo-Jen; Tseng, Judy C. R.; Hwang, Gwo-Haur

    2008-01-01

    Cooperative learning has been proven to be helpful in enhancing the learning performance of students. The goal of a cooperative learning group is to maximize all members' learning, which is accomplished via promoting each other's success, through assisting, sharing, mentoring, explaining, and encouragement. To achieve the goal of cooperative…

  17. An Investigative, Cooperative Learning Approach to the General Microbiology Laboratory

    ERIC Educational Resources Information Center

    Seifert, Kyle; Fenster, Amy; Dilts, Judith A.; Temple, Louise

    2009-01-01

    Investigative- and cooperative-based learning strategies have been used effectively in a variety of classrooms to enhance student learning and engagement. In the General Microbiology laboratory for juniors and seniors at James Madison University, these strategies were combined to make a semester-long, investigative, cooperative learning experience…

  18. The Controversy over Group Rewards in Cooperative Classrooms.

    ERIC Educational Resources Information Center

    Graves, Ted

    1991-01-01

    Suggests ways to minimize the negative effects of extrinsic group rewards in cooperative classrooms, explains how to use intrinsic rewards, and outlines conditions calling for extrinsic rewards. The "social rewards" of working cooperatively probably enhance intrinsic motivation and are among the great advantages of employing cooperative…

  19. Cooperative Learning for Educational Reform in Armenia

    ERIC Educational Resources Information Center

    Hovhannisyan, Aleksan; Sahlberg, Pasi

    2010-01-01

    Armenia is in the midst of major educational reforms in which teacher professional development is a key component. Much of the energy devoted to developing education in Armenia is targeted towards enhancing student-centred teaching, especially cooperative learning. This has become a significant challenge for many schools and teachers as they cope…

  20. International Programming in the Cooperative Extension System.

    ERIC Educational Resources Information Center

    Lambur, Michael; And Others

    "Understanding World Agriculture" is a 3-year project (1984-1987) designed to mobilize resources of the Cooperative Extension Service (CES) to enhance citizen understanding of political, economic, technical, and social factors relating to world problems of hunger and poverty and to the stake of the United States in international…

  1. Cooperative Education: An Educational Gold Mine.

    ERIC Educational Resources Information Center

    Kickhaefer, Scott

    1988-01-01

    Describes the experiences of a secondary education major in speech and drama as a counselor with The Salvation Army Summer Camp. The author found that his cooperative education experience served him well as a career enhancement and dry run in the real world of the workplace. (JOW)

  2. Enhancing nuclear emergency response through international cooperation.

    PubMed

    Ugletveit, Finn; Aaltonen, Hannele

    2004-01-01

    Nuclear and radiological emergencies may easily become severe international emergencies requiring substantial resources in several or many states for an adequate response, which in some cases may require resources exceeding national capabilities. Through the development of a consistent, coherent and sustainable joint programme for improved and more efficient international responses to nuclear and radiological emergencies, it is believed that we could achieve a better and more cost-effective response capability for nuclear and radiological emergencies. This requires, however, that we be willing and able to establish mechanisms of assistance where information and resources are globally shared and that standardised/harmonised procedures be developed and implemented. If we are willing to make this investment, we believe that, in the long term, there will be a significant benefit for all of us.

  3. Helenalin Acetate, a Natural Sesquiterpene Lactone with Anti-inflammatory and Anti-cancer Activity, Disrupts the Cooperation of CCAAT Box/Enhancer-binding Protein β (C/EBPβ) and Co-activator p300.

    PubMed

    Jakobs, Anke; Steinmann, Simone; Henrich, Sarah Marie; Schmidt, Thomas J; Klempnauer, Karl-Heinz

    2016-12-09

    Recent work has demonstrated pro-oncogenic functions of the transcription factor CCAAT box/enhancer-binding protein β (C/EBPβ) in various tumors, implicating C/EBPβ as an interesting target for the development of small-molecule inhibitors. We have previously discovered that the sesquiterpene lactone helenalin acetate, a natural compound known to inhibit NF-κB, is a potent C/EBPβ inhibitor. We have now examined the inhibitory mechanism of helenalin acetate in more detail. We demonstrate that helenalin acetate is a significantly more potent inhibitor of C/EBPβ than of NF-κB. Our work shows that helenalin acetate inhibits C/EBPβ by binding to the N-terminal part of C/EBPβ, thereby disrupting the cooperation of C/EBPβ with the co-activator p300. C/EBPβ is expressed in several isoforms from alternative translational start codons. We have previously demonstrated that helenalin acetate selectively inhibits only the full-length (liver-enriched activating protein* (LAP*)) isoform but not the slightly shorter (LAP) isoform. Consistent with this, helenalin acetate binds to the LAP* but not to the LAP isoform, explaining why its inhibitory activity is selective for LAP*. Although helenalin acetate contains reactive groups that are able to interact covalently with cysteine residues, as exemplified by its effect on NF-κB, the inhibition of C/EBPβ by helenalin acetate is not due to irreversible reaction with cysteine residues of C/EBPβ. In summary, helenalin acetate is the first highly active small-molecule C/EBPβ inhibitor that inhibits C/EBPβ by a direct binding mechanism. Its selectivity for the LAP* isoform also makes helenalin acetate an interesting tool to dissect the functions of the LAP* and LAP isoforms.

  4. Loss of cooperativity of secreted CD40L and increased dose-response to IL4 on CLL cell viability correlates with enhanced activation of NF-kB and STAT6.

    PubMed

    Bhattacharya, Nupur; Reichenzeller, Michaela; Caudron-Herger, Maiwen; Haebe, Sarah; Brady, Nathan; Diener, Susanne; Nothing, Maria; Döhner, Hartmut; Stilgenbauer, Stephan; Rippe, Karsten; Mertens, Daniel

    2015-01-01

    Chronic lymphocytic leukemia (CLL) cells fail to enter apoptosis in vivo as opposed to their non-malignant B-lymphocyte counterparts. The ability of CLL cells to escape apoptosis is highly dependent on their microenvironment. Compared to non-malignant B cells, CLL cells are more responsive to complex stimuli that can be reproduced in vitro by the addition of cytokines. To understand the molecular mechanism of the environment-dependent anti-apoptotic signaling circuitry of CLL cells, we quantified the effect of the SDF-1, BAFF, APRIL, anti-IgM, interleukin-4 (IL4) and secreted CD40L (sCD40L) on the survival of in vitro cultured CLL cells and found IL4 and sCD40L to be most efficient in rescuing CLL cells from apoptosis. In quantitative dose-response experiments using cell survival as readout, the binding affinity of IL4 to its receptor was similar between malignant and non-malignant cells. However, the downstream signaling in terms of the amount of STAT6 and its degree of phosphorylation was highly stimulated in CLL cells. In contrast, the response to sCD40L showed a loss of cooperative binding in CLL cells but displayed a largely increased ligand binding affinity. Although a high-throughput microscopy analysis did not reveal a significant difference in the spatial CD40 receptor organization, the downstream signaling showed an enhanced activation of the NF-kB pathway in the malignant cells. Thus, we propose that the anti-apoptotic phenotype of CLL involves a sensitized response for IL4 dependent STAT6 phosphorylation, and an activation of NF-kB signaling due to an increased affinity of sCD40L to its receptor.

  5. What drives cooperative breeding?

    PubMed

    Koenig, Walter D

    2017-06-01

    Cooperative breeding, in which more than a pair of conspecifics cooperate to raise young at a single nest or brood, is widespread among vertebrates but highly variable in its geographic distribution. Particularly vexing has been identifying the ecological correlates of this phenomenon, which has been suggested to be favored in populations inhabiting both relatively stable, productive environments and in populations living under highly variable and unpredictable conditions. Griesser et al. provide a novel approach to this problem, performing a phylogenetic analysis indicating that family living is an intermediate step between nonsocial and cooperative breeding birds. They then examine the ecological and climatic conditions associated with these different social systems, concluding that cooperative breeding emerges when family living is favored in highly productive environments, followed secondarily by selection for cooperative breeding when environmental conditions deteriorate and within-year variability increases. Combined with recent work addressing the fitness consequences of cooperative breeding, Griesser et al.'s contribution stands to move the field forward by demonstrating that the evolution of complex adaptations such as cooperative breeding may only be understood when each of the steps leading to it are identified and carefully integrated.

  6. Globalization and human cooperation.

    PubMed

    Buchan, Nancy R; Grimalda, Gianluca; Wilson, Rick; Brewer, Marilynn; Fatas, Enrique; Foddy, Margaret

    2009-03-17

    Globalization magnifies the problems that affect all people and that require large-scale human cooperation, for example, the overharvesting of natural resources and human-induced global warming. However, what does globalization imply for the cooperation needed to address such global social dilemmas? Two competing hypotheses are offered. One hypothesis is that globalization prompts reactionary movements that reinforce parochial distinctions among people. Large-scale cooperation then focuses on favoring one's own ethnic, racial, or language group. The alternative hypothesis suggests that globalization strengthens cosmopolitan attitudes by weakening the relevance of ethnicity, locality, or nationhood as sources of identification. In essence, globalization, the increasing interconnectedness of people worldwide, broadens the group boundaries within which individuals perceive they belong. We test these hypotheses by measuring globalization at both the country and individual levels and analyzing the relationship between globalization and individual cooperation with distal others in multilevel sequential cooperation experiments in which players can contribute to individual, local, and/or global accounts. Our samples were drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. We find that as country and individual levels of globalization increase, so too does individual cooperation at the global level vis-à-vis the local level. In essence, "globalized" individuals draw broader group boundaries than others, eschewing parochial motivations in favor of cosmopolitan ones. Globalization may thus be fundamental in shaping contemporary large-scale cooperation and may be a positive force toward the provision of global public goods.

  7. Globalization and human cooperation

    PubMed Central

    Buchan, Nancy R.; Grimalda, Gianluca; Wilson, Rick; Brewer, Marilynn; Fatas, Enrique; Foddy, Margaret

    2009-01-01

    Globalization magnifies the problems that affect all people and that require large-scale human cooperation, for example, the overharvesting of natural resources and human-induced global warming. However, what does globalization imply for the cooperation needed to address such global social dilemmas? Two competing hypotheses are offered. One hypothesis is that globalization prompts reactionary movements that reinforce parochial distinctions among people. Large-scale cooperation then focuses on favoring one's own ethnic, racial, or language group. The alternative hypothesis suggests that globalization strengthens cosmopolitan attitudes by weakening the relevance of ethnicity, locality, or nationhood as sources of identification. In essence, globalization, the increasing interconnectedness of people worldwide, broadens the group boundaries within which individuals perceive they belong. We test these hypotheses by measuring globalization at both the country and individual levels and analyzing the relationship between globalization and individual cooperation with distal others in multilevel sequential cooperation experiments in which players can contribute to individual, local, and/or global accounts. Our samples were drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. We find that as country and individual levels of globalization increase, so too does individual cooperation at the global level vis-à-vis the local level. In essence, “globalized” individuals draw broader group boundaries than others, eschewing parochial motivations in favor of cosmopolitan ones. Globalization may thus be fundamental in shaping contemporary large-scale cooperation and may be a positive force toward the provision of global public goods. PMID:19255433

  8. Proposals Requested for Cooperative Agreement to Train Healthcare Providers

    EPA Pesticide Factsheets

    EPA is soliciting applications from eligible organizations to manage up to two cooperative agreements to enhance the goals of the EPA’s National Strategies for Health Care Providers: Pesticides Initiative.

  9. An Enhanced Role of the Economics Element of National Power in Military Operations: The Mexican Economy as a Case Study for U.S. Northern Command Theater Security Cooperation (TSC) Planning

    DTIC Science & Technology

    2011-10-26

    Cooperation (TSC) Planning 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...Theater Security Cooperation (TSC) plan focused on economics might be implemented to improve Mexico’s trade and commerce. Five recommendations based on...effective solutions developed by various nations facing challenges similar to those of Mexico are proposed in support of a TSC plan . These lines of

  10. Cooperative Learning Strategies.

    ERIC Educational Resources Information Center

    Pratt, Sandra

    2003-01-01

    Describes the effectiveness of cooperative learning on discipline problems, interdependence between students, and teacher-student interactions. Explains how to group students and introduces a laboratory activity on covalent and ionic bonds. (YDS)

  11. Cooperative processing data bases

    NASA Technical Reports Server (NTRS)

    Hasta, Juzar

    1991-01-01

    Cooperative processing for the 1990's using client-server technology is addressed. The main theme is concepts of downsizing from mainframes and minicomputers to workstations on a local area network (LAN). This document is presented in view graph form.

  12. How Myxobacteria Cooperate.

    PubMed

    Cao, Pengbo; Dey, Arup; Vassallo, Christopher N; Wall, Daniel

    2015-11-20

    Prokaryotes often reside in groups where a high degree of relatedness has allowed the evolution of cooperative behaviors. However, very few bacteria or archaea have made the successful transition from unicellular to obligate multicellular life. A notable exception is the myxobacteria, in which cells cooperate to perform group functions highlighted by fruiting body development, an obligate multicellular function. Like all multicellular organisms, myxobacteria face challenges in how to organize and maintain multicellularity. These challenges include maintaining population homeostasis, carrying out tissue repair and regulating the behavior of non-cooperators. Here, we describe the major cooperative behaviors that myxobacteria use: motility, predation and development. In addition, this review emphasizes recent discoveries in the social behavior of outer membrane exchange, wherein kin share outer membrane contents. Finally, we review evidence that outer membrane exchange may be involved in regulating population homeostasis, thus serving as a social tool for myxobacteria to make the cyclic transitions from unicellular to multicellular states.

  13. Cooperative Learning in Statistics.

    ERIC Educational Resources Information Center

    Keeler, Carolyn M.; And Others

    1994-01-01

    Formal use of cooperative learning techniques proved effective in improving student performance and retention in a freshman level statistics course. Lectures interspersed with group activities proved effective in increasing conceptual understanding and overall class performance. (11 references) (Author)

  14. Cooperative Learning Strategies.

    ERIC Educational Resources Information Center

    Pratt, Sandra

    2003-01-01

    Describes the effectiveness of cooperative learning on discipline problems, interdependence between students, and teacher-student interactions. Explains how to group students and introduces a laboratory activity on covalent and ionic bonds. (YDS)

  15. Cooperative Education: Industry Involvement.

    ERIC Educational Resources Information Center

    Davies, Geoffrey; McClelland, Alan L.

    1980-01-01

    Contains information from three large chemical companies having a long-standing interest in cooperative education with chemistry students. Questions and answers are provided for specific information regarding DuPont, 3M, and Dow Chemical. (CS)

  16. Cooperative Purchasing Reduces Costs.

    ERIC Educational Resources Information Center

    Kula, Edwin J.

    1981-01-01

    Several suburban Chicago (Illinois) school districts are members of the South Suburban School Purchasing Cooperative, which serves as a conduit for volume purchases of educational supplies. (Author/MLF)

  17. Stochastic dynamics of the prisoner's dilemma with cooperation facilitators.

    PubMed

    Mobilia, Mauro

    2012-07-01

    In the framework of the paradigmatic prisoner's dilemma game, we investigate the evolutionary dynamics of social dilemmas in the presence of "cooperation facilitators." In our model, cooperators and defectors interact as in the classical prisoner's dilemma, where selection favors defection. However, here the presence of a small number of cooperation facilitators enhances the fitness (reproductive potential) of cooperators, while it does not alter that of defectors. In a finite population of size N, the dynamics of the prisoner's dilemma with facilitators is characterized by the probability that cooperation takes over (fixation probability) by the mean times to reach the absorbing states. These quantities are computed exactly using Fokker-Planck equations. Our findings, corroborated by stochastic simulations, demonstrate that the influence of facilitators crucially depends on the difference between their density z and the game's cost-to-benefit ratio r. When z > r, the fixation of cooperators is likely in a large population and, under weak selection pressure, invasion and replacement of defection by cooperation is favored by selection if b(z - r)(1 - z) > N(-1), where 0cooperation payoff benefit. When z < r, the fixation probability of cooperators is exponentially enhanced by the presence of facilitators but defection is the dominating strategy.

  18. Conditional imitation might promote cooperation under high temptations to defect.

    PubMed

    Dai, Qionglin; Li, Haihong; Cheng, Hongyan; Qian, Xiaolan; Zhang, Mei; Yang, Junzhong

    2012-07-01

    In this paper we introduce a conditional imitation rule into an evolutionary game, in which the imitation probabilities of individuals are determined by a function of payoff difference and two crucial parameters μ and σ. The parameter μ characterizes the most adequate goal for individuals and the parameter σ characterizes the tolerance of individuals. By using the pair approximation method and numerical simulations, we find an anomalous cooperation enhancement in which the cooperation level shows a nonmonotonic variation with the increase of temptation. The parameter μ affects the regime of the payoff parameter which supports the anomalous cooperation enhancement, whereas the parameter σ plays a decisive role on the appearance of the nonmonotonic variation of the cooperation level. Furthermore, to give explicit implications for the parameters μ and σ we present an alterative form of the conditional imitation rule based on the benefit and the cost incurred to individuals during strategy updates. In this way, we also provide a phenomenological interpretation for the nonmonotonic behavior of cooperation with the increase of temptation. The results give a clue that a higher cooperation level could be obtained under adverse environments for cooperation by applying the conditional imitation rule, which is possible to be manipulated in real life. More generally, the results in this work might point out an efficient way to maintain cooperation in the risky environments to cooperators.

  19. Conditional imitation might promote cooperation under high temptations to defect

    NASA Astrophysics Data System (ADS)

    Dai, Qionglin; Li, Haihong; Cheng, Hongyan; Qian, Xiaolan; Zhang, Mei; Yang, Junzhong

    2012-07-01

    In this paper we introduce a conditional imitation rule into an evolutionary game, in which the imitation probabilities of individuals are determined by a function of payoff difference and two crucial parameters μ and σ. The parameter μ characterizes the most adequate goal for individuals and the parameter σ characterizes the tolerance of individuals. By using the pair approximation method and numerical simulations, we find an anomalous cooperation enhancement in which the cooperation level shows a nonmonotonic variation with the increase of temptation. The parameter μ affects the regime of the payoff parameter which supports the anomalous cooperation enhancement, whereas the parameter σ plays a decisive role on the appearance of the nonmonotonic variation of the cooperation level. Furthermore, to give explicit implications for the parameters μ and σ we present an alterative form of the conditional imitation rule based on the benefit and the cost incurred to individuals during strategy updates. In this way, we also provide a phenomenological interpretation for the nonmonotonic behavior of cooperation with the increase of temptation. The results give a clue that a higher cooperation level could be obtained under adverse environments for cooperation by applying the conditional imitation rule, which is possible to be manipulated in real life. More generally, the results in this work might point out an efficient way to maintain cooperation in the risky environments to cooperators.

  20. Cooperating mobile robots

    DOEpatents

    Harrington, John J.; Eskridge, Steven E.; Hurtado, John E.; Byrne, Raymond H.

    2004-02-03

    A miniature mobile robot provides a relatively inexpensive mobile robot. A mobile robot for searching an area provides a way for multiple mobile robots in cooperating teams. A robotic system with a team of mobile robots communicating information among each other provides a way to locate a source in cooperation. A mobile robot with a sensor, a communication system, and a processor, provides a way to execute a strategy for searching an area.

  1. Expectation and cooperation in prisoner's dilemmas: The moderating role of game riskiness.

    PubMed

    Ng, Gary Ting Tat; Au, Wing Tung

    2016-04-01

    This paper investigated the effect of risk orientation, game riskiness, and expectation of cooperation on cooperation in one-shot prisoner's dilemmas (PD). Participants in pairs played PD games that varied on game riskiness such that for half of the games cooperation was more risky than defection (more risky games) while for another half cooperation was less risky (less risky games). They estimated how likely it was that the other player was going to cooperate (expectation of cooperation) before they made their cooperation/defection decision on each game. Supporting the Goal/Expectation Hypothesis, we replicated the effect that expectation of cooperation enhanced cooperation. We also found that risk-seeking individuals cooperated more in more risky games whereas risk-averse individuals cooperated more in less risky games. More importantly, we found that game riskiness moderated the effect of expectation of cooperation on cooperation. The positive effect of expectation of cooperation on cooperation was stronger for more risky games than for less risky games. Our results illustrated how the relation between expectation and cooperation as stipulated by the Goal/Expectation Hypothesis was moderated by riskiness of the situations.

  2. Cooperative spreading processes in multiplex networks

    NASA Astrophysics Data System (ADS)

    Wei, Xiang; Chen, Shihua; Wu, Xiaoqun; Ning, Di; Lu, Jun-an

    2016-06-01

    This study is concerned with the dynamic behaviors of epidemic spreading in multiplex networks. A model composed of two interacting complex networks is proposed to describe cooperative spreading processes, wherein the virus spreading in one layer can penetrate into the other to promote the spreading process. The global epidemic threshold of the model is smaller than the epidemic thresholds of the corresponding isolated networks. Thus, global epidemic onset arises in the interacting networks even though an epidemic onset does not arise in each isolated network. Simulations verify the analysis results and indicate that cooperative spreading processes in multiplex networks enhance the final infection fraction.

  3. Cooperation and depressive symptoms.

    PubMed

    Brendan Clark, C; Thorne, Christopher B; Hardy, Sonya; Cropsey, Karen L

    2013-09-25

    Deficits in pro-social cooperation are common in many individuals with mental illnesses such as depression. For decades, researchers have used economic game paradigms to compare cross-cultural cooperative behavior. However, research using economic games to assess cooperative behavior in clinical populations is in the early stages. We hypothesized that individuals with greater depressive symptoms would struggle to maintain reciprocity in iterative games, but not in single-iteration games measuring personal values. Participants (n=41) played four computer-based economic games (prisoner's dilemma, the public goods game, the ultimatum game, and the trust game) measuring different aspects of cooperation. Participants completed the Depression Anxiety and Stress Scale (DASS) and other measures of personality and demographics. Analyses assessed the relationships between game performance and psychological distress as measured by the DASS. Significant correlations were found between game performance and depressive symptoms, but not symptoms of anxiety or stress. Performance in the prisoner's dilemma and public goods game was significantly related to depression in a linear regression even when known associations with depressive affect such as age, gender, race, education, marital status, and neuroticism were controlled for. Depressive symptoms were associated with an inability to sustain reciprocal cooperation. Participants showed the predicted deficits in cooperation in these economic games. Economic games show the potential for assessing the social deficits associated with depressive symptoms. © 2013 Elsevier B.V. All rights reserved.

  4. Enhancing Access to Space Science Literature

    NASA Astrophysics Data System (ADS)

    Bigwood, D. P.

    2006-03-01

    By participating in the Name Authority Program Component and Subject Authority Cooperative Program of the Program for Cooperative Cataloging of the Library of Congress even the smallest libraries can enhance access to the space science literature.

  5. The evolution of cooperation by the Hankshaw effect.

    PubMed

    Hammarlund, Sarah P; Connelly, Brian D; Dickinson, Katherine J; Kerr, Benjamin

    2016-06-01

    The evolution of cooperation-costly behavior that benefits others-faces one clear obstacle. Namely, cooperators are always at a competitive disadvantage relative to defectors, individuals that reap the benefits, but evade the cost of cooperation. One solution to this problem involves genetic hitchhiking, where the allele encoding cooperation becomes linked to a beneficial mutation, allowing cooperation to rise in abundance. Here, we explore hitchhiking in the context of adaptation to a stressful environment by cooperators and defectors with spatially limited dispersal. Under such conditions, clustered cooperators reach higher local densities, thereby experiencing more mutational opportunities than defectors. Thus, the allele encoding cooperation has a greater probability of hitchhiking with alleles conferring stress adaptation. We label this probabilistic enhancement the "Hankshaw effect" after the character Sissy Hankshaw, whose anomalously large thumbs made her a singularly effective hitchhiker. Using an agent-based model, we reveal a broad set of conditions that allow the evolution of cooperation through this effect. Additionally, we show that spite, a costly behavior that harms others, can evolve by the Hankshaw effect. While in an unchanging environment these costly social behaviors have transient success, in a dynamic environment, cooperation and spite can persist indefinitely.

  6. Coevolution of cooperation and network structure under natural selection

    NASA Astrophysics Data System (ADS)

    Yang, D.-P.; Lin, H.; Shuai, J. W.

    2011-02-01

    A coevolution model by coupling mortality and fertility selection is introduced to investigate the evolution of cooperation and network structure in the prisoner's dilemma game. The cooperation level goes through a continuous phase transition vs. defection temptation b for low mortality selection intensity β and through a discontinuous one for infinite β. The cooperation level is enhanced most at β≈1 for any b. The local and global properties of the network structure, such as cluster and cooperating k-core, are investigated for the understanding of cooperation evolution. Cooperation is promoted by forming a tight cooperating k-core at moderate β, but too large β will destroy the cooperating k-core rapidly resulting in a rapid drop of the cooperation level. Importantly, the infinite β changes the normalized sucker's payoff S from 0 to 1-b and its dynamics of the cooperation level undergoes a very slow power-law decay, which leads the evolution into the regime of neutral evolution.

  7. Reward and cooperation in the spatial public goods game

    NASA Astrophysics Data System (ADS)

    Szolnoki, A.; Perc, M.

    2010-11-01

    The promise of punishment and reward in promoting public cooperation is debatable. While punishment is traditionally considered more successful than reward, the fact that the cost of punishment frequently fails to offset gains from enhanced cooperation has lead some to reconsider reward as the main catalyst behind collaborative efforts. Here we elaborate on the "stick vs. carrot" dilemma by studying the evolution of cooperation in the spatial public goods game, where besides the traditional cooperators and defectors, rewarding cooperators supplement the array of possible strategies. The latter are willing to reward cooperative actions at a personal cost, thus effectively downgrading pure cooperators to second-order free-riders due to their unwillingness to bear these additional costs. Consequently, we find that defection remains viable, especially if the rewarding is costly. Rewards, however, can promote cooperation, especially if the synergetic effects of cooperation are low. Surprisingly, moderate rewards may promote cooperation better than high rewards, which is due to the spontaneous emergence of cyclic dominance between the three strategies.

  8. Cooperative Learning in the Classroom.

    ERIC Educational Resources Information Center

    James, Cecile Burnett

    1989-01-01

    Discusses the rationale for cooperative learning and examines the teacher's role in creating groups. Provides examples of cooperative learning experiences in an integrated unit and as applied to computer education. Lists the advantages of using cooperative learning, while noting its pitfalls. Cautions that cooperative learning should be used in…

  9. LMS Moodle: Distance International Education in Cooperation of Higher Education Institutions of Different Countries

    ERIC Educational Resources Information Center

    Kerimbayev, N.; Kultan, J.; Abdykarimova, S.; Akramova, A.

    2017-01-01

    The development of international cooperation requires cooperation in the sphere of education. An enhanced sharing of experience in the sphere of practical teaching activities implies the increase of the quality of teaching process and of scientific cooperation. Sharing of experience in educational activities implies understanding among…

  10. Principles of cooperation across systems: from human sharing to multicellularity and cancer.

    PubMed

    Aktipis, Athena

    2016-01-01

    From cells to societies, several general principles arise again and again that facilitate cooperation and suppress conflict. In this study, I describe three general principles of cooperation and how they operate across systems including human sharing, cooperation in animal and insect societies and the massively large-scale cooperation that occurs in our multicellular bodies. The first principle is that of Walk Away: that cooperation is enhanced when individuals can leave uncooperative partners. The second principle is that resource sharing is often based on the need of the recipient (i.e., need-based transfers) rather than on strict account-keeping. And the last principle is that effective scaling up of cooperation requires increasingly sophisticated and costly cheater suppression mechanisms. By comparing how these principles operate across systems, we can better understand the constraints on cooperation. This can facilitate the discovery of novel ways to enhance cooperation and suppress cheating in its many forms, from social exploitation to cancer.

  11. International cooperation in water resources

    USGS Publications Warehouse

    Jones, J.R.; Beall, R.M.; Giusti, E.V.

    1979-01-01

    Advancements in hydrology proceeded slowly until the late 1800's when new ventures created a surge of interest and accomplishment. Progress waned again until the middle 20th century when an International Hydrological Decade was conceived, eventually receiving wide multinational support from governmental agencies and nongovernmental institutions. Organized by UNESCO, the Decade program was launched January 1, 1965. Participation included 107 nations, six United Nations agencies, and more than a dozen international scientific organizations. The initial program emphasized scientific research, and international cooperation; the second half of the Decade, emphasized technical assistance and technology transfer, largerly through education, training and demonstration. The success of the Decade led to the establishment of the International Hydrological Program, again under the aegis of UNESCO, to continue the work of the Decade indefinitely. The five major program activities, now involving about 90 countries and several international organizations, include: the scientific program, the promotion of education and training, the enhancement of information exchange, support of technical assistance, and the enlargement of regional cooperation. A significant amount of activity related to hydrological data networks and forecasting is carried on in an Operational Hydrology Programme by the WMO, chiefly through its Commission for Hydrology. Other international governmental organizations with a strong interest in water include the UN, the UN Development Programme, the FAO, the WHO, the International Atomic Energy Agency, the UN Environment Programme, the International Standardization Organization, and developmental institutions such as the World Bank. The specialized interests of researchers outside of the governmental structure, are met through association in various scientific and technical organizations which are world wide in scope and membership. Notwithstanding a sometimes

  12. International Cooperation at NASA

    NASA Astrophysics Data System (ADS)

    Tawney, Timothy; Feldstein, Karen

    International cooperation is a cornerstone principle of NASA’s activities, especially within the activities of the Science Mission Directorate. Nearly two thirds of the flight missions in which NASA leads or participates involve international cooperation. Numerous ground based activities also rely on international cooperation, whether because of unique expertise, unique geography, or the need for a global response. Going forward, in an era of tighter budgets and a more integrated global perspective, NASA and the rest of the space agencies around the world will be forced to work more closely together, in a broader array of activities than ever before, in order to be able to afford to push the boundaries of space exploration. The goal of this presentation is to provide an overview of NASA’s current international science cooperative activities. It will include a discussion of why NASA conducts international cooperation and look at the mechanisms through which international cooperation can occur at NASA, including peer-to-peer development of relationships. It will also discuss some of the limiting factors of international cooperation, such as export control, and ways in which to manage those constraints. Finally, the presentation would look at some of the present examples where NASA is working to increase international cooperation and improve coordination. Case studies will be used to demonstrate these mechanisms and concepts. For example, NASA continues to participate in international coordination groups such as the International Mars Exploration Working Group (IMEWG) and International Space Exploration Coordination Group (ISECG), but is expanding into new areas as well. NASA is one of the leaders in expanding and improving international coordination in the area of Near-Earth Object detection, characterization, and mitigation. Having participated in the first meetings of such groups as the International Asteroid Warning Network (IAWN) and Space Missions Planning

  13. Cooper Pair Insulators

    NASA Astrophysics Data System (ADS)

    Valles, James

    One of the recent advances in the field of the Superconductor to Insulator Transition (SIT) has been the discovery and characterization of the Cooper Pair Insulator phase. This bosonic insulator, which consists of localized Cooper pairs, exhibits activated transport and a giant magneto-resistance peak. These features differ markedly from the weakly localized transport that emerges as pairs break at a ``fermionic'' SIT. I will describe how our experiments on films nano-patterned with a nearly triangular array of holes have enabled us to 1) distinguish bosonic insulators from fermionic insulators, 2) show that Cooper pairs, rather than quasi-particles dominate the transport in the Cooper Pair insulator phase, 3) demonstrate that very weak, sub nano-meter thickness inhomogeneities control whether a bosonic or fermionic insulator forms at an SIT and 4) reveal that Cooper pairs disintegrate rather than becoming more tightly bound deep in the localized phase. We have also developed a method, using a magnetic field, to tune flux disorder reversibly in these films. I will present our latest results on the influence of magnetic flux disorder and random gauge fields on phenomena near bosonic SITs. This work was performed in collaboration with M. D. Stewart, Jr., Hung Q. Nguyen, Shawna M. Hollen, Jimmy Joy, Xue Zhang, Gustavo Fernandez, Jeffrey Shainline and Jimmy Xu. It was supported by NSF Grants DMR 1307290 and DMR-0907357.

  14. Short versus long term benefits and the evolution of cooperation in the prisoner's dilemma game.

    PubMed

    Brede, Markus

    2013-01-01

    In this paper I investigate the evolution of cooperation in the prisoner's dilemma when individuals change their strategies subject to performance evaluation of their neighbours over variable time horizons. In the monochrome setting, in which all agents per default share the same performance evaluation rule, weighing past events strongly dramatically enhances the prevalence of cooperators. For co-evolutionary models, in which evaluation time horizons and strategies can co-evolve, I demonstrate that cooperation naturally associates with long-term evaluation of others while defection is typically paired with very short time horizons. Moreover, considering the continuous spectrum in between enhanced and discounted weights of past performance, cooperation is optimally supported when cooperators neither give enhanced weight to past nor more recent events, but simply average payoffs. Payoff averaging is also found to emerge as the dominant strategy for cooperators in co-evolutionary models, thus proposing a natural route to the evolution of cooperation in viscous populations.

  15. Collective chasing behavior between cooperators and defectors in the spatial prisoner's dilemma.

    PubMed

    Ichinose, Genki; Saito, Masaya; Suzuki, Shinsuke

    2013-01-01

    Cooperation is one of the essential factors for all biological organisms in major evolutionary transitions. Recent studies have investigated the effect of migration for the evolution of cooperation. However, little is known about whether and how an individuals' cooperativeness coevolves with mobility. One possibility is that mobility enhances cooperation by enabling cooperators to escape from defectors and form clusters; the other possibility is that mobility inhibits cooperation by helping the defectors to catch and exploit the groups of cooperators. In this study we investigate the coevolutionary dynamics by using the prisoner's dilemma game model on a lattice structure. The computer simulations demonstrate that natural selection maintains cooperation in the form of evolutionary chasing between the cooperators and defectors. First, cooperative groups grow and collectively move in the same direction. Then, mutant defectors emerge and invade the cooperative groups, after which the defectors exploit the cooperators. Then other cooperative groups emerge due to mutation and the cycle is repeated. Here, it is worth noting that, as a result of natural selection, the mobility evolves towards directional migration, but not to random or completely fixed migration. Furthermore, with directional migration, the rate of global population extinction is lower when compared with other cases without the evolution of mobility (i.e., when mobility is preset to random or fixed). These findings illustrate the coevolutionary dynamics of cooperation and mobility through the directional chasing between cooperators and defectors.

  16. Retaliation and the role for punishment in the evolution of cooperation.

    PubMed

    Wolff, Irenaeus

    2012-12-21

    Models of evolutionary game theory have shown that punishment may be an adaptive behaviour in environments characterised by a social-dilemma situation. Experimental evidence closely corresponds to this finding but questions the cooperation-enhancing effect of punishment if players are allowed to retaliate against their punishers. This study provides a theoretical explanation for the existence of retaliating behaviour in the context of repeated social dilemmas and analyses the role punishment can play in the evolution of cooperation under these conditions. We show a punishing strategy can pave the way for a partially cooperative equilibrium of conditional cooperators and defecting types and, under positive mutation rates, foster the cooperation level in this equilibrium by prompting reluctant cooperators to cooperate. However, when rare mutations occur, it cannot sustain cooperation by itself as punishment costs favour the spread of non-punishing cooperators.

  17. A 90 kDa fragment of filamin A promotes Casodex-induced growth inhibition in Casodex-resistant androgen receptor positive C4-2 prostate cancer cells.

    PubMed

    Wang, Y; Kreisberg, J I; Bedolla, R G; Mikhailova, M; deVere White, R W; Ghosh, P M

    2007-09-06

    Prostate tumors are initially dependent on androgens for growth, but the majority of patients treated with anti-androgen therapy progress to androgen-independence characterized by resistance to such treatment. This study investigates a novel role for filamin A (FlnA), a 280 kDa cytoskeletal protein (consisting of an actin-binding domain (ABD) followed by 24 sequential repeats), in androgen-independent (AI) growth. Full-length FlnA is cleaved to 170 kDa (ABD+FlnA1-15) and 110 kDa fragments (FlnA16-24); the latter is further cleaved to a 90 kDa fragment (repeats 16-23) capable of nuclear translocation and androgen receptor (AR) binding. Here, we demonstrate that in androgen-dependent LNCaP prostate cancer cells, the cleaved 90 kDa fragment is localized to the nucleus, whereas in its AI subline C4-2, FlnA failed to cleave and remained cytoplasmic. Transfection of FlnA16-24 cDNA in C4-2 cells restored expression and nuclear localization of 90 kDa FlnA. Unlike LNCaP, C4-2 cells proliferate in androgen-reduced medium and in the presence of the AR-antagonist Casodex. They also exhibit increased Akt phosphorylation compared to LNCaP, which may contribute to their AI phenotype. Nuclear expression of 90 kDa FlnA in C4-2 cells decreased Akt phosphorylation, prevented proliferation in androgen-reduced medium and restored Casodex sensitivity. This effect was inhibited by constitutive activation of Akt indicating that FlnA restored Casodex sensitivity in C4-2 cells by decreasing Akt phosphorylation. In addition, FlnA-specific siRNA which depleted FlnA levels, but not control siRNA, induced resistance to Casodex in LNCaP cells. Our results demonstrate that expression of nuclear FlnA is necessary for androgen dependence in these cells.

  18. Problems and Countermeasures of Zhejiang High-Tech Enterprises Industry-University-Institute Cooperation in China

    NASA Astrophysics Data System (ADS)

    Zhou, Qing; Mao, Chong-Feng; Hou, Lin

    Industry-university-institute cooperation is an important means to accelerate technical development and achievements for high-tech enterprises. Considering that Zhejiang high-tech enterprises existed some problems which included low cooperative level, single distribution, weak secondary R&D ability, obvious risk and so on, government should play an guiding role on improving information service system, enhancing cooperative level, promoting scientific intermediary service organization system construction, and building better environment for Industry-university-institute cooperation.

  19. Asymmetric evaluation promotes cooperation in network population

    NASA Astrophysics Data System (ADS)

    Shen, Chen; Li, Xiaoping; Shi, Lei; Deng, Zhenghong

    2017-05-01

    The evolution of cooperation remains a fundamental challenge in human society. Many previous studies investigated these questions via spatial reciprocity, where players obtain their payoffs by interacting with their direct neighbors. It has also been verified that environmental factors can influence the evolution of cooperation theoretically and empirically. In reality, however, individuals may have the limit knowledge about their indirect neighbors. Inspired by this fact, we consider an asymmetric fitness calculation mechanism, which only integrates the environment factors into the focal player, to explore the evolution of cooperation. Here, the environmental factor is defined as the average payoff of all individual neighbors, which is regulated by a tunable parameter u. Through numerical simulation, we find that, compared with the traditional version (u = 0), that the cooperation level can be greatly enhanced when u is positive. Interestingly, the larger the value of u, the higher the level of cooperation. Finally, to explore the generality of this finding, we have tested the results on different topologies.

  20. DOE/ABACC safeguards cooperation

    SciTech Connect

    Whitaker, J.M.; Alvim, C.F.; Toth, P.; Rubio, J.

    1995-12-31

    In 1994, the US Department of Energy (DOE) and the Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials (ABACC) signed a safeguards cooperation agreement. The agreement provides for cooperation in the areas of nuclear material control, accountancy, verification, and advanced containment and surveillance technologies for international safeguards applications. ABACC is an international safeguards organization responsible for verifying the commitments of a 1991 bilateral agreement between Argentina and Brazil in which both countries agreed to submit all nuclear material in all nuclear activities to a Common System of Accounting and Control of Nuclear Materials (SCCC). DOE provides critical assistance (including equipment and training) through the Office of Nonproliferation and National Security to countries and international organizations to enhance their capabilities to control and verify nuclear material inventories. Specific activities initiated under the safeguards agreement include: (1) active US participation in ABACC`s safeguards training courses, (2) joint development of specialized measurement training workshops, (3) characterization of laboratory standards, and (4) development and application of an extensive analytical laboratory comparison program. The results realized from these initial activities have been mutually beneficial in regard to strengthening the application of international safeguards in Argentina and Brazil.

  1. Cooper Pairs in Insulators?!

    ScienceCinema

    James Valles

    2016-07-12

    Nearly 50 years elapsed between the discovery of superconductivity and the emergence of the microscopic theory describing this zero resistance state. The explanation required a novel phase of matter in which conduction electrons joined in weakly bound pairs and condensed with other pairs into a single quantum state. Surprisingly, this Cooper pair formation has also been invoked to account for recently uncovered high-resistance or insulating phases of matter. To address this possibility, we have used nanotechnology to create an insulating system that we can probe directly for Cooper pairs. I will present the evidence that Cooper pairs exist and dominate the electrical transport in these insulators and I will discuss how these findings provide new insight into superconductor to insulator quantum phase transitions. 

  2. Synchrony and cooperation.

    PubMed

    Wiltermuth, Scott S; Heath, Chip

    2009-01-01

    Armies, churches, organizations, and communities often engage in activities-for example, marching, singing, and dancing-that lead group members to act in synchrony with each other. Anthropologists and sociologists have speculated that rituals involving synchronous activity may produce positive emotions that weaken the psychological boundaries between the self and the group. This article explores whether synchronous activity may serve as a partial solution to the free-rider problem facing groups that need to motivate their members to contribute toward the collective good. Across three experiments, people acting in synchrony with others cooperated more in subsequent group economic exercises, even in situations requiring personal sacrifice. Our results also showed that positive emotions need not be generated for synchrony to foster cooperation. In total, the results suggest that acting in synchrony with others can increase cooperation by strengthening social attachment among group members.

  3. Evolution, epigenetics and cooperation.

    PubMed

    Bateson, Patrick

    2014-04-01

    Explanations for biological evolution in terms of changes in gene frequencies refer to outcomes rather than process. Integrating epigenetic studies with older evolutionary theories has drawn attention to the ways in which evolution occurs. Adaptation at the level of the gene is givingway to adaptation at the level of the organism and higher-order assemblages of organisms. These ideas impact on the theories of how cooperation might have evolved. Two of the theories, i.e. that cooperating individuals are genetically related or that they cooperate for self-interested reasons, have been accepted for a long time. The idea that adaptation takes place at the level of groups is much more controversial. However, bringing together studies of development with those of evolution is taking away much of the heat in the debate about the evolution of group behaviour.

  4. Cooperation in the prisoner's dilemma game on tunable community networks

    NASA Astrophysics Data System (ADS)

    Liu, Penghui; Liu, Jing

    2017-04-01

    Community networks have attracted lots of attention as they widely exist in the real world and are essential to study properties of networks. As the game theory illustrates the competitive relationship among individuals, studying the iterated prisoner's dilemma games (PDG) on community networks is meaningful. In this paper, we focus on investigating the relationship between the cooperation level of community networks and that of their communities in the prisoner's dilemma games. With this purpose in mind, a type of tunable community networks whose communities inherit not only the scale-free property, but also the characteristic of adjustable cooperation level of Holme and Kim (HK) networks is designed. Both uniform and non-uniform community networks are investigated. We find out that cooperation enhancement of communities can improve the cooperation level of the whole networks. Moreover, simulation results indicate that a large community is a better choice than a small community to improve the cooperation level of the whole networks. Thus, improving the cooperation level of community networks can be divided into a number of sub-problems targeting at improving the cooperation level of individual communities, which can save the computation cost and deal with the problem of improving the cooperation level of huge community networks. Moreover, as the larger community is a better choice, it is reasonable to start with large communities, according to the greedy strategy when the number of nodes can participate in the enhancement is limited.

  5. Neural basis of conditional cooperation.

    PubMed

    Suzuki, Shinsuke; Niki, Kazuhisa; Fujisaki, Syoken; Akiyama, Eizo

    2011-06-01

    Cooperation among genetically unrelated individuals is a fundamental aspect of society, but it has been a longstanding puzzle in biological and social sciences. Recently, theoretical studies in biology and economics showed that conditional cooperation-cooperating only with those who have exhibited cooperative behavior-can spread over a society. Furthermore, experimental studies in psychology demonstrated that people are actually conditional cooperators. In this study, we used functional magnetic resonance imaging to investigate the neural system underlying conditional cooperation by scanning participants during interaction with cooperative, neutral and non-cooperative opponents in prisoner's dilemma games. The results showed that: (i) participants cooperated more frequently with both cooperative and neutral opponents than with non-cooperative opponents; and (ii) a brain area related to cognitive inhibition of pre-potent responses (right dorsolateral prefrontal cortex) showed greater activation, especially when participants confronted non-cooperative opponents. Consequently, we suggest that cognitive inhibition of the motivation to cooperate with non-cooperators drives the conditional behavior.

  6. Critical mass of public goods and its coevolution with cooperation

    NASA Astrophysics Data System (ADS)

    Shi, Dong-Mei; Wang, Bing-Hong

    2017-07-01

    In this study, the enhancing parameter represented the value of the public goods to the public in public goods game, and was rescaled to a Fermi-Dirac distribution function of critical mass. Public goods were divided into two categories, consumable and reusable public goods, and their coevolution with cooperative behavior was studied. We observed that for both types of public goods, cooperation was promoted as the enhancing parameter increased when the value of critical mass was not very large. An optimal value of critical mass which led to the best cooperation was identified. We also found that cooperations emerged earlier for reusable public goods, and defections became extinct earlier for the consumable public goods. Moreover, we observed that a moderate depreciation rate for public goods resulted in an optimal cooperation, and this range became wider as the enhancing parameter increased. The noise influence on cooperation was studied, and it was shown that cooperation density varied non-monotonically as noise amplitude increased for reusable public goods, whereas decreased monotonically for consumable public goods. Furthermore, existence of the optimal critical mass was also identified in other three regular networks. Finally, simulation results were utilized to analyze the provision of public goods in detail.

  7. Collective-Goal Ascription Increases Cooperation in Humans

    PubMed Central

    Mitkidis, Panagiotis; Sørensen, Jesper; Nielbo, Kristoffer L.; Andersen, Marc; Lienard, Pierre

    2013-01-01

    Background Cooperation is necessary in many types of human joint activity and relations. Evidence suggests that cooperation has direct and indirect benefits for the cooperators. Given how beneficial cooperation is overall, it seems relevant to investigate the various ways of enhancing individuals' willingness to invest in cooperative endeavors. We studied whether ascription of a transparent collective goal in a joint action promotes cooperation in a group. Methods A total of 48 participants were assigned in teams of 4 individuals to either a “transparent goal-ascription” or an “opaque goal-ascription” condition. After the manipulation, the participants played an anonymous public goods game with another member of their team. We measured the willingness of participants to cooperate and their expectations about the other player's contribution. Results Between subjects analyses showed that transparent goal ascription impacts participants' likelihood to cooperate with each other in the future, thereby greatly increasing the benefits from social interactions. Further analysis showed that this could be explained with a change in expectations about the partner's behavior and by an emotional alignment of the participants. Conclusion The study found that a transparent goal ascription is associated with an increase of cooperation. We propose several high-level mechanisms that could explain the observed effect: general affect modulation, trust, expectation and perception of collective efficacy. PMID:23705011

  8. Collective-goal ascription increases cooperation in humans.

    PubMed

    Mitkidis, Panagiotis; Sørensen, Jesper; Nielbo, Kristoffer L; Andersen, Marc; Lienard, Pierre

    2013-01-01

    Cooperation is necessary in many types of human joint activity and relations. Evidence suggests that cooperation has direct and indirect benefits for the cooperators. Given how beneficial cooperation is overall, it seems relevant to investigate the various ways of enhancing individuals' willingness to invest in cooperative endeavors. We studied whether ascription of a transparent collective goal in a joint action promotes cooperation in a group. A total of 48 participants were assigned in teams of 4 individuals to either a "transparent goal-ascription" or an "opaque goal-ascription" condition. After the manipulation, the participants played an anonymous public goods game with another member of their team. We measured the willingness of participants to cooperate and their expectations about the other player's contribution. Between subjects analyses showed that transparent goal ascription impacts participants' likelihood to cooperate with each other in the future, thereby greatly increasing the benefits from social interactions. Further analysis showed that this could be explained with a change in expectations about the partner's behavior and by an emotional alignment of the participants. The study found that a transparent goal ascription is associated with an increase of cooperation. We propose several high-level mechanisms that could explain the observed effect: general affect modulation, trust, expectation and perception of collective efficacy.

  9. We can work it out: an enactive look at cooperation.

    PubMed

    Fantasia, Valentina; De Jaegher, Hanne; Fasulo, Alessandra

    2014-01-01

    The past years have seen an increasing debate on cooperation and its unique human character. Philosophers and psychologists have proposed that cooperative activities are characterized by shared goals to which participants are committed through the ability to understand each other's intentions. Despite its popularity, some serious issues arise with this approach to cooperation. First, one may challenge the assumption that high-level mental processes are necessary for engaging in acting cooperatively. If they are, then how do agents that do not possess such ability (preverbal children, or children with autism who are often claimed to be mind-blind) engage in cooperative exchanges, as the evidence suggests? Secondly, to define cooperation as the result of two de-contextualized minds reading each other's intentions may fail to fully acknowledge the complexity of situated, interactional dynamics and the interplay of variables such as the participants' relational and personal history and experience. In this paper we challenge such accounts of cooperation, calling for an embodied approach that sees cooperation not only as an individual attitude toward the other, but also as a property of interaction processes. Taking an enactive perspective, we argue that cooperation is an intrinsic part of any interaction, and that there can be cooperative interaction before complex communicative abilities are achieved. The issue then is not whether one is able or not to read the other's intentions, but what it takes to participate in joint action. From this basic account, it should be possible to build up more complex forms of cooperation as needed. Addressing the study of cooperation in these terms may enhance our understanding of human social development, and foster our knowledge of different ways of engaging with others, as in the case of autism.

  10. We can work it out: an enactive look at cooperation

    PubMed Central

    Fantasia, Valentina; De Jaegher, Hanne; Fasulo, Alessandra

    2014-01-01

    The past years have seen an increasing debate on cooperation and its unique human character. Philosophers and psychologists have proposed that cooperative activities are characterized by shared goals to which participants are committed through the ability to understand each other’s intentions. Despite its popularity, some serious issues arise with this approach to cooperation. First, one may challenge the assumption that high-level mental processes are necessary for engaging in acting cooperatively. If they are, then how do agents that do not possess such ability (preverbal children, or children with autism who are often claimed to be mind-blind) engage in cooperative exchanges, as the evidence suggests? Secondly, to define cooperation as the result of two de-contextualized minds reading each other’s intentions may fail to fully acknowledge the complexity of situated, interactional dynamics and the interplay of variables such as the participants’ relational and personal history and experience. In this paper we challenge such accounts of cooperation, calling for an embodied approach that sees cooperation not only as an individual attitude toward the other, but also as a property of interaction processes. Taking an enactive perspective, we argue that cooperation is an intrinsic part of any interaction, and that there can be cooperative interaction before complex communicative abilities are achieved. The issue then is not whether one is able or not to read the other’s intentions, but what it takes to participate in joint action. From this basic account, it should be possible to build up more complex forms of cooperation as needed. Addressing the study of cooperation in these terms may enhance our understanding of human social development, and foster our knowledge of different ways of engaging with others, as in the case of autism. PMID:25152745

  11. To Cooperate or Not to Cooperate: Why Behavioural Mechanisms Matter

    PubMed Central

    2016-01-01

    Mutualistic cooperation often requires multiple individuals to behave in a coordinated fashion. Hence, while the evolutionary stability of mutualistic cooperation poses no particular theoretical difficulty, its evolutionary emergence faces a chicken and egg problem: an individual cannot benefit from cooperating unless other individuals already do so. Here, we use evolutionary robotic simulations to study the consequences of this problem for the evolution of cooperation. In contrast with standard game-theoretic results, we find that the transition from solitary to cooperative strategies is very unlikely, whether interacting individuals are genetically related (cooperation evolves in 20% of all simulations) or unrelated (only 3% of all simulations). We also observe that successful cooperation between individuals requires the evolution of a specific and rather complex behaviour. This behavioural complexity creates a large fitness valley between solitary and cooperative strategies, making the evolutionary transition difficult. These results reveal the need for research on biological mechanisms which may facilitate this transition. PMID:27148874

  12. Cooperative control of visual displays for telemanipulation

    NASA Technical Reports Server (NTRS)

    Kim, Won S.; Stark, Lawrence W.

    1989-01-01

    Two cooperative control schemes for telerobot visual displays are addressed. In the first scheme, on-the-screen visual enhancements such as reference lines indicating the vertical height of the robot hand, a stick figure model of the robot hand, and its projection on the horizontal grid plane are constructed by the interactive cooperation between the human operator and the telerobotic system, and then superimposed on the video screen. Experimental results with a five-degree-of-freedom robot and a frame grabber indicate that superimposition of visual enhancements on the video screen greatly improves telemanipulation task performance. In the second scheme, the position and orientation of an object on video screens are determined interactively; these then assist the telerobotic system in executing the human operator's task-level commands autonomously.

  13. Cooperative Learning and Teaching

    ERIC Educational Resources Information Center

    Jacobs, G. M.; Kimura, H.

    2013-01-01

    In and out of the classroom, life would be unthinkable without interacting with fellow humans. This book urges more cooperative and group activities in the English language classroom for all the advantages: students use the target language more, help each other with comprehension, receive attention from peers as well as the teacher, are motivated…

  14. Cooperative Education Student Guide.

    ERIC Educational Resources Information Center

    Dallas County Community Coll. District, TX.

    Designed for students in the Dallas County Community College District's (DCCCD's) cooperative education program, this guide provides information on obtaining college credit for the development and achievement of learning objectives through current work experience. After introductory material on the benefits of participating in the program,…

  15. Cooper pairs and bipolarons

    NASA Astrophysics Data System (ADS)

    Lakhno, Victor

    2016-11-01

    It is shown that Cooper pairs are a solution of the bipolaron problem for model Fröhlich Hamiltonian. The total energy of a pair for the initial Fröhlich Hamiltonian is found. Differences between the solutions for the model and initial two-particle problems are discussed.

  16. Foundations of Cooperative Learning.

    ERIC Educational Resources Information Center

    Jacobs, George M.

    Five cooperative learning methods are described with the theories that support them. The five methods are: (1) Group Investigation (GI), developed by S. Sharan and others; (2) Jigsaw, developed by E. Aronson and others; (3) Student Teams Achievement Divisions (STAD), developed by R. E. Slavin and others; (4) Learning Together, developed by D. W.…

  17. Educating for World Cooperation.

    ERIC Educational Resources Information Center

    Berman, Louise M.; Miel, Alice

    This booklet presents a variety of perspectives on educating for world cooperation. Section 1 discusses major world problems and calls for the reorientation of education as a potential solution. Section 2 deals with the design of such a reorientation and offers three approaches to teaching and curriculum development--knowing, being, and doing. In…

  18. Cooperative Performance Incentive Plans.

    ERIC Educational Resources Information Center

    Raham, Helen

    2000-01-01

    Discusses what is known about cooperative performance incentive (CPI) plans, which are award programs that offer teachers and other school staff pay bonuses for achievement of specific schoolwide educational objectives. The paper describes and compares existing CPI models worldwide, analyzes their impact on student learning and school practices,…

  19. The Power of Cooperation

    ERIC Educational Resources Information Center

    Nevin, John A.

    2010-01-01

    In "The Power of Cooperation," Tony Nevin tells how the townspeople of Martha's Vineyard, Massachusetts, are attempting to replicate a successful alternative-energy project in Samso, Denmark, where thinking about ways to reduce fossil-fuel use "became a kind of sport." Nevin says that thinking and acting locally helps people to…

  20. Educating for World Cooperation.

    ERIC Educational Resources Information Center

    Berman, Louise M.; Miel, Alice

    This booklet presents a variety of perspectives on educating for world cooperation. Section 1 discusses major world problems and calls for the reorientation of education as a potential solution. Section 2 deals with the design of such a reorientation and offers three approaches to teaching and curriculum development--knowing, being, and doing. In…

  1. Cooperative Electronics Program Credit.

    ERIC Educational Resources Information Center

    Johnson, Wayne

    The Cooperative Electronics Program was developed through the joint efforts of Linn-Benton Community College (LBCC), West Albany High, and Lebanon High, all of which are in the Linn-Benton Education Service District serving Albany, Oregon. The project, which was undertaken in the spring of 1988, is intended to result in a program whereby high…

  2. Cooperative Alaska Forest Inventory

    Treesearch

    Thomas Malone; Jingjing Liang; Edmond C. Packee

    2009-01-01

    The Cooperative Alaska Forest Inventory (CAFI) is a comprehensive database of boreal forest conditions and dynamics in Alaska. The CAFI consists of field-gathered information from numerous permanent sample plots distributed across interior and south-central Alaska including the Kenai Peninsula. The CAFI currently has 570 permanent sample plots on 190 sites...

  3. Combat or Cooperation?

    ERIC Educational Resources Information Center

    Tate, Thomas F.; Copas, Randall L.

    2010-01-01

    The best intentioned efforts of adults are often sabotaged by coercive climates of bullying among peers and conflict with adults. The solution is to create cultures where youth cooperate with authority and treat one another with respect. In this article, the authors stress the task of the staff to create a condition in which students see more…

  4. Cooperative Education. Final Report.

    ERIC Educational Resources Information Center

    Stauber, Dick T.

    In order to investigate the feasibility of adding a cooperative education option to the curricular offerings of Moraine Park Technical Institute (MPTI), interviews were conducted with randomly selected representatives of 12 industries and 17 employers in the marketing and merchandising businesses located in the MPTI service area. In addition,…

  5. Space Cooperation Working Group

    NASA Image and Video Library

    2010-11-18

    NASA Administrator Charles Bolden, left, and NASA Deputy Administrator Lori Garver, welcome Head of the Russian Federal Space Agency Anatoly Perminov, right, for the third Space Cooperation Working Group meeting of the U.S. – Russia Bilateral Presidential Commission on Thursday, Nov. 18, 2010 in Washington. Photo Credit: (NASA/Bill Ingalls)

  6. Morality and Cooperation.

    ERIC Educational Resources Information Center

    Korthals, Michiel

    1992-01-01

    Suggests that Piaget's early theory on moral development and moral education can elucidate the discussion about broad or narrow definitions of morality. Explores the connection between interaction and morality, mutual respect, and cooperation. Argues that Piaget's concept of mutual respect is an important educational device for dealing with…

  7. Cooperative Learning and Teaching

    ERIC Educational Resources Information Center

    Jacobs, G. M.; Kimura, H.

    2013-01-01

    In and out of the classroom, life would be unthinkable without interacting with fellow humans. This book urges more cooperative and group activities in the English language classroom for all the advantages: students use the target language more, help each other with comprehension, receive attention from peers as well as the teacher, are motivated…

  8. Cooperative Mobile Sensing Networks

    SciTech Connect

    Roberts, R S; Kent, C A; Jones, E D; Cunningham, C T; Armstrong, G W

    2003-02-10

    A cooperative control architecture is presented that allows a fleet of Unmanned Air Vehicles (UAVs) to collect data in a parallel, coordinated and optimal manner. The architecture is designed to react to a set of unpredictable events thereby allowing data collection to continue in an optimal manner.

  9. Predicting Human Cooperation

    DOE PAGES

    Nay, John J.; Vorobeychik, Yevgeniy; Xia, Cheng -Yi

    2016-05-12

    The Prisoner’s Dilemma has been a subject of extensive research due to its importance in understanding the ever-present tension between individual self-interest and social benefit. A strictly dominant strategy in a Prisoner’s Dilemma (defection), when played by both players, is mutually harmful. Repetition of the Prisoner’s Dilemma can give rise to cooperation as an equilibrium, but defection is as well, and this ambiguity is difficult to resolve. The numerous behavioral experiments investigating the Prisoner’s Dilemma highlight that players often cooperate, but the level of cooperation varies significantly with the specifics of the experimental predicament. We present the first computational modelmore » of human behavior in repeated Prisoner’s Dilemma games that unifies the diversity of experimental observations in a systematic and quantitatively reliable manner. Our model relies on data we integrated from many experiments, comprising 168,386 individual decisions. The model is composed of two pieces: the first predicts the first-period action using solely the structural game parameters, while the second predicts dynamic actions using both game parameters and history of play. Our model is successful not merely at fitting the data, but in predicting behavior at multiple scales in experimental designs not used for calibration, using only information about the game structure. As a result, we demonstrate the power of our approach through a simulation analysis revealing how to best promote human cooperation.« less

  10. Predicting Human Cooperation

    SciTech Connect

    Nay, John J.; Vorobeychik, Yevgeniy; Xia, Cheng -Yi

    2016-05-12

    The Prisoner’s Dilemma has been a subject of extensive research due to its importance in understanding the ever-present tension between individual self-interest and social benefit. A strictly dominant strategy in a Prisoner’s Dilemma (defection), when played by both players, is mutually harmful. Repetition of the Prisoner’s Dilemma can give rise to cooperation as an equilibrium, but defection is as well, and this ambiguity is difficult to resolve. The numerous behavioral experiments investigating the Prisoner’s Dilemma highlight that players often cooperate, but the level of cooperation varies significantly with the specifics of the experimental predicament. We present the first computational model of human behavior in repeated Prisoner’s Dilemma games that unifies the diversity of experimental observations in a systematic and quantitatively reliable manner. Our model relies on data we integrated from many experiments, comprising 168,386 individual decisions. The model is composed of two pieces: the first predicts the first-period action using solely the structural game parameters, while the second predicts dynamic actions using both game parameters and history of play. Our model is successful not merely at fitting the data, but in predicting behavior at multiple scales in experimental designs not used for calibration, using only information about the game structure. As a result, we demonstrate the power of our approach through a simulation analysis revealing how to best promote human cooperation.

  11. Consortia and Interinstitutional Cooperation.

    ERIC Educational Resources Information Center

    Neal, Donn C., Ed.

    Opportunities for cooperation in higher education are described in this book, particularly how institutional linkages through a consortium can help colleges and universities improve the quality of instruction, deal with rising costs, meet the demands of new institutional roles, and confront such challenges as incorporating new technologies. Ways…

  12. Cooperative Education. Final Report.

    ERIC Educational Resources Information Center

    Stauber, Dick T.

    In order to investigate the feasibility of adding a cooperative education option to the curricular offerings of Moraine Park Technical Institute (MPTI), interviews were conducted with randomly selected representatives of 12 industries and 17 employers in the marketing and merchandising businesses located in the MPTI service area. In addition,…

  13. Communication, Coordination, Cooperation.

    ERIC Educational Resources Information Center

    Rose, Nancy Oft; Wiper, Kathie Tippens

    Speech communication teachers at both secondary and postsecondary school levels must cooperate to improve oral communication education. Despite the importance of oral communication skills, speech courses are rarely required in high school. Teachers must tell school boards, higher education boards, and faculties of the importance of speaking and…

  14. Science & Cooperative Learning.

    ERIC Educational Resources Information Center

    Ehret, Betty

    This is an activity book designed for students in grades 3 through 6. These activities incorporate science themes and cooperative learning. Students explore topics by working with others as team members to complete the science activities. This book contains five units on the following topics: weather, insects, plants, dinosaurs, and space. Each…

  15. The Power of Cooperation

    ERIC Educational Resources Information Center

    Nevin, John A.

    2010-01-01

    In "The Power of Cooperation," Tony Nevin tells how the townspeople of Martha's Vineyard, Massachusetts, are attempting to replicate a successful alternative-energy project in Samso, Denmark, where thinking about ways to reduce fossil-fuel use "became a kind of sport." Nevin says that thinking and acting locally helps people to…

  16. Cooperative Office Education Manual.

    ERIC Educational Resources Information Center

    Clemson Univ., SC. Vocational Education Media Center.

    This manual, intended for inexperienced and experienced coordinators, school administrators, and guidance personnel, is designed to provide practical suggestions for initiating, developing, operating, coordinating, improving, and evaluating cooperative office education programs. Major content is presented primarily in outline form under the…

  17. Cooper's Hawk (Accipiter cooperii)

    Treesearch

    Jean-Luc E. Cartron; Patricia L. Kennedy; Rob Yaksich; Scott H. Stoleson

    2010-01-01

    The Cooper's Hawk (Accipiter cooperii) is intermediate in size between the Northern Goshawk (Accipiter gentilis) and the Sharp-shinned Hawk (A. striatus), northern North America's other two accipiters. The two sexes are almost alike in plumage, but as in both of the other species, the female is noticeably larger. According to Wheeler and Clark (1995), a...

  18. Neural basis of conditional cooperation

    PubMed Central

    Niki, Kazuhisa; Fujisaki, Syoken; Akiyama, Eizo

    2011-01-01

    Cooperation among genetically unrelated individuals is a fundamental aspect of society, but it has been a longstanding puzzle in biological and social sciences. Recently, theoretical studies in biology and economics showed that conditional cooperation—cooperating only with those who have exhibited cooperative behavior—can spread over a society. Furthermore, experimental studies in psychology demonstrated that people are actually conditional cooperators. In this study, we used functional magnetic resonance imaging to investigate the neural system underlying conditional cooperation by scanning participants during interaction with cooperative, neutral and non-cooperative opponents in prisoner's dilemma games. The results showed that: (i) participants cooperated more frequently with both cooperative and neutral opponents than with non-cooperative opponents; and (ii) a brain area related to cognitive inhibition of pre-potent responses (right dorsolateral prefrontal cortex) showed greater activation, especially when participants confronted non-cooperative opponents. Consequently, we suggest that cognitive inhibition of the motivation to cooperate with non-cooperators drives the conditional behavior. PMID:20501484

  19. [Social cooperatives in Italy].

    PubMed

    Villotti, P; Zaniboni, S; Fraccaroli, F

    2014-06-01

    This paper describes the role of social cooperatives in Italy as a type of economic, non-profit organization and their role in contributing to the economic and social growth of the country. The purpose of this paper is to learn more about the experience of the Italian social cooperatives in promoting the work integration process of disadvantaged workers, especially those suffering from mental disorders, from a theoretical and an empirical point of view. Social enterprise is the most popular and consolidated legal and organizational model for social enterprises in Italy, introduced by Law 381/91. Developed during the early 1980s, and formally recognized by law in the early 1990s, social cooperatives aim at pursuing the general interest of the community to promote the human needs and social inclusion of citizens. They are orientated towards aims that go beyond the interest of the business owners, the primary beneficiary of their activities is the community, or groups of disadvantaged people. In Italy, Law 381/91 distinguishes between two categories of social cooperatives, those producing goods of social utility, such as culture, welfare and educational services (A-type), and those providing economic activities for the integration of disadvantaged people into employment (B-type). The main purpose of B-type social cooperatives is to integrate disadvantaged people into the open labour market. This goal is reached after a period of training and working experience inside the firm, during which the staff works to improve both the social and professional abilities of disadvantaged people. During the years, B-type social co-ops acquired a particular relevance in the care of people with mental disorders by offering them with job opportunities. Having a job is central in the recovery process of people suffering from mental diseases, meaning that B-type social co-ops in Italy play an important rehabilitative and integrative role for this vulnerable population of workers. The

  20. A Course of Study in Cooperation and Cooperatives.

    ERIC Educational Resources Information Center

    Bjoraker, Walter T., Ed.

    Designed for teachers with limited experience in cooperatives, this course of study was prepared by seminar students for use in high school or adult education programs, and emphasizes the principles of cooperation, the operation and management of cooperatives, and the communication required for their effective functioning. Units requiring a total…

  1. The risk of predation favors cooperation among breeding prey.

    PubMed

    Krams, Indrikis; Krama, Tatjana; Berzins, Arnis; Rantala, Markus J

    2010-05-01

    Empirical studies have shown that animals often focus on short-term benefits under conditions of predation risk, which reduces the likelihood that they will cooperate with others. However, some theoretical studies predict that animals in adverse conditions should not avoid cooperation with their neighbors since it may decrease individual risks and increase long-term benefits of reciprocal help. We experimentally tested these two alternatives to find out whether increased predation risk enhances or diminishes the occurrence of cooperation in mobbing, a common anti-predator behavior, among breeding pied flycatchers, Ficedula hypoleuca. Our results show that birds attended mobs initiated by their neighbors 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. This study demonstrates a positive impact of predation risk on cooperation in breeding songbirds, which might help to explain the emergence and evolution of cooperation.

  2. The risk of predation favors cooperation among breeding prey

    PubMed Central

    Krama, Tatjana; Berzins, Arnis; Rantala, Markus J

    2010-01-01

    Empirical studies have shown that animals often focus on short-term benefits under conditions of predation risk, which reduces the likelihood that they will cooperate with others. However, some theoretical studies predict that animals in adverse conditions should not avoid cooperation with their neighbors since it may decrease individual risks and increase long-term benefits of reciprocal help. We experimentally tested these two alternatives to find out whether increased predation risk enhances or diminishes the occurrence of cooperation in mobbing, a common anti-predator behavior, among breeding pied flycatchers, Ficedula hypoleuca. Our results show that birds attended mobs initiated by their neighbors 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. This study demonstrates a positive impact of predation risk on cooperation in breeding songbirds, which might help to explain the emergence and evolution of cooperation. PMID:20714404

  3. Can Cooperative Learning Be Evaluated?

    ERIC Educational Resources Information Center

    Watson, Dan; Rangel, Lyle

    1989-01-01

    The most frequently used cooperative learning models feature five common components: heterogeneous teams, teammate interdependence, team interdependence, accountability, and activity appropriateness. These elements are explained to assist supervisors desiring to evaluate teachers using cooperative learning methods. Includes seven references. (MLH)

  4. Cooperation and cheating in microbes

    NASA Astrophysics Data System (ADS)

    Gore, Jeff

    2011-03-01

    Understanding the cooperative and competitive dynamics within and between species is a central challenge in evolutionary biology. Microbial model systems represent a unique opportunity to experimentally test fundamental theories regarding the evolution of cooperative behaviors. In this talk I will describe our experiments probing cooperation in microbes. In particular, I will compare the cooperative growth of yeast in sucrose and the cooperative inactivation of antibiotics by bacteria. In both cases we find that cheater strains---which don't contribute to the public welfare---are able to take advantage of the cooperator strains. However, this ability of cheaters to out-compete cooperators occurs only when cheaters are present at low frequency, thus leading to steady-state coexistence. These microbial experiments provide fresh insight into the evolutionary origin of cooperation.

  5. Cognitive consequences of cooperative breeding in primates?

    PubMed

    Burkart, Judith Maria; van Schaik, Carel P

    2010-01-01

    Several hypotheses propose that cooperative breeding leads to increased cognitive performance, in both nonhuman and human primates, but systematic evidence for such a relationship is missing. A causal link might exist because motivational and cognitive processes necessary for the execution and coordination of helping behaviors could also favor cognitive performance in contexts not directly related to caregiving. In callitrichids, which among primates rely most strongly on cooperative breeding, these motivational and cognitive processes include attentional biases toward monitoring others, the ability to coordinate actions spatially and temporally, increased social tolerance, increased responsiveness to others' signals, and spontaneous prosociality. These processes are likely to enhance performance particularly in socio-cognitive contexts. Therefore, cooperatively breeding primates are expected to outperform their independently breeding sister taxa in socio-cognitive tasks. We evaluate this prediction by reviewing the literature and comparing cognitive performance in callitrichids with that of their sister taxa, i.e. squirrel monkeys, which are independent breeders, and capuchin monkeys, which show an intermediate breeding system. Consistent with our prediction, this review reveals that callitrichids systematically and significantly outperform their sister taxa in the socio-cognitive, but not in the non-social domain. This comparison is complemented with more qualitative evaluations of prosociality and cognitive performance in non-primate cooperative breeders, which suggest that among mammals, cooperative breeding generally produces conditions conducive to socio-cognitive performance. In the hominid lineage, however, the adoption of extensive allomaternal care presumably resulted in more pervasive cognitive consequences, because the motivational consequences of cooperative breeding was added to an ape-level cognitive system already capable of understanding simple

  6. Heterogeneous Multi-Robot Cooperation

    DTIC Science & Technology

    1994-02-01

    Approaches to Multi-Robot Cooperative Control ................ 196 8.2.1 " Swarm " Cooperation ....... ...................... 196 8.2.2 "Intentional...involves the study of emergent cooperation in colonies, or swarms , of robots - an approach comparable to differentiating animal societies. This...using intention- ally cooperating robots to guide the activities of smaller groups of swarm robots in a coordinated way. The research presented in this

  7. Cooperative Learning for Effective Mainstreaming.

    ERIC Educational Resources Information Center

    Male, Mary

    1986-01-01

    Reviews benefits of using cooperative learning strategies and computer assisted instruction (CAI) in classrooms with mainstreamed students; describes teacher's role in implementing cooperative learning; presents examples demonstrating potential of cooperative learning and CAI in language and social skills development; and outlines steps in…

  8. Cooperative Learning for LEP Students.

    ERIC Educational Resources Information Center

    Calderon, Margarita

    1989-01-01

    Substantial evidence suggests that students working together in small cooperative groups can master material better than students working on their own, and that cooperative learning structures higher self-esteem and learning motivation. Cooperative learning (CL) has been proposed for use with language minority children, as well as with other…

  9. Cooperative Learning in Elementary Schools

    ERIC Educational Resources Information Center

    Slavin, Robert E.

    2015-01-01

    Cooperative learning refers to instructional methods in which students work in small groups to help each other learn. Although cooperative learning methods are used for different age groups, they are particularly popular in elementary (primary) schools. This article discusses methods and theoretical perspectives on cooperative learning for the…

  10. An Odyssey into Cooperative Learning.

    ERIC Educational Resources Information Center

    Lemke, Thomas L.; Basile, Carole

    1997-01-01

    An experiment using cooperative learning in a introductory pharmacy course in medicinal chemistry revealed general acceptance of the cooperative learning approach by students, and some perceived advantages for both students and teachers. Although quantitative evidence supporting superiority of the cooperative learning approach was not found,…

  11. International Cooperation: A Positive Response.

    ERIC Educational Resources Information Center

    Soria, Oscar

    Conditions for developing international university cooperation are identified, along with stages of international cooperation in education. Guidelines to promote cooperation are provided. The dominant focus and new role of universities has become problem-solving and community development, as distinct from the previous institutional-building…

  12. An Odyssey into Cooperative Learning.

    ERIC Educational Resources Information Center

    Lemke, Thomas L.; Basile, Carole

    1997-01-01

    An experiment using cooperative learning in a introductory pharmacy course in medicinal chemistry revealed general acceptance of the cooperative learning approach by students, and some perceived advantages for both students and teachers. Although quantitative evidence supporting superiority of the cooperative learning approach was not found,…

  13. Cooperative Learning in Elementary Schools

    ERIC Educational Resources Information Center

    Slavin, Robert E.

    2015-01-01

    Cooperative learning refers to instructional methods in which students work in small groups to help each other learn. Although cooperative learning methods are used for different age groups, they are particularly popular in elementary (primary) schools. This article discusses methods and theoretical perspectives on cooperative learning for the…

  14. Cooperative Learning and Student Motivation.

    ERIC Educational Resources Information Center

    Nichols, Joe D.; Miller, Raymond B.

    1994-01-01

    Effects of cooperative group learning on students' motivation and achievement were studied for 62 high school students assigned to cooperative learning or traditional lecture groups. Greater gains were made in achievement, efficacy, valuing of algebra, and learning goal orientation for the cooperative-learning group. (SLD)

  15. Cooperative functions: meeting members' needs

    Treesearch

    Mark G. Rickenbach

    2006-01-01

    Cooperatives are effective when they meet the needs of the members. In past and current offerings by cooperatives as a whole and forestry cooperatives in particular, four functional categories cover the typical services a forest landowner might gain access to through joining (Cobia 1989). The four categories - marketing, supply, service, and social - are defined and...

  16. Forestry cooperatives: past and present

    Treesearch

    Mark G. Rickenbach

    2006-01-01

    Forest landowner cooperatives are not a new phenomenon, but past efforts to create and sustain these businesses have been largely unsuccessful in the U.S. Before and just after World War II saw significant investment in cooperative development that failed to create durable business. The purpose of this chapter is to briefly describe the history of forestry cooperatives...

  17. Cooperative Learning: Developments in Research

    ERIC Educational Resources Information Center

    Gillies, Robyn M.

    2014-01-01

    Cooperative learning is widely recognized as a pedagogical practice that promotes socialization and learning among students from kindergarten through to college level and across different subject areas. Cooperative learning involves students working together to achieve common goals or complete group tasks. Interest in cooperative learning has…

  18. Antisocial pool rewarding does not deter public cooperation.

    PubMed

    Szolnoki, Attila; Perc, Matjaž

    2015-10-07

    Rewarding cooperation is in many ways expected behaviour from social players. However, strategies that promote antisocial behaviour are also surprisingly common, not just in human societies, but also among eusocial insects and bacteria. Examples include sanctioning of individuals who behave prosocially, or rewarding of free-riders who do not contribute to collective enterprises. We therefore study the public goods game with antisocial and prosocial pool rewarding in order to determine the potential negative consequences on the effectiveness of positive incentives to promote cooperation. Contrary to a naive expectation, we show that the ability of defectors to distribute rewards to their like does not deter public cooperation as long as cooperators are able to do the same. Even in the presence of antisocial rewarding, the spatial selection for cooperation in evolutionary social dilemmas is enhanced. Since the administration of rewards to either strategy requires a considerable degree of aggregation, cooperators can enjoy the benefits of their prosocial contributions as well as the corresponding rewards. Defectors when aggregated, on the other hand, can enjoy antisocial rewards, but due to their lack of contributions to the public good they ultimately succumb to their inherent inability to secure a sustainable future. Strategies that facilitate the aggregation of akin players, even if they seek to promote antisocial behaviour, thus always enhance the long-term benefits of cooperation.

  19. Antisocial pool rewarding does not deter public cooperation

    PubMed Central

    Szolnoki, Attila; Perc, Matjaž

    2015-01-01

    Rewarding cooperation is in many ways expected behaviour from social players. However, strategies that promote antisocial behaviour are also surprisingly common, not just in human societies, but also among eusocial insects and bacteria. Examples include sanctioning of individuals who behave prosocially, or rewarding of free-riders who do not contribute to collective enterprises. We therefore study the public goods game with antisocial and prosocial pool rewarding in order to determine the potential negative consequences on the effectiveness of positive incentives to promote cooperation. Contrary to a naive expectation, we show that the ability of defectors to distribute rewards to their like does not deter public cooperation as long as cooperators are able to do the same. Even in the presence of antisocial rewarding, the spatial selection for cooperation in evolutionary social dilemmas is enhanced. Since the administration of rewards to either strategy requires a considerable degree of aggregation, cooperators can enjoy the benefits of their prosocial contributions as well as the corresponding rewards. Defectors when aggregated, on the other hand, can enjoy antisocial rewards, but due to their lack of contributions to the public good they ultimately succumb to their inherent inability to secure a sustainable future. Strategies that facilitate the aggregation of akin players, even if they seek to promote antisocial behaviour, thus always enhance the long-term benefits of cooperation. PMID:26400746

  20. Better Together: Outcomes of Cooperation Versus Competition in Social Exergaming.

    PubMed

    Marker, Arwen M; Staiano, Amanda E

    2015-02-01

    Children and adolescents most often play active videogames, or exergames, in a social environment. Social play may enhance the potential benefits of an exergaming experience, much like group exercise and team sports are observed to improve physical activity-related outcomes above those of solitary exercise. Two ubiquitous elements of exergames are cooperation and competition. Previous literature suggests that cooperative and competitive aspects of exergames may affect physiological and psychosocial changes. Competitive play has been found to increase energy expenditure and aggression in short bouts of exergaming. Cooperative exergaming has been found to increase motivation, promote continued play, enhance self-efficacy, and increase pro-social behaviors. In one study, a cooperative exergaming condition also resulted in significant weight loss for overweight and obese adolescents. Individual player differences such as individual preferences, competitiveness, weight status, age, gender, and ethnicity may moderate effects. Although the current volume of literature on competition and cooperation in exergaming is small, social exergames hold promise as an engaging alternative to traditional physical activity interventions and may promote a broad range of positive outcomes for children and adolescents. Principles of cooperation and competition are applicable for developers of health-promoting games. Future research is needed to further understand the mechanisms of how competition and cooperation in social exergaming impact physiological and psychosocial outcomes.

  1. Better Together: Outcomes of Cooperation Versus Competition in Social Exergaming

    PubMed Central

    Marker, Arwen M.

    2015-01-01

    Abstract Children and adolescents most often play active videogames, or exergames, in a social environment. Social play may enhance the potential benefits of an exergaming experience, much like group exercise and team sports are observed to improve physical activity–related outcomes above those of solitary exercise. Two ubiquitous elements of exergames are cooperation and competition. Previous literature suggests that cooperative and competitive aspects of exergames may affect physiological and psychosocial changes. Competitive play has been found to increase energy expenditure and aggression in short bouts of exergaming. Cooperative exergaming has been found to increase motivation, promote continued play, enhance self-efficacy, and increase pro-social behaviors. In one study, a cooperative exergaming condition also resulted in significant weight loss for overweight and obese adolescents. Individual player differences such as individual preferences, competitiveness, weight status, age, gender, and ethnicity may moderate effects. Although the current volume of literature on competition and cooperation in exergaming is small, social exergames hold promise as an engaging alternative to traditional physical activity interventions and may promote a broad range of positive outcomes for children and adolescents. Principles of cooperation and competition are applicable for developers of health-promoting games. Future research is needed to further understand the mechanisms of how competition and cooperation in social exergaming impact physiological and psychosocial outcomes. PMID:26181677

  2. Confrontational scavenging as a possible source for language and cooperation

    PubMed Central

    2011-01-01

    The emergence of language and the high degree of cooperation found among humans seems to require more than a straightforward enhancement of primate traits. Some triggering episode unique to human ancestors was likely necessary. Here it is argued that confrontational scavenging was such an episode. Arguments for and against an established confrontational scavenging niche are discussed, as well as the probable effects of such a niche on language and co-operation. Finally, several possible directions for future research are suggested. PMID:21933413

  3. Cooperation in space

    NASA Technical Reports Server (NTRS)

    Guastaferro, A.

    1992-01-01

    The topics from the Technical Interchange Meeting for the NASA Space Exploration Initiative are presented in viewgraph form. The objective is to share a perspective of a cost-effective cooperation management structure of NASA and industry as we move towards the 21st century and the national commitment to continue our exploration in space with humans. Some of the topics covered include a personal background, today's culture, new approaches, congressional oversight, programmatic impact, and recommendations.

  4. Cooperative disease management programs.

    PubMed

    Jedrey, C M; Chaurette, K A; Winn, L B

    2001-01-01

    Cooperative disease management programs sponsored by pharmaceutical companies and managed care organizations or health care providers can offer significant benefits to patients. They can be structured so as to comply with applicable OIG, FDA, and IRS regulations. Such programs must be structured for the benefit of patients, and not to require the use of or otherwise directly promote the selection of the sponsoring pharmaceutical company's products.

  5. Automated Cooperative Trajectories

    NASA Technical Reports Server (NTRS)

    Hanson, Curt; Pahle, Joseph; Brown, Nelson

    2015-01-01

    This presentation is an overview of the Automated Cooperative Trajectories project. An introduction to the phenomena of wake vortices is given, along with a summary of past research into the possibility of extracting energy from the wake by flying close parallel trajectories. Challenges and barriers to adoption of civilian automatic wake surfing technology are identified. A hardware-in-the-loop simulation is described that will support future research. Finally, a roadmap for future research and technology transition is proposed.

  6. Hydrodynamics of Bacterial Cooperation

    NASA Astrophysics Data System (ADS)

    Petroff, A.; Libchaber, A.

    2012-12-01

    Over the course of the last several decades, the study of microbial communities has identified countless examples of cooperation between microorganisms. Generally—as in the case of quorum sensing—cooperation is coordinated by a chemical signal that diffuses through the community. Less well understood is a second class of cooperation that is mediated through physical interactions between individuals. To better understand how the bacteria use hydrodynamics to manipulate their environment and coordinate their actions, we study the sulfur-oxidizing bacterium Thiovulum majus. These bacteria live in the diffusive boundary layer just above the muddy bottoms of ponds. As buried organic material decays, sulfide diffuses out of the mud. Oxygen from the pond diffuses into the boundary layer from above. These bacteria form communities—called veils— which are able to transport nutrients through the boundary layer faster than diffusion, thereby increasing their metabolic rate. In these communities, bacteria attach to surfaces and swim in place. As millions of bacteria beat their flagella, the community induces a macroscopic fluid flow, which mix the boundary layer. Here we present experimental observations and mathematical models that elucidate the hydrodynamics linking the behavior of an individual bacterium to the collective dynamics of the community. We begin by characterizing the flow of water around an individual bacterium swimming in place. We then discuss the flow of water and nutrients around a small number of individuals. Finally, we present observations and models detailing the macroscopic dynamics of a Thiovulum veil.

  7. Endogenous Cooperation Network Formation

    NASA Astrophysics Data System (ADS)

    Angus, S.

    This paper employs insights from Complex Systems literature to develop a computational model of endogenous strategic network formation. Artificial Adaptive Agents (AAAs), implemented as finite state automata, play a modified two-player Iterated Prisoner's Dilemma game with an option to further develop the interaction space as part of their strategy. Several insights result from this relatively minor modification: first, I find that network formation is a necessary condition for cooperation to be sustainable but that both the frequency of interaction and the degree to which edge formation impacts agent mixing are both necessary conditions for cooperative networks. Second, within the FSA-modified IPD frame-work, a rich ecology of agents and network topologies is observed, with consequent payoff symmetry and network 'purity' seen to be further contributors to robust cooperative networks. Third, the dynamics of the strategic system under network formation show that initially simple dynamics with small interaction length between agents gives way to complex, a-periodic dynamics when interaction lengths are increased by a single step.

  8. Endogenous Cooperation Network Formation

    NASA Astrophysics Data System (ADS)

    Angus, S.

    This paper employs insights from Complex Systems literature to develop a computational model of endogenous strategic network formation. Artificial Adaptive Agents (AAAs), implemented as finite state automata, play a modified two-player Iterated Prisoner's Dilemma game with an option to further develop the interaction space as part of their strategy. Several insights result from this relatively minor modification: first, I find that network formation is a necessary condition for cooperation to be sustainable but that both the frequency of interaction and the degree to which edge formation impacts agent mixing are both necessary conditions for cooperative networks. Second, within the FSA-modified IPD frame-work, a rich ecology of agents and network topologies is observed, with consequent payoff symmetry and network `purity' seen to be further contributors to robust cooperative networks. Third, the dynamics of the strategic system under network formation show that initially simple dynamics with small interaction length between agents gives way to complex, a-periodic dynamics when interaction lengths are increased by a single step.

  9. Understanding cooperative behavior in structurally disordered populations

    NASA Astrophysics Data System (ADS)

    Xu, C.; Zhang, W.; Du, P.; Choi, C. W.; Hui, P. M.

    2016-06-01

    The effects of an inhomogeneous competing environment on the extent of cooperation are studied within the context of a site-diluted evolutionary snowdrift game on a square lattice, with the occupied sites representing the players, both numerically and analytically. The frequency of cooperation ℱ C generally shows a non-monotonic dependence on the fraction of occupied sites ρ, for different values of the payoff parameter r. Slightly diluting a lattice leads to a lower cooperation for small and high values of r. For a range of r, however, dilution leads to an enhanced cooperation. An analytic treatment is developed for ℱC I + ℱC II, with ℱC I emphasizing the importance of the small clusters of players especially for ℱC II from the other players is shown to be inadequate. A local configuration approximation (LCA) that treats the local competing configurations as the variables and amounts to include spatial correlation up to the neighborhood of a player's neighbors is developed. Results of ℱ C ( ρ) and the number of different local configurations from LCA are in good agreement with simulation results. A transparent physical picture of the dynamics stemming from LCA is also presented. The theoretical approach provides a framework that can be readily applied to competing agent-based models in structurally ordered and disordered populations.

  10. Molecular Basis of Actin Nucleation Factor Cooperativity

    PubMed Central

    Zeth, Kornelius; Pechlivanis, Markos; Samol, Annette; Pleiser, Sandra; Vonrhein, Clemens; Kerkhoff, Eugen

    2011-01-01

    The distinct actin nucleation factors of the Spir and formin subgroup families cooperate in actin nucleation. The Spir/formin cooperativity has been identified to direct two essential steps in mammalian oocyte maturation, the asymmetric spindle positioning and polar body extrusion during meiosis. Understanding the nature and regulation of the Spir/Fmn cooperation is an important requirement to comprehend mammalian reproduction. Recently we dissected the structural elements of the Spir and Fmn family proteins, which physically link the two actin nucleation factors. The trans-regulatory interaction is mediated by the Spir kinase non-catalytic C-lobe domain (KIND) and the C-terminal formin Spir interaction motif (FSI). The interaction inhibits formin nucleation activity and enhances the Spir activity. To get insights into the molecular mechanism of the Spir/Fmn interaction, we determined the crystal structure of the KIND domain alone and in complex with the C-terminal Fmn-2 FSI peptide. Together they confirm the proposed structural homology of the KIND domain to the protein kinase fold and reveal the basis of the Spir/formin interaction. The complex structure showed a large interface with conserved and positively charged residues of the Fmn FSI peptide mediating major contacts to an acidic groove on the surface of KIND. Protein interaction studies verified the electrostatic nature of the interaction. The data presented here provide the molecular basis of the Spir/formin interaction and give a first structural view into the mechanisms of actin nucleation factor cooperativity. PMID:21705804

  11. Interpreted Cooper-Harper for broader use

    NASA Technical Reports Server (NTRS)

    Green, David L.; Andrews, Hal; Gallagher, Donald W.

    1993-01-01

    The current aircraft assessment process typically makes extensive use of operational personnel during simulations and operational evaluations, with increased emphasis on evaluating the many pilot and/or operator/aircraft control loops. The need for a crew assessment in this broader arena has produced a variety of rating scales. The Cooper-Harper Rating Scale is frequently misused and routinely overlooked in the process, for these applications often extend the scale's use beyond its originally intended application. This paper agrees with the broader application of the Cooper-Harper Rating Scale and presents a concept for the development of a 'use unique' Interpreted Cooper-Harper Scale to help achieve this objective. This interpreted scale concept was conceived during efforts to support an FAA evaluation of a night vision enhancement system. It includes descriptive extensions, which are faithful to the intent of the current Cooper-Harper Scale and should provide the kind of detail that has historically been provided by trained test pilots in their explanatory comments.

  12. Cooperativeness and competitiveness as two distinct constructs: validating the Cooperative and Competitive Personality Scale in a social dilemma context.

    PubMed

    Lu, Su; Au, Wing-Tung; Jiang, Feng; Xie, Xiaofei; Yam, Paton

    2013-01-01

    The present research validated the construct and criterion validities of the Cooperative and Competitive Personality Scale (CCPS) in a social dilemma context. The results from three studies supported the notion that cooperativeness and competitiveness are two independent dimensions, challenging the traditional view that they are two ends of a single continuum. First, confirmatory factor analyses revealed that a two-factor structure fit the data significantly better than a one-factor structure. Moreover, cooperativeness and competitiveness were either not significantly correlated (Studies 1 and 3) or only moderately positively correlated (Study 2). Second, cooperativeness and competitiveness were differentially associated with Schwartz's Personal Values. These results further supported the idea that cooperativeness and competitiveness are two distinct constructs. Specifically, the individuals who were highly cooperative emphasized self-transcendent values (i.e., universalism and benevolence) more, whereas the individuals who were highly competitive emphasized self-enhancement values (i.e., power and achievement) more. Finally, the CCPS, which adheres to the trait perspective of personality, was found to be a useful supplement to more prevalent social motive measures (i.e., social value orientation) in predicting cooperative behaviors. Specifically, in Study 2, when social value orientation was controlled for, the CCPS significantly predicted cooperative behaviors in a public goods dilemma (individuals who score higher on cooperativeness scale contributed more to the public goods). In Study 3, when social value orientation was controlled for, the CCPS significantly predicted cooperative behaviors in commons dilemmas (individuals who score higher on cooperativeness scale requested fewer resources from the common resource pool). The practical implications of the CCPS in conflict resolution, as well as in recruitment and selection settings, are discussed.

  13. The Effect of Geographical Proximity on Scientific Cooperation among Chinese Cities from 1990 to 2010

    PubMed Central

    Ma, Haitao; Fang, Chuanglin; Pang, Bo; Li, Guangdong

    2014-01-01

    Background The relations between geographical proximity and spatial distance constitute a popular topic of concern. Thus, how geographical proximity affects scientific cooperation, and whether geographically proximate scientific cooperation activities in fact exhibit geographic scale features should be investigated. Methodology Selected statistics from the ISI database on cooperatively authored papers, the authors of which resided in 60 typical cites in China, and which were published in the years 1990, 1995, 2000, 2005, and 2010, were used to establish matrices of geographic distance and cooperation levels between cities. By constructing a distance-cooperation model, the degree of scientific cooperation based on spatial distance was calculated. The relationship between geographical proximity and scientific cooperation, as well as changes in that relationship, was explored using the fitting function. Result (1) Instead of declining, the role of geographical proximity in inter-city scientific cooperation has increased gradually but significantly with the popularization of telecommunication technologies; (2) the relationship between geographical proximity and scientific cooperation has not followed a perfect declining curve, and at certain spatial scales, the distance-decay regularity does not work; (3) the Chinese scientific cooperation network gathers around different regional center cities, showing a trend towards a regional network; within this cooperation network the amount of inter-city cooperation occurring at close range increased greatly. Conclusion The relationship between inter-city geographical distance and scientific cooperation has been enhanced and strengthened over time. PMID:25365449

  14. Asynchronous updates can promote the evolution of cooperation on multiplex networks

    NASA Astrophysics Data System (ADS)

    Allen, James M.; Hoyle, Rebecca B.

    2017-04-01

    We study the importance to the frequency of cooperation of the choice of updating strategies in a game played asynchronously or synchronously across layers in a multiplex network. Updating asynchronously in the public goods game leads to higher frequencies of cooperation compared to synchronous updates. How large this effect is depends on the sensitivity of the game dynamics to changes in the number of cooperators surrounding a player, with the largest effect observed when players payoffs are small. The discovery of this effect enhances understanding of cooperation on multiplex networks, and demonstrates a new way to maintain cooperation in these systems.

  15. Increased costs of cooperation help cooperators in the long run.

    PubMed

    Smaldino, Paul E; Schank, Jeffrey C; McElreath, Richard

    2013-04-01

    It has long been proposed that cooperation should increase in harsh environments, but this claim still lacks theoretical underpinnings. We modeled a scenario in which benefiting from altruistic behavior was essential to survival and reproduction. We used a spatial agent-based model to represent mutual cooperation enforced by environmental adversity. We studied two factors, the cost of unreciprocated cooperation and the environmental cost of living, which highlight a conflict between the short- and long-term rewards of cooperation. In the long run, cooperation is favored because only groups with a sufficient number of cooperators will survive. In the short run, however, harsh environmental costs increase the advantage of defectors in cooperator-defector interactions because the loss of resources leads to death. Our analysis sheds new light on the evolution of cooperation via interdependence and illustrates how selfish groups can incur short-term benefits at the cost of their eventual demise. We demonstrate how harsh environments select for cooperative phenotypes and suggest an explanation for the adoption of cooperative breeding strategies in human evolution. We also highlight the importance of variable population size and the role of socio-spatial organization in harsh environments.

  16. From Additivity to Cooperativity in Chemistry: Can Cooperativity Be Measured?

    PubMed

    Tebben, Ludger; Mück-Lichtenfeld, Christian; Fernández, Gustavo; Grimme, Stefan; Studer, Armido

    2017-05-02

    Cooperative effects can be observed in various research areas in chemistry; cooperative catalysis is well-established, the assembly of compounds on surfaces can be steered by cooperative effects, and supramolecular polymerization can proceed in a cooperative manner. In biological systems, cooperativity is observed in protein-protein, protein-lipid and protein-molecule interactions. Synergistic effects are relevant in frustrated Lewis pairs, organic multispin systems, multimetallic clusters and also in nanoparticles. However, a general approach to determine cooperativity in the different chemical systems is currently not known. In the present concept paper it is suggested that, at least for simpler systems that can be described at the molecular level, cooperativity can be defined based on energy considerations. For systems in which no chemical transformation occurs, determination of interaction energies of the whole system with respect to the interaction energies between all individual component pairs (subsystems) will allow determination of cooperativity. For systems comprising of chemical transformations, cooperativity can be evaluated by determining the activation energy of the synergistic system and by comparing this with activation energies of the corresponding subsystems that lack an activating moiety. For more complex systems, cooperativity is generally determined at a qualitative level. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Post-Synthetic Modification of Porphyrin-Encapsulating Metal-Organic Materials by Cooperative Addition of Inorganic Salts to Enhance CO2/CH4 Selectivity

    SciTech Connect

    Zhang, Zhenjie; Gao, Wen-Yang; Wojtas, Lukasz; Ma, Shengqian; Eddaoudi, Mohamed; Zaworotko, Michael J

    2012-11-26

    Keeping MOM: Reaction of biphenyl-3,4',5-tricarboxylate and Cd(NO3)2 in the presence of meso-tetra(N-methyl-4-pyridyl)porphine tetratosylate afforded porph@MOM-11, a microporous metal–organic material (MOM) that encapsulates cationic porphyrins and solvent in alternating open channels. Porph@MOM-11 has cation and anion binding sites that facilitate cooperative addition of inorganic salts (such as M+Cl-) in a stoichiometric fashion.

  18. How is human cooperation different?

    PubMed Central

    Melis, Alicia P.; Semmann, Dirk

    2010-01-01

    Although cooperation is a widespread phenomenon in nature, human cooperation exceeds that of all other species with regard to the scale and range of cooperative activities. Here we review and discuss differences between humans and non-humans in the strategies employed to maintain cooperation and control free-riders. We distinguish forms of cooperative behaviour based on their influence on the immediate payoffs of actor and recipient. If the actor has immediate costs and only the recipient obtains immediate benefits, we term this investment. If the behaviour has immediate positive effects for both actor and recipient, we call this a self-serving mutually beneficial behaviour or mutual cooperation. We argue that humans, in contrast to all other species, employ a wider range of enforcement mechanisms, which allow higher levels of cooperation to evolve and stabilize among unrelated individuals and in large groups. We also discuss proximate mechanisms underlying cooperative behaviour and focus on our experimental work with humans and our closest primate relatives. Differences in the proximate mechanisms also seem to contribute to explaining humans' greater ability to cooperate and enforce cooperation. PMID:20679110

  19. How is human cooperation different?

    PubMed

    Melis, Alicia P; Semmann, Dirk

    2010-09-12

    Although cooperation is a widespread phenomenon in nature, human cooperation exceeds that of all other species with regard to the scale and range of cooperative activities. Here we review and discuss differences between humans and non-humans in the strategies employed to maintain cooperation and control free-riders. We distinguish forms of cooperative behaviour based on their influence on the immediate payoffs of actor and recipient. If the actor has immediate costs and only the recipient obtains immediate benefits, we term this investment. If the behaviour has immediate positive effects for both actor and recipient, we call this a self-serving mutually beneficial behaviour or mutual cooperation. We argue that humans, in contrast to all other species, employ a wider range of enforcement mechanisms, which allow higher levels of cooperation to evolve and stabilize among unrelated individuals and in large groups. We also discuss proximate mechanisms underlying cooperative behaviour and focus on our experimental work with humans and our closest primate relatives. Differences in the proximate mechanisms also seem to contribute to explaining humans' greater ability to cooperate and enforce cooperation.

  20. Extended cooperative control synthesis

    NASA Technical Reports Server (NTRS)

    Davidson, John B.; Schmidt, David K.

    1994-01-01

    This paper reports on research for extending the Cooperative Control Synthesis methodology to include a more accurate modeling of the pilot's controller dynamics. Cooperative Control Synthesis (CCS) is a methodology that addresses the problem of how to design control laws for piloted, high-order, multivariate systems and/or non-conventional dynamic configurations in the absence of flying qualities specifications. This is accomplished by emphasizing the parallel structure inherent in any pilot-controlled, augmented vehicle. The original CCS methodology is extended to include the Modified Optimal Control Model (MOCM), which is based upon the optimal control model of the human operator developed by Kleinman, Baron, and Levison in 1970. This model provides a modeling of the pilot's compensation dynamics that is more accurate than the simplified pilot dynamic representation currently in the CCS methodology. Inclusion of the MOCM into the CCS also enables the modeling of pilot-observation perception thresholds and pilot-observation attention allocation affects. This Extended Cooperative Control Synthesis (ECCS) allows for the direct calculation of pilot and system open- and closed-loop transfer functions in pole/zero form and is readily implemented in current software capable of analysis and design for dynamic systems. Example results based upon synthesizing an augmentation control law for an acceleration command system in a compensatory tracking task using the ECCS are compared with a similar synthesis performed by using the original CCS methodology. The ECCS is shown to provide augmentation control laws that yield more favorable, predicted closed-loop flying qualities and tracking performance than those synthesized using the original CCS methodology.