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  1. IFT46 plays crucial roles in craniofacial and cilia development.

    PubMed

    Park, Inji; Lee, Hyun-Kyung; Kim, Chowon; Ismail, Tayaba; Kim, Yoo-Kyung; Park, Jeen-Woo; Kwon, Oh-Shin; Kang, Beom Sik; Lee, Dong-Seok; Park, Tae-Joo; Park, Mae-Ja; Choi, Sun-Cheol; Lee, Hyun-Shik

    2016-08-26

    The intraflagellar transport (IFT) system is essential for bidirectional movement of ciliary components from the basal body to the tip beneath the ciliary sheath and is conserved for cilia and flagella formation in most vertebrates. IFT complex A is involved in anterograde trafficking, whereas complex B is involved in retrograde trafficking. IFT46 is well known as a crucial component of IFT complex B, however, its developmental functions are poorly understood. In this study, we investigated the novel functions of IFT46 during vertebrate development, especially, ciliogenesis and neurogenesis, because IFT46 is strongly expressed in both multiciliated cells of epithelial and neural tissues. Knockdown of IFT46 using morpholino microinjections caused shortening of the body axis as well as the formation of fewer and shorter cilia. Furthermore, loss of IFT46 down-regulated the expression of the neural plate and neural tube markers, thus may influence Wnt/planar cell polarity and the sonic hedgehog signaling pathway during neurogenesis. In addition, loss of IFT46 caused craniofacial defects by interfering with cartilage formation. In conclusion, our results depict that IFT46 plays important roles in cilia as well as in neural and craniofacial development. PMID:27320864

  2. Phosphoenolpyruvate Carboxylase in Arabidopsis Leaves Plays a Crucial Role in Carbon and Nitrogen Metabolism1

    PubMed Central

    Shi, Jianghua; Yi, Keke; Liu, Yu; Xie, Li; Zhou, Zhongjing; Chen, Yue; Hu, Zhanghua; Zheng, Tao; Liu, Renhu; Chen, Yunlong; Chen, Jinqing

    2015-01-01

    Phosphoenolpyruvate carboxylase (PEPC) is a crucial enzyme that catalyzes an irreversible primary metabolic reaction in plants. Previous studies have used transgenic plants expressing ectopic PEPC forms with diminished feedback inhibition to examine the role of PEPC in carbon and nitrogen metabolism. To date, the in vivo role of PEPC in carbon and nitrogen metabolism has not been analyzed in plants. In this study, we examined the role of PEPC in plants, demonstrating that PPC1 and PPC2 were highly expressed genes encoding PEPC in Arabidopsis (Arabidopsis thaliana) leaves and that PPC1 and PPC2 accounted for approximately 93% of total PEPC activity in the leaves. A double mutant, ppc1/ppc2, was constructed that exhibited a severe growth-arrest phenotype. The ppc1/ppc2 mutant accumulated more starch and sucrose than wild-type plants when seedlings were grown under normal conditions. Physiological and metabolic analysis revealed that decreased PEPC activity in the ppc1/ppc2 mutant greatly reduced the synthesis of malate and citrate and severely suppressed ammonium assimilation. Furthermore, nitrate levels in the ppc1/ppc2 mutant were significantly lower than those in wild-type plants due to the suppression of ammonium assimilation. Interestingly, starch and sucrose accumulation could be prevented and nitrate levels could be maintained by supplying the ppc1/ppc2 mutant with exogenous malate and glutamate, suggesting that low nitrogen status resulted in the alteration of carbon metabolism and prompted the accumulation of starch and sucrose in the ppc1/ppc2 mutant. Our results demonstrate that PEPC in leaves plays a crucial role in modulating the balance of carbon and nitrogen metabolism in Arabidopsis. PMID:25588735

  3. Histidine biosynthesis plays a crucial role in metal homeostasis and virulence of Aspergillus fumigatus

    PubMed Central

    Dietl, Anna-Maria; Amich, Jorge; Leal, Sixto; Beckmann, Nicola; Binder, Ulrike; Beilhack, Andreas; Pearlman, Eric; Haas, Hubertus

    2016-01-01

    Abstract Aspergillus fumigatus is the most prevalent airborne fungal pathogen causing invasive fungal infections in immunosuppressed individuals. The histidine biosynthetic pathway is found in bacteria, archaebacteria, lower eukaryotes, and plants, but is absent in mammals. Here we demonstrate that deletion of the gene encoding imidazoleglycerol-phosphate dehydratase (HisB) in A. fumigatus causes (i) histidine auxotrophy, (ii) decreased resistance to both starvation and excess of various heavy metals, including iron, copper and zinc, which play a pivotal role in antimicrobial host defense, (iii) attenuation of pathogenicity in 4 virulence models: murine pulmonary infection, murine systemic infection, murine corneal infection, and wax moth larvae. In agreement with the in vivo importance of histidine biosynthesis, the HisB inhibitor 3-amino-1,2,4-triazole reduced the virulence of the A. fumigatus wild type and histidine supplementation partially rescued virulence of the histidine-auxotrophic mutant in the wax moth model. Taken together, this study reveals limited histidine availability in diverse A. fumigatus host niches, a crucial role for histidine in metal homeostasis, and the histidine biosynthetic pathway as being an attractive target for development of novel antifungal therapy approaches. PMID:26854126

  4. Histidine biosynthesis plays a crucial role in metal homeostasis and virulence of Aspergillus fumigatus.

    PubMed

    Dietl, Anna-Maria; Amich, Jorge; Leal, Sixto; Beckmann, Nicola; Binder, Ulrike; Beilhack, Andreas; Pearlman, Eric; Haas, Hubertus

    2016-05-18

    Aspergillus fumigatus is the most prevalent airborne fungal pathogen causing invasive fungal infections in immunosuppressed individuals. The histidine biosynthetic pathway is found in bacteria, archaebacteria, lower eukaryotes, and plants, but is absent in mammals. Here we demonstrate that deletion of the gene encoding imidazoleglycerol-phosphate dehydratase (HisB) in A. fumigatus causes (i) histidine auxotrophy, (ii) decreased resistance to both starvation and excess of various heavy metals, including iron, copper and zinc, which play a pivotal role in antimicrobial host defense, (iii) attenuation of pathogenicity in 4 virulence models: murine pulmonary infection, murine systemic infection, murine corneal infection, and wax moth larvae. In agreement with the in vivo importance of histidine biosynthesis, the HisB inhibitor 3-amino-1,2,4-triazole reduced the virulence of the A. fumigatus wild type and histidine supplementation partially rescued virulence of the histidine-auxotrophic mutant in the wax moth model. Taken together, this study reveals limited histidine availability in diverse A. fumigatus host niches, a crucial role for histidine in metal homeostasis, and the histidine biosynthetic pathway as being an attractive target for development of novel antifungal therapy approaches. PMID:26854126

  5. Domain II plays a crucial role in the function of ribosome recycling factor

    PubMed Central

    2005-01-01

    RRF (ribosome recycling factor) consists of two domains, and in concert with EF-G (elongation factor-G), triggers dissociation of the post-termination ribosomal complex. However, the function of the individual domains of RRF remains unclear. To clarify this, two RRF chimaeras, EcoDI/TteDII and TteDI/EcoDII, were created by domain swaps between the proteins from Escherichia coli and Thermoanaerobacter tengcongensis. The ribosome recycling activity of the RRF chimaeras was compared with their wild-type RRFs by using in vivo and in vitro activity assays. Like wild-type TteRRF (T. tengcongensis RRF), the EcoDI/TteDII chimaera is non-functional in E. coli, but both wild-type TteRRF, and EcoDI/TteDII can be activated by coexpression of T. tengcongensis EF-G in E. coli. By contrast, like wild-type E. coli RRF (EcoRRF), TteDI/EcoDII is fully functional in E. coli. These findings suggest that domain II of RRF plays a crucial role in the concerted action of RRF and EF-G for the post-termination complex disassembly, and the specific interaction between RRF and EF-G on ribosomes mainly depends on the interaction between domain II of RRF and EF-G. This study provides direct genetic and biochemical evidence for the function of the individual domains of RRF. PMID:16262604

  6. The pseudokinase tribbles homologue-3 plays a crucial role in cannabinoid anticancer action.

    PubMed

    Salazar, María; Lorente, Mar; García-Taboada, Elena; Hernández-Tiedra, Sonia; Davila, David; Francis, Sheila E; Guzmán, Manuel; Kiss-Toth, Endre; Velasco, Guillermo

    2013-10-01

    Δ(9)-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer. This effect relies, at least in part, on the up-regulation of several endoplasmic reticulum stress-related proteins including the pseudokinase tribbles homologue-3 (TRIB3), which leads in turn to the inhibition of the AKT/mTORC1 axis and the subsequent stimulation of autophagy-mediated apoptosis in tumor cells. Here, we took advantage of the use of cells derived from Trib3-deficient mice to investigate the precise mechanisms by which TRIB3 regulates the anti-cancer action of THC. Our data show that RasV(12)/E1A-transformed embryonic fibroblasts derived from Trib3-deficient mice are resistant to THC-induced cell death. We also show that genetic inactivation of this protein abolishes the ability of THC to inhibit the phosphorylation of AKT and several of its downstream targets, including those involved in the regulation of the AKT/mammalian target of rapamycin complex 1 (mTORC1) axis. Our data support the idea that THC-induced TRIB3 up-regulation inhibits AKT phosphorylation by regulating the accessibility of AKT to its upstream activatory kinase (the mammalian target of rapamycin complex 2; mTORC2). Finally, we found that tumors generated by inoculation of Trib3-deficient cells in nude mice are resistant to THC anticancer action. Altogether, the observations presented here strongly support that TRIB3 plays a crucial role on THC anti-neoplastic activity. This article is part of a Special Issue entitled Lipid Metabolism in Cancer. PMID:23567453

  7. A Host Small GTP-binding Protein ARL8 Plays Crucial Roles in Tobamovirus RNA Replication

    PubMed Central

    Nishikiori, Masaki; Mori, Masashi; Dohi, Koji; Okamura, Hideyasu; Katoh, Etsuko; Naito, Satoshi; Meshi, Tetsuo; Ishikawa, Masayuki

    2011-01-01

    Tomato mosaic virus (ToMV), like other eukaryotic positive-strand RNA viruses, replicates its genomic RNA in replication complexes formed on intracellular membranes. Previous studies showed that a host seven-pass transmembrane protein TOM1 is necessary for efficient ToMV multiplication. Here, we show that a small GTP-binding protein ARL8, along with TOM1, is co-purified with a FLAG epitope-tagged ToMV 180K replication protein from solubilized membranes of ToMV-infected tobacco (Nicotiana tabacum) cells. When solubilized membranes of ToMV-infected tobacco cells that expressed FLAG-tagged ARL8 were subjected to immunopurification with anti-FLAG antibody, ToMV 130K and 180K replication proteins and TOM1 were co-purified and the purified fraction showed RNA-dependent RNA polymerase activity that transcribed ToMV RNA. From uninfected cells, TOM1 co-purified with FLAG-tagged ARL8 less efficiently, suggesting that a complex containing ToMV replication proteins, TOM1, and ARL8 are formed on membranes in infected cells. In Arabidopsis thaliana, ARL8 consists of four family members. Simultaneous mutations in two specific ARL8 genes completely inhibited tobamovirus multiplication. In an in vitro ToMV RNA translation-replication system, the lack of either TOM1 or ARL8 proteins inhibited the production of replicative-form RNA, indicating that TOM1 and ARL8 are required for efficient negative-strand RNA synthesis. When ToMV 130K protein was co-expressed with TOM1 and ARL8 in yeast, RNA 5′-capping activity was detected in the membrane fraction. This activity was undetectable or very weak when the 130K protein was expressed alone or with either TOM1 or ARL8. Taken together, these results suggest that TOM1 and ARL8 are components of ToMV RNA replication complexes and play crucial roles in a process toward activation of the replication proteins' RNA synthesizing and capping functions. PMID:22174675

  8. A host small GTP-binding protein ARL8 plays crucial roles in tobamovirus RNA replication.

    PubMed

    Nishikiori, Masaki; Mori, Masashi; Dohi, Koji; Okamura, Hideyasu; Katoh, Etsuko; Naito, Satoshi; Meshi, Tetsuo; Ishikawa, Masayuki

    2011-12-01

    Tomato mosaic virus (ToMV), like other eukaryotic positive-strand RNA viruses, replicates its genomic RNA in replication complexes formed on intracellular membranes. Previous studies showed that a host seven-pass transmembrane protein TOM1 is necessary for efficient ToMV multiplication. Here, we show that a small GTP-binding protein ARL8, along with TOM1, is co-purified with a FLAG epitope-tagged ToMV 180K replication protein from solubilized membranes of ToMV-infected tobacco (Nicotiana tabacum) cells. When solubilized membranes of ToMV-infected tobacco cells that expressed FLAG-tagged ARL8 were subjected to immunopurification with anti-FLAG antibody, ToMV 130K and 180K replication proteins and TOM1 were co-purified and the purified fraction showed RNA-dependent RNA polymerase activity that transcribed ToMV RNA. From uninfected cells, TOM1 co-purified with FLAG-tagged ARL8 less efficiently, suggesting that a complex containing ToMV replication proteins, TOM1, and ARL8 are formed on membranes in infected cells. In Arabidopsis thaliana, ARL8 consists of four family members. Simultaneous mutations in two specific ARL8 genes completely inhibited tobamovirus multiplication. In an in vitro ToMV RNA translation-replication system, the lack of either TOM1 or ARL8 proteins inhibited the production of replicative-form RNA, indicating that TOM1 and ARL8 are required for efficient negative-strand RNA synthesis. When ToMV 130K protein was co-expressed with TOM1 and ARL8 in yeast, RNA 5'-capping activity was detected in the membrane fraction. This activity was undetectable or very weak when the 130K protein was expressed alone or with either TOM1 or ARL8. Taken together, these results suggest that TOM1 and ARL8 are components of ToMV RNA replication complexes and play crucial roles in a process toward activation of the replication proteins' RNA synthesizing and capping functions. PMID:22174675

  9. Reversible Aggregation Plays a Crucial Role on the Folding Landscape of p53 Core Domain

    PubMed Central

    Ishimaru, Daniella; Lima, Luis M. T. R.; Maia, Lenize F.; Lopez, Priscila M.; Ano Bom, Ana P.; Valente, Ana P.; Silva, Jerson L.

    2004-01-01

    The role of tumor suppressor protein p53 in cell cycle control depends on its flexible and partially unstructured conformation, which makes it crucial to understand its folding landscape. Here we report an intermediate structure of the core domain of the tumor suppressor protein p53 (p53C) during equilibrium and kinetic folding/unfolding transitions induced by guanidinium chloride. This partially folded structure was undetectable when investigated by intrinsic fluorescence. Indeed, the fluorescence data showed a simple two-state transition. On the other hand, analysis of far ultraviolet circular dichroism in 1.0 M guanidinium chloride demonstrated a high content of secondary structure, and the use of an extrinsic fluorescent probe, 4,4′-dianilino-1,1′ binaphthyl-5,5′-disulfonic acid, indicated an increase in exposure of the hydrophobic core at 1 M guanidinium chloride. This partially folded conformation of p53C was plagued by aggregation, as suggested by one-dimensional NMR and demonstrated by light-scattering and gel-filtration chromatography. Dissociation by high pressure of these aggregates reveals the reversibility of the process and that the aggregates have water-excluded cavities. Kinetic measurements show that the intermediate formed in a parallel reaction between unfolded and folded structures and that it is under fine energetic control. They are not only crucial to the folding pathway of p53C but may explain as well the vulnerability of p53C to undergo departure of the native to an inactive state, which makes the cell susceptible to malignant transformation. PMID:15298872

  10. Trichoderma viride Laccase Plays a Crucial Role in Defense Mechanism against Antagonistic Organisms

    PubMed Central

    Divya, Lakshmanan; Sadasivan, C.

    2016-01-01

    Fungal laccases are involved in a variety of physiological functions such as delignification, morphogenesis, and parasitism. In addition to these functions, we suggest that fungal laccases are involved in defense mechanisms. When the laccase secreting Trichoderma viride was grown in the presence of a range of microorganisms including bacteria and fungi, laccase secretion was enhanced in response to antagonistic organisms alone. In addition, growth of antagonistic microbes was restricted by the secreting fungi. Besides, our study for the first time shows the inability of the secreting fungi (T. viride) to compete with antagonistic organism when laccase activity is inhibited, further emphasizing its involvement in rendering a survival advantage to the secreting organism. When laccase inhibitor was added to the media, the zone of inhibition exerted by the antagonist organism was more pronounced and consequently growth of T. viride was significantly restricted. Based on these observations we accentuate that, laccase plays an important role in defense mechanism and provides endurance to the organism when encountered with an antagonistic organism in its surrounding. PMID:27242756

  11. CTE Plays a Crucial Role in Health Care for the Elderly

    ERIC Educational Resources Information Center

    Reese, Susan

    2007-01-01

    The health care skill gap is expected to worsen, but Career and Technical Education (CTE) is playing an integral part in preparing the next generation of workers. This article discusses the efforts of Greentree Health Science Academy in addressing the need to develop the next generation of health care professionals. In collaboration with…

  12. Phosphoenolpyruvate carboxylase intrinsically located in the chloroplast of rice plays a crucial role in ammonium assimilation

    PubMed Central

    Masumoto, Chisato; Miyazawa, Shin-Ichi; Ohkawa, Hiroshi; Fukuda, Takuya; Taniguchi, Yojiro; Murayama, Seiji; Kusano, Miyako; Saito, Kazuki; Fukayama, Hiroshi; Miyao, Mitsue

    2010-01-01

    Phosphoenolpyruvate carboxylase (PEPC) is a key enzyme of primary metabolism in bacteria, algae, and vascular plants, and is believed to be cytosolic. Here we show that rice (Oryza sativa L.) has a plant-type PEPC, Osppc4, that is targeted to the chloroplast. Osppc4 was expressed in all organs tested and showed high expression in the leaves. Its expression in the leaves was confined to mesophyll cells, and Osppc4 accounted for approximately one-third of total PEPC protein in the leaf blade. Recombinant Osppc4 was active in the PEPC reaction, showing Vmax comparable to cytosolic isozymes. Knockdown of Osppc4 expression by the RNAi technique resulted in stunting at the vegetative stage, which was much more marked when rice plants were grown with ammonium than with nitrate as the nitrogen source. Comparison of leaf metabolomes of ammonium-grown plants suggested that the knockdown suppressed ammonium assimilation and subsequent amino acid synthesis by reducing levels of organic acids, which are carbon skeleton donors for these processes. We also identified the chloroplastic PEPC gene in other Oryza species, all of which are adapted to waterlogged soil where the major nitrogen source is ammonium. This suggests that, in addition to glycolysis, the genus Oryza has a unique route to provide organic acids for ammonium assimilation that involves a chloroplastic PEPC, and that this route is crucial for growth with ammonium. This work provides evidence for diversity of primary ammonium assimilation in the leaves of vascular plants. PMID:20194759

  13. Understanding ‘what’ others do: mirror mechanisms play a crucial role in action perception

    PubMed Central

    Avenanti, Alessio; Urgesi, Cosimo

    2011-01-01

    Neurophysiological and imaging studies suggest that the inferior frontal cortex (IFC) implements a mechanism that matches perceived actions to one’s motor representation of similar actions (mirror mechanism) and recent lesion studies have also established that IFC is critical for action perception. However, to date causative evidence that action perception requires activation within the same populations of IFC neurons involved in action execution is lacking. In this issue, Cattaneo and colleagues provide the first direct evidence that mirror mechanisms in IFC influence action perception. We discuss the implications of these findings for the understanding of the functional role of mirror mechanisms. PMID:21653637

  14. Understanding 'what' others do: mirror mechanisms play a crucial role in action perception.

    PubMed

    Avenanti, Alessio; Urgesi, Cosimo

    2011-06-01

    Neurophysiological and imaging studies suggest that the inferior frontal cortex (IFC) implements a mechanism that matches perceived actions to one's motor representation of similar actions (mirror mechanism) and recent lesion studies have also established that IFC is critical for action perception. However, to date causative evidence that action perception requires activation within the same populations of IFC neurons involved in action execution is lacking. In this issue, Cattaneo and colleagues provide the first direct evidence that mirror mechanisms in IFC influence action perception. We discuss the implications of these findings for the understanding of the functional role of mirror mechanisms. PMID:21653637

  15. Yap and Taz play a crucial role in neural crest-derived craniofacial development.

    PubMed

    Wang, Jun; Xiao, Yang; Hsu, Chih-Wei; Martinez-Traverso, Idaliz M; Zhang, Min; Bai, Yan; Ishii, Mamoru; Maxson, Robert E; Olson, Eric N; Dickinson, Mary E; Wythe, Joshua D; Martin, James F

    2016-02-01

    The role of the Hippo signaling pathway in cranial neural crest (CNC) development is poorly understood. We used the Wnt1(Cre) and Wnt1(Cre2SOR) drivers to conditionally ablate both Yap and Taz in the CNC of mice. When using either Cre driver, Yap and Taz deficiency in the CNC resulted in enlarged, hemorrhaging branchial arch blood vessels and hydrocephalus. However, Wnt1(Cre2SOR) mutants had an open cranial neural tube phenotype that was not evident in Wnt1(Cre) mutants. In O9-1 CNC cells, the loss of Yap impaired smooth muscle cell differentiation. RNA-sequencing data indicated that Yap and Taz regulate genes encoding Fox transcription factors, specifically Foxc1. Proliferation was reduced in the branchial arch mesenchyme of Yap and Taz CNC conditional knockout (CKO) embryos. Moreover, Yap and Taz CKO embryos had cerebellar aplasia similar to Dandy-Walker spectrum malformations observed in human patients and mouse embryos with mutations in Foxc1. In embryos and O9-1 cells deficient for Yap and Taz, Foxc1 expression was significantly reduced. Analysis of Foxc1 regulatory regions revealed a conserved recognition element for the Yap and Taz DNA binding co-factor Tead. ChIP-PCR experiments supported the conclusion that Foxc1 is directly regulated by the Yap-Tead complex. Our findings uncover important roles for Yap and Taz in CNC diversification and development. PMID:26718006

  16. The LINC complex component Sun4 plays a crucial role in sperm head formation and fertility

    PubMed Central

    Pasch, Elisabeth; Link, Jana; Beck, Carolin; Scheuerle, Stefanie; Alsheimer, Manfred

    2015-01-01

    ABSTRACT LINC complexes are evolutionarily conserved nuclear envelope bridges, physically connecting the nucleus to the peripheral cytoskeleton. They are pivotal for dynamic cellular and developmental processes, like nuclear migration, anchoring and positioning, meiotic chromosome movements and maintenance of cell polarity and nuclear shape. Active nuclear reshaping is a hallmark of mammalian sperm development and, by transducing cytoskeletal forces to the nuclear envelope, LINC complexes could be vital for sperm head formation as well. We here analyzed in detail the behavior and function of Sun4, a bona fide testis-specific LINC component. We demonstrate that Sun4 is solely expressed in spermatids and there localizes to the posterior nuclear envelope, likely interacting with Sun3/Nesprin1 LINC components. Our study revealed that Sun4 deficiency severely impacts the nucleocytoplasmic junction, leads to mislocalization of other LINC components and interferes with the formation of the microtubule manchette, which finally culminates in a globozoospermia-like phenotype. Together, our study provides direct evidence for a critical role of LINC complexes in mammalian sperm head formation and male fertility. PMID:26621829

  17. Abscisic Acid Uridine Diphosphate Glucosyltransferases Play a Crucial Role in Abscisic Acid Homeostasis in Arabidopsis1[C][W

    PubMed Central

    Dong, Ting; Xu, Zheng-Yi; Park, Youngmin; Kim, Dae Heon; Lee, Yongjik; Hwang, Inhwan

    2014-01-01

    The phytohormone abscisic acid (ABA) is crucial for plant growth and adaptive responses to various stress conditions. Plants continuously adjust the ABA level to meet physiological needs, but how ABA homeostasis occurs is not fully understood. This study provides evidence that UGT71B6, an ABA uridine diphosphate glucosyltransferase (UGT), and its two closely related homologs, UGT71B7 and UGT71B8, play crucial roles in ABA homeostasis and in adaptation to dehydration, osmotic stress, and high-salinity stresses in Arabidopsis (Arabidopsis thaliana). UGT RNA interference plants that had low levels of these three UGT transcripts displayed hypersensitivity to exogenous ABA and high-salt conditions during germination and exhibited a defect in plant growth. However, the ectopic expression of UGT71B6 in the atbg1 (for β-glucosidase) mutant background aggravated the ABA-deficient phenotype of atbg1 mutant plants. In addition, modulation of the expression of the three UGTs affects the expression of CYP707A1 to CYP707A4, which encode ABA 8′-hydroxylases; four CYP707As were expressed at higher levels in the UGT RNA interference plants but at lower levels in the UGT71B6:GFP-overexpressing plants. Based on these data, this study proposes that UGT71B6 and its two homologs play a critical role in ABA homeostasis by converting active ABA to an inactive form (abscisic acid-glucose ester) depending on intrinsic cellular and environmental conditions in plants. PMID:24676855

  18. Human S100A10 plays a crucial role in the acquisition of the endometrial receptivity phenotype.

    PubMed

    Bissonnette, Laurence; Drissennek, Loubna; Antoine, Yannick; Tiers, Laurent; Hirtz, Christophe; Lehmann, Sylvain; Perrochia, Hélène; Bissonnette, François; Kadoch, Isaac-Jacques; Haouzi, Delphine; Hamamah, Samir

    2016-05-01

    In assisted reproduction, about 30% of embryo implantation failures are related to inadequate endometrial receptivity. To identify molecules involved in endometrial receptivity acquisition, we investigated, using a SELDI-TOF approach, the protein expression profile of early-secretory and mid-secretory endometrium samples. Among the proteins upregulated in mid-secretory endometrium, we investigated the function of S100A10 in endometrial receptivity and implantation process. S100A10 was expressed in epithelial and stromal cells of the endometrium of fertile patients during the implantation windows. Conversely, it was downregulated in the mid-secretory endometrium of infertile patients diagnosed as non-receptive. Transcriptome analysis of human endometrial epithelial and stromal cells where S100A10 was silenced by shRNA revealed the deregulation of 37 and 256 genes, respectively, related to components of the extracellular matrix and intercellular connections. Functional annotations of these deregulated genes highlighted alterations of the leukocyte extravasation signaling and angiogenesis pathways that play a crucial role during implantation. S100A10 silencing also affected the migration of primary endometrial epithelial and stromal cells, decidualization and secretory transformation of primary endometrial stromal cells and epithelial cells respectively, and promoted apoptosis in serum-starved endometrial epithelial cells. Our findings identify S100A10 as a player in endometrial receptivity acquisition. PMID:26760977

  19. Peroxisome proliferator-activated receptor alpha plays a crucial role in behavioral repetition and cognitive flexibility in mice

    PubMed Central

    D'Agostino, Giuseppe; Cristiano, Claudia; Lyons, David J.; Citraro, Rita; Russo, Emilio; Avagliano, Carmen; Russo, Roberto; Raso, Giuseppina Mattace; Meli, Rosaria; De Sarro, Giovambattista; Heisler, Lora K.; Calignano, Antonio

    2015-01-01

    Background/objectives Nuclear peroxisome proliferator activated receptor-α (PPAR-α) plays a fundamental role in the regulation of lipid homeostasis and is the target of medications used to treat dyslipidemia. However, little is known about the role of PPAR-α in mouse behavior. Methods To investigate the function of Ppar-α in cognitive functions, a behavioral phenotype analysis of mice with a targeted genetic disruption of Ppar-α was performed in combination with neuroanatomical, biochemical and pharmacological manipulations. The therapeutic exploitability of PPAR-α was probed in mice using a pharmacological model of psychosis and a genetic model (BTBR T + tf/J) exhibiting a high rate of repetitive behavior. Results An unexpected role for brain Ppar-α in the regulation of cognitive behavior in mice was revealed. Specifically, we observed that Ppar-α genetic perturbation promotes rewiring of cortical and hippocampal regions and a behavioral phenotype of cognitive inflexibility, perseveration and blunted responses to psychomimetic drugs. Furthermore, we demonstrate that the antipsychotic and autism spectrum disorder (ASD) medication risperidone ameliorates the behavioral profile of Ppar-α deficient mice. Importantly, we reveal that pharmacological PPAR-α agonist treatment in mice improves behavior in a pharmacological model of ketamine-induced behavioral dysinhibition and repetitive behavior in BTBR T + tf/J mice. Conclusion Our data indicate that Ppar-α is required for normal cognitive function and that pharmacological stimulation of PPAR-α improves cognitive function in pharmacological and genetic models of impaired cognitive function in mice. These results thereby reveal an unforeseen therapeutic application for a class of drugs currently in human use. PMID:26137440

  20. A Dictyostelium myosin I plays a crucial role in regulating the frequency of pseudopods formed on the substratum.

    PubMed

    Wessels, D; Titus, M; Soll, D R

    1996-01-01

    Analysis of the motile behavior of a strain of Dictyostelium lacking a myosin I, myoA, revealed that this mutant strain formed pseudopods and turned twice as frequently as wild type cells [Titus et al., 1993: Mol. Biol. Cell 4:233-246]. The basis for this aberrant behavior has been explored using three-dimensional reconstructions of translocating cells. Wild type cells form approximately 40% of pseudopods on the substratum and 60% off the substratum. The majority of pseudopods formed on the substratum initiate sharp turns while the majority of pseudopods formed off the substratum are retracted. Although myoA- cells form pseudopods at roughly twice the frequency of wild type cells, the increase in frequency is specific for only those pseudopods formed on the substratum. This increase is the basis for the aberrant increase in turning in myoA- cells. The selective increase in the frequency of pseudopods formed on the substratum correlates with a number of additional abnormalities in myoA- pseuodpod formation. First, myoA- cells can simultaneously extend more than one pseudopod, whereas wild type cells extend only one pseudopod at a time. Second, although wild type and myoA- pseudopods achieve the same final volumes, myoA- pseudopods grow at half the rate of wild type pseudopods and, therefore, take longer to achieve final volume. Third, while a wild type pseudopod grows in a continuous fashion, a myoA- pseudopod grows in a discontinuous fashion. Together, these results demonstrate that myoA plays a fundamental role in controlling the frequency of only those pseudopods formed on the substratum, and that maintenance of the normal frequency of pseudopod formation appears to be necessary for the normal velocity of cellular translocation, the normal frequency of turning, the normal rate of average pseudopod growth, and the high efficiency of chemotaxis. These results in turn indicate that pseudopod formation is precisely coordinated in space and time, and actin

  1. Uterine autonomic nerve innervation plays a crucial role in regulating rat uterine mast cell functions during embryo implantation.

    PubMed

    Yuan, Xue-Jun; Huang, Li-Bo; Qiao, Hui-Li; Deng, Ze-Pei; Fa, Jing-Jing

    2009-12-01

    To explore the potential mechanism of how uterine innervations would affect the uterine mast cell (MC) population and functions during the periimplantation. We herein first examined the consequence of uterine neurectomy on embryo implantation events. We observed that amputation of autonomic nerves innervating the uterus led to on-time implantation failure in rats. Exploiting MC culture and ELISA approaches, we then further analyzed the effect of neurectomy on cellular histamine levels and its release from uterine MCs, to elucidate the relation of the autonomic nerves and local cellular immunity in the uterine during early pregnancy. We observed that disconnection of autonomic nerve innervation significantly increased the population of uterine MCs. Most interestingly, these increased number of uterine MCs in neuroectomized rats contained a much reduced cellular level of histamine. Our subsequent challenge experiments revealed that uterine MCs in nerve amputated rats exhibited enhanced histamine releasing rate in response to substance P and antiIgE, suggesting loss of nerve innervation in the uterus not only increases the population of uterine MCs, but also facilitates the release of histamine from MCs, thus subsequently interfere with the normal implantation process. Collectively, our findings provide a new line of evidence supporting the concept that immune-neuro-endocrine network plays important role during pregnancy establishment and maintenance. PMID:19765668

  2. Aquaporin7 plays a crucial role in tolerance to hyperosmotic stress and in the survival of oocytes during cryopreservation

    PubMed Central

    Tan, Ya-Jing; Zhang, Xue-Ying; Ding, Guo-Lian; Li, Rong; Wang, Li; Jin, Li; Lin, Xian-Hua; Gao, Ling; Sheng, Jian-Zhong; Huang, He-Feng

    2015-01-01

    Hyperosmotic stress may induce apoptosis of different cells. However, oocytes show tolerance to osmotic stress during cryopreservation by vitrification, which is an assisted reproductive technique. The underlying mechanism is still not understood. Here, we demonstrated that hyperosmosis produced by high concentrations of cryoprotectants, including DMSO, ethylene glycol and sucrose, significantly upregulated the protein levels of aquaporin (AQP) 7, but not AQP3 and AQP9, in mouse oocytes. Knockdown of AQP7 expression by siRNA-injection significantly reduced the survival of oocytes after vitrification. In oocytes, AQP7 was shown to bind with F-actin, a protein involved in almost all biological events. Moreover, we found that hyperosmosis could upregulate the phosphorylation levels of CPE-binding protein (CPEB) and Aurora A. Inhibition of the PI3K and PKC pathways blocked the hyperosmosis-induced upregulation of AQP7 and the phosphorylation of CPEB and Aurora A in oocytes. In conclusion, hyperosmosis could upregulate the expression of AQP7 via Aurora A/CPEB phosphorylation mediated by the PI3K and PKC pathways, and upregulation of AQP7 plays an important role in improving of tolerance to hyperosmotic stress and survival of oocytes during cryopreservation by vitrification. PMID:26634435

  3. TolC plays a crucial role in immune protection conferred by Edwardsiella tarda whole-cell vaccines

    PubMed Central

    Wang, Chao; Peng, Bo; Li, Hui; Peng, Xuan-xian

    2016-01-01

    Although vaccines developed from live organisms have better efficacy than those developed from dead organisms, the mechanisms underlying this differential efficacy remain unexplored. In this study, we combined sub-immunoproteomics with immune challenge to investigate the action of the outer membrane proteome in the immune protection conferred by four Edwardsiella tarda whole-cell vaccines prepared via different treatments and to identify protective immunogens that play a key role in this immune protection. Thirteen spots representing five outer membrane proteins and one cytoplasmic protein were identified, and it was found that their abundance was altered in relation with the immune protective abilities of the four vaccines. Among these proteins, TolC and OmpA were found to be the key immunogens conferring the first and second highest degrees of protection, respectively. TolC was detected in the two effective vaccines (live and inactivated-30-F). The total antiserum and anti-OmpA titers were higher for the two effective vaccines than for the two ineffective vaccines (inactivated-80-F and inactivated-100). Further evidence demonstrated that the live and inactivated-30-F vaccines demonstrated stronger abilities to induce CD8+ and CD4+ T cell differentiation than the other two evaluated vaccines. Our results indicate that the outer membrane proteome changes dramatically following different treatments, which contributes to the effectiveness of whole-cell vaccines. PMID:27406266

  4. TolC plays a crucial role in immune protection conferred by Edwardsiella tarda whole-cell vaccines.

    PubMed

    Wang, Chao; Peng, Bo; Li, Hui; Peng, Xuan-Xian

    2016-01-01

    Although vaccines developed from live organisms have better efficacy than those developed from dead organisms, the mechanisms underlying this differential efficacy remain unexplored. In this study, we combined sub-immunoproteomics with immune challenge to investigate the action of the outer membrane proteome in the immune protection conferred by four Edwardsiella tarda whole-cell vaccines prepared via different treatments and to identify protective immunogens that play a key role in this immune protection. Thirteen spots representing five outer membrane proteins and one cytoplasmic protein were identified, and it was found that their abundance was altered in relation with the immune protective abilities of the four vaccines. Among these proteins, TolC and OmpA were found to be the key immunogens conferring the first and second highest degrees of protection, respectively. TolC was detected in the two effective vaccines (live and inactivated-30-F). The total antiserum and anti-OmpA titers were higher for the two effective vaccines than for the two ineffective vaccines (inactivated-80-F and inactivated-100). Further evidence demonstrated that the live and inactivated-30-F vaccines demonstrated stronger abilities to induce CD8+ and CD4+ T cell differentiation than the other two evaluated vaccines. Our results indicate that the outer membrane proteome changes dramatically following different treatments, which contributes to the effectiveness of whole-cell vaccines. PMID:27406266

  5. PKR, a p53 target gene, plays a crucial role in the tumor-suppressor function of p53

    PubMed Central

    Yoon, Cheol-Hee; Lee, Eun-Soo; Lim, Dae-Seog; Bae, Yong-Soo

    2009-01-01

    Type I IFN-induced expression of dsRNA-activated protein kinase (PKR) during viral infection is a well-established antiviral mechanism. However, little is known about the expression of PKR in the context of p53 and about PKR involvement in p53-mediated tumor suppression. Here, we report that PKR is a p53 target gene and plays an important role in the tumor-suppressor function of p53. Activation of p53 by genotoxic stress induces a significant level of PKR expression by acting on the newly identified cis-acting element (ISRE), which is separated from the IFN-stimulated responsive element on the PKR promoter, resulting in translational inhibition and cell apoptosis. The genotoxin-mediated inhibition of translation is associated with the p53/PKR/elF2a (eukaryotic initiation factor-2α) pathway. To some extent, p53 activation induced by DNA damage facilitates cell apoptosis by activating PKR. PKR-knockdown human colon cancer cells grew rapidly in nude mice and proved resistant to anti-cancer drugs. These data indicate that p53-mediated tumor suppression can be attributed at least in part to the biological functions of PKR induced by p53 in genotoxic conditions. PMID:19416861

  6. Oct4 plays a crucial role in the maintenance of gefitinib-resistant lung cancer stem cells.

    PubMed

    Kobayashi, Isao; Takahashi, Fumiyuki; Nurwidya, Fariz; Nara, Takeshi; Hashimoto, Muneaki; Murakami, Akiko; Yagishita, Shigehiro; Tajima, Ken; Hidayat, Moulid; Shimada, Naoko; Suina, Kentaro; Yoshioka, Yasuko; Sasaki, Shinichi; Moriyama, Mariko; Moriyama, Hiroyuki; Takahashi, Kazuhisa

    2016-04-22

    Several recent studies have suggested that cancer stem cells (CSCs) are involved in resistance to gefitinib in non-small cell lung cancer (NSCLC). Oct4, a member of the POU-domain transcription factor family, has been shown to be involved in CSC properties of various cancers. We previously reported that Oct4 and the putative lung CSC marker CD133 were highly expressed in gefitinib-resistant persisters (GRPs) in NSCLC cells, and GRPs exhibited characteristic features of the CSCs phenotype. The aim of this study was to elucidate the role of Oct4 in the resistance to gefitinib in NSCLC cells with an activating epidermal growth factor receptor (EGFR) mutation. NSCLC cell lines, PC9, which express the EGFR exon 19 deletion mutation, were transplanted into NOG mice, and were treated with gefitinib in vivo. After 14-17 days of gefitinib treatment, the tumors still remained; these tumors were referred to as gefitinib-resistant tumors (GRTs). PC9-GRTs showed higher expression of Oct4 and CD133. To investigate the role of Oct4 in the maintenance of gefitinib-resistant lung CSCs, we introduced the Oct4 gene into PC9 and HCC827 cells carrying an activating EGFR mutation by lentiviral infection. Transfection of Oct4 significantly increased CD133-positive GRPs and the number of sphere formation, reflecting the self-renewal activity, of PC9 and HCC827 cells under the high concentration of gefitinib in vitro. Furthermore, Oct4-overexpressing PC9 cells (PC9-Oct4) significantly formed tumors at 1 × 10 cells/injection in NOG mice as compared to control cells. In addition, PC9-Oct4 tumors were more resistant to gefitinib treatment as compared to control cells in vivo. Finally, immunohistochemical analysis revealed that Oct4 was highly expressed in tumor specimens of EGFR-mutant NSCLC patients with acquired resistance to gefitinib. Collectively, these findings suggest that Oct4 plays a pivotal role in the maintenance of lung CSCs resistant to gefitinib in EGFR mutation

  7. Integrin subunit beta3 plays a crucial role in the movement of osteoclasts from the periosteum to the bone surface.

    PubMed

    Holt, I; Marshall, M J

    1998-04-01

    We have shown that, when mouse parietal bones were incubated in culture medium containing indomethacin, the number of tartrate-resistant acid phosphatase-positive osteoclasts (TRAP + OCs) on the bone surface was drastically reduced (down-regulation), and the number on the periosteal membrane adjacent to the resorbing surface was increased. Subsequent incubation of bones with prostaglandin E2 (PGE2) rapidly reversed these changes (up-regulation). In the work reported here, the osteoclast-associated integrin subunit beta3 was stained by immunohistochemistry. The beta3-positive osteoclast (beta3 + OC) population on freshly isolated bone was comprised of about 67% TRAP + OCs and 33% TRAP OCs. Like TRAP + OCs, beta3 + OCs were reduced in number on the surface of bones incubated with indomethacin, but, in contrast to the TRAP + OCs, beta3 + OCs were not seen on the periosteal membrane. Following up-regulation of TRAP + OCs with PGE2, large numbers of beta3 + OCs appeared on the bone surface and, again, were not seen on the periosteal membrane. Echistatin, a peptide that binds to the alphavbeta3 integrin on osteoclasts, was found to inhibit the up-regulation of TRAP + OCs in a dose-dependent manner but had no effect on the down-regulation of TRAP + OCs. Similarly, echistatin inhibited the upregulation of beta3 + OCs on the bone surface, and, under these conditions, beta3 + OCs were observed on the periosteal membrane. The addition of anti-beta3 antibody also inhibited the up-regulation of TRAP + OCs in response to PGE2. The association of beta3 protein expression with the up-regulated osteoclast and the inhibition of up-regulation by echistatin and by anti-beta3 antibody provide strong evidence that beta3 plays an essential role in the movement of osteoclasts from the membrane to the bone. PMID:9491775

  8. Peripheral Blood Mononuclear Cell Traffic Plays a Crucial Role in Mother-to-Infant Transmission of Hepatitis B Virus

    PubMed Central

    Xu, Yuan-Yong; Liu, Hui-Hui; Zhong, Yan-Wei; Liu, Chang; Wang, Yong; Jia, Lei-Li; Qiao, Fei; Li, Xin-Xin; Zhang, Chuan-Fu; Li, Shen-Long; Li, Peng; Song, Hong-Bin; Li, Qiao

    2015-01-01

    The role of peripheral blood mononuclear cells (PBMCs) in HBV intrauterine infection is not fully defined. Particularly the origin of PBMCs in HBV-infected neonates remains to be addressed. We carried out a population-based nested case-control study by enrolling 312 HBsAg-positive mothers and their babies. PBMC HBV DNA as well as serum HBsAg and HBV DNA was tested in cohort entry samples. Totally, 45.5% (142/312) of the newborns were found to be infected with HBV in perinatal transmission. 119 mother-infant pairs were identified to be different in the genetic profile of maternal and fetal PBMCs by AS-PCR and hemi-nested PCR. Among them, 57.1% (68/119) of the maternal PBMCs in index cases were positive for HBV DNA while 83.8% (57/68) of the HBV DNA positive maternal PBMCs passed the placental barrier and entered the fetus. Furthermore, maternal PBMC HBV infection was significantly associated with newborn infants HBV infection. PBMC traffic from mother to fetus resulted in a 9.5-fold increased risk of HBV infection in PBMC HBV DNA positive newborn infants. These data indicate that maternal PBMCs infected with HBV contribute to HBV intrauterine infection of newborn infants via PBMC traffic from mother to fetus. PMID:25678845

  9. The Arabidopsis BLAP75/Rmi1 Homologue Plays Crucial Roles in Meiotic Double-Strand Break Repair

    PubMed Central

    Chelysheva, Liudmila; Vezon, Daniel; Belcram, Katia; Gendrot, Ghislaine; Grelon, Mathilde

    2008-01-01

    In human cells and in Saccharomyces cerevisiae, BLAP75/Rmi1 acts together with BLM/Sgs1 and TopoIIIα/Top3 to maintain genome stability by limiting crossover (CO) formation in favour of NCO events, probably through the dissolution of double Holliday junction intermediates (dHJ). So far, very limited data is available on the involvement of these complexes in meiotic DNA repair. In this paper, we present the first meiotic study of a member of the BLAP75 family through characterisation of the Arabidopsis thaliana homologue. In A. thaliana blap75 mutants, meiotic recombination is initiated, and recombination progresses until the formation of bivalent-like structures, even in the absence of ZMM proteins. However, chromosome fragmentation can be detected as soon as metaphase I and is drastic at anaphase I, while no second meiotic division is observed. Using genetic and imunolocalisation studies, we showed that these defects reflect a role of A. thaliana BLAP75 in meiotic double-strand break (DSB) repair—that it acts after the invasion step mediated by RAD51 and associated proteins and that it is necessary to repair meiotic DSBs onto sister chromatids as well as onto the homologous chromosome. In conclusion, our results show for the first time that BLAP75/Rmi1 is a key protein of the meiotic homologous recombination machinery. In A. thaliana, we found that this protein is dispensable for homologous chromosome recognition and synapsis but necessary for the repair of meiotic DSBs. Furthermore, in the absence of BLAP75, bivalent formation can happen even in the absence of ZMM proteins, showing that in blap75 mutants, recombination intermediates exist that are stable enough to form bivalent structures, even when ZMM are absent. PMID:19096505

  10. The mammalian efferent vestibular system plays a crucial role in the high-frequency response and short-term adaptation of the vestibuloocular reflex.

    PubMed

    Hübner, Patrick P; Khan, Serajul I; Migliaccio, Americo A

    2015-12-01

    Although anatomically well described, the functional role of the mammalian efferent vestibular system (EVS) remains unclear. Unlike in fish and reptiles, the mammalian EVS does not seem to play a role in modulation of primary afferent activity in anticipation of active head movements. However, it could play a role in modulating long-term mechanisms requiring plasticity such as vestibular adaptation. We measured the efficacy of vestibuloocular reflex (VOR) adaptation in α9-knockout mice. These mice carry a missense mutation of the gene encoding the α9 nicotinic acetylcholine receptor (nAChR) subunit. The α9 nAChR subunit is expressed in the vestibular and auditory periphery, and its loss of function could compromise peripheral input from the predominantly cholinergic EVS. We measured the VOR gain (eye velocity/head velocity) in 26 α9-knockout mice and 27 cba129 control mice. Mice were randomly assigned to one of three groups: gain-increase adaptation (1.5×), gain-decrease adaptation (0.5×), or no adaptation (baseline, 1×). After adaptation training (horizontal rotations at 0.5 Hz with peak velocity 20°/s), we measured the sinusoidal (0.2-10 Hz, 20-100°/s) and transient (1,500-6,000°/s(2)) VOR in complete darkness. α9-Knockout mice had significantly lower baseline gains compared with control mice. This difference increased with stimulus frequency (∼ 5% <1 Hz to ∼ 25% >1 Hz). Moreover, vestibular adaptation (difference in VOR gain of gain-increase and gain-decrease adaptation groups as % of gain increase) was significantly reduced in α9-knockout mice (17%) compared with control mice (53%), a reduction of ∼ 70%. Our results show that the loss of α9 nAChRs moderately affects the VOR but severely affects VOR adaptation, suggesting that the EVS plays a crucial role in vestibular plasticity. PMID:26424577

  11. Mannose binding lectin plays a crucial role in innate immunity against yeast by enhanced complement activation and enhanced uptake of polymorphonuclear cells

    PubMed Central

    van Asbeck, Eveline C; Hoepelman, Andy IM; Scharringa, Jelle; Herpers, Bjorn L; Verhoef, Jan

    2008-01-01

    Background Mannose binding lectin (MBL) is an important host defence protein against opportunistic fungal pathogens. This carbohydrate-binding protein, an opsonin and lectin pathway activator, binds through multiple lectin domains to the repeating sugar arrays displayed on the surface of a wide range of clinically relevant microbial species. We investigated the contribution of MBL to antifungal innate immunity towards C. parapsilosis in vitro. Results High avidity binding was observed between MBL and C. albicans and C. parapsilosis. Addition of MBL to MBL deficient serum increased the deposition of C4 and C3b and enhanced the uptake of C. albicans, C. parapsilosis and acapsular C. neoformans by polymorphonuclear cells (PMNs). Compared to other microorganisms, such as Escherichia coli, Staphylococcus aureus and Cryptococcus neoformans, C. parapsilosis and Candida albicans were potent activators of the lectin pathway. Conclusion Our results suggest that MBL plays a crucial role in the innate immunity against infections caused by yeast by increasing uptake by PMN. PMID:19094203

  12. Analysis of self-association of West Nile virus capsid protein and the crucial role played by Trp 69 in homodimerization.

    PubMed

    Bhuvanakantham, Raghavan; Ng, Mah-Lee

    2005-04-01

    The understanding of capsid (C) protein interactions with itself would provide important data on how the core is organized in flaviviruses during assembly. In this study, West Nile (WN) virus C protein was shown to form homodimers using yeast two-hybrid analysis in conjunction with mammalian two-hybrid and in vivo co-immunoprecipitation assays. To delineate the region on the C protein which mediates C-C dimerization, truncation studies were carried out. The results obtained clearly showed that the internal hydrophobic segment flanked by helix I and helix III of WN virus C protein is essential for the self-association of C protein. The crucial role played by Trp 69 in stabilizing the self-association of C protein was also demonstrated by mutating Trp to Gly/Arg/Phe. Substitution of the Trp residue with Gly/Arg abolished the dimerization, whereas substitution with Phe decreased the self-association significantly. The results of this study pinpoint a critical residue in the C protein that potentially plays a role in stabilizing the homotypic interaction. PMID:15721300

  13. Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.

    PubMed

    Syamsunarno, Mas Rizky A A; Iso, Tatsuya; Yamaguchi, Aiko; Hanaoka, Hirofumi; Putri, Mirasari; Obokata, Masaru; Sunaga, Hiroaki; Koitabashi, Norimichi; Matsui, Hiroki; Maeda, Kazuhisa; Endo, Keigo; Tsushima, Yoshito; Yokoyama, Tomoyuki; Kurabayashi, Masahiko

    2014-01-01

    Hypothermia is rapidly induced during cold exposure when thermoregulatory mechanisms, including fatty acid (FA) utilization, are disturbed. FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipose tissues and macrophages, have been identified as key molecules in the pathogenesis of overnutrition-related diseases, such as insulin resistance and atherosclerosis. We have recently shown that FABP4/5 are prominently expressed in capillary endothelial cells in the heart and skeletal muscle and play a crucial role in FA utilization in these tissues. However, the role of FABP4/5 in thermogenesis remains to be determined. In this study, we showed that thermogenesis is severely impaired in mice lacking both FABP4 and FABP5 (DKO mice), as manifested shortly after cold exposure during fasting. In DKO mice, the storage of both triacylglycerol in brown adipose tissue (BAT) and glycogen in skeletal muscle (SkM) was nearly depleted after fasting, and a biodistribution analysis using 125I-BMIPP revealed that non-esterified FAs (NEFAs) are not efficiently taken up by BAT despite the robustly elevated levels of serum NEFAs. In addition to the severe hypoglycemia observed in DKO mice during fasting, cold exposure did not induce the uptake of glucose analogue 18F-FDG by BAT. These findings strongly suggest that DKO mice exhibit pronounced hypothermia after fasting due to the depletion of energy storage in BAT and SkM and the reduced supply of energy substrates to these tissues. In conclusion, FABP4/5 play an indispensable role in thermogenesis in BAT and SkM. Our study underscores the importance of FABP4/5 for overcoming life-threatening environments, such as cold and starvation. PMID:24603714

  14. An aromatic amino acid in the coiled-coil 1 domain plays a crucial role in the auto-inhibitory mechanism of STIM1.

    PubMed

    Yu, Junwei; Zhang, Haining; Zhang, Mingshu; Deng, Yongqiang; Wang, Huiyu; Lu, Jingze; Xu, Tao; Xu, Pingyong

    2013-09-15

    STIM1 (stromal interaction molecule 1) is one of the key elements that mediate store-operated Ca²⁺ entry via CRAC (Ca²⁺- release-activated Ca²⁺) channels in immune and non-excitable cells. Under physiological conditions, the intramolecular auto-inhibitions in STIM1 C- and STIM1 N-termini play essential roles in keeping STIM1 in an inactive state. However, the auto-inhibitory mechanism of the STIM1 C-terminus is still unclear. In the present study, we first predicted a short inhibitory domain (residues 310-317) in human STIM1 that might determine the different localizations of human STIM1 from Caenorhabditis elegans STIM1 in resting cells. Next, we confirmed the prediction and further identified an aromatic amino acid residue, Tyr³¹⁶, that played a crucial role in maintaining STIM1 in a closed conformation in quiescent cells. Full-length STIM1-Y316A formed constitutive clusters near the plasma membrane and activated the CRAC channel in the resting state when co-expressed with Orai1. The introduction of a Y316A mutation caused the higher-order oligomerization of the in vitro purified STIM1 fragment containing both the auto-inhibitory domain and CAD(CRAC-activating domain).We propose that the Tyr³¹⁶ residue may be involved in the auto-inhibitory mechanism of the STIM1 C-terminus in the quiescent state. This inhibition could be achieved either by interacting with the CAD using hydrogen and/or hydrophobic bonds, or by an intermolecular interaction using repulsive forces, which maintained a dimeric STIM1. PMID:23795811

  15. L-type calcium channels play a crucial role in the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells

    SciTech Connect

    Wen, Li; Wang, Yu; Wang, Huan; Kong, Lingmin; Zhang, Liang; Chen, Xin; Ding, Yin

    2012-08-03

    results suggest that VDCC{sub L} plays a crucial role in the proliferation and osteogenic differentiation of rMSCs.

  16. Interactions between Transmembrane Helices within Monomers of the Aquaporin AtPIP2;1 Play a Crucial Role in Tetramer Formation.

    PubMed

    Yoo, Yun-Joo; Lee, Hyun Kyung; Han, Wonhee; Kim, Dae Heon; Lee, Myoung Hui; Jeon, Jouhyun; Lee, Dong Wook; Lee, Junho; Lee, Yongjik; Lee, Juhun; Kim, Jin Seok; Cho, Yunje; Han, Jin-Kwan; Hwang, Inhwan

    2016-07-01

    Aquaporin (AQP) is a water channel protein found in various subcellular membranes of both prokaryotic and eukaryotic cells. The physiological functions of AQPs have been elucidated in many organisms. However, understanding their biogenesis remains elusive, particularly regarding how they assemble into tetramers. Here, we investigated the amino acid residues involved in the tetramer formation of the Arabidopsis plasma membrane AQP AtPIP2;1 using extensive amino acid substitution mutagenesis. The mutant proteins V41A/E44A, F51A/L52A, F87A/I91A, F92A/I93A, V95A/Y96A, and H216A/L217A, harboring alanine substitutions in the transmembrane (TM) helices of AtPIP2;1 polymerized into multiple oligomeric complexes with a variable number of subunits greater than four. Moreover, these mutant proteins failed to traffic to the plasma membrane, instead of accumulating in the endoplasmic reticulum (ER). Structure-based modeling revealed that these residues are largely involved in interactions between TM helices within monomers. These results suggest that inter-TM interactions occurring both within and between monomers play crucial roles in tetramer formation in the AtPIP2;1 complex. Moreover, the assembly of AtPIP2;1 tetramers is critical for their trafficking from the ER to the plasma membrane, as well as water permeability. PMID:27142778

  17. TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments

    PubMed Central

    Liu, W; Liu, Y; Guo, T; Hu, C; Luo, H; Zhang, L; Shi, S; Cai, T; Ding, Y; Jin, Y

    2013-01-01

    Wnt signaling pathways are a highly conserved pathway, which plays an important role from the embryonic development to bone formation. The effect of Wnt pathway on osteogenesis relies on their cellular environment and the expression of target genes. However, the molecular mechanism of that remains unclear. On the basis of the preliminary results, we observed the contrary effect of canonical Wnt signaling on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in the different culture environment. Furthermore, we found that the expression level of miR-17 was also varied with the change in the culture environment. Therefore, we hypothesized that miR-17 and canonical Wnt signaling may have potential interactions, particularly the inner regulation relationship in different microenvironments. In this paper, we observed that canonical Wnt signaling promoted osteogenesis of PDLSCs in the fully culture medium, while inhibited it in the osteogenic differentiation medium. Interestingly, alteration in the expression level of endogenous miR-17 could partially reverse the different effect of canonical Wnt signaling. Furthermore, the role of miR-17 was because of its target gene TCF3 (transcription factor 3), a key transcription factor of canonical Wnt pathway. Overexpression of TCF3 attenuated the effect of miR-17 on modulating canonical Wnt signaling. Finally, we elucidated that TCF3 enhanced osteogenesis both in vitro and in vivo. In brief, the different level of miR-17 was the main cause of the different effect of canonical Wnt signaling, and TCF3 was the crucial node of miR-17–canonial Wnt signaling regulation loop. This understanding of microRNAs regulating signaling pathways in different microenvironments may pave the way for fine-tuning the process of osteogenesis in bone-related disorders. PMID:23492770

  18. Transcription of DWARF4 Plays a Crucial Role in Auxin-Regulated Root Elongation in Addition to Brassinosteroid Homeostasis in Arabidopsis thaliana

    PubMed Central

    Yoshimitsu, Yuya; Tanaka, Kiwamu; Fukuda, Wataru; Asami, Tadao; Yoshida, Shigeo; Hayashi, Ken-ichiro; Kamiya, Yuji; Jikumaru, Yusuke; Shigeta, Tomoaki; Nakamura, Yasushi; Matsuo, Tomoaki; Okamoto, Shigehisa

    2011-01-01

    The expression of DWARF4 (DWF4), which encodes a C-22 hydroxylase, is crucial for brassinosteroid (BR) biosynthesis and for the feedback control of endogenous BR levels. To advance our knowledge of BRs, we examined the effects of different plant hormones on DWF4 transcription in Arabidopsis thaliana. Semi-quantitative reverse-transcriptase PCR showed that the amount of the DWF4 mRNA precursor either decreased or increased, similarly with its mature form, in response to an exogenously applied bioactive BR, brassinolide (BL), and a BR biosynthesis inhibitor, brassinazole (Brz), respectively. The response to these chemicals in the levels of β-glucuronidase (GUS) mRNA and its enzymatic activity is similar to the response of native DWF4 mRNA in DWF4::GUS plants. Contrary to the effects of BL, exogenous auxin induced GUS activity, but this enhancement was suppressed by anti-auxins, such as α-(phenylethyl-2-one)-IAA and α-tert-butoxycarbonylaminohexyl-IAA, suggesting the involvement of SCFTIR1-mediated auxin signaling in auxin-induced DWF4 transcription. Auxin-enhanced GUS activity was observed exclusively in roots; it was the most prominent in the elongation zones of both primary and lateral roots. Furthermore, auxin-induced lateral root elongation was suppressed by both Brz application and the dwf4 mutation, and this suppression was rescued by BL, suggesting that BRs act positively on root elongation under the control of auxin. Altogether, our results indicate that DWF4 transcription plays a novel role in the BR-auxin crosstalk associated with root elongation, in addition to its role in BR homeostasis. PMID:21909364

  19. Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice.

    PubMed

    Noguchi, Takaaki; Ebina, Kosuke; Hirao, Makoto; Kawase, Ryota; Ohama, Tohru; Yamashita, Shizuya; Morimoto, Tokimitsu; Koizumi, Kota; Kitaguchi, Kazuma; Matsuoka, Hozo; Kaneshiro, Shoichi; Yoshikawa, Hideki

    2015-09-25

    A close correlation between atherosclerosis, inflammation, and osteoporosis has been recognized, although the precise mechanism remains unclear. The growth factor progranulin (PGRN) is expressed in various cells such as macrophages, leukocytes, and chondrocytes. PGRN plays critical roles in a variety of diseases, such as atherosclerosis and arthritis by inhibiting Tumor Necrosis Factor-α (TNF-α) signaling. The purpose of this study was to investigate the effect of PGRN on bone metabolism. Forty-eight-week old female homozygous PGRN knockout mice (PGRN-KO) (n = 8) demonstrated severe low bone mass in the distal femur compared to age- and sex-matched wild type C57BL/6J mice (WT) (n = 8) [BV/TV (%): 5.8 vs. 16.6; p < 0.001, trabecular number (1/mm): 1.6 vs. 3.8; p < 0.001]. In vitro, PGRN inhibited TNF-α-induced osteoclastogenesis from spleen cells of PGRN-KO mice. Moreover, PGRN significantly promoted ALP activity, osteoblast-related mRNA (ALP, osteocalcin) expression in a dose-dependent manner and up-regulated osteoblastic differentiation by down-regulating phosphorylation of ERK1/2 in mouse calvarial cells. In conclusion, PGRN may be a promising treatment target for both atherosclerosis and inflammation-related osteoporosis. PMID:26297947

  20. β-Ketoacyl-acyl Carrier Protein Synthase I (KASI) Plays Crucial Roles in the Plant Growth and Fatty Acids Synthesis in Tobacco

    PubMed Central

    Yang, Tianquan; Xu, Ronghua; Chen, Jianghua; Liu, Aizhong

    2016-01-01

    Fatty acids serve many functions in plants, but the effects of some key genes involved in fatty acids biosynthesis on plants growth and development are not well understood yet. To understand the functions of 3-ketoacyl-acyl-carrier protein synthase I (KASI) in tobacco, we isolated two KASI homologs, which we have designated NtKASI-1 and NtKASI-2. Expression analysis showed that these two KASI genes were transcribed constitutively in all tissues examined. Over-expression of NtKASI-1 in tobacco changed the fatty acid content in leaves, whereas over-expressed lines of NtKASI-2 exhibited distinct phenotypic features such as slightly variegated leaves and reduction of the fatty acid content in leaves, similar to the silencing plants of NtKASI-1 gene. Interestingly, the silencing of NtKASI-2 gene had no discernibly altered phenotypes compared to wild type. The double silencing plants of these two genes enhanced the phenotypic changes during vegetative and reproductive growth compared to wild type. These results uncovered that these two KASI genes had the partially functional redundancy, and that the KASI genes played a key role in regulating fatty acids synthesis and in mediating plant growth and development in tobacco. PMID:27509494

  1. PI3k/Akt signalling pathway plays a crucial role in the anti-inflammatory effects of curcumin in LPS-activated microglia.

    PubMed

    Cianciulli, Antonia; Calvello, Rosa; Porro, Chiara; Trotta, Teresa; Salvatore, Rosaria; Panaro, Maria Antonietta

    2016-07-01

    Microglia are resident macrophages in the central nervous system (CNS) deputed to defend against pathogens. Persistent or acute inflammation of microglia leads to CNS disorders, so regulation of pro-inflammatory responses of microglial cells is thought to be a promising therapeutic strategy to attenuate abnormal inflammatory responses observed in neurodegenerative disease. We hypothesized that curcumin supplementation could reduce the inflammatory responses of activated microglial cells modulating PI3K/Akt pathway. Different curcumin concentrations were administered as BV-2 microglia pre-treatment 1h prior to LPS stimulation. Nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression were determined by Griess reagent and western blotting, respectively. Inflammatory cytokines release was evaluated by ELISA and qRT-PCR. PI3K/Akt expression was analyzed by western blotting analysis. Curcumin significantly attenuated, in a dose-dependent manner, LPS-induced release of NO and pro-inflammatory cytokines, as well as iNOS expression. Interestingly, curcumin was able to reduce, again in a dose-dependent manner, PI3K/Akt phosphorylation as well as NF-κB activation in LPS-activated microglial cells. Overall these results suggest that curcumin plays an important role in the attenuation of LPS-induced inflammatory responses in microglial cells and that the mechanisms involve down-regulation of the PI3K/Akt signalling. PMID:27208432

  2. β-Ketoacyl-acyl Carrier Protein Synthase I (KASI) Plays Crucial Roles in the Plant Growth and Fatty Acids Synthesis in Tobacco.

    PubMed

    Yang, Tianquan; Xu, Ronghua; Chen, Jianghua; Liu, Aizhong

    2016-01-01

    Fatty acids serve many functions in plants, but the effects of some key genes involved in fatty acids biosynthesis on plants growth and development are not well understood yet. To understand the functions of 3-ketoacyl-acyl-carrier protein synthase I (KASI) in tobacco, we isolated two KASI homologs, which we have designated NtKASI-1 and NtKASI-2. Expression analysis showed that these two KASI genes were transcribed constitutively in all tissues examined. Over-expression of NtKASI-1 in tobacco changed the fatty acid content in leaves, whereas over-expressed lines of NtKASI-2 exhibited distinct phenotypic features such as slightly variegated leaves and reduction of the fatty acid content in leaves, similar to the silencing plants of NtKASI-1 gene. Interestingly, the silencing of NtKASI-2 gene had no discernibly altered phenotypes compared to wild type. The double silencing plants of these two genes enhanced the phenotypic changes during vegetative and reproductive growth compared to wild type. These results uncovered that these two KASI genes had the partially functional redundancy, and that the KASI genes played a key role in regulating fatty acids synthesis and in mediating plant growth and development in tobacco. PMID:27509494

  3. A novel aldo-keto reductase from Jatropha curcas L. (JcAKR) plays a crucial role in the detoxification of methylglyoxal, a potent electrophile.

    PubMed

    Mudalkar, Shalini; Sreeharsha, Rachapudi Venkata; Reddy, Attipalli Ramachandra

    2016-05-20

    Abiotic stress leads to the generation of reactive oxygen species (ROS) which further results in the production of reactive carbonyls (RCs) including methylglyoxal (MG). MG, an α, β-dicarbonyl aldehyde, is highly toxic to plants and the mechanism behind its detoxification is not well understood. Aldo-keto reductases (AKRs) play a role in detoxification of reactive aldehydes and ketones. In the present study, we cloned and characterised a putative AKR from Jatropha curcas (JcAKR). Phylogenetically, it forms a small clade with AKRs of Glycine max and Rauwolfia serpentina. JcAKR was heterologously expressed in Escherichia coli BL-21(DE3) cells and the identity of the purified protein was confirmed through MALDI-TOF analysis. The recombinant protein had high enzyme activity and catalytic efficiency in assays containing MG as the substrate. Protein modelling and docking studies revealed MG was efficiently bound to JcAKR. Under progressive drought and salinity stress, the enzyme and transcript levels of JcAKR were higher in leaves compared to roots. Further, the bacterial and yeast cells expressing JcAKR showed more tolerance towards PEG (5%), NaCl (200mM) and MG (5mM) treatments compared to controls. In conclusion, our results project JcAKR as a possible and potential target in crop improvement for abiotic stress tolerance. PMID:26995646

  4. A CD153+CD4+ T follicular cell population with cell-senescence features plays a crucial role in lupus pathogenesis via osteopontin production.

    PubMed

    Tahir, Suhail; Fukushima, Yuji; Sakamoto, Keiko; Sato, Kyosuke; Fujita, Harumi; Inoue, Joe; Uede, Toshimitsu; Hamazaki, Yoko; Hattori, Masakazu; Minato, Nagahiro

    2015-06-15

    Immune aging results in diminished adaptive immunity and increased risk for autoimmunity. We previously reported a unique PD-1(+) CD44(high)CD4(+) T cell population that increases with age in normal mice. In this study, we indicate that the age-dependent PD-1(+) CD44(high)CD4(+) T cells develop as unique T follicular (TF) cells in a B cell-dependent manner and consist of two subpopulations, as follows: CD153(+) cells preferentially secreting abundant osteopontin on TCR stimulation and CD153(-) cells that are apparently TCR anergic. These unique TF cells with essentially similar features increase much earlier and are accumulated in the spontaneous germinal centers (GCs) in lupus-prone female BWF1 (f-BWF1) mice. These TF cells showed characteristic cell-senescence features and developed in association with extensive CD4(+) T cell proliferation in vivo, suggesting replicative senescence. Although the CD153(+) TF cells were defective in proliferation capacity, they were quite stable and specifically responded to self GC-B cells to secret abundant osteopontin, which inhibited B cell receptor-induced GC-B cell apoptosis in f-BWF1 mice. Transfer of CD153(+) PD-1(+) CD4(+) T cells promoted the growth of spontaneous GCs, whereas administration of anti-osteopontin Ab suppressed GC enlargement and anti-nuclear Ab production and ameliorated clinical lupus nephritis of f-BWF1 mice. Current results suggest that senescent CD153(+) TF cells generated as a consequence of extensive endogenous CD4(+) T cell proliferation play an essential, if not sufficient, role in lupus pathogenesis in lupus-prone genetic background and may also contribute to an increased autoimmunity risk with age. PMID:25972477

  5. The Thioredoxin GbNRX1 Plays a Crucial Role in Homeostasis of Apoplastic Reactive Oxygen Species in Response to Verticillium dahliae Infection in Cotton.

    PubMed

    Li, Yuan-Bao; Han, Li-Bo; Wang, Hai-Yun; Zhang, Jie; Sun, Shu-Tao; Feng, De-Qin; Yang, Chun-Lin; Sun, Yong-Duo; Zhong, Nai-Qin; Xia, Gui-Xian

    2016-04-01

    Examining the proteins that plants secrete into the apoplast in response to pathogen attack provides crucial information for understanding the molecular mechanisms underlying plant innate immunity. In this study, we analyzed the changes in the root apoplast secretome of the Verticillium wilt-resistant island cotton cv Hai 7124 (Gossypium barbadense) upon infection with Verticillium dahliae Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry analysis identified 68 significantly altered spots, corresponding to 49 different proteins. Gene ontology annotation indicated that most of these proteins function in reactive oxygen species (ROS) metabolism and defense response. Of the ROS-related proteins identified, we further characterized a thioredoxin, GbNRX1, which increased in abundance in response to V. dahliae challenge, finding that GbNRX1 functions in apoplastic ROS scavenging after the ROS burst that occurs upon recognition of V. dahliae Silencing of GbNRX1 resulted in defective dissipation of apoplastic ROS, which led to higher ROS accumulation in protoplasts. As a result, the GbNRX1-silenced plants showed reduced wilt resistance, indicating that the initial defense response in the root apoplast requires the antioxidant activity of GbNRX1. Together, our results demonstrate that apoplastic ROS generation and scavenging occur in tandem in response to pathogen attack; also, the rapid balancing of redox to maintain homeostasis after the ROS burst, which involves GbNRX1, is critical for the apoplastic immune response. PMID:26869704

  6. Amino acid residues 201-205 in C-terminal acidic tail region plays a crucial role in antibacterial activity of HMGB1

    PubMed Central

    2009-01-01

    Background Antibacterial activity is a novel function of high-mobility group box 1 (HMGB1). However, the functional site for this new effect is presently unknown. Methods and Results In this study, recombinant human HMGB1 A box and B box (rHMGB1 A box, rHMGB1 B box), recombinant human HMGB1 (rHMGB1) and the truncated C-terminal acidic tail mutant (tHMGB1) were prepared by the prokaryotic expression system. The C-terminal acidic tail (C peptide) was synthesized, which was composed of 30 amino acid residues. Antibacterial assays showed that both the full length rHMGB1 and the synthetic C peptide alone could efficiently inhibit bacteria proliferation, but rHMGB1 A box and B box, and tHMGB1 lacking the C-terminal acidic tail had no antibacterial function. These results suggest that C-terminal acidic tail is the key region for the antibacterial activity of HMGB1. Furthermore, we prepared eleven different deleted mutants lacking several amino acid residues in C-terminal acidic tail of HMGB1. Antibacterial assays of these mutants demonstrate that the amino acid residues 201-205 in C-terminal acidic tail region is the core functional site for the antibacterial activity of the molecule. Conclusion In sum, these results define the key region and the crucial site in HMGB1 for its antibacterial function, which is helpful to illustrating the antibacterial mechanisms of HMGB1. PMID:19751520

  7. The Thioredoxin GbNRX1 Plays a Crucial Role in Homeostasis of Apoplastic Reactive Oxygen Species in Response to Verticillium dahliae Infection in Cotton1[OPEN

    PubMed Central

    Zhang, Jie; Sun, Shu-Tao; Feng, De-Qin; Yang, Chun-Lin; Sun, Yong-Duo; Zhong, Nai-Qin

    2016-01-01

    Examining the proteins that plants secrete into the apoplast in response to pathogen attack provides crucial information for understanding the molecular mechanisms underlying plant innate immunity. In this study, we analyzed the changes in the root apoplast secretome of the Verticillium wilt-resistant island cotton cv Hai 7124 (Gossypium barbadense) upon infection with Verticillium dahliae. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry analysis identified 68 significantly altered spots, corresponding to 49 different proteins. Gene ontology annotation indicated that most of these proteins function in reactive oxygen species (ROS) metabolism and defense response. Of the ROS-related proteins identified, we further characterized a thioredoxin, GbNRX1, which increased in abundance in response to V. dahliae challenge, finding that GbNRX1 functions in apoplastic ROS scavenging after the ROS burst that occurs upon recognition of V. dahliae. Silencing of GbNRX1 resulted in defective dissipation of apoplastic ROS, which led to higher ROS accumulation in protoplasts. As a result, the GbNRX1-silenced plants showed reduced wilt resistance, indicating that the initial defense response in the root apoplast requires the antioxidant activity of GbNRX1. Together, our results demonstrate that apoplastic ROS generation and scavenging occur in tandem in response to pathogen attack; also, the rapid balancing of redox to maintain homeostasis after the ROS burst, which involves GbNRX1, is critical for the apoplastic immune response. PMID:26869704

  8. Evidence for Emergency Vaccination Having Played a Crucial Role to Control the 1965/66 Foot-and-Mouth Disease Outbreak in Switzerland

    PubMed Central

    Zingg, Dana; Häsler, Stephan; Schuepbach-Regula, Gertraud; Schwermer, Heinzpeter; Dürr, Salome

    2015-01-01

    Foot-and-mouth disease (FMD) is a highly contagious disease that caused several large outbreaks in Europe in the last century. The last important outbreak in Switzerland took place in 1965/66 and affected more than 900 premises and more than 50,000 animals were slaughtered. Large-scale emergency vaccination of the cattle and pig population has been applied to control the epidemic. In recent years, many studies have used infectious disease models to assess the impact of different disease control measures, including models developed for diseases exotic for the specific region of interest. Often, the absence of real outbreak data makes a validation of such models impossible. This study aimed to evaluate whether a spatial, stochastic simulation model (the Davis Animal Disease Simulation model) can predict the course of a Swiss FMD epidemic based on the available historic input data on population structure, contact rates, epidemiology of the virus, and quality of the vaccine. In addition, the potential outcome of the 1965/66 FMD epidemic without application of vaccination was investigated. Comparing the model outcomes to reality, only the largest 10% of the simulated outbreaks approximated the number of animals being culled. However, the simulation model highly overestimated the number of culled premises. While the outbreak duration could not be well reproduced by the model compared to the 1965/66 epidemic, it was able to accurately estimate the size of the area infected. Without application of vaccination, the model predicted a much higher mean number of culled animals than with vaccination, demonstrating that vaccination was likely crucial in disease control for the Swiss FMD outbreak in 1965/66. The study demonstrated the feasibility to analyze historical outbreak data with modern analytical tools. However, it also confirmed that predicted epidemics from a most carefully parameterized model cannot integrate all eventualities of a real epidemic. Therefore, decision

  9. Lcl of Legionella pneumophila Is an Immunogenic GAG Binding Adhesin That Promotes Interactions with Lung Epithelial Cells and Plays a Crucial Role in Biofilm Formation ▿

    PubMed Central

    Duncan, Carla; Prashar, Akriti; So, Jannice; Tang, Patrick; Low, Donald E.; Terebiznik, Mauricio; Guyard, Cyril

    2011-01-01

    Legionellosis is mostly caused by Legionella pneumophila and is defined by a severe respiratory illness with a case fatality rate ranging from 5 to 80%. In vitro and in vivo, interactions of L. pneumophila with lung epithelial cells are mediated by the sulfated glycosaminoglycans (GAGs) of the host extracellular matrix. In this study, we have identified several Legionella heparin binding proteins. We have shown that one of these proteins, designated Lcl, is a polymorphic adhesin of L. pneumophila that is produced during legionellosis. Homologues of Lcl are ubiquitous in L. pneumophila serogroups but are undetected in other Legionella species. Recombinant Lcl binds to GAGs, and a Δlpg2644 mutant demonstrated reduced binding to GAGs and human lung epithelial cells. Importantly, we showed that the Δlpg2644 strain is dramatically impaired in biofilm formation. These data delineate the role of Lcl in the GAG binding properties of L. pneumophila and provide molecular evidence regarding its role in L. pneumophila adherence and biofilm formation. PMID:21422183

  10. Lcl of Legionella pneumophila is an immunogenic GAG binding adhesin that promotes interactions with lung epithelial cells and plays a crucial role in biofilm formation.

    PubMed

    Duncan, Carla; Prashar, Akriti; So, Jannice; Tang, Patrick; Low, Donald E; Terebiznik, Mauricio; Guyard, Cyril

    2011-06-01

    Legionellosis is mostly caused by Legionella pneumophila and is defined by a severe respiratory illness with a case fatality rate ranging from 5 to 80%. In vitro and in vivo, interactions of L. pneumophila with lung epithelial cells are mediated by the sulfated glycosaminoglycans (GAGs) of the host extracellular matrix. In this study, we have identified several Legionella heparin binding proteins. We have shown that one of these proteins, designated Lcl, is a polymorphic adhesin of L. pneumophila that is produced during legionellosis. Homologues of Lcl are ubiquitous in L. pneumophila serogroups but are undetected in other Legionella species. Recombinant Lcl binds to GAGs, and a Δlpg2644 mutant demonstrated reduced binding to GAGs and human lung epithelial cells. Importantly, we showed that the Δlpg2644 strain is dramatically impaired in biofilm formation. These data delineate the role of Lcl in the GAG binding properties of L. pneumophila and provide molecular evidence regarding its role in L. pneumophila adherence and biofilm formation. PMID:21422183

  11. The Arabidopsis homolog of human minor spliceosomal protein U11-48K plays a crucial role in U12 intron splicing and plant development.

    PubMed

    Xu, Tao; Kim, Bo Mi; Kwak, Kyung Jin; Jung, Hyun Ju; Kang, Hunseung

    2016-05-01

    The minor U12 introns are removed from precursor mRNAs by the U12 intron-specific minor spliceosome. Among the seven ribonucleoproteins unique to the minor spliceosome, denoted as U11/U12-20K, U11/U12-25K, U11/U12-31K, U11/U12-65K, U11-35K, U11-48K, and U11-59K, the roles of only U11/U12-31K and U11/U12-65K have been demonstrated in U12 intron splicing and plant development. Here, the functional role of the Arabidopsis homolog of human U11-48K in U12 intron splicing and the development of Arabidopsis thaliana was examined using transgenic knockdown plants. The u11-48k mutants exhibited several defects in growth and development, such as severely arrested primary inflorescence stems, formation of serrated leaves, production of many rosette leaves after bolting, and delayed senescence. The splicing of most U12 introns analyzed was impaired in the u11-48k mutants. Comparative analysis of the splicing defects and phenotypes among the u11/u12-31k, u11-48k, and u11/12-65k mutants showed that the severity of abnormal development was closely correlated with the degree of impairment in U12 intron splicing. Taken together, these results provide compelling evidence that the Arabidopsis homolog of human U11-48K protein, as well as U11/U12-31K and U11/U12-65K proteins, is necessary for correct splicing of U12 introns and normal plant growth and development. PMID:27091878

  12. The Arabidopsis homolog of human minor spliceosomal protein U11-48K plays a crucial role in U12 intron splicing and plant development

    PubMed Central

    Xu, Tao; Kim, Bo Mi; Kwak, Kyung Jin; Jung, Hyun Ju; Kang, Hunseung

    2016-01-01

    The minor U12 introns are removed from precursor mRNAs by the U12 intron-specific minor spliceosome. Among the seven ribonucleoproteins unique to the minor spliceosome, denoted as U11/U12-20K, U11/U12-25K, U11/U12-31K, U11/U12-65K, U11-35K, U11-48K, and U11-59K, the roles of only U11/U12-31K and U11/U12-65K have been demonstrated in U12 intron splicing and plant development. Here, the functional role of the Arabidopsis homolog of human U11-48K in U12 intron splicing and the development of Arabidopsis thaliana was examined using transgenic knockdown plants. The u11-48k mutants exhibited several defects in growth and development, such as severely arrested primary inflorescence stems, formation of serrated leaves, production of many rosette leaves after bolting, and delayed senescence. The splicing of most U12 introns analyzed was impaired in the u11-48k mutants. Comparative analysis of the splicing defects and phenotypes among the u11/u12-31k, u11-48k, and u11/12-65k mutants showed that the severity of abnormal development was closely correlated with the degree of impairment in U12 intron splicing. Taken together, these results provide compelling evidence that the Arabidopsis homolog of human U11-48K protein, as well as U11/U12-31K and U11/U12-65K proteins, is necessary for correct splicing of U12 introns and normal plant growth and development. PMID:27091878

  13. Glucose-regulated protein 78 may play a crucial role in promoting the pulmonary microvascular remodeling in a rat model of hepatopulmonary syndrome

    PubMed Central

    Zhang, Huiying; Lv, Minli; Zhao, Zhongfu; Jia, Jiantao; Zhang, Lili; Xiao, Peng; Wang, Limin; Li, Chen; Ji, Jingquan; Tian, Xiaoxia; Li, Xujiong; Fan, Yimin; Lai, Lina; Liu, Yan; Li, Baohong; Zhang, Cuiying; Liu, Mingshe; Guo, Jianhong; Han, Dewu; Ji, Cheng

    2015-01-01

    Objective This study is to investigate the role of glucose-regulated protein 78 (GRP78) in the pulmonary microvascular remodeling during hepatopulmonary syndrome (HPS) development. Methods The rat models with liver cirrhosis and HPS were induced by multiple pathogenic factors for 4 to 8 wk. The concentrations of alanine transferase (ALT) and endotoxin in plasma were detected in the models, followed by the detection of GRP78 expression. RT-PCR, quantitative real-time PCR and Western blotting were employed to assess the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), respectively. Immunohistochemistry staining was used to examine the expression of a specific vascular marker, factor VIII-related antigen (FVIII-RAg), and several cell proliferation- and apoptosis-related proteins, including CHOP/GADD153, caspase-12, Bcl-2 and nuclear factor (NF)-κB. Results The levels of endotoxin and ALT in plasma were gradually increased as the disease progressed, so did GRP78, which were in a positive correlation. The expression levels of VEGF (both mRNA and protein) and FVIII-RAg were significantly elevated in the HPS models, indicating active angiogenesis, which was also positively correlated with GRP78 expression. Furthermore, the expression levels of the pro-apoptotic proteins of CHOP/GADD153 and caspase-12 were dramatically decreased, while the anti-apoptotic proteins of Bcl-2 and NF-κB were significantly elevated, in the HPS models. There were also close correlations between these proteins and GRP78. Conclusions Over-expression of GRP78 in lungs may be the critical pathogenic factor for HPS. Through promoting cell proliferation and survival and inhibiting apoptosis, GRP78 may promote the pulmonary microvascular remodeling in HPS pathogenesis. Our results provide a potential therapeutic target for clinical prevention and treatment for HPS and related complications. PMID:24768185

  14. Induction of Heme Oxygenase-1 by Na+-H+ Exchanger 1 Protein Plays a Crucial Role in Imatinib-resistant Chronic Myeloid Leukemia Cells*

    PubMed Central

    Ma, Dan; Fang, Qin; Wang, Ping; Gao, Rui; Wu, Weibing; Lu, Tangsheng; Cao, Lu; Hu, Xiuying; Wang, Jishi

    2015-01-01

    Resistance toward imatinib (IM) and other BCR/ABL tyrosine kinase inhibitors remains troublesome in the treatment of advanced stage chronic myeloid leukemia (CML). The aim of this study was to estimate the reversal effects of down-regulation of Na+/H+ exchanger 1 (NHE1) on the chemoresistance of BCR-ABL-positive leukemia patients' cells and cell lines. After treatment with the specific NHE1 inhibitor cariporide to decrease intracellular pH (pHi), the heme oxygenase-1 (HO-1) levels of the K562R cell line and cells from IM-insensitive CML patients decreased. HO-1, as a Bcr/Abl-dependent survival molecule in CML cells, is important for the resistance to tyrosine kinase inhibitors in patients with newly diagnosed CML or IM-resistant CML. Silencing PKC-β and Nrf-2 or treatment with inhibitors of p38 pathways obviously blocked NHE1-induced HO-1 expression. Furthermore, treatment with HO-1 or p38 inhibitor plus IM increased the apoptosis of the K562R cell line and IM-insensitive CML patients' cells. Inhibiting HO-1 enhanced the activation of caspase-3 and poly(ADP-ribose) polymerase-1. Hence, the results support the anti-apoptotic role of HO-1 induced by NHE1 in the K562R cell line and IM-insensitive CML patients and provide a mechanism by which inducing HO-1 expression via the PKC-β/p38-MAPK pathway may promote tumor resistance to oxidative stress. PMID:25802333

  15. Modulation of Macrophage Polarization and HMGB1-TLR2/TLR4 Cascade Plays a Crucial Role for Cardiac Remodeling in Senescence-Accelerated Prone Mice

    PubMed Central

    Arumugam, Somasundaram; Sreedhar, Remya; Palaniyandi, Suresh S.; Krishnamurthy, Prasanna; Quevedo, Joao; Watanabe, Kenichi; Konishi, Tetsuya; Thandavarayan, Rajarajan A.

    2016-01-01

    The aim of this study was to investigate the role of macrophage polarization in aging heart. Macrophage differentiation is pathogenically linked to many inflammatory and immune disorders. It is often preceded by myocardial inflammation, which is characterized by increased cardiac damage and pro-inflammatory cytokine levels. Therefore, we investigated the hypothesis that senescence accelerated-prone (SAMP8) mice cardiac tissue would develop macrophage polarization compared with senescence-resistant control (SAMR1) mice. Both SAMP8 and SAMR1 mice were sacrificed when they became six month old. We evaluated, histo-pathological changes and modifications in protein expression by Western blotting and immuno-histochemical staining for M1 and M2 macrophage markers, high mobility group protein (HMG)B1 and its cascade proteins, pro-inflammatory factors and inflammatory cytokines in cardiac tissue. We observed significant upregulation of HMGB1, toll-like receptor (TLR)2, TLR4, nuclear factor (NF)κB p65, tumor necrosis factor (TNF)α, cyclooxygenase (COX)2, interferon (IFN)γ, interleukin (IL)-1β, IL-6 and M1 like macrophage specific marker cluster of differentiation (CD)68 expressions in SAMP8 heart. In contrast, M2 macrophage specific marker CD36, and IL-10 expressions were down-regulated in SAMP8 mice. The results from the study demonstrated that, HMGB1-TLR2/TLR4 signaling cascade and induction of phenotypic switching to M1 macrophage polarization in SAMP8 mice heart would be one of the possible reasons behind the cardiac dysfunction and thus it could become an important therapeutic target to improve the age related cardiac dysfunction. PMID:27070323

  16. Learning through Role Play.

    ERIC Educational Resources Information Center

    Simmons, Sandra

    2001-01-01

    Explains how role playing can provide enriching experiences that develop children's literacy and numeracy skills. Lists key ingredients of good role playing and suggests ways to plan them and prepare space for them. (SK)

  17. Colleges Play Crucial Role in Military's Restructuring

    ERIC Educational Resources Information Center

    Fischer, Karin

    2009-01-01

    Across the U.S., colleges like Anne Arundel Community College (Maryland) are devising strategies and designing curricula to meet the demands created by the substantial troop shifts. They are adding degree and certificate programs and refashioning or expanding others, in areas as diverse as network security, procurement and contracting, and…

  18. Role-Playing Mitosis.

    ERIC Educational Resources Information Center

    Wyn, Mark A.; Stegink, Steven J.

    2000-01-01

    Introduces a role playing activity that actively engages students in the learning process of mitosis. Students play either chromosomes carrying information, or cells in the cell membrane. (Contains 11 references.) (Author/YDS)

  19. Role Playing and Skits

    ERIC Educational Resources Information Center

    Letwin, Robert, Ed.

    1975-01-01

    Explores non-scripted role playing, dialogue role playing, sociodrama, and skits as variations of simulation techniques. Provides step-by-step guidelines for conducting such sessions. Successful Meetings, Bill Communications, Inc., 1422 Chestnut Street, Philadelphia, Pa. 19102. Subscription Rates: yearly (US, Canada, Mexico) $14.00; elsewhere,…

  20. The crucial role of recess in school.

    PubMed

    Murray, Robert; Ramstetter, Catherine

    2013-01-01

    Recess is at the heart of a vigorous debate over the role of schools in promoting the optimal development of the whole child. A growing trend toward reallocating time in school to accentuate the more academic subjects has put this important facet of a child's school day at risk. Recess serves as a necessary break from the rigors of concentrated, academic challenges in the classroom. But equally important is the fact that safe and well-supervised recess offers cognitive, social, emotional, and physical benefits that may not be fully appreciated when a decision is made to diminish it. Recess is unique from, and a complement to, physical education--not a substitute for it. The American Academy of Pediatrics believes that recess is a crucial and necessary component of a child's development and, as such, it should not be withheld for punitive or academic reasons. PMID:23277311

  1. The RNA-Binding Chaperone Hfq Is an Important Global Regulator of Gene Expression in Pasteurella multocida and Plays a Crucial Role in Production of a Number of Virulence Factors, Including Hyaluronic Acid Capsule.

    PubMed

    Mégroz, Marianne; Kleifeld, Oded; Wright, Amy; Powell, David; Harrison, Paul; Adler, Ben; Harper, Marina; Boyce, John D

    2016-05-01

    The Gram-negative bacterium Pasteurella multocida is the causative agent of a number of economically important animal diseases, including avian fowl cholera. Numerous P. multocida virulence factors have been identified, including capsule, lipopolysaccharide (LPS), and filamentous hemagglutinin, but little is known about how the expression of these virulence factors is regulated. Hfq is an RNA-binding protein that facilitates riboregulation via interaction with small noncoding RNA (sRNA) molecules and their mRNA targets. Here, we show that a P. multocida hfq mutant produces significantly less hyaluronic acid capsule during all growth phases and displays reduced in vivo fitness. Transcriptional and proteomic analyses of the hfq mutant during mid-exponential-phase growth revealed altered transcript levels for 128 genes and altered protein levels for 78 proteins. Further proteomic analyses of the hfq mutant during the early exponential growth phase identified 106 proteins that were produced at altered levels. Both the transcript and protein levels for genes/proteins involved in capsule biosynthesis were reduced in the hfq mutant, as were the levels of the filamentous hemagglutinin protein PfhB2 and its secretion partner LspB2. In contrast, there were increased expression levels of three LPS biosynthesis genes, encoding proteins involved in phosphocholine and phosphoethanolamine addition to LPS, suggesting that these genes are negatively regulated by Hfq-dependent mechanisms. Taken together, these data provide the first evidence that Hfq plays a crucial role in regulating the global expression of P. multocida genes, including the regulation of key P. multocida virulence factors, capsule, LPS, and filamentous hemagglutinin. PMID:26883595

  2. The Crucial Role of Recess in Schools

    ERIC Educational Resources Information Center

    Ramstetter, Catherine L.; Murray, Robert; Garner, Andrew S.

    2010-01-01

    Background: Recess is at the heart of a vigorous debate over the role of schools in promoting optimal child development and well-being. Reallocating time to accentuate academic concerns is a growing trend and has put recess at risk. Conversely, pressure to increase activity in school has come from efforts to combat childhood obesity. The purpose…

  3. The Drosophila melanogaster DNA Ligase IV gene plays a crucial role in the repair of radiation-induced DNA double-strand breaks and acts synergistically with Rad54.

    PubMed Central

    Gorski, Marcin M; Eeken, Jan C J; de Jong, Anja W M; Klink, Ilse; Loos, Marjan; Romeijn, Ron J; van Veen, Bert L; Mullenders, Leon H; Ferro, Wouter; Pastink, Albert

    2003-01-01

    DNA Ligase IV has a crucial role in double-strand break (DSB) repair through nonhomologous end joining (NHEJ). Most notably, its inactivation leads to embryonic lethality in mammals. To elucidate the role of DNA Ligase IV (Lig4) in DSB repair in a multicellular lower eukaryote, we generated viable Lig4-deficient Drosophila strains by P-element-mediated mutagenesis. Embryos and larvae of mutant lines are hypersensitive to ionizing radiation but hardly so to methyl methanesulfonate (MMS) or the crosslinking agent cis-diamminedichloroplatinum (cisDDP). To determine the relative contribution of NHEJ and homologous recombination (HR) in Drosophila, Lig4; Rad54 double-mutant flies were generated. Survival studies demonstrated that both HR and NHEJ have a major role in DSB repair. The synergistic increase in sensitivity seen in the double mutant, in comparison with both single mutants, indicates that both pathways partially overlap. However, during the very first hours after fertilization NHEJ has a minor role in DSB repair after exposure to ionizing radiation. Throughout the first stages of embryogenesis of the fly, HR is the predominant pathway in DSB repair. At late stages of development NHEJ also becomes less important. The residual survival of double mutants after irradiation strongly suggests the existence of a third pathway for the repair of DSBs in Drosophila. PMID:14704177

  4. The crucial role of neutrophil granulocytes in bone fracture healing.

    PubMed

    Kovtun, A; Bergdolt, S; Wiegner, R; Radermacher, P; Huber-Lang, M; Ignatius, A

    2016-01-01

    Delayed bone fracture healing and the formation of non-unions represent an important clinical problem, particularly in polytrauma patients who suffer from posttraumatic systemic inflammation. However, the underlying pathomechanisms remain unclear. Neutrophil granulocytes are crucial effector cells in the systemic immune response and represent the most abundant immune cell population in the early fracture haematoma. Here we investigated the role of neutrophils in a mouse model of uncomplicated fracture healing and compromised fracture healing induced by an additional thoracic trauma. Twenty four hours before injury, 50 % of the mice were systemically treated with an anti-Ly-6G-antibody to reduce neutrophil numbers. In the isolated fracture model, Ly-6G-Ab treatment significantly increased the concentration of both pro- and anti-inflammatory cytokines, including interleukin (IL)-6 and IL-10, and chemokines, for example, C-X-C motif ligand 1 (CXCL1) and monocyte chemotactic protein-1 (MCP-1), in the fracture haematoma. Monocyte/macrophage recruitment was also significantly enhanced. After 21 d, bone regeneration was considerably impaired as demonstrated by significantly diminished bone content and impaired mechanical properties of the fracture callus. These results indicate that undisturbed neutrophil recruitment and function in the inflammatory phase after fracture is crucial to initiate downstream responses leading to bone regeneration. In the combined trauma model, the reduction of neutrophil numbers ameliorated pulmonary inflammation but did not provoke any significant effect on bone regeneration, suggesting that neutrophils may not play a crucial pathomechanistic role in compromised fracture healing induced by an additional thoracic trauma. PMID:27452963

  5. Hydrogen embrittlement of aluminum: the crucial role of vacancies.

    PubMed

    Lu, Gang; Kaxiras, Efthimios

    2005-04-22

    We report first-principles calculations which demonstrate that vacancies can combine with hydrogen impurities in bulk aluminum and play a crucial role in the embrittlement of this prototypical ductile solid. Our studies of hydrogen-induced vacancy superabundant formation and vacancy clusterization in aluminum lead to the conclusion that a large number of H atoms (up to 12) can be trapped at a single vacancy, which overcompensates the energy cost to form the defect. In the presence of trapped H atoms, three nearest-neighbor single vacancies which normally would repel each other, aggregate to form a trivacancy on the slip plane of Al, acting as embryos for microvoids and cracks and resulting in ductile rupture along these planes. PMID:15904157

  6. Crucial Role of Vitamin D in the Musculoskeletal System.

    PubMed

    Wintermeyer, Elke; Ihle, Christoph; Ehnert, Sabrina; Stöckle, Ulrich; Ochs, Gunnar; de Zwart, Peter; Flesch, Ingo; Bahrs, Christian; Nussler, Andreas K

    2016-01-01

    Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when the skin is exposed to initiate vitamin D synthesis. However, since vitamin D is biologically inert when obtained from sun exposure or diet, it must first be activated in human beings before functioning. The kidney and the liver play here a crucial role by hydroxylation of vitamin D to 25-hydroxyvitamin D in the liver and to 1,25-dihydroxyvitamin D in the kidney. In the past decades, it has been proven that vitamin D deficiency is involved in many diseases. Due to vitamin D's central role in the musculoskeletal system and consequently the strong negative impact on bone health in cases of vitamin D deficiency, our aim was to underline its importance in bone physiology by summarizing recent findings on the correlation of vitamin D status and rickets, osteomalacia, osteopenia, primary and secondary osteoporosis as well as sarcopenia and musculoskeletal pain. While these diseases all positively correlate with a vitamin D deficiency, there is a great controversy regarding the appropriate vitamin D supplementation as both positive and negative effects on bone mineral density, musculoskeletal pain and incidence of falls are reported. PMID:27258303

  7. Crucial Role of Vitamin D in the Musculoskeletal System

    PubMed Central

    Wintermeyer, Elke; Ihle, Christoph; Ehnert, Sabrina; Stöckle, Ulrich; Ochs, Gunnar; de Zwart, Peter; Flesch, Ingo; Bahrs, Christian; Nussler, Andreas K.

    2016-01-01

    Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when the skin is exposed to initiate vitamin D synthesis. However, since vitamin D is biologically inert when obtained from sun exposure or diet, it must first be activated in human beings before functioning. The kidney and the liver play here a crucial role by hydroxylation of vitamin D to 25-hydroxyvitamin D in the liver and to 1,25-dihydroxyvitamin D in the kidney. In the past decades, it has been proven that vitamin D deficiency is involved in many diseases. Due to vitamin D’s central role in the musculoskeletal system and consequently the strong negative impact on bone health in cases of vitamin D deficiency, our aim was to underline its importance in bone physiology by summarizing recent findings on the correlation of vitamin D status and rickets, osteomalacia, osteopenia, primary and secondary osteoporosis as well as sarcopenia and musculoskeletal pain. While these diseases all positively correlate with a vitamin D deficiency, there is a great controversy regarding the appropriate vitamin D supplementation as both positive and negative effects on bone mineral density, musculoskeletal pain and incidence of falls are reported. PMID:27258303

  8. Red clover HCT2, a hydroxycinnamoyl-coenzyme A:malate hydroxycinnamoyl transferase, plays a crucial role in biosynthesis of phaselic acid and other hydroxycinnamoyl-malate esters in vivo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In red clover (Trifolium pratense) leaves, phaselic acid (2-O-caffeoyl-L-malate) accumulates to several mmol kg-1 fresh weight and is a crucial component of a natural system that prevents protein breakdown during harvest and storage of this forage crop. Previously, we identified HCT2, a red clover g...

  9. Gas nanobubbles and aqueous nanostructures: the crucial role of dynamization.

    PubMed

    Demangeat, Jean-Louis

    2015-04-01

    Nanobubbles (NBs) have been a subject of intensive research over the past decade. Their peculiar characteristics, including extremely low buoyancy, longevity, enhanced solubility of oxygen in water, zeta potentials and burst during collapse, have led to many applications in the industrial, biological and medical fields. NBs may form spontaneously from dissolved gas but the process is greatly enhanced by gas supersaturation and mechanical actions such as dynamization. Therefore, the formation of NBs during the preparation of homeopathic dilutions under atmospheric pressure cannot be ignored. I suggested in 2009 the involvement of NBs in nanometric superstructures revealed in high dilutions using NMR relaxation. These superstructures seemed to increase in size with dilution, well into the ultramolecular range (>12c). I report here new experiments that confirm the involvement of NBs and prove the crucial role of dynamization to create superstructures specific to the solute. A second dynamization was shown to enhance or regenerate these superstructures. I postulate that superstructures result from a nucleation process of NBs around the solute, with shells of highly organized water (with ions and silicates if any) which protect the solute against out-diffusion and behave as nucleation centres for further dilution steps. The sampling tip may play an active role by catching the superstructures and thus carry the encaged solute across the dilution range, possibly up to the ultramolecular range. The superstructures were not observed at low dilution, probably because of a destructuring of the solvent by the solute and/or of an inadequate gas/solute ratio. PMID:25869975

  10. Dielectric boundary force and its crucial role in gramicidin

    NASA Astrophysics Data System (ADS)

    Nadler, Boaz; Hollerbach, Uwe; Eisenberg, R. S.

    2003-08-01

    In an electrostatic problem with nonuniform geometry, a charge Q in one region induces surface charges [called dielectric boundary charges (DBC)] at boundaries between different dielectrics. These induced surface charges, in return, exert a force [called dielectric boundary force (DBF)] on the charge Q that induced them. The DBF is often overlooked. It is not present in standard continuum theories of (point) ions in or near membranes and proteins, such as Gouy-Chapman, Debye-Huckel, Poisson-Boltzmann or Poisson-Nernst- Planck. The DBF is important when a charge Q is near dielectric interfaces, for example, when ions permeate through protein channels embedded in biological membranes. In this paper, we define the DBF and calculate it explicitly for a planar dielectric wall and for a tunnel geometry resembling the ionic channel gramicidin. In general, we formulate the DBF in a form useful for continuum theories, namely, as a solution of a partial differential equation with boundary conditions. The DBF plays a crucial role in the permeation of ions through the gramicidin channel. A positive ion in the channel produces a DBF of opposite sign to that of the fixed charge force (FCF) produced by the permanent charge of the gramicidin polypeptide, and so the net force on the positive ion is reduced. A negative ion creates a DBF of the same sign as the FCF and so the net (repulsive) force on the negative ion is increased. Thus, a positive ion can permeate the channel, while a negative ion is excluded from it. In gramicidin, it is this balance between the FCF and DBF that allows only singly charged positive ions to move into and through the channel. The DBF is not directly responsible, however, for selectivity between the alkali metal ions (e.g., Li+, Na+, K+): we prove that the DBF on a mobile spherical ion is independent of the ion’s radius.

  11. Crucial role of astrocytes in temporal lobe epilepsy.

    PubMed

    Steinhäuser, C; Grunnet, M; Carmignoto, G

    2016-05-26

    Astrocytes sense and respond to synaptic activity through activation of different neurotransmitter receptors and transporters. Astrocytes are also coupled by gap junctions, which allow these cells to redistribute through the glial network the K(+) ions excessively accumulated at sites of intense neuronal activity. Work over the past two decades has revealed important roles for astrocytes in brain physiology, and it is therefore not surprising that recent studies unveiled their involvement in the etiology of neurological disorders such as epilepsy. Investigation of specimens from patients with pharmacoresistant temporal lobe epilepsy and epilepsy models revealed alterations in expression, localization and function of astrocytic connexins, K(+) and water channels. In addition, disturbed gliotransmission as well as malfunction of glutamate transporters and of the astrocytic glutamate- and adenosine-converting enzymes - glutamine synthetase and adenosine kinase, respectively - have been observed in epileptic tissues. Accordingly, increasing evidence indicates that dysfunctional astrocytes are crucially involved in processes leading to epilepsy. These new insights might foster the search for new targets for the development of new, more efficient anti-epileptogenic therapies. PMID:25592426

  12. Psychiatrists' Perceptions of Role-Playing Games.

    PubMed

    Lis, Eric; Chiniara, Carl; Biskin, Robert; Montoro, Richard

    2015-09-01

    The literature has seen a surge in research on the mental health impacts of technologies such as Facebook, video games, and massively-multiplayer online role-playing games such as World of Warcraft, but little is known regarding the mental health impact of non-video role-playing games, such as Dungeons & Dragons. The present study examines how psychiatrists' perceive role-playing games and whether they play them. Psychiatrists at a tertiary care centre in Canada completed a questionnaire assessing history of playing role-playing games and whether they associate them with psychopathology. Forty-eight psychiatrists responded. Twenty-three percent have played a role-playing game over their lifetimes. Twenty-two percent believed there was an association between psychopathology and role-playing games. A majority of psychiatrists who responded do not associate role-playing games with psychopathology. Implications for clinical practice and future research are discussed. PMID:25589035

  13. Restaurant Role-Play in Psychology

    ERIC Educational Resources Information Center

    Borya, Anthony

    2013-01-01

    Research methods is perceived as a technical and difficult topic by some students. Using role-play to teach it can make it more accessible, meaningful and engaging. Role-playing the familiar roles of customer and waiting staff at a restaurant and discussing the variables that may affect the size of tips can help students to learn some of the key…

  14. ROLE-PLAYING AND THE POOR.

    ERIC Educational Resources Information Center

    GOLDFARB, JEAN; RIESSMAN, FRANK

    ROLE-PLAYING IS A VALUABLE TECHNIQUE FOR WORKING WITH DISADVANTAGED PEOPLE BECAUSE IT IS CONGENIAL WITH THE LOW-INCOME PERSON'S STYLE. ROLE-PLAYING ALLOWS THE PRACTITIONER TO REDUCE THE DISTANCE BETWEEN HIMSELF AND THE DISADVANTAGED, IT PERMITS MORE LEARNING ABOUT THE CULTURE OF THE LOW-INCOME PERSON FROM THE "INSIDE," AND IT IS AN EXCELLENT…

  15. Using Role Play to Debate Animal Testing

    ERIC Educational Resources Information Center

    Agell, Laia; Soria, Vanessa; Carrió, Mar

    2015-01-01

    The use of animals in biomedical research is a socio-scientific issue in which decision-making is complicated. In this article, we describe an experience involving a role play activity performed during school visits to the Barcelona Biomedical Research Park (PRBB) to debate animal testing. Role playing games require students to defend different…

  16. Role-Playing Methods in the Classroom.

    ERIC Educational Resources Information Center

    Chesler, Mark; Fox, Robert

    This book, one of three Teacher Resource Booklets on Classroom Social Relations and Learning developed at the Center for Research on Utilization of Scientific Knowledge at the University of Michigan, discusses the theoretical background of role playing and gives a step-by-step discussion of how to use role playing in the classroom. There are…

  17. Crucial role of macrophage selenoproteins in experimental colitis

    PubMed Central

    Kaushal, Naveen; Kudva, Avinash K.; Patterson, Andrew D.; Chiaro, Christopher; Kennett, Mary J.; Desai, Dhimant; Amin, Shantu; Carlson, Bradley A.; Cantorna, Margherita T.; Prabhu, K. Sandeep

    2014-01-01

    Inflammation is a hallmark of inflammatory bowel disease (IBD) that involves macrophages. Given the inverse link between selenium (Se) status and IBD-induced inflammation, our objective was to demonstrate that selenoproteins in macrophages were essential to suppress pro-inflammatory mediators, in part, by the modulation of arachidonic acid metabolism. Acute colitis was induced using 4% DSS in wild type mice maintained on Se-deficient (<0.01 ppm Se), Se-adequate (0.1 ppm; sodium selenite), and two supraphysiological levels in the form of Se-supplemented (0.4 ppm; sodium selenite) and high Se (1.0 ppm; sodium selenite) diets. Transfer RNASec (tRNA[sec]) knockout mice (Trspfl/flLysMCre) were used to examine the role of selenoproteins in macrophages on disease progression and severity using histopathological evaluation, expression of pro-inflammatory and anti-inflammatory genes, and modulation of prostaglandin (PG) metabolites in urine and plasma. While Se-deficient and Se-adequate mice showed increased colitis and exhibited poor survival, Se supplementation at 0.4 and 1.0 ppm increased survival of mice and decreased colitis-associated inflammation with an up-regulation of expression of pro-inflammatory and anti-inflammatory genes. Metabolomic profiling of urine suggested increased oxidation of PGE2 at supraphysiological levels of Se that also correlated well with Se-dependent upregulation of 15-hydroxy-PG dehydrogenase (15-PGDH) in macrophages. Pharmacological inhibition of 15-PGDH, lack of selenoprotein expression in macrophages, and depletion of infiltrating macrophages indicated that macrophage-specific selenoproteins and upregulation of 15-PGDH expression were key for Se-dependent anti-inflammatory and pro-resolving effects. Selenoproteins in macrophages protect mice from DSS-colitis by enhancing 15-PGDH-dependent oxidation of PGE2 to alleviate inflammation, suggesting a therapeutic role for Se in IBD. PMID:25187657

  18. The Crucial Role of Atg5 in Cortical Neurogenesis During Early Brain Development

    PubMed Central

    Lv, Xiaohui; Jiang, Huihui; Li, Baoguo; Liang, Qingli; Wang, Shukun; Zhao, Qianwei; Jiao, Jianwei

    2014-01-01

    Autophagy plays an important role in the central nervous system. However, it is unknown how autophagy regulates cortical neurogenesis during early brain development. Here, we report that autophagy-related gene 5 (Atg5) expression increased with cortical development and differentiation. The suppression of Atg5 expression by knockdown led to inhibited differentiation and increased proliferation of cortical neural progenitor cells (NPCs). Additionally, Atg5 suppression impaired cortical neuronal cell morphology. We lastly observed that Atg5 was involved in the regulation of the β-Catenin signaling pathway. The β-Catenin phosphorylation level decreased when Atg5 was blocked. Atg5 cooperated with β-Catenin to modulate cortical NPCs differentiation and proliferation. Our results revealed that Atg5 has a crucial role in cortical neurogenesis during early embryonic brain development, which may contribute to the understanding of neurodevelopmental disorders caused by autophagy dysregulation. PMID:25109817

  19. Role-Play in the Science Classroom

    ERIC Educational Resources Information Center

    Worch, Eric A.; Scheuermann, Amy M.; Haney, Jodi J.

    2009-01-01

    The activity shared here is an animal role-playing lesson developed, field-tested, and refined for "Nature's Neighborhood", a newly designed children's education facility at the Toledo Zoo. The activity is targeted at students in kindergarten through second grade, but it can be adapted for use in grades three and four as well. Through students'…

  20. A Role-Play Rorschach Procedure

    ERIC Educational Resources Information Center

    Bricklin, Barry

    1975-01-01

    Three subjects were used in a role playing study based on the subject's own Rorschach responses. The results proved to be valuable as an aspect of therapeutic involvement. Results also help to expand and clarify the psychological meaning of Rorschach images. (Author/DEP)

  1. Geriatrix: A Role-Playing Game.

    ERIC Educational Resources Information Center

    Hoffman, Stephanie B.; And Others

    1985-01-01

    To sensitize medical students to the complexities of geriatric patient care, the geriatrics faculty of Upstate Medical Center's Clinical Campus developed Geriatrix, a role-playing game. Students attempt to win points in a board game containing Fact, Concept, and Crisis Squares. Crises promote exposure to ethical dilemmas and invite intense debate…

  2. Crucial roles of the Arp2/3 complex during mammalian corticogenesis

    PubMed Central

    Wang, Pei-Shan; Chou, Fu-Sheng; Ramachandran, Sreekumar; Xia, Sheng; Chen, Huei-Ying; Guo, Fengli; Suraneni, Praveen; Maher, Brady J.

    2016-01-01

    The polarity and organization of radial glial cells (RGCs), which serve as both stem cells and scaffolds for neuronal migration, are crucial for cortical development. However, the cytoskeletal mechanisms that drive radial glial outgrowth and maintain RGC polarity remain poorly understood. Here, we show that the Arp2/3 complex – the unique actin nucleator that produces branched actin networks – plays essential roles in RGC polarity and morphogenesis. Disruption of the Arp2/3 complex in murine RGCs retards process outgrowth toward the basal surface and impairs apical polarity and adherens junctions. Whereas the former is correlated with an abnormal actin-based leading edge, the latter is consistent with blockage in membrane trafficking. These defects result in altered cell fate, disrupted cortical lamination and abnormal angiogenesis. In addition, we present evidence that the Arp2/3 complex is a cell-autonomous regulator of neuronal migration. Our data suggest that Arp2/3-mediated actin assembly might be particularly important for neuronal cell motility in a soft or poorly adhesive matrix environment. PMID:27385014

  3. The possible crucial role of iron accumulation combined with low tryptophan, zinc and manganese in carcinogenesis.

    PubMed

    Johnson, S

    2001-11-01

    Iron can react with citric acid, interfering with the Krebs cycle, hence with oxidative phosphorylation. Free iron (Fe) can cause considerable oxidative damage both through Fenton reactions and by activating xanthine oxidase, which produces both superoxide (O(2-)) and uric acid (abundant in many cancers). It can also react with lactic acid, reducing its elimination and increasing the acidity of the cytoplasm. Fe can also wreak havoc by reacting with tryptophan, the least abundant and most delicate essential amino acid, which is necessary for the production of serotonin and other substances required by the immune system to fight cancer. On the other hand, in the presence of iron, the tryptophan metabolite quinolinate causes intense lipid peroxidation. Similarly, several other carcinogenic metabolites of tryptophan are particularly dangerous in the presence of Fe. Excess Fe may also interfere with manganese superoxide dismutase and impair the initiation of apoptosis by the mitochondrion, rendering the cells impervious to all the signals to undergo apoptosis from without and from within the cell. Moreover, Fe may also play a crucial role on telomere repair, by activating telomerase. Therefore, by inhibiting apoptosis and enhancing chromosome repair, Fe may bestow immortality upon the cancer cell. Furthermore, Fe is one of the triggers for mitosis. Therefore, increased Fe levels may be essential for the rapid growth characteristic of many malignancies. In turn, the rapid growth further depletes resources from the healthy tissues, exacerbating the deficiencies of the other elements and reducing the ability to fight the malignancy. PMID:11735307

  4. Crucial roles of the Arp2/3 complex during mammalian corticogenesis.

    PubMed

    Wang, Pei-Shan; Chou, Fu-Sheng; Ramachandran, Sreekumar; Xia, Sheng; Chen, Huei-Ying; Guo, Fengli; Suraneni, Praveen; Maher, Brady J; Li, Rong

    2016-08-01

    The polarity and organization of radial glial cells (RGCs), which serve as both stem cells and scaffolds for neuronal migration, are crucial for cortical development. However, the cytoskeletal mechanisms that drive radial glial outgrowth and maintain RGC polarity remain poorly understood. Here, we show that the Arp2/3 complex - the unique actin nucleator that produces branched actin networks - plays essential roles in RGC polarity and morphogenesis. Disruption of the Arp2/3 complex in murine RGCs retards process outgrowth toward the basal surface and impairs apical polarity and adherens junctions. Whereas the former is correlated with an abnormal actin-based leading edge, the latter is consistent with blockage in membrane trafficking. These defects result in altered cell fate, disrupted cortical lamination and abnormal angiogenesis. In addition, we present evidence that the Arp2/3 complex is a cell-autonomous regulator of neuronal migration. Our data suggest that Arp2/3-mediated actin assembly might be particularly important for neuronal cell motility in a soft or poorly adhesive matrix environment. PMID:27385014

  5. Leptin plays a catabolic role on articular cartilage.

    PubMed

    Bao, Jia-peng; Chen, Wei-ping; Feng, Jie; Hu, Peng-fei; Shi, Zhong-li; Wu, Li-dong

    2010-10-01

    Leptin has been shown to play a crucial role in the regulation of body weight. There is also evidence that this adipokine plays a key role in the process of osteoarthritis. However, the precise role of leptin on articular cartilage metabolism is not clear. We investigate the role of leptin on articular cartilage in vivo in this study. Recombinant rat leptin (100 μg) was injected into the knee joints of rats, 48 h later, messenger RNA (mRNA) expression and protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), cathepsin D, and collagen II from articular cartilage were analyzed by real-time quantitative polymerase chain reaction (PCR) and western blot. Two important aggrecanases ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) were also analyzed by real-time quantitative PCR. Besides, articular cartilage was also assessed for proteoglycan/GAG content by Safranin O staining. Leptin significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage. Moreover, the gene expression of ADAMTS-4 and -5 were markedly increased, and histologically assessed depletion of proteoglycan in articular cartilage was observed after treatment with leptin. These results strongly suggest that leptin plays a catabolic role on cartilage metabolism and may be a disadvantage factor involve in the pathological process of OA. PMID:19876764

  6. The TIR-domain-containing adapter inducing interferon-β-dependent signaling cascade plays a crucial role in ischemia–reperfusion-induced retinal injury, whereas the contribution of the myeloid differentiation primary response 88-dependent signaling cascade is not as pivotal

    PubMed Central

    Dvoriantchikova, Galina; Santos, Andrea Rachelle C; Danek, Dagmara; Dvoriantchikova, Xenia; Ivanov, Dmitry

    2014-01-01

    Toll-like receptor 4 (Tlr4) plays an important role in ischemia–reperfusion (IR)-induced retinal inflammation and damage. However, the role of two Tlr4-dependent signaling cascades, myeloid differentiation primary response 88 (Myd88) and TIR-domain-containing adapter inducing interferon-β (Trif), in retinal IR injury is poorly understood. In this study, we investigated the contribution of the Myd88-dependent and Trif-dependent signaling cascades in retinal damage and inflammation triggered by IR, by using Myd88 knockout (Myd88KO) and Trif knockout (TrifKO) mice. Retinal IR injury was induced by unilateral elevation of intraocular pressure for 45 min by direct corneal cannulation. To study IR-induced retinal ganglion cell (RGC) death in vitro, we used an oxygen and glucose deprivation (OGD) model. Our data suggested that Myd88 was present in many retinal layers of sham-operated and ischemic mice, whereas Trif was mainly present in the ganglion cell layer (GCL). The level of Myd88 was increased in the retina after IR. We found that retinas of TrifKO mice had a significantly reduced neurotoxic pro-inflammatory response and significantly increased survival of the GCL neurons after IR. Although Myd88KO mice had relatively low levels of inflammation in ischemic retinas, their levels of IR-induced retinal damage were notably higher than those of TrifKO mice. We also found that Trif-deficient RGCs were more resistant to death induced by OGD than were RGCs isolated from Myd88KO mice. These data suggested that, as compared with the Myd88-dependent signaling cascade, Trif signaling contributes significantly to retinal damage after IR. PMID:24754835

  7. Role Engagement and Anonymity in Synchronous Online Role Play

    ERIC Educational Resources Information Center

    Cornelius, Sarah; Gordon, Carole; Harris, Margaret

    2011-01-01

    Role play activities provide opportunities for learners to adopt unfamiliar roles, engage in interactions with others, and get involved in realistic tasks. They are often recommended to foster the development of soft skills and a wider perspective of the world. Such activities are widely used as an online teaching approach, with examples ranging…

  8. Towards Smaller Families: The Crucial Role of the Private Sector. Draper Fund Report Number 15.

    ERIC Educational Resources Information Center

    Camp, Sharon L., Ed.; And Others

    The Draper Fund was established within the Population Crisis Committee (PCC) in 1975. Contributions to the fund are used by the PCC to encourage and expand those activities which promise the greatest impact in slowing world population growth. Seven papers written around that theme are included in this report: "The Crucial Role of the Private…

  9. "Prey Play": Learning about Predators and Prey through an Interactive, Role-Play Game

    ERIC Educational Resources Information Center

    Deaton, Cynthia C. M.; Dodd, Kristen; Drennon, Katherine; Nagle, Jack

    2012-01-01

    "Prey Play" is an interactive role-play activity that provides fifth-grade students with opportunities to examine predator-prey interactions. This four-part, role-play activity allows students to take on the role of a predator and prey as they reflect on the behaviors animals exhibit as they collect food and interact with one another, as well as…

  10. CD109 Plays a Role in Osteoclastogenesis

    PubMed Central

    Jiang, Hongwei; Tenenbaum, Howard; Glogauer, Michael

    2013-01-01

    Osteoclasts are large multinucleated cells that arise from the fusion of cells from the monocyte/macrophage lineage. Osteoclastogenesis is mediated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL) and involves a complex multistep process that requires numerous other elements, many of which remain undefined. The primary aim of this project was to identify novel factors which regulate osteoclastogenesis. To carry out this investigation, microarray analysis was performed comparing two pre-osteoclast cell lines generated from RAW264.7 macrophages: one that has the capacity to fuse forming large multinucleated cells and one that does not fuse. It was found that CD109 was up-regulated by>17-fold in the osteoclast forming cell line when compared to the cell line that does not fuse, at day 2 of the differentiation process. Results obtained with microarray were confirmed by RT-qPCR and Western blot analyses in the two cell lines, in the parental RAW264.7 cell line, as well as primary murine monocytes from bone marrow. A significant increase of CD109 mRNA and protein expression during osteoclastogenesis occurred in all tested cell types. In order to characterize the role of CD109 in osteoclastogenesis, CD109 stable knockdown cell lines were established and fusion of osteoclast precursors into osteoclasts was assessed. It was found that CD109 knockdown cell lines were less capable of forming large multinucleated osteoclasts. It has been shown here that CD109 is expressed in monocytes undergoing RANKL-induced osteoclastogenesis. Moreover, when CD109 expression is suppressed in vitro, osteoclast formation decreases. This suggests that CD109 might be an important regulator of osteoclastogenesis. Further research is needed in order to characterize the role played by CD109 in regulation of osteoclast differentiation. PMID:23593435

  11. Virtual Playgrounds? Assessing the Playfulness of Massively Multiplayer Online Role-Playing Games

    ERIC Educational Resources Information Center

    Graham, Kerrie Lewis

    2010-01-01

    Millions of children and adults devote much of their leisure time to playing massively multiplayer online role-playing games (MMORPGs). Most observers commonly categorize computer games as a play activity, but this article asks whether MMORPGs contain activities that might not be play. The author examines the phenomenon of online gaming and…

  12. Role Playing as an Imaginative Experience for Language Growth.

    ERIC Educational Resources Information Center

    Yawkey, Thomas Daniels

    This paper discusses the value of role play in facilitating children's language development and suggests strategies for using role play effectively in early childhood and intermediate classrooms. Role play requires the child (1) to listen and observe peer talk and action and to use language memory, attention and concentration behaviors; (2) to…

  13. Role-Play and Student Engagement: Reflections from the Classroom

    ERIC Educational Resources Information Center

    Stevens, Rachel

    2015-01-01

    Role-play is viewed by scholars as an effective active learning strategy: it encourages participation among passive learners, adds dynamism to the classroom and promotes the retention of material. But what do students think of role-play? This study surveyed 144 students after a role-play activity in a history course and asked them to identify what…

  14. Designing and Evaluating an Online Role Play in Conflict Management

    ERIC Educational Resources Information Center

    Hrastinski, Stefan; Watson, Jason

    2009-01-01

    Purpose: This paper aims to identify, through a literature review, key issues regarding how online role plays can be designed and to apply them when designing a role play on conflict management. Design/methodology/approach: By drawing on the key issues identified in the literature review, a role play on conflict management was designed and…

  15. TESL: The Crucial Role of Formal and Explicit Instruction and Learners' Prior Knowledge--An Example in Learners of Chinese Background.

    ERIC Educational Resources Information Center

    Zhang, May Xiu-qin

    This paper argues that formal and explicit instruction and learners' prior knowledge play a crucial role in teaching and learning English as a second language (ESL), and that a pure communicative approach is inadequate in achieving optimum results. The discussion is presented in two parts. The first outlines the issues under consideration,…

  16. Rethinking Role Play in the Reception Class

    ERIC Educational Resources Information Center

    Rogers, Sue; Evans, Julie

    2007-01-01

    Background: In 2000 the so-called "Reception" class was re-conceived (in curricular terms, at least) as the second and final year of the Foundation Stage, a distinctive educational phase for children aged 3 until entry to key stage 1 at 5 or 6 years old. The "Curriculum guidance for the Foundation Stage" endorses a play-based, informal curriculum…

  17. Reality and Second-Language Role-Play.

    ERIC Educational Resources Information Center

    Piper, David; Piper, Terry

    1983-01-01

    Although role playing is a well-established and useful method of second language instruction, its success is often undermined by assignment of roles alien to the students' needs and experience. Redefinition of role playing to include the roles an individual assumes in everyday life will help the teacher plan more appropriate activities. (MSE)

  18. The crucial role of cooling in the making of molecular clouds and stars

    NASA Technical Reports Server (NTRS)

    Tohline, Joel E.; Bodenheimer, Peter H.; Christodoulou, Dimitris M.

    1987-01-01

    The role that velocity or pressure fluctuations in the H I clouds medium can play in initiating compression of sub-Jeans mass diffuse clouds is outlined. The frequently discussed idea is reviewed that substantial overpressures arising in the warm, medium and/or highly supersonic compressions of H I clouds can push sub-Jeans mass clumps to densities where gravity can take over and complete the star formation process. A nonequilibrium model is used to analyze the impact of external disturbances on gas clouds, and estimates of the required disturbance amplitudes are substantially reduced from previous estimates based on equilibrium arguments. The results reveal that a cloud which cools under compression is particularly sensitive to mild disturbances from its environment. Furthermore, the specific energy required to trigger effective compressions in a cooling medium is nearly independent of the cloud's mass. It is proposed that mildly nonlinear disturbances play a primary role in the formation of molecular cloud and stars.

  19. TLR4 plays a crucial role in MSC-induced inhibition of NK cell function

    SciTech Connect

    Lu, Ying; Liu, Jin; Liu, Yang; Qin, Yaru; Luo, Qun; Wang, Quanli; Duan, Haifeng

    2015-08-21

    Mesenchymal stem cells (MSC) are a kind of stromal cell within the tumor microenvironment. In our research, MSC derived from acute myeloid leukemia patients' bone marrow (AML-MSC) and lung cancer tissues (LC-MSC) as well as normal bone marrow-derived MSC (BM-MSC) cultured in conditioned medium of HeLa cells were found to have higher expressions of Toll-like receptor (TLR4) mRNA compared with BM-MSC. The sorted TLR4-positive MSC (TLR4+ MSC) differed in cytokine (interleukin-6, interleukin-8, and monocyte chemoattractant protein-1) secretion from those of unsorted MSC. MSC was reported to inhibit natural killer (NK) cell proliferation and function. In this research, we confirmed that TLR4+ MSC aggravate this suppression. Furthermore, when TLR4 in the sorted cells were stimulated by LPS or following blocked by antibody, the suppression on NK cell proliferation and cytotoxicity were more intensive or recovered respectively. Compared to unsorted MSC, NKG2D receptor expression on NK cells were also inhibited by TLR4+ MSC. These findings suggest that activation of TLR4 pathway is important for TLR4+ MSC and MSC to obstruct anti-tumor immunity by inhibiting NK cell function, which may provide a potential stroma-targeted tumor therapy. - Highlights: • TLR4+ MSC inhibit NK cell proliferation in vivo and in vitro. • TLR4+ MSC inhibit NKG2D expression on NK cells and NK cell cytotoxicity. • The distinguished cytokine expression of TLR4+ MSC may contribute to the inhibition on NK cell function.

  20. Intercentrosomal angular separation during mitosis plays a crucial role for maintaining spindle stability

    NASA Astrophysics Data System (ADS)

    Sutradhar, S.; Basu, S.; Paul, R.

    2015-10-01

    Cell division through proper spindle formation is one of the key puzzles in cell biology. In most mammalian cells, chromosomes spontaneously arrange to achieve a stable bipolar spindle during metaphase which eventually ensures proper segregation of the DNA into the daughter cells. In this paper, we present a robust three-dimensional mechanistic model to investigate the formation and maintenance of a bipolar mitotic spindle in mammalian cells under different physiological constraints. Using realistic parameters, we test spindle viability by measuring the spindle length and studying the chromosomal configuration. The model strikingly predicts a feature of the spindle instability arising from the insufficient intercentrosomal angular separation and impaired sliding of the interpolar microtubules. In addition, our model successfully reproduces chromosomal patterns observed in mammalian cells, when activity of different motor proteins is perturbed.

  1. Calcium-Sensing Receptors of Human Neural Cells Play Crucial Roles in Alzheimer's Disease

    PubMed Central

    Chiarini, Anna; Armato, Ubaldo; Liu, Daisong; Dal Prà, Ilaria

    2016-01-01

    In aged subjects, late-onset Alzheimer's disease (LOAD) starts in the lateral entorhinal allocortex where a failure of clearance mechanisms triggers an accumulation of neurotoxic amyloid-β42 oligomers (Aβ42-os). In neurons and astrocytes, Aβ42-os enhance the transcription of Aβ precursor protein (APP) and β-secretase/BACE1 genes. Thus, by acting together with γ-secretase, the surpluses of APP and BACE1 amplify the endogenous production of Aβ42-os which pile up, damage mitochondria, and are oversecreted. At the plasmalemma, exogenous Aβ42-os bind neurons' and astrocytes' calcium-sensing receptors (CaSRs) activating a set of intracellular signaling pathways which upkeep Aβ42-os intracellular accumulation and oversecretion by hindering Aβ42-os proteolysis. In addition, Aβ42-os accumulating in the extracellular milieu spread and reach mounting numbers of adjacent and remoter teams of neurons and astrocytes which in turn are recruited, again via Aβ42-os•CaSR-governed mechanisms, to produce and release additional Aβ42-os amounts. This relentless self-sustaining mechanism drives AD progression toward upper cortical areas. Later on accumulating Aβ42-os elicit the advent of hyperphosphorylated (p)-Tau oligomers which acting together with Aβ42-os and other glial neurotoxins cooperatively destroy wider and wider cognition-related cortical areas. In parallel, Aβ42-os•CaSR signals also elicit an excess production and secretion of nitric oxide and vascular endothelial growth factor-A from astrocytes, of Aβ42-os and myelin basic protein from oligodendrocytes, and of proinflammatory cytokines, nitric oxide and (likely) Aβ42-os from microglia. Activated astrocytes and microglia survive the toxic onslaught, whereas neurons and oligodendrocytes increasingly die. However, we have shown that highly selective allosteric CaSR antagonists (calcilytics), like NPS 2143 and NPS 89626, efficiently suppress all the neurotoxic effects Aβ42-os•CaSR signaling drives in cultured cortical untransformed human neurons and astrocytes. In fact, calcilytics increase Aβ42 proteolysis and discontinue the oversecretion of Aβ42-os, nitric oxide, and vascular endothelial growth factor-A from both astrocytes and neurons. Seemingly, calcilytics would also benefit the other types of glial cells and cerebrovascular cells otherwise damaged by the effects of Aβ42-os•CaSR signaling. Thus, given at amnestic minor cognitive impairment (aMCI) or initial symptomatic stages, calcilytics could prevent or terminate the propagation of LOAD neuropathology and preserve human neurons' viability and hence patients' cognitive abilities. PMID:27199760

  2. Does Instructional Approach Matter? How Elaboration Plays a Crucial Role in Multimedia Learning

    ERIC Educational Resources Information Center

    Eysink, Tessa H. S.; de Jong, Ton

    2012-01-01

    This study compared the affordances of 4 multimedia learning environments for specific learning processes. The environments covered the same domain but used different instructional approaches: (a) hypermedia learning, (b) observational learning, (c) self-explanation-based learning, and (d) inquiry learning. Although they all promote an active…

  3. Arabinosylation Plays a Crucial Role in Extensin Cross-linking In Vitro

    PubMed Central

    Chen, Yuning; Dong, Wen; Tan, Li; Held, Michael A; Kieliszewski, Marcia J

    2015-01-01

    Extensins (EXTs) are hydroxyproline-rich glycoproteins (HRGPs) that are structural components of the plant primary cell wall. They are basic proteins and are highly glycosylated with carbohydrate accounting for >50% of their dry weight. Carbohydrate occurs as monogalactosyl serine and arabinosyl hydroxyproline, with arabinosides ranging in size from ~1 to 4 or 5 residues. Proposed functions of EXT arabinosylation include stabilizing the polyproline II helix structure and facilitating EXT cross-linking. Here, the involvement of arabinosylation in EXT cross-linking was investigated by assaying the initial cross-linking rate and degree of cross-linking of partially or fully de-arabinosylated EXTs using an in vitro cross-linking assay followed by gel permeation chromatography. Our results indicate that EXT arabinosylation is required for EXT cross-linking in vitro and the fourth arabinosyl residue in the tetraarabinoside chain, which is uniquely α-linked, may determine the initial cross-linking rate. Our results also confirm the conserved structure of the oligoarabinosides across species, indicating an evolutionary significance for EXT arabinosylation. PMID:26568683

  4. TRANSCRIPTION FACTOR Bmsage PLAYS A CRUCIAL ROLE IN SILK GLAND GENERATION IN SILKWORM, Bombyx mori.

    PubMed

    Xin, Hu-hu; Zhang, Deng-pan; Chen, Rui-ting; Cai, Zi-zheng; Lu, Yan; Liang, Shuang; Miao, Yun-gen

    2015-10-01

    Salivary gland secretion is altered in Drosophila embryos with loss of function of the sage gene. Saliva has a reduced volume and an increased electron density according to transmission electron microscopy, resulting in regions of tube dilation and constriction with intermittent tube closure. However, the precise functions of Bmsage in silkworm (Bombyx mori) are unknown, although its sequence had been deposited in SilkDB. From this, Bmsage is inferred to be a transcription factor that regulates the synthesis of silk fibroin and interacts with another silk gland-specific transcription factor, namely, silk gland factor-1. In this study, we introduced a germline mutation of Bmsage using the Cas9/sgRNA system, a genome-editing technology, resulting in deletion of Bmsage from the genome of B. mori. Of the 15 tested samples, seven displayed alterations at the target site. The mutagenesis efficiency was about 46.7% and there were no obvious off-target effects. In the screened homozygous mutants, silk glands developed poorly and the middle and posterior silk glands (MSG and PSG) were absent, which was significantly different from the wild type. The offspring of G0 mosaic silkworms had indel mutations causing 2- or 9-bp deletions at the target site, but exhibited the same abnormal silk gland structure. Mutant larvae containing different open-reading frames of Bmsage had the same silk gland phenotype. This illustrated that the mutant phenotype was due to Bmsage knockout. We conclude that Bmsage participates in embryonic development of the silk gland. PMID:25917878

  5. Intercentrosomal angular separation during mitosis plays a crucial role for maintaining spindle stability.

    PubMed

    Sutradhar, S; Basu, S; Paul, R

    2015-10-01

    Cell division through proper spindle formation is one of the key puzzles in cell biology. In most mammalian cells, chromosomes spontaneously arrange to achieve a stable bipolar spindle during metaphase which eventually ensures proper segregation of the DNA into the daughter cells. In this paper, we present a robust three-dimensional mechanistic model to investigate the formation and maintenance of a bipolar mitotic spindle in mammalian cells under different physiological constraints. Using realistic parameters, we test spindle viability by measuring the spindle length and studying the chromosomal configuration. The model strikingly predicts a feature of the spindle instability arising from the insufficient intercentrosomal angular separation and impaired sliding of the interpolar microtubules. In addition, our model successfully reproduces chromosomal patterns observed in mammalian cells, when activity of different motor proteins is perturbed. PMID:26565279

  6. Endangered Play, Endangered Development: A Constructivist View of the Role of Play in Development and Learning.

    ERIC Educational Resources Information Center

    Levin, Diane E.

    Piagetian and Vygotskian theories may be used as starting points to examine the role of play in development and learning from a constructivist perspective, including how children use play to deepen their understanding and skills, encounter new problems, and incorporate newly mastered skills into their play. Contemporary factors such as an emphasis…

  7. Teaching clinical interviewing skills using role-playing: conveying empathy to performing a suicide assessment: a primer for individual role-playing and scripted group role-playing.

    PubMed

    Shea, Shawn Christopher; Barney, Christine

    2015-03-01

    This article provides a useful introduction to the art of role-playing in both the individual format and the group format using scripted group role-playing (SGRP). Role-playing can provide powerful learning opportunities, but to do so it must be done well. This article imparts guidance toward this goal. SGRP may greatly enhance the acquisition of critical complex interviewing skills, such as suicide assessment and uncovering domestic violence, in health care providers across all disciplines, an educational goal that has not been achievable to date. Although research is at an early stage of development, the hope represented by SGRP is tangible. PMID:25725575

  8. TLR3 Plays Significant Roles against HBV-Associated HCC

    PubMed Central

    Chen, Xiao-lan; Xu, Yu-yin; Chen, Li; Wang, Gui-lan; Shen, Yin

    2015-01-01

    Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in immune signaling and plays a crucial role in survival by being able to recognize various viral components including double-stranded RNA (dsRNA). The role of TLR3 in hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infections is not well understood. To investigate the ability of TLR3 in regulating HBV replication in HCC, 80 cases of human HCC were collected and their tissue microarray was made. In HCC cells, the expression and location of TLR3, hepatitis-associated virus, and interstitial immunoreactive cells were assayed with immunohistochemical staining. The apoptosis of tumor cells was also detected by TUNEL stain. Correlations between TLR3 expression and HBV infection, interstitial immunoreactive cells, and cells apoptosis in HCC were investigated. In addition, we explored whether TLR3 agonist dsRNA can inhibit HepG2.2.15 cells secreting HBV. We found that the cytoplasmic expression of TLR3 in HCC is positively related to HBsAg infection and HCC with cirrhosis and promotes interstitial immunoreactive cells infiltration and cancer cells apoptosis. In HepG2.2.15 cells, dsRNA inhibited the secretion of HBV and induced apoptosis. These results indicate that TLR3 signaling activity may be involved in immune responses against HBV in HCC. PMID:25983748

  9. Online Role-Play Environments for Higher Education

    ERIC Educational Resources Information Center

    Russell, Carol; Shepherd, John

    2010-01-01

    As online environments and tools have evolved over the last 15-20 years, their use for role-based learning has expanded. This analysis draws on work for an Australian project that has been sharing and developing knowledge about the use of online role-plays in higher education. We describe the learning needs that online role-play can meet, and give…

  10. A Role Play for Revising Style and Applying Management Theories

    ERIC Educational Resources Information Center

    Griggs, Karen

    2005-01-01

    Role-playing is a well regarded learning activity. By participating in this activity, students can apply their knowledge through their assigned roles in a realistic but risk-free situation. The role play stimulates class discussion, dramatizes rhetorical principles about purpose, shows how to adapt a text to an audience of employees in a…

  11. A crucial role of L-selectin in C protein-induced experimental polymyositis of mice

    PubMed Central

    Oishi, Kyosuke; Hamaguchi, Yasuhito; Matsushita, Takashi; Hasegawa, Minoru; Okiyama, Naoko; Dernedde, Jens; Weinhart, Marie; Haag, Rainer; Tedder, Thomas F.; Takehara, Kazuhiko; Kohsaka, Hitoshi; Fujimoto, Manabu

    2014-01-01

    Objective To investigate the role of adhesion molecules in C protein-induced myositis (CIM), a murine model for polymyositis (PM). Methods CIM was induced in wild type mice, L-selectin-deficient (L-selectin-/-) mice, ICAM-1-deficient (ICAM-1-/-) mice, and both L-selectin- and ICAM-1-deficient (L-selectin-/-ICAM-1-/-) mice. The severity of myositis, inflammatory cell infiltration, and mRNA expression in the inflamed muscles were examined. The effect of dendritic polyglycerol sulfate (dPGS), a synthetic inhibitor that suppresses the function of L-selectin and endothelial P-selectin, was also examined. Results L-selectin-/- mice and L-selectin-/-ICAM-1-/- mice developed significantly less severe myositis compared to wild type mice, while ICAM-1 deficiency did not inhibit the development of myositis. L-selectin-/- mice transferred with wild type T cells developed myositis. Wild type mice treated with dPGS significantly diminished the severity of myositis compared to control-treated wild type mice. Conclusions These data indicate that L-selectin plays a major role in the development of CIM, whereas ICAM-1 plays a lesser, if any, role in the development of CIM. L-selectin-targeted therapy may be a candidate for the treatment of PM. PMID:24644046

  12. The role-playing: the art to catch the eye

    NASA Astrophysics Data System (ADS)

    Crescimbene, Massimo; La Longa, Federica; Lanza, Tiziana

    2015-04-01

    We present some interactive, immersive, authentic role-plays simulation designed to teach to different public: tertiary, secondary and primary students and an experience with a teachers group, after April 6 2009 L'Aquila Earthquake. We will discuss about the basics of the role-play and its applications to the geosciences in outreach projects. Role-play is a powerful method to educate to risk mitigation with particular we will discuss our experience regarding seismic risk. Finally, we will present some data on the effectiveness of the role-play in different settings in which we used it.

  13. Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo

    SciTech Connect

    Kioka, Noriyuki; Ito, Takuya; Yamashita, Hiroshi; Uekawa, Natsuko; Umemoto, Tsutomu; Motoyoshi, Soh; Imai, Hiroshi; Takahashi, Kenzo; Watanabe, Hideto; Yamada, Masayasu; Ueda, Kazumitsu

    2010-06-10

    In the process of tissue injury and repair, epithelial cells rapidly migrate and form epithelial sheets. Vinexin is a cytoplasmic molecule of the integrin-containing cell adhesion complex localized at focal contacts in vitro. Here, we investigated the roles of vinexin in keratinocyte migration in vitro and wound healing in vivo. Vinexin knockdown using siRNA delayed migration of both HaCaT human keratinocytes and A431 epidermoid carcinoma cells in scratch assay but did not affect cell proliferation. Induction of cell migration by scratching the confluent monolayer culture of these cells activated both EGFR and ERK, and their inhibitors AG1478 and U0126 substantially suppressed scratch-induced keratinocyte migration. Vinexin knockdown in these cells inhibited the scratch-induced activation of EGFR, but not that of ERK, suggesting that vinexin promotes cell migration via activation of EGFR. We further generated vinexin (-/-) mice and isolated their keratinocytes. They similarly showed slow migration in scratch assay. Furthermore, vinexin (-/-) mice exhibited a delay in cutaneous wound healing in both the back skin and tail without affecting the proliferation of keratinocytes. Together, these results strongly suggest a crucial role of vinexin in keratinocyte migration in vitro and cutaneous wound healing in vivo.

  14. Rim Sim: A Role-Play Simulation

    USGS Publications Warehouse

    Barrett, Robert C.; Frew, Suzanne L.; Howell, David G.; Karl, Herman A.; Rudin, Emily B.

    2003-01-01

    Rim Sim is a 6-hour, eight-party negotiation that focuses on creating a framework for the long-term disaster-recovery efforts. It involves a range of players from five countries affected by two natural disasters: a typhoon about a year ago and an earthquake about 6 months ago. The players are members of an International Disaster Working Group (IDWG) that has been created by an international commission. The IDWG has been charged with drawing up a framework for managing two issues: the reconstruction of regionally significant infrastructure and the design of a mechanism for allocating funding to each country for reconstruction of local infrastructure and ongoing humanitarian needs. The first issue will involve making choices among five options (two harbor options, two airport options, and one rail-line option), each of which will have three levels at which to rebuild. The second issue will involve five starting-point options. Participants are encouraged to invent other options for both issues. The goal of Rim Sim is to raise questions about traditional approaches to disaster-preparedness planning and reconstruction efforts in an international setting, in this case the Pacific Rim. Players must confront the reverberating effects of disasters and the problems of using science and technical information in decisionmaking, and are introduced to a consensus-building approach emphasizing face-to-face dialog and multinational cooperation in dealing with humanitarian concerns, as well as long-term efforts to reconstruct local and regional infrastructure. The Rim Sim simulation raises four key points: ripple effects of disasters, role of science, multiparty negotiation, and building personal relationships.

  15. Foreign Ludicity in Online Role-Playing Games

    ERIC Educational Resources Information Center

    Liang, Mei-Ya

    2012-01-01

    This article reports on an explorative case study which, in the first place, aimed to ascertain different types of foreign language play in online role-playing in "Second Life," and which, secondly aimed to describe how various sources of contextual support can explain this foreign language play. Students' written conversation was analyzed and…

  16. Museum Superheroes: The Role of Play in Young Children's Lives

    ERIC Educational Resources Information Center

    Krakowski, Pamela

    2012-01-01

    This article explores the role of play in an art museum. Reflecting upon a kindergarten field trip to the Warhol Museum in which children's play was the centerpiece of the museum experience, the author examines what early childhood theorists have written about the value of play in young children's lives. She shows how the Warhol's program for…

  17. Using Role-Playing Games to Teach Astronomy: An Evaluation

    ERIC Educational Resources Information Center

    Francis, Paul

    2005-01-01

    Since 1998, I've been experimenting with the use of role-playing games to teach astronomy. Students play the role of competing teams of researchers, racing to solve some astrophysical mystery. In this article, I review what has been learned from using these games around the world over the last eight years. The most common problem encountered is a…

  18. Table-Top Role Playing Game and Creativity

    ERIC Educational Resources Information Center

    Chung, Tsui-shan

    2013-01-01

    The current study aims to observe whether individuals who engaged in table-top role playing game (TRPG) were more creative. Participants total 170 (52 TRPG players, 54 electronic role playing game (ERPG) players and 64 Non-players) aged from 19 to 63. In the current study, an online questionnaire is used, adopting the verbal subtests of…

  19. Role-Playing and Religion: Using Games to Educate Millennials

    ERIC Educational Resources Information Center

    Porter, Adam L.

    2008-01-01

    I have been experimenting with using role-playing and games in my religion classes for several years and have found that students respond well to these pedagogical tools and methods. After reviewing my experiences, I explore the reasons for students' positive response. I argue that role-playing games capitalize on our students' educational…

  20. Online Role-Play: Anonymity, Engagement and Risk.

    ERIC Educational Resources Information Center

    Bell, Maureen

    2001-01-01

    Discussion of role-play focuses on a case study of an asynchronous, anonymous online role-play at an Australian university within a WebCT bulletin board that was designed as an alternative to an existing face-to-face workshop to offer more flexible access for participants. Suggests further research needs. (Author/LRW)

  1. Blended Learning Using Role-Plays, Wikis and Blogs

    ERIC Educational Resources Information Center

    Ruyters, Michele; Douglas, Kathy; Law, Siew Fang

    2011-01-01

    Student learning about legal skills in legal education is increasingly seen as important. These legal skills include advocacy and negotiation. These skills are often taught through role-play. This article discusses the combination of role-plays with online tools, including wikis and blogs, to assist students to master legal skills. The article…

  2. The Use of Role Play To Teach Communication Skills.

    ERIC Educational Resources Information Center

    O'Donnell, Nancy; Shaver, Lisa

    Role play (a dramatic technique in which individuals improvise behaviors that illustrate acts expected of persons involved in defined situations) has several advantages for the classroom. Role play: (1) involves little or no additional instructional costs; (2) allows students to practice behaviors and skills; (3) closes the gap between training…

  3. Understanding Public Land Management through Role-Playing

    ERIC Educational Resources Information Center

    Oberle, Alex P.

    2004-01-01

    Role-playing activities are an example of active learning that introduces students to "real-world" situations. This paper discusses the development and assessment of a role-play that involves an undergraduate geography class in a local public land management process. This particular case study is useful because it reflects broader themes and…

  4. ROLE-PLAYING WITH LOW-INCOME PEOPLE.

    ERIC Educational Resources Information Center

    GOLDFARB, JEAN; RIESSMAN, FRANK

    ROLE-PLAYING, THE FLEXIBLE ACTING OUT OF VARIOUS TYPES OF PROBLEMS IN A PERMISSIVE GROUP ATMOSPHERE, WAS AIMED AT DEVELOPING A FULL, INNER FEELING ABOUT A SITUATION FROM ACTING OUT HOW OTHER PEOPLE ACTUALLY FELT IN THE SITUATION. ROLE-PLAYING WAS ESPECIALLY USEFUL FOR LOW-INCOME GROUPS BECAUSE THEY EXPRESS THEMSELVES MORE READILY WHEN REACTING TO…

  5. "Playing The Role": Classroom Performance Approaches to Characterization.

    ERIC Educational Resources Information Center

    Ratliff, Gerald Lee

    Dynamic classroom role-playing is an essential ingredient in interpretation and performance if the student actor is to learn the technical skills of believable characterization. One of the first classroom performance principles in playing the role is for the student actor to read the playscript with a critical eye to grasp the creative suggestions…

  6. Role Playing: Applications in Hostage and Crisis Negotiation Skills Training

    ERIC Educational Resources Information Center

    Van Hasselt, Vincent B.; Romano, Stephen J.; Vecchi, Gregory M.

    2008-01-01

    Role playing has been a mainstay of behavioral assessment for decades. In recent years, however, this analogue strategy has also enjoyed widespread application in the field of law enforcement. Most notably, role-play procedures have become an integral component of assessment and training efforts in hostage and crisis negotiation, which attempts to…

  7. A Historical Journey in Science Education through Role Playing

    ERIC Educational Resources Information Center

    Guha, Smita

    2013-01-01

    In order to avoid a routine classroom environment, teachers often employ the use of role-plays. This is an effective strategy because it is essential for teachers to engage their students with information through various methods. Role-playing provides the children with the opportunity to incorporate multiple senses into a knowledge-based, fun…

  8. The crucial role of mechanical heterogeneity in regulating follicle development and ovulation with engineered ovarian microtissue

    PubMed Central

    Choi, Jung Kyu; Agarwal, Pranay; Huang, Haishui; Zhao, Shuting; He, Xiaoming

    2014-01-01

    Contemporary systems for in vitro culture of ovarian follicles do not recapitulate the mechanical heterogeneity in mammalian ovary. Here we report microfluidic generation of biomimetic ovarian microtissue for miniaturized three-dimensional (3D) culture of early secondary preantral follicles by using alginate (harder) and collagen (softer) to fabricate the ovarian cortical and medullary tissues, respectively. This biomimetic configuration greatly facilitates follicle development to antral stage. Moreover, it enables in vitro ovulation of cumulus-oocyte complex (COC) from the antral follicles in the absence of luteinizing hormone (LH) and epidermal growth factor (EGF) that are well accepted to be responsible for ovulation in contemporary literature. These data reveal the crucial role of mechanical heterogeneity in the mammalian ovary in regulating follicle development and ovulation. The biomimetic ovarian microtissue and the microfluidic technology developed in this study are valuable for improving in vitro culture of follicles to preserve fertility and for understanding the mechanism of follicle development and ovulation to facilitate the search of cures to infertility due to ovarian disorders. PMID:24702961

  9. Crucial role of posttranslational modifications of integrin α3 in interstitial lung disease and nephrotic syndrome.

    PubMed

    Yalcin, Ebru G; He, Yinghong; Orhan, Diclehan; Pazzagli, Chiara; Emiralioglu, Nagehan; Has, Cristina

    2015-07-01

    Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). The full spectrum of manifestations and genotype-phenotype correlations is still poorly characterized. Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. The present report also underscores that ITGA3 mutations may account for atypical cases solely with early onset respiratory and renal involvement. PMID:25810266

  10. Time perspective as a predictor of massive multiplayer online role-playing game playing.

    PubMed

    Lukavska, Katerina

    2012-01-01

    This article focuses on the relationship between the time perspective (TP) personality trait and massive multiplayer online role-playing game (MMORPG) playing. We investigate the question of frequency of playing. The TP was measured with Zimbardo's TP Inventory (ZTPI), which includes five factors-past negative, past positive, present hedonistic, present fatalistic, and future. The study used data from 154 MMORPG players. We demonstrated that TP partially explained differences within a group of players with respect to the frequency of playing. Significant positive correlations were found between present factors and the amount of time spent playing MMORPGs, and significant negative correlation was found between the future factor and the time spent playing MMORPGs. Our study also revealed the influence of future-present balance on playing time. Players who scored lower in future-present balance variables (their present score was relatively high compared with their future score) reported higher values in playing time. In contrast to referential studies on TP and drug abuse and gambling, present fatalistic TP was demonstrated to be a stronger predictor of extensive playing than present hedonistic TP, which opened the question of motivation for playing. The advantage of our study compared with other personality-based studies lies in the fact that TP is a stable but malleable personality trait with a direct link to playing behavior. Therefore, TP is a promising conceptual resource for excessive playing therapy. PMID:22032796

  11. Crucial Role of Elovl6 in Chondrocyte Growth and Differentiation during Growth Plate Development in Mice

    PubMed Central

    Kikuchi, Manami; Matsuzaka, Takashi; Ishii, Kiyoaki; Nakagawa, Yoshimi; Takayanagi, Misa; Yamada, Nobuhiro; Shimano, Hitoshi

    2016-01-01

    ELOVL family member 6, elongation of very long chain fatty acids (Elovl6) is a microsomal enzyme, which regulates the elongation of C12-16 saturated and monounsaturated fatty acids. Elovl6 has been shown to be associated with various pathophysiologies including insulin resistance, atherosclerosis, and non-alcoholic steatohepatitis. To investigate a potential role of Elovl6 during bone development, we here examined a skeletal phenotype of Elovl6 knockout (Elovl6-/-) mice. The Elovl6-/- skeleton was smaller than that of controls, but exhibited no obvious patterning defects. Histological analysis revealed a reduced length of proliferating and an elongated length of hypertrophic chondrocyte layer, and decreased trabecular bone in Elovl6-/- mice compared with controls. These results were presumably due to a modest decrease in chondrocyte proliferation and accelerated differentiation of cells of the chondrocyte lineage. Consistent with the increased length of the hypertrophic chondrocyte layer in Elovl6-/- mice, Collagen10α1 was identified as one of the most affected genes by ablation of Elovl6 in chondrocytes. Furthermore, this elevated expression of Collagen10α1 of Elovl6-null chondrocytes was likely associated with increased levels of Foxa2/a3 and Mef2c mRNA expression. Relative increases in protein levels of nuclear Foxa2 and cytoplasmic histone deacethylase 4/5/7 were also observed in Elovl6 knockdown cells of the chondrocyte lineage. Collectively, our data suggest that Elovl6 plays a critical role for proper development of embryonic growth plate. PMID:27467521

  12. A crucial role of Flagellin in the induction of airway mucus production by Pseudomonas aeruginosa.

    PubMed

    Ben Mohamed, Fatima; Mohamed, Fatima Ben; Garcia-Verdugo, Ignacio; Medina, Mathieu; Balloy, Viviane; Chignard, Michel; Ramphal, Reuben; Touqui, Lhousseine

    2012-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen involved in nosocomial infections. Flagellin is a P. aeruginosa virulence factor involved in host response to this pathogen. We examined the role of flagellin in P. aeruginosa-induced mucus secretion. Using a mouse model of pulmonary infection we showed that PAK, a wild type strain of P. aeruginosa, induced airway mucus secretion and mucin muc5ac expression at higher levels than its flagellin-deficient mutant (ΔFliC). PAK induced expression of MUC5AC and MUC2 in both human airway epithelial NCI-H292 cell line and in primary epithelial cells. In contrast, ΔFliC infection had lower to no effect on MUC5AC and MUC2 expressions. A purified P. aeruginosa flagellin induced MUC5AC expression in parallel to IL-8 secretion in NCI-H292 cells. Accordingly, ΔFliC mutant stimulated IL-8 secretion at significantly lower levels compared to PAK. Incubation of NCI-H292 cells with exogenous IL-8 induced MUC5AC expression and pre-incubation of these cells with an anti-IL-8 antibody abrogated flagellin-mediated MUC5AC expression. Silencing of TLR5 and Naip, siRNA inhibited both flagellin-induced MUC5AC expression and IL-8 secretion. Finally, inhibition of ERK abolished the expression of both PAK- and flagellin-induced MUC5AC. We conclude that: (i) flagellin is crucial in P. aeruginosa-induced mucus hyper-secretion through TLR5 and Naip pathways; (ii) this process is mediated by ERK and amplified by IL-8. Our findings help understand the mechanisms involved in mucus secretion during pulmonary infectious disease induced by P. aeruginosa, such as in cystic fibrosis. PMID:22768318

  13. Play.

    ERIC Educational Resources Information Center

    Rogers, Fred; Sharapan, Hedda

    1993-01-01

    Contends that, in childhood, work and play seem to come together. Says that for young children their play is their work, and the more adults encourage children to play, the more they emphasize important lifelong resource. Examines some uses of children's play, making and building, artwork, dramatic play, monsters and superheroes, gun play, and…

  14. Crucial Roles of Abscisic Acid Biogenesis in Virulence of Rice Blast Fungus Magnaporthe oryzae

    PubMed Central

    Spence, Carla A.; Lakshmanan, Venkatachalam; Donofrio, Nicole; Bais, Harsh P.

    2015-01-01

    Rice suffers dramatic yield losses due to blast pathogen Magnaporthe oryzae. Pseudomonas chlororaphis EA105, a bacterium that was isolated from the rice rhizosphere, inhibits M. oryzae. It was shown previously that pre-treatment of rice with EA105 reduced the size of blast lesions through jasmonic acid (JA)- and ethylene (ETH)-mediated ISR. Abscisic acid (ABA) acts antagonistically toward salicylic acid (SA), JA, and ETH signaling, to impede plant defense responses. EA105 may be reducing the virulence of M. oryzae by preventing the pathogen from up-regulating the key ABA biosynthetic gene NCED3 in rice roots, as well as a β-glucosidase likely involved in activating conjugated inactive forms of ABA. However, changes in total ABA concentrations were not apparent, provoking the question of whether ABA concentration is an indicator of ABA signaling and response. In the rice-M. oryzae interaction, ABA plays a dual role in disease severity by increasing plant susceptibility and accelerating pathogenesis in the fungus itself. ABA is biosynthesized by M. oryzae. Further, exogenous ABA increased spore germination and appressoria formation, distinct from other plant growth regulators. EA105, which inhibits appressoria formation, counteracted the virulence-promoting effects of ABA on M. oryzae. The role of endogenous fungal ABA in blast disease was confirmed through the inability of a knockout mutant impaired in ABA biosynthesis to form lesions on rice. Therefore, it appears that EA105 is invoking multiple strategies in its protection of rice from blast including direct mechanisms as well as those mediated through plant signaling. ABA is a molecule that is likely implicated in both tactics. PMID:26648962

  15. Role Playing Using a Simulated Pharmacy and Therapeutics Committee Model

    ERIC Educational Resources Information Center

    Fletcher, H. Patrick; Popvich, Nicholas G.

    1977-01-01

    Within a simulated Pharmacy and Therapeutics Committee format, role play is used at Purdue University to illustrate to students the concepts of drug product evaluation and selection as these apply to a hospital formulary system. (Author/LBH)

  16. What Role Does Obstetrical Care Play in Childbirth?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications What role does obstetrical care play in childbirth? Skip sharing on ... has ruptured (the woman’s water breaks), but labor does not start within 24 to 48 hours When ...

  17. Resonant tectorial membrane motion in the inner ear: its crucial role in frequency tuning.

    PubMed Central

    Gummer, A W; Hemmert, W; Zenner, H P

    1996-01-01

    The tectorial membrane has long been postulated as playing a role in the exquisite sensitivity of the cochlea. In particular, it has been proposed that the tectorial membrane provides a second resonant system, in addition to that of the basilar membrane, which contributes to the amplification of the motion of the cochlear partition. Until now, technical difficulties had prevented vibration measurements of the tectorial membrane and, therefore, precluded direct evidence of a mechanical resonance. In the study reported here, the vibration of the tectorial membrane was measured in two orthogonal directions by using a novel method of combining laser interferometry with a photodiode technique. It is shown experimentally that the motion of the tectorial membrane is resonant at a frequency of 0.5 octave (oct) below the resonant frequency of the basilar membrane and polarized parallel to the reticular lamina. It is concluded that the resonant motion of the tectorial membrane is due to a parallel resonance between the mass of the tectorial membrane and the compliance of the stereocilia of the outer hair cells. Moreover, in combination with the contractile force of outer hair cells, it is proposed that inertial motion of the tectorial membrane provides the necessary conditions to allow positive feedback of mechanical energy into the cochlear partition, thereby amplifying and tuning the cochlear response. PMID:8710939

  18. A crucial role of the thymus in induction by the lprcg gene of lymphadenopathy with autoimmunity in the mouse.

    PubMed

    Matsuzawa, A; Moriyama, T; Ogata, Y; Katagiri, T; Kimura, M

    1992-04-01

    The new mutation at the lpr locus, lprcg, induces massive lymphoproliferation characterized by the selective expansion of CD4-, CD8-, B220+, Thy-1+ cells or double-negative T lymphocytes and production of autoantibodies as does lpr. The thymus is necessary for the induction of anomalous double-negative T lymphocytes and autoimmune symptoms by lpr. To determine whether or not the thymus is also indispensable to expression of the function of lrpcg, lprcg homozygous athymic nude mice (lprcg/lprcg nu/nu; lprcg nudes) were constructed by crossing CBA/KlJms-lprcg/lprcg (CBA-lprcg) and DDD/l-nu/nu mice and observed for lymphoid organ hyperplasia and autoantibody production with or without thymus grafts from various strains of mice including CBA-lprcg. Neither lymphoproliferation nor significantly increased production of autoantibodies was observed in unmanipulated lprcg nudes. In contrast, thymus grafts of both +/+ and lprcg/lprcg genotypes caused lymphoid organ hyperplasia composed of anomalous double-negative T lymphocytes and significantly augmented the production of antibodies against single-stranded DNA (ssDNA). Interestingly, serum Ig and anti-ssDNA antibody levels rose in response to thymus grafts only in IgG but not in IgM classes. These results indicate that the thymus plays a crucial role in the induction of abnormal T-cell differentiation by lprcg and that thymic genotype is irrelevant. PMID:1592441

  19. Crucial roles of the pentatricopeptide repeat protein SOAR1 in Arabidopsis response to drought, salt and cold stresses.

    PubMed

    Jiang, Shang-Chuan; Mei, Chao; Liang, Shan; Yu, Yong-Tao; Lu, Kai; Wu, Zhen; Wang, Xiao-Fang; Zhang, Da-Peng

    2015-07-01

    Whereas several mitochondrial/chloroplast pentatricopeptide repeat (PPR) proteins have been reported to regulate plant responses to abiotic stresses, no nucleus-localized PPR protein has been found to play role in these processes. In the present experiment, we provide evidence that a cytosol-nucleus dual-localized PPR protein SOAR1, functioning to negatively regulate abscisic acid (ABA) signaling in seed germination and postgermination growth, is a crucial, positive regulator of plant response to abiotic stresses. Downregulation of SOAR1 expression reduces, but upregulation of SOAR1 expression enhances, ABA sensitivity in ABA-induced promotion of stomatal closure and inhibition of stomatal opening, and plant tolerance to multiple, major abiotic stresses including drought, high salinity and low temperature. Interestingly and importantly, the SOAR1-overexpression lines display strong abilities to tolerate drought, salt and cold stresses, with surprisingly high resistance to salt stress in germination and postgermination growth of seeds that are able to potentially germinate in seawater, while no negative effect on plant growth and development was observed. So, the SOAR1 gene is likely useful for improvement of crops by transgenic manipulation to enhance crop productivity in stressful conditions. Further experimental data suggest that SOAR1 likely regulates plant stress responses at least partly by integrating ABA-dependent and independent signaling pathways, which is different from the ABI2/ABI1 type 2C protein phosphatase-mediated ABA signaling. These findings help to understand highly complicated stress and ABA signalling network. PMID:26093896

  20. Representation of Cultural Role-Play for Training

    NASA Technical Reports Server (NTRS)

    Santarelli, Thomas; Pepe, Aaron; Rosenzweiz, Larry; Paulus, John; Yi, Ahn Na

    2010-01-01

    The Department of Defense (000) has successfully applied a number of methods for cultural familiarization training ranging from stand-up classroom training, to face-to-face live role-play, to so-called smart-cards. Recent interest has turned to the use of single and mUlti-player gaming technologies to augment these traditional methods of cultural familiarization. One such system, termed CulturePad, has been designed as a game-based role-play environment suitable for use in training and experimentation involving cultural roleplay scenarios. This paper describes the initial CulturePad effort focused on a literature review regarding the use of role-play for cultural training and a feasibility assessment of using a game-mediated environment for role-play. A small-scale pilot involving cultural experts was conducted to collect qualitative behavioral data comparing live role-play to game-mediated role-play in a multiplayer gaming engine.

  1. The Role of Play in Children’s Palliative Care

    PubMed Central

    Boucher, Sue; Downing, Julia; Shemilt, Rise

    2014-01-01

    Play is the universal language of childhood and the time and opportunity to play is every child’s right. The role of play as a vehicle for communication, a tool for distraction and its value in the holistic development of a normal child is without dispute. The role and value of play increases proportionately when a child is made more vulnerable through illness or disability. Despite this, providing time and opportunities to play can be overlooked or considered to be of little importance or relevance when the focus of the adult carers is the amelioration of clinical symptoms of the illness and on lessening the psychological impact the illness may have on the child. This paper outlines the role and the value of play as an integral component in the provision of palliative care for children with chronic, life-threatening and life-limiting conditions. It will show how providing appropriate equipment, sufficient time and relevant play opportunities not only improves the very sick child’s psychological wellbeing, but also allows the child to cast aside the confines and restrictions imposed upon them by their illness and for a few golden moments to be nothing more than a child at play. PMID:27417481

  2. Quantifying GHG Emissions From Terrestrial Ecosystems In Africa - The Crucial Role Of Livestock Systems

    NASA Astrophysics Data System (ADS)

    Butterbach-Bahl, K.; Pelster, D.; Goopy, J.

    2015-12-01

    Knowledge on GHG fluxes from terrestrial ecosystems in Africa remains limited. Published field trials on soil GHG fluxes are summarized in approx. 10 research papers. Emissions related to livestock production, which are dominating most current estimates, rely on modelling work. Thus, uncertainties for African GHG fluxes are likely the highest at continental scale. Even though total GHG fluxes from agricultural soils seem to be low (insufficient fertilizer use/ soil degradation) the opposite might be true for livestock systems. Emissions per kg edible milk protein in SSA are a magnitude higher as for Europe (>100 kg CO2eq kg-1). Differences are related to feed intake, quality and availability, species and breeds, etc. Besides, handling of animal wastes is often less sophisticated, resulting in high nutrient losses and GHG fluxes. Estimates remain unconstrained, since in-situ measurements are missing and emission factors, developed elsewhere, are applied without verification to the African situation. To support African countries to improve emission reporting, to improve productivity of the agricultural sector while minimizing GHG fluxes and to allow them to play a vital role in emission trading, , requires to build in-continent research capacity. The International Livestock Research Institute (ILRI), has recently established a state-of-the art GHG laboratory in East Africa, which is envisioned to build a knowledge hub for environmental research. First measurement results indicate that EF for excreta applications to rangelands might be largely overestimated, mainly due to its rather low N concentrations. On the other hand, EF for ruminant CH4 emissions might be strongly underestimated, since those do not consider that livestock is often held at sub-maintenance levels. Thus, an international initiative is needed to support African countries to learn about land based GHG fluxes and to build research capacity. When do we start?

  3. The crucial protective role of glutathione against tienilic acid hepatotoxicity in rats

    SciTech Connect

    Nishiya, Takayoshi Mori, Kazuhiko Hattori, Chiharu Kai, Kiyonori Kataoka, Hiroko Masubuchi, Noriko Jindo, Toshimasa Manabe, Sunao

    2008-10-15

    To investigate the hepatotoxic potential of tienilic acid in vivo, we administered a single oral dose of tienilic acid to Sprague-Dawley rats and performed general clinicopathological examinations and hepatic gene expression analysis using Affymetrix microarrays. No change in the serum transaminases was noted at up to 1000 mg/kg, although slight elevation of the serum bile acid and bilirubin, and very mild hepatotoxic changes in morphology were observed. In contrast to the marginal clinicopathological changes, marked upregulation of the genes involved in glutathione biosynthesis [glutathione synthetase and glutamate-cysteine ligase (Gcl)], oxidative stress response [heme oxygenase-1 and NAD(P)H dehydrogenase quinone 1] and phase II drug metabolism (glutathione S-transferase and UDP glycosyltransferase 1A6) were noted after 3 or 6 h post-dosing. The hepatic reduced glutathione level decreased at 3-6 h, and then increased at 24 or 48 h, indicating that the upregulation of NF-E2-related factor 2 (Nrf2)-regulated gene and the late increase in hepatic glutathione are protective responses against the oxidative and/or electrophilic stresses caused by tienilic acid. In a subsequent experiment, tienilic acid in combination with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of Gcl caused marked elevation of serum alanine aminotransferase (ALT) with extensive centrilobular hepatocyte necrosis, whereas BSO alone showed no hepatotoxicity. The elevation of ALT by this combination was observed at the same dose levels of tienilic acid as the upregulation of the Nrf2-regulated genes by tienilic acid alone. In conclusion, these results suggest that the impairment of glutathione biosynthesis may play a critical role in the development of tienilic acid hepatotoxicity through extensive oxidative and/or electrophilic stresses.

  4. Role Play in Nutrition Education for the Young Child.

    ERIC Educational Resources Information Center

    Marbach, Ellen S.; Yawkey, Thomas Daniels

    The Curry and Arnaud model for role playing is described and discussed as it relates to nutrition education for young children. The components of the model are: (1) developing the role, (2) using thematic content, (3) displaying feelings (in socially acceptable ways), (4) distinguishing between reality and fantasy, and (5) forming interpersonal…

  5. "Free Vote": Role-Playing Parliament in Action

    ERIC Educational Resources Information Center

    Myers, Lynn

    1977-01-01

    A Canadian political role-playing sequence helps secondary students understand the workings of Parliament and clarify their own values. The issue under debate is abolition or retention of capital punishment. Article describes rationale, teacher's instructions, roles, related legislature, rules of Parliamentary debate, public opinion polls, news…

  6. Empathic Features and Absorption in Fantasy Role-Playing.

    PubMed

    Rivers, Anissa; Wickramasekera, Ian E; Pekala, Ronald J; Rivers, Jennifer A

    2016-01-01

    This study examined the levels of empathy and absorption of individuals who regularly play fantasy and science fiction role-playing games. A hypothesis was developed that higher levels of empathy would be found in individuals who fantasy role-play based upon previous research in hypnosis such as J. R. Hilgard's (1970) imaginative involvement hypothesis, research into the "fantasy prone" personality type (Wilson & Barber, 1981), and the empathic involvement hypothesis (Wickramasekera II & Szlyk, 2003). The participants in the current study were 127 fantasy role-players who volunteered and completed the Davis Interpersonal Reactivity Index (empathy) and the Tellegen Absorption Scale (absorption). The results demonstrated that those who play fantasy role-playing games scored significantly higher than the comparison group on the IRI scale of empathy, confirming the hypothesis that fantasy role-players report experiencing higher levels of empathic involvement with others. Correlational analysis between the measures demonstrated a significant positive correlation between empathy and absorption (r = .43, p < .001). These results collectively suggest that fantasy role-players have a uniquely empathically-imaginative style. The results also confirm and extend previous findings on the relationship between empathy and absorption as predicted by the Empathic Involvement Hypothesis (Wickramasekera II & Szlyk, 2003). PMID:26675155

  7. Adapting a Face-to-Face Role-Playing Simulation for Online Play

    ERIC Educational Resources Information Center

    Bos, Nathan; Shami, N. Sadat

    2006-01-01

    The rapid acceleration of online course offerings presents a design challenge for instructors who want to take materials developed for face-to-face settings and adapt them for asynchronous online usage. Broadcast lectures are relatively easy to transfer, but adapting content is harder when classes use small-group discussions, as in role-playing or…

  8. Playing by the Rules: Instruction and Acculturation in Role-Playing Games

    ERIC Educational Resources Information Center

    Neuenschwander, Bryn

    2008-01-01

    The open-ended, informal, and socially negotiated nature of role-playing games creates a distinct learning challenge for newcomers to the hobby. The explicit rules of the game provide only an incomplete framework for structuring the actions of players, and the expectations and mores of a given group will add other, unspoken rules that discourage…

  9. (Role) Playing Politics in an Environmental Chemistry Lecture Course

    NASA Astrophysics Data System (ADS)

    Smythe, A. Meredith; Higgins, Daniel A.

    2007-02-01

    Mock congressional hearings are described as an active learning, role-playing activity for the environmental chemistry lecture course. Each student plays dual roles in this activity, alternately serving as a witness and committee member on hearing topics selected by the class. As witnesses, the students assume the roles of scientists, politicians, industrial representatives, and environmental group representatives and present both written and oral arguments for or against a particular issue. At other times, they play the role of congressional committee members and question the witnesses. Hearings are held on topics related to renewable and nonrenewable energy; hazardous waste; water, soil, and air pollution; water quality; and genetic engineering. This activity greatly enriches the educational experience for the students by allowing them to become actively engaged in learning and debating specific issues related to course materials.

  10. Crucial role of Toll-like receptors in the zinc/nickel-induced inflammatory response in vascular endothelial cells

    SciTech Connect

    Tsou, Tsui-Chun; Liou, Saou-Hsing; Yeh, Szu-Ching; Tsai, Feng-Yuan; Chao, How-Ran

    2013-12-15

    Our previous studies indicated that zinc induced inflammatory response in both vascular endothelial cells and promonocytes. Here, we asked if other metals could cause the similar effect on vascular endothelial cells and tried to determine its underlying mechanism. Following screening of fifteen metals, zinc and nickel were identified with a marked proinflammatory effect, as determined by ICAM-1 and IL-8 induction, on human umbilical vein endothelial cells (HUVECs). Inhibiting protein expression of myeloid differentiation primary response protein-88 (MyD88), a Toll-like receptor (TLR) adaptor acting as a TLR-signaling transducer, significantly attenuated the zinc/nickel-induced inflammatory response, suggesting the critical roles of TLRs in the inflammatory response. Blockage of TLR-4 signaling by CLI-095, a TLR-4 inhibitor, completely inhibited the nickel-induced ICAM-1 and IL-8 expression and NFκB activation. The same CLI-095 treatment significantly blocked the zinc-induced IL-8 expression, however with no significant effect on the ICAM-1 expression and a minor inhibitory effect on the NFκB activation. The finding demonstrated the differential role of TLR-4 in regulation of the zinc/nickel-induced inflammatory response, where TLR-4 played a dominant role in NFκB activation by nickel, but not by zinc. Moreover, inhibition of NFκB by adenovirus-mediated IκBα expression and Bay 11-7025, an inhibitor of cytokine-induced IκB-α phosphorylation, significantly attenuated the zinc/nickel-induced inflammatory responses, indicating the critical of NFκB in the process. The study demonstrates the crucial role of TLRs in the zinc/nickel-induced inflammatory response in vascular endothelial cells and herein deciphers a potential important difference in NFκB activation via TLRs. The study provides a molecular basis for linkage between zinc/nickel exposure and pathogenesis of the metal-related inflammatory vascular disease. - Highlights: • Both zinc and nickel cause

  11. Detection of faking on role-play tests of assertiveness.

    PubMed

    Kern, J M

    1994-04-01

    Faking and demand characteristics can represent significant threats to the validity of role-play tests of social competence. The present study examined whether faking could be detected via the global judgments of experienced and inexperienced assessors. 26 undergraduates low in assertiveness were induced to fake their performances on the Idiographic Role-play Test via instructions and information. Experienced judges successfully differentiated faking subjects from highly assertive subjects (n = 27) who had been provided with information and nonfaking instructions (98% accuracy). Inexperienced assessors correctly classified 79% of the subjects. Within the discussed limitations of this study, it appears that it is possible to detect faking on role-play tests of assertiveness. PMID:8197276

  12. Crucial role of strategy updating for coexistence of strategies in interaction networks

    NASA Astrophysics Data System (ADS)

    Zhang, Jianlei; Zhang, Chunyan; Cao, Ming; Weissing, Franz J.

    2015-04-01

    Network models are useful tools for studying the dynamics of social interactions in a structured population. After a round of interactions with the players in their local neighborhood, players update their strategy based on the comparison of their own payoff with the payoff of one of their neighbors. Here we show that the assumptions made on strategy updating are of crucial importance for the strategy dynamics. In the first step, we demonstrate that seemingly small deviations from the standard assumptions on updating have major implications for the evolutionary outcome of two cooperation games: cooperation can more easily persist in a Prisoner's Dilemma game, while it can go more easily extinct in a Snowdrift game. To explain these outcomes, we develop a general model for the updating of states in a network that allows us to derive conditions for the steady-state coexistence of states (or strategies). The analysis reveals that coexistence crucially depends on the number of agents consulted for updating. We conclude that updating rules are as important for evolution on a network as network structure and the nature of the interaction.

  13. Confronting Prejudiced Comments: Effectiveness of a Role-Playing Exercise

    ERIC Educational Resources Information Center

    Lawson, Timothy J.; McDonough, Tracy A.; Bodle, James H.

    2010-01-01

    We examined whether a role-playing exercise, similar to that developed by Plous (2000), increases students' ability to generate effective responses to prejudiced comments. We assessed social psychology students' (n = 23) ability to respond to prejudiced comments before and after the exercise, and compared their performance to that of 2 other…

  14. [Anthropology play a key role in simulated portrait].

    PubMed

    Xu, Zhi-Biao

    2006-08-15

    The technology of simulated portrait played a key role in criminal cases' deterction recently, while anthropology is attached to it tightly. This paper analyzed and discussed the impact of anthropology in simulated portrait by means of studying the relationship between races, regions figures skeletons and physiognomy. PMID:17080677

  15. A Recruiting and Hiring Role-Play: An Experiential Simulation

    ERIC Educational Resources Information Center

    Newberry, Robert; Collins, Marianne K.

    2012-01-01

    Creating experiential learning opportunities that engage students, meet marketing curricula objectives, and fit the application in a traditional semester course is extremely challenging. This paper describes a role-playing simulation offered concurrently to the professional selling and sales management classes in which the selling students act as…

  16. Biography and Role Playing: Fostering Empathy in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Poorman, Paula B.

    2002-01-01

    Discusses a means for increasing undergraduate and graduate students' level of empathy. Assigned students to write about and role play a character that they create who suffers from a psychological disorder. Explains that after quantitative and qualitative analyses it was demonstrated that students' empathy increased. (CMK)

  17. The Ecology of Role Play: Intentionality and Cultural Evolution

    ERIC Educational Resources Information Center

    Papadopoulou, Marianna

    2012-01-01

    This study examines the evolutionary function of children's pretence. The everyday, cultural environment that children engage with is of a highly complex structure. Human adaptation, thus, becomes, by analogy, an equally complex process that requires the development of life skills. Whilst in role play children engage in "mimesis" and recreate the…

  18. Role Play and Simulation: Returning to Teaching for Understanding

    ERIC Educational Resources Information Center

    Clapper, Timothy C.

    2010-01-01

    This article describes how simulation and role play can be important learning strategies that will create long-lasting understanding. Simulation involves participating in a very real learning experience that closely resembles an actual setting. These actual settings may be replicated by either employing models or mannequins or in the case of role…

  19. The Korean War: A Role-Play to Remember

    ERIC Educational Resources Information Center

    Krebs, Marjori M.

    2009-01-01

    The Korean War is often given a cursory glance, if that, in U.S. foreign relations today. This article provides all the information necessary to conduct a role-play in one class period to help students understand the events of the war. Introductory and follow-up questions are also included to stimulate discussion and to connect the events of a war…

  20. A Forensic Psychology Exercise: Role Playing and the Insanity Defense.

    ERIC Educational Resources Information Center

    Fass, Michael E.

    1999-01-01

    Presents a role playing exercise that provides students with an introduction to forensic psychology and the insanity defense. Reports that 87% of the students found this exercise to be an enjoyable teaching technique and useful in providing an understanding of the insanity defense. Concludes that the exercise increases student interest and…

  1. A Role Play on Export Decisions and the Exchange Rate.

    ERIC Educational Resources Information Center

    Cotterell, Ann

    1987-01-01

    Explains that the goal of this exercise is to encourage an understanding of the effects of exchange rate changes and the use of forward rates. Provides a role play that involves students working in groups to decide whether to export a consignment of golf trollies to Italy and shortbread to Canada. (BSR)

  2. Try This: Role-Play Party: Talking about Jobs

    ERIC Educational Resources Information Center

    Benucci, Heather

    2015-01-01

    This article presents a stand-alone language-learning activity emphasizing speaking. Specifically, students will participate in role plays to describe occupations and job-related duties. The level of the activity is upper beginner or low intermediate and the time required is 45-60 minutes. The goals are: (1) to ask and answer small-talk questions…

  3. Reusable, Lifelike Virtual Humans for Mentoring and Role-Playing

    ERIC Educational Resources Information Center

    Sims, Edward M.

    2007-01-01

    Lifelike, interactive digital characters, serving as mentors and role-playing actors, have been shown to significantly improve learner motivation and retention. However, the cost of modeling such characters, authoring and editing their interactions, and delivering them over limited-bandwidth connections can be prohibitive. This paper describes a…

  4. The Role Play: More than Make-Believe.

    ERIC Educational Resources Information Center

    Siegel, Martin

    At the University of Akron's Community and Technical College, the major student project for "Principles of Advertising" is the development of ad campaigns for an assigned product. Two groups of students, playing the role of advertising agencies, compete with each other while the remaining students in the class act as the clients. Among the…

  5. Role-Playing Games and Simulations for International Issues Courses

    ERIC Educational Resources Information Center

    Wheeler, Sarah M.

    2006-01-01

    This paper proposes criteria that instructors should be sensitive to when evaluating simulations or role-plays for use in international/comparative politics courses. The potential benefits and drawbacks to these interactive exercises are addressed as well as the special circumstances that must be taken into consideration to reap the full promise…

  6. Using Online Role Play to Teach Internet Safety Awareness

    ERIC Educational Resources Information Center

    Wishart, J. M.; Oades, C. E.; Morris, M.

    2007-01-01

    This paper reports on an evaluation of Net-Detectives, a creative online role play activity aimed at 9-12 year olds. Net-Detectives forms part of Kidsmart, an Internet awareness programme aimed at school children. It was evaluated through a multiple method data collection using questionnaire surveys, follow up telephone interviews with teachers…

  7. Role Playing and Mind Mapping Issues on Nitrate Contamination.

    ERIC Educational Resources Information Center

    Pan, W. L.

    1996-01-01

    Presents mind-mapping and role-playing exercises designed to guide students in the exploration, expression, and integration of varying viewpoints and opinions of a controversial topic (nitrate contamination of water supply); illustrate the importance of applying soil fertility principles to environmental and agronomic management; and encourage…

  8. Interdisciplinary Role Play between Social Work and Theater Students

    ERIC Educational Resources Information Center

    Dennison, Susan T.

    2011-01-01

    Teaching BSW and MSW students beginning interviewing and relationship-building skills is essential in order to prepare them for practice with clients. In social work methods courses, role plays are commonly-used instructional strategies for helping foundation-level students acquire these initial practice skills. Despite the popularity of this…

  9. Development of Confidence in Child Behavior Management through Role Playing.

    ERIC Educational Resources Information Center

    Kress, Gerard C., Jr.; Ehrlichs, Melvin A.

    1990-01-01

    In a preclinical course in pediatric dentistry, 76 students were taught child behavior management through role playing of 7-10 common management situations. Pre- and postcourse measures of student confidence found that, although older students were more confident, all gained significantly from the training. Other student characteristics were also…

  10. Exploring the Concept of Sustainable Development through Role-Playing

    ERIC Educational Resources Information Center

    Buchs, Arnaud; Blanchard, Odile

    2011-01-01

    The concept of sustainable development is used in everyday life by the general public, alongside researchers, institutions, and private companies. Nevertheless, its definition is far from being unequivocal. Clarifying the outline of the concept seems necessary. We have created a role-play for this purpose. Our article aims at depicting its main…

  11. From MMORPG to a Classroom Multiplayer Presential Role Playing Game

    ERIC Educational Resources Information Center

    Susaeta, Heinz; Jimenez, Felipe; Nussbaum, Miguel; Gajardo, Ignacio; Andreu, Juan Jose; Villalta, Marco

    2010-01-01

    The popularity of massively multiplayer online role-playing games (MMORPGs) has grown enormously, with communities of players reaching into the millions. Their fantasy narratives present multiple challenges created by the virtual environment and/or other players. The games' potential for education stems from the fact that players are immersed in a…

  12. Role-playing in nursing theory: engaging online students.

    PubMed

    Levitt, Cheryle; Adelman, Deborah S

    2010-04-01

    The teaching and learning of nursing theory, at all program levels, is challenging due to the complexity and abstract nature of its content, the dry nature in which the study of theory often is approached, a perception of disconnect from practice, and faculty discomfort and avoidance of the subject matter. Adapting creative educational strategies to the online environment is an ongoing challenge for educators. Role-play relates well to the constructivist basis of creating personal meaning based on the individual's experiences. This article examines the use of role-play as an educational strategy for teaching nursing theory in an online baccalaureate program. In a core professional issues course, students adopt the persona of a specific nursing theorist, interacting with other "nursing theorists" played by their peers. Student engagement and active learning reflect excitement and interest, and course evaluations have been extremely positive for this content and method. PMID:20055329

  13. Crucial role of detailed function, task, timeline, link and human vulnerability analyses in HRA

    SciTech Connect

    Ryan, T.G.; Haney, L.N.; Ostrom, L.T.

    1992-10-01

    This paper addresses one major cause for large uncertainties in human reliability analysis (HRA) results, that is, an absence of detailed function, task, timeline, link and human vulnerability analyses. All too often this crucial step in the HRA process is done in a cursory fashion using word of mouth or written procedures which themselves may incompletely or inaccurately represent the human action sequences and human error vulnerabilities being analyzed. The paper examines the potential contributions these detailed analyses can make in achieving quantitative and qualitative HRA results which are: (1) creditable, that is, minimize uncertainty, (2) auditable, that is, systematically linking quantitative results and qualitative information from which the results are derived, (3) capable of supporting root cause analyses on human reliability factors determined to be major contributors to risk, and (4) capable of repeated measures and being combined with similar results from other analyses to examine HRA issues transcending individual systems and facilities. Based on experience analyzing test and commercial nuclear reactors, and medical applications of nuclear technology, an iterative process is suggested for doing detailed function, task, timeline, link and human vulnerability analyses using documentation reviews, open-ended and structured interviews, direct observations, and group techniques. Finally, the paper concludes that detailed analyses done in this manner by knowledgeable human factors practitioners, can contribute significantly to the credibility, auditability, causal factor analysis, and combining goals of the HRA.

  14. The Crucial Role of School Nurses: Ensuring Immunization Compliance, Education, and Documentation.

    ERIC Educational Resources Information Center

    Dychkowski, Linda

    2000-01-01

    Discusses the current status of immunizations, the latest immunization recommendations, and the important role of school nurses in ensuring that all students are properly immunized with the correct immunizations at the correct time. An alphabetical listing of immunizations provides specific details. The paper also discusses myths versus facts…

  15. Environmental consequences of shale gas exploitation and the crucial role of rock microfracturing

    NASA Astrophysics Data System (ADS)

    Renard, Francois

    2015-04-01

    The growing exploitation of unconventional gas and oil resources has dramatically changed the international market of hydrocarbons in the past ten years. However, several environmental concerns have also been identified such as the increased microseismicity, the leakage of gas into freshwater aquifers, and the enhanced water-rock interactions inducing the release of heavy metals and other toxic elements in the produced water. In all these processes, fluids are transported into a network of fracture, ranging from nanoscale microcracks at the interface between minerals and the kerogen of the source rock, to well-developed fractures at the meter scale. Characterizing the fracture network and the mechanisms of its formation remains a crucial goal. A major difficulty when analyzing fractures from core samples drilled at depth is that some of them are produced by the coring process, while some other are produced naturally at depth by the coupling between geochemical and mechanical forces. Here, I present new results of high resolution synchrotron 3D X-ray microtomography imaging of shale samples, at different resolutions, to characterize their microfractures and their mechanisms of formation. The heterogeneities of rock microstructure are also imaged, as they create local stress concentrations where cracks may nucleate or along which they propagate. The main results are that microcracks form preferentially along kerogen-mineral interfaces and propagate along initial heterogeneities according to the local stress direction, connecting to increase the total volume of fractured rock. Their lifetime is also an important parameter because they may seal by fluid circulation, fluid-rock interactions, and precipitation of a cement. Understanding the multi-scale processes of fracture network development in shales and the coupling with fluid circulation represents a key challenge for future research directions.

  16. Play a Starring Role in Your Textbook: A Digital Web Platform with an Embedded Role-Playing Game

    ERIC Educational Resources Information Center

    Spielvogel, Laura; Spielvogel, Christian

    2014-01-01

    In this report, we introduce our digital e-textbook web platform with an integrated role-playing game, which has been created for "introduction to anthropology" courses. We believe that textbooks have the potential to do more to motivate students' pursuit of learning if their material (topically organised chapters supported by…

  17. A crucial role for HVEM and BTLA in preventing intestinal inflammation.

    PubMed

    Steinberg, Marcos W; Turovskaya, Olga; Shaikh, Raziya B; Kim, Gisen; McCole, Declan F; Pfeffer, Klaus; Murphy, Kenneth M; Ware, Carl F; Kronenberg, Mitchell

    2008-06-01

    The interaction between the tumor necrosis factor (TNF) family member LIGHT and the TNF family receptor herpes virus entry mediator (HVEM) co-stimulates T cells and promotes inflammation. However, HVEM also triggers inhibitory signals by acting as a ligand that binds to B and T lymphocyte attenuator (BTLA), an immunoglobulin super family member. The contribution of HVEM interacting with these two binding partners in inflammatory processes remains unknown. In this study, we investigated the role of HVEM in the development of colitis induced by the transfer of CD4(+)CD45RB(high) T cells into recombination activating gene (Rag)(-/-) mice. Although the absence of HVEM on the donor T cells led to a slight decrease in pathogenesis, surprisingly, the absence of HVEM in the Rag(-/-) recipients led to the opposite effect, a dramatic acceleration of intestinal inflammation. Furthermore, the critical role of HVEM in preventing colitis acceleration mainly involved HVEM expression by radioresistant cells in the Rag(-/-) recipients interacting with BTLA. Our experiments emphasize the antiinflammatory role of HVEM and the importance of HVEM expression by innate immune cells in preventing runaway inflammation in the intestine. PMID:18519647

  18. Legume NADPH Oxidases Have Crucial Roles at Different Stages of Nodulation

    PubMed Central

    Montiel, Jesús; Arthikala, Manoj-Kumar; Cárdenas, Luis; Quinto, Carmen

    2016-01-01

    Plant NADPH oxidases, formerly known as respiratory burst oxidase homologues (RBOHs), are plasma membrane enzymes dedicated to reactive oxygen species (ROS) production. These oxidases are implicated in a wide variety of processes, ranging from tissue and organ growth and development to signaling pathways in response to abiotic and biotic stimuli. Research on the roles of RBOHs in the plant’s response to biotic stresses has mainly focused on plant-pathogen interactions; nonetheless, recent findings have shown that these oxidases are also involved in the legume-rhizobia symbiosis. The legume-rhizobia symbiosis leads to the formation of the root nodule, where rhizobia reduce atmospheric nitrogen to ammonia. A complex signaling and developmental pathway in the legume root hair and root facilitate rhizobial entrance and nodule organogenesis, respectively. Interestingly, several reports demonstrate that RBOH-mediated ROS production displays versatile roles at different stages of nodulation. The evidence collected to date indicates that ROS act as signaling molecules that regulate rhizobial invasion and also function in nodule senescence. This review summarizes discoveries that support the key and versatile roles of various RBOH members in the legume-rhizobia symbiosis. PMID:27213330

  19. Legume NADPH Oxidases Have Crucial Roles at Different Stages of Nodulation.

    PubMed

    Montiel, Jesús; Arthikala, Manoj-Kumar; Cárdenas, Luis; Quinto, Carmen

    2016-01-01

    Plant NADPH oxidases, formerly known as respiratory burst oxidase homologues (RBOHs), are plasma membrane enzymes dedicated to reactive oxygen species (ROS) production. These oxidases are implicated in a wide variety of processes, ranging from tissue and organ growth and development to signaling pathways in response to abiotic and biotic stimuli. Research on the roles of RBOHs in the plant's response to biotic stresses has mainly focused on plant-pathogen interactions; nonetheless, recent findings have shown that these oxidases are also involved in the legume-rhizobia symbiosis. The legume-rhizobia symbiosis leads to the formation of the root nodule, where rhizobia reduce atmospheric nitrogen to ammonia. A complex signaling and developmental pathway in the legume root hair and root facilitate rhizobial entrance and nodule organogenesis, respectively. Interestingly, several reports demonstrate that RBOH-mediated ROS production displays versatile roles at different stages of nodulation. The evidence collected to date indicates that ROS act as signaling molecules that regulate rhizobial invasion and also function in nodule senescence. This review summarizes discoveries that support the key and versatile roles of various RBOH members in the legume-rhizobia symbiosis. PMID:27213330

  20. The crucial role of zona pellucida in cryopreservation of oocytes by vitrification.

    PubMed

    Choi, Jung Kyu; Yue, Tao; Huang, Haishui; Zhao, Gang; Zhang, Mingjun; He, Xiaoming

    2015-10-01

    Mammalian oocytes have a proteinaceous hydrogel-like outer shell known as the zona pellucida (ZP) that semi-encloses their plasma membrane and cytoplasm. In this study, we cryopreserved mouse oocytes either with or without ZP by vitrification. Our results show that the presence of an intact ZP could significantly improve the post-vitrification survival of oocytes to 92.1% from 13.3% for oocytes without ZP. Moreover, there was no significant difference in embryonic development between fresh and cryopreserved oocytes with ZP after in vitro fertilization (IVF). Further atomic force microscopy (AFM) analysis showed that the intact oocytes with ZP have an elastic modulus that is more than 85 times higher than that of oocytes without ZP. This may partially explain the important role of ZP in protecting the oocytes by resisting the mechanical stress due to possible ice formation during cryopreservation by vitrification. Collectively, this study reveals a new biophysical role of ZP during vitrification of oocytes and suggests microencapsulation of the many mammalian cells without a ZP in ZP-like hydrogel is an effective strategy to improve their survival post cryopreservation by vitrification. PMID:26297946

  1. GeoQuest an Interactive Role Playing game

    NASA Astrophysics Data System (ADS)

    Maraffi, Sabina; Sacerdoti, Francesco; Scamardella, Alessandra

    2015-04-01

    The acquisition of knowledge and enhancing skills at actual time requires different approaches, involving students as much as possible, taking advantage of informal learning strengths and opportunities of formal learning. In this perspective, the game seems to be a perfect vehicle, not a single student's playing but a cooperative one. The GeoQuest project consists of an interactive role-playing game which involves all students using a patented system: the "teaching projector". This system allows the interaction of the class group through the use of smartphones and tablets, and it shows in real-time the game progress to the whole class. Our role-playing game is based on three routes at different degrees. The students, divided into several categories (physicist, chemists, disseminators, technicians, historians) have to follow a geological trail in order to discover the present and the past of the Earth. During the path, students have to pass some doors in teamwork; they allow assessment and represent the main sharing/disclosure moment. The doors allow to modulate the activities according to single lesson, teaching unit, module. Main Objectives: Working on PC by themselves, students could be even more alone: it needs a best fitting between ICT and cooperative learning. Role-playing helps students to reach their goals easily through cooperation; this in order to avoid the risk of loneliness of Inquiry Based Science Education, preserving entirely the educational value. Science Research now is based on field expert interaction: the role-playing game categories reflect the necessary team to get their goal. The several roles allow everyone to enhance their own skills. the "teaching projector" allows students to comment and to evaluate the groups activities and route them, providing real-time corrections to everybody. The playing categories represent all the aspects of the research areas: from scientists (physicists, chemists), to technicians, to disseminators and

  2. Character selecting advisor for a role-playing game

    NASA Technical Reports Server (NTRS)

    Redfield, Carol L.; Berlanga, Felicia

    1994-01-01

    Role-playing games have been a source of much pleasure and merriment for people of all ages. The process of developing a character for a role-playing game is usually very, very time consuming, delaying what many players consider the most entertaining part of the game. An expert system has been written to assist a player in creating a character by guiding the player through a series of questions. This paper discusses the selection of this topic, the knowledge engineering, the software development, and the resulting program that cuts the time of character development from about 4 hours to 30 minutes. The program was written on a PC and an Apollo in CLIPS 4.3 and currently runs on the Apollo.

  3. Using Role-Playing Games to Teach Astronomy: An Evaluation

    NASA Astrophysics Data System (ADS)

    Francis, Paul

    Since 1998, I've been experimenting with the use of role-playing games to teach astronomy. Students play the role of competing teams of researchers, racing to solve some astrophysical mystery. In this article, I review what has been learned from using these games around the world over the last eight years. The most common problem encountered is a tendency for students to become overly political. An unexpected benefit of these games is the boost that they give to student self- confidence. Overall, they seem to work well with a wide range of students, ranging from ninth grade to graduate school, and students exposed to this game comment repeatedly on how the games changed their attitudes toward the scientific process.

  4. Filamentous hemagglutinin of Bordetella pertussis: nucleotide sequence and crucial role in adherence.

    PubMed Central

    Relman, D A; Domenighini, M; Tuomanen, E; Rappuoli, R; Falkow, S

    1989-01-01

    Filamentous hemagglutinin is a surface-associated adherence protein of Bordetella pertussis, which is a component of some new acellular pertussis vaccines. The nucleotide sequence of an open reading frame that encompasses the filamentous hemagglutinin structural gene, fhaB, suggests that proteolytic processing is necessary to generate the mature 220-kDa filamentous hemagglutinin product. An Arg-Gly-Asp (RGD) tripeptide is found within filamentous hemagglutinin that may be involved in its adherence properties. An internal in-frame deletion in fhaB, encompassing the RGD region, causes loss of B. pertussis-binding to ciliated eukaryotic cells, confirming a potential role for this protein in host-cell binding and infection. Images PMID:2539596

  5. Not just inductive: a crucial mechanical role for the endoderm during heart tube assembly

    PubMed Central

    Varner, Victor D.; Taber, Larry A.

    2012-01-01

    The heart is the first functioning organ to form during development. During gastrulation, the cardiac progenitors reside in the lateral plate mesoderm but maintain close contact with the underlying endoderm. In amniotes, these bilateral heart fields are initially organized as a pair of flat epithelia that move towards the embryonic midline and fuse above the anterior intestinal portal (AIP) to form the heart tube. This medial motion is typically attributed to active mesodermal migration over the underlying endoderm. In this model, the role of the endoderm is twofold: to serve as a mechanically passive substrate for the crawling mesoderm and to secrete various growth factors necessary for cardiac specification and differentiation. Here, using computational modeling and experiments on chick embryos, we present evidence supporting an active mechanical role for the endoderm during heart tube assembly. Label-tracking experiments suggest that active endodermal shortening around the AIP accounts for most of the heart field motion towards the midline. Results indicate that this shortening is driven by cytoskeletal contraction, as exposure to the myosin-II inhibitor blebbistatin arrested any shortening and also decreased both tissue stiffness (measured by microindentation) and mechanical tension (measured by cutting experiments). In addition, blebbistatin treatment often resulted in cardia bifida and abnormal foregut morphogenesis. Moreover, finite element simulations of our cutting experiments suggest that the endoderm (not the mesoderm) is the primary contractile tissue layer during this process. Taken together, these results indicate that contraction of the endoderm actively pulls the heart fields towards the embryonic midline, where they fuse to form the heart tube. PMID:22492358

  6. Play

    NASA Astrophysics Data System (ADS)

    Harteveld, Casper

    Designing a game with a serious purpose involves considering the worlds of Reality and Meaning yet it is undeniably impossible to create a game without a third world, one that is specifically concerned with what makes a game a game: the play elements. This third world, the world of people like designers and artists, and disciplines as computer science and game design, I call the world of Play and this level is devoted to it. The level starts off with some of the misperceptions people have of play. Unlike some may think, we play all the time, even when we grow old—this was also very noticeable in designing the game Levee Patroller as the team exhibited very playful behavior at many occasions. From there, I go into the aspects that characterize this world. The first concerns the goal of the game. This relates to the objectives people have to achieve within the game. This is constituted by the second aspect: the gameplay. Taking actions and facing challenges is subsequently constituted by a gameworld, which concerns the third aspect. And all of it is not possible without the fourth and final aspect, the type of technology that creates and facilitates the game. The four aspects together make up a “game concept” and from this world such a concept can be judged on the basis of three closely interrelated criteria: engagement, immersion, and fun.

  7. Rockin' Role Plays. A Collection of the Finest for Mediation Trainers.

    ERIC Educational Resources Information Center

    Davis, Barbara A.; Corley, Sarah V.

    This guide offers suggestions for implementing role plays to teach conflict resolution skills and provides a variety of role plays useful in different settings. It describes how to effectively prepare for role plays, how to implement role play strategies, and how to debrief and provide feedback to role play participants. Potential problems are…

  8. Crucial role of acetaldehyde in alcohol activation of the mesolimbic dopamine system.

    PubMed

    Diana, Marco; Peana, Alessandra Tiziana; Sirca, Donatella; Lintas, Alessandra; Melis, Miriam; Enrico, Paolo

    2008-10-01

    Ethyl alcohol (EtOH), the main psychoactive ingredient of alcoholic drinks, is widely considered responsible for alcohol abuse and alcoholism through its positive motivational properties, which depend, at least partially, on the activation of the mesolimbic dopaminergic system. On the other hand, acetaldehyde (ACD), EtOH's first metabolite, has been classically considered aversive and useful in the pharmacologic therapy of alcoholics. Here we show that EtOH-derived ACD is necessary for EtOH-induced place preference, a preclinical test with high predictive validity for reward liability. We also found that ACD is essential for EtOH-increased microdialysate dopamine (DA) levels in the nucleus accumbens (NAcc), and that this effect is mimicked by ACD administration to the intraventral tegmental area (VTA). Furthermore, in vitro, ACD enhances VTA DA neuronal firing. Coherently, EtOH-stimulating properties on DA neurons are prevented by pharmacologic blockade of local catalase: the main metabolic step for biotransformation of EtOH into ACD in the central nervous system. These results provide in vivo and in vitro evidence for a key role of ACD in EtOH motivational properties and its activation of the mesolimbic DA system. Additionally, these observations suggest that ACD, by increasing VTA DA neuronal activity, would oppose its well-known peripherally originating aversive properties. These findings could help in devising new effective pharmacologic therapies in alcoholism. PMID:18991876

  9. Quantifying the crucial role of snow in supplying human water demand

    NASA Astrophysics Data System (ADS)

    Mankin, J. S.; Viviroli, D.; Mekonnen, M. M.; Hoekstra, A. Y. Y.; Diffenbaugh, N. S.

    2014-12-01

    Snow is considered essential to ecosystems, people, and climate, regulating water availability by mediating runoff and soil moisture throughout the year, and altering planetary radiative balance. Like canary in a coalmine, snow also serves as a kind of sentinel system, providing a benchmark by which we can measure the advance of global warming. Yet recent analyses reveal that the relationship between snow and warming is more complex: Despite warming, for example, the magnitude of internal climate variability suggests some Northern Hemisphere regions may experience snow increases for at least the next 50 years. While studies demonstrate that snow supply is vital and in critical danger, such assessments are based only on projections of annualized supply-side changes, such as the fraction of total annual runoff coming from snowfall. These measures do not consider a region's unique seasonal patterns of water supply and, in particular, water demand. We therefore do not know snow's relative importance to each region's water supply portfolio, and thus how great a risk global warming presents to regional water availability. Here we present the first quantification of snow's observed role in fulfilling monthly water demand for people in the Northern Hemisphere given each basin's unique sub-annual patterns of snow accumulation and melt. This quantification also reconciles the requirements of ecosystems and includes the buffering capacity of existing artificial storage, such as dams and reservoirs. Our results provide a meaningful baseline against which projected snow changes (from global warming) or demand changes (from population or land-use change) can be evaluated to identify regions at acute risk of disequilibria between future snow water supply and its demand.

  10. The crucial role of nomothetic and idiographic conceptions of time: interdisciplinary collaboration in nuclear waste management.

    PubMed

    Moser, Corinne; Stauffacher, Michael; Krütli, Pius; Scholz, Roland W

    2012-01-01

    The disposal of nuclear waste involves extensive time scales. Technical experts consider up to 1 million years for the disposal of spent fuel and high-level waste in their safety assessment. Yet nuclear waste is not only a technical but also a so-called sociotechnical problem and, therefore, requires interdisciplinary collaboration between technical, natural, social sciences, and the humanities in its management. Given that these disciplines differ in their language, epistemics, and interests, such collaboration might be problematic. Based on evidence from cognitive psychology, we suggest that, in particular, a concept like time is presumably critical and can be understood differently. This study explores how different scientific disciplines understand extensive time scales in general and then focuses on nuclear waste. Eighteen qualitative exploratory interviews were conducted with experts for time-related phenomena of different disciplines, among them experts working in nuclear waste management. Analyses revealed two distinct conceptions of time corresponding to idiographic and nomothetic research approaches: scientists from the humanities and social sciences tend to have a more open, undetermined conception of time, whereas natural scientists tend to focus on a more determined conception that includes some undetermined aspects. Our analyses lead to reflections on potential difficulties for interdisciplinary teams in nuclear waste management. We focus on the understanding of the safety assessment, on potential implications for communication between experts from different disciplines (e.g., between experts from the humanities and engineering for risk assessment and risk communication), and we reflect on the roles of different disciplines in nuclear waste management. PMID:21651596

  11. The crucial role of posterior frontal regions in modality specific components of the spelling process.

    PubMed

    Hillis, Argye E; Chang, Shannon; Breese, Elisabeth; Heidler, Jennifer

    2004-04-01

    Although it is commonly assumed that posterior temporo-parietal regions are the regions of the brain essential for accessing orthographic representations for written output, patients with lesions in these areas also have reading and/or naming impairments at least early after stroke onset. This observation raises the possibility that these regions are important for components of spelling that are not specific to written output. The goal of the present study was to identify any regions of the brain that, when damaged, result in selective impairment in accessing orthographic representations for written output. We studied 54 consecutive right-handed patients with acute, left hemisphere ischemic stroke, who were barely able to perform the motor aspects of writing with the right hand and had at least 10th grade education, on a battery of lexical tasks designed to identify impaired and spared cognitive processes underlying spelling and with advanced magnetic resonance imaging. Only five patients had pure agraphia, and had evidence of impaired access to lexical-orthographic representations for output; and all five had infarct or ischemia in Brodmann's area 44 and 45. Analysis of performance across tasks of three of these patients, whose performance has not been previously reported, provides evidence for additional impairment in converting graphemes to letter shapes or letter-specific motor programs. These three patients, unlike previously reported patients with lexical-orthographic impairment and compromised function in Brodmann's area 44 and 45, also had infarcts in Brodmann's area 6. On the basis of these cases, and those in the literature, we propose a network of brain regions involved in writing words, each with a separate function. This proposal emphasizes the role of the left posterior frontal regions in modality-specific output processes. PMID:15788255

  12. Does hypoxia play a role in infantile hemangioma?

    PubMed

    de Jong, Sophie; Itinteang, Tinte; Withers, Aaron H J; Davis, Paul F; Tan, Swee T

    2016-05-01

    Infantile hemangioma (IH), the most common tumor of infancy, is characterized by rapid growth during infancy, followed by spontaneous involution over 5-10 years. Certain clinical observations have led to the suggestion that IH is triggered and maintained by hypoxia. We review the literature on the possible role of hypoxia in the etiology of IH, in particular, (1) the role of hypoxia inducible factor-1α (HIF-1α) and its downstream targets including GLUT-1 and VEGF; (2) the pathophysiological link between IH and retinopathy of prematurity; (3) hypoxic events in the early life including placental insufficiency, pre-eclampsia and low birthweight that have the potential to promote hypoxic stress; and (4) the evidence supporting the development of IH independent of HIF-1α. We also discuss these observations in the context of recent evidence of the crucial role of stem cells and the cytokines niche that governs their proliferation and inevitable differentiation, offering novel insights into the biology of IH. We propose that various triggers may simultaneously up-regulate HIF-1α, which is downstream of the renin-angiotensin system, specifically angiotensin II, which promotes production of HIF-1α. These developments shed light to the understanding of this enigmatic condition. PMID:26940670

  13. Online gaming addiction? Motives predict addictive play behavior in massively multiplayer online role-playing games.

    PubMed

    Kuss, Daria J; Louws, Jorik; Wiers, Reinout W

    2012-09-01

    Recently, there have been growing concerns about excessive online gaming. Playing Massively Multiplayer Online Role-Playing Games (MMORPGs) appears to be particularly problematic, because these games require a high degree of commitment and time investment from the players to the detriment of occupational, social, and other recreational activities and relations. A number of gaming motives have been linked to excessive online gaming in adolescents and young adults. We assessed 175 current MMORPG players and 90 nonplayers using a Web-based questionnaire regarding their gaming behavior, problems as consequences of gaming, and game motivations and tested their statistical associations. Results indicated that (a) MMORPG players are significantly more likely to experience gaming-related problems relative to nonplayers, and that (b) the gaming motivations escapism and mechanics significantly predicted excessive gaming and appeared as stronger predictors than time investment in game. The findings support the necessity of using measures that distinguish between different types of online games. In addition, this study proves useful regarding the current discussion on establishing (online) gaming addiction as a diagnosis in future categorizations of psychopathology. PMID:22974351

  14. Drama and Role Playing in Teaching Practice: The Role of Group Works

    ERIC Educational Resources Information Center

    Çerkez, Yagmur; Altinay, Zehra; Altinay, Fahriye; Bashirova, Elnara

    2012-01-01

    The research study aims to explore the essence of group work in drama and role playing for teaching practice inline with the nature of collaborative learning process. This research study has qualitative nature by capturing experiences of volunteer ninety pre-service teachers about group works, gained skills from drama and role playing in their…

  15. A Novel Ras Effector Pathway Found to Play Significant Role in Tumor Suppression | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer; photo by Richard Frederickson, Staff Photographer Normal cells have mechanisms to prevent the development of cancer. Among these is a type of tumor suppressor mechanism known as oncogene-induced senescence, or OIS, which halts the uncontrolled growth of cells caused by mutations in oncogenes. The oncogene Ras plays a crucial role in inducing OIS through a specific cascade of proteins, as reported in a recent article in Molecular and Cellular Biology by Jacqueline Salotti, Ph.D., and colleagues in the Eukaryotic Transcriptional Regulation Section of the Mouse Cancer Genetics Program, Center for Cancer Research (CCR).

  16. A Novel Ras Effector Pathway Found to Play Significant Role in Tumor Suppression | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer; photo by Richard Frederickson, Staff Photographer Normal cells have mechanisms to prevent the development of cancer. Among these is a type of tumor suppressor mechanism known as oncogene-induced senescence, or OIS, which halts the uncontrolled growth of cells caused by mutations in oncogenes. The oncogene Ras plays a crucial role in inducing OIS through a specific cascade of proteins, as reported in a recent article in Molecular and Cellular Biology by Jacqueline Salotti, Ph.D., and colleagues in the Eukaryotic Transcriptional Regulation Section of the Mouse Cancer Genetics Program, Center for Cancer Research (CCR).

  17. Does epigenetics play a role in human asthma?

    PubMed

    Vercelli, Donata

    2016-04-01

    Asthma and other allergic diseases are among the most prevalent chronic non-communicable diseases of childhood. According to the World Health Organization, asthma affects >7.0 million children under 18 in the United States, with an economic burden that is estimated to exceed that of tuberculosis and HIV/AIDS combined. Despite much research, the natural history of asthma and its pathogenesis are still in many ways elusive. This review discusses our current understanding of the role epigenetic processes play in asthma pathogenesis, focusing on genome-wide, population-based studies. PMID:26778244

  18. Benchmark problems in which equality plays the major role

    SciTech Connect

    Lusk, E.; Wos, L.

    1992-05-01

    We have recently heard rumors that researchers are again studying paramodulation [Wos87] in the context of strategy for its control. In part to facilitate such research, and in part to provide test problems for evaluating other approaches to equality-oriented reasoning, we offer in this article a set of benchmark problems in which equality plays the dominant role. The test problems are taken from group theory, Robbins algebra, combinatory logic, and other areas. For each problem, we include appropriate clauses and comment as to its status with regard to provability by an unaided automated reasoning program.

  19. Benchmark problems in which equality plays the major role

    SciTech Connect

    Lusk, E.; Wos, L.

    1992-01-01

    We have recently heard rumors that researchers are again studying paramodulation (Wos87) in the context of strategy for its control. In part to facilitate such research, and in part to provide test problems for evaluating other approaches to equality-oriented reasoning, we offer in this article a set of benchmark problems in which equality plays the dominant role. The test problems are taken from group theory, Robbins algebra, combinatory logic, and other areas. For each problem, we include appropriate clauses and comment as to its status with regard to provability by an unaided automated reasoning program.

  20. Mitophagy plays a central role in mitochondrial ageing.

    PubMed

    Diot, Alan; Morten, Karl; Poulton, Joanna

    2016-08-01

    The mechanisms underlying ageing have been discussed for decades, and advances in molecular and cell biology of the last three decades have accelerated research in this area. Over this period, it has become clear that mitochondrial function, which plays a major role in many cellular pathways from ATP production to nuclear gene expression and epigenetics alterations, declines with age. The emerging concepts suggest novel mechanisms, involving mtDNA quality, mitochondrial dynamics or mitochondrial quality control. In this review, we discuss the impact of mitochondria in the ageing process, the role of mitochondria in reactive oxygen species production, in nuclear gene expression, the accumulation of mtDNA damage and the importance of mitochondrial dynamics and recycling. Declining mitophagy (mitochondrial quality control) may be an important component of human ageing. PMID:27352213

  1. TFIIH plays an essential role in RNA polymerase I transcription.

    PubMed

    Iben, Sebastian; Tschochner, Herbert; Bier, Mirko; Hoogstraten, Deborah; Hozák, Pavel; Egly, Jean Marc; Grummt, Ingrid

    2002-05-01

    TFIIH is a multisubunit protein complex that plays an essential role in nucleotide excision repair and transcription of protein-coding genes. Here, we report that TFIIH is also required for ribosomal RNA synthesis in vivo and in vitro. In yeast, pre-rRNA synthesis is impaired in TFIIH ts strains. In a mouse, part of cellular TFIIH is localized within the nucleolus and is associated with subpopulations of both RNA polymerase I and the basal factor TIF-IB. Transcription systems lacking TFIIH are inactive and exogenous TFIIH restores transcriptional activity. TFIIH is required for productive but not abortive rDNA transcription, implying a postinitiation role in transcription. The results provide a molecular link between RNA polymerase I transcription and transcription-coupled repair of active ribosomal RNA genes. PMID:12015980

  2. The Role of Adults in Facilitating the Play of Preschoolers.

    ERIC Educational Resources Information Center

    Culpepper, Susan

    1998-01-01

    Suggests that adults have a responsibility and opportunity to support preschoolers' play by: (1) manifesting positive attitudes toward play; (2) establishing exciting play environments; and (3) offering ideas and play objects. Explores how best to accomplish these supports. (HTH)

  3. Glucocorticoids Play a Key Role in Circadian Cell Cycle Rhythms

    PubMed Central

    Dickmeis, Thomas; Lahiri, Kajori; Nica, Gabriela; Vallone, Daniela; Santoriello, Cristina; Neumann, Carl J; Hammerschmidt, Matthias; Foulkes, Nicholas S

    2007-01-01

    Clock output pathways play a pivotal role by relaying timing information from the circadian clock to a diversity of physiological systems. Both cell-autonomous and systemic mechanisms have been implicated as clock outputs; however, the relative importance and interplay between these mechanisms are poorly understood. The cell cycle represents a highly conserved regulatory target of the circadian timing system. Previously, we have demonstrated that in zebrafish, the circadian clock has the capacity to generate daily rhythms of S phase by a cell-autonomous mechanism in vitro. Here, by studying a panel of zebrafish mutants, we reveal that the pituitary–adrenal axis also plays an essential role in establishing these rhythms in the whole animal. Mutants with a reduction or a complete absence of corticotrope pituitary cells show attenuated cell-proliferation rhythms, whereas expression of circadian clock genes is not affected. We show that the corticotrope deficiency is associated with reduced cortisol levels, implicating glucocorticoids as a component of a systemic signaling pathway required for circadian cell cycle rhythmicity. Strikingly, high-amplitude rhythms can be rescued by exposing mutant larvae to a tonic concentration of a glucocorticoid agonist. Our work suggests that cell-autonomous clock mechanisms are not sufficient to establish circadian cell cycle rhythms at the whole-animal level. Instead, they act in concert with a systemic signaling environment of which glucocorticoids are an essential part. PMID:17373855

  4. ERK Plays a Role in Chromosome Alignment and Participates in M-Phase Progression.

    PubMed

    Iwamoto, Erika; Ueta, Natsumi; Matsui, Yuki; Kamijo, Keiju; Kuga, Takahisa; Saito, Youhei; Yamaguchi, Naoto; Nakayama, Yuji

    2016-06-01

    Cell division, a prerequisite for cell proliferation, is a process in which each daughter cell inherits one complete set of chromosomes. The mitotic spindle is a dedicated apparatus for the alignment and segregation of chromosomes. Extracellular signal-regulated kinase (ERK) 1/2 plays crucial roles in cell cycle progression, particularly during M-phase. Although, association with the mitotic spindle has been reported, the precise roles played by ERK in the dynamics of the mitotic spindle and in M-phase progression remain to be elucidated. In this study, we used MEK inhibitors U0126 and GSK1120212 to dissect the roles of ERK in M-phase progression and chromosome alignment. Fluorescence microscopy revealed that ERK is localized to the spindle microtubules in a manner independent of Src kinase, which is one of the kinases upstream of ERK at mitotic entry. ERK inhibition induces an increase in the number of prophase cells and a decrease in the number of anaphase cells. Time-lapse imaging revealed that ERK inhibition perturbs chromosome alignment, thereby preventing cells from entering anaphase. These results suggest that ERK plays a role in M-phase progression by regulating chromosome alignment and demonstrate one of the mechanisms by which the aberration of ERK signaling may produce cancer cells. J. Cell. Biochem. 117: 1340-1351, 2016. © 2015 Wiley Periodicals, Inc. PMID:26529125

  5. Does Adipose Tissue Thermogenesis Play a Role in Metabolic Health?

    PubMed Central

    Porter, Craig; Børsheim, Elisabet; Sidossis, Labros S.

    2013-01-01

    The function ascribed to brown adipose tissue in humans has long been confined to thermoregulation in neonates, where this thermogenic capacity was thought lost with maturation. Recently, brown adipose tissue depots have been identified in adult humans. The significant oxidative capacity of brown adipocytes and the ability of their mitochondria to respire independently of ATP production, has led to renewed interest in the role that these adipocytes play in human energy metabolism. In our view, there is a need for robust physiological studies determining the relationship between molecular signatures of brown adipose tissue, adipose tissue mitochondrial function, and whole body energy metabolism, in order to elucidate the significance of thermogenic adipose tissue in humans. Until such information is available, the role of thermogenic adipose tissue in human metabolism and the potential that these adipocytes may prevent or treat obesity and metabolic diseases in humans will remain unknown. In this article, we summarize the recent literature pertaining to brown adipose tissue function with the aims of drawing the readers' attention to the lack of data concerning the role of brown adipocytes in human physiology, and to the potential limitations of current research strategies. PMID:23691283

  6. Significant roles played by interleukin-10 in outcome of pregnancy

    PubMed Central

    Mobini, Masoud; Mortazavi, Maryam; Nadi, Somayeh; Zare-Bidaki, Mohammad; Pourtalebi, Somayeh; Arababadi, Mohammad Kazemi

    2016-01-01

    Imbalanced immune responses against fetus alloantigens can lead to abnormality in pregnancy. Interleukin-10 (IL-10) plays key roles in regulation of immune responses against self and foreign antigens to induce tolerance to these antigens. Therefore, alteration in expression of IL-10 during pregnancy may result in several pathologic conditions such as preterm labor. IL-10 leads to a normal pregnancy via several molecular mechanisms including development of tolerogenic dendritic cells, T regulatory lymphocytes and activation of the JAK1/STAT3 pathway in the target cells. This review has collected recent data regarding the status of IL-10 expression during term and preterm deliveries and also its molecular mechanisms that lead to a normal pregnancy. PMID:27081455

  7. Field Effects in the CNS Play Functional Roles

    PubMed Central

    Weiss, Shennan A.; Faber, Donald S.

    2010-01-01

    An endogenous electrical field effect, i.e., ephaptic transmission, occurs when an electric field associated with activity occurring in one neuron polarizes the membrane of another neuron. It is well established that field effects occur during pathological conditions, such as epilepsy, but less clear if they play a functional role in the healthy brain. Here, we describe the principles of field effect interactions, discuss identified field effects in diverse brain structures from the teleost Mauthner cell to the mammalian cortex, and speculate on the function of these interactions. Recent evidence supports that relatively weak endogenous and exogenous field effects in laminar structures reach significance because they are amplified by network interactions. Such interactions may be important in rhythmogenesis for the cortical slow wave and hippocampal sharp wave–ripple, and also during transcranial stimulation. PMID:20508749

  8. The role thermal physiology plays in species invasion

    PubMed Central

    Kelley, Amanda L.

    2014-01-01

    The characterization of physiological phenotypes that may play a part in the establishment of non-native species can broaden our understanding about the ecology of species invasion. Here, an assessment was carried out by comparing the responses of invasive and native species to thermal stress. The goal was to identify physiological patterns that facilitate invasion success and to investigate whether these traits are widespread among invasive ectotherms. Four hypotheses were generated and tested using a review of the literature to determine whether they could be supported across taxonomically diverse invasive organisms. The four hypotheses are as follows: (i) broad geographical temperature tolerances (thermal width) confer a higher upper thermal tolerance threshold for invasive rather than native species; (ii) the upper thermal extreme experienced in nature is more highly correlated with upper thermal tolerance threshold for invasive vs. native animals; (iii) protein chaperone expression—a cellular mechanism that underlies an organism's thermal tolerance threshold—is greater in invasive organisms than in native ones; and (iv) acclimation to higher temperatures can promote a greater range of thermal tolerance for invasive compared with native species. Each hypothesis was supported by a meta-analysis of the invasive/thermal physiology literature, providing further evidence that physiology plays a substantial role in the establishment of invasive ectotherms. PMID:27293666

  9. Microbiota Plays a Role in Oral Immune Priming in Tribolium castaneum.

    PubMed

    Futo, Momir; Armitage, Sophie A O; Kurtz, Joachim

    2015-01-01

    Animals are inhabited by a diverse community of microorganisms. The relevance of such microbiota is increasingly being recognized across a broad spectrum of species, ranging from sponges to primates, revealing various beneficial roles that microbes can play. The red flour beetle Tribolium castaneum represents a well-established experimental model organism for studying questions in ecology and evolution, however, the relevance of its microbial community is still largely unknown. T. castaneum larvae orally exposed to bacterial components of the entomopathogen Bacillus thuringiensis bv. tenebrionis showed increased survival upon a subsequent challenge with spores of this bacterium. To investigate whether T. castaneum microbiota plays a role in this phenomenon, we established a protocol for raising microbe-free larvae and subsequently tested whether they differ in their ability to mount such a priming response. Here we demonstrate that larvae with significantly lowered microbial loads, show decreased survival upon secondary challenge with B. thuringiensis bv. tenebrionis spores, compared to animals that were allowed to regain their microbiota before priming. Although the exact mechanism of oral immune priming is unclear, we here suggest that microbiota plays a crucial role in oral immune priming in this species. PMID:26779124

  10. Microbiota Plays a Role in Oral Immune Priming in Tribolium castaneum

    PubMed Central

    Futo, Momir; Armitage, Sophie A. O.; Kurtz, Joachim

    2016-01-01

    Animals are inhabited by a diverse community of microorganisms. The relevance of such microbiota is increasingly being recognized across a broad spectrum of species, ranging from sponges to primates, revealing various beneficial roles that microbes can play. The red flour beetle Tribolium castaneum represents a well-established experimental model organism for studying questions in ecology and evolution, however, the relevance of its microbial community is still largely unknown. T. castaneum larvae orally exposed to bacterial components of the entomopathogen Bacillus thuringiensis bv. tenebrionis showed increased survival upon a subsequent challenge with spores of this bacterium. To investigate whether T. castaneum microbiota plays a role in this phenomenon, we established a protocol for raising microbe-free larvae and subsequently tested whether they differ in their ability to mount such a priming response. Here we demonstrate that larvae with significantly lowered microbial loads, show decreased survival upon secondary challenge with B. thuringiensis bv. tenebrionis spores, compared to animals that were allowed to regain their microbiota before priming. Although the exact mechanism of oral immune priming is unclear, we here suggest that microbiota plays a crucial role in oral immune priming in this species. PMID:26779124

  11. BAP1 PLAYS A SURVIVAL ROLE IN CUTANEOUS MELANOMA

    PubMed Central

    Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny Ching-Ni; Jönsson, Göran; Frederick, Dennie Tompers; Tsao, Hensin

    2014-01-01

    Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous/ocular melanoma (CM/OM) predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of cutaneous melanoma is not fully understood. We thus set out to characterize BAP1 in cutaneous melanoma and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared to nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony forming capability, induced apoptosis and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may play a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology which is context and cell dependent. PMID:25521456

  12. Doublecortin May Play a Role in Defining Chondrocyte Phenotype

    PubMed Central

    Ge, Dongxia; Zhang, Qing-Song; Zabaleta, Jovanny; Zhang, Qiuyang; Liu, Sen; Reiser, Brendan; Bunnell, Bruce A.; Braun, Stephen E.; O’Brien, Michael J.; Savoie, Felix H.; You, Zongbing

    2014-01-01

    Embryonic development of articular cartilage has not been well understood and the role of doublecortin (DCX) in determination of chondrocyte phenotype is unknown. Here, we use a DCX promoter-driven eGFP reporter mouse model to study the dynamic gene expression profiles in mouse embryonic handplates at E12.5 to E13.5 when the condensed mesenchymal cells differentiate into either endochondral chondrocytes or joint interzone cells. Illumina microarray analysis identified a variety of genes that were expressed differentially in the different regions of mouse handplate. The unique expression patterns of many genes were revealed. Cytl1 and 3110032G18RIK were highly expressed in the proximal region of E12.5 handplate and the carpal region of E13.5 handplate, whereas Olfr538, Kctd15, and Cited1 were highly expressed in the distal region of E12.5 and the metacarpal region of E13.5 handplates. There was an increasing gradient of Hrc expression in the proximal to distal direction in E13.5 handplate. Furthermore, when human DCX protein was expressed in human adipose stem cells, collagen II was decreased while aggrecan, matrilin 2, and GDF5 were increased during the 14-day pellet culture. These findings suggest that DCX may play a role in defining chondrocyte phenotype. PMID:24758934

  13. Parliamentarians play key role in linking population and social development.

    PubMed

    1995-01-01

    Mr. Hirofunti Ando, Deputy Executive Director of the UNFPA, delivered the statement of Dr. Nafis Sadik, Executive Director of the UNFPA at the International Meeting of Parliamentarians on Population and Social Development. The International Conference of Parliamentarians on Population and Development (ICPPD) in Cairo in September 1994 made a significant impact on the attitudes and support of parliamentarians regarding population issues. The Asian Forum of Parliamentarians on Population and Development (AFPPD) brought together a group of parliamentarians from all over the world to discuss population issues and social development. The World Summit included in its deliberations the accumulated experiences of earlier international conferences dealing with social economic issues. The ICPD Program of Action addressed concerns relevant to the agenda of the Social Summit: the crucial contribution that early population stabilization will make towards the attainment of sustainable development; the significant role of integrated policies on population and development in creating employment; the importance of population policies and programs in alleviating poverty; the contributions of reproductive health policies, including high-quality family planning services, to the enhancement of the status of women and to the achievement of gender equality; the synergy between education, family planning, and the general improvement of the human condition; and the relationship between population pressures, poverty, and environmental degradation. The ICPD Program of Action also identified critically important population and development objectives, such as ensuring access to education, especially of girls; reducing infant, child, and maternal mortality; and providing universal access to reproductive health and family planning services. Now the challenge is to mobilize the necessary resources for the Social Summit. PMID:12289910

  14. Potassium channel openers and prostacyclin play a crucial role in mediating the vasorelaxant activity of Gynura procumbens

    PubMed Central

    2013-01-01

    Background Previous studies of Gynura procumbens (G. procumbens) have shown that partially purified fractions of the leaves are capable of lowering the blood pressure of rats by inhibiting angiotensin-converting enzymic activity and causing vasodilatation. The objectives of this study were therefore to further purify the active compounds that exhibited selective effects on blood vessels, determine the mechanism of actions, and to qualitatively analyse the putative compounds present. Methods The butanolic fraction (BU) of the crude ethanolic extract was purified using column chromatography to obtain several sub-fractions of different polarities. The in vitro effects of BU and the sub-fractions on vascular tension were subsequently determined using isolated rat thoracic aortic rings. The most potent sub-fraction (F1) alone was then investigated for its mechanisms of the vasorelaxant activity. In another experiment, thin-layer chromatography was used to qualitatively analyse the active compounds found in F1. Results The BU and the sub-fractions ranging from 10-7 to 10-2 g/ml significantly (p < 0.05) inhibited the sustained tonic contractions induced by phenylephrine and potassium chloride in a concentration-dependent manner with various degree of potency. The most potent sub-fraction (F1) antagonised the calcium-induced vasocontractions (1 x 10-4 – 1 x 10-2 M) in calcium-free with high concentration of potassium as well as in calcium- and potassium-free Krebs-Henseleit solutions. Contractions induced by noradrenaline and caffeine were not affected by F1. The vasorelaxing effect caused by F1 was significantly attenuated with preincubation of potassium channel blockers (glibenclamide and 4-aminopyridine) and prostacyclin inhibitor (indomethacin) while it was not affected by preincubation with tetraethylammonium, l-nitro-arginine methyl esther, propanolol, atropine, oxadiazolo quinoxalin one and methylene blue. The qualitative phytochemical analysis of F1 indicated the presence of flavonoids. Conclusion These results confirm previous findings that G. procumbens causes vasodilatory effects by blocking calcium channels. In addition, the present study further demonstrates that the vasodilatory effect of G. procumbens may also be due to the opening of potassium channels and the stimulation of prostacyclin production. The putative compounds are probably flavonoids in nature. PMID:23879679

  15. Keratinocyte expression of inflammatory mediators plays a crucial role in substance P-induced acute and chronic pain

    PubMed Central

    2012-01-01

    Tibia fracture in rats followed by cast immobilization leads to nociceptive, trophic, vascular and bone-related changes similar to those seen in Complex Regional Pain Syndrome (CRPS). Substance P (SP) mediated neurogenic inflammation may be responsible for some of the signs of CRPS in humans. We therefore hypothesized that SP acting through the SP receptor (NK1) leads to the CRPS-like changes found in the rat model. In the present study, we intradermally injected rats with SP and monitored hindpaw mechanical allodynia, temperature, and thickness as well as tissue levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6), and nerve growth factor-β (NGF) for 72 h. Anti-NGF antibody was utilized to block the effects of SP-induced NGF up-regulation. Fracture rats treated with the selective NK1 receptor antagonist LY303870 prior to cast removal were assessed for BrdU, a DNA synthesis marker, incorporation in skin cells to examine cellular proliferation. Bone microarchitecture was measured using micro computed tomography (μCT). We observed that: (1) SP intraplantar injection induced mechanical allodynia, warmth and edema as well as the expression of nociceptive mediators in the hindpaw skin of normal rats, (2) LY303870 administered intraperitoneally after fracture attenuated allodynia, hindpaw unweighting, warmth, and edema, as well as cytokine and NGF expression, (3) LY303870 blocked fracture-induced epidermal thickening and BrdU incorporation after fracture, (4) anti-NGF antibody blocked SP-induced allodynia but not warmth or edema, and (5) LY303870 had no effect on bone microarchitecture. Collectively our data indicate that SP acting through NK1 receptors supports the nociceptive and vascular components of CRPS, but not the bone-related changes. PMID:22824437

  16. Autoinducer-2 Plays a Crucial Role in Gut Colonization and Probiotic Functionality of Bifidobacterium breve UCC2003

    PubMed Central

    Bottacini, Francesca; Lanigan, Noreen; Casey, Pat G.; Huys, Geert; Nelis, Hans J.; van Sinderen, Douwe; Coenye, Tom

    2014-01-01

    In the present study we show that luxS of Bifidobacterium breve UCC2003 is involved in the production of the interspecies signaling molecule autoinducer-2 (AI-2), and that this gene is essential for gastrointestinal colonization of a murine host, while it is also involved in providing protection against Salmonella infection in Caenorhabditis elegans. We demonstrate that a B. breve luxS-insertion mutant is significantly more susceptible to iron chelators than the WT strain and that this sensitivity can be partially reverted in the presence of the AI-2 precursor DPD. Furthermore, we show that several genes of an iron starvation-induced gene cluster, which are downregulated in the luxS-insertion mutant and which encodes a presumed iron-uptake system, are transcriptionally upregulated under in vivo conditions. Mutation of two genes of this cluster in B. breve UCC2003 renders the derived mutant strains sensitive to iron chelators while deficient in their ability to confer gut pathogen protection to Salmonella-infected nematodes. Since a functional luxS gene is present in all tested members of the genus Bifidobacterium, we conclude that bifidobacteria operate a LuxS-mediated system for gut colonization and pathogen protection that is correlated with iron acquisition. PMID:24871429

  17. Mucosal maltase-glucoamylase plays a crucial role in starch digestion and prandial glucose homeostasis of mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starch is the major source of food glucose, and its digestion requires small intestinal alpha-glucosidic activities provided by the 2 soluble amylases and 4 enzymes bound to the mucosal surface of enterocytes. Two of these mucosal activities are associated with sucrase-isomaltase complex, while anot...

  18. Vulnerability in early life to changes in the rearing environment plays a crucial role in the aetiopathology of psychiatric disorders.

    PubMed

    Niwa, Minae; Matsumoto, Yurie; Mouri, Akihiro; Ozaki, Norio; Nabeshima, Toshitaka

    2011-05-01

    Adverse events early in life, including maternal separation and social isolation, profoundly affect brain development and adult behaviour and may contribute to the occurrence of psychiatric disorders such as schizophrenia and mood disorders in genetically predisposed individuals. The molecular mechanisms underlying these environmentally induced developmental adaptations are unclear and best evaluated in animal paradigms with translational salience. In this study, we examined the effects in mice of maternal separation and/or social isolation for 6 h/d between postnatal days 15 and 21 on performance during adulthood in the open-field, social interaction, elevated plus-maze, forced swimming, Y-maze, novel object recognition, conditioned fear-learning, prepulse inhibition, and locomotor activity tests, to investigate whether this animal model could show the phenotypes for schizophrenia and mood disorders. The stress of maternal separation and isolation led to adult behavioural deficits, activation of the hypothalamic-pituitary-adrenal axis, and decreases in the levels of norepinephrine and dopamine in the frontal cortex and metabolites of dopamine and serotonin in the amygdala, showing the involvement of endocrine and neuronal risk in behavioural deficits. The results suggest that the frontal cortex and amygdala undergo structural remodelling induced by the stress of maternal separation and isolation, which alters behavioural and physiological responses in adulthood, including anxiety, memory and other cognitive processes. Further, social isolation enhanced the behavioural dysfunctions induced by maternal separation. These findings indicate that maternal separation and social isolation early in life can lead to long-lasting abnormal behaviour and pathophysiological impairments including schizophrenia and mood disorders. PMID:20950517

  19. RAD51 plays a crucial role in halting cell death program induced by ionizing radiation in bovine oocytes.

    PubMed

    Kujjo, Loro L; Ronningen, Reg; Ross, Pablo; Pereira, Ricardo J G; Rodriguez, Ramon; Beyhan, Zeki; Goissis, Marcelo D; Baumann, Thomas; Kagawa, Wataru; Camsari, Cagri; Smith, George W; Kurumizaka, Hitoshi; Yokoyama, Shigeyuki; Cibelli, Jose B; Perez, Gloria I

    2012-03-01

    Reproductive health of humans and animals exposed to daily irradiants from solar/cosmic particles remains largely understudied. We evaluated the sensitivities of bovine and mouse oocytes to bombardment by krypton-78 (1 Gy) or ultraviolet B (UV-B; 100 microjoules). Mouse oocytes responded to irradiation by undergoing massive activation of caspases, rapid loss of energy without cytochrome-c release, and subsequent necrotic death. In contrast, bovine oocytes became positive for annexin-V, exhibited cytochrome-c release, and displayed mild activation of caspases and downstream DNAses but with the absence of a complete cell death program; therefore, cytoplasmic fragmentation was never observed. However, massive cytoplasmic fragmentation and increased DNA damage were induced experimentally by both inhibiting RAD51 and increasing caspase 3 activity before irradiation. Microinjection of recombinant human RAD51 prior to irradiation markedly decreased both cytoplasmic fragmentation and DNA damage in both bovine and mouse oocytes. RAD51 response to damaged DNA occurred faster in bovine oocytes than in mouse oocytes. Therefore, we conclude that upon exposure to irradiation, bovine oocytes create a physiologically indeterminate state of partial cell death, attributed to rapid induction of DNA repair and low activation of caspases. The persistence of these damaged cells may represent an adaptive mechanism with potential implications for livestock productivity and long-term health risks associated with human activity in space. PMID:22190703

  20. Far Upstream Element Binding Protein Plays a Crucial Role in Embryonic Development, Hematopoiesis, and Stabilizing Myc Expression Levels.

    PubMed

    Zhou, Weixin; Chung, Yang Jo; Parrilla Castellar, Edgardo R; Zheng, Ying; Chung, Hye-Jung; Bandle, Russell; Liu, Juhong; Tessarollo, Lino; Batchelor, Eric; Aplan, Peter D; Levens, David

    2016-03-01

    The transcription factor far upstream element binding protein (FBP) binds and activates the MYC promoter when far upstream element is via TFIIH helicase activity early in the transcription cycle. The fundamental biology and pathology of FBP are complex. In some tumors FBP seems pro-oncogenic, whereas in others it is a tumor suppressor. We generated an FBP knockout (Fubp1(-/-)) mouse to study FBP deficiency. FBP is embryo lethal from embryonic day 10.5 to birth. A spectrum of pathology is associated with FBP loss; besides cerebral hyperplasia and pulmonary hypoplasia, pale livers, hypoplastic spleen, thymus, and bone marrow, cardiac hypertrophy, placental distress, and small size were all indicative of anemia. Immunophenotyping of hematopoietic cells in wild-type versus knockout livers revealed irregular trilineage anemia, with deficits in colony formation. Despite normal numbers of hematopoietic stem cells, transplantation of Fubp1(-/-) hematopoietic stem cells into irradiated mice entirely failed to reconstitute hematopoiesis. In competitive transplantation assays against wild-type donor bone marrow, Fubp1(-/-) hematopoietic stem cells functioned only sporadically at a low level. Although cultures of wild-type mouse embryo fibroblasts set Myc levels precisely, Myc levels of mouse varied wildly between fibroblasts harvested from different Fubp1(-/-) embryos, suggesting that FBP contributes to Myc set point fixation. FBP helps to hold multiple physiologic processes to close tolerances, at least in part by constraining Myc expression. PMID:26774856

  1. Active Learning in the Classroom: The Use of Group Role Plays.

    ERIC Educational Resources Information Center

    Kitzerow, Phyllis

    1990-01-01

    Describes group role-playing activities that have been used to teach about education, criminology, and sex roles. Suggests that role play helps students to absorb and retain many of the insights about the issues involved. (DB)

  2. Mechanistic origins of chemo- and regioselectivity of Ru(II)-catalyzed reactions involving ortho-alkenylarylacetylene, alkyne, and methanol: the crucial role of a chameleon-like intermediate.

    PubMed

    Dang, Yanfeng; Qu, Shuanglin; Tao, Yuan; Song, Chunyu; Wang, Zhi-Xiang

    2014-10-01

    M06-DFT computations have been applied to understand four catalytic systems which involved [Ru(Cp*)(MeCN)3]PF6 or [Ru(Tp)(PPh3)(MeCN)2]PF6 as mediator and ortho-alkenylarylacetylene, terminal alkyne, and methanol as reactants. Potentially, the products of these systems could be dihydrobiphenylenes, 1,3-dienyl ether, and naphthalene. Remarkably, each system afforded product selectively. Our computed mechanisms successfully account for the chemo- and regioselectivities of these systems. Furthermore, the study demonstrates that the chameleon-like mono(carbene) intermediates formed via the intermolecular alkyne-alkyne oxidative coupling play a crucial role to complete the reactions. According to their geometric and electronic structures, three resonance structures were introduced to characterize their reactivity properties, which address the features of the classical alkyne-alkyne oxidative coupling intermediates, mono(carbene) species, and electrophilicity of the intermediates, respectively. The reactivity properties lead to three channels isomerizing the intermediates to three isomers. Surprisingly, the bis(carbene) isomers, which are similar to the bis(carbene) intermediates generally considered to be crucial in the neutral RuCp*Cl-catalyzed systems, are accessible but not reactive enough to continue the subsequent reaction steps partially due to aromaticity. The other two isomers continue subsequent reaction steps. These findings may help not only to understand the four specific catalytic reactions but also to advance the [2 + 2 + 2] synthetic methodology. PMID:25222525

  3. Role-Play and Language Socialization among Bilingual Korean Children in the United States

    ERIC Educational Resources Information Center

    Yun, Seongwon

    2008-01-01

    This article examines children's role-play within the framework of language socialization, as well as the relations between (a) utterances made by young bilingual Korean children within the role-play frame and (b) metacommunicative utterances about the play. It analyzes the language features that children use to set up the context of role-play and…

  4. Copy number variation plays an important role in clinical epilepsy

    PubMed Central

    Olson, Heather; Shen, Yiping; Avallone, Jennifer; Sheidley, Beth R.; Pinsky, Rebecca; Bergin, Ann M.; Berry, Gerard T.; Duffy, Frank H.; Eksioglu, Yaman; Harris, David J.; Hisama, Fuki M.; Ho, Eugenia; Irons, Mira; Jacobsen, Christina M.; James, Philip; Kothare, Sanjeev; Khwaja, Omar; Lipton, Jonathan; Loddenkemper, Tobias; Markowitz, Jennifer; Maski, Kiran; Megerian, J. Thomas; Neilan, Edward; Raffalli, Peter C.; Robbins, Michael; Roberts, Amy; Roe, Eugene; Rollins, Caitlin; Sahin, Mustafa; Sarco, Dean; Schonwald, Alison; Smith, Sharon E.; Soul, Janet; Stoler, Joan M.; Takeoka, Masanori; Tan, Wen-Han; Torres, Alcy R.; Tsai, Peter; Urion, David K.; Weissman, Laura; Wolff, Robert; Wu, Bai-Lin; Miller, David T.; Poduri, Annapurna

    2015-01-01

    Objective To evaluate the role of copy number abnormalities detectable by chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center. Methods We identified patients with ICD-9 codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children’s Hospital. We reviewed medical records and included patients meeting criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA. Results Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1–4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18 kb to 142 Mb, and 34% were over 500 kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or “hotspots.” We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy. Interpretation Copy number abnormalities play an important role in patients with epilepsy. Given that the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy. PMID:24811917

  5. HERG Protein Plays a Role in Moxifloxacin-Induced Hypoglycemia

    PubMed Central

    Qiu, Hai-Yan; Yuan, Sha-Sha; Yang, Fang-Yuan; Shi, Ting-Ting; Yang, Jin-Kui

    2016-01-01

    The purpose of this study was to investigate the effect of moxifloxacin on HERG channel protein and glucose metabolism. HERG expression was investigated using immunohistochemistry. The whole-cell patch clamp method was used to examine the effect of moxifloxacin on HERG channel currents. A glucose tolerance test was used to analyze the effects of moxifloxacin on blood glucose and insulin concentrations in mice. Results show that HERG protein was expressed in human pancreatic β-cells. Moxifloxacin inhibited HERG time-dependent and tail currents in HEK293 cells in a concentration-dependent manner. The IC50 of moxifloxacin inhibition was 36.65 μmol/L. Moxifloxacin (200 mg/kg) reduced blood glucose levels and increased insulin secretion in wild-type mice at 60 min after the start of the glucose tolerance test. In contrast, moxifloxacin did not significantly alter blood glucose and insulin levels in HERG knockout mice. Serum glucose levels increased and insulin concentrations decreased in HERG knockout mice when compared to wild-type mice. The moxifloxacin-induced decrease in blood glucose and increase in insulin secretion occurred via the HERG protein; thus, HERG protein plays a role in insulin secretion. PMID:26649323

  6. Sex Differences in Depression: Does Inflammation Play a Role?

    PubMed Central

    Derry, Heather M.; Padin, Avelina C.; Kuo, Jennifer L.; Hughes, Spenser; Kiecolt-Glaser, Janice K.

    2016-01-01

    Women become depressed more frequently than men, a consistent pattern across cultures. Inflammation plays a key role in initiating depression among a subset of individuals, and depression also has inflammatory consequences. Notably, women experience higher levels of inflammation and greater autoimmune disease risk compared to men. In the current review, we explore the bidirectional relationship between inflammation and depression and describe how this link may be particularly relevant for women. Compared to men, women may be more vulnerable to inflammation-induced mood and behavior changes. For example, transient elevations in inflammation prompt greater feelings of loneliness and social disconnection for women than for men, which can contribute to the onset of depression. Women also appear to be disproportionately affected by several factors that elevate inflammation, including prior depression, somatic symptomatology, interpersonal stressors, childhood adversity, obesity, and physical inactivity. Relationship distress and obesity, both of which elevate depression risk, are also more strongly tied to inflammation for women than for men. Taken together, these findings suggest that women’s susceptibility to inflammation and its mood effects may contribute to sex differences in depression. Depression continues to be a leading cause of disability worldwide, with women experiencing greater risk than men. Due to the depression-inflammation connection, these patterns may promote additional health risks for women. Considering the impact of inflammation on women’s mental health may foster a better understanding of sex differences in depression, as well as the selection of effective depression treatments. PMID:26272539

  7. Aluminum-induced pulmonary fibrosis: do fibers play a role?

    PubMed

    Gilks, B; Churg, A

    1987-07-01

    A 50-yr-old man with a history of 19 yr of work in the aluminum smelting industry, including 14 years in the potrooms, was found to have diffuse interstitial fibrosis, slightly more severe in the upper zones. He died of respiratory insufficiency 5 yr after initial presentation. Analysis of lung by electron optical techniques revealed 15,000,000,000 nonfibrous particles and 1,300,000,000 fibrous particles of aluminum oxide/g dry lung, values representing approximately a 1,000-fold increase over background exposure. The nonfibrous particles had a geometric mean diameter of 0.4 mu, and the fibers had a geometric mean length of 1.0 mu, a width of 0.06 mu, and an aspect ratio of 16. X-ray diffraction demonstrated alpha but not gamma aluminum oxide. These studies indicate that previous suggestions relating aluminum-induced fibrosis to the presence of gamma aluminum oxide are not correct. Although pulmonary fibrosis in this case may be a response to a very high total aluminum particle burden, the presence of large numbers of fibers raises the possibility that fibers play a role in aluminum fibrosis. PMID:3605831

  8. Negative ratings play a positive role in information filtering

    NASA Astrophysics Data System (ADS)

    Zeng, Wei; Zhu, Yu-Xiao; Lü, Linyuan; Zhou, Tao

    2011-11-01

    The explosive growth of information asks for advanced information filtering techniques to solve the so-called information overload problem. A promising way is the recommender system which analyzes the historical records of users’ activities and accordingly provides personalized recommendations. Most recommender systems can be represented by user-object bipartite networks where users can evaluate and vote for objects, and ratings such as “dislike” and “I hate it” are treated straightforwardly as negative factors or are completely ignored in traditional approaches. Applying a local diffusion algorithm on three benchmark data sets, MovieLens, Netflix and Amazon, our study arrives at a very surprising result, namely the negative ratings may play a positive role especially for very sparse data sets. In-depth analysis at the microscopic level indicates that the negative ratings from less active users to less popular objects could probably have positive impacts on the recommendations, while the ones connecting active users and popular objects mostly should be treated negatively. We finally outline the significant relevance of our results to the two long-term challenges in information filtering: the sparsity problem and the cold-start problem.

  9. Sex Differences in Depression: Does Inflammation Play a Role?

    PubMed

    Derry, Heather M; Padin, Avelina C; Kuo, Jennifer L; Hughes, Spenser; Kiecolt-Glaser, Janice K

    2015-10-01

    Women become depressed more frequently than men, a consistent pattern across cultures. Inflammation plays a key role in initiating depression among a subset of individuals, and depression also has inflammatory consequences. Notably, women experience higher levels of inflammation and greater autoimmune disease risk compared to men. In the current review, we explore the bidirectional relationship between inflammation and depression and describe how this link may be particularly relevant for women. Compared to men, women may be more vulnerable to inflammation-induced mood and behavior changes. For example, transient elevations in inflammation prompt greater feelings of loneliness and social disconnection for women than for men, which can contribute to the onset of depression. Women also appear to be disproportionately affected by several factors that elevate inflammation, including prior depression, somatic symptomatology, interpersonal stressors, childhood adversity, obesity, and physical inactivity. Relationship distress and obesity, both of which elevate depression risk, are also more strongly tied to inflammation for women than for men. Taken together, these findings suggest that women's susceptibility to inflammation and its mood effects may contribute to sex differences in depression. Depression continues to be a leading cause of disability worldwide, with women experiencing greater risk than men. Due to the depression-inflammation connection, these patterns may promote additional health risks for women. Considering the impact of inflammation on women's mental health may foster a better understanding of sex differences in depression, as well as the selection of effective depression treatments. PMID:26272539

  10. Extra Microchromosomes Play Male Determination Role in Polyploid Gibel Carp.

    PubMed

    Li, Xi-Yin; Zhang, Qi-Ya; Zhang, Jun; Zhou, Li; Li, Zhi; Zhang, Xiao-Juan; Wang, Da; Gui, Jian-Fang

    2016-07-01

    Sex is generally determined by sex chromosomes in vertebrates, and sex chromosomes exhibit the most rapidly-evolving traits. Sex chromosome evolution has been revealed previously in numerous cases, but the association between sex chromosome origin and the reproduction mode transition from unisexual to sexual reproduction remains unclear. Here, we have isolated a male-specific sequence via analysis of amplified fragment length polymorphism from polyploid gibel carp (Carassius gibelio), a species that not only has the ability to reproduce unisexually but also contains males in wild populations. Subsequently, we have found through FISH analysis that males have several extra microchromosomes with repetitive sequences and transposable elements when compared to females. Moreover, we produced sex-reversed physiological females with a male-specific marker by using estradiol hormone treatment, and two gynogenetic families were established from them. In addition, the male incidence rates of two gynogenetic families were revealed to be closely associated with the extra microchromosome number of the sex-reversed physiological females. These results suggest that the extra microchromosomes in males might resemble a common feature of sex chromosomes and might play a significant role in male determination during the evolutionary trajectory of the reproduction mode transition from unisexual to sexual reproduction in the polyploid fish. PMID:27017622

  11. Hepatic ERK activity plays a role in energy metabolism.

    PubMed

    Jiao, Ping; Feng, Bin; Li, Yujie; He, Qin; Xu, Haiyan

    2013-08-15

    Mitogen activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK) and P38, have been reported to play important roles in energy homeostasis. In this study, we show that the activity of extracellular signal-regulated kinase (ERK) is increased in the livers of diet induced and genetically obese mice. Activation of ERK in the livers of lean mice by over-expressing the constitutively active MAPK kinase 1 (MEK CA) results in decreased energy expenditure, lowered expression of genes involved in fatty acid oxidation, increases fasting hyperglycemia and causes systemic insulin resistance. Interestingly, hepatic glycogen content is markedly increased and expression of G6Pase gene is decreased in mice over-expressing MEK CA compared to control mice expressing green fluorescent protein (GFP), therefore hepatic glucose output is not likely the major contributor of hyperglycemia. One potential mechanism of decreased expression of G6Pase gene by MEK CA is likely due to ERK mediated phosphorylation and cytosolic retention of FOXO1. Adipocytes isolated from MEK CA mice display increased lipolysis. Circulating levels of free fatty acids (FFAs) in these mice are also increased, which possibly contribute to systemic insulin resistance and subsequent hyperglycemia. Consistent with these results, knocking down ERK expression in the liver of diet induced obese (DIO) mice improves systemic insulin and glucose tolerance. These results indicate that increased hepatic ERK activity in DIO mice may contribute to increased liver glycogen content and decreased energy expenditure in obesity. PMID:23732116

  12. The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment.

    PubMed

    Sionov, Ronit Vogt; Fridlender, Zvi G; Granot, Zvi

    2015-12-01

    Neutrophils are myeloid cells that constitute 50-70 % of all white blood cells in the human circulation. Traditionally, neutrophils are viewed as the first line of defense against infections and as a major component of the inflammatory process. In addition, accumulating evidence suggest that neutrophils may also play a key role in multiple aspects of cancer biology. The possible involvement of neutrophils in cancer prevention and promotion was already suggested more than half a century ago, however, despite being the major component of the immune system, their contribution has often been overshadowed by other immune components such as lymphocytes and macrophages. Neutrophils seem to have conflicting functions in cancer and can be classified into anti-tumor (N1) and pro-tumor (N2) sub-populations. The aim of this review is to discuss the varying nature of neutrophil function in the cancer microenvironment with a specific emphasis on the mechanisms that regulate neutrophil mobilization, recruitment and activation. PMID:24895166

  13. Genome-wide siRNA Screening at Biosafety Level 4 Reveals a Crucial Role for Fibrillarin in Henipavirus Infection

    PubMed Central

    Foo, Chwan Hong; Rootes, Christina L.; Gould, Cathryn M.; Grusovin, Julian; Monaghan, Paul; Lo, Michael K.; Tompkins, S. Mark; Adams, Timothy E.; Lowenthal, John W.; Simpson, Kaylene J.; Stewart, Cameron R.; Bean, Andrew G. D.; Wang, Lin-Fa

    2016-01-01

    Hendra and Nipah viruses (genus Henipavirus, family Paramyxoviridae) are highly pathogenic bat-borne viruses. The need for high biocontainment when studying henipaviruses has hindered the development of therapeutics and knowledge of the viral infection cycle. We have performed a genome-wide siRNA screen at biosafety level 4 that identified 585 human proteins required for henipavirus infection. The host protein with the largest impact was fibrillarin, a nucleolar methyltransferase that was also required by measles, mumps and respiratory syncytial viruses for infection. While not required for cell entry, henipavirus RNA and protein syntheses were greatly impaired in cells lacking fibrillarin, indicating a crucial role in the RNA replication phase of infection. During infection, the Hendra virus matrix protein co-localized with fibrillarin in cell nucleoli, and co-associated as a complex in pulldown studies, while its nuclear import was unaffected in fibrillarin-depleted cells. Mutagenesis studies showed that the methyltransferase activity of fibrillarin was required for henipavirus infection, suggesting that this enzyme could be targeted therapeutically to combat henipavirus infections. PMID:27010548

  14. Genome-wide siRNA Screening at Biosafety Level 4 Reveals a Crucial Role for Fibrillarin in Henipavirus Infection.

    PubMed

    Deffrasnes, Celine; Marsh, Glenn A; Foo, Chwan Hong; Rootes, Christina L; Gould, Cathryn M; Grusovin, Julian; Monaghan, Paul; Lo, Michael K; Tompkins, S Mark; Adams, Timothy E; Lowenthal, John W; Simpson, Kaylene J; Stewart, Cameron R; Bean, Andrew G D; Wang, Lin-Fa

    2016-03-01

    Hendra and Nipah viruses (genus Henipavirus, family Paramyxoviridae) are highly pathogenic bat-borne viruses. The need for high biocontainment when studying henipaviruses has hindered the development of therapeutics and knowledge of the viral infection cycle. We have performed a genome-wide siRNA screen at biosafety level 4 that identified 585 human proteins required for henipavirus infection. The host protein with the largest impact was fibrillarin, a nucleolar methyltransferase that was also required by measles, mumps and respiratory syncytial viruses for infection. While not required for cell entry, henipavirus RNA and protein syntheses were greatly impaired in cells lacking fibrillarin, indicating a crucial role in the RNA replication phase of infection. During infection, the Hendra virus matrix protein co-localized with fibrillarin in cell nucleoli, and co-associated as a complex in pulldown studies, while its nuclear import was unaffected in fibrillarin-depleted cells. Mutagenesis studies showed that the methyltransferase activity of fibrillarin was required for henipavirus infection, suggesting that this enzyme could be targeted therapeutically to combat henipavirus infections. PMID:27010548

  15. Tim Wirth: playing a leading role. Newsmaker interview.

    PubMed

    Pickett, S

    1995-01-01

    An interview with Timothy Wirth, who has been Under Secretary of State for Global Affairs, is presented. The US played a new role as a partner at several recent UN conferences that focused on a multiplicity of issues that harbinger the 21st century. The 4th World Conference on Women in Beijing in September 1995 underscored the importance of women as agents of change, confirmed the importance of nongovernmental organizations in affecting global change in governance, and revealed the strength of women's groups in developing countries. The US made some pledges at the 1994 UN Population and Development Conference in Cairo as laid down in the program of action. US financial commitment to population stabilization increased as did the commitment from Japan and other developed countries. Egypt, Indonesia, Tunisia, and Mexico with effective family planning programs are also sharing their experiences with other developing countries. The US has an interest in investing in foreign assistance in view of runaway population growth in countries like Haiti. Haiti's excess population would be heading for Florida. The President's Council on Sustainable Development's task force on population and consumption concluded that the US should commit itself to population stabilization because of the high consumption rate of the average American, the number of unplanned and unwanted pregnancies, and the problem of teenage pregnancies. Consumption rather than investment should taxed, subsidies should be removed from the use of natural resources and agriculture, and environmental degradation should be priced properly. Poverty is at the root of economic deprivation and environmental destruction. Micro-enterprises have been successful in Asia, Africa, and Latin America, which experiences could be used by the US as well. The broader empowerment of women could also encourage political change, which, in turn could bring about full access to family planning and support to women and their families

  16. A Crucial Role for the p110δ Subunit of Phosphatidylinositol 3-Kinase in B Cell Development and Activation

    PubMed Central

    Clayton, Elizabeth; Bardi, Giuseppe; Bell, Sarah E.; Chantry, David; Downes, C. Peter; Gray, Alexander; Humphries, Lisa A.; Rawlings, David; Reynolds, Helen; Vigorito, Elena; Turner, Martin

    2002-01-01

    Mice lacking the p110δ catalytic subunit of phosphatidylinositol 3-kinase have reduced numbers of B1 and marginal zone B cells, reduced levels of serum immunoglobulins, respond poorly to immunization with type II thymus-independent antigen, and are defective in their primary and secondary responses to thymus-dependent antigen. p110δ−/− B cells proliferate poorly in response to B cell receptor (BCR) or CD40 signals in vitro, fail to activate protein kinase B, and are prone to apoptosis. p110δ function is required for BCR-mediated calcium flux, activation of phosphlipaseCγ2, and Bruton's tyrosine kinase. Thus, p110δ plays a critical role in B cell homeostasis and function. PMID:12235209

  17. Controversies over the mechanisms underlying the crucial role of the left fronto-parietal areas in the representation of tools

    PubMed Central

    Gainotti, Guido

    2013-01-01

    Anatomo-clinical and neuroimaging data show that the left fronto-parietal areas play an important role in representing tools. As manipulation is an important source of knowledge about tools, it has been assumed that motor activity explains the link between tool knowledge and the left fronto-parietal areas. However, controversies exist over the exact mechanisms underlying this relationship. According to a strong version of the “embodied cognition theory,” activation of a tool concept necessarily involves re-enactment of the corresponding kind of action. Impairment of the ability to use tools should, therefore, lead to impairment of tool knowledge. Both the “domains of knowledge hypothesis” and the “sensory-motor model of conceptual knowledge” refute the strong version of the “embodied cognition hypothesis” but acknowledge that manipulation and other action schemata play an important role in our knowledge of tools. The basic difference between these two models is that the former is based on an innate model and the latter holds that the brain’s organization of categories is experience dependent. Data supporting and arguing against each of these models are briefly reviewed. In particular, the following lines of research, which argue against the innate nature of the brain’s categorical organization, are discussed: (1) the observation that in patients with category-specific disorders the semantic impairment does not respect the boundaries between biological entities and artifact items; (2) data showing that experience-driven neuroplasticity in musicians is not confined to alterations of perceptual and motor maps but also leads to the establishment of higher-level semantic representations for musical instruments; (3) results of experiments using previously unfamiliar materials showing that the history of our sensory-motor experience with an object significantly affects its neural representation. PMID:24137144

  18. Predicting procedural pain after ureteroscopy: does hydrodistention play a role?

    PubMed Central

    Gul, Zeynep; Alazem, Kareem; Li, Ina; Monga, Manoj

    2016-01-01

    ABSTRACT Purpose: To identify perioperative predictors of immediate pain after ureteroscopy, specifically evaluating the impact of hydrodistention from irrigation on pain. Materials and Methods: We retrospectively identified patients who underwent ureteroscopy for the treatment of calculi. Data recorded for these patients included their maximum pain score in the post-anesthesia care unit (PACU), average flow rate of irrigant used during the procedure, patient and stone characteristics, operative procedure, and details of patients' immediate, post-operative course. Spearman's rho was used to determine the relationship between non-parametric, continuous variables. Then, a linear regression was performed to assess which variables could predict the peak pain score. Results: A total of 131 patients were included in the study. A non-parametric correlation analysis revealed that maximum pain score was negatively correlated with being male (r = −0.18, p=0.04), age (r = −0.34, p<0.001), and post-op foley placement (r = −0.20, p=0.02) but positively correlated with the preoperative pain score (r = 0.41, p<0.001), time in the PACU (r = 0.19, p = 0.03), and the morphine equivalent dose (MED) of narcotics administered in the PACU (r = 0.67, p<0.001). On linear regression, the significant variables were age, preoperative pain score, and stent placement. For every ten-year increase in age post-operative pain score decreased by 4/10 of a point (p = 0.03). For every 1 point increase in preoperative pain score there was a 3/10 of a point increase in the maximum pain score (p = 0.01), and leaving a stent in place post-operatively was associated with a 1.6 point increase in the maximum pain score. Conclusions: Hydrodistention does not play a role in post-ureteroscopy pain. Patients who are younger, have higher preoperative pain scores, or who are stented will experience more post-operative pain after ureteroscopy. PMID:27564284

  19. Do Diacritical Marks Play a Role at the Early Stages of Word Recognition in Arabic?

    PubMed

    Perea, Manuel; Abu Mallouh, Reem; Mohammed, Ahmed; Khalifa, Batoul; Carreiras, Manuel

    2016-01-01

    A crucial question in the domain of visual word recognition is whether letter similarity plays a role in the early stages of visual word processing. Here we focused on Arabic because in this language there are various groups of letters that share the same basic shape and only differ in the number/location of diacritical points. We conducted a masked priming lexical decision experiment in which a target word was preceded by: (i) an identity prime; (ii) a prime in which the critical letter was replaced by a letter with the same shape that differed in the number of diacritics (e.g., ); or (iii) a prime in which the critical letter was replaced by a letter with different shape (e.g., ). Results showed a sizable advantage of the identity condition over the two substituted-letter priming conditions (i.e., diacritical information is rapidly processed). Thus, diacritical marks play an essential role in the "feature letter" level of models of visual word recognition in Arabic. PMID:27597838

  20. Do Diacritical Marks Play a Role at the Early Stages of Word Recognition in Arabic?

    PubMed Central

    Perea, Manuel; Abu Mallouh, Reem; Mohammed, Ahmed; Khalifa, Batoul; Carreiras, Manuel

    2016-01-01

    A crucial question in the domain of visual word recognition is whether letter similarity plays a role in the early stages of visual word processing. Here we focused on Arabic because in this language there are various groups of letters that share the same basic shape and only differ in the number/location of diacritical points. We conducted a masked priming lexical decision experiment in which a target word was preceded by: (i) an identity prime; (ii) a prime in which the critical letter was replaced by a letter with the same shape that differed in the number of diacritics (e.g., ); or (iii) a prime in which the critical letter was replaced by a letter with different shape (e.g., ). Results showed a sizable advantage of the identity condition over the two substituted-letter priming conditions (i.e., diacritical information is rapidly processed). Thus, diacritical marks play an essential role in the “feature letter” level of models of visual word recognition in Arabic. PMID:27597838

  1. Does black hole spin play a key role in the FSRQ/BL Lac dichotomy?

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Debbijoy; Sreekumar, Parameswaran; Mukhopadhyay, Banibrata; Tomar, Ishan

    2016-04-01

    Blazars are characterized by large intensity and spectral variations across the electromagnetic spectrum It is believed that jets emerging from them are almost aligned with the line-of-sight. The majority of identified extragalactic sources in γ-ray catalogs of EGRET and Fermi are blazars. Observationally, blazars can be divided into two classes: flat spectrum radio quasars (FSRQs) and BL Lacs. BL Lacs usually exhibit lower γ-ray luminosity and harder power law spectra at γ-ray energies than FSRQs. We attempt to explain the high energy properties of FSRQs and BL Lacs from Fermi γ-ray space telescope observations. It was argued previously that the difference in accretion rates is mainly responsible for the large mismatch in observed luminosity in γ-ray. However, when intrinsic luminosities are derived by correcting for beaming effects, this difference in γ-ray luminosity between the two classes is significantly reduced. In order to explain this difference in intrinsic luminosities, we propose that spin plays an important role in the luminosity distribution dichotomy of BL Lacs and FSRQs. As the outflow power of a blazar increases with increasing spin of a central black hole, we suggest that the spin plays a crucial role in making BL Lac sources low luminous and slow rotators compared to FSRQ sources.

  2. Correspondence of Motivational Interviewing Adherence and Competence Ratings in Real and Role-Played Client Sessions

    ERIC Educational Resources Information Center

    Decker, Suzanne E.; Carroll, Kathleen M.; Nich, Charla; Canning-Ball, Monica; Martino, Steve

    2013-01-01

    Treatment integrity ratings (adherence and competence) are frequently used as outcome measures in clinician training studies, drawn from recorded real client or role-played client sessions. However, it is unknown whether clinician adherence and competence are similar in real client and role-played sessions or whether real and role-play clients…

  3. Attacking the Personal Fable: Role-Play and Its Effect on Teen Attitudes toward Sexual Abstinence.

    ERIC Educational Resources Information Center

    Saltz, Eli; And Others

    1994-01-01

    Examines role playing as a tool for changing teenagers' attitudes about sex behavior and the consequences of teen pregnancy. A sample of 267 ninth-grade students attending a high-risk urban school participated. Role playing and watching videos of friends' role playing significantly increased favorable attitudes toward abstinence in girls but not…

  4. Oh, Garbage! Decisions about Waste Disposal. Creative Role-Playing Exercises in Science and Technology Series.

    ERIC Educational Resources Information Center

    Parisi, Lynn; Pearson, Janice

    This document is one of a series of role plays that focus on science-related social issues of concern in contemporary public policy formation. The role plays are designed to help students develop information-processing and decision making skills needed to deal effectively with such issues. The role plays guide students in analyzing science related…

  5. A Case Study of an Online Role Play for Academic Staff.

    ERIC Educational Resources Information Center

    Bell, Maureen

    Role play is a powerful technique for skills and attitude development. It is now possible to combine the advantages of face-to-face role play with the potential of the online environment. This paper reports on a case study of an asynchronous, anonymous, online role play conducted within a teaching course for academic staff. The following key…

  6. Using Role-Play for Expert Science Communication with Professional Stakeholders in Flood Risk Management

    ERIC Educational Resources Information Center

    McEwen, Lindsey; Stokes, Alison; Crowley, Kate; Roberts, Carolyn

    2014-01-01

    This paper explores role-play pedagogies in learning and communicating about cutting-edge flood science by flood risk management professionals in local government. It outlines role-play process/structure and evaluates participant perceptions of their learning experiences. Issues were impacts of prior role-play experience on attitudes brought to…

  7. Assessing Women's Responses to Sexual Threat: Validity of a Virtual Role-Play Procedure

    ERIC Educational Resources Information Center

    Jouriles, Ernest N.; Rowe, Lorelei Simpson; McDonald, Renee; Platt, Cora G.; Gomez, Gabriella S.

    2011-01-01

    This study evaluated the validity of a role-play procedure that uses virtual reality technology to assess women's responses to sexual threat. Forty-eight female undergraduate students were randomly assigned to either a standard, face-to-face role-play (RP) or a virtual role-play (VRP) of a sexually coercive situation. A multimethod assessment…

  8. Could borate have played a role in the RNA World?

    NASA Astrophysics Data System (ADS)

    Grew, E. S.; Bada, J. L.; Hazen, R. M.

    2012-12-01

    Two scenarios have been proposed for boron to play a critical role in the stabilization of ribose and other sugars in the ribonucleic acid (RNA) World, >3.8 Ga ago. One scenario envisages oligomeric RNA being synthesized in subaerial intermountane desert valleys in which groundwater was enriched in borate from breakdown of tourmaline (Benner et al. 2012 doi: 10.1021/ar200332w). In the alternative scenario, borates are enriched in hydrothermal environments (<150°C) in oceanic crust where ferromagnesian minerals are altered to brucite, serpentine and other minerals that can extract borate from the circulating seawater (Holm et al. 2006 doi:10.1186/1467-4866-7-7). Both scenarios presume that (1) B concentrations in non-marine water or sea water were about the same at >3.8 Ma as they are today and (2) plate tectonics was the prevailing regime. The postulated non-marine borate deposits would have been associated with continental collision and subduction with volcanism releasing B, whereas in the second scenario, ocean floor caught up in an early phase of subduction is considered a favorable site for borate formation. Because borate deposits are typically ephemeral and poorly preserved, the lack of evidence in the geologic record for these scenarios does not invalidate them. For example, the oldest reported non-marine borate deposits analogous to the type postulated in first scenario are only 20 Ma, but metamorphosed borates of Precambrian age have been interpreted to have non-marine evaporite precursors, the oldest being 2.4-2.1 Ga in the Liaoning-Jilin area, China. The first B minerals so far reported in the geologic record are metamorphic dravite-schorl tourmalines in the 3.7-3.8 Ga Isua supracrustal belt (southern West Greenland), where there is good evidence for seafloor spreading and subduction. The precursors to the Isua tourmalines are reported to include B-bearing marine clay minerals and detrital tourmaline. The relatively high Li contents in zircon from Jack

  9. Broca's Area Plays a Causal Role in Morphosyntactic Processing

    ERIC Educational Resources Information Center

    Carreiras, Manuel; Pattamadilok, Chotiga; Meseguer, Enrique; Barber, Horacio; Devlin, Joseph T.

    2012-01-01

    Although there is strong evidence that Broca's area is important for syntax, this may simply be a by-product of greater working memory and/or cognitive control demands for more complex syntactic structures. Here we report an experiment with event-related transcranial magnetic stimulation (TMS) to investigate whether Broca's area plays a causal…

  10. The Role of Play in the Accultural Process.

    ERIC Educational Resources Information Center

    Cooper, Renatta M.

    Play, possibly the dominant socializing agent for children's social competence and identity development, is heavily influenced by media-defined images. It is important for media images of minority cultures to be filtered by parents' reactions and comments in order to counter prevalent negative images. Children's interaction with the media is…

  11. Distance Learning and Role Play: A Web-Bard Pedagogy

    ERIC Educational Resources Information Center

    Kolloff, Mary Ann; Rahimzadeh, Kevin

    2004-01-01

    As most any high school or college English teacher can verify, it is the rare group of students that approaches the study of Shakespeare with anything other than a mixture of anxiety over the difficulty of making sense of the plays' language and annoyance that, once again, they will be forced to engage in an activity they find both unjustifiably…

  12. Thin film lubrication of hexadecane confined by iron and iron oxide surfaces: A crucial role of surface structure.

    PubMed

    Ta, D T; Tieu, A K; Zhu, H T; Kosasih, B

    2015-10-28

    A comparative analysis of thin film lubrication of hexadecane between different iron and its oxide surfaces has been carried out using classical molecular dynamic simulation. An ab initio force-field, COMPASS, was applied for n-hexadecane using explicit atom model. An effective potential derived from density functional theory calculation was utilized for the interfacial interaction between hexadecane and the tribo-surfaces. A quantitative surface parameterization was introduced to investigate the influence of surface properties on the structure, rheological properties, and tribological performance of the lubricant. The results show that although the wall-fluid attraction of hexadecane on pure iron surfaces is significantly stronger than its oxides, there is a considerable reduction of shear stress of confined n-hexadecane film between Fe(100) and Fe(110) surfaces compared with FeO(110), FeO(111), Fe2O3(001), and Fe2O3(012). It was found that, in thin film lubrication of hexadecane between smooth iron and iron oxide surfaces, the surface corrugation plays a role more important than the wall-fluid adhesion strength. PMID:26520538

  13. Thin film lubrication of hexadecane confined by iron and iron oxide surfaces: A crucial role of surface structure

    NASA Astrophysics Data System (ADS)

    Ta, D. T.; Tieu, A. K.; Zhu, H. T.; Kosasih, B.

    2015-10-01

    A comparative analysis of thin film lubrication of hexadecane between different iron and its oxide surfaces has been carried out using classical molecular dynamic simulation. An ab initio force-field, COMPASS, was applied for n-hexadecane using explicit atom model. An effective potential derived from density functional theory calculation was utilized for the interfacial interaction between hexadecane and the tribo-surfaces. A quantitative surface parameterization was introduced to investigate the influence of surface properties on the structure, rheological properties, and tribological performance of the lubricant. The results show that although the wall-fluid attraction of hexadecane on pure iron surfaces is significantly stronger than its oxides, there is a considerable reduction of shear stress of confined n-hexadecane film between Fe(100) and Fe(110) surfaces compared with FeO(110), FeO(111), Fe2O3(001), and Fe2O3(012). It was found that, in thin film lubrication of hexadecane between smooth iron and iron oxide surfaces, the surface corrugation plays a role more important than the wall-fluid adhesion strength.

  14. Combination therapy with zinc gluconate and PUVA for alopecia areata totalis: an adjunctive but crucial role of zinc supplementation.

    PubMed

    Lux-Battistelli, Christine

    2015-01-01

    Spontaneous remission occurs in less than 10% of patients suffering from alopecia areata (AA) totalis for more than 2 years. The efficacy of PUVA therapy is controversial due to recurrence of hair loss after cessation. We report two cases presenting with AA totalis and AA universalis. After hair regrowth, relapse of hair loss occurred upon cessation of PUVA and zinc gluconate combination therapy. However, hair regrowth was noted upon the reintroduction of zinc gluconate and sulfur amino acids without PUVA in the first case and with episodic PUVA in the second case. The chronology of events appears to support the notion that zinc has a significant effect. Our findings suggest the possibility of a subgroup of zinc-responsive patients, but the identification of these patients remains difficult. Metallothioneins and zinc transporters regulating the entrance and exit of zinc in cells might play a key role. Combination therapy with immunomodulators may be administered to facilitate enhanced zinc-targeted action. Taking into account the safety profile of zinc, 30-40 mg/day of zinc metal may be used during at least 1 year, although we recommend to monitor its serum and hair levels. Studies with a larger number of patients are required to further investigate the therapeutic effect of zinc. PMID:25754430

  15. Thin film lubrication of hexadecane confined by iron and iron oxide surfaces: A crucial role of surface structure

    SciTech Connect

    Ta, D. T.; Tieu, A. K.; Zhu, H. T. Kosasih, B.

    2015-10-28

    A comparative analysis of thin film lubrication of hexadecane between different iron and its oxide surfaces has been carried out using classical molecular dynamic simulation. An ab initio force-field, COMPASS, was applied for n-hexadecane using explicit atom model. An effective potential derived from density functional theory calculation was utilized for the interfacial interaction between hexadecane and the tribo-surfaces. A quantitative surface parameterization was introduced to investigate the influence of surface properties on the structure, rheological properties, and tribological performance of the lubricant. The results show that although the wall-fluid attraction of hexadecane on pure iron surfaces is significantly stronger than its oxides, there is a considerable reduction of shear stress of confined n-hexadecane film between Fe(100) and Fe(110) surfaces compared with FeO(110), FeO(111), Fe{sub 2}O{sub 3}(001), and Fe{sub 2}O{sub 3}(012). It was found that, in thin film lubrication of hexadecane between smooth iron and iron oxide surfaces, the surface corrugation plays a role more important than the wall-fluid adhesion strength.

  16. Emotional Role Playing, Attitude Change, and Attraction Toward a Disabled Person.

    ERIC Educational Resources Information Center

    Clore, Gerald L.; Jeffery, Katherine McMillan

    The effects of emotional role playing on interpersonal attitudes toward the disabled are explored. Three treatment groups (role players, vicarious role players, and controls) were involved. Role playing consisted of traveling about the campus in a wheel chair for an hour. Results indicated that, compared to the control experience, both direct and…

  17. Playing in "Trelis Weyr": Investigating Collaborative Practices in a "Dragons of Pern" Role-Play-Game Forum

    ERIC Educational Resources Information Center

    Alley, Kathleen M.

    2013-01-01

    This descriptive case study examined adolescents' and emerging adults' literate and social practices within the context of a role-play-game (RPG) forum, investigating the ways participants read and collaboratively composed within this space. As a researcher, I was interested in how this space functioned and how the interactions between…

  18. Turing's theory of morphogenesis of 1952 and the subsequent discovery of the crucial role of local self-enhancement and long-range inhibition.

    PubMed

    Meinhardt, Hans

    2012-08-01

    In his pioneering work, Alan Turing showed that de novo pattern formation is possible if two substances interact that differ in their diffusion range. Since then, we have shown that pattern formation is possible if, and only if, a self-enhancing reaction is coupled with an antagonistic process of longer range. Knowing this crucial condition has enabled us to include nonlinear interactions, which are required to design molecularly realistic interactions. Different reaction schemes and their relation to Turing's proposal are discussed and compared with more recent observations on the molecular-genetic level. The antagonistic reaction may be accomplished by an inhibitor that is produced in the activated region or by a depletion of a component that is used up during the self-enhancing reaction. The autocatalysis may be realized by an inhibition of an inhibition. Activating molecules can be processed into molecules that have an inhibiting function; patterning of the Wnt pathway is proposed to depend on such a mechanism. Three-component systems, as discussed in Turing's paper, are shown to play a major role in the generation of highly dynamic patterns that never reach a stable state. PMID:23919125

  19. The Role of Structural Characteristics in Problematic Video Game Play: An Empirical Study

    ERIC Educational Resources Information Center

    King, Daniel L.; Delfabbro, Paul H.; Griffiths, Mark D.

    2011-01-01

    The research literature suggests that the structural characteristics of video games may play a considerable role in the initiation, development and maintenance of problematic video game playing. The present study investigated the role of structural characteristics in video game playing behaviour within a sample of 421 video game players aged…

  20. Beyond self-selection in video game play: an experimental examination of the consequences of massively multiplayer online role-playing game play.

    PubMed

    Smyth, Joshua M

    2007-10-01

    There is burgeoning interest in the study of video games. Existing work is limited by the use of correlational designs and is thus unable to make causal inferences or remove self-selection biases from observed results. The recent development of online, socially integrated video games (massively multiplayer online role-playing games [MMORPGs]) has created a new experience for gamers. This randomized, longitudinal study examined the effects of being assigned to play different video game types on game usage, health, well-being, sleep, socializing, and academics. One hundred 18- to 20-year-old participants (73% male; 68% Caucasian) were randomly assigned to play arcade, console, solo computer, or MMORPG games for 1 month. The MMORPG group differed significantly from other groups after 1 month, reporting more hours spent playing, worse health, worse sleep quality, and greater interference in "real-life" socializing and academic work. In contrast, this group also reported greater enjoyment in playing, greater interest in continuing to play, and greater acquisition of new friendships. MMORPGs represent a different gaming experience with different consequences than other types of video games and appear to pose both unique risks and benefits from their use. PMID:17927543

  1. Role Playing in the History of Economic Thought.

    ERIC Educational Resources Information Center

    Oberhofer, Tom

    1999-01-01

    Describes a one-semester economics course in which students assume the role of key figures in the development of economic thought, ranging from the mercantilists through the early neoclassicists. Structures class discussion thematically rather than chronologically, so characters are conversationally engaged in each class. (DSK)

  2. A Michigan Faculty Group Plays Role of Watchdog

    ERIC Educational Resources Information Center

    Gose, Ben

    2008-01-01

    New administrative offices for diversity are popping up at universities around the country, and one can usually count on them to cast minority-recruiting efforts in a favorable light. There is still, however, a role for the old-school rabble-rousers, as a new report from a faculty committee at the University of Michigan at Ann Arbor makes clear.…

  3. On Two Roles Decision Support Systems Can Play in Negotiations.

    ERIC Educational Resources Information Center

    Kersten, Gregory E.

    1987-01-01

    Focuses on the role of the computer system in group decision making. Two systems used in solving negotiating problems--NEGO and MEDIATOR--and three procedures that can be utilized to develop group decision support systems are analyzed, based on multicriteria decision analysis and mathematical programming models. (Author/LRW)

  4. Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development.

    PubMed

    Baardman, Maria E; Zwier, Mathijs V; Wisse, Lambertus J; Gittenberger-de Groot, Adriana C; Kerstjens-Frederikse, Wilhelmina S; Hofstra, Robert M W; Jurdzinski, Angelika; Hierck, Beerend P; Jongbloed, Monique R M; Berger, Rolf M F; Plösch, Torsten; DeRuiter, Marco C

    2016-04-01

    Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts ofLrp2knockout (KO) mice have not yet been investigated. We studied the cardiovascular development ofLrp2KO mice between embryonic day 10.5 (E10.5) and E15.5, applying morphometry and immunohistochemistry, using antibodies against Tfap2α (neural crest cells), Nkx2.5 (second heart field), WT1 (epicardium derived cells), tropomyosin (myocardium) and LRP2. TheLrp2KO mice display a range of severe cardiovascular abnormalities, including aortic arch anomalies, common arterial trunk (persistent truncus arteriosus) with coronary artery anomalies, ventricular septal defects, overriding of the tricuspid valve and marked thinning of the ventricular myocardium. Both the neural crest cells and second heart field, which are essential for the lengthening and growth of the right ventricular outflow tract, are abnormally positioned in theLrp2KO. This explains the absence of the aorto-pulmonary septum, which leads to common arterial trunk and ventricular septal defects. Severe blebbing of the epicardial cells covering the ventricles is seen. Epithelial-mesenchymal transition does occur; however, there are fewer WT1-positive epicardium-derived cells in the ventricular wall as compared to normal, coinciding with the myocardial thinning and deep intertrabecular spaces. LRP2 plays a crucial role in cardiovascular development in mice. This corroborates findings of cardiac anomalies in humans withLRP2mutations. Future studies should reveal the underlying signaling mechanisms in which LRP2 is involved during cardiogenesis. PMID:26822476

  5. Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development

    PubMed Central

    Baardman, Maria E.; Zwier, Mathijs V.; Wisse, Lambertus J.; Gittenberger-de Groot, Adriana C.; Kerstjens-Frederikse, Wilhelmina S.; Hofstra, Robert M. W.; Jurdzinski, Angelika; Hierck, Beerend P.; Jongbloed, Monique R. M.; Berger, Rolf M. F.; Plösch, Torsten; DeRuiter, Marco C.

    2016-01-01

    ABSTRACT Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the cardiovascular development of Lrp2 KO mice between embryonic day 10.5 (E10.5) and E15.5, applying morphometry and immunohistochemistry, using antibodies against Tfap2α (neural crest cells), Nkx2.5 (second heart field), WT1 (epicardium derived cells), tropomyosin (myocardium) and LRP2. The Lrp2 KO mice display a range of severe cardiovascular abnormalities, including aortic arch anomalies, common arterial trunk (persistent truncus arteriosus) with coronary artery anomalies, ventricular septal defects, overriding of the tricuspid valve and marked thinning of the ventricular myocardium. Both the neural crest cells and second heart field, which are essential for the lengthening and growth of the right ventricular outflow tract, are abnormally positioned in the Lrp2 KO. This explains the absence of the aorto-pulmonary septum, which leads to common arterial trunk and ventricular septal defects. Severe blebbing of the epicardial cells covering the ventricles is seen. Epithelial-mesenchymal transition does occur; however, there are fewer WT1-positive epicardium-derived cells in the ventricular wall as compared to normal, coinciding with the myocardial thinning and deep intertrabecular spaces. LRP2 plays a crucial role in cardiovascular development in mice. This corroborates findings of cardiac anomalies in humans with LRP2 mutations. Future studies should reveal the underlying signaling mechanisms in which LRP2 is involved during cardiogenesis. PMID:26822476

  6. Student feedback about the use of role plays in Sparshanam, a medical humanities module

    PubMed Central

    Shankar, P Ravi

    2012-01-01

    Background: At KIST Medical College, Lalitpur, Nepal, a Medical Humanities module for first year medical students has been conducted. Role plays are used to explore social, medical and sexual issues in the Nepalese context. The present study obtained student feedback about the role plays used in the module, the difficulties faced, and obtained suggestions for further improvement. Method: The module was conducted from January to August 2011 using a total of 15 role plays. Student feedback was obtained using a semi-structured questionnaire. Informal discussions were held and a questionnaire was circulated among the first year students who had participated in the module. Results: Ninety-eight of the 100 students in the module participated in the study. The overall opinion regarding the role plays was positive. Students stated role plays helped to make module objectives concrete and interesting, made students identify with the problem being investigated and improved communication skills. Role plays were designed to address important health issues in Nepal and prepare students for addressing these issues in future practice. A lack of sufficient time for preparing the role plays and initial problems with group dynamics were mentioned by the respondents during the study. Conclusions: Student feedback about the use of role plays during the module was positive. Role plays helped in making module objectives more concrete and interesting, improved communication skills and addressed important health issues in Nepal. Role plays are not resource intensive and can be considered for use in medical schools in developing nations. PMID:24358816

  7. Epigenetics and Chromatin Remodeling Play a Role in Lung Disease

    PubMed Central

    Mortaz, Esmaeil; Masjedi, Mohammad Reza; Barnes, Peter J

    2011-01-01

    Epigenetics is defined as heritable changes that affect gene expression without altering the DNA sequence. Epigenetic regulation of gene expression is facilitated through different mechanisms such as DNA methylation, histone modifications and RNA-associated silencing by small non-coding RNAs. All these mechanisms are crucial for normal development, differentiation and tissue-specific gene expression. These three systems interact and stabilize one another and can initiate and sustain epigenetic silencing, thus determining heritable changes in gene expression. Histone acetylation regulates diverse cellular functions including inflammatory gene expression, DNA repair and cell proliferation. Transcriptional coactivators possess intrinsic histone acetyltransferase activity and this activity drives inflammatory gene expression. Eleven classical histone deacetylases (HDACs) act to regulate the expression of distinct subsets of inflammatory/immune genes. Thus, loss of HDAC activity or the presence of HDAC inhibitors can further enhance inflammatory gene expression by producing a gene-specific change in HAT activity. For example, HDAC2 expression and activity are reduced in lung macrophages, biopsy specimens, and blood cells from patients with severe asthma and smoking asthmatics, as well as in patients with chronic obstructive pulmonary disease (COPD). This may account, at least in part, for the enhanced inflammation and reduced steroid responsiveness seen in these patients. Other proteins, particularly transcription factors, are also acetylated and are targets for deacetylation by HDACs and sirtuins, a related family of 7 predominantly protein deacetylases. Thus the acetylation/deacetylation status of NF-κB and the glucocorticoid receptor can also affect the overall expression pattern of inflammatory genes and regulate the inflammatory response. Understanding and targeting specific enzymes involved in this process might lead to new therapeutic agents, particularly in

  8. Some personal notes on role plays as an excellent teaching tool : commentary on "using and developing role plays in teaching aimed at preparing for social responsibility".

    PubMed

    Hunger, Iris

    2013-12-01

    Role plays are extremely valuable tools to address different aspects of teaching social responsibility, because they allow students to "live through" complex ethical decision making dilemmas. While role plays are getting high marks from students because their entertainment value is high, their educational value depends on their closeness to students' work experience and the skills of the teacher in helping students comprehend the lessons they are meant to convey. PMID:24101438

  9. Critical period for first language: the crucial role of language input during the first year of life.

    PubMed

    Friedmann, Naama; Rusou, Dana

    2015-12-01

    The critical period for language acquisition is often explored in the context of second language acquisition. We focus on a crucially different notion of critical period for language, with a crucially different time scale: that of a critical period for first language acquisition. We approach this question by examining the language outcomes of children who missed their critical period for acquiring a first language: children who did not receive the required language input because they grew in isolation or due to hearing impairment and children whose brain has not developed normally because of thiamine deficiency. We find that the acquisition of syntax in a first language has a critical period that ends during the first year of life, and children who missed this window of opportunity later show severe syntactic impairments. PMID:26111432

  10. Retinoblastoma Protein Plays Multiple Essential Roles in the Terminal Differentiation of Sertoli Cells

    PubMed Central

    Nalam, Roopa L.; Andreu-Vieyra, Claudia; Braun, Robert E.; Akiyama, Haruhiko; Matzuk, Martin M.

    2009-01-01

    Retinoblastoma protein (RB) plays crucial roles in cell cycle control and cellular differentiation. Specifically, RB impairs the G1 to S phase transition by acting as a repressor of the E2F family of transcriptional activators while also contributing towards terminal differentiation by modulating the activity of tissue-specific transcription factors. To examine the role of RB in Sertoli cells, the androgen-dependant somatic support cell of the testis, we created a Sertoli cell-specific conditional knockout of Rb. Initially, loss of RB has no gross effect on Sertoli cell function because the mice are fertile with normal testis weights at 6 wk of age. However, by 10–14 wk of age, mutant mice demonstrate severe Sertoli cell dysfunction and infertility. We show that mutant mature Sertoli cells continue cycling with defective regulation of multiple E2F1- and androgen-regulated genes and concurrent activation of apoptotic and p53-regulated genes. The most striking defects in mature Sertoli cell function are increased permeability of the blood-testis barrier, impaired tissue remodeling, and defective germ cell-Sertoli cell interactions. Our results demonstrate that RB is essential for proper terminal differentiation of Sertoli cells. PMID:19819985

  11. What Roles Can Scientists Play in Public Discourse?

    NASA Astrophysics Data System (ADS)

    Oppenheimer, Michael

    2011-04-01

    What is a useful and proper role for scientists in the public arena? How can we best discriminate where the boundary lies between expert knowledge and values or political opinion, and how can we properly honor that line? What can we expect in the way of reception for our interventions, and how can we increase their efficacy? Involvement in public policy debates is a common and accepted role for scientists in many disciplines. In the sciences related to public health, it is taken for granted that experts will talk about the implications of their research for public policy, whether in regard to smoking, diet, or disease spread. There is also a remarkable track record of geoscientists taking a lead role in the public arena and actually affecting public policy—F. Sherwood Rowland and Mario Molina collaborated on ozone depletion research at the Department of Chemistry at University of California, Irvine and then went on to make outstanding public contributions, as have James Hansen (at NASA's Goddard Institute for Space Studies); Robert Watson (first at NASA, then at the University of East Anglia); and, of course, the late Stephen Schneider (first at the U.S. National Center for Atmospheric Research, then Stanford) on climate. Some “public” geoscientists have restricted their activities to interpreting science for the wider public, while others have endorsed specific policy initiatives (see Figure 1). I firmly believe that the quality of public discourse and the information reaching policy makers were better for their interventions.

  12. Motivation within Role-Playing as a Means to Intensify College Students' Educational Activity

    ERIC Educational Resources Information Center

    Burenkova, Olga Mikhailovna; Arkhipova, Irina Vladimirovna; Semenov, Sergei Aleksandrovich; Samarenkina, Saniya Zakirzyanovna

    2015-01-01

    This article covers college students' educational activity issues while studying a foreign language; analyzes special aspects of motivation introduction, their specific features. It also defines role and structure of role-playing. The authors come to the conclusion that introduction of role-playing in an educational process will bring it closer to…

  13. Deletion of Caldicellulosiruptor bescii CelA reveals its crucial role in the deconstruction of lignocellulosic biomass

    SciTech Connect

    Young, Jenna; Chung, Daehwan; Bomble, Yannick J.; Himmel, Michael E.; Westpheling, Janet

    2014-10-09

    release on Avicel compared with the parent and wild-type strains. In conclusion: The exoglucanase activity of the GH48 domain of CelA plays a major role in biomass degradation within the suite of C. bescii biomass-degrading enzymes.

  14. Deletion of Caldicellulosiruptor bescii CelA reveals its crucial role in the deconstruction of lignocellulosic biomass

    DOE PAGESBeta

    Young, Jenna; Chung, Daehwan; Bomble, Yannick J.; Himmel, Michael E.; Westpheling, Janet

    2014-10-09

    sugar release on Avicel compared with the parent and wild-type strains. In conclusion: The exoglucanase activity of the GH48 domain of CelA plays a major role in biomass degradation within the suite of C. bescii biomass-degrading enzymes.« less

  15. Crucial roles of the CHRNB3–CHRNA6 gene cluster on chromosome 8 in nicotine dependence: update and subjects for future research

    PubMed Central

    Wen, L; Yang, Z; Cui, W; Li, M D

    2016-01-01

    Cigarette smoking is a leading cause of preventable death throughout the world. Nicotine, the primary addictive compound in tobacco, plays a vital role in the initiation and maintenance of its use. Nicotine exerts its pharmacological roles through nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels consisting of five membrane-spanning subunits. Besides the CHRNA4, CHRNB2 and CHRNA5/A3/B4 cluster on chromosome 15, which has been investigated intensively, recent evidence from both genome-wide association studies and candidate gene-based association studies has revealed the crucial roles of the CHRNB3–CHRNA6 gene cluster on chromosome 8 in nicotine dependence (ND). These studies demonstrate two distinct loci within this region. The first one is tagged by rs13277254, upstream of the CHRNB3 gene, and the other is tagged by rs4952, a coding single nucleotide polymorphism in exon 5 of that gene. Functional studies by genetic manipulation in mice have shown that α6*-nAChRs, located in the ventral tegmental area (VTA), are of great importance in controlling nicotine self-administration. However, when the α6 subunit is selectively re-expressed in the VTA of the α6−/− mouse by a lentiviral vector, the reinforcing property of nicotine is restored. To further determine the role of α6*-nAChRs in the process of nicotine-induced reward and withdrawal, genetic knock-in strains have been examined, which showed that replacement of Leu with Ser in the 9′ residue in the M2 domain of α6 produces nicotine-hypersensitive mice (α6 L9′S) with enhanced dopamine release. Moreover, nicotine-induced upregulation may be another ingredient in the pathology of nicotine addiction although the effect of chronic nicotine exposure on the expression of α6-containing receptors is controversial. To gain a better understanding of the pathological processes underlying ND and ND-related behaviors and to promote the development of effective smoking cessation

  16. Crucial roles of the CHRNB3-CHRNA6 gene cluster on chromosome 8 in nicotine dependence: update and subjects for future research.

    PubMed

    Wen, L; Yang, Z; Cui, W; Li, M D

    2016-01-01

    Cigarette smoking is a leading cause of preventable death throughout the world. Nicotine, the primary addictive compound in tobacco, plays a vital role in the initiation and maintenance of its use. Nicotine exerts its pharmacological roles through nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels consisting of five membrane-spanning subunits. Besides the CHRNA4, CHRNB2 and CHRNA5/A3/B4 cluster on chromosome 15, which has been investigated intensively, recent evidence from both genome-wide association studies and candidate gene-based association studies has revealed the crucial roles of the CHRNB3-CHRNA6 gene cluster on chromosome 8 in nicotine dependence (ND). These studies demonstrate two distinct loci within this region. The first one is tagged by rs13277254, upstream of the CHRNB3 gene, and the other is tagged by rs4952, a coding single nucleotide polymorphism in exon 5 of that gene. Functional studies by genetic manipulation in mice have shown that α6*-nAChRs, located in the ventral tegmental area (VTA), are of great importance in controlling nicotine self-administration. However, when the α6 subunit is selectively re-expressed in the VTA of the α6(-/-) mouse by a lentiviral vector, the reinforcing property of nicotine is restored. To further determine the role of α6*-nAChRs in the process of nicotine-induced reward and withdrawal, genetic knock-in strains have been examined, which showed that replacement of Leu with Ser in the 9' residue in the M2 domain of α6 produces nicotine-hypersensitive mice (α6 L9'S) with enhanced dopamine release. Moreover, nicotine-induced upregulation may be another ingredient in the pathology of nicotine addiction although the effect of chronic nicotine exposure on the expression of α6-containing receptors is controversial. To gain a better understanding of the pathological processes underlying ND and ND-related behaviors and to promote the development of effective smoking cessation therapies, we

  17. CGRP and Migraine: Could PACAP Play a Role Too?

    PubMed Central

    Kaiser, Eric A.; Russo, Andrew F.

    2013-01-01

    Migraine is a debilitating neurological disorder that affects about 12% of the population. In the past decade, the role of the neuropeptide calcitonin gene-related peptide (CGRP) in migraine has been firmly established by clinical studies. CGRP administration can trigger migraines, and CGRP receptor antagonists ameliorate migraine. In this review, we will describe multifunctional activities of CGRP that could potentially contribute to migraine. These include roles in light aversion, neurogenic inflammation, peripheral and central sensitization of nociceptive pathways, cortical spreading depression, and regulation of nitric oxide production. Yet clearly there will be many other contributing genes that could act in concert with CGRP. One candidate is pituitary adenylate cyclase-activating peptide (PACAP), which shares some of the same actions as CGRP, including the ability to induce migraine in migraineurs and light aversive behavior in rodents. Interestingly, both CGRP and PACAP act on receptors that share an accessory subunit called receptor activity modifying protein-1 (RAMP1). Thus, comparisons between the actions of these two migraine-inducing neuropeptides, CGRP and PACAP, may provide new insights into migraine pathophysiology. PMID:24210136

  18. ASXL1 plays an important role in erythropoiesis

    PubMed Central

    Shi, Hui; Yamamoto, Shohei; Sheng, Mengyao; Bai, Jie; Zhang, Peng; Chen, Runze; Chen, Shi; Shi, Lihong; Abdel-Wahab, Omar; Xu, Mingjiang; Zhou, Yuan; Yang, Feng-Chun

    2016-01-01

    ASXL1 mutations are found in a spectrum of myeloid malignancies with poor prognosis. Recently, we reported that Asxl1+/− mice develop myelodysplastic syndrome (MDS) or MDS and myeloproliferative neoplasms (MPN) overlapping diseases (MDS/MPN). Although defective erythroid maturation and anemia are associated with the prognosis of patients with MDS or MDS/MPN, the role of ASXL1 in erythropoiesis remains unclear. Here, we showed that chronic myelomonocytic leukemia (CMML) patients with ASXL1 mutations exhibited more severe anemia with a significantly increased proportion of bone marrow (BM) early stage erythroblasts and reduced enucleated erythrocytes compared to CMML patients with WT ASXL1. Knockdown of ASXL1 in cord blood CD34+ cells reduced erythropoiesis and impaired erythrocyte enucleation. Consistently, the BM and spleens of VavCre+;Asxl1f/f (Asxl1∆/∆) mice had less numbers of erythroid progenitors than Asxl1f/f controls. Asxl1∆/∆ mice also had an increased percentage of erythroblasts and a reduced erythrocyte enucleation in their BM compared to littermate controls. Furthermore, Asxl1∆/∆ erythroblasts revealed altered expression of genes involved in erythroid development and homeostasis, which was associated with lower levels of H3K27me3 and H3K4me3. Our study unveils a key role for ASXL1 in erythropoiesis and indicates that ASXL1 loss hinders erythroid development/maturation, which could be of prognostic value for MDS/MPN patients. PMID:27352931

  19. Lysophosphatidylcholine plays critical role in allergic airway disease manifestation

    PubMed Central

    Bansal, Preeti; Gaur, Shailendera Nath; Arora, Naveen

    2016-01-01

    Phospholipase A2 (sPLA2), pivotal for allergic and inflammatory response, hydrolyses phosphatidylcholine (PC) to lysophosphatidylcholine (LPC). In present study, the role of LPC in allergic airway disease manifestation was studied using mouse model. Balb/c mice were immunized using cockroach extract (CE) and LPC release was blocked by sPLA2 inhibitor. Airway hyperresponse (AHR), lung-histology, total and differential leukocyte count (TLC&DLC), Th2 type cytokines, sPLA2 activity and LPC levels in bronchoalveolar lavage fluid (BALF) were measured. Exogenous LPC was given to the mice with or without CE sensitization, to demonstrate its role in allergic airway disease manifestation. Anti-CD1d antibody was given to study the involvement of natural killer T (NKT) cells in LPC induced response. AHR, lung-inflammation, TLC, DLC, Th2 type cytokines, sPLA2 activity and LPC levels were increased on CE challenge. sPLA2 activity and LPC release was blocked by sPLA2-inhibitor, which decreased AHR, and inflammatory parameters. Exogenous LPC with or without CE sensitization increased above parameters. CE challenge or LPC exposure increased LY49C+TCRβ+ NKT cells in BALF and spleen, which was reduced by anti-CD1d antibody, accompanied with reduction in AHR and allergic airway inflammation parameters. Conclusively, LPC induces allergic airway disease manifestation and it does so probably via CD1d-restricted LY49C+TCRβ+ NKT cells. PMID:27282246

  20. Lysophosphatidylcholine plays critical role in allergic airway disease manifestation.

    PubMed

    Bansal, Preeti; Gaur, Shailendera Nath; Arora, Naveen

    2016-01-01

    Phospholipase A2 (sPLA2), pivotal for allergic and inflammatory response, hydrolyses phosphatidylcholine (PC) to lysophosphatidylcholine (LPC). In present study, the role of LPC in allergic airway disease manifestation was studied using mouse model. Balb/c mice were immunized using cockroach extract (CE) and LPC release was blocked by sPLA2 inhibitor. Airway hyperresponse (AHR), lung-histology, total and differential leukocyte count (TLC&DLC), Th2 type cytokines, sPLA2 activity and LPC levels in bronchoalveolar lavage fluid (BALF) were measured. Exogenous LPC was given to the mice with or without CE sensitization, to demonstrate its role in allergic airway disease manifestation. Anti-CD1d antibody was given to study the involvement of natural killer T (NKT) cells in LPC induced response. AHR, lung-inflammation, TLC, DLC, Th2 type cytokines, sPLA2 activity and LPC levels were increased on CE challenge. sPLA2 activity and LPC release was blocked by sPLA2-inhibitor, which decreased AHR, and inflammatory parameters. Exogenous LPC with or without CE sensitization increased above parameters. CE challenge or LPC exposure increased LY49C(+)TCRβ(+) NKT cells in BALF and spleen, which was reduced by anti-CD1d antibody, accompanied with reduction in AHR and allergic airway inflammation parameters. Conclusively, LPC induces allergic airway disease manifestation and it does so probably via CD1d-restricted LY49C(+)TCRβ(+) NKT cells. PMID:27282246

  1. ASXL1 plays an important role in erythropoiesis.

    PubMed

    Shi, Hui; Yamamoto, Shohei; Sheng, Mengyao; Bai, Jie; Zhang, Peng; Chen, Runze; Chen, Shi; Shi, Lihong; Abdel-Wahab, Omar; Xu, Mingjiang; Zhou, Yuan; Yang, Feng-Chun

    2016-01-01

    ASXL1 mutations are found in a spectrum of myeloid malignancies with poor prognosis. Recently, we reported that Asxl1(+/-) mice develop myelodysplastic syndrome (MDS) or MDS and myeloproliferative neoplasms (MPN) overlapping diseases (MDS/MPN). Although defective erythroid maturation and anemia are associated with the prognosis of patients with MDS or MDS/MPN, the role of ASXL1 in erythropoiesis remains unclear. Here, we showed that chronic myelomonocytic leukemia (CMML) patients with ASXL1 mutations exhibited more severe anemia with a significantly increased proportion of bone marrow (BM) early stage erythroblasts and reduced enucleated erythrocytes compared to CMML patients with WT ASXL1. Knockdown of ASXL1 in cord blood CD34(+) cells reduced erythropoiesis and impaired erythrocyte enucleation. Consistently, the BM and spleens of VavCre(+);Asxl1(f/f) (Asxl1(∆/∆)) mice had less numbers of erythroid progenitors than Asxl1(f/f) controls. Asxl1(∆/∆) mice also had an increased percentage of erythroblasts and a reduced erythrocyte enucleation in their BM compared to littermate controls. Furthermore, Asxl1(∆/∆) erythroblasts revealed altered expression of genes involved in erythroid development and homeostasis, which was associated with lower levels of H3K27me3 and H3K4me3. Our study unveils a key role for ASXL1 in erythropoiesis and indicates that ASXL1 loss hinders erythroid development/maturation, which could be of prognostic value for MDS/MPN patients. PMID:27352931

  2. Piezo1 plays a role in erythrocyte volume homeostasis

    PubMed Central

    Faucherre, Adèle; Kissa, Karima; Nargeot, Joël; Mangoni, Matteo E.; Jopling, Chris

    2014-01-01

    Mechanosensitivity is an inherent property of virtually all cell types, allowing them to sense and respond to physical environmental stimuli. Stretch-activated ion channels represent a class of mechanosensitive proteins which allow cells to respond rapidly to changes in membrane tension; however their identity has remained elusive. The piezo genes have recently been identified as a family of stretch-activated mechanosensitive ion channels. We set out to determine the role of piezo1 during zebrafish development. Here we report that morpholino-mediated knockdown of piezo1 impairs erythrocyte survival without affecting hematopoiesis or differentiation. Our results demonstrate that piezo1 is involved in erythrocyte volume homeostasis, disruption of which results in swelling/lysis of red blood cells and consequent anemia. PMID:23872304

  3. NADPH oxidase 2 plays a role in experimental corneal neovascularization.

    PubMed

    Chan, Elsa C; van Wijngaarden, Peter; Chan, Elsie; Ngo, Darleen; Wang, Jiang-Hui; Peshavariya, Hitesh M; Dusting, Gregory J; Liu, Guei-Sheung

    2016-05-01

    Corneal neovascularization, the growth of new blood vessels in the cornea, is a leading cause of vision impairment after corneal injury. Neovascularization typically occurs in response to corneal injury such as that caused by infection, physical trauma, chemical burns or in the setting of corneal transplant rejection. The NADPH oxidase enzyme complex is involved in cell signalling for wound-healing angiogenesis, but its role in corneal neovascularization has not been studied. We have now analysed the role of the Nox2 isoform of NADPH oxidase in corneal neovascularization in mice following chemical injury. C57BL/6 mice aged 8-14 weeks were cauterized with an applicator coated with 75% silver nitrate and 25% potassium nitrate for 8 s. Neovascularization extending radially from limbal vessels was observed in corneal whole-mounts from cauterized wild type mice and CD31+ vessels were identified in cauterized corneal sections at day 7. In contrast, in Nox2 knockout (Nox2 KO) mice vascular endothelial growth factor-A (Vegf-A), Flt1 mRNA expression, and the extent of corneal neovascularization were all markedly reduced compared with their wild type controls. The accumulation of Iba-1+ microglia and macrophages in the cornea was significantly less in Nox2 KO than in wild type mice. In conclusion, we have demonstrated that Nox2 is implicated in the inflammatory and neovascular response to corneal chemical injury in mice and clearly VEGF is a mediator of this effect. This work raises the possibility that therapies targeting Nox2 may have potential for suppressing corneal neovascularization and inflammation in humans. PMID:26814205

  4. Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3'-triiodothyronine in the protection of the fetal brain.

    PubMed Central

    Calvo, R; Obregón, M J; Ruiz de Oña, C; Escobar del Rey, F; Morreale de Escobar, G

    1990-01-01

    To study the protective effects of maternal thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in congenital hypothyroidism, we gave pregnant rats methimazole (MMI), an antithyroid drug that crosses the placenta, and infused them with three different doses of T4 or T3. The concentrations of both T4 and T3 were determined in maternal and fetal plasma and tissues (obtained near term) by specific RIAs. Several thyroid hormone-dependent biological end-points were also measured. MMI treatment resulted in marked fetal T4 and T3 deficiency. Infusion of T4 into the mothers increased both these pools in a dose-dependent fashion. There was a preferential increase of T3 in the fetal brain. Thus, with a T4 dose maintaining maternal euthyroidism, fetal brain T3 reached normal values, although fetal plasma T4 was 40% of normal and plasma TSH was high. The infusion of T3 pool into the mothers increased the total fetal extrathyroidal T3 pool in a dose-dependent fashion. The fetal T4 pools were not increased, however, and this deprived the fetal brain (and possibly the pituitary) of local generation of T3 from T4. As a consequence, fetal brain T3 deficiency was not mitigated even when dams were infused with a toxic dose of T3. The results show that (a) there is a preferential protection of the brain of the hypothyroid fetus from T3 deficiency; (b) maternal T4, but not T3, plays a crucial role in this protection, and (c) any condition which lowers maternal T4 (including treatment with T3) is potentially harmful for the brain of a hypothyroid fetus. Recent confirmation of transplacental passage of T4 in women at term suggests that present results are relevant for human fetuses with impairment of thyroid function. Finding signs of hypothyroidism at birth does not necessarily mean that the brain was unprotected in utero, provided maternal T4 is normal. It is crucial to realize that maintainance of maternal "euthyroidism" is not sufficient, as despite hypothyroxinemia, the mothers may be

  5. [The pharmacist should play an active role in family planning].

    PubMed

    Portes, M

    1983-01-01

    Although pharmacies now dispense primarily modern products originating in large multinational corporations, the community pharmacist has not been replaced by any ultramodern technological advance. Many thousand persons acquire family planning products in pharmacies. The pharmacist works many hours a day, is always available, and provides free advice to his clients. Pharmacists are consulted daily on numerous topics, especially on family planning. Many prsons in rural areas are without the services of a physician and rely on pharmacists all the more. Pharmacists could orient the public on family planning in general, help in choosing the most appropriate of available methods, and refer patients to physicians in case of problems. Participants at the recent International Conference on the Role of Retail Pharmacists in Family Planning, held in Alexandria, Egypt, concluded that pharmacists should cooperate with physicians and other health professionals to provide family planning services and should participate in elaboration of laws regulating the manufacture, storage, prices, and distribution of contraceptives. The prices of contraceptive supplies to the consumer could be reduced if taxes and import duties were removed, if supplies were produced locally, or if supplies were subsidized by some donor organization. PMID:12178199

  6. Immunoglobulin E plays an immunoregulatory role in lupus.

    PubMed

    Dema, Barbara; Charles, Nicolas; Pellefigues, Christophe; Ricks, Tiffany K; Suzuki, Ryo; Jiang, Chao; Scheffel, Jorg; Hasni, Sarfaraz; Hoffman, Victoria; Jablonski, Mathieu; Sacré, Karim; Gobert, Delphine; Papo, Thomas; Daugas, Eric; Crampton, Steve; Bolland, Silvia; Rivera, Juan

    2014-10-20

    The (patho)physiological role of IgE in nonallergic inflammatory diseases is not well understood. Here, we explored the effect of IgE deficiency on the inflammatory response in FcγRIIB-deficient mice as well as in mice carrying both a deletion of FcγRIIB and the chromosomal translocation of Y-linked autoimmune acceleration (Yaa) that hastens and results in a more aggressive lupuslike disease in these mice. The findings show that deficiency of IgE delays disease development and severity as demonstrated by reduced autoantibody production and amelioration of organ pathologies. This was associated with decreased numbers of plasma cells and reduced levels of IgG2b and IgG3. Unexpectedly, the loss of IgE also caused a striking decrease of immune cell infiltration in secondary lymphoid organs with a marked effect on the presence of dendritic cells, monocytes, neutrophils, and eosinophils in these organs and decreased activation of basophils. The presence of autoreactive IgE in human systemic lupus erythematosus subjects was also associated with increased basophil activation and enhanced disease activity. These findings argue that IgE facilitates the amplification of autoimmune inflammation. PMID:25267791

  7. IFT46 plays an essential role in cilia development

    PubMed Central

    Lee, Mi-Sun; Hwang, Kyu-Seok; Oh, Hyun-Woo; Ji-Ae, Kim; Kim, Hyun-Taek; Cho, Hyun-Soo; Lee, Jeong-Ju; Ko, Je Yeong; Choi, Jung-Hwa; Jeong, Yun-Mi; You, Kwan-Hee; Kim, Joon; Park, Doo-Sang; Nam, Ki-Hoan; Aizawa, Shinichi; Kiyonari, Hiroshi; Shioi, Go; Park, Jong-Hoon; Zhou, Weibin; Kim, Nam-Soon; Kim, Cheol-Hee

    2015-01-01

    Cilia are microtubule-based structures that project into the extracellular space. Ciliary defects are associated with several human diseases, including polycystic kidney disease, primary ciliary dyskinesia, left-right axis patterning, hydrocephalus and retinal degeneration. However, the genetic and cellular biological control of ciliogenesis remains poorly understood. The IFT46 is one of the highly conserved intraflagellar transport complex B proteins. In zebrafish, ift46 is expressed in various ciliated tissues such as Kupffer’s vesicle, pronephric ducts, ears and spinal cord. We show that ift46 is localized to the basal body. Knockdown of ift46 gene results in multiple phenotypes associated with various ciliopathies including kidney cysts, pericardial edema and ventral axis curvature. In ift46 morphants, cilia in kidney and spinal canal are shortened and abnormal. Similar ciliary defects are observed in otic vesicles, lateral line hair cells, olfactory pits, but not in Kupffer’s vesicle. To explore the functions of Ift46 during mouse development, we have generated Ift46 knock-out mice. The Ift46 mutants have developmental defects in brain, neural tube and heart. In particular Ift46(−/−) homozygotes displays randomization of the embryo heart looping, which is a hallmark of defective left-right (L/R) axis patterning. Taken together, our results demonstrated that IFT46 has an essential role in vertebrate ciliary development. PMID:25722189

  8. Transition to university: the role played by emotion.

    PubMed

    McMillan, W

    2013-08-01

    Students experience transition to university as challenging. Recent studies implicate emotion in university success. This article reports on a pilot study to examine the extent to which school to university transition is experienced as emotional. Understanding the role of emotion in this transition can inform mechanisms for student support. This qualitative study used focus group interviews to elicit insider accounts of transition. The pilot cohort consisted of a tutorial group of twenty-eight students from within the class of one hundred and eight-first-year students at one Faculty of Dentistry in South Africa. Three focus group interviews were conducted. Issues identified in the literature as significant were used to analyse the data. Eleven descriptive tags related to transition and associated with emotion were identified from the data. These were clustered into four themes - 'academic challenges', 'friends and family', 'outside constraints' and 'identity'. Findings suggest that emotions are a natural part of the experience of transition. Drawing on insights of students' emotional needs, it is suggested that students in transition need a roadmap and a guide. A framework, to be used as a roadmap, is suggested. Peer mentoring is discussed as a mechanism for mediating the framework and thus for supporting students in the transition. PMID:23815694

  9. DNABII proteins play a central role in UPEC biofilm structure

    PubMed Central

    Devaraj, Aishwarya; Justice, Sheryl S.; Bakaletz, Lauren O.; Goodman, Steven D.

    2015-01-01

    Summary Most chronic and recurrent bacterial infections involve a biofilm component, the foundation of which is the extracellular polymeric substance (EPS). Extracellular DNA (eDNA) is a conserved and key component of the EPS of pathogenic biofilms. The DNABII protein family includes integration host factor (IHF) and Histone-like protein (HU); both are present in the extracellular milieu. We have shown previously that the DNABII proteins are often found in association with eDNA and are critical for the structural integrity of bacterial communities that utilize eDNA as a matrix component. Here, we demonstrated that Uropathogenic E. coli (UPEC) strain UTI89 incorporates eDNA within its biofilm matrix and that the DNABII proteins are not only important for biofilm growth, but are limiting; exogenous addition of these proteins promotes biofilm formation that is dependent on eDNA. In addition, we show that both subunits of IHF, yet only one subunit of HU (HupB), are critical for UPEC biofilm development. We discuss the roles of these proteins in context of the UPEC EPS. PMID:25757804

  10. Does lysozyme play a role in the pathogenesis of COPD?

    PubMed

    Cantor, Jerome; Shteyngart, Bronislava

    2015-06-01

    Elastic fiber injury is an important process in the pathogenesis of chronic obstructive pulmonary disease (COPD), particularly with regard to the development of pulmonary emphysema. Damage to these fibers results in uneven distribution of mechanical forces in the lung, leading to dilatation and rupture of alveolar walls. While the role of various enzymes and oxidants in this process has been well-documented, we propose that a previously unsuspected agent, lysozyme, may contribute significantly to the changes in elastic fibers observed in this disease. Studies from our laboratory have previously shown that lysozyme preferentially binds to elastic fibers in human emphysematous lungs. On the basis of this finding, it is hypothesized that the attachment of lysozyme to these fibers enhances their susceptibility to injury, and further impairs the transfer of mechanical forces in the lung, leading to increased alveolar wall damage and enhanced progression of COPD. The hypothesized effects of lysozyme are predicated on its interaction with hyaluronan (HA), a long-chain polysaccharide that is found in close proximity to elastic fibers. By preventing the binding of HA to elastic fibers in COPD, lysozyme may interfere with the protective effect of this polysaccharide against enzymes and oxidants that degrade these fibers. Furthermore, the loss of the hydrating effect of HA on these fibers may impair their elastic properties, greatly increasing the probability of their fragmentation in response to mechanical forces. The proposed hypothesis may explain why the content of HA is significantly lower in the lungs of COPD patients. It may also contribute to the design of clinical trials involving the use of exogenously administered HA as a potential treatment for COPD. PMID:25769706

  11. The Hiroshima and Nagasaki bombs: role-play and students' interest in physics

    NASA Astrophysics Data System (ADS)

    Heise Kofoed, Mikkel

    2006-11-01

    Role-play as a way of teaching is seldom used in physics. One reason is that role-play is usually constructed so as to contain some sort of conflict and conflicts do not often appear in the course of normal physics teaching. When it comes to the role of physics in war, role-play is an ideal way of presenting content to students. By taking part in role-play students become actively engaged in the teaching situation, developing their interest in physics. They also get a chance to understand the ethical issues involved. This article presents an example of a role-play based educational programme concerning the development of, the decisions behind, and the use of the Hiroshima and Nagasaki bombs during World War II. Some early research results are presented from evaluating the educational programme in lower and upper secondary schools in Denmark.

  12. Mitochondrial OXA Translocase Plays a Major Role in Biogenesis of Inner-Membrane Proteins.

    PubMed

    Stiller, Sebastian B; Höpker, Jan; Oeljeklaus, Silke; Schütze, Conny; Schrempp, Sandra G; Vent-Schmidt, Jens; Horvath, Susanne E; Frazier, Ann E; Gebert, Natalia; van der Laan, Martin; Bohnert, Maria; Warscheid, Bettina; Pfanner, Nikolaus; Wiedemann, Nils

    2016-05-10

    The mitochondrial inner membrane harbors three protein translocases. Presequence translocase and carrier translocase are essential for importing nuclear-encoded proteins. The oxidase assembly (OXA) translocase is required for exporting mitochondrial-encoded proteins; however, different views exist about its relevance for nuclear-encoded proteins. We report that OXA plays a dual role in the biogenesis of nuclear-encoded mitochondrial proteins. First, a systematic analysis of OXA-deficient mitochondria led to an unexpected expansion of the spectrum of OXA substrates imported via the presequence pathway. Second, biogenesis of numerous metabolite carriers depends on OXA, although they are not imported by the presequence pathway. We show that OXA is crucial for the biogenesis of the Tim18-Sdh3 module of the carrier translocase. The export translocase OXA is thus required for the import of metabolite carriers by promoting assembly of the carrier translocase. We conclude that OXA is of central importance for the biogenesis of the mitochondrial inner membrane. PMID:27166948

  13. Role Playing in Physical Education to Teach in the Affective Domain

    ERIC Educational Resources Information Center

    Samalot-Rivera, Amaury

    2014-01-01

    Using role playing during physical education provides limitless opportunities for intervention and for the demonstration of personal and social qualities. The purpose of this article is to provide easy steps for implementing role playing as a strategy to teach social skills to students in the physical education setting.

  14. The Strategic Micro-Firm: A Role Play In Management Training for Dynamic Businesses

    ERIC Educational Resources Information Center

    Barnabe, Federico; Busco, Cristiano; Davidsen, Pal I.; Lambri, Maurizio; Zatta, Gianfranco

    2013-01-01

    Purpose: The purpose of this paper is to present the main characteristics of the role-playing game "Strategic Micro-Firm" which aims to reproduce the fundamental features of a complex supply chain. Design/methodology/approach: A specific role-playing game is presented, in which a Balanced Scorecard is used as the reporting device and is…

  15. The Evaluation of Role-Playing in the Context of Teaching Climate Change

    ERIC Educational Resources Information Center

    Belova, Nadja; Eilks, Ingo; Feierabend, Timo

    2015-01-01

    Role-plays are a common pedagogical tool in the Social Sciences. As an imitation of societal practices, role-plays are thought to support the development of argumentation and decision-making skills among learners. However, argumentation and decision making are also goals in science education in general and in socioscientific issues-oriented…

  16. E-learning Constructive Role Plays for EFL Learners in China's Tertiary Education

    ERIC Educational Resources Information Center

    Shen, Lin; Suwanthep, Jitpanat

    2011-01-01

    Recently, speaking has played an increasingly important role in second/foreign language settings. However, in many Chinese universities, EFL students rarely communicate in English with other people effectively. The existing behavioristic role plays on New Horizon College English (NHCE) e-learning do not function successfully in supplementing EFL…

  17. Development of an Electronic Role-Play Assessment Initiative in Bioscience for Nursing Students

    ERIC Educational Resources Information Center

    Craft, Judy; Ainscough, Louise

    2015-01-01

    Devising authentic assessments for subjects with large enrolments is a challenge. This study describes an electronic role-play assessment for approximately 600 first-year nursing students to learn and apply pathophysiology (bioscience) concepts to nursing practice. Students used Microsoft Office PowerPoint[R] to prepare electronic role-plays both…

  18. The Effects of Children's Stories on Behavior and Attitudes: Modeling and Vicarious Role Playing.

    ERIC Educational Resources Information Center

    Clore, Gerald L.; Bray, Robert M.

    Stories were read to 62 male third grade children from two elementary schools in Urbana, Illinois. They were randomly assigned to one of four story conditions: vicarious role playing, symbolic modeling, a combination of the two, and a control condition. The basis of the present experiment is the assumption that vicarious role playing is similar to…

  19. Correspondence of Motivational Interviewing Adherence and Competence Ratings in Real and Role-Played Client Sessions

    PubMed Central

    Decker, Suzanne E.; Carroll, Kathleen M.; Nich, Charla; Canning-Ball, Monica; Martino, Steve

    2013-01-01

    Treatment integrity ratings (adherence and competence) are frequently used as outcome measures in clinician training studies, drawn from recorded real client or role-played client sessions. However, it is unknown whether clinician adherence and competence are similar in real client and role-played sessions or whether real and role-play clients provide similar opportunities for skill demonstration. This study examined the correspondence of treatment adherence and competence ratings obtained in real client and role-played sessions for 91 clinicians trained in Motivational Interviewing (MI), using data from a multi-site trial examining three methods of clinician training (Martino et al., 2011). Results indicated overall poor integrity rating correspondence across the two session types, as indicated by weak correlations (r = .05–.27). Clinicians were rated significantly more MI adherent overall and specifically used more advanced MI strategies in role-played than real client sessions at several assessment time points (d = 0.36, 0.42). Real clients, in comparison to the role-play actor, demonstrated greater motivation at the beginning of the session (d = 1.09), discussion of unrelated topics (d = 0.70), and alliance with the clinician (d = 0.72). These findings suggest that MI integrity rating data obtained from real client and role-played sessions may not be interchangeable. More research is needed to improve the procedures and psychometric strength of treatment integrity assessment based on role-played sessions. PMID:23205626

  20. Comparing Role-Playing Activities in Second Life and Face-to-Face Environments

    ERIC Educational Resources Information Center

    Gao, Fei; Noh, Jeongmin J.; Koehler, Matthew J.

    2009-01-01

    This study compared student performances in role-playing activities in both a face-to-face (FTF) environment and a virtual 3D environment, Second Life (SL). We found that students produced a similar amount of communication in the two environments, but the communication styles were different. In SL role-playing activities, students took more…

  1. Breathing Life into History: Using Role-Playing to Engage Students

    ERIC Educational Resources Information Center

    Cruz, Barbara C.; Murthy, Shalini A.

    2006-01-01

    Alternately referred to as historical role-playing, dramatic improvisation, sociodrama, or first-person characterization, role playing is a teaching strategy that often uses official accounts, personal narratives, and diaries to recreate a particular time period, specific event, or breathe life into a character from history. Historical…

  2. Role Playing: The Atomic Bomb and the End of World War II

    ERIC Educational Resources Information Center

    Eggleston, Noel C.

    1978-01-01

    Describes how a role playing exercise can be used to teach students in a college level history course about the use of the atomic bomb in World War II. Information is presented on general use of role playing in history courses, objectives, questions to consider about use of the atomic bomb, and course evaluation. For journal availability, see so…

  3. What Students Need: Exploring Teachers' Views via Imagined Role-Playing

    ERIC Educational Resources Information Center

    Zazkis, Rina; Nejad, Masomeh Jamshid

    2014-01-01

    Role-playing is an unscripted dramatic technique that encourages participants to improvise behaviors that illustrate expected actions of persons involved in defined situations. However, among various uses in developing professionals, the use of role-playing in teacher education is rather rare. To give all students the opportunity to participate in…

  4. Using Role-Play and Case Studies to Improve Preservice Teacher Attitudes toward Classroom Management

    ERIC Educational Resources Information Center

    Rudolph, Amanda

    2008-01-01

    Classroom management is a concern for preservice teachers (Charles, 2008). Teacher educators struggle to find the most effective ways to teach preservice teachers classroom management. Role-playing, combined with classroom management content, may offer a productive approach. As such, this study focused on the use of role-play with case studies to…

  5. Role-Playing in Science Education: An Effective Strategy for Developing Multiple Perspectives

    ERIC Educational Resources Information Center

    Howes, Elaine V.; Cruz, Barbara C.

    2009-01-01

    Role-playing can be an engaging and creative strategy to use in the college classroom. Using official accounts, personal narratives, and diaries to recreate a particular time period, event, or personality, the instructional strategy alternately referred to as role-playing, dramatic improvisation, or first-person characterization can be an…

  6. Understanding Protein Synthesis: A Role-Play Approach in Large Undergraduate Human Anatomy and Physiology Classes

    ERIC Educational Resources Information Center

    Sturges, Diana; Maurer, Trent W.; Cole, Oladipo

    2009-01-01

    This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section…

  7. Online Role-Plays: Combining Situational and Interactional Authenticity in Foreign Language Learning

    ERIC Educational Resources Information Center

    Correia Martins, Maria de Lurdes; Moreira, Gillian; Moreira, António

    2013-01-01

    Role-plays have been almost ubiquitous in foreign language classes and their potential has been widely recognised. In the last decade, the dissemination of Web 2.0 has created a wide range of possibilities for this type of activity, including conducting online role-plays between institutions, the opportunity to combine synchronous and asynchronous…

  8. You Must Participate: Violating Research Ethical Principles through Role-Play

    ERIC Educational Resources Information Center

    Kraus, Rachel

    2008-01-01

    The author discusses the use of role-play to teach research ethics in three semesters of a research methods class. Small groups of students were assigned one of nine ethical norms discussed in the course textbook and the American Sociological Association Code of Ethics. Each group role-played the violation of their assigned ethic to the class. The…

  9. Fostering Argumentative Knowledge Construction through Enactive Role Play in "Second Life"

    ERIC Educational Resources Information Center

    Jamaludin, Azilawati; Chee, Yam San; Ho, Caroline Mei Lin

    2009-01-01

    This paper examines how pre-university students shared and constructed knowledge in the context of GP (general paper) by interacting through individual virtual characters across five cycles of enactive role play sessions. Contextualized scenarios on the topic of euthanasia were developed in "Second Life". Role-playing the virtual characters…

  10. Rules out of Roles: Differences in Play Language and Their Developmental Significance

    ERIC Educational Resources Information Center

    Kim, Yongho; Kellogg, David

    2007-01-01

    Using a discourse analytic approach from the work of Hoey (1991) and a dual processing model from Wray (2000), this paper compares the language produced by the same classes of children when they are engaged in role-play and when they are playing rule-based games. We find that role-play tends to be richer in "frozen" pair parts, where the responses…

  11. Using and developing role plays in teaching aimed at preparing for social responsibility.

    PubMed

    Doorn, Neelke; Kroesen, J Otto

    2013-12-01

    In this paper, we discuss the use of role plays in ethics education for engineering students. After presenting a rough taxonomy of different objectives, we illustrate how role plays can be used to broaden students' perspectives. We do this on the basis of our experiences with a newly developed role play about a Dutch political controversy concerning pig transport. The role play is special in that the discussion is about setting up an institutional framework for responsible action that goes beyond individual action. In that sense, the role play serves a double purpose. It not only aims at teaching students to become aware of the different dimensions in decision making, it also encourages students to think about what such an institutional framework for responsible action might possibly look like. PMID:22183420

  12. Role-play for medical students learning about communication: Guidelines for maximising benefits

    PubMed Central

    Nestel, Debra; Tierney, Tanya

    2007-01-01

    Background Role-play is widely used as an educational method for learning about communication in medical education. Although educational theory provides a sound rationale for using this form of simulation, there is little published evidence for its effectiveness. Students' prior experiences of role-play may influence the way in which they engage in this method. This paper explores students' experiences with the aim of producing guidelines for maximising the benefits of role-play within this learning context. Methods First-year undergraduate medical students participated in a role-play session as part of their communication programme. Before and after the session, students completed questionnaires. In the pre-session questionnaire, students were asked about their experiences of role-play and asked to identify helpful and unhelpful elements. Immediately after the session, students answered similar questions in relation to the role-play activity they had just completed. Descriptive statistics were used to analyse quantitative data and qualitative data was thematically analysed. Results 284 students completed evaluation forms. Although 63 (22.2%) had prior unhelpful experiences, most students (n = 274; 96.5%) found this experience helpful. Summary findings were that students reported the key aspects of helpful role-play were opportunities for observation, rehearsal and discussion, realistic roles and alignment of roles with other aspects of the curriculum. Unhelpful aspects were those that evoked strong negative emotional responses and factors that contributed to a lack of realism. Conclusion Role-play was valued by students in the acquisition of communication skills even though some had prior unhelpful experiences. Guidelines for effective role-play include adequate preparation, alignment of roles and tasks with level of practice, structured feedback guidelines and acknowledgment of the importance of social interactions for learning. PMID:17335561

  13. Crucial role of detailed function, task, timeline, link and human vulnerability analyses in HRA. [Human Reliability Analysis (HRA)

    SciTech Connect

    Ryan, T.G.; Haney, L.N.; Ostrom, L.T.

    1992-01-01

    This paper addresses one major cause for large uncertainties in human reliability analysis (HRA) results, that is, an absence of detailed function, task, timeline, link and human vulnerability analyses. All too often this crucial step in the HRA process is done in a cursory fashion using word of mouth or written procedures which themselves may incompletely or inaccurately represent the human action sequences and human error vulnerabilities being analyzed. The paper examines the potential contributions these detailed analyses can make in achieving quantitative and qualitative HRA results which are: (1) creditable, that is, minimize uncertainty, (2) auditable, that is, systematically linking quantitative results and qualitative information from which the results are derived, (3) capable of supporting root cause analyses on human reliability factors determined to be major contributors to risk, and (4) capable of repeated measures and being combined with similar results from other analyses to examine HRA issues transcending individual systems and facilities. Based on experience analyzing test and commercial nuclear reactors, and medical applications of nuclear technology, an iterative process is suggested for doing detailed function, task, timeline, link and human vulnerability analyses using documentation reviews, open-ended and structured interviews, direct observations, and group techniques. Finally, the paper concludes that detailed analyses done in this manner by knowledgeable human factors practitioners, can contribute significantly to the credibility, auditability, causal factor analysis, and combining goals of the HRA.

  14. Evidence for a crucial modulating role of the sodium channel in the QTc prolongation related to antipsychotics.

    PubMed

    Silvestre, Jordi S; O'Neill, Michael F; Prous, Josep R

    2014-04-01

    Blockade of the cardiac hERG channel is recognized as the main mechanism underlying the QT prolongation induced by many classes of drugs, including antipsychotics. However, antipsychotics interact with a variety of other pharmacological targets that could also modulate cardiac function. The present study aims to identify those key factors involved in the QT prolongation induced by antipsychotics. The interactions of 28 antipsychotics were measured on a variety of pharmacological targets. Binding affinity (K(i)), functional channel blockade (IC₅₀), and the corresponding ratios to total and free plasma drug concentration were compared with the corrected QT changes (QTc) associated with the therapeutic use of these drugs by multivariable linear regression analysis to determine the best predictors of QTc. Besides confirming hERG as the primary predictor of QTc, all analyses consistently show the concomitant involvement of Na(V)1.5 channel as modulating factor of the QTc related to hERG blockade. In particular, the hERG/Na(V)1.5 ratio explains the 57% of the overall QTc variability associated with antipsychotics. Since it is known that inhibition of late I Na could offset the dysfunctional effects of hERG blockade, we hypothesize the inhibition of late I(Na) as a crucial compensatory mechanism of the QTc associated with antipsychotics and hence an important factor to consider concomitantly with hERG blockade to appraise the arrhythmogenic risk of these drugs more accurately. PMID:24327451

  15. Comparative transcriptome analysis highlights the crucial roles of photosynthetic system in drought stress adaptation in upland rice

    PubMed Central

    Zhang, Zheng-Feng; Li, Yuan-Yuan; Xiao, Ben-Ze

    2016-01-01

    Drought stress is one of the major adverse environmental factors reducing plant growth. With the aim to elucidate the underlying molecular basis of rice response to drought stress, comparative transcriptome analysis was conducted between drought susceptible rice cultivar Zhenshan97 and tolerant cultivar IRAT109 at the seedling stage. 436 genes showed differential expression and mainly enriched in the Gene Ontology (GO) terms of stress defence. A large number of variations exist between these two genotypes including 2564 high-quality insertion and deletions (INDELs) and 70,264 single nucleotide polymorphism (SNPs). 1041 orthologous gene pairs show the ratio of nonsynonymous nucleotide substitution rate to synonymous nucleotide substitutions rate (Ka/Ks) larger than 1.5, indicating the rapid adaptation to different environments during domestication. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of positive selection genes suggested that photosynthesis represents the most significant category. The collocation of positively selected genes with the QTLs of photosynthesis and the different photosynthesis performance of these two cultivars further illuminate the crucial function of photosynthesis in rice adaptation to drought stress. Our results also provide fruitful functional markers and candidate genes for future genetic research and improvement of drought tolerance in rice. PMID:26777777

  16. Functional characterization of the homeodomain leucine zipper I transcription factor AtHB13 reveals a crucial role in Arabidopsis development.

    PubMed

    Ribone, Pamela A; Capella, Matías; Chan, Raquel L

    2015-09-01

    AtHB13 is a homeodomain leucine zipper I transcription factor whose function in development is largely unknown. AtHB13 and AtHB23 mutant and silenced lines were characterized by expression studies, reciprocal crosses, complementation, molecular analyses, and developmental phenotypes. The athb13-1 and athb13-2 mutants, athb23 silenced, and athb13/athb23 double-silenced plants exhibited faster elongation rates of their inflorescence stems, whereas only athb13-1 and the double-knockdown athb13/athb23 exhibited shorter siliques, fewer seeds, and unfertilized ovules compared with the wild type (WT). The cell sizes of mutant and WT plants were similar, indicating that these transcription factors probably affect cell division. Reciprocal crosses between athb13-1 and the WT genotype indicated that the silique defect was male specific. Pollen hydration assays indicated that the pollen grains of the athb13-1 mutant were unable to germinate on stigmas. AtHB23-silenced plants exhibited normal siliques, whereas double-knockdown athb13/athb23 plants were similar to athb13-1 plants. Both AtHB13 and AtHB23 were able to rescue the abnormal silique phenotype. AtHB23 was upregulated in athb13-2 plants, whereas its transcript levels in athb13-1 mutants were not significantly increased. Transcriptome analysis comparing athb13-1 and WT inflorescences revealed that a large number of genes, including several involved in pollen coat formation, are regulated by AtHB13. Finally, athb13-1 complementation with mutated versions of AtHB13 confirmed that two different tryptophans in its C terminus are essential. We conclude that AtHB13 and AtHB23 play independent, negative developmental roles in stem elongation, whereas only AtHB13 is crucial for pollen germination. Furthermore, AtHB23, which does not normally exert a functional role in pollen, can act as a substitute for AtHB13. PMID:26136262

  17. Schooling in the "Iron Cage" and the Crucial Role of Interpretive, Normative, and Critical Perspectives in Social Foundations Studies

    ERIC Educational Resources Information Center

    Dotts, Brian

    2013-01-01

    This article addresses the unique role performed by social foundations programs in colleges of education and in addressing broader issues facing education today, which fundamentally include the development of interpretive, normative, and critical perspectives in academia. All three perspectives serve to create a scholarly framework within which…

  18. YY1 plays an essential role at all stages of B-cell differentiation.

    PubMed

    Kleiman, Eden; Jia, Haiqun; Loguercio, Salvatore; Su, Andrew I; Feeney, Ann J

    2016-07-01

    Ying Yang 1 (YY1) is a ubiquitously expressed transcription factor shown to be essential for pro-B-cell development. However, the role of YY1 in other B-cell populations has never been investigated. Recent bioinformatics analysis data have implicated YY1 in the germinal center (GC) B-cell transcriptional program. In accord with this prediction, we demonstrated that deletion of YY1 by Cγ1-Cre completely prevented differentiation of GC B cells and plasma cells. To determine if YY1 was also required for the differentiation of other B-cell populations, we deleted YY1 with CD19-Cre and found that all peripheral B-cell subsets, including B1 B cells, require YY1 for their differentiation. Transitional 1 (T1) B cells were the most dependent upon YY1, being sensitive to even a half-dosage of YY1 and also to short-term YY1 deletion by tamoxifen-induced Cre. We show that YY1 exerts its effects, in part, by promoting B-cell survival and proliferation. ChIP-sequencing shows that YY1 predominantly binds to promoters, and pathway analysis of the genes that bind YY1 show enrichment in ribosomal functions, mitochondrial functions such as bioenergetics, and functions related to transcription such as mRNA splicing. By RNA-sequencing analysis of differentially expressed genes, we demonstrated that YY1 normally activates genes involved in mitochondrial bioenergetics, whereas it normally down-regulates genes involved in transcription, mRNA splicing, NF-κB signaling pathways, the AP-1 transcription factor network, chromatin remodeling, cytokine signaling pathways, cell adhesion, and cell proliferation. Our results show the crucial role that YY1 plays in regulating broad general processes throughout all stages of B-cell differentiation. PMID:27335461

  19. Mast Cells Play No Role in the Pathogenesis of Postoperative Ileus Induced by Intestinal Manipulation

    PubMed Central

    Gomez-Pinilla, Pedro J.; Farro, Giovanna; Di Giovangiulio, Martina; Stakenborg, Nathalie; Némethova, Andrea; de Vries, Annick; Liston, Adrian; Feyerabend, Thorsten B.; Rodewald, Hans-Reimwer; Boeckxstaens, Guy E.; Matteoli, Gianluca

    2014-01-01

    Introduction Intestinal manipulation (IM) during abdominal surgery results in intestinal inflammation leading to hypomotility or ileus. Mast cell activation is thought to play a crucial role in the pathophysiology of postoperative ileus (POI). However, this conclusion was mainly drawn using mast cell-deficient mouse models with abnormal Kit signaling. These mice also lack interstitial cells of Cajal (ICC) resulting in aberrant gastrointestinal motility even prior to surgery, compromising their use as model to study POI. To avoid these experimental weaknesses we took advantage of a newly developed knock-in mouse model, Cpa3Cre/+, devoid of mast cells but with intact Kit signaling. Design The role of mast cells in the development of POI and intestinal inflammation was evaluated assessing gastrointestinal transit and muscularis externa inflammation after IM in two strains of mice lacking mast cells, i.e. KitW-sh/W-sh and Cpa3Cre/+ mice, and by use of the mast cell stabilizer cromolyn. Results KitW-sh/W-sh mice lack ICC networks and already revealed significantly delayed gastrointestinal transit even before surgery. IM did not further delay intestinal transit, but induced infiltration of myeloperoxidase positive cells, expression of inflammatory cytokines and recruitment of monocytes and neutrophils into the muscularis externa. On the contrary, Cpa3Cre/+ mice have a normal network of ICC and normal gastrointestinal. Surprisingly, IM in Cpa3Cre/+ mice caused delay in gut motility and intestinal inflammation as in wild type littermates mice (Cpa3+/+). Furthermore, treatment with the mast cell inhibitor cromolyn resulted in an inhibition of mast cells without preventing POI. Conclusions Here, we confirm that IM induced mast cell degranulation. However, our data demonstrate that mast cells are not required for the pathogenesis of POI in mice. Although there might be species differences between mouse and human, our results argue against mast cell inhibitors as a therapeutic

  20. Peptidoglycan Crosslinking Relaxation Plays an Important Role in Staphylococcus aureus WalKR-Dependent Cell Viability

    PubMed Central

    Delaune, Aurelia; Poupel, Olivier; Mallet, Adeline; Coic, Yves-Marie; Msadek, Tarek; Dubrac, Sarah

    2011-01-01

    The WalKR two-component system is essential for viability of Staphylococcus aureus, a major pathogen. We have shown that WalKR acts as the master controller of peptidoglycan metabolism, yet none of the identified regulon genes explain its requirement for cell viability. Transmission electron micrographs revealed cell wall thickening and aberrant division septa in the absence of WalKR, suggesting its requirement may be linked to its role in coordinating cell wall metabolism and cell division. We therefore tested whether uncoupling autolysin gene expression from WalKR-dependent regulation could compensate for its essential nature. Uncoupled expression of genes encoding lytic transglycosylases or amidases did not restore growth to a WalKR-depleted strain. We identified only two WalKR-regulon genes whose expression restored cell viability in the absence of WalKR: lytM and ssaA. Neither of these two genes are essential under our conditions and a ΔlytM ΔssaA mutant does not present any growth defect. LytM is a glycyl–glycyl endopeptidase, hydrolyzing the pentaglycine interpeptide crossbridge, and SsaA belongs to the CHAP amidase family, members of which such as LysK and LytA have been shown to have D-alanyl-glycyl endopeptidase activity, cleaving between the crossbridge and the stem peptide. Taken together, our results strongly suggest that peptidoglycan crosslinking relaxation through crossbridge hydrolysis plays a crucial role in the essential requirement of the WalKR system for cell viability. PMID:21386961

  1. Wind Energy's New Role in Supplying the World's Energy: What Role Will Structural Health Monitoring Play?

    SciTech Connect

    Butterfield, S.; Sheng, S.; Oyague, F.

    2009-12-01

    Wind energy installations are leading all other forms of new energy installations in the United States and Europe. In Europe, large wind plants are supplying as much as 25% of Denmark's energy needs and 8% of the electric needs for Germany and Spain, who have more ambitious goals on the horizon. Although wind energy only produces about 2% of the current electricity demand in the United States, the U.S. Department of Energy, in collaboration with wind industry experts, has drafted a plan that would bring the U.S. installed wind capacity up to 20% of the nation's total electrical supply. To meet these expectations, wind energy must be extremely reliable. Structural health monitoring will play a critical role in making this goal successful.

  2. Acid-induced molten globule state of a prion protein: crucial role of Strand 1-Helix 1-Strand 2 segment.

    PubMed

    Honda, Ryo P; Yamaguchi, Kei-ichi; Kuwata, Kazuo

    2014-10-31

    The conversion of a cellular prion protein (PrP(C)) to its pathogenic isoform (PrP(Sc)) is a critical event in the pathogenesis of prion diseases. Pathogenic conversion is usually associated with the oligomerization process; therefore, the conformational characteristics of the pre-oligomer state may provide insights into the conversion process. Previous studies indicate that PrP(C) is prone to oligomer formation at low pH, but the conformation of the pre-oligomer state remains unknown. In this study, we systematically analyzed the acid-induced conformational changes of PrP(C) and discovered a unique acid-induced molten globule state at pH 2.0 termed the "A-state." We characterized the structure of the A-state using far/near-UV CD, 1-anilino-8-naphthalene sulfonate fluorescence, size exclusion chromatography, and NMR. Deuterium exchange experiments with NMR detection revealed its first unique structure ever reported thus far; i.e. the Strand 1-Helix 1-Strand 2 segment at the N terminus was preferentially unfolded, whereas the Helix 2-Helix 3 segment at the C terminus remained marginally stable. This conformational change could be triggered by the protonation of Asp(144), Asp(147), and Glu(196), followed by disruption of key salt bridges in PrP(C). Moreover, the initial population of the A-state at low pH (pH 2.0-5.0) was well correlated with the rate of the β-rich oligomer formation, suggesting that the A-state is the pre-oligomer state. Thus, the specific conformation of the A-state would provide crucial insights into the mechanisms of oligomerization and further pathogenic conversion as well as facilitating the design of novel medical chaperones for treating prion diseases. PMID:25217639

  3. The Red Hat Society: Exploring the role of play, liminality, and communitas in older women's lives.

    PubMed

    Mackay Yarnal, Careen

    2006-01-01

    There is an extensive literature on play. Yet, the role of play in older adults' lives has received limited attention. Strikingly absent is research on play and older women. Missing from the literature is how older women use play as a liminal context for social interaction and communitas. This is odd because by 2030 one in four American women will be over the age of sixty-five. The primary purpose of this study is to explore the roles of play, liminality, and communitas in older women's lives. The focus is the Red Hat Society, a social group for women over age 50 that fosters play and fun. Using qualitative interviews with focus groups and participant observation of a regional Red Hat Society event, the study highlights some of the strengths and weaknesses of current conceptualizations of play, liminality, and communitas. PMID:17000619

  4. Survival following a vertical free fall from 300 feet: the crucial role of body position to impact surface.

    PubMed

    Weckbach, Sebastian; Flierl, Michael A; Blei, Michael; Burlew, Clay Cothren; Moore, Ernest E; Stahel, Philip F

    2011-01-01

    We report the case of a 28-year old rock climber who survived an "unsurvivable" injury consisting of a vertical free fall from 300 feet onto a solid rock surface. The trauma mechanism and injury kinetics are analyzed, with a particular focus on the relevance of body positioning to ground surface at the time of impact. The role of early patient transfer to a level 1 trauma center, and "damage control" management protocols for avoiding delayed morbidity and mortality in this critically injured patient are discussed. PMID:22027092

  5. Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis

    PubMed Central

    Ohta, Tomokazu; Sugiyama, Masanaka; Hemmi, Hiroaki; Yamazaki, Chihiro; Okura, Soichiro; Sasaki, Izumi; Fukuda, Yuri; Orimo, Takashi; Ishii, Ken J.; Hoshino, Katsuaki; Ginhoux, Florent; Kaisho, Tsuneyasu

    2016-01-01

    Intestinal immune homeostasis requires dynamic crosstalk between innate and adaptive immune cells. Dendritic cells (DCs) exist as multiple phenotypically and functionally distinct sub-populations within tissues, where they initiate immune responses and promote homeostasis. In the gut, there exists a minor DC subset defined as CD103+CD11b− that also expresses the chemokine receptor XCR1. In other tissues, XCR1+ DCs cross-present antigen and contribute to immunity against viruses and cancer, however the roles of XCR1+ DCs and XCR1 in the intestine are unknown. We showed that mice lacking XCR1+ DCs are specifically deficient in intraepithelial and lamina propria (LP) T cell populations, with remaining T cells exhibiting an atypical phenotype and being prone to death, and are also more susceptible to chemically-induced colitis. Mice deficient in either XCR1 or its ligand, XCL1, similarly possess diminished intestinal T cell populations, and an accumulation of XCR1+ DCs in the gut. Combined with transcriptome and surface marker expression analysis, these observations lead us to hypothesise that T cell-derived XCL1 facilitates intestinal XCR1+ DC activation and migration, and that XCR1+ DCs in turn provide support for T cell survival and function. Thus XCR1+ DCs and the XCR1/XCL1 chemokine axis have previously-unappreciated roles in intestinal immune homeostasis. PMID:27005831

  6. Unbalanced upregulation of ryanodine receptor 2 plays a particular role in early development of daunorubicin cardiomyopathy

    PubMed Central

    Kucerova, Dana; Doka, Gabriel; Kruzliak, Peter; Turcekova, Katarina; Kmecova, Jana; Brnoliakova, Zuzana; Kyselovic, Jan; Kirchhefer, Uwe; Müller, Frank U; Krenek, Peter; Boknik, Peter; Klimas, Jan

    2015-01-01

    Calcium release channel on the sarcoplasmic reticulum of cardiomyocytes (ryanodine receptor type 2, RyR2) plays a critical role in the regulation of calcium and was identified as a crucial factor for development of chronic anthracycline cardiomyopathy. Its early stages are less well described although these determine the later development. Hence, we tested the effect of repeated, short-term anthracycline (daunorubicin) administration on cardiac performance, cardiomyocyte function and accompanied changes in calcium regulating proteins expression. Ten-twelve weeks old male Wistar rats were administered with 6 doses of daunorubicin (DAU, 3 mg/kg, i.p., every 48 h), controls (CON) received vehicle. Left ventricular function (left ventricular pressure, LVP; rate of pressure development, +dP/dt and decline, -dP/dt) was measured using left ventricular catheterization under tribromethanol anaesthesia (15 ml/kg b.w.). Cell shortening was measured in enzymatically isolated cardiomyocytes. The expressions of RyR2 and associated intracellular calcium regulating proteins, cytoskeletal proteins (alpha-actinin, alpha-tubul in) as well as oxidative stress regulating enzymes (gp91phox, MnSOD) were detected in ventricular tissue samples using immunoblotting. mRNA expressions of cardiac damage markers (Nppa and Nppb, atrial and brain natriuretic peptides; Myh6, Myh7 and Myh7b, myosin heavy chain alpha and beta) were detected using RT-PCR. Thiobarbituric acid reactive substances concentration was measured to estimate oxidative stress. DAU rats exhibited significantly depressed left ventricular features (LVP by 14%, +dP/dt by 36% and -dP/dt by 30%; for all P<0.05), in line with concomitant increase in Nppa and Nppb gene expressions (3.23- and 2.18-fold, for both P<0.05), and a 4.34-fold increase in Myh7 (P<0.05). Controversially, we observed increased cell shortening of isolated cardiac cells by 31% (p<0.05). DAU administration was associated with a twofold upregulation of RyR2 (P<0

  7. Crucial role of HMGA1 in the self-renewal and drug resistance of ovarian cancer stem cells

    PubMed Central

    Kim, Dae Kyoung; Seo, Eun Jin; Choi, Eun J; Lee, Su In; Kwon, Yang Woo; Jang, Il Ho; Kim, Seung-Chul; Kim, Ki-Hyung; Suh, Dong-Soo; Seong-Jang, Kim; Lee, Sang Chul; Kim, Jae Ho

    2016-01-01

    Cancer stem cells are a subpopulation of cancer cells characterized by self-renewal ability, tumorigenesis and drug resistance. The aim of this study was to investigate the role of HMGA1, a chromatin remodeling factor abundantly expressed in many different cancers, in the regulation of cancer stem cells in ovarian cancer. Spheroid-forming cancer stem cells were isolated from A2780, SKOV3 and PA1 ovarian cancer cells by three-dimensional spheroid culture. Elevated expression of HMGA1 was observed in spheroid cells along with increased expression of stemness-related genes, such as SOX2, KLF4, ALDH, ABCB1 and ABCG2. Furthermore, spheroid A2780 cells, compared with adherent cells, showed higher resistance to chemotherapeutic agents such as paclitaxel and doxorubicin. HMGA1 knockdown in spheroid cells reduced the proliferative advantage and spheroid-forming efficiency of the cells and the expression of stemness-related genes. HMGA1 overexpression in adherent A2780 cells increased cancer stem cell properties, including proliferation, spheroid-forming efficiency and the expression of stemness-related genes. In addition, HMGA1 regulated ABCG2 promoter activity through HMGA1-binding sites. Knockdown of HMGA1 in spheroid cells reduced resistance to chemotherapeutic agents, whereas the overexpression of HMGA1 in adherent ovarian cancer cells increased resistance to chemotherapeutic agents in vitro. Furthermore, HMGA1-overexpressing A2780 cells showed a significant survival advantage after chemotherapeutic agent treatment in a xenograft tumorigenicity assay. Together, our results provide novel insights regarding the critical role of HMGA1 in the regulation of the cancer stem cell characteristics of ovarian cancer cells, thus suggesting that HMGA1 may be an important target in the development of therapeutics for ovarian cancer patients. PMID:27561949

  8. Crucial role of HMGA1 in the self-renewal and drug resistance of ovarian cancer stem cells.

    PubMed

    Kim, Dae Kyoung; Seo, Eun Jin; Choi, Eun J; Lee, Su In; Kwon, Yang Woo; Jang, Il Ho; Kim, Seung-Chul; Kim, Ki-Hyung; Suh, Dong-Soo; Seong-Jang, Kim; Lee, Sang Chul; Kim, Jae Ho

    2016-01-01

    Cancer stem cells are a subpopulation of cancer cells characterized by self-renewal ability, tumorigenesis and drug resistance. The aim of this study was to investigate the role of HMGA1, a chromatin remodeling factor abundantly expressed in many different cancers, in the regulation of cancer stem cells in ovarian cancer. Spheroid-forming cancer stem cells were isolated from A2780, SKOV3 and PA1 ovarian cancer cells by three-dimensional spheroid culture. Elevated expression of HMGA1 was observed in spheroid cells along with increased expression of stemness-related genes, such as SOX2, KLF4, ALDH, ABCB1 and ABCG2. Furthermore, spheroid A2780 cells, compared with adherent cells, showed higher resistance to chemotherapeutic agents such as paclitaxel and doxorubicin. HMGA1 knockdown in spheroid cells reduced the proliferative advantage and spheroid-forming efficiency of the cells and the expression of stemness-related genes. HMGA1 overexpression in adherent A2780 cells increased cancer stem cell properties, including proliferation, spheroid-forming efficiency and the expression of stemness-related genes. In addition, HMGA1 regulated ABCG2 promoter activity through HMGA1-binding sites. Knockdown of HMGA1 in spheroid cells reduced resistance to chemotherapeutic agents, whereas the overexpression of HMGA1 in adherent ovarian cancer cells increased resistance to chemotherapeutic agents in vitro. Furthermore, HMGA1-overexpressing A2780 cells showed a significant survival advantage after chemotherapeutic agent treatment in a xenograft tumorigenicity assay. Together, our results provide novel insights regarding the critical role of HMGA1 in the regulation of the cancer stem cell characteristics of ovarian cancer cells, thus suggesting that HMGA1 may be an important target in the development of therapeutics for ovarian cancer patients. PMID:27561949

  9. Stromal Cell-Derived Factor-1α Plays a Crucial Role Based on Neuroprotective Role in Neonatal Brain Injury in Rats

    PubMed Central

    Mori, Miki; Matsubara, Keiichi; Matsubara, Yuko; Uchikura, Yuka; Hashimoto, Hisashi; Fujioka, Toru; Matsumoto, Takashi

    2015-01-01

    Owing to progress in perinatal medicine, the survival of preterm newborns has markedly increased. However, the incidence of cerebral palsy has risen in association with increased preterm birth. Cerebral palsy is largely caused by cerebral hypoxic ischemia (HI), for which there are no effective medical treatments. We evaluated the effects of stromal cell-derived factor-1α (SDF-1α) on neonatal brain damage in rats. Left common carotid (LCC) arteries of seven-day-old Wistar rat pups were ligated, and animals were exposed to hypoxic gas to cause cerebral HI. Behavioral tests revealed that the memory and spatial perception abilities were disturbed in HI animals, and that SDF-1α treatment improved these cognitive functions. Motor coordination was also impaired after HI but was unimproved by SDF-1α treatment. SDF-1α reduced intracranial inflammation and induced cerebral remyelination, as indicated by the immunohistochemistry results. These data suggest that SDF-1α specifically influences spatial perception abilities in neonatal HI encephalopathy. PMID:26251894

  10. Cultural scripts, memories of childhood abuse, and multiple identities: a study of role-played enactments.

    PubMed

    Stafford, Jane; Lynn, Steven Jay

    2002-01-01

    This study compared the reports of satanic, sexual, and physical abuse of persons instructed to role-play either dissociative identity disorder (DID) (n = 33), major depression (n = 33), or a college student who experienced minor adjustment problems ("normal") (n = 33) across a number of trials that included role-played hypnosis. As hypothesized, more of the participants who were asked to role-play DID reported at least one instance of satanic ritual abuse and sexual abuse compared with those who role-played depression or a college student with minor adjustment problems. DID role-players reported more incidents of sexual abuse and more severe physical and sexual abuse than did the major depression role-players. Further, the DID role-players differed from the normal role-players on all the measures of frequency and severity of physical and sexual abuse. Participants in all groups reported more frequent and severe incidents of physical abuse after role-played hypnosis than they did prior to it. PMID:11778708

  11. A deep look into the spray coating process in real-time-the crucial role of x-rays.

    PubMed

    Roth, Stephan V

    2016-10-12

    Tailoring functional thin films and coating by rapid solvent-based processes is the basis for the fabrication of large scale high-end applications in nanotechnology. Due to solvent loss of the solution or dispersion inherent in the installation of functional thin films and multilayers the spraying and drying processes are strongly governed by non-equilibrium kinetics, often passing through transient states, until the final structure is installed. Therefore, the challenge is to observe the structural build-up during these coating processes in a spatially and time-resolved manner on multiple time and length scales, from the nanostructure to macroscopic length scales. During installation, the interaction of solid-fluid interfaces and between the different layers, the flow and evaporation themselves determine the structure of the coating. Advanced x-ray scattering methods open a powerful pathway for observing the involved processes in situ, from the spray to the coating, and allow for gaining deep insight in the nanostructuring processes. This review first provides an overview over these rapidly evolving methods, with main focus on functional coatings, organic photovoltaics and organic electronics. Secondly the role and decisive advantage of x-rays is outlined. Thirdly, focusing on spray deposition as a rapidly emerging method, recent advances in investigations of spray deposition of functional materials and devices via advanced x-ray scattering methods are presented. PMID:27537198

  12. Crucial role of molecular planarity on the second order nonlinear optical property of pyridine based chalcone single crystals

    NASA Astrophysics Data System (ADS)

    Menezes, Anthoni Praveen; Jayarama, A.; Ng, Seik Weng

    2015-05-01

    An efficient nonlinear optical material 2E-3-(4-bromophenyl)-1-(pyridin-3-yl) prop-2-en-1-one (BPP) was synthesized and single crystals were grown using slow evaporation solution growth technique at room temperature. Grown crystal had prismatic morphology and its structure was confirmed by various spectroscopic studies, elemental analysis, and single crystal X-ray diffraction (XRD) technique. The single crystal XRD of the crystal showed that BPP crystallizes in monoclinic system with noncentrosymmetric space group P21 and the cell parameters are a = 5.6428(7) Å, b = 3.8637(6) Å, c = 26.411(2) Å, β = 97.568(11) deg and v = 575.82(12) Å3. The UV-Visible spectrum reveals that the crystal is optically transparent and has high optical energy band gap of 3.1 eV. The powder second harmonic generation efficiency (SHG) of BPP is 6.8 times that of KDP. From thermal analysis it is found that the crystal melts at 139 °C and decomposes at 264 °C. High optical transparency down to blue region, higher powder SHG efficiency and better thermal stability than that of urea makes this chalcone derivative a promising candidate for SHG applications. Furthermore, effect of molecular planarity on SHG efficiency and role of pyridine ring adjacent to carbonyl group in forming noncentrosymmetric crystal systems of chalcone family is also discussed.

  13. Regulation of Macrophage Motility by the Water Channel Aquaporin-1: Crucial Role of M0/M2 Phenotype Switch

    PubMed Central

    Tyteca, Donatienne; Nishino, Tomoya; Debaix, Huguette; Van Der Smissen, Patrick; N'Kuli, Francisca; Hoffmann, Delia; Cnops, Yvette; Rabolli, Virginie; van Loo, Geert; Beyaert, Rudi; Huaux, François; Devuyst, Olivier; Courtoy, Pierre J.

    2015-01-01

    The water channel aquaporin-1 (AQP1) promotes migration of many cell types. Although AQP1 is expressed in macrophages, its potential role in macrophage motility, particularly in relation with phenotype polarization, remains unknown. We here addressed these issues in peritoneal macrophages isolated from AQP1-deficient mice, either undifferentiated (M0) or stimulated with LPS to orientate towards pro-inflammatory phenotype (classical macrophage activation; M1). In non-stimulated macrophages, ablation of AQP1 (like inhibition by HgCl2) increased by 2–3 fold spontaneous migration in a Src/PI3K/Rac-dependent manner. This correlated with cell elongation and formation of lamellipodia/ruffles, resulting in membrane lipid and F4/80 recruitment to the leading edge. This indicated that AQP1 normally suppresses migration of resting macrophages, as opposed to other cell types. Resting Aqp1-/- macrophages exhibited CD206 redistribution into ruffles and increased arginase activity like IL4/IL13 (alternative macrophage activation; M2), indicating a M0-M2 shift. In contrast, upon M1 orientation by LPS in vitro or peritoneal inflammation in vivo, migration of Aqp1-/- macrophages was reduced. Taken together, these data indicate that AQP1 oppositely regulates macrophage migration, depending on stimulation or not by LPS, and that macrophage phenotypic and migratory changes may be regulated independently of external cues. PMID:25719758

  14. Regulation of macrophage motility by the water channel aquaporin-1: crucial role of M0/M2 phenotype switch.

    PubMed

    Tyteca, Donatienne; Nishino, Tomoya; Debaix, Huguette; Van Der Smissen, Patrick; N'Kuli, Francisca; Hoffmann, Delia; Cnops, Yvette; Rabolli, Virginie; van Loo, Geert; Beyaert, Rudi; Huaux, François; Devuyst, Olivier; Courtoy, Pierre J

    2015-01-01

    The water channel aquaporin-1 (AQP1) promotes migration of many cell types. Although AQP1 is expressed in macrophages, its potential role in macrophage motility, particularly in relation with phenotype polarization, remains unknown. We here addressed these issues in peritoneal macrophages isolated from AQP1-deficient mice, either undifferentiated (M0) or stimulated with LPS to orientate towards pro-inflammatory phenotype (classical macrophage activation; M1). In non-stimulated macrophages, ablation of AQP1 (like inhibition by HgCl2) increased by 2-3 fold spontaneous migration in a Src/PI3K/Rac-dependent manner. This correlated with cell elongation and formation of lamellipodia/ruffles, resulting in membrane lipid and F4/80 recruitment to the leading edge. This indicated that AQP1 normally suppresses migration of resting macrophages, as opposed to other cell types. Resting Aqp1-/- macrophages exhibited CD206 redistribution into ruffles and increased arginase activity like IL4/IL13 (alternative macrophage activation; M2), indicating a M0-M2 shift. In contrast, upon M1 orientation by LPS in vitro or peritoneal inflammation in vivo, migration of Aqp1-/- macrophages was reduced. Taken together, these data indicate that AQP1 oppositely regulates macrophage migration, depending on stimulation or not by LPS, and that macrophage phenotypic and migratory changes may be regulated independently of external cues. PMID:25719758

  15. Crucial role of interleukin-1beta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice.

    PubMed

    Srivastava, Kamal D; Rom, William N; Jagirdar, Jaishree; Yie, Ting-An; Gordon, Terry; Tchou-Wong, Kam-Meng

    2002-02-15

    Crystalline silica stimulates macrophages in vitro to release interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) and induces apoptosis of macrophages. Because the fibrogenic potential of a particulate paralleled its ability to induce apoptosis in macrophages, we investigated the underlying mechanisms by which IL-1beta and NO mediate apoptosis and inflammation in murine silicosis. First, we demonstrated that silica induced NO production and apoptosis in vitro using the IC-21 macrophage cell line. Both NO release and apoptosis could be inhibited by neutralizing anti-IL-1beta antibody or the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME), demonstrating the requirement for IL-1beta-mediated NO release in silica-induced apoptosis. We exposed IL-1beta knockout (IL-1beta(-/-)) mice, inducible NOS knockout (iNOS(-/-)) mice, and wild-type mice to 250 mg/m(3) silica for 5 h/d for 10 d using an inhalation chamber. Exposure of wild-type mice to silica resulted in lung inflammation, apoptosis, and significantly larger and more numerous silicotic lesions than in IL-1beta(-/-) mice over a 12-wk course. We also exposed iNOS(-/-) mice via inhalation in the same protocol and compared with wild-type mice and demonstrated that iNOS(-/-) mice had significantly reduced apoptosis and inflammation. These results demonstrated an association between apoptosis and inflammation in murine silicosis and support a potential role for IL-1beta-dependent NO-mediated apoptosis in the evolution of silicosis. PMID:11850347

  16. Crucial Role for Early Growth Response-1 in the Transcriptional Regulation of miR-20b in Breast Cancer

    PubMed Central

    Li, Dongping; Ilnytskyy, Yaroslav; Kovalchuk, Anna; Khachigian, Levon M.; Bronson, Roderick T.; Wang, Bo; Kovalchuk, Olga

    2013-01-01

    Transcriptional regulation of miRNAs that control the pathogenesis of breast cancer remains largely unknown. Here, we showed that ionizing radiation, a known breast carcinogen, triggered the differential expression of miR-20b in mammary tissues. We identified several GC-rich consensus binding motifs for the zinc finger transcription factor early growth response-1 (EGR1) in miR-20b promoter. miR-20b was upregulated by IR and its upregulation correlated with EGR1 expression in the breast cancer cell line HCC1806. Therefore, we used HCC1806 cells as a model system to explore the role of EGR1 in miR-20b transcription. siRNA knockdown of EGR1 attenuated miR-20b expression. Luciferase assays showed that whereas EGR1 stimulated luciferase activity driven by the wild-type miR-20b promoter, this induction was abolished in the mutant miR-20 promoter construct. We noted significant enrichment of EGR1 at miR-20b promoter in HCC1806 cells compared with normal human mammary epithelial cells. Suppression of miR-20b significantly inhibited HCC1806 cell proliferation and migration, and led to G 0/G 1 and S phase arrest. In vitro RNA-pull down assays indicated that miR-20b targets numerous tumor suppressors, including PTEN and BRCA1, which were downregulated in HCC1806. Conversely, suppression of miR-20b increased PTEN and BRCA1 levels. Moreover, immunohistochemical and FISH analyses showed that the miR-20b expression correlated significantly with EGR1 levels in breast cancer tissues. Our findings thus demonstrate for the first time that EGR1 is a key player in the transcriptional control of miR-20b, and miR-20b may in turn function as an oncogene by contributing to breast tumorigenesis via tumor suppressor targeting. PMID:23945289

  17. Crucial Roles of Systemic and Tissue Lipid Peroxidation Levels and Anti-Oxidant Defences Following Contrast Agent Application

    PubMed Central

    Sitar, Gungor; Kucuk, Mehmet; Erinc Sitar, Mustafa; Yasar, Ozgur; Aydin, Seval; Yanar, Karolin; Cakatay, Ufuk; Buyukpınarbasili, Nur

    2016-01-01

    Background One of the most important side effects of contrast pharmaceutical agents, which are used very common in routine radiology practice, is contrast induced nephropathy. Even ischemia, oxidative stress and osmolality related cytotoxic effects are considered, the molecular mechanisms underlying this pathology have not been identified completely yet. Objectives The aim of the current study was to reveal the role of oxidative stress and antioxidant enzymatic defence mechanisms in the aetiopathogenesis of contrast-induced nephropathy. We also studied possible alleviating effects of N-acetylcysteine (NAC), a potent antioxidant, to obtain extra information regarding the molecular mechanisms underlying this pathology. Materials and Methods This is an clinical-experimental study, This study was conducted of Istanbul/Turkey between September 15, 2012 and April 15, 2013. Three groups of male rats were randomly set up as a control group (C), a 100 mg/kg intraperitoneal NAC + 7 mL/kg contrast agent group (N + CIN) and a 7 mL/kg intraperitoneal contrast agent group (CIN). They were placed in individual metabolic cages 48 hours after agent administration to obtain 24-hour urine samples. Renal function tests (albumin, urea, creatinine, total protein) were conducted, oxidative stress parameters (Cu, Zn superoxide dismutase activity - Cu, Zn-SOD; advanced oxidation protein products - AOPP; protein carbonyls - PCO; total thiol groups - T-SH; and lipid hydroperoxides -LHP) were measured and tissues were analysed histopathologically. Results Compared with the control group, groups CIN and N + CIN had significantly higher urea and LHP levels (P < 0.05 and P < 0.001, respectively) and significantly lower Cu, Zn-SOD activity and creatinine clearance (P < 0.05). There was no statistically significant difference between the groups in PCO or AOPP levels despite differences in descriptive statistics. Conclusions Contrast-agent-induced nephropathic changes are more closely related to

  18. Heme oxygenase/carbon monoxide pathway inhibition plays a role in ameliorating fibrosis following splenectomy.

    PubMed

    Wang, Qiu-Ming; Duan, Zhi-Jun; Du, Jian-Ling; Guo, Shi-Bin; Sun, Xiao-Yu; Liu, Zhen

    2013-05-01

    Splenectomy is a recognized therapy for liver cirrhosis with splenomegaly, since it decreases free iron concentration that accompanies the destruction of red blood cells. Heme oxygenase (HO)-1 and its by-products, iron and carbon monoxide (CO), play crucial roles in hepatic fibrosis. The aim of the present study was to determine whether splenectomy in cirrhotic rats induced by bile duct ligation (BDL), through the HO/CO pathway, could slow down the development of liver fibrosis. Male Sprague-Dawley rats were divided randomly into the sham, BDL, splenectomy, Fe, zinc protoporphyrin (Znpp) and cobalt protoporphyrin (Copp) treatment groups, for inhibiting and inducing HO-1 expression. The level of HO-1 was detected by western blot analysis and reverse transcription-polymerase chain reaction. Serum carboxyhemoglobin (COHb), iron and portal vein pressure (PVP) were also quantified. Liver iron was measured by atomic absorption spectrometry with acetylene-air flame atomization. HO-1 and α-smooth muscle actin (α-SMA) were localized by immunohistochemistry. Liver and spleen iron were visualized by Perls' Prussian blue staining. Hepatic fibrosis was assessed using hematoxylin and eosin (H&E) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum transforming growth factor-β1 (TGF-β1). The results showed that liver, spleen and serum levels of HO-1, COHb and iron were greatly enhanced in the BDL group compared with the sham group; they were reduced following splenectomy and Znpp treatment, but were elevated in the Copp and Fe groups. Hydroxyproline, TGF-β1, α-SMA, PVP and malonaldehyde levels were lower in the splenectomy and Znpp groups compared to BDL, while higher levels were observed in the Copp and Fe-treated groups. Our study shows that splenectomy reduces iron and CO levels in part by reducing HO-1 expression, and it decreases portal pressure and slightly decreases hepatic fibroproliferation. PMID:23525258

  19. Annexin5 Plays a Vital Role in Arabidopsis Pollen Development via Ca2+-Dependent Membrane Trafficking

    PubMed Central

    Zhu, Jingen; Wu, Xiaorong; Yuan, Shunjie; Qian, Dong; Nan, Qiong

    2014-01-01

    The regulation of pollen development and pollen tube growth is a complicated biological process that is crucial for sexual reproduction in flowering plants. Annexins are widely distributed from protists to higher eukaryotes and play multiple roles in numerous cellular events by acting as a putative “linker” between Ca2+ signaling, the actin cytoskeleton and the membrane, which are required for pollen development and pollen tube growth. Our recent report suggested that downregulation of the function of Arabidopsis annexin 5 (Ann5) in transgenic Ann5-RNAi lines caused severely sterile pollen grains. However, little is known about the underlying mechanisms of the function of Ann5 in pollen. This study demonstrated that Ann5 associates with phospholipid membrane and this association is stimulated by Ca2+ in vitro. Brefeldin A (BFA) interferes with endomembrane trafficking and inhibits pollen germination and pollen tube growth. Both pollen germination and pollen tube growth of Ann5-overexpressing plants showed increased resistance to BFA treatment, and this effect was regulated by calcium. Overexpression of Ann5 promoted Ca2+-dependent cytoplasmic streaming in pollen tubes in vivo in response to BFA. Lactrunculin (LatB) significantly prohibited pollen germination and tube growth by binding with high affinity to monomeric actin and preferentially targeting dynamic actin filament arrays and preventing actin polymerization. Overexpression of Ann5 did not affect pollen germination or pollen tube growth in response to LatB compared with wild-type, although Ann5 interacts with actin filaments in a manner similar to some animal annexins. In addition, the sterile pollen phenotype could be only partially rescued by Ann5 mutants at Ca2+-binding sites when compared to the complete recovery by wild-type Ann5. These data demonstrated that Ann5 is involved in pollen development, germination and pollen tube growth through the promotion of endomembrane trafficking modulated by

  20. Exercise and Drinking May Play a Role in Vision Impairment Risk

    MedlinePlus

    ... Exercise and Drinking May Play a Role in Vision Impairment Risk Mar. 20, 2014 In 2020, the ... 477–85. Related Stories Age-Related Macular Degeneration Vision Simulator Mar 01, 2016 What Is Optical Coherence ...

  1. Bringing the U.S. Senate to Your Classroom: A Role Play Activity.

    ERIC Educational Resources Information Center

    Hack, Ken

    1989-01-01

    Advocates role playing for teaching a unit on the legislative branch of government. Students were divided into political parties, sat on committees, and produced legislation. Concludes that experiencing the governmental process enhances citizen participation. (GG)

  2. Charting the Experiential Territory: Clarifying Definitions and Uses of Computer Simulation, Games, and Role Play.

    ERIC Educational Resources Information Center

    Feinstein, Andrew Hale; Mann, Stuart; Corsun, David L.

    2002-01-01

    Provides a classification scheme for computer simulation, role playing, and educational games. Discusses outcomes of each when applied in business and management education and training. (Contains 52 references.) (SK)

  3. Simulating Dynamics: Using Role-Playing to Teach the Process of Bankruptcy Reorganization.

    ERIC Educational Resources Information Center

    Fry, Patricia Brumfield

    1987-01-01

    A course focusing on bankruptcy reorganization uses simulation and role-playing to increase the depth and speed of students' comprehension of the substantive concepts inherent in reorganization proceedings and their place in the process. (MSE)

  4. Study Shows Just How Big a Role Cellphones Play in Car Crashes

    MedlinePlus

    ... a Role Cellphones Play in Car Crashes In-vehicle videos highlight other distractions, such as reading, writing ... for the better numbers, including safety improvements in vehicles and roads. "Despite this improvement, though, the U.S. ...

  5. Evaluating the impact of role-playing simulations on global competency in an online transnational engineering course

    NASA Astrophysics Data System (ADS)

    Wold, Kari

    Successfully interacting with those from different cultures is essential to excel in any field, particularly when global, transnational collaborations in the workplace are increasingly common. However, many higher education students in engineering are not explicitly taught how to display the global competency skills desired by future employers. To display global competency skills means students must be able to visibly respect and recognize differences among those from different cultures. Global competency also means students must be able to show they can adjust their behaviors and integrate others' ideas when working with those with cultural backgrounds other than their own. While these skills are now deemed essential for future engineers, many institutions are struggling with determining which strategies and activities are universally effective to allow students to practice the global competency skills now crucial for success. Immersing engineering students in interactive role-playing simulations in transnational environments is one way institutions are encouraging students to illustrate and develop global competency skills. Role-playing simulations in transnational education provide environments where students adopt roles, interact with other students, and together explore and address realistic global problems. However, no studies have addressed whether or how role-playing simulations can help develop global competency in transnational engineering courses, students' perceptions regarding whether they change their abilities to display global competency in those environments, and their perspectives the effectiveness of using role-playing simulations for this purpose. To address this gap, this study assesses the impact of two subsequent role-playing simulations involving nuclear energy policy in a transnational course involving engineering students from the University of Virginia in Charlottesville, Virginia, and from Technische Universitat Dortmund in Dortmund

  6. What Can Students Learn in an Extended Role-Play Simulation on Technology and Society?

    ERIC Educational Resources Information Center

    Loui, Michael C.

    2009-01-01

    In a small course on technology and society, students participated in an extended role-play simulation for two weeks. Each student played a different adult character in a fictional community, which faces technological decisions in three scenarios set in the near future. The three scenarios involved stem cell research, nanotechnology, and privacy.…

  7. Exploring Kindergarten Teachers' Views and Roles Regarding Children's Outdoor Play Environments in Oman

    ERIC Educational Resources Information Center

    Ihmeideh, Fathi M.; Al-Qaryouti, Ibrahim A.

    2016-01-01

    The purpose of this study was to explore kindergarten teachers' views and roles regarding outdoor play environments in Omani kindergartens. Thirty kindergarten teachers from 15 private kindergartens were observed and interviewed. The results indicated that teachers recognize the importance of outdoor play in children's development and learning.…

  8. FtsH11 Proteases play a critical role in high temperature stress tolerance in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    FtsHs (Filamentous temperature sensitive H), ATP-dependent zinc metalloproteases of the AAA-superfamily, play essential roles in the turn over of thylakoid proteins damaged by high light stress during photosynthesis. Here, we show that FtsH11, one of the 12 FtsH members in Arabidopsis, plays critic...

  9. Learner Interaction in a Massively Multiplayer Online Role Playing Game (MMORPG): A Sociocultural Discourse Analysis

    ERIC Educational Resources Information Center

    Peterson, Mark

    2012-01-01

    This exploratory study investigates the linguistic and social interaction of four intermediate EFL learners during game play in a massively multiplayer online role playing game (MMORPG). Twelve illustrative episodes drawn from the participants' text chat, collected in four 70-minute sessions held over a one-month period, are analyzed from a…

  10. Teaching to Play Performing a Main Role -- Effective Method of Pretend Play Facilitation in Preschool-Age Children

    ERIC Educational Resources Information Center

    Gmitrova, Vlasta

    2013-01-01

    We compared the efficiency of teacher's direct and indirect intervention into pretend play. Three hundred sixty-eight kindergarten children and 92 qualified kindergarten teachers were involved in the study. In the control group, a teacher indirectly initiated a play, creating a playing corner adjusted to the theme of the pretend play and…

  11. Using Analogy Role-Play Activity in an Undergraduate Biology Classroom to Show Central Dogma Revision

    ERIC Educational Resources Information Center

    Takemura, Masaharu; Kurabayashi, Mario

    2014-01-01

    For the study of biology in an undergraduate classroom, a classroom exercise was developed: an analogy role-play to learn mechanisms of gene transcription and protein translation (central dogma). To develop the central dogma role-play exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress hanger, and amino acids using Lego®…

  12. Reforming Higher Education in the United States: What Role Can States Play?

    ERIC Educational Resources Information Center

    21st Century Policy Review, 1992

    1992-01-01

    This interview with George J. Funario, Deputy Secretary of the Maryland Higher Education Commission, examines the roles that states can play in reforming higher education, drawing on Maryland's experience. The importance of educating minority group members is emphasized, and the role of the federal government in making a financial commitment is…

  13. Reflecting on Role Play in Geographic Education: The Case of the Banana War

    ERIC Educational Resources Information Center

    Kurtz, Hilda E.

    2004-01-01

    Debates over the nature and extent of globalization raise many issues to be addressed in a geographic education. In this paper, I briefly review case method instruction and role-play as teaching strategies suitable for material on globalization and other geographic subject matter, and then sketch an overview of an undergraduate geography role-play…

  14. Psychometric Characteristics of Role-Play Assessments of Social Skill in Schizophrenia

    ERIC Educational Resources Information Center

    Bellack, Alan S.; Brown, Clayton H.; Thomas-Lohrman, Shannon

    2006-01-01

    There is an extensive literature documenting that people with schizophrenia have marked impairments in social role functioning and social skill. One of the most widely employed strategies for assessing social skill has been role-play tests: simulated social interactions that are videotaped for subsequent behavioral coding. There has been…

  15. 25 CFR 900.229 - What role will the awarding official play during an appeal?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false What role will the awarding official play during an appeal? 900.229 Section 900.229 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR, AND INDIAN... EDUCATION ASSISTANCE ACT Post-Award Contract Disputes § 900.229 What role will the awarding official...

  16. 25 CFR 900.229 - What role will the awarding official play during an appeal?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false What role will the awarding official play during an appeal? 900.229 Section 900.229 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR, AND INDIAN... EDUCATION ASSISTANCE ACT Post-Award Contract Disputes § 900.229 What role will the awarding official...

  17. The Role Played by Grandparents in Family Support and Learning: Considerations for Mainstream and Special Schools

    ERIC Educational Resources Information Center

    Mitchell, Wendy

    2008-01-01

    The twenty-first century family faces many demographic changes. Despite this, the importance of intergenerational relationships remains. This article initially reviews the literature surrounding the role that grandparents play in their children's families, highlighting a growing body of research demonstrating the important support role that…

  18. Whipping Them in: Role-Playing Party Cohesion with a Chief Whip

    ERIC Educational Resources Information Center

    Cowley, Philip; Stuart, Mark

    2015-01-01

    We have used a role-play exercise to help students understand the role of the whips in British parliamentary politics, a subject with which students often struggle. In itself, this proved a valuable learning and teaching tool, but we found it became even more useful when we incorporated a practitioner into the exercise. This overcame some of the…

  19. Using Social Networking for Online Role-Plays to Develop Students' Argumentative Strategies

    ERIC Educational Resources Information Center

    Beach, Richard; Doerr-Stevens, Candance

    2011-01-01

    Social networking sites may include argumentative writing about particular issues in which participants adopt competing perspective and discourses on those issues. This study examined roles and discourses adopted by high school students participating in an online role-play conducted on a Ning platform regarding their school's Internet policies on…

  20. Science and Math through Role-Play Centers in the Elementary School Classroom.

    ERIC Educational Resources Information Center

    Jarrett, Olga S.

    1997-01-01

    Describes role-play centers in which children can do math problems, invent, experiment, write with a purpose, and act out adult career roles. Examples of centers include a doctor's office, a supermarket, a fix-it or inventor's workshop, a post office, a pet store, a zoo, a veterinary clinic, a museum, and a restaurant. (DKM)

  1. NEUTROPHILS PLAY A CRITICAL ROLE IN THE DEVELOPMENT OF LPS-INDUCED AIRWAY DISEASE

    EPA Science Inventory

    ETD-02-045 (GAVETT) GPRA # 10108

    Neutrophils Play a Critical Role in the Development of LPS-Induced Airway Disease.
    Jordan D. Savov, Stephen H. Gavett*, David M. Brass, Daniel L. Costa*, and David A. Schwartz

    ABSTRACT
    We investigated the role of neutrophils...

  2. The ULT trxG Fatcors play a role in Arabidopsis Fertilization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Trithorax group (trxG) and Polycomb group (PcG) proteins are epigenetic modifiers that play key roles in eukaryotic development by promoting active or repressive gene expression states, respectively. Although PcG proteins have well-defined roles in controlling developmental transitions, cell fate de...

  3. An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways

    PubMed Central

    Deuis, Jennifer R; Zimmermann, Katharina; Romanovsky, Andrej A; Possani, Lourival D; Cabot, Peter J; Lewis, Richard J; Vetter, Irina

    2013-01-01

    Cold allodynia, pain in response to cooling, occurs during or within hours of oxaliplatin infusion and is thought to arise from a direct effect of oxaliplatin on peripheral sensory neurons. To characterize the pathophysiological mechanisms underlying acute oxaliplatin-induced cold allodynia, we established a new intraplantar oxaliplatin mouse model that rapidly developed long-lasting cold allodynia mediated entirely through tetrodotoxin-sensitive Nav pathways. Using selective inhibitors and knockout animals, we found that Nav1.6 was the key isoform involved, while thermosensitive transient receptor potential channels were not involved. Consistent with a crucial role for delayed-rectifier potassium channels in excitability in response to cold, intraplantar administration of the K+-channel blocker 4-aminopyridine mimicked oxaliplatin-induced cold allodynia and was also inhibited by Navl.6 blockers. Intraplantar injection of the Nav1.6-activator Cn2 elicited spontaneous pain, mechanical allodynia and enhanced 4-aminopyridine-induced cold allodynia. These findings provide behavioural evidence for a crucial role of Nav1.6 in multiple peripheral pain pathways including cold allodynia. PMID:23711479

  4. Toy-playing behavior, sex-role orientation, spatial ability, and science achievement

    NASA Astrophysics Data System (ADS)

    Tracy, Dyanne M.

    The purpose of this correlational study was to examine the possible relationships among children's extracurricular toy-playing habits, sex-role orientations, spatial abilities, and science achievement. Data were gathered from 282 midwestern, suburban, fifth-grade students. It was found that boys had significantly higher spatial skills than girls. No significant differences in spatial ability were found among students with different sex-role orientations. No significant differences in science achievement were found between girls and boys, or among students with the four different sex-role orientations. Students who had high spatial ability also had significantly higher science achievement scores than students with low spatial ability. Femininely oriented boys who reported low playing in the two-dimensional, gross-body-movement, and proportional-arrangement toy categories scored significantly higher on the test of science achievement than girls with the same sex-role and toy-playing behavior.

  5. The crucial role of collagen-binding integrins in maintaining the mechanical properties of human scleral fibroblasts-seeded collagen matrix

    PubMed Central

    Hu, Shoulong; Cui, Dongmei; Yang, Xiao; Hu, Jianmin; Wan, Wenjuan

    2011-01-01

    (p<0.01). However, the creep extension and creep rate of the integrin α2β1 antibody (1 μg/ml or 4 μg/ml) group were not significantly different from those in the integrin α1β1 antibody (1 μg/ml or 4 μg/ml) group (p>0.05). Conclusions Our findings suggested that HSF integrin α1β1 and α2β1 participated in maintaining the mechanical creep properties of the HSFs-seeded collagen matrix. Furthermore, integrin α2β1 might play a more crucial role in maintaining the mechanical creep properties of the collagen matrix than does integrin α1β1. PMID:21647271

  6. Role-Play Experience Facilitates Reading the Mind of Individuals with Different Perception

    PubMed Central

    Furumi, Fumikazu; Koyasu, Masuo

    2013-01-01

    The present study examined effects of role-play experience on reading the mind of people with different perception. It is normally difficult but very important in daily life to understand people with different characteristics, including those with restricted color vision. We explored the mechanisms of reading the mind of people with different perception. Forty university students were introduced to a communication task in which the use of mindreading was essential. During each trial, participants viewed a shelf, presented on a laptop computer, which contained several familiar objects, and they were instructed to touch an object on the shelf following an instruction issued by a partner who stood at the opposite side of the shelf. There were two partners: one was a monkey with normal color vision and the other was a dog with restricted color vision. The monkey could see all the objects in the same colors as the participants, whereas the dog saw some objects in different colors (e.g., he saw as yellow objects that the participants saw as red). Participants were required to respond according to the partner's instruction. In the restricted color vision condition, the dog saw the colors of objects differently; thus, participants had to work out his intentions (i.e., mind read), according to his different perspective. In the normal color vision condition, all objects were in the same colors as those seen by the monkey. Before the test phase, the role-play group had a role-play experience in which participants assumed the role of people with restricted color vision. No-role-play participants made significantly more errors in the restricted color vision condition than in the normal color vision condition, whereas among role-play participants, there was no difference between conditions. These results suggest that role-play experience facilitates reading the mind of people with perceptual experiences different from our own. PMID:24023966

  7. The Pepper Lipoxygenase CaLOX1 Plays a Role in Osmotic, Drought and High Salinity Stress Response.

    PubMed

    Lim, Chae Woo; Han, Sang-Wook; Hwang, In Sun; Kim, Dae Sung; Hwang, Byung Kook; Lee, Sung Chul

    2015-05-01

    In plants, lipoxygenases (LOXs) are involved in various physiological processes, including defense responses to biotic and abiotic stresses. Our previous study had shown that the pepper 9-LOX gene, CaLOX1, plays a crucial role in cell death due to pathogen infection. Here, the function of CaLOX1 in response to osmotic, drought and high salinity stress was examined using CaLOX1-overexpressing (CaLOX1-OX) Arabidopsis plants. Changes in the temporal expression pattern of the CaLOX1 gene were observed when pepper leaves were treated with drought and high salinity, but not when treated with ABA, the primary hormone in response to drought stress. During seed germination and seedling development, CaLOX1-OX plants were more tolerant to ABA, mannitol and high salinity than wild-type plants. In contrast, expression of the ABA-responsive marker genes RAB18 and RD29B was higher in CaLOX1-OX Arabidopsis plants than in wild-type plants. In response to high salinity, CaLOX1-OX plants exhibited enhanced tolerance, compared with the wild type, which was accompanied by decreased accumulation of H2O2 and high levels of RD20, RD29A, RD29B and P5CS gene expression. Similarly, CaLOX1-OX plants were also more tolerant than wild-type plants to severe drought stress. H2O2 production and the relative increase in lipid peroxidation were lower, and the expression of COR15A, DREB2A, RD20, RD29A and RD29B was higher in CaLOX1-OX plants, relative to wild-type plants. Taken together, our results indicate that CaLOX1 plays a crucial role in plant stress responses by modulating the expression of ABA- and stress-responsive marker genes, lipid peroxidation and H2O2 production. PMID:25657344

  8. Analyzing Members' Motivations to Participate in Role-Playing and Self-Expression Based Virtual Communities

    NASA Astrophysics Data System (ADS)

    Lee, Young Eun; Saharia, Aditya

    With the rapid growth of computer mediated communication technologies in the last two decades, various types of virtual communities have emerged. Some communities provide a role playing arena, enabled by avatars, while others provide an arena for expressing and promoting detailed personal profiles to enhance their offline social networks. Due to different focus of these virtual communities, different factors motivate members to participate in these communities. In this study, we examine differences in members’ motivations to participate in role-playing versus self-expression based virtual communities. To achieve this goal, we apply the Wang and Fesenmaier (2004) framework, which explains members’ participation in terms of their functional, social, psychological, and hedonic needs. The primary contributions of this study are two folds: First, it demonstrates differences between role-playing and self-expression based communities. Second, it provides a comprehensive framework describing members’ motivation to participate in virtual communities.

  9. Using virtual worlds for role play simulation in child and adolescent psychiatry: an evaluation study

    PubMed Central

    Vallance, Aaron K.; Hemani, Ashish; Fernandez, Victoria; Livingstone, Daniel; McCusker, Kerri; Toro-Troconis, Maria

    2014-01-01

    Aims and method To develop and evaluate a novel teaching session on clinical assessment using role play simulation. Teaching and research sessions occurred sequentially in computer laboratories. Ten medical students were divided into two online small-group teaching sessions. Students role-played as clinician avatars and the teacher played a suicidal adolescent avatar. Questionnaire and focus-group methodology evaluated participants’ attitudes to the learning experience. Quantitative data were analysed using SPSS, qualitative data through nominal-group and thematic analyses. Results Participants reported improvements in psychiatric skills/knowledge, expressing less anxiety and more enjoyment than role-playing face to face. Data demonstrated a positive relationship between simulator fidelity and perceived utility. Some participants expressed concern about added value over other learning methods and non-verbal communication. Clinical implications The study shows that virtual worlds can successfully host role play simulation, valued by students as a useful learning method. The potential for distance learning would allow delivery irrespective of geographical distance and boundaries. PMID:25285217

  10. The nucleolar GTPase nucleostemin-like 1 plays a role in plant growth and senescence by modulating ribosome biogenesis

    PubMed Central

    Jeon, Young; Park, Yong-Joon; Cho, Hui Kyung; Jung, Hyun Ju; Ahn, Tae-Kyu; Kang, Hunseung; Pai, Hyun-Sook

    2015-01-01

    Nucleostemin is a nucleolar GTP-binding protein that is involved in stem cell proliferation, embryonic development, and ribosome biogenesis in mammals. Plant nucleostemin-like 1 (NSN1) plays a role in embryogenesis, and apical and floral meristem development. In this study, a nucleolar function of NSN1 in the regulation of ribosome biogenesis was identified. Green fluorescent protein (GFP)-fused NSN1 localized to the nucleolus, which was primarily determined by its N-terminal domain. Recombinant NSN1 and its N-terminal domain (NSN1-N) bound to RNA in vitro. Recombinant NSN1 expressed GTPase activity in vitro. NSN1 silencing in Arabidopsis thaliana and Nicotiana benthamiana led to growth retardation and premature senescence. NSN1 interacted with Pescadillo and EBNA1 binding protein 2 (EBP2), which are nucleolar proteins involved in ribosome biogenesis, and with several ribosomal proteins. NSN1, NSN1-N, and EBP2 co-fractionated primarily with the 60S ribosomal large subunit in vivo. Depletion of NSN1 delayed 25S rRNA maturation and biogenesis of the 60S ribosome subunit, and repressed global translation. NSN1-deficient plants exhibited premature leaf senescence, excessive accumulation of reactive oxygen species, and senescence-related gene expression. Taken together, these results suggest that NSN1 plays a crucial role in plant growth and senescence by modulating ribosome biogenesis. PMID:26163696

  11. Skills Development Using Role-Play in a First-Year Pharmacy Practice Course

    PubMed Central

    2011-01-01

    Objectives. To evaluate the usefulness of a role-play model in developing students’ patient-care skills in a first-year undergraduate pharmacy practice course. Design. A role-play model was developed and implemented in workshops across 2 semesters of a year-long course. Students performed different roles, including that of a pharmacist and a patient, and documented case notes in a single interaction. Assessment. Student perceptions of the usefulness of the approach in acquiring skills were measured by surveying students during both semesters. All student assessments (N=130 in semester1; N=129 in semester 2) also were analyzed for skills in verbal communication, information gathering, counselling and making recommendations, and accurately documenting information. A majority of students found the approach useful in developing skills. An analysis of student assessments revealed that role-playing was not as effective in building skills related to accurate documentation as it was in other areas of patient care. Conclusions. Role play is useful for developing patient-care skills in communication and information gathering but not for documentation of case notes. PMID:21829258

  12. Exploring the Impact of Role-Playing on Peer Feedback in an Online Case-Based Learning Activity

    ERIC Educational Resources Information Center

    Ching, Yu-Hui

    2014-01-01

    This study explored the impact of role-playing on the quality of peer feedback and learners' perception of this strategy in a case-based learning activity with VoiceThread in an online course. The findings revealed potential positive impact of role-playing on learners' generation of constructive feedback as role-playing was associated…

  13. Experiencing the Elicitation of User Requirements and Recording Them in Use Case Diagrams through Role-Play

    ERIC Educational Resources Information Center

    Costain, Gay; McKenna, Brad

    2011-01-01

    This paper describes a role-play exercise used in a second-year tertiary Systems Analysis and Design course, and the quantitative and qualitative analysis of the students' responses to a survey that solicited their perceptions of that role-play experience. The role-play involved students in eliciting user requirements from customers during a Joint…

  14. To What Extent Might Role Play Be a Useful Tool for Learning Mathematics?

    ERIC Educational Resources Information Center

    Williams, Helen

    2012-01-01

    To most children in primary school role-play is just something you do, and something you enjoy. It is part-and-parcel of being at school, part of the normal classroom activity. So, why can it not just be a normal part of learning mathematics? Can we study learners "in role", and make judgments about what they learn, and how they learn? This is the…

  15. From board to bedside – training the communication competences of medical students with role plays

    PubMed Central

    2014-01-01

    Background Role plays and standardized patients are often used in medical education and have proven to be effective tools for enhancing the communication skills of medical students. Most course concepts need additional time and teaching staff, and there are only a few studies about role plays in the preclinical segment. Methods We developed a highly consolidated concept for the curricular course of 2nd-year medical students, including ten role plays about five subjects: anamnesis, shared decision making, prevention, breaking bad news, and so-called “difficult interactions”. Before the course, all students were asked about their expectations and attitudes toward the course. After the course, all students rated the course, their individual learning progress, whether their expectations had been fulfilled, and re-evaluated their attitudes. Questionnaires were self-report measures and had a quantitative and a short qualitative section and were analyzed with descriptive statistics. Group differences (sex, age, role played) were evaluated with t tests at a Bonferonni-corrected significance level of p = .03 and the non-parametric U-tests. Results Implementing this practical course concept is possible without incurring additional costs. This paper not only shows how that can be done but also provides 5 examples of role scripts for different training subjects. The course concept was highly appreciated by the students. More than 75% felt that they had learned important communication techniques and would be better able to handle difficult situations. Playing the doctor’s role was felt to be more useful than playing the patient’s role. Women admitted a higher degree of shyness in the beginning and gave higher ratings to their learning progress than men. Students’ most frequent wish in the qualitative analysis was to be able to play the doctor’s role at least once. The students’ answers showed a differentiated pattern, thus suggesting that the influence of

  16. Role-play facilitates children’s mindreading of those with atypical color perception

    PubMed Central

    Furumi, Fumikazu; Koyasu, Masuo

    2014-01-01

    The present study examined the effects of role-play experience on children’s mindreading ability. Forty-one primary school children (20 boys, 21 girls, mean age: 9.37 years, range: 8–11 years) were introduced to a communication task in which the use of mindreading was essential. During each trial, participants viewed a shelf, presented on a laptop, which contained several familiar objects, and they were instructed to touch an object on the shelf following an order issued by a “manager” who stood at the opposite side of the shelf. There were two managers: one was a monkey manager with normal color vision, and the other was a dog manager with restricted color vision. The monkey manager could see all the objects in the same colors as the participants, whereas the dog manager saw some objects in different colors. Participants were required to respond according to the manager’s instruction. In the restricted color vision condition, the dog manager saw the colors of objects differently; thus, participants had to work out his intentions, according to his different perspective. In the normal color vision condition, all objects were in the same colors as those seen by the monkey manager. Before the test phase, participants in the role-play group were provided a role-play experience in which they assumed the role of the dog manager with restricted color vision. The experimental data were analyzed using a 2 × 2 mixed-design ANOVA (role-play condition × communication partner condition) to examine differences in the error rate. Both main effects and its interaction were significant. According to the post-hoc analyses, participants in the no-role-play condition made significantly more errors in the restricted color vision condition than in the normal color vision condition, whereas no such difference was found among participants in the role-play condition. These results suggest that role-play experience could facilitate mindreading of characters with restricted color

  17. Crucial role of the biological barrier at the primary targeted organs in controlling the translocation and toxicity of multi-walled carbon nanotubes in the nematode Caenorhabditis elegans

    NASA Astrophysics Data System (ADS)

    Wu, Qiuli; Li, Yinxia; Li, Yiping; Zhao, Yunli; Ge, Ling; Wang, Haifang; Wang, Dayong

    2013-10-01

    Multi-walled carbon nanotubes (MWCNTs) can be translocated into the targeted organs of organisms. We employed a model organism of the nematode Caenorhabditis elegans to investigate the role of a biological barrier at the primary targeted organs in regulating the translocation and toxicity formation of MWCNTs. A prolonged exposure to MWCNTs at predicted environmental relevant concentrations caused adverse effects associated with both the primary and secondary targeted organs on nematodes. The function of PEGylated modification in reducing MWCNTs toxicity might be mainly due to the suppression of their translocation into secondary targeted organs through the primary targeted organs. A biological barrier at the primary targeted organs contributed greatly to the control of MWCNTs translocation into secondary targeted organs, as indicated by functions of Mn-SODs required for prevention of oxidative stress in the primary targeted organs. Over-expression of Mn-SODs in primary targeted organs effectively suppressed the translocation and toxicity of MWCNTs. Our work highlights the crucial role of the biological barrier at the primary targeted organs in regulating the translocation and toxicity formation of MWCNTs. Our data also shed light on the future development of engineered nanomaterials (ENMs) with improved biocompatibility and design of prevention strategies against ENMs toxicity.Multi-walled carbon nanotubes (MWCNTs) can be translocated into the targeted organs of organisms. We employed a model organism of the nematode Caenorhabditis elegans to investigate the role of a biological barrier at the primary targeted organs in regulating the translocation and toxicity formation of MWCNTs. A prolonged exposure to MWCNTs at predicted environmental relevant concentrations caused adverse effects associated with both the primary and secondary targeted organs on nematodes. The function of PEGylated modification in reducing MWCNTs toxicity might be mainly due to the suppression

  18. Health Education in Practice. Let's Party: Teaching Responsible Alcohol Consumption Through Role Play.

    ERIC Educational Resources Information Center

    Lyde, Adrian R.; Temple, Mark A.

    1998-01-01

    Role play can teach college students responsible alcohol consumption behavior. The paper presents a technique to help students develop skills and attitudes that lead to responsible alcohol use behaviors. The technique models appropriate behaviors for party hosts, helps students put knowledge into action, and lets students explore the potential…

  19. Experiential Learning through Interactive Drama: An Alternative to Student Role Plays

    ERIC Educational Resources Information Center

    Boggs, James G.; Mickel, Amy E.; Holtom, Brooks C.

    2007-01-01

    This article introduces interactive drama as an alternative to student role-plays. Interactive drama increases student engagement and explores complex issues in management. It features scenes from organizational life being performed live by trained actors before a student audience, stopping at pivotal points so the audience can interact with the…

  20. Das Spiel mit dem Rollenspiel (The Game with Role-Playing)

    ERIC Educational Resources Information Center

    Hohmann, Heinz-Otto

    1977-01-01

    Maintains that role-play should not become the pre-eminent method in foreign language teaching, since it does not reach the broad goals of learning, such as the systematic acquisition of language material, achievement measuring, or the expression of personal views of many participants in adult education (Text is in German.) (IFS/WGA)

  1. The Role Ethnicity Plays in Who Elementary Students Choose as Friends

    ERIC Educational Resources Information Center

    Waite, Bryan; Anderson, Genan; Byrd, Elaine; Hudgins, Talitha; Nelson, Julie; Patch, Mike; Simmerman, Sue

    2010-01-01

    Friendships and their formation are an important part of the educational experience for K-12 students. With the ever increasing ethnic and racial diversity that is filling our schools, it is paramount that we examine how children choose their friends. This study examined whether or not race and ethnicity play a role in how children choose with…

  2. Role Playing and Behavior Modification: A Demonstration with Mentally Retarded Children

    ERIC Educational Resources Information Center

    Buchan, L. Gerald; And Others

    1976-01-01

    Within the last few years a "new wave" of therapeutic techniques for teaching the mentally retarded has emerged in this country. Describes how the behavior of two demonstration groups of mentally retarded children utilize the accomodations of role playing and behavior modification to develop social skills. (Author/RK)

  3. What Are the Roles that Children's Drawings Play in Inquiry of Science Concepts?

    ERIC Educational Resources Information Center

    Chang, Ni

    2012-01-01

    This study was designed to identify the roles that drawing played in the process of children's acquisition of science concepts. Seventy pre-service teachers through four semesters from a Midwest University in the USA developed lesson plans on science concepts and then taught them to 70 young children ages 4-7, respectively. This experience was…

  4. The Role the Collegiate American Marketing Association Plays in Professional and Entrepreneurial Skill Development

    ERIC Educational Resources Information Center

    Peltier, James W.; Scovotti, Carol; Pointer, Lucille

    2008-01-01

    Professional student organizations offer members a wide range of learning opportunities for applied marketing experiences. Little research exists in the marketing education literature on the role student organizations play in preparing their members for life beyond school. Understanding what students seek as members of such organizations and how…

  5. E-Drama: Facilitating Online Role-Play Using an AI Actor and Emotionally Expressive Characters

    ERIC Educational Resources Information Center

    Zhang, Li; Gillies, Marco; Dhaliwal, Kulwant; Gower, Amanda; Robertson, Dale; Crabtree, Barry

    2009-01-01

    This paper describes a multi-user role-playing environment, referred to as "e-drama", which enables groups of people to converse online, in scenario driven virtual environments. The starting point of this research, is an existing application known as "edrama", a 2D graphical environment in which users are represented by static cartoon figures.…

  6. The Ethanol Project: Exploring Alternative Energy with Role-Play and Writing

    ERIC Educational Resources Information Center

    Winter, Julia

    2013-01-01

    This article describes a project that includes a two-week series of researching, essay writing, and speaking lessons exploring the broader implications of using ethanol as a fuel. The author, a chemistry teacher, describes how she uses a senate hearing discussion of ethanol fuel subsidies as the forum for a role-play. The four components of the…

  7. Teacher's Skill Improvement by Role-Play and Simulations on Collaborative Educational Virtual Worlds

    ERIC Educational Resources Information Center

    Lorenzo, Carlos-Miguel

    2014-01-01

    This study looked at teachers' role-play and simulations in order to increase teachers' skills in psycho-pedagogical support on educational virtual worlds. We put forward a proposal to encourage the use of 3D scenarios where teachers can improve their skills for situations of cultural and ethical concerns that require a high level…

  8. Integration of Games, Music, and Role-Playing into Your ESL Classroom

    ERIC Educational Resources Information Center

    Hauptman, Philip C.

    1976-01-01

    Problem-solving is a necessary stage for all learning. Students who are learning English must pass through such a stage. The teacher must isolate problem-solving activities for use in the classroom. Role-playing, music and games (language puzzles, verbal or board games, action games) are suitable activities. (CFM)

  9. Trading Spaces: An Educator's Ethnographic Exploration of Adolescents' Digital Role-Play

    ERIC Educational Resources Information Center

    Haynes-Moore, Stacy

    2015-01-01

    In this work, the author examines a digital role-play in which participants composed an alternate version of "The Hunger Games" (Collins, 2008). Participants imagined characters and posted more than 400 scenes in the online collaboration. The author draws upon ethnographic methods (Merriam, 2009) to describe her participant-observer…

  10. A Role-Play Game to Facilitate the Development of Students' Reflective Internet Skills

    ERIC Educational Resources Information Center

    Admiraal, Wilfried

    2015-01-01

    Although adolescents are currently the most frequent users of the Internet, many youngsters still have difficulties with a critical, reflective, and responsible use of the Internet. A study was carried out on teaching with a digital role-play game to increase students' reflective Internet skills. In this game, students had to promote a fictional…

  11. "Try Walking in Our Shoes": Teaching Acculturation and Related Cultural Adjustment Processes through Role-Play

    ERIC Educational Resources Information Center

    Zamboanga, Byron L.; Ham, Lindsay S.; Tomaso, Cara C.; Audley, Shannon; Pole, Nnamdi

    2016-01-01

    In this article, we describe several role-playing exercises on acculturation and relevant cultural adjustment processes that we incorporated into Tomcho and Foel's classroom activity on acculturation, and we report data that examine subsequent changes in students' responses on pretest and posttest measures shortly after the activity and present…

  12. Students as "Humans Chromosomes" in Role-Playing Mitosis and Meiosis

    ERIC Educational Resources Information Center

    Chinnici, Joseph P.; Yue, Joyce W.; Torres, Kieron M.

    2004-01-01

    Students often find it challenging to understand mitosis and meiosis and determine their processes. To develop an easier way to understand these terms, students are asked to role-play mitosis and meiosis and students themselves act as human chromosomes, which help students to learn differences between mitosis and meiosis.

  13. Use of an Empathy Algorithm with a Role-Played Client.

    ERIC Educational Resources Information Center

    Shaffer, Warren F.; Hasegawa, Carol S.

    1984-01-01

    Presented an empathy algorithm, a procedure for deciding whether to use an interchangeable or an additive empathy response and instructions for the construction of each response, to a randomly chosen group of novice counselors (N=23). The experimental group performed significantly better in counseling a role-played client than did controls.…

  14. Building Fictional Ethos: Analysing the Rhetorical Strategies of Persona Design for Online Role Play

    ERIC Educational Resources Information Center

    Doerr-Stevens, Candance

    2011-01-01

    This article presents a qualitative case study that uses discourse and social semiotic analysis methods in order to examine the rhetorical construction of fictional personas within an online role play used for learning in the college classroom. Of special focus are the differing patterns of semiotic resource use (for example, language and…

  15. Role-Playing Simulation as a Communication Tool in Community Dialogue: Karkonosze Mountains Case Study

    ERIC Educational Resources Information Center

    Krolikowska, Karolina; Kronenberg, Jakub; Maliszewska, Karolina; Sendzimir, Jan; Magnuszewski, Piotr; Dunajski, Andrzej; Slodka, Anna

    2007-01-01

    This article describes a process of role-playing simulation (RPS) as it was used during an educational exercise in community dialogue in the Karkonosze Mountains region of southwest Poland. Over the past decade Karkonosze National Park, a regional tourist magnet, has provided an excellent example of environmental conflict emerging from the…

  16. A Role-Play to Illustrate the Energy Changes Occurring in an Exothermic Reaction.

    ERIC Educational Resources Information Center

    Tyas, Toby; Cabot, John

    1999-01-01

    Describes a role-play activity designed to help students understand the energy changes involved in an exothermic reaction by modeling the concepts of bond-breaking takes in energy, activation energy, temperature rise, and bond breaking gives out energy. (WRM)

  17. Mother and Peer Influences on Children's Sex-Role Play Behaviors.

    ERIC Educational Resources Information Center

    Downs, A. Chris; Langlois, Judith H.

    One of a series of studies originating in Austin, Texas examining the relative contribution of the primary socializing agents on the child's sex-role development, their study was designed to determine whether mother and peers of nursery school children differentially reward or punish play with sex-appropriate or sex-inappropriate toys. The study…

  18. Using Role-Play to Enhance Foodborne Illness Crisis Management Capacity in the Produce Industry

    ERIC Educational Resources Information Center

    Kreske, Audrey; Ducharme, Diane; Gunter, Chris; Phister, Trevor

    2013-01-01

    Foodborne illness outbreaks have measurable public health effects and often lead to negative produce industry impacts. Reducing loss following a crisis event requires a management plan, although many fresh produce industry members don't have one. Evidence-based workshops using a role-play simulated outbreak were delivered to impact crisis…

  19. What Do Students Learn from a Role-Play Simulation of an International Negotiation?

    ERIC Educational Resources Information Center

    Schnurr, Matthew A.; De Santo, Elizabeth M.; Green, Amanda D.

    2014-01-01

    This article uses pre- and post-surveys to assess learning outcomes associated with a role-play simulation set within a fictionalized extension of the Convention on Biological Diversity. Quantitative and qualitative data suggest that the simulation increased student appreciation of the complexity of international negotiation, but decreased student…

  20. Teaching Constitutional Law and Related Courses Through Problem-Solving and Role-Playing.

    ERIC Educational Resources Information Center

    Davidow, Robert P.

    1984-01-01

    Problem-solving and role-playing can be used successfully even in the second semester of law school, serving as a bridge between traditional analytical and doctrinal education and the more realistic simulation and clinical experiences of the third year. Students can gain sufficient experience to perform proficiently in more advanced courses. (MSE)

  1. Understanding Our Environment: Challenge. Clear Water Challenge: A Role Play Activity.

    ERIC Educational Resources Information Center

    Lieblich, Suzanne, Ed.

    Part of the Understanding Our Environment project that is designed to engage students in investigating specific environmental problems through concrete activity and direct experience, this unit contains a role-play activity in the form of a public inquiry into the cause of a fish kill on a river that runs through the fictional town of Oakwood. A…

  2. Does Gender Play a Role in the Assessment of Oral Proficiency?

    ERIC Educational Resources Information Center

    Motallebzadeh, Khalil; Nematizadeh, Shaahin

    2011-01-01

    Gender has been a controversial issue which affects the language learning process. McNamara (1996) has proposed that there are some variables affecting second language performance one of which is sex. In much the same way, it has been reported that gender plays a role in the area of language testing (Brown, 2003; Lumley & O'Sullivan, 2005;…

  3. Role-Playing Games for Capacity Building in Water and Land Management: Some Brazilian Experiences

    ERIC Educational Resources Information Center

    Camargo, Maria Eugenia; Jacobi, Pedro Roberto; Ducrot, Raphaele

    2007-01-01

    Role-playing games in natural resource management are currently being tested as research, training, and intervention tools all over the world. Various studies point out their potential to deal with complex issues and to contribute to training processes. The objective of this contribution is to analyze the limits and potentialities of this tool for…

  4. The Roles That Librarians and Libraries Play in Distance Education Settings

    ERIC Educational Resources Information Center

    Corbett, Amanda; Brown, Abbie

    2015-01-01

    This article explores the literature that focuses on the various roles librarians and libraries play in distance education settings. Learners visit libraries either in person or via networked computing technology to ask for help with their online courses. Questions range from how to upload a document with a learning management system, to how to…

  5. Teachers' Roles in Infants' Play and Its Changing Nature in a Dynamic Group Care Context

    ERIC Educational Resources Information Center

    Jung, Jeesun

    2013-01-01

    Using a qualitative research approach, this article explores teachers' roles in infants' play and its changing nature in an infant group care setting. Three infant teachers in a child care center were followed over three months. Observations, interviews, ongoing conversations, emails, and reflective notes were used as data sources. Findings…

  6. Teaching Conflict Resolution Skills to Middle and High School Students through Interactive Drama and Role Play

    ERIC Educational Resources Information Center

    Graves, Kelly N.; Frabutt, James M.; Vigliano, Debra

    2007-01-01

    In response to the rising levels of school conflict, the present study investigated a new approach to conflict resolution for middle and high school students using interactive drama and role play called the Win-Win Resolutions program. The standardized curriculum delivered within the school setting includes strategies for self-control and anger…

  7. Using a Role-Play Video to Convey Expectations about Academic Integrity

    ERIC Educational Resources Information Center

    Bullard, Lisa G.; Melvin, Adam T.

    2011-01-01

    We have developed an instructional video that uses role-play to illustrate the differences between acceptable behavior and cheating on assignments. Since we began showing it in an introductory chemical engineering course, the average number of confirmed instances of cheating decreased slightly, but the average percentage of students who were…

  8. Eco-Act: A Role-Playing Game to Clarify Environmental Values, High School Level

    ERIC Educational Resources Information Center

    Allen, Rodney F.; LaHart, David E.

    1976-01-01

    Describes a noncompetitive simulation game in which students role play situations described on a card to investigate their feelings, values, and behavior toward nature and toward others. Available from: NAAHE, the University of Tulsa, 600 South College, Tulsa, Oklahoma 74104. (Author/DB)

  9. Researching Travel Behavior and Adaptability: Using a Virtual Reality Role-Playing Game

    ERIC Educational Resources Information Center

    Watcharasukarn, Montira; Krumdieck, Susan; Green, Richard; Dantas, Andre

    2011-01-01

    This article describes a virtual reality role-playing game that was developed as a survey tool to collect travel behavior data and explore and monitor travel behavior adaptation. The Advanced Energy and Material Systems Laboratory has designed, developed a prototype, and tested such a game platform survey tool, called Travel Activity Constraint…

  10. How to Develop Creative Imagination? Assumptions, Aims and Effectiveness of Role Play Training in Creativity (RPTC)

    ERIC Educational Resources Information Center

    Karwowski, Maciej; Soszynski, Marcin

    2008-01-01

    There are hundreds of ways to develop creativity among children, youths and adults. Developing new ideas and ways of teaching creativity should also incorporate youth's interests and hobbies. The article presents the main information about the new way of developing creative abilities, especially creative imagination, the Role Play Training in…

  11. Using Role-Play to Foster Transformational and Social Action Multiculturalism in the ESL Classroom

    ERIC Educational Resources Information Center

    Gordon, Tatiana

    2012-01-01

    This article discusses the use of role-play as an effective strategy for enhancing the quality of multicultural curricula in the English as a second language (ESL) classroom. The author critiques the use of the simplistic additive approach to multicultural instruction and furthers the work of those theorists who advocate the use of the more…

  12. The Role of Imaging in Determining Return to Play.

    PubMed

    Casagranda, Bethany U; Thurlow, Peter C

    2016-09-01

    Return-to-play (RTP) predictions focus on how long it takes an athlete to return to their full athletic activity after sustaining an injury. This article focuses on the role of imaging and the radiologist in RTP predictions for the most common and controversial injuries affecting athletes. PMID:27545432

  13. Designing After-School Learning Using the Massively Multiplayer Online Role-Playing Game

    ERIC Educational Resources Information Center

    King, Elizabeth M.

    2015-01-01

    Digital games have become popular for engaging students in a range of learning goals, both in the classroom and the after-school space. In this article, I discuss a specific genre of video game, the massively multiplayer online role-playing game (MMO), which has been identified as a dynamic environment for encountering 21st-century workplace…

  14. Massively Multiplayer Online Role-Playing Games as Arenas for Second Language Learning

    ERIC Educational Resources Information Center

    Peterson, Mark

    2010-01-01

    This article investigates contemporary research on the use of massively multiplayer online role-playing games (MMORPGs) in language education. The development and key features of these games are explored. This is followed by an examination of the theories proposed as a basis for game-based learning, and the claims made regarding the value of…

  15. Excessive Use of Massively Multi-Player Online Role-Playing Games: A Pilot Study

    ERIC Educational Resources Information Center

    Hussain, Zaheer; Griffiths, Mark D.

    2009-01-01

    Massively multiplayer online role-playing games (MMORPGs) are one of the most interesting innovations in the area of online computer gaming. This pilot study set out to examine the psychological and social effects of online gaming using an online questionnaire with particular reference to excessive and "dependent" online gaming. A self-selecting…

  16. Personality Correlates of Self-Report, Role-Playing, and In Vivo Measures of Assertiveness.

    ERIC Educational Resources Information Center

    Green, Samuel B.; And Others

    1979-01-01

    Undergraduates completed self-report inventories of assertiveness, participated in behavior role-playing tasks and in vivo measures of assertiveness, and completed the Personality Research Form E (PRF-E). Of 22 PRF-E scales, 11 had at least one significant correlation with assertiveness measures. Some composites of PRF-E scales were related to…

  17. Simulation Games and Role Playing. Social Studies for the Elementary School. Proficiency Module #6.

    ERIC Educational Resources Information Center

    Bagley, Earl G.; Pierfy, David A.

    Designed as part of a series to develop teaching strategies for the elementary curriculum, this module focuses on simulation games and role playing as two important teaching devices. The first part describes games and simulation; and factors that should be considered in selecting, using, and debriefing games in the classroom. Exercises to test…

  18. General Federation of Women's Clubs: A Role Playing Exercise for Studying the Progressive Era.

    ERIC Educational Resources Information Center

    Barker, Sherman

    1986-01-01

    Provides an example of a role-playing exercise which takes place as a result of an imaginary caucus of women's groups meeting in the fall of 1912. The purpose of the caucus is to determine which of four presidential candidates--Woodrow Wilson, Theodore Roosevelt, William Howard Taft, and Eugene Debs--will receive the endorsement of the women's…

  19. Choices and Chances: The Sociology Role-Playing Game--The Sociological Imagination in Practice

    ERIC Educational Resources Information Center

    Simpson, Joseph M.; Elias, Vicky L.

    2011-01-01

    This article introduces a sociology role-playing game (RPG) used to demonstrate the broad range of social forces, institutions, and structures in a semester-long series of in-class and homework assignments. RPGs and other simulation games have been frequently suggested as a useful teaching methodology because of their unique ability to allow…

  20. The Effect of Role Playing by the Culturally Disadvantaged on Attitudes toward Bidialectalism. Final Report.

    ERIC Educational Resources Information Center

    Brandes, Paul D.

    In an effort to motivate culturally different students to learn standard English while they remain proud of their dialect and retain it as their informal manner of speaking, 120 blacks at three grade levels role played from scripts the parts of employers, college admissions officers, and applicants. The scripts rewarded applicants who could and…

  1. Parenting Talent: A Qualitative Investigation of the Roles Parents Play in Talent Development

    ERIC Educational Resources Information Center

    Witte, Amanda L.; Kiewra, Kenneth A.; Kasson, Sarah C.; Perry, Kyle R.

    2015-01-01

    Previous research has linked talent development to four factors--early experience, coaching, practice, and motivation. In addition to these factors, contemporary talent experts suggest that parents play a critical role in talent development. The purpose of the present study was to uncover parents' in-time perspectives on the talent development…

  2. Female Superintendents in California and the Role That Mentoring and Networking Have Played in Their Success

    ERIC Educational Resources Information Center

    Dudek, Vicky

    2012-01-01

    This study examined the role that mentoring, formal networking, and informal networking have played in the lives of women who have obtained the position of superintendent in the state of California. The researcher explored the access that female administrators had to mentors and networks, followed by the perceived benefits they received when they…

  3. Solutions-Focused Role Play: Its Use in Training Peer Helpers

    ERIC Educational Resources Information Center

    Beale, Andrew V.; Hall, Kimberly R.

    2005-01-01

    Solutions-focused role play provides students with structured opportunities to transfer what they have learned to authentic situations they are likely to encounter as peer helpers. Rather than coming up with a single way to solve a problem, students are encouraged to explore multiple possible solutions. Peer training programs have traditionally…

  4. Informal Workplace Communication--What Roles Can Microblogging Play in It?

    ERIC Educational Resources Information Center

    Zhao, Dejin

    2012-01-01

    Informal communication, e.g., unplanned "water-cooler" conversations, has been suggested to play important roles in collaborative work and organizational innovation. It provides opportunities among employees for exchanging work-relevant information, initiating potential collaboration, maintaining awareness of workplace context; and…

  5. Playing the Role of an Outsider Within: Teaching Intercultural Communication through an Ethnographic Project

    ERIC Educational Resources Information Center

    Yueh, Hsin-I Sydney

    2015-01-01

    One of the methods used to enhance students' ability not only to identify different cultures but also to describe their own cultures with proper analytical vocabulary is to teach students how to play the role of an outsider of their culture and de-familiarize their everyday practice so that they can distinguish cultural patterns and…

  6. Using Massively Multiplayer Online Role-Playing Games for Online Learning

    ERIC Educational Resources Information Center

    Childress, Marcus D.; Braswell, Ray

    2006-01-01

    This article addresses the use of a massively multiplayer online role-playing game (MMORPG) to foster communication and interaction and to facilitate cooperative learning in an online course. The authors delineate the definition and history of massively multiplayer online games (MMOGs), and describe current uses of MMORPGs in education, including…

  7. Naturalistic Observations of Children's Activities and Roles While Playing with Their Siblings and Friends.

    ERIC Educational Resources Information Center

    Stoneman, Zolinda; And Others

    1984-01-01

    Reports studies of children's interactions at home with younger siblings and/or best friends. Finds gender and group composition differences in the play activities selected, amount of positive and negative interaction, and assumption of the roles of teacher/learner, manager/manager and playmate. (CB)

  8. Can Pesticide Delivery Methods Play a Role in Sustainable Pest Management?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Conventional insecticides continue to play an important role in greenhouse pest management programs. Penetrating a dense plant canopy can be difficult with a handgun, and there is some evidence that boom sprayers or broadcast applications result in a more uniform deposition than handguns. A large-...

  9. Xylella fastidiosa Extracellular Genomic DNA May Play a Role For Enhancing Biofilm Formation In Vitro

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Xylella fastidiosa (Xf) produces extracellular DNA in PD3 liquid medium. This extracellular DNA may play a role in enhancing biofilm formation, a factor that is required by Xf to establish infection in host plants. Amounts of extracellular DNA generated by Xf in vitro were positively correlated with...

  10. Understanding Bullying: Using Role-Play with 12-Year-Old Boys in Cyprus

    ERIC Educational Resources Information Center

    Kaloyirou, Chrystalla; Lindsay, Geoff

    2014-01-01

    This study examines the use of role-play in order to investigate bullies' intentions, feelings and perceptions through identification and projection. The study was conducted with nine 12-year-old boys that presented high levels of bullying behaviour, according to their teachers and peers, from three state primary schools in Nicosia, Cyprus,…

  11. Developing Adolescents' Resistance to Sexual Coercion through Role-Playing Activities in a Virtual World

    ERIC Educational Resources Information Center

    McGinn, Marion; Arnedillo-Sánchez, Inmaculada

    2015-01-01

    This paper explores the use of a three dimensional virtual world (3-DVW) to delivery assertiveness training to young adolescents. The case study aims to understand how a sense of presence in VWs facilitates and affect the performance of students role-playing activities to enhance their ability to resist sexual coercion. The results indicate that a…

  12. Using a Collaborative Virtual Role-Play Environment To Foster Characterization in Stories.

    ERIC Educational Resources Information Center

    Robertson, Judy; Good, Judith

    2003-01-01

    Reports the results of a field study evaluation of a virtual role-play environment, "Ghostwriter," which was designed as a preparation activity for writing stories. Examines the effects of "Ghostwriter" has on characterization in children's imaginative writing. Participants were 60 children aged between 10-12 years. Results support the view that…

  13. Does Web-Based Role-Play Establish a High Quality Learning Environment? Design versus Evaluation

    ERIC Educational Resources Information Center

    Ludewig, Alexandra; Ludewig-Rohwer, Iris

    2013-01-01

    Online role-plays have been celebrated for providing an environment which allows for high quality learning. Innovative approaches have been embraced in foreign language studies, especially in countries where a great distance to the target country needs to be overcome, not only to expose students to the target language but also to provide them with…

  14. Role Play in Blended Learning: A Case Study Exploring the Impact of Story and Other Elements

    ERIC Educational Resources Information Center

    Dracup, Mary

    2008-01-01

    Role play is an increasingly popular technique in tertiary education, being student centred, constructivist and suitable for a range of subject areas. The choice of formats is wide open, with options ranging from the traditional face to face performance through to multi-user online computer games. Some teachers prefer to take advantage of features…

  15. Exploring Game Experiences and Game Leadership in Massively Multiplayer Online Role-Playing Games

    ERIC Educational Resources Information Center

    Jang, YeiBeech; Ryu, SeoungHo

    2011-01-01

    This study explored the in-game experiences of massively multiplayer online role-playing game (MMORPG) players focusing on game leadership and offline leadership. MMORPGs have enormous potential to provide gameplayers with rich social experiences through various interactions along with social activities such as joining a game community, team play…

  16. Understanding Collectivism and Female Genital Cutting through a Family Role-Playing Exercise

    ERIC Educational Resources Information Center

    Miller, Carol

    2014-01-01

    This study is a test of the effectiveness of a classroom role-playing exercise used to increase the understanding of cultural practices with which many Midwestern college students are uncomfortable. I employed a pre-test/post-test comparison group design. Students enrolled in two sections of a general education global issues course (N = 56) were…

  17. Role Play Simulations: The Assessment of an Active Learning Technique and Comparisons with Traditional Lectures.

    ERIC Educational Resources Information Center

    DeNeve, Kristina; Heppner, Mary J.

    1997-01-01

    Use of active learning techniques of role-playing and simulation in an industrial psychology course (n=29 students) is described and assessed. Subjective reports and objective assessments of knowledge retention indicate the approach was effective. The differential importance of active learning and passive learning (lecture) in the college…

  18. Enhancing Information Systems Auditing Knowledge with Role-Playing Game: An Experimental Investigation

    ERIC Educational Resources Information Center

    Wongpinunwatana, Nitaya

    2013-01-01

    This study examined the use and effect of a role-playing game on learners' ability in information systems audit. The study is based on experimental research. Information systems control and audit case study and video had been developed. A total of 75 graduate students undertaking a Master's degree in accounting participated in the experiment. The…

  19. A Description Grid to Support the Design of Learning Role-Play Games

    ERIC Educational Resources Information Center

    Mariais, Christelle; Michau, Florence; Pernin, Jean-Philippe

    2012-01-01

    To strengthen the motivation of learners, the professional training sector is focusing more and more on game-based learning. In this context, the authors have become interested in the design of Learning Role-Play Game (LRPG) scenarios. The aim of this article is to improve the designers' confidence in the validity of the game-based learning…

  20. Student Voices about the Role Feedback Plays in the Enhancement of Their Learning

    ERIC Educational Resources Information Center

    Plank, Christine; Dixon, Helen; Ward, Gillian

    2014-01-01

    If feedback is to be framed as purposeful dialogue then both students and teachers have significant roles to play. Students must be willing and able to provide feedback to teachers not only about their learning needs but also about the teaching they experience. In turn, teachers must create the conditions that support active student learning and…

  1. Student Perceptions of a Role-Playing Simulation in an Introductory International Relations Course

    ERIC Educational Resources Information Center

    Giovanello, Sean P.; Kirk, Jason A.; Kromer, Mileah K.

    2013-01-01

    An emerging assumption in undergraduate political science education is that role-playing simulations are an effective teaching tool. While previous studies have addressed the pedagogical advantages of simulations as compared to more traditional teaching techniques, less attention has been paid to student perceptions of these simulations. This…

  2. Using analogy role-play activity in an undergraduate biology classroom to show central dogma revision.

    PubMed

    Takemura, Masaharu; Kurabayashi, Mario

    2014-01-01

    For the study of biology in an undergraduate classroom, a classroom exercise was developed: an analogy role-play to learn mechanisms of gene transcription and protein translation (central dogma). To develop the central dogma role-play exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress hanger, and amino acids using Lego® blocks (Lego System A/S, Denmark). Students were studying in the course of mathematics, physics, or chemistry, so biology was not among their usual studies. In this exercise, students perform the central dogma role-play and respectively act out nuclear matrix proteins, a transcription factor, an RNA polymerase II, an mRNA transport protein, nuclear pore proteins, a large ribosomal subunit, a small ribosomal subunit, and several amino-acyl tRNA synthetases. Questionnaire results obtained after the activity show that this central dogma role-play analogy holds student interest in the practical molecular biological processes of transcription and translation. PMID:24898113

  3. Role-Play Game-Enhanced English for a Specific-Purpose Vocabulary-Acquisition Framework

    ERIC Educational Resources Information Center

    Lu, Fang-Chen; Chang, Ben

    2016-01-01

    With the advantages of an engaged and authentic role-play game (RPG), this study aims to develop an RPG-enhanced English for specific purposes (ESP) vocabulary-acquisition framework, providing teachers and students a systematic way to incorporate RPG into ESP learning. The framework is composed of five parts: goal, three-level vocabulary sets, RPG…

  4. Interaction with the game and motivation among players of massively multiplayer online role-playing games.

    PubMed

    Fuster, Héctor; Carbonell, Xavier; Chamarro, Andrés; Oberst, Ursula

    2013-01-01

    Knowledge about users interacting with Massively Multiplayer Online Role-Playing Games (MMORPG) is fundamental in order to prevent their potential negative effects on behavior. For this reason, the present study analyzed the relationship between styles of play and motivations. An online questionnaire asking for socio-demographic details, playing style, characteristics of the game played and motivations for playing, was answered by 430 Spanish-speaking MMORPG players (45.1% males). The identified profile for players, far away from the stereotype of an adolescent, consisted in a person who mainly plays on PvP (Player versus Player) servers, choosing the type of game according to his experience. Regarding motivations, they were interested in relating with other players through the game (Socialization), in discovering the game's possibilities and development of its adventures (Exploration), to a lesser extent in leadership and prestige (Achievement) and, lastly, identification with an avatar and escape from reality (Dissociation). Although part of the reason for playing was escapism and/or stress relief, the main motivation had a social nature. We conclude that MMORPG offer an attractive environment for a broad spectrum of people, and we have not been able to confirm the stereotype of a loner avoiding reality, taking refuge in games. PMID:23866239

  5. Competence of medical students in communicating drug therapy: Value of role-play demonstrations

    PubMed Central

    Tayem, Yasin I.; Altabtabaei, Abdulaziz S.; Mohamed, Mohamed W.; Arrfedi, Mansour M.; Aljawder, Hasan S.; Aldebous, Fahad A.; James, Henry; Al Khaja, Khalid A. J.; Sequeira, Reginald P.

    2016-01-01

    Objectives: This study used role-play demonstrations to train medical students to communicate drug therapy and evaluated the perceptions on this instructional approach. Materials and Methods: The second-year medical students who attended a prescription writing session (n = 133), participated in this study. Prescription communication was introduced by using role-play demonstrations. Participant's perceptions were explored by a self-administered questionnaire and focus group discussion. The academic achievement of attendees and nonattendees was compared with an objective structured performance evaluation (OSPE) station that tested students’ competence in this skill. Results: Most attendees responded to the questionnaire (81.2%). Almost all respondents expressed their desire to have similar demonstrations in other units. A large proportion of participants reported that role-play demonstrations helped them develop their communication skills, in general, confidence to communicate drug-related information in a prescription, and the ability to explain the aim of drug therapy to patients. Most trainees thought also that they developed skills to communicate instructions on drug use including drug dose, frequency of administration, duration of therapy, adverse drug reactions, and warnings. During the focus group interviews, students thought that role-play was useful but would be more beneficial if conducted frequently in small group as part of the curriculum implementation. The majority of students also reported improved competence in writing a complete prescription. Analysis of attendees and nonattendees grades in the OSPE showed that the former scored higher than the latter group (P = 0.016). Conclusions: Role-play demonstrations were well accepted by medical students and led to the development of their competence in communicating drug therapy to patients. PMID:26997720

  6. Developing Children's Views of the Nature of Science Through Role Play

    NASA Astrophysics Data System (ADS)

    Cakici, Yilmaz; Bayir, Eylem

    2012-05-01

    The purpose of this study is to investigate the effect of using role play (portraying a scientist's life story) on the children's views of the nature of science (NOS). The study was carried out at the Children's University of Trakya in Turkey during the summer of 2010. The participants consisted of 18 children, aged 10-11. They met for 10 days for approximately 3 h per day. All children completed the pre- and post-tests including 16 open-ended questions in order to reveal changes in their views of the NOS prior to and at the completion of the role-play activities. The results revealed that the children had more informed views of the target NOS aspects in comparison with their views prior to the role-play activities. A large majority of the children (around 80-85%) started out with naive conceptions of the target NOS aspects. Following the role-play activities portraying scientists' lives, there was a 40-45% positive change in children's views of the tentative, empirical and creative/imaginative aspect of the NOS, and a 50-60% positive change in their views regarding the subjective/theory-laden and social-cultural embeddedness of science. The most substantial change occurred in their views concerning scientific method, with a shift of 72%. The percentage of informed views on images of scientists showed diversity. Overall results indicate that role-play/drama-oriented activities portraying scientist's life stories could be used as one of the exciting, informative and constructive ways of developing understanding of the NOS among children.

  7. Highly Conserved Histidine Plays a Dual Catalytic Role in Protein Splicing: a pKa Shift Mechanism

    PubMed Central

    Du, Zhenming; Shemella, Philip T.; Liu, Yangzhong; McCallum, Scott A.; Pereira, Brian; Nayak, Saroj K.; Belfort, Georges; Belfort, Marlene; Wang, Chunyu

    2009-01-01

    Protein splicing is a precise auto-catalytic process in which an intein excises itself from a precursor with the concomitant ligation of the flanking sequences. Protein splicing occurs through acid-base catalysis in which the ionization states of active site residues are crucial to the reaction mechanism. In inteins, several conserved histidines have been shown to play important roles in protein splicing, including the most conserved “B-block” histidine. In this study, we have combined NMR pKa determination with quantum mechanics/molecular mechanics (QM/MM) modeling to study engineered inteins from Mycobacterium tuberculosis (Mtu) RecA intein. We demonstrate a dramatic pKa shift for the invariant B-block histidine, the most conserved residue among inteins. The B-block histidine has a pKa of 7.3 ± 0.6 in a precursor and a pKa of < 3.5 in a spliced intein. The pKa values and QM/MM data suggest that the B-block histidine has a dual role in the acid-base catalysis of protein splicing. This histidine likely acts as a general base to initiate splicing with an acyl shift and then as a general acid to cause the breakdown of the scissile bond. The proposed pKa shift mechanism accounts for the biochemical data supporting the essential role for the B-block histidine and for the absolute sequence conservation of this residue. PMID:19630416

  8. ARGININE DEIMINASE PLAYS MULTIPLE REGULATORY ROLES IN THE BIOLOGY OF GIARDIA LAMBLIA

    PubMed Central

    Touz, Maria Carolina; Ropolo, Andrea Silvana; Rivero, Maria Romina; Vranych, Cecilia Veronica; Conrad, John Thomas; Svard, Staffan Gunnar; Nash, Theodore Elliot

    2008-01-01

    SUMMARY The protozoan parasite Giardia lamblia utilizes arginine deiminase (gADI) to produce energy from free L-arginine under anaerobic conditions. In this work, we demonstrate that in addition to its known role as a metabolic enzyme, it also functions as a pepidtyl-arginine deiminase converting protein-bound arginine into citrulline. gADI specifically binds to and citrullinates the arginine in the conserved CRGKA tail of variant-specific surface proteins (VSPs) affecting both antigenic switching and antibody mediated cell death. During encystation gADI translocates from the cytoplasm to the nucleus and appear to play a regulatory role in the expression of encystation specific genes. gADI is also sumoylated, which may modulate its activity. Our findings reveal a dual role played by gADI and define novel regulatory pathways used by Giardia for survival. PMID:18697833

  9. Real-Time Imaging of Interactions of Neutrophils with Cryptococcus neoformans Demonstrates a Crucial Role of Complement C5a-C5aR Signaling

    PubMed Central

    Sun, Donglei; Zhang, Mingshun; Liu, Gongguan; Wu, Hui; Zhu, Xiaoping; Zhou, Hong

    2015-01-01

    Neutrophils have been shown to efficiently kill Cryptococcus neoformans, a causative agent of meningoencephalitis. Here, using live-cell imaging, we characterize the dynamic interactions of neutrophils with C. neoformans and the underlying mechanisms in real time. Neutrophils were directly seen to chase C. neoformans cells and then rapidly internalize them. Complement C5a-C5aR signaling guided neutrophils to migrate to the yeast cells, resulting in optimal phagocytosis and subsequent killing of the organisms. The addition of recombinant complement C5a enhanced neutrophil movement but did not induce chemotaxis, suggesting that the C5a gradient is crucial. Incubation with C. neoformans resulted in enhanced activation of Erk and p38 mitogen-activated protein (MAP) kinases (MAPKs) in neutrophils. Inhibition of the p38 MAPK pathway, but not the Erk pathway, significantly impaired neutrophil migration and its subsequent killing of C. neoformans. Deficiency of CD11b or blocking of CD11b did not affect the migration of neutrophils toward C. neoformans but almost completely abolished phagocytosis and killing of the organisms by neutrophils. C5a-C5aR signaling induced enhanced surface expression of CD11b. Interestingly, the original surface expression of CD11b was essential and sufficient for neutrophils to attach to C. neoformans but was unable to mediate phagocytosis. In contrast, the enhanced surface expression of CD11b induced by C5a-C5aR signaling was essential for neutrophil phagocytosis and subsequent killing of yeast cells. Collectively, this is the first report of the dynamic interactions of neutrophils with C. neoformans, demonstrating a crucial role of C5a-C5aR signaling in neutrophil killing of C. neoformans in real time. PMID:26502909

  10. The Counselor's Role Communication Skills, or The Roles Counselors Play: A Conceptual Model.

    ERIC Educational Resources Information Center

    Doyle, Robert E.

    1982-01-01

    Presents a two-dimensional conceptual model which outlines a comprehensive approach to skill-oriented counselor training. Discusses eight major counselor roles: attender; clarifier; informer or describer; prober or inquirer; supporter or reassurer; motivator or prescriber; evaluator or analyzer; and problem solver. (Author)

  11. Social Roles, Role-Playing, and Education: On the High School as Prison

    ERIC Educational Resources Information Center

    Haney, Craig; Zimbardo, Philip G.

    1973-01-01

    A description and discussion of an experiment which placed normal college males into a prison-like environment related the term "prison" to any environment restricting human freedom, and explored the control of behavior by situations and roles with reference to educational settings, specifically the high school. (Author/KM)

  12. Computer-supported games and role plays in teaching water management

    NASA Astrophysics Data System (ADS)

    Hoekstra, A. Y.

    2012-08-01

    There is an increasing demand for an interdisciplinary approach in teaching water management. Computer-supported games and role plays offer the potential of creating an environment in which different disciplines come together and in which students are challenged to develop integrated understanding. Two examples are discussed. The River Basin Game is a common-pool resource game in which participants experience the risk of over-abstractions of water in a river basin and learn how this risk relates to the complexity of the system, the conflict between individual and group optimums and the difficulty in achieving good cooperation. The Globalization of Water Role Play makes participants familiar with the global dimension of water management by letting them experience how national governments can integrate considerations of water scarcity and domestic water productivities into decisions on international trade in commodities like food, cotton and bio-energy. The two examples illustrate that play sessions inspire participants to think about the functioning of systems as a whole and to develop good cooperative courses of action, whereby both uncertainties about the system and the presence of different values and perspectives among participants play a role.

  13. Computer-supported games and role plays in teaching water management

    NASA Astrophysics Data System (ADS)

    Hoekstra, A. Y.

    2012-02-01

    There is an increasing demand for an interdisciplinary approach in teaching water management. Computer-supported games and role plays offer the potential of creating an environment in which different disciplines come together and in which students are challenged to develop integrated understanding. Two examples are discussed. The River Basin Game is a common-pool resource game in which participants experience the risk of over-abstractions of water in a river basin and learn how this risk relates to the complexity of the system, the conflict between individual and group optimum and the difficulty to come to good cooperation. The Globalization of Water Role Play makes participants familiar with the global dimension of water management by letting them experience how national governments can integrate considerations of water scarcity and domestic water productivities into decisions on international trade in commodities like food, cotton and bio-energy. The two examples illustrate that plays inspire participants to think about the functioning of systems as a whole and to develop good cooperative courses of action, whereby both uncertainties about the system and the presence of different values and perspectives among participants play a role.

  14. Do advanced glycation end-products play a role in malaria susceptibility?

    PubMed Central

    Traoré, Karim; Arama, Charles; Médebielle, Maurice; Doumbo, Ogobara; Picot, Stéphane

    2016-01-01

    There are growing data supporting the differences in susceptibility to malaria described between sympatric populations with different lifestyles. Evidence has also been growing for some time that nutritional status and the host’s metabolism are part of the complex mechanisms underlying these differences. The role of dietary advanced glycation end-products (AGEs) in the modulation of immune responses (innate and adaptive responses) and chronic oxidative stress has been established. But less is known about AGE implication in naturally acquired immunity and susceptibility to malaria. Since inflammatory immune responses and oxidative events have been demonstrated as the hallmark of malaria infection, it seems crucial to investigate the role of AGE in susceptibility or resistance to malaria. This review provides new insight into the relationship between nutrition, metabolic disorders, and infections, and how this may influence the mechanisms of susceptibility or resistance to malaria in endemic areas. PMID:27012162

  15. The crucial role of Φ- and K-segments in the in vitro functionality of Vitis vinifera dehydrin DHN1a.

    PubMed

    Rosales, Raquel; Romero, Irene; Escribano, Ma Isabel; Merodio, Carmen; Sanchez-Ballesta, Ma Teresa

    2014-12-01

    Dehydrins (DHNs), group II LEA (Late Embryogenesis Abundant) proteins, are among the most commonly observed proteins which accumulate in plants in response to cold and any other environmental factors, causing the dehydration of cells. In previous studies, we isolated a YSK2-type VvcDHN1a gene from table grapes (Vitis vinifera cv. Cardinal) which presented two spliced variants (the spliced, DHN1a_s and the unspliced, DHN1a_u). Their expression was induced by low temperature storage and CO2, although with different accumulation patterns. DHN1a_u codifies for a truncated YS protein lacking Ф- and K-segments, which might affect its functionality. In this work, we expressed both DHN1a_s and DHN1a_u recombinant proteins in Escherichia coli. We carried out a number of in vitro assays to analyze the implications that Ф- and K-segments have in the protective role of VvcDHN1 against different abiotic stresses and their antifungal activity against the fungal pathogen Botrytis cinerea. Our results showed that unlike DHN1a_u, DHN1a_s has a potent cryoprotective effect on lactate dehydrogenase activity, protects malate dehydrogenase against dehydration and partially inhibits B. cinerea growth. Moreover, the DHN1a promoter presented cis-regulatory elements related to cold and drought, as well as biotic stress-related elements. We also observed that both spliced variants interact weakly with DNA, suggesting that K-segments are not involved in DNA binding. Overall, this work highlights the crucial role of Ф- and K-segments in DHNs function in plant response to abiotic stress showing for the first time, the potential role of the V. vinifera DHN1a_s in the protection against freezing and dehydration as well as inhibiting B. cinerea growth. PMID:25457499

  16. A Quantitative Content Analysis of Leveled Vocabulary Embedded within Massively Multiplayer Online Role-Playing Games (MMORPGs)

    ERIC Educational Resources Information Center

    Haas, Leslie

    2012-01-01

    This content analysis examined levels of vocabulary within massively multiplayer online role-playing games (MMORPGs). A total of six MMORPGs were studied; three were pay-to-play (P2P), and three were free-to-play (F2P). Sixty hours of game play (10 hours per game) provided the researcher with 50,240 embedded vocabulary words. Each MMORPG was…

  17. NCP1/AtMOB1A Plays Key Roles in Auxin-Mediated Arabidopsis Development

    PubMed Central

    Song, Lizhen; Wang, Yanli; Cheng, Youfa

    2016-01-01

    MOB1 protein is a core component of the Hippo signaling pathway in animals where it is involved in controlling tissue growth and tumor suppression. Plant MOB1 proteins display high sequence homology to animal MOB1 proteins, but little is known regarding their role in plant growth and development. Herein we report the critical roles of Arabidopsis MOB1 (AtMOB1A) in auxin-mediated development in Arabidopsis. We found that loss-of-function mutations in AtMOB1A completely eliminated the formation of cotyledons when combined with mutations in PINOID (PID), which encodes a Ser/Thr protein kinase that participates in auxin signaling and transport. We showed that atmob1a was fully rescued by its Drosophila counterpart, suggesting functional conservation. The atmob1a pid double mutants phenocopied several well-characterized mutant combinations that are defective in auxin biosynthesis or transport. Moreover, we demonstrated that atmob1a greatly enhanced several other known auxin mutants, suggesting that AtMOB1A plays a key role in auxin-mediated plant development. The atmob1a single mutant displayed defects in early embryogenesis and had shorter root and smaller flowers than wild type plants. AtMOB1A is uniformly expressed in embryos and suspensor cells during embryogenesis, consistent with its role in embryo development. AtMOB1A protein is localized to nucleus, cytoplasm, and associated to plasma membrane, suggesting that it plays roles in these subcellular localizations. Furthermore, we showed that disruption of AtMOB1A led to a reduced sensitivity to exogenous auxin. Our results demonstrated that AtMOB1A plays an important role in Arabidopsis development by promoting auxin signaling. PMID:26942722

  18. NCP1/AtMOB1A Plays Key Roles in Auxin-Mediated Arabidopsis Development.

    PubMed

    Cui, Xiaona; Guo, Zhiai; Song, Lizhen; Wang, Yanli; Cheng, Youfa

    2016-03-01

    MOB1 protein is a core component of the Hippo signaling pathway in animals where it is involved in controlling tissue growth and tumor suppression. Plant MOB1 proteins display high sequence homology to animal MOB1 proteins, but little is known regarding their role in plant growth and development. Herein we report the critical roles of Arabidopsis MOB1 (AtMOB1A) in auxin-mediated development in Arabidopsis. We found that loss-of-function mutations in AtMOB1A completely eliminated the formation of cotyledons when combined with mutations in PINOID (PID), which encodes a Ser/Thr protein kinase that participates in auxin signaling and transport. We showed that atmob1a was fully rescued by its Drosophila counterpart, suggesting functional conservation. The atmob1a pid double mutants phenocopied several well-characterized mutant combinations that are defective in auxin biosynthesis or transport. Moreover, we demonstrated that atmob1a greatly enhanced several other known auxin mutants, suggesting that AtMOB1A plays a key role in auxin-mediated plant development. The atmob1a single mutant displayed defects in early embryogenesis and had shorter root and smaller flowers than wild type plants. AtMOB1A is uniformly expressed in embryos and suspensor cells during embryogenesis, consistent with its role in embryo development. AtMOB1A protein is localized to nucleus, cytoplasm, and associated to plasma membrane, suggesting that it plays roles in these subcellular localizations. Furthermore, we showed that disruption of AtMOB1A led to a reduced sensitivity to exogenous auxin. Our results demonstrated that AtMOB1A plays an important role in Arabidopsis development by promoting auxin signaling. PMID:26942722

  19. Peer review role-playing as a method of teaching senior undergraduate science

    NASA Astrophysics Data System (ADS)

    Johnston-Hollitt, Melanie

    2008-11-01

    We present a case study of the use of role-playing as a method of enhancing course delivery in senior undergraduate science courses. Specifically we examine the use of simulating peer review of scientific proposals for time on major international telescopes in a third year astrophysics course at the University of Tasmania. We find that 90% of participating students found the experience to be both enjoyable and a good method for learning and that 100% of students felt that the exercise had aided their understanding of the course material. Furthermore 80% of students felt that the role-playing had enhanced their understanding of scientific decision making while 70% believed that they had learnt to apply principles from the course in new situations.

  20. AtPDCD5 plays a role during dark-senescence in Arabidopsis.

    PubMed

    Falcone Ferreyra, María Lorena; Casati, Paula

    2016-06-01

    In this work, we investigated the role of an Arabidopsis protein, AtPDCD5, during senescence after a 24h-dark period. Previously, we demonstrated that AtPDCD5 participates in programmed cell death (PCD) after UV-B exposure and in age-induced senescence. The results presented here, together with previous data, demonstrate that AtPDCD5 not only plays an important role during DNA damage responses induced by UV-B radiation, but also takes part in PCD programs such as dark-induced senescence in Arabidopsis. PMID:27096161

  1. Playable Stories: Making Programming and 3D Role-Playing Game Design Personally and Socially Relevant

    ERIC Educational Resources Information Center

    Ingram-Goble, Adam

    2013-01-01

    This is an exploratory design study of a novel system for learning programming and 3D role-playing game design as tools for social change. This study was conducted at two sites. Participants in the study were ages 9-14 and worked for up to 15 hours with the platform to learn how to program and design video games with personally or socially…

  2. Serotonin in peripheral blood reflects oxidative stress and plays a crucial role in atherosclerosis: Novel insights toward holistic anti-atherothrombotic strategy.

    PubMed

    Sugiura, Tomonori; Dohi, Yasuaki; Yamashita, Sumiyo; Hirowatari, Yuji; Fujii, Satoshi; Ohte, Nobuyuki

    2016-03-01

    We enrolled 132 outpatients with cardiovascular risk factors to evaluate the serotonin levels in platelet-poor plasma (PPP) and whole blood (WB). PPP serotonin levels and PPP/WB serotonin ratio were significantly correlated with levels of oxidative stress measured by derivative reactive oxygen metabolites (d-ROM). Twenty-five subjects were revealed to have stable coronary artery disease (CAD), and the levels CRP, d-ROM, and PPP/WB serotonin ratio were significantly higher in subjects with CAD than in those without CAD. Logistic regression analysis performed with the endpoint of having CAD revealed that the PPP/WB serotonin ratio was independently associated with CAD (odds ratio 3.37, 95% confidence interval 1.04-10.9, P = 0.04). Receiver operating characteristic (ROC) curve analyses to discriminate subjects with CAD from those without CAD indicated that combining PPP/WB serotonin ratio and d-ROM improved diagnostic utility. Targeting the serotonin-oxidative stress axis as part of a holistic anti-atherothrombotic strategy could be beneficial for patients with atherosclerosis. PMID:26784327

  3. Malate Plays a Crucial Role in Starch Metabolism, Ripening, and Soluble Solid Content of Tomato Fruit and Affects Postharvest Softening[W][OA

    PubMed Central

    Centeno, Danilo C.; Osorio, Sonia; Nunes-Nesi, Adriano; Bertolo, Ana L.F.; Carneiro, Raphael T.; Araújo, Wagner L.; Steinhauser, Marie-Caroline; Michalska, Justyna; Rohrmann, Johannes; Geigenberger, Peter; Oliver, Sandra N.; Stitt, Mark; Carrari, Fernando; Rose, Jocelyn K.C.; Fernie, Alisdair R.

    2011-01-01

    Despite the fact that the organic acid content of a fruit is regarded as one of its most commercially important quality traits when assessed by the consumer, relatively little is known concerning the physiological importance of organic acid metabolism for the fruit itself. Here, we evaluate the effect of modifying malate metabolism in a fruit-specific manner, by reduction of the activities of either mitochondrial malate dehydrogenase or fumarase, via targeted antisense approaches in tomato (Solanum lycopersicum). While these genetic perturbations had relatively little effect on the total fruit yield, they had dramatic consequences for fruit metabolism, as well as unanticipated changes in postharvest shelf life and susceptibility to bacterial infection. Detailed characterization suggested that the rate of ripening was essentially unaltered but that lines containing higher malate were characterized by lower levels of transitory starch and a lower soluble sugars content at harvest, whereas those with lower malate contained higher levels of these carbohydrates. Analysis of the activation state of ADP-glucose pyrophosphorylase revealed that it correlated with the accumulation of transitory starch. Taken together with the altered activation state of the plastidial malate dehydrogenase and the modified pigment biosynthesis of the transgenic lines, these results suggest that the phenotypes are due to an altered cellular redox status. The combined data reveal the importance of malate metabolism in tomato fruit metabolism and development and confirm the importance of transitory starch in the determination of agronomic yield in this species. PMID:21239646

  4. Dendritic cells and anergic type I NKT cells play a crucial role in sulfatide-mediated immune regulation in experimental autoimmune encephalomyelitis

    PubMed Central

    Maricic, Igor; Halder, Ramesh; Bischof, Felix; Kumar, Vipin

    2014-01-01

    CD1d-restricted NKT cells can be divided into two groups: type I NKT cells utilize a semi-invariant TCR whereas type II express a relatively diverse set of TCRs. A major subset of type II NKT cells recognizes myelin-derived sulfatides and is selectively enriched in the central nervous system tissue during experimental autoimmune encephalomyelitis (EAE). We have shown that activation of sulfatide-reactive type II NKT cells by sulfatide prevents induction of EAE. Here we have addressed the mechanism of regulation as well as whether a single immunodominant form of synthetic sulfatide can treat ongoing chronic and relapsing EAE in SJL/J mice. We have shown that the activation of sulfatide-reactive type II NKT cells leads to a significant reduction in the frequency and effector function of PLP139-151/I-As–tetramer+ cells in lymphoid and CNS tissues. In addition, type I NKT cells and dendritic cells in the periphery as well as CNS-resident microglia are inactivated following sulfatide administration, and mice deficient in type I NKT cells are not protected from disease. Moreover tolerized DCs from sulfatide-treated animals can adoptively transfer protection into naive mice. Treatment of SJL/J mice with a synthetic cis-tetracosenoyl sulfatide, but not αGalCer, reverses ongoing chronic and relapsing EAE. Our data highlight a novel immune regulatory pathway involving NKT subset interactions leading to inactivation of type I NKT cells, DCs, and microglial cells in suppression of autoimmunity. Since CD1 molecules are non-polymorphic, the sulfatide-mediated immune regulatory pathway can be targeted for development of non-HLA-dependent therapeutic approaches to T cell-mediated autoimmune diseases. PMID:24973441

  5. Polarization of IRON-REGULATED TRANSPORTER 1 (IRT1) to the plant-soil interface plays crucial role in metal homeostasis

    PubMed Central

    Barberon, Marie; Dubeaux, Guillaume; Kolb, Cornelia; Isono, Erika; Zelazny, Enric; Vert, Grégory

    2014-01-01

    In plants, the controlled absorption of soil nutrients by root epidermal cells is critical for growth and development. IRON-REGULATED TRANSPORTER 1 (IRT1) is the main root transporter taking up iron from the soil and is also the main entry route in plants for potentially toxic metals such as manganese, zinc, cobalt, and cadmium. Previous work demonstrated that the IRT1 protein localizes to early endosomes/trans-Golgi network (EE/TGN) and is constitutively endocytosed through a monoubiquitin- and clathrin-dependent mechanism. Here, we show that the availability of secondary non-iron metal substrates of IRT1 (Zn, Mn, and Co) controls the localization of IRT1 between the outer polar domain of the plasma membrane and EE/TGN in root epidermal cells. We also identify FYVE1, a phosphatidylinositol-3-phosphate-binding protein recruited to late endosomes, as an important regulator of IRT1-dependent metal transport and metal homeostasis in plants. FYVE1 controls IRT1 recycling to the plasma membrane and impacts the polar delivery of this transporter to the outer plasma membrane domain. This work establishes a functional link between the dynamics and the lateral polarity of IRT1 and the transport of its substrates, and identifies a molecular mechanism driving polar localization of a cell surface protein in plants. PMID:24843126

  6. The plasma membrane NADPH oxidase OsRbohA plays a crucial role in developmental regulation and drought-stress response in rice.

    PubMed

    Wang, Xiang; Zhang, Mao-Mao; Wang, Ya-Jing; Gao, Yin-Tao; Li, Ri; Wang, Gang-Feng; Li, Wen-Qiang; Liu, Wen-Ting; Chen, Kun-Ming

    2016-04-01

    Plasma membrane NADPH oxidases are major producers of reactive oxygen species (ROS) in plant cells under normal growth and stress conditions. In the present study the total activity of rice NADPH oxidases and the transcription of OsRbohA, which encodes an Oryza sativa plasma membrane NADPH oxidase, were stimulated by drought. OsRbohA was expressed in all tissues examined throughout development. Its mRNA was upregulated by a number of factors, including heat, drought, salt, oxidative stress and methyl jasmonate treatment. Compared with wild-type (WT), the OsRbohA-knockout mutant osrbohA exhibited upregulated expression of other respiratory burst oxidase homolog genes and multiple abnormal agronomic traits, including reduced biomass, low germination rate and decreased pollen viability and seed fertility. However, OsRbohA-overexpressing transgenic plants showed no differences in these traits compared with WT. Although osrbohA leaves and roots produced more ROS than WT, the mutant had lesser intracellular ROS. In contrast, OsRbohA-overexpressing transgenic plants exhibited higher ROS production at the intracellular level and in tissues. Ablation of OsRbohA impaired the tolerance of plants to various water stresses, whereas its overexpression enhanced the tolerance. In addition, a number of genes related to energy supply, substrate transport, stress response and transcriptional regulation were differentially expressed in osrbohA plants even under normal growth conditions, suggesting that OsRbohA has fundamental and broad functions in rice. These results indicate that OsRbohA-mediated processes are governed by complex signaling pathways that function during the developmental regulation and drought-stress response in rice. PMID:26400148

  7. Human rpL3 plays a crucial role in cell response to nucleolar stress induced by 5-FU and L-OHP.

    PubMed

    Esposito, Davide; Crescenzi, Elvira; Sagar, Vinay; Loreni, Fabrizio; Russo, Annapina; Russo, Giulia

    2014-11-30

    Recent evidence showed that a variety of DNA damaging agents including 5-FU and L-OHP impairs ribosomal biogenesis activating a ribosomal stress pathway. Here, we demonstrate that in lung and colon cancer cell lines devoid of p53, the efficacy of 5-FU and L-OHP chemotherapy depends on rpL3 status. Specifically, we demonstrate that ribosomal stress induced by 5-FU and L-OHP is associated to up-regulation of rpL3 and its accumulation as ribosome-free form. We show that rpL3 participates in the cell response to chemotherapy acting as a critical regulator of cell cycle, apoptosis and DNA repair, by modulating p21 expression. Moreover, we demonstrate that rpL3 is able to control DNA repair also independently from p21 status of cell. It is noteworthy that silencing of rpL3 abolishes the cytotoxic effects of 5-FU and L-OH indicating that the loss of rpL3 makes chemotherapy drugs ineffective. Taking together our results shed light on 5-FU and L-OHP mechanism of action and contribute to more effective clinical use of these drugs in cancer therapy. PMID:25473889

  8. CREB-mediated synaptogenesis and neurogenesis is crucial for the role of 5-HT1a receptors in modulating anxiety behaviors

    PubMed Central

    Zhang, Jing; Cai, Cheng-Yun; Wu, Hai-Yin; Zhu, Li-Juan; Luo, Chun-Xia; Zhu, Dong-Ya

    2016-01-01

    Serotonin 1a-receptor (5-HT1aR) has been specifically implicated in the pathogenesis of anxiety. However, the mechanism underlying the role of 5-HT1aR in anxiety remains poorly understood. Here we show in mice that the transcription factor cAMP response element binding protein (CREB) in the hippocampus functions as an effector of 5-HT1aR in modulating anxiety-related behaviors. We generated recombinant lentivirus LV-CREB133-GFP expressing a dominant negative CREB which could not be phosphorylated at Ser133 to specifically reduce CREB activity, and LV-VP16-CREB-GFP expressing a constitutively active fusion protein VP16-CREB which could be phosphorylated by itself to specifically enhance CREB activity. LV-CREB133-GFP neutralized 5-HT1aR agonist-induced up-regulation of synapse density, spine density, dendrite complexity, neurogenesis, and the expression of synapsin and spinophilin, two well-characterized synaptic proteins, and abolished the anxiolytic effect of 5-HT1aR agonist; whereas LV-VP16-CREB-GFP rescued the 5-HT1aR antagonist-induced down-regulation of synapse density, spine density, dendrite complexity, neurogenesis and synapsin and spinophilin expression, and reversed the anxiogenic effect of 5-HT1aR antagonist. The deletion of neurogenesis by irradiation or the diminution of synaptogenesis by knockdown of synapsin expression abolished the anxiolytic effects of both CREB and 5-HT1aR activation. These findings suggest that CREB-mediated hippoacampus structural plasticity is crucial for the role of 5-HT1aR in modulating anxiety-related behaviors. PMID:27404655

  9. Facebook Role Play Addiction - A Comorbidity with Multiple Compulsive-Impulsive Spectrum Disorders.

    PubMed

    Nathan, Deeepa; Shukla, Lekhansh; Kandasamy, Arun; Benegal, Vivek

    2016-06-01

    Background Problematic Internet use (PIU) is an emerging entity with varied contents. Behavioral addictions have high comorbidity of attention deficit hyperactivity disorder and obsessive-compulsive spectrum disorders. Social networking site (SNS) addiction and role playing game (RPG) addiction are traditionally studied as separate entities. We present a case with excessive Internet use, with a particular focus on phenomenology and psychiatric comorbidities. Case presentation Fifteen-year-old girl with childhood onset attention deficit disorder, obsessive-compulsive disorder, adolescent onset trichotillomania, and disturbed family environment presented with excessive Facebook use. Main online activity was creating profiles in names of mainstream fictional characters and assuming their identity (background, linguistic attributes, etc.). This was a group activity with significant socialization in the virtual world. Craving, salience, withdrawal, mood modification, and conflict were clearly elucidated and significant social and occupational dysfunction was evident. Discussion This case highlights various vulnerability and sociofamilial factors contributing to behavioral addiction. It also highlights the presence of untreated comorbidities in such cases. The difference from contemporary RPGs and uniqueness of role playing on SNS is discussed. SNS role playing as a separate genre of PIU and its potential to reach epidemic proportions are discussed. Conclusions Individuals with temperamental vulnerability are likely to develop behavioral addictions. Identification and management of comorbid conditions are important. The content of PIU continues to evolve and needs further study. PMID:27156380

  10. Teaching communication skills using role-play: an experience-based guide for educators.

    PubMed

    Jackson, Vicki A; Back, Anthony L

    2011-06-01

    Teaching advanced communication skills requires educators who are not only excellent communicators themselves but have the ability to deconstruct the components of the interaction and develop a cognitive approach that can be used across a variety of learners, diverse content, and under different time constraints while helping the learner develop the skill of self-reflection in a 'safe' and effective learning environment. The use of role-play in small groups is an important method to help learners cultivate the skills required to engage in nuanced, often difficult conversations with seriously ill patients. To be effective, educators utilizing role-play must help learners set realistic goals and know when and how to provide feedback to the learners in a way that allows a deepening of skills and a promotion of self-awareness. The challenge is to do this in a manner that does not cause too much anxiety for the learner. In this article we outline an approach to teaching communication skills to advanced learners through the use of different types of role-play, feedback, and debriefing. PMID:21651366

  11. Teaching Communication Skills Using Role-Play: An Experience-Based Guide for Educators

    PubMed Central

    Back, Anthony L.

    2011-01-01

    Abstract Teaching advanced communication skills requires educators who are not only excellent communicators themselves but have the ability to deconstruct the components of the interaction and develop a cognitive approach that can be used across a variety of learners, diverse content, and under different time constraints while helping the learner develop the skill of self-reflection in a ‘safe’ and effective learning environment. The use of role-play in small groups is an important method to help learners cultivate the skills required to engage in nuanced, often difficult conversations with seriously ill patients. To be effective, educators utilizing role-play must help learners set realistic goals and know when and how to provide feedback to the learners in a way that allows a deepening of skills and a promotion of self-awareness. The challenge is to do this in a manner that does not cause too much anxiety for the learner. In this article we outline an approach to teaching communication skills to advanced learners through the use of different types of role-play, feedback, and debriefing. PMID:21651366

  12. Use of interactive theater and role play to develop medical students' skills in breaking bad news.

    PubMed

    Skye, Eric P; Wagenschutz, Heather; Steiger, Jeffrey A; Kumagai, Arno K

    2014-12-01

    Creative arts have been increasingly implemented in medical education. This study investigated the use of interactive theater and role play with professional actors in teaching breaking bad news to medical students. The objectives were to explore the contexts, approaches, experiences, and reactions in giving and receiving bad news. Second-year medical students participated in a required educational session that utilized interactive theater which helps students learn about the issues of breaking bad news to a patient with cancer. Following the interactive theater piece, professional actors provided students role play experiences in small groups with breaking bad news. Anonymous evaluation surveys were given out to all second-year medical students at the conclusion of the breaking bad news session. Surveys contained quantitative and qualitative responses. Three years of evaluations were analyzed. A total of 451 (88 %) students completed the evaluations. Comments were thematically analyzed. Ninety-four percent agreed that the theater piece prompted reflection on patient-provider communications, and 89 % agreed that it stimulated discussion on complex issues with breaking bad news. The two most common themes in student comments concerned the importance of realism in the theater piece, and the value of experiencing multiple perspectives. Use of professional actors during the role play exercises enhances the realism and pushed the students out of their own "comfort zones" in ways that may more closely approximate real life clinical situations. Interactive theater can be a potentially powerful tool to teach breaking bad news during medical school. PMID:24683056

  13. Developing Pharmacy Student Communication Skills through Role-Playing and Active Learning

    PubMed Central

    Zeszotarski, Paula; Ma, Carolyn

    2015-01-01

    Objective. To evaluate the impact on pharmacy students of a communication course, which used role-playing to develop active-learning skills. Design. Students role-playing pharmacists in patient care scenarios were critiqued by students and pharmacist faculty members. Grading was performed using the rubric inspired by Bruce Berger’s Communication Skills for Pharmacists. Written skills were evaluated using student written critique questionnaires. Students completed precourse and postcourse self-assessment surveys. Preceptor evaluations were analyzed for course impact. Assessment. Students demonstrated improvement in oral skills based on role-play scores (45.87/50) after practice sessions. The average score based on the student questionnaire was 9.31/10. Gain was demonstrated in all defined course objectives. Impact on introductory pharmacy practice experience (IPPE) communication objectives was insignificant. Student evaluations for course and teaching strategy reflected a high average. Conclusion. Study results demonstrated improvement in oral and written communication skills that may help improve interprofessional teamwork between pharmacists and other health care providers. PMID:25995519

  14. Role-play simulations for climate change adaptation education and engagement

    NASA Astrophysics Data System (ADS)

    Rumore, Danya; Schenk, Todd; Susskind, Lawrence

    2016-08-01

    In order to effectively adapt to climate change, public officials and other stakeholders need to rapidly enhance their understanding of local risks and their ability to collaboratively and adaptively respond to them. We argue that science-based role-play simulation exercises -- a type of 'serious game' involving face-to-face mock decision-making -- have considerable potential as education and engagement tools for enhancing readiness to adapt. Prior research suggests role-play simulations and other serious games can foster public learning and encourage collective action in public policy-making contexts. However, the effectiveness of such exercises in the context of climate change adaptation education and engagement has heretofore been underexplored. We share results from two research projects that demonstrate the effectiveness of role-play simulations in cultivating climate change adaptation literacy, enhancing collaborative capacity and facilitating social learning. Based on our findings, we suggest such exercises should be more widely embraced as part of adaptation professionals' education and engagement toolkits.

  15. Smyd5 plays pivotal roles in both primitive and definitive hematopoiesis during zebrafish embryogenesis

    PubMed Central

    Fujii, Tomoaki; Tsunesumi, Shin-ichiro; Sagara, Hiroshi; Munakata, Miyo; Hisaki, Yoshihiro; Sekiya, Takao; Furukawa, Yoichi; Sakamoto, Kazuhiro; Watanabe, Sumiko

    2016-01-01

    Methylation of histone tails plays a pivotal role in the regulation of a wide range of biological processes. SET and MYND domain-containing protein (SMYD) is a methyltransferase, five family members of which have been identified in humans. SMYD1, SMYD2, SMYD3, and SMYD4 have been found to play critical roles in carcinogenesis and/or the development of heart and skeletal muscle. However, the physiological functions of SMYD5 remain unknown. To investigate the function of Smyd5 in vivo, zebrafish were utilised as a model system. We first examined smyd5 expression patterns in developing zebrafish embryos. Smyd5 transcripts were abundantly expressed at early developmental stages and then gradually decreased. Smyd5 was expressed in all adult tissues examined. Loss-of-function analysis of Smyd5 was then performed in zebrafish embryos using smyd5 morpholino oligonucleotide (MO). Embryos injected with smyd5-MO showed normal gross morphological development, including of heart and skeletal muscle. However, increased expression of both primitive and definitive hematopoietic markers, including pu.1, mpx, l-plastin, and cmyb, were observed. These phenotypes of smyd5-MO zebrafish embryos were also observed when we introduced mutations in smyd5 gene with the CRISPR/Cas9 system. As the expression of myeloid markers was elevated in smyd5 loss-of-function zebrafish, we propose that Smyd5 plays critical roles in hematopoiesis. PMID:27377701

  16. Smyd5 plays pivotal roles in both primitive and definitive hematopoiesis during zebrafish embryogenesis.

    PubMed

    Fujii, Tomoaki; Tsunesumi, Shin-Ichiro; Sagara, Hiroshi; Munakata, Miyo; Hisaki, Yoshihiro; Sekiya, Takao; Furukawa, Yoichi; Sakamoto, Kazuhiro; Watanabe, Sumiko

    2016-01-01

    Methylation of histone tails plays a pivotal role in the regulation of a wide range of biological processes. SET and MYND domain-containing protein (SMYD) is a methyltransferase, five family members of which have been identified in humans. SMYD1, SMYD2, SMYD3, and SMYD4 have been found to play critical roles in carcinogenesis and/or the development of heart and skeletal muscle. However, the physiological functions of SMYD5 remain unknown. To investigate the function of Smyd5 in vivo, zebrafish were utilised as a model system. We first examined smyd5 expression patterns in developing zebrafish embryos. Smyd5 transcripts were abundantly expressed at early developmental stages and then gradually decreased. Smyd5 was expressed in all adult tissues examined. Loss-of-function analysis of Smyd5 was then performed in zebrafish embryos using smyd5 morpholino oligonucleotide (MO). Embryos injected with smyd5-MO showed normal gross morphological development, including of heart and skeletal muscle. However, increased expression of both primitive and definitive hematopoietic markers, including pu.1, mpx, l-plastin, and cmyb, were observed. These phenotypes of smyd5-MO zebrafish embryos were also observed when we introduced mutations in smyd5 gene with the CRISPR/Cas9 system. As the expression of myeloid markers was elevated in smyd5 loss-of-function zebrafish, we propose that Smyd5 plays critical roles in hematopoiesis. PMID:27377701

  17. The metallochaperone Atox1 plays a critical role in perinatal copper homeostasis.

    PubMed

    Hamza, I; Faisst, A; Prohaska, J; Chen, J; Gruss, P; Gitlin, J D

    2001-06-01

    Copper plays a fundamental role in the biochemistry of all aerobic organisms. The delivery of this metal to specific intracellular targets is mediated by metallochaperones. To elucidate the role of the metallochaperone Atox1, we analyzed mice with a disruption of the Atox1 locus. Atox1(-/-) mice failed to thrive immediately after birth, with 45% of pups dying before weaning. Surviving animals exhibited growth failure, skin laxity, hypopigmentation, and seizures because of perinatal copper deficiency. Maternal Atox1 deficiency markedly increased the severity of Atox1(-/-) phenotype, resulting in increased perinatal mortality as well as severe growth retardation and congenital malformations among surviving Atox1(-/-) progeny. Furthermore, Atox1-deficient cells accumulated high levels of intracellular copper, and metabolic studies indicated that this defect was because of impaired cellular copper efflux. Taken together, these data reveal a direct role for Atox1 in trafficking of intracellular copper to the secretory pathway of mammalian cells and demonstrate that this metallochaperone plays a critical role in perinatal copper homeostasis. PMID:11391006

  18. Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization.

    PubMed

    Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru

    2016-09-01

    Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY-dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage. PMID:26803756

  19. PRKX, a Novel cAMP-Dependent Protein Kinase Member, Plays an Important Role in Development.

    PubMed

    Huang, Sizhou; Li, Qian; Alberts, Ian; Li, Xiaohong

    2016-03-01

    The human protein kinase X gene (PRKX) and cAMP-dependent protein kinase (PKA) are both c-AMP-dependent serine/threonine protein kinases within the protein kinase AGC subgroup. Of all the protein kinases in this group, PRKX is the least studied. PRKX has been isolated from patients with chondrodysplasia punctate and is involved in numerous processes, including sexual differentiation and fertilization, normal kidney development and autosomal dominant polycystic kidney disease (ADPKD), blood maturation, neural development, and angiogenesis in vitro. Although the role of PRKX in development and disease has been reported recently, the underlying mechanism of PRKX activity is largely unknown. In addition, based on the expression pattern of PRKX and the extensive role of PKA in disease and development, PRKX might have additional crucial functions that have not been addressed in the literature. In this review, we summarize the characteristics and developmental functions of PRKX that have been reported by recent studies. In particular, we elucidate the structural and functional differences between PRKX and PKA, as well as the possible roles of PRKX in development and related diseases. Finally, we propose future studies that could lead to important discoveries of more PRKX functions and the underlying mechanisms involved. PMID:26252946

  20. Spatial Factors Play a Major Role as Determinants of Endemic Ground Beetle Beta Diversity of Madeira Island Laurisilva

    PubMed Central

    Boieiro, Mário; Carvalho, José C.; Cardoso, Pedro; Aguiar, Carlos A. S.; Rego, Carla; de Faria e Silva, Israel; Amorim, Isabel R.; Pereira, Fernando; Azevedo, Eduardo B.; Borges, Paulo A. V.; Serrano, Artur R. M.

    2013-01-01

    The development in recent years of new beta diversity analytical approaches highlighted valuable information on the different processes structuring ecological communities. A crucial development for the understanding of beta diversity patterns was also its differentiation in two components: species turnover and richness differences. In this study, we evaluate beta diversity patterns of ground beetles from 26 sites in Madeira Island distributed throughout Laurisilva – a relict forest restricted to the Macaronesian archipelagos. We assess how the two components of ground beetle beta diversity (βrepl – species turnover and βrich - species richness differences) relate with differences in climate, geography, landscape composition matrix, woody plant species richness and soil characteristics and the relative importance of the effects of these variables at different spatial scales. We sampled 1025 specimens from 31 species, most of which are endemic to Madeira Island. A spatially explicit analysis was used to evaluate the contribution of pure environmental, pure spatial and environmental spatially structured effects on variation in ground beetle species richness and composition. Variation partitioning showed that 31.9% of species turnover (βrepl) and 40.7% of species richness variation (βrich) could be explained by the environmental and spatial variables. However, different environmental variables controlled the two types of beta diversity: βrepl was influenced by climate, disturbance and soil organic matter content whilst βrich was controlled by altitude and slope. Furthermore, spatial variables, represented through Moran’s eigenvector maps, played a significant role in explaining both βrepl and βrich, suggesting that both dispersal ability and Madeira Island complex orography are crucial for the understanding of beta diversity patterns in this group of beetles. PMID:23724065

  1. Serious Simulation Role-Playing Games for Transformative Climate Change Education: "World Climate" and "Future Climate"

    NASA Astrophysics Data System (ADS)

    Rooney-Varga, J. N.; Sterman, J.; Sawin, E.; Jones, A.; Merhi, H.; Hunt, C.

    2012-12-01

    Climate change, its mitigation, and adaption to its impacts are among the greatest challenges of our times. Despite the importance of societal decisions in determining climate change outcomes, flawed mental models about climate change remain widespread, are often deeply entrenched, and present significant barriers to understanding and decision-making around climate change. Here, we describe two simulation role-playing games that combine active, affective, and analytical learning to enable shifts of deeply held conceptions about climate change. The games, World Climate and Future Climate, use a state-of-the-art decision support simulation, C-ROADS (Climate Rapid Overview and Decision Support) to provide users with immediate feedback on the outcomes of their mitigation strategies at the national level, including global greenhouse gas (GHG) emissions and concentrations, mean temperature changes, sea level rise, and ocean acidification. C-ROADS outcomes are consistent with the atmosphere-ocean general circulation models (AOGCMS), such as those used by the IPCC, but runs in less than one second on ordinary laptops, providing immediate feedback to participants on the consequences of their proposed policies. Both World Climate and Future Climate role-playing games provide immersive, situated learning experiences that motivate active engagement with climate science and policy. In World Climate, participants play the role of United Nations climate treaty negotiators. Participant emissions reductions proposals are continually assessed through interactive exploration of the best available science through C-ROADS. Future Climate focuses on time delays in the climate and energy systems. Participants play the roles of three generations: today's policymakers, today's youth, and 'just born.' The game unfolds in three rounds 25 simulated years apart. In the first round, only today's policymakers make decisions; In the next round, the young become the policymakers and inherit the

  2. SLA-PGN-primed dendritic cell-based vaccination induces Th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of PKCβ.

    PubMed

    Jawed, Junaid Jibran; Majumder, Saikat; Bandyopadhyay, Syamdas; Biswas, Satabdi; Parveen, Shabina; Majumdar, Subrata

    2016-07-01

    Emergence of drug resistance during visceral leishmaniasis (VL) is a major obstacle imposed during successful therapy. An effective vaccine strategy against this disease is therefore necessary. Our present study exploited the SLA (soluble leishmanial antigen) and PGN (peptidoglycan) stimulated bone marrow-derived dendritic cells (DCs) as a suitable vaccine candidate during experimental VL. SLA-PGN-stimulated DCs showed a significant decrease in hepatic and splenic parasite burden, which were associated with increased production of nitric oxide and pro-inflammatory cytokines such as IL-12, IFN-γ and IL-17. Elevated level of IL-17 was accompanied with the generation of more Th17 cells. Further studies on DC provided the evidence that these SLA-PGN-stimulated DCs played an important role in providing necessary cytokines such as IL-6, IL-23 and TGF-β for the generation of Th17 cells. Interestingly, inhibition of protein kinase C-β (PKCβ) in DCs led to decreased production of Th17 polarizing cytokines, causing reduction of the Th17 population size. Altogether, our finding highlighted the important role of DC-based PKCβ in regulation of the function and generation of Th17 cells. PMID:27150838

  3. Prototyping Tool for Web-Based Multiuser Online Role-Playing Game

    NASA Astrophysics Data System (ADS)

    Okamoto, Shusuke; Kamada, Masaru; Yonekura, Tatsuhiro

    This letter proposes a prototyping tool for Web-based Multiuser Online Role-Playing Game (MORPG). The design goal is to make this tool simple and powerful. The tool is comprised of a GUI editor, a translator and a runtime environment. The GUI editor is used to edit state-transition diagrams, each of which defines the behavior of the fictional characters. The state-transition diagrams are translated into C program codes, which plays the role of a game engine in RPG system. The runtime environment includes PHP, JavaScript with Ajax and HTML. So the prototype system can be played on the usual Web browser, such as Fire-fox, Safari and IE. On a click or key press by a player, the Web browser sends it to the Web server to reflect its consequence on the screens which other players are looking at. Prospected users of this tool include programming novices and schoolchildren. The knowledge or skill of any specific programming languages is not required to create state-transition diagrams. Its structure is not only suitable for the definition of a character behavior but also intuitive to help novices understand. Therefore, the users can easily create Web-based MORPG system with the tool.

  4. The role of conserved Cys residues in Brassica rapa auxin amidohydrolase: Cys139 is crucial for the enzyme activity and Cys320 regulates enzyme stability.

    PubMed

    Smolko, Ana; Šupljika, Filip; Martinčić, Jelena; Jajčanin-Jozić, Nina; Grabar-Branilović, Marina; Tomić, Sanja; Ludwig-Müller, Jutta; Piantanida, Ivo; Salopek-Sondi, Branka

    2016-04-01

    Brassica rapa auxin amidohydrolase (BrILL2) participates in the homeostasis of the plant hormones auxins by hydrolyzing the amino acid conjugates of auxins, thereby releasing the free active form of hormones. Herein, the potential role of the two conserved Cys residues of BrILL2 (at sequence positions 139 and 320) has been investigated by using interdisciplinary approaches and methods of molecular biology, biochemistry, biophysics and molecular modelling. The obtained results show that both Cys residues participate in the regulation of enzyme activity. Cys320 located in the satellite domain of the enzyme is mainly responsible for protein stability and regulation of enzyme activity through polymer formation, as has been revealed by enzyme kinetics and differential scanning calorimetry analysis of the BrILL2 wild type and mutants C320S and C139S. Cys139 positioned in the active site of the catalytic domain is involved in the coordination of one Mn(2+) ion of the bimetal center and is crucial for the enzymatic activity. Although the point mutation Cys139 to Ser causes the loss of enzyme activity, it does not affect the metal binding to the BrILL2 enzyme, as has been shown by isothermal titration calorimetry, circular dichroism spectropolarimetry and differential scanning calorimetry data. MD simulations (200 ns) revealed a different active site architecture of the BrILL2C139S mutant in comparison to the wild type enzyme. Additional possible reasons for the inactivity of the BrILL2C139S mutant have been discussed based on MD simulations and MM-PBSA free energy calculations of BrILL2 enzyme complexes (wt and C139S mutant) with IPA-Ala as a substrate. PMID:26959939

  5. Two nucleus-localized CDK-like kinases with crucial roles for malaria parasite erythrocytic replication are involved in phosphorylation of splicing factor.

    PubMed

    Agarwal, Shruti; Kern, Selina; Halbert, Jean; Przyborski, Jude M; Baumeister, Stefan; Dandekar, Thomas; Doerig, Christian; Pradel, Gabriele

    2011-05-01

    The kinome of the human malaria parasite Plasmodium falciparum comprises representatives of most eukaryotic protein kinase groups, including kinases which regulate proliferation and differentiation processes. Despite extensive research on most plasmodial enzymes, little information is available regarding the four identified members of the cyclin-dependent kinase-like kinase (CLK) family. In other eukaryotes, CLKs regulate mRNA splicing through phosphorylation of Serine/Arginine-rich proteins. Here, we investigate two of the PfCLKs, the Lammer kinase homolog PfCLK-1, and PfCLK-2. Both PfCLKs show homology with the yeast Serine/Arginine protein kinase Sky1p and are transcribed throughout the asexual blood stages and in gametocytes. PfCLK-1/Lammer possesses two nuclear localization signal sites and PfCLK-2 possesses one of these signal sites upstream of the C-terminal catalytic domains. Indirect immunofluorescence, Western blot, and electron microscopy data confirm that the kinases are primarily localized in the parasite nucleus, and PfCLK-2 is further present in the cytoplasm. The two kinases are important for completion of the asexual replication cycle of P. falciparum, as demonstrated by reverse genetics approaches. In vitro kinase assays show substrate phosphorylation by the PfCLKs, including the Sky1p substrate, splicing factor Npl3p, and the plasmodial alternative splicing factor PfASF-1. Mass spectrometric analysis of co-immunoprecipitated proteins indicates assembly of the two PfCLKs with proteins with predicted nuclease, phosphatase, or helicase functions. Our data indicate a crucial role of PfCLKs for malaria blood stage parasites, presumably by participating in gene regulation through the post-transcriptional modification of mRNA. PMID:21312235

  6. Recruitment of Gβγ controls the basal activity of G-protein coupled inwardly rectifying potassium (GIRK) channels: crucial role of distal C terminus of GIRK1

    PubMed Central

    Kahanovitch, Uri; Tsemakhovich, Vladimir; Berlin, Shai; Rubinstein, Moran; Styr, Boaz; Castel, Ruth; Peleg, Sagit; Tabak, Galit; Dessauer, Carmen W; Ivanina, Tatiana; Dascal, Nathan

    2014-01-01

    The G-protein coupled inwardly rectifying potassium (GIRK, or Kir3) channels are important mediators of inhibitory neurotransmission via activation of G-protein coupled receptors (GPCRs). GIRK channels are tetramers comprising combinations of subunits (GIRK1–4), activated by direct binding of the Gβγ subunit of Gi/o proteins. Heterologously expressed GIRK1/2 exhibit high, Gβγ-dependent basal currents (Ibasal) and a modest activation by GPCR or coexpressed Gβγ. Inversely, the GIRK2 homotetramers exhibit low Ibasal and strong activation by Gβγ. The high Ibasal of GIRK1 seems to be associated with its unique distal C terminus (G1-dCT), which is not present in the other subunits. We investigated the role of G1-dCT using electrophysiological and fluorescence assays in Xenopus laevis oocytes and protein interaction assays. We show that expression of GIRK1/2 increases the plasma membrane level of coexpressed Gβγ (a phenomenon we term ‘Gβγ recruitment’) but not of coexpressed Gαi3. All GIRK1-containing channels, but not GIRK2 homomers, recruited Gβγ to the plasma membrane. In biochemical assays, truncation of G1-dCT reduces the binding between the cytosolic parts of GIRK1 and Gβγ, but not Gαi3. Nevertheless, the truncation of G1-dCT does not impair activation by Gβγ. In fluorescently labelled homotetrameric GIRK1 channels and in the heterotetrameric GIRK1/2 channel, the truncation of G1-dCT abolishes Gβγ recruitment and decreases Ibasal. Thus, we conclude that G1-dCT carries an essential role in Gβγ recruitment by GIRK1 and, consequently, in determining its high basal activity. Our results indicate that G1-dCT is a crucial part of a Gβγ anchoring site of GIRK1-containing channels, spatially and functionally distinct from the site of channel activation by Gβγ. PMID:25384780

  7. Canonical Notch signaling plays an instructive role in auditory supporting cell development

    PubMed Central

    Campbell, Dean P.; Chrysostomou, Elena; Doetzlhofer, Angelika

    2016-01-01

    The auditory sensory epithelium, composed of mechano-sensory hair cells (HCs) and highly specialized glial-like supporting cells (SCs), is critical for our ability to detect sound. SCs provide structural and functional support to HCs and play an essential role in cochlear development, homeostasis and repair. Despite their importance, however, surprisingly little is known about the molecular mechanisms guiding SC differentiation. Here, we provide evidence that in addition to its well-characterized inhibitory function, canonical Notch signaling plays a positive, instructive role in the differentiation of SCs. Using γ-secretase inhibitor DAPT to acutely block canonical Notch signaling, we identified a cohort of Notch-regulated SC-specific genes, with diverse functions in cell signaling, cell differentiation, neuronal innervation and synaptogenesis. We validated the newly identified Notch-regulated genes in vivo using genetic gain (Emx2Cre/+; Rosa26N1ICD/+) and loss-of-function approaches (Emx2Cre/+; Rosa26DnMAML1/+). Furthermore, we demonstrate that Notch over-activation in the differentiating murine cochlea (Emx2Cre/+; Rosa26N1ICD/+) actively promotes a SC-specific gene expression program. Finally, we show that outer SCs –so called Deiters’ cells are selectively lost by prolonged reduction (Emx2Cre/+; Rosa26DnMAML1/+/+) or abolishment of canonical Notch signaling (Fgfr3-iCreER; Rbpj−/Δ), indicating a critical role for Notch signaling in Deiters’ cell development. PMID:26786414

  8. Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.

    PubMed

    Belousov, Andrei B; Wang, Yongfu; Song, Ji-Hoon; Denisova, Janna V; Berman, Nancy E; Fontes, Joseph D

    2012-08-22

    In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death. PMID:22781494

  9. Canonical Notch signaling plays an instructive role in auditory supporting cell development.

    PubMed

    Campbell, Dean P; Chrysostomou, Elena; Doetzlhofer, Angelika

    2016-01-01

    The auditory sensory epithelium, composed of mechano-sensory hair cells (HCs) and highly specialized glial-like supporting cells (SCs), is critical for our ability to detect sound. SCs provide structural and functional support to HCs and play an essential role in cochlear development, homeostasis and repair. Despite their importance, however, surprisingly little is known about the molecular mechanisms guiding SC differentiation. Here, we provide evidence that in addition to its well-characterized inhibitory function, canonical Notch signaling plays a positive, instructive role in the differentiation of SCs. Using γ-secretase inhibitor DAPT to acutely block canonical Notch signaling, we identified a cohort of Notch-regulated SC-specific genes, with diverse functions in cell signaling, cell differentiation, neuronal innervation and synaptogenesis. We validated the newly identified Notch-regulated genes in vivo using genetic gain (Emx2(Cre/+); Rosa26(N1ICD/+)) and loss-of-function approaches (Emx2(Cre/+); Rosa26(DnMAML1/+)). Furthermore, we demonstrate that Notch over-activation in the differentiating murine cochlea (Emx2(Cre/+); Rosa26(N1ICD/+)) actively promotes a SC-specific gene expression program. Finally, we show that outer SCs -so called Deiters' cells are selectively lost by prolonged reduction (Emx2(Cre/+); Rosa26(DnMAML1/+/+)) or abolishment of canonical Notch signaling (Fgfr3-iCreER; Rbpj(-/Δ)), indicating a critical role for Notch signaling in Deiters' cell development. PMID:26786414

  10. Simulating Social and Political Influences on Hazard Analysis through a Classroom Role Playing Exercise

    NASA Astrophysics Data System (ADS)

    Hales, T. C.; Cashman, K. V.

    2006-12-01

    Geological hazard mitigation is a complicated process that involves both detailed scientific research and negotiations between community members with competing interests in the solution. Geological hazards classes based around traditional lecture methods have difficulty conveying the decision-making processes that go into these negotiations. To address this deficiency, we have spent five years developing and testing a role- playing exercise based on mitigation of a dam outburst hazard on Ruapehu volcano, New Zealand. In our exercise, students are asked to undertake one of five different roles and decide the best way to mitigate the hazard. Over the course of their discussion students are challenged to reach a consensus decision despite the presence of strongly opposed positions. Key to the success of the exercise are (1) the presence of a facilitator and recorder for each meeting, (2) the provision of unique information for each interested party, and (3) the division of the class into multiple meeting groups, such that everyone is required to participate and individual groups can evolve to different conclusions. The exercise can be completed in a single hour and twenty minute classroom session that is divided into four parts: an introduction, a meeting between members of the same interested party to discuss strategy, a meeting between different interested parties, and a debriefing session. This framework can be readily translated to any classroom hazard problem. In our experience, students have responded positively to the use of role-playing to supplement lectures.

  11. SATB1 Plays a Critical Role in Establishment of Immune Tolerance.

    PubMed

    Kondo, Motonari; Tanaka, Yuriko; Kuwabara, Taku; Naito, Taku; Kohwi-Shigematsu, Terumi; Watanabe, Akiko

    2016-01-15

    Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer that is expressed by T cells. T cell development is severely impaired in SATB1 null mice; however, because SATB1 null mice die by 3 wk of age, the roles of SATB1 in T cell development have not been well clarified. In this study, we generated and analyzed SATB1 conditional knockout (cKO) mice, in which the SATB1 gene was deleted from all hematopoietic cells. T cell numbers were reduced in these mice, mainly because of a deficiency in positive selection at the CD4(+)CD8(+) double-positive stage during T cell development in the thymus. We also found that SATB1 cKO mice developed autoimmune diseases within 16 wk after birth. In SATB1 cKO mice, the numbers of Foxp3(+) regulatory T (Treg) cells were significantly reduced at 2 wk of age compared with wild-type littermates. Although the numbers gradually increased upon aging, Treg cells in SATB1 cKO mice were still less than those in wild-type littermates at adulthood. Suppressive functions of Treg cells, which play a major role in establishment of peripheral tolerance, were also affected in the absence of SATB1. In addition, negative selection during T cell development in the thymus was severely impaired in SATB1 deficient mice. These results suggest that SATB1 plays an essential role in establishment of immune tolerance. PMID:26667169

  12. The Caenorhabditis elegans LET-418/Mi2 plays a conserved role in lifespan regulation.

    PubMed

    De Vaux, Véronique; Pfefferli, Catherine; Passannante, Myriam; Belhaj, Khaoula; von Essen, Alina; Sprecher, Simon G; Müller, Fritz; Wicky, Chantal

    2013-12-01

    The evolutionarily conserved nucleosome-remodeling protein Mi2 is involved in transcriptional repression during development in various model systems, plays a role in embryonic patterning and germ line development, and participates in DNA repair and cell cycle progression. It is the catalytic subunit of the nucleosome remodeling and histone deacetylase (NuRD) complex, a key determinant of differentiation in mammalian embryonic stem cells. In addition, the Drosophila and C. elegans Mi2 homologs participate in another complex, the MEC complex, which also plays an important developmental role in these organisms. Here we show a new and unexpected feature of the C. elegans Mi2 homolog, LET-418/Mi2. Lack of LET-418/Mi2 results in longevity and enhanced stress resistance, a feature that we found to be conserved in Drosophila and in Arabidopsis. The fact that depletion of other components of the NuRD and the MEC complexes did not result in longevity suggests that LET-418 may regulate lifespan in a different molecular context. Genetic interaction studies suggest that let-418 could act in the germ-cell-loss pathway, downstream of kri-1 and tcer-1. On the basis of our data and on previous findings showing a role for let-418 during development, we propose that LET-418/Mi2 could be part of a system that drives development and reproduction with concomitant life-reducing effects later in life. PMID:23815345

  13. p21 induction plays a dual role in anti-cancer activity of ursolic acid.

    PubMed

    Zhang, Xudong; Song, Xinhua; Yin, Shutao; Zhao, Chong; Fan, Lihong; Hu, Hongbo

    2016-03-01

    Previous studies have shown that induction of G1 arrest and apoptosis by ursolic acid is associated with up-regulation of cyclin-dependent kinase inhibitor (CDKI) protein p21 in multiple types of cancer cells. However, the functional role of p21 induction in G1 cell cycle arrest and apoptosis, and the mechanisms of p21 induction by ursolic acid have not been critically addressed. In the current study, we demonstrated that p21 played a mediator role in G1 cell cycle arrest by ursolic acid, whereas p21-mediated up-regulation of Mcl-1 compromised apoptotic effect of ursolic acid. These results suggest that p21 induction plays a dual role in the anti-cancer activity of ursolic acid in terms of cell cycle and apoptosis regulation. p21 induction by ursolic acid was attributed to p53 transcriptional activation. Moreover, we found that ursolic acid was able to inhibit murine double minute-2 protein (MDM2) and T-LAK cell-originated protein kinase (TOPK), the two negative regulator of p53, which in turn contributed to ursolic acid-induced p53 activation. Our findings provided novel insights into understanding of the mechanisms involved in cell cycle arrest and apoptosis induction in response to ursolic acid exposure. PMID:26582056

  14. Cadherin2 (N-cadherin) plays an essential role in zebrafish cardiovascular development

    PubMed Central

    Bagatto, Brian; Francl, Jessie; Liu, Bei; Liu, Qin

    2006-01-01

    Background Cadherins are cell surface adhesion molecules that play important roles in development of vertebrate tissues and organs. We studied cadherin2 expression in developing zebrafish heart using in situ hybridization and immunocytochemical methods, and we found that cadherin2 was strongly expressed by the myocardium of the embryonic zebrafish. To gain insight into cadherin2 role in the formation and function of the heart, we analyzed cardiac differentiation and performance in a cadherin2 mutant, glass onion (glo). Results We found that the cadherin2 mutant had enlarged pericardial cavity, disorganized atrium and ventricle, and reduced expression of a ventricular specific marker vmhc. Individual myocardiocytes in the glo mutant embryos became round shaped and loosely aggregated. In vivo measurements of cardiac performance revealed that the mutant heart had significantly reduced heart rate, stroke volume and cardiac output compared to control embryos. Formation of the embryonic vascular system in the glo mutants was also affected. Conclusion Our results suggest that cadherin2 plays an essential role in zebrafish cardiovascular development. Although the exact mechanisms remain unknown as to the formation of the enlarged pericardium and reduced peripheral blood flow, it is clear that myocardiocyte differentiation and physiological cardiovascular performance is impaired when cadherin2 function is disrupted. PMID:16719917

  15. Does psychosocial stress play a role in the exacerbation of psoriasis?

    PubMed

    Hunter, H J A; Griffiths, C E M; Kleyn, C E

    2013-11-01

    It is widely accepted that psychosocial stress can result from the daily strains of living with a diagnosis of psoriasis. There is now an evolving body of work to suggest that psychosocial stress may also play a role in the exacerbation of psoriasis. We discuss the historical evidence supporting a temporal relationship between psychosocial stress and the exacerbation of psoriasis. The underlying pathophysiological mechanisms by which this occurs are largely unknown, but current evidence points towards a role for nerve-related factors, namely their interaction with mast cells and the potentiation of neurogenic inflammation in this regard. It is also likely that the physiological stress response in patients with psoriasis differs from that in healthy individuals, as evidenced by alterations in the hypothalamic-pituitary-adrenal axis and sympathetic-adrenal-medullary system function. Psychological stress results in a redistribution of leucocytes with increased trafficking of inflammatory cells into the skin, which may exacerbate psoriasis. Langerhans cells play a role in the stress response of normal skin; their function in the stress response of patients with psoriasis is open to speculation. We discuss the influence of stress reactivity in patients with psoriasis and the impact of stress reduction strategies in the management of psoriasis. Finally, we suggest potentially fruitful areas for future research. PMID:23796214

  16. Leu1 plays a role in iron metabolism and is required for virulence in Cryptococcus neoformans

    PubMed Central

    Do, Eunsoo; Hu, Guanggan; Caza, Mélissa; Oliveira, Debora; Kronstad, James W.; Jung, Won Hee

    2015-01-01

    Amino acid biosynthetic pathways that are absent in mammals are considered an attractive target for antifungal therapy. Leucine biosynthesis is one such target pathway, consisting of a five-step conversion process starting from the valine precursor 2-keto-isovalerate. Isopropylmalate dehydrogenase (Leu1) is an Fe-S cluster protein that is required for leucine biosynthesis in the model fungus Saccharomyces cerevisiae. The human pathogenic fungus Cryptococcus neoformans possesses an ortholog of S. cerevisiae Leu1, and our previous transcriptome data showed that the expression of LEU1 is regulated by iron availability. In this study, we characterized the role of Leu1 in iron homeostasis and the virulence of C. neoformans. We found that deletion of LEU1 caused leucine auxotrophy and that Leu1 may play a role in the mitochondrial-cytoplasmic Fe-S cluster balance. Whereas cytoplasmic Fe-S protein levels were not affected, mitochondrial Fe-S proteins were up- regulated in the leu1 mutant, suggesting that Leu1 mainly influences mitochondrial iron metabolism. The leu1 mutant also displayed increased sensitivity to oxidative stress and cell wall/membrane disrupting agents, which may have been caused by mitochondrial dysfunction. Furthermore, the leu1 mutant was deficient in capsule formation and showed attenuated virulence in a mouse inhalation model of cryptococcosis. Overall, our results indicate that Leu1 plays a role in iron metabolism and is required for virulence in C. neoformans. PMID:25554701

  17. RABEX-5 plays an oncogenic role in breast cancer by activating MMP-9 pathway

    PubMed Central

    2013-01-01

    Background RABEX-5, a guanine nucleotide exchange factor (GEF) for RAB-5, plays an important role in cell mobility and altered expression associated with tumor metastasis. This study aimed to investigate the role of RABEX-5 in proliferation and metastasis of breast cancer in vitro and ex vivo. Methods RABEX-5 expression was examined in breast cancer, benign tumor and normal breast tissues by immunohistochemistry and western blot. Two stable cell lines were established, the MCF-7/NC negative control cell line and the MCF-7/KD cell line, which stably expressed an RNA interference (RNAi) construct that induced downregulation of RABEX-5 expression. These cell lines were utilized to evaluate the role of RABEX-5 in cell proliferation and migration in vitro and tumorigenicity in vivo. The possible role of RABEX-5 in the regulation of matrix metallopeptidase 9 (MMP-9) was evaluated using western blot and real-time PCR. Results RABEX-5 expression was found to be significantly higher in breast cancer tissues compared with benign tumor and normal breast tissues. High levels of RABEX-5 expression were associated with axillary lymph node metastasis. In addition, RABEX-5 silencing significantly reduced cancer cell proliferation, colony formation and migration ability in vitro and inhibited tumor growth in vivo. RABEX −5 knockdown also attenuated the migration of breast cancer cells via modulation of MMP-9 transcriptional activity. Conclusions Our results indicate that RABEX-5 plays an oncogenic role in breast cancer by modulating the proliferation and metastasis potential of breast cancer cells. Thus, RABEX-5 is a promising prognostic indicator for patients with breast cancer. PMID:23941575

  18. Trusted Sources: The Role Scientific Societies Can Play in Improving Public Opinions on Climate Change

    NASA Astrophysics Data System (ADS)

    McEntee, C.; Cairns, A.; Buhrman, J.

    2012-12-01

    Public acceptance of the scientific consensus regarding climate change has eroded and misinformation designed to confuse the public is rapidly proliferating. Those issues, combined with an increase of politically motivated attacks on climate scientists and their research, have led to a place where ideology can trump scientific consensus as the foundation for developing policy solutions. The scientific community has been, thus far, unprepared to respond effectively to these developments. However, as a scientific society whose members engage in climate science research, and one whose organizational mission and vision are centered on the concepts of science for the benefit of humanity and ensuring a sustainable future, the American Geophysical Union can, and should, play an important role in reversing this trend. To that end, in 2011, AGU convened a Leadership Summit on Climate Science Communication, in which presidents, executive directors, and senior public policy staff from 17 scientific organizations engaged with experts in the social sciences regarding effective communication of climate science and with practitioners from agriculture, energy, and the military. The discussions focused on three key issues: the environment of climate science communication; public understanding of climate change; and the perspectives of consumers of climate science-based information who work with specific audiences. Participants diagnosed previous challenges and failings, enumerated the key constituencies that need to be effectively engaged, and identified the critical role played by cultural cognition—the influence of group values, particularly around equality and authority, individualism, and community; and the perceptions of risk. Since that meeting, AGU has consistently worked to identify and explore ways that it, and its members, and improve the effectiveness of their communication with the public about climate change. This presentation will focus on the insights AGU has

  19. DICER-LIKE2 plays a primary role in transitive silencing of transgenes in Arabidopsis.

    PubMed

    Mlotshwa, Sizolwenkosi; Pruss, Gail J; Peragine, Angela; Endres, Matthew W; Li, Junjie; Chen, Xuemei; Poethig, R Scott; Bowman, Lewis H; Vance, Vicki

    2008-01-01

    Dicer-like (DCL) enzymes play a pivotal role in RNA silencing in plants, processing the long double-stranded RNA (dsRNA) that triggers silencing into the primary short interfering RNAs (siRNAs) that mediate it. The siRNA population can be augmented and silencing amplified via transitivity, an RNA-dependent RNA polymerase (RDR)-dependent pathway that uses the target RNA as substrate to generate secondary siRNAs. Here we report that Arabidopsis DCL2-but not DCL4-is required for transitivity in cell-autonomous, post-transcriptional silencing of transgenes. An insertion mutation in DCL2 blocked sense transgene-induced silencing and eliminated accumulation of the associated RDR-dependent siRNAs. In hairpin transgene-induced silencing, the dcl2 mutation likewise eliminated accumulation of secondary siRNAs and blocked transitive silencing, but did not block silencing mediated by primary siRNAs. Strikingly, in all cases, the dcl2 mutation eliminated accumulation of all secondary siRNAs, including those generated by other DCL enzymes. In contrast, mutations in DCL4 promoted a dramatic shift to transitive silencing in the case of the hairpin transgene and enhanced silencing induced by the sense transgene. Suppression of hairpin and sense transgene silencing by the P1/HC-Pro and P38 viral suppressors was associated with elimination of secondary siRNA accumulation, but the suppressors did not block processing of the stem of the hairpin transcript into primary siRNAs. Thus, these viral suppressors resemble the dcl2 mutation in their effects on siRNA biogenesis. We conclude that DCL2 plays an essential, as opposed to redundant, role in transitive silencing of transgenes and may play a more important role in silencing of viruses than currently thought. PMID:18335032

  20. The MAT Locus Genes Play Different Roles in Sexual Reproduction and Pathogenesis in Fusarium graminearum

    PubMed Central

    Juanyu; Zhang; Ma, Jiwen; Wu, Zhongshou; Wang, Guanghui; Wang, Chenfang; Xu, Jin-Rong

    2013-01-01

    Sexual reproduction plays a critical role in the infection cycle of Fusarium graminearum because ascospores are the primary inoculum. As a homothallic ascomycete, F. graminearum contains both the MAT1-1 and MAT1-2-1 loci in the genome. To better understand their functions and regulations in sexual reproduction and pathogenesis, in this study we assayed the expression, interactions, and mutant phenotypes of individual MAT locus genes. Whereas the expression of MAT1-1-1 and MAT12-1 rapidly increased after perithecial induction and began to decline after 1 day post-perithecial induction (dpi), the expression of MAT1-1-2 and MAT1-1-3 peaked at 4 dpi. MAT1-1-2 and MAT1-1-3 had a similar expression profile and likely are controlled by a bidirectional promoter. Although none of the MAT locus genes were essential for perithecium formation, all of them were required for ascosporogenesis in self-crosses. In outcrosses, the mat11-1-2 and mat11-1-3 mutants were fertile but the mat1-1-1 and mat1-2-1 mutants displayed male- and female-specific defects, respectively. The mat1-2-1 mutant was reduced in FgSO expression and hyphal fusion. Mat1-1-2 interacted with all other MAT locus transcription factors, suggesting that they may form a protein complex during sexual reproduction. Mat1-1-1 also interacted with FgMcm1, which may play a role in controlling cell identity and sexual development. Interestingly, the mat1-1-1 and mat1-2-1 mutants were reduced in virulence in corn stalk rot assays although none of the MAT locus genes was important for wheat infection. The MAT1-1-1 and MAT1-2-1 genes may play a host-specific role in colonization of corn stalks. PMID:23826182