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  1. [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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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)

  7. Graft-infiltrating host dendritic cells play a key role in organ transplant rejection.

    PubMed

    Zhuang, Quan; Liu, Quan; Divito, Sherrie J; Zeng, Qiang; Yatim, Karim M; Hughes, Andrew D; Rojas-Canales, Darling M; Nakao, A; Shufesky, William J; Williams, Amanda L; Humar, Rishab; Hoffman, Rosemary A; Shlomchik, Warren D; Oberbarnscheidt, Martin H; Lakkis, Fadi G; Morelli, Adrian E

    2016-01-01

    Successful engraftment of organ transplants has traditionally relied on preventing the activation of recipient (host) T cells. Once T-cell activation has occurred, however, stalling the rejection process becomes increasingly difficult, leading to graft failure. Here we demonstrate that graft-infiltrating, recipient (host) dendritic cells (DCs) play a key role in driving the rejection of transplanted organs by activated (effector) T cells. We show that donor DCs that accompany heart or kidney grafts are rapidly replaced by recipient DCs. The DCs originate from non-classical monocytes and form stable, cognate interactions with effector T cells in the graft. Eliminating recipient DCs reduces the proliferation and survival of graft-infiltrating T cells and abrogates ongoing rejection or rejection mediated by transferred effector T cells. Therefore, host DCs that infiltrate transplanted organs sustain the alloimmune response after T-cell activation has already occurred. Targeting these cells provides a means for preventing or treating rejection. PMID:27554168

  8. Graft-infiltrating host dendritic cells play a key role in organ transplant rejection

    PubMed Central

    Zhuang, Quan; Liu, Quan; Divito, Sherrie J.; Zeng, Qiang; Yatim, Karim M.; Hughes, Andrew D.; Rojas-Canales, Darling M.; Nakao, A.; Shufesky, William J.; Williams, Amanda L.; Humar, Rishab; Hoffman, Rosemary A.; Shlomchik, Warren D.; Oberbarnscheidt, Martin H.; Lakkis, Fadi G.; Morelli, Adrian E.

    2016-01-01

    Successful engraftment of organ transplants has traditionally relied on preventing the activation of recipient (host) T cells. Once T-cell activation has occurred, however, stalling the rejection process becomes increasingly difficult, leading to graft failure. Here we demonstrate that graft-infiltrating, recipient (host) dendritic cells (DCs) play a key role in driving the rejection of transplanted organs by activated (effector) T cells. We show that donor DCs that accompany heart or kidney grafts are rapidly replaced by recipient DCs. The DCs originate from non-classical monocytes and form stable, cognate interactions with effector T cells in the graft. Eliminating recipient DCs reduces the proliferation and survival of graft-infiltrating T cells and abrogates ongoing rejection or rejection mediated by transferred effector T cells. Therefore, host DCs that infiltrate transplanted organs sustain the alloimmune response after T-cell activation has already occurred. Targeting these cells provides a means for preventing or treating rejection. PMID:27554168

  9. The polygalacturonase FaPG1 gene plays a key role in strawberry fruit softening.

    PubMed

    García-Gago, Juan A; Posé, Sara; Muñoz-Blanco, Juan; Quesada, Miguel A; Mercado, José A

    2009-08-01

    The loss of firm texture is one of the most characteristic physiological processes that occur during the ripening of fleshy fruits. It is generally accepted that the disassembly of primary cell wall and middle lamella is the main factor involved in fruit softening. In this process, polygalacturonase (PG) has been implicated in the degradation of the polyuronide network in several fruits. However, the minor effect of PG downregulation on tomato softening, reported during the nineties, minimized the role of this enzyme in softening. Further works in other fruits are challenging this general assumption, as is occurring in strawberry. The strawberry (Fragaria x ananassa) fruit undergoes an extensive and fast softening that limit its shelf life and postharvest. Traditionally, it has also been considered that PG plays a minor role on this process, due to the low PG activity found in ripened strawberry fruits. Transgenic strawberry plants expressing an antisense sequence of the ripening-specific PG gene FaPG1 have been generated to get an insight into the role of this gene in softening. Half of the transgenic lines analyzed yielded fruits significantly firmer than control, without being affected other fruit parameters such as weight, color or soluble solids. The increase on firmness was maintained after several days of posharvest. In these firmer lines, FaPG1 was silenced to 95%, but total PG activity was only minor reduced. At the cell wall level, transgenic fruits contained a higher amount of covalently bound pectins whereas the soluble fraction was diminished. A microarray analysis of genes expressed in ripened receptacle did not show any significant change between control and transgenic fruits. Thus, contrary to the most accepted view, it is concluded that PG plays a key role on pectin metabolism and softening of strawberry fruit. PMID:19820312

  10. Novel Pectate Lyase Genes of Heterodera glycines Play Key Roles in the Early Stage of Parasitism.

    PubMed

    Peng, Huan; Cui, Jiangkuan; Long, Haibo; Huang, Wenkun; Kong, Lingan; Liu, Shiming; He, Wenting; Hu, Xianqi; Peng, Deliang

    2016-01-01

    Pectate lyases are known to play a key role in pectin degradation by catalyzing the random cleavage of internal polymer linkages (endo-pectinases). In this paper, four novel cDNAs, designated Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7, that encode pectate lyases were cloned and characterized from the soybean cyst nematode, Heterodera glycines. The predicted protein sequences of HG-PEL-3, HG-PEL-4 and HG-PEL-6 differed significantly in both their amino acid sequences and their genomic structures from other pectate lyases of H. glycines (HG-PEL-1, HG-PEL-2 and HG-PEL-7). A phylogenetic study revealed that the pectate lyase proteins of H. glycines are clustered into distinct clades and have distinct numbers and positioning of introns, which suggests that the pectate lyase genes of H. glycines may have evolved from at least two ancestral genes. A Southern blot analysis revealed that multiple Hg-pel-6-like genes were present in the H. glycines genome. In situ hybridization showed that four novel pectate lyases (Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7) were actively transcribed in the subventral esophageal gland cells. A semi-quantitative RT-PCR assay supported the finding that the expression of these genes was strong in the egg, pre-parasitic second-stage juvenile (J2) and early parasitic J2 stages and that it declined in further developmental stages of the nematode. This expression pattern suggests that these proteins play a role in the migratory phase of the nematode life cycle. Knocking down Hg-pel-6 using in vitro RNA interference resulted in a 46.9% reduction of the number of nematodes that invaded the plants and a 61.5% suppression of the development of H. glycines females within roots compared to the GFP-dsRNA control. Plant host-derived RNAi induced the silencing of the Hg-pel-6gene, which significantly reduced the nematode infection levels at 7 Days post inoculation (dpi). Similarly, this procedure reduced the number of female adults at 40 dpi, which suggests

  11. Novel Pectate Lyase Genes of Heterodera glycines Play Key Roles in the Early Stage of Parasitism

    PubMed Central

    Peng, Huan; Cui, Jiangkuan; Long, Haibo; Huang, Wenkun; Kong, Lingan; Liu, Shiming; He, Wenting; Hu, Xianqi; Peng, Deliang

    2016-01-01

    Pectate lyases are known to play a key role in pectin degradation by catalyzing the random cleavage of internal polymer linkages (endo-pectinases). In this paper, four novel cDNAs, designated Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7, that encode pectate lyases were cloned and characterized from the soybean cyst nematode, Heterodera glycines. The predicted protein sequences of HG-PEL-3, HG-PEL-4 and HG-PEL-6 differed significantly in both their amino acid sequences and their genomic structures from other pectate lyases of H. glycines (HG-PEL-1, HG-PEL-2 and HG-PEL-7). A phylogenetic study revealed that the pectate lyase proteins of H. glycines are clustered into distinct clades and have distinct numbers and positioning of introns, which suggests that the pectate lyase genes of H. glycines may have evolved from at least two ancestral genes. A Southern blot analysis revealed that multiple Hg-pel-6-like genes were present in the H. glycines genome. In situ hybridization showed that four novel pectate lyases (Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7) were actively transcribed in the subventral esophageal gland cells. A semi-quantitative RT-PCR assay supported the finding that the expression of these genes was strong in the egg, pre-parasitic second-stage juvenile (J2) and early parasitic J2 stages and that it declined in further developmental stages of the nematode. This expression pattern suggests that these proteins play a role in the migratory phase of the nematode life cycle. Knocking down Hg-pel-6 using in vitro RNA interference resulted in a 46.9% reduction of the number of nematodes that invaded the plants and a 61.5% suppression of the development of H. glycines females within roots compared to the GFP-dsRNA control. Plant host-derived RNAi induced the silencing of the Hg-pel-6gene, which significantly reduced the nematode infection levels at 7 Days post inoculation (dpi). Similarly, this procedure reduced the number of female adults at 40 dpi, which suggests

  12. The Nonstructural Proteins of Nipah Virus Play a Key Role in Pathogenicity in Experimentally Infected Animals

    PubMed Central

    Yoneda, Misako; Guillaume, Vanessa; Sato, Hiroki; Fujita, Kentaro; Georges-Courbot, Marie-Claude; Ikeda, Fusako; Omi, Mio; Muto-Terao, Yuri; Wild, T. Fabian; Kai, Chieko

    2010-01-01

    Nipah virus (NiV) P gene encodes P protein and three accessory proteins (V, C and W). It has been reported that all four P gene products have IFN antagonist activity when the proteins were transiently expressed. However, the role of those accessory proteins in natural infection with NiV remains unknown. We generated recombinant NiVs lacking V, C or W protein, rNiV(V−), rNiV(C−), and rNiV(W−), respectively, to analyze the functions of these proteins in infected cells and the implications in in vivo pathogenicity. All the recombinants grew well in cell culture, although the maximum titers of rNiV(V−) and rNiV(C−) were lower than the other recombinants. The rNiV(V−), rNiV(C−) and rNiV(W−) suppressed the IFN response as well as the parental rNiV, thereby indicating that the lack of each accessory protein does not significantly affect the inhibition of IFN signaling in infected cells. In experimentally infected golden hamsters, rNiV(V−) and rNiV(C−) but not the rNiV(W−) virus showed a significant reduction in virulence. These results suggest that V and C proteins play key roles in NiV pathogenicity, and the roles are independent of their IFN-antagonist activity. This is the first report that identifies the molecular determinants of NiV in pathogenicity in vivo. PMID:20856799

  13. 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

  14. Long Noncoding RNA Plays a Key Role in Metastasis and Prognosis of Hepatocellular Carcinoma

    PubMed Central

    Li, Guangbing; Zhang, Haohai; Wan, Xueshuai; Yang, Xiaobo; Zhu, Chengpei; Wang, Anqiang; He, Lian; Miao, Ruoyu; Chen, Shuguang; Zhao, Haitao

    2014-01-01

    Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets. PMID:24757675

  15. 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.

  16. The Aquilegia FRUITFULL-like genes play key roles in leaf morphogenesis and inflorescence development.

    PubMed

    Pabón-Mora, Natalia; Sharma, Bharti; Holappa, Lynn D; Kramer, Elena M; Litt, Amy

    2013-04-01

    The APETALA1/FRUITFULL (AP1/FUL) MADS box transcription factors are best known for the role of AP1 in Arabidopsis sepal and petal identity, the canonical A function of the ABC model of flower development. However, this gene lineage underwent multiple duplication events during angiosperm evolution, providing different taxa with unique gene complements. One such duplication correlates with the origin of the core eudicots, and produced the euAP1 and euFUL clades. Together, euAP1 and euFUL genes function in proper floral meristem identity and repression of axillary meristem growth. Independently, euAP1 genes function in floral meristem and sepal identity, whereas euFUL genes control phase transition, cauline leaf growth and fruit development. To investigate the impact of the core eudicot duplication on the functional diversification of this gene lineage, we studied the role of pre-duplication FUL-like genes in columbine (Aquilegia coerulea). Our results show that AqcFL1 genes are broadly expressed in vegetative and reproductive meristems, leaves and flowers. Virus-induced gene silencing of the loci results in plants with increased branching, shorter inflorescences with fewer flowers, and dramatic changes in leaf shape and complexity. However, aqcfl1 plants have normal flowers and fruits. Our results show that, in contrast to characterized AP1/FUL genes, the AqcFL1 loci are either genetically redundant or have been decoupled from the floral genetic program, and play a major role in leaf morphogenesis. We analyze the results in the context of the core eudicot duplication, and discuss the implications of our findings in terms of the genetic regulation of leaf morphogenesis in Aquilegia and other flowering plants. PMID:23294330

  17. Cellular glutathione plays a key role in copper uptake mediated by human copper transporter 1

    PubMed Central

    Maryon, Edward B.; Molloy, Shannon A.

    2013-01-01

    Copper is an essential micronutrient. Following entry via the human copper transporter 1 (hCTR1), copper is delivered to several copper chaperones, which subsequently transfer the metal to specific targets via protein:protein interactions. It is has been assumed, but not demonstrated, that chaperones acquire copper directly from hCTR1. However, some reports have pointed to an intermediary role for glutathione (GSH), an abundant copper-binding tri-peptide. To address the issue of how transported copper is acquired by the copper chaperones in vivo, we measured the initial rate of 64Cu uptake in cells in which the cellular levels of copper chaperones or GSH were substantially depleted or elevated. Knockdown or overexpression of copper chaperones ATOX1, CCS, or both had no effect on the initial rate of 64Cu entry into HEK293 cells having endogenous or overexpressed hCTR1. In contrast, depleting cellular GSH using l-buthionine-sulfoximine (BSO) caused a 50% decrease in the initial rate of 64Cu entry in HEK293 cells and other cell types. This decrease was reversed by washout of BSO or GSH replenishment with a permeable ester. BSO treatment under our experimental conditions had no significant effects on the viability, ATP levels, or metal content of the cells. Attenuated 64Cu uptake in BSO was not due to oxidation of the cysteine in the putative metal-binding motif (HCH) at the intracellular hCTR1 COOH terminus, because a mutant lacking this motif was fully active, and 64Cu uptake was still reduced by BSO treatment. Our data suggest that GSH plays an important role in copper handling at the entry step. PMID:23426973

  18. Autocrine abscisic acid plays a key role in quartz-induced macrophage activation.

    PubMed

    Magnone, Mirko; Sturla, Laura; Jacchetti, Emanuela; Scarfì, Sonia; Bruzzone, Santina; Usai, Cesare; Guida, Lucrezia; Salis, Annalisa; Damonte, Gianluca; De Flora, Antonio; Zocchi, Elena

    2012-03-01

    Inhalation of quartz induces silicosis, a lung disease where alveolar macrophages release inflammatory mediators, including prostaglandin-E(2) (PGE(2)) and tumor necrosis factor α (TNF-α). Here we report the pivotal role of abscisic acid (ABA), a recently discovered human inflammatory hormone, in silica-induced activation of murine RAW264.7 macrophages and of rat alveolar macrophages (AMs). Stimulation of both RAW264.7 cells and AMs with quartz induced a significant increase of ABA release (5- and 10-fold, respectively), compared to untreated cells. In RAW264.7 cells, autocrine ABA released after quartz stimulation sequentially activates the plasma membrane receptor LANCL2 and NADPH oxidase, generating a Ca(2+) influx resulting in NFκ B nuclear translocation and PGE(2) and TNF-α release (3-, 2-, and 3.5-fold increase, respectively, compared to control, unstimulated cells). Quartz-stimulated RAW264.7 cells silenced for LANCL2 or preincubated with a monoclonal antibody against ABA show an almost complete inhibition of NFκ B nuclear translocation and PGE(2) and TNF-α release compared to controls electroporated with a scramble oligonucleotide or preincubated with an unrelated antibody. AMs showed similar early and late ABA-induced responses as RAW264.7 cells. These findings identify ABA and LANCL2 as key mediators in quartz-induced inflammation, providing possible new targets for antisilicotic therapy. PMID:22042223

  19. RTX Toxin Plays a Key Role in Kingella kingae Virulence in an Infant Rat Model

    PubMed Central

    Chang, Dennis W.; Nudell, Yoav A.; Lau, Jenny; Zakharian, Eleonora

    2014-01-01

    Kingella kingae is a human oral bacterium that can cause diseases of the skeletal system in children and infective endocarditis in children and adults. K. kingae produces a toxin of the RTX group, RtxA. To investigate the role of RtxA in disease pathogenesis in vivo, K. kingae strain PYKK081 and its isogenic RtxA-deficient strain KKNB100 were tested for their virulence and pathological consequences upon intraperitoneal injections in 7-day-postnatal (PN 7) rats. At the doses above 8.0 × 106 cells/animal, PYKK081 was able to cause a fatal illness, resulting in rapid weight loss, bacteremia, and abdominal necrotic lesion formation. Significant histopathology was observed in thymus, spleen, and bone marrow. Strain KKNB100 was less toxic to animals. Neither weight loss, bacteremia, nor histopathological changes were evident. Animals injected with KKNB100 exhibited a significantly elevated circulating white blood cell (WBC) count, whereas animals injected with PYKK081 had a WBC count that resembled that of the uninfected control. This observation parallels the subtleties associated with clinical presentation of K. kingae disease in humans and suggests that the toxin contributes to WBC depletion. Thus, our results demonstrate that RtxA is a key K. kingae virulence factor. Furthermore, our findings suggest that the PN 7 rat can serve as a useful model for understanding disease caused by K. kingae and for elucidating diagnostic parameters in human patients. PMID:24664507

  20. Amygdalar glutamatergic neuronal systems play a key role on the hibernating state of hamsters

    PubMed Central

    2011-01-01

    Background Excitatory transmitting mechanisms are proving to play a critical role on neuronal homeostasis conditions of facultative hibernators such as the Syrian golden hamster. Indeed works have shown that the glutamatergic system of the main olfactory brain station (amygdala) is capable of controlling thermoregulatory responses, which are considered vital for the different hibernating states. In the present study the role of amygdalar glutamatergic circuits on non-hibernating (NHIB) and hibernating (HIB) hamsters were assessed on drinking stimuli and subsequently compared to expression variations of some glutamatergic subtype mRNA levels in limbic areas. For this study the two major glutamatergic antagonists and namely that of N-methyl-D-aspartate receptor (NMDAR), 3-(+)-2-carboxypiperazin-4-yl-propyl-1-phosphonate (CPP) plus that of the acid α-amine-3-hydroxy-5-metil-4-isoxazol-propionic receptor (AMPAR) site, cyano-7-nitro-quinoxaline-2,3-dione (CNQX) were infused into the basolateral amygdala nucleus. Attempts were made to establish the type of effects evoked by amygdalar glutamatergic cross-talking processes during drinking stimuli, a response that may corroborate their major role at least during some stages of this physiological activity in hibernators. Results From the behavioral results it appears that the two glutamatergic compounds exerted distinct effects. In the first case local infusion of basolateral complexes (BLA) with NMDAR antagonist caused very great (p < 0.001) drinking rhythms while moderately increased feeding (p < 0.05) responses during arousal with respect to moderately increased drinking levels in euthermics. Conversely, treatment with CNQX did not modify drinking rhythms and so animals spent more time executing exploratory behaviors. These same antagonists accounted for altered glutamatergic transcription activities as displayed by greatly reduced GluR1, NR1 and GluR2 levels in hippocampus, ventromedial hypothalamic nucleus (VMN) and

  1. Fibril growth and seeding capacity play key roles in α-synuclein-mediated apoptotic cell death.

    PubMed

    Mahul-Mellier, A-L; Vercruysse, F; Maco, B; Ait-Bouziad, N; De Roo, M; Muller, D; Lashuel, H A

    2015-12-01

    The role of extracellular α-synuclein (α-syn) in the initiation and the spreading of neurodegeneration in Parkinson's disease (PD) has been studied extensively over the past 10 years. However, the nature of the α-syn toxic species and the molecular mechanisms by which they may contribute to neuronal cell loss remain controversial. In this study, we show that fully characterized recombinant monomeric, fibrillar or stabilized forms of oligomeric α-syn do not trigger significant cell death when added individually to neuroblastoma cell lines. However, a mixture of preformed fibrils (PFFs) with monomeric α-syn becomes toxic under conditions that promote their growth and amyloid formation. In hippocampal primary neurons and ex vivo hippocampal slice cultures, α-syn PFFs are capable of inducing a moderate toxicity over time that is greatly exacerbated upon promoting fibril growth by addition of monomeric α-syn. The causal relationship between α-syn aggregation and cellular toxicity was further investigated by assessing the effect of inhibiting fibrillization on α-syn-induced cell death. Remarkably, our data show that blocking fibril growth by treatment with known pharmacological inhibitor of α-syn fibrillization (Tolcapone) or replacing monomeric α-syn by monomeric β-synuclein in α-syn mixture composition prevent α-syn-induced toxicity in both neuroblastoma cell lines and hippocampal primary neurons. We demonstrate that exogenously added α-syn fibrils bind to the plasma membrane and serve as nucleation sites for the formation of α-syn fibrils and promote the accumulation and internalization of these aggregates that in turn activate both the extrinsic and intrinsic apoptotic cell death pathways in our cellular models. Our results support the hypothesis that ongoing aggregation and fibrillization of extracellular α-syn play central roles in α-syn extracellular toxicity, and suggest that inhibiting fibril growth and seeding capacity constitute a viable

  2. Integrin Receptors Play a Key Role in the Regulation of Hepatic CYP3A.

    PubMed

    Jonsson-Schmunk, Kristina; Wonganan, Piynauch; Choi, Jin Huk; Callahan, Shellie M; Croyle, Maria A

    2016-05-01

    Landmark studies describing the effect of microbial infection on the expression and activity of hepatic CYP3A used bacterial lipopolysaccharide as a model antigen. Our efforts to determine whether these findings were translatable to viral infections led us to observations suggesting that engagement of integrin receptors is key in the initiation of processes responsible for changes in hepatic CYP3A4 during infection and inflammation. Studies outlined in this article were designed to evaluate whether engagement of integrins, receptors commonly used by a variety of microbes to enter cellular targets, is vital in the regulation of CYP3A in the presence and absence of virus infection. Mice infected with a recombinant adenovirus (AdlacZ) experienced a 70% reduction in hepatic CYP3A catalytic activity. Infection with a mutant virus with integrin-binding arginine-glycine-aspartic acid (RGD) sequences deleted from the penton base protein of the virus capsid (AdΔRGD) did not alter CYP3A activity. CYP3A mRNA and protein levels in AdlacZ-treated animals were also suppressed, whereas those of mice given AdΔRGD were not significantly different from uninfected control mice. Silencing of the integrinβ-subunit reverted adenovirus-mediated CYP3A4 suppression in vitro. Silencing of theα-subunit did not. Suppression of integrin subunits had a profound effect on nuclear receptors pregnane X receptor and constitutive androstane receptor, whereas retinoid X receptorαwas largely unaffected. To our knowledge, this is the first time that extracellular receptors, like integrins, have been indicated in the regulation of CYP3A. This finding has several implications owing to the important role of integrins in normal physiologic process and in many disease states. PMID:26868618

  3. The linker connecting the two kringles plays a key role in prothrombin activation

    PubMed Central

    Pozzi, Nicola; Chen, Zhiwei; Pelc, Leslie A.; Shropshire, Daniel B.; Di Cera, Enrico

    2014-01-01

    The zymogen prothrombin is proteolytically converted by factor Xa to the active protease thrombin in a reaction that is accelerated >3,000-fold by cofactor Va. This physiologically important effect is paradigmatic of analogous cofactor-dependent reactions in the coagulation and complement cascades, but its structural determinants remain poorly understood. Prothrombin has three linkers connecting the N-terminal Gla domain to kringle-1 (Lnk1), the two kringles (Lnk2), and kringle-2 to the C-terminal protease domain (Lnk3). Recent developments indicate that the linkers, and particularly Lnk2, confer on the zymogen significant flexibility in solution and enable prothrombin to sample alternative conformations. The role of this flexibility in the context of prothrombin activation was tested with several deletions. Removal of Lnk2 in almost its entirety (ProTΔ146–167) drastically reduces the enhancement of thrombin generation by cofactor Va from >3,000-fold to 60-fold because of a significant increase in the rate of activation in the absence of cofactor. Deletion of Lnk2 mimics the action of cofactor Va and offers insights into how prothrombin is activated at the molecular level. The crystal structure of ProTΔ146–167 reveals a contorted architecture where the domains are not vertically stacked, kringle-1 comes within 9 Å of the protease domain, and the Gla-domain primed for membrane binding comes in contact with kringle-2. These findings broaden our molecular understanding of a key reaction of the blood coagulation cascade where cofactor Va enhances activation of prothrombin by factor Xa by compressing Lnk2 and morphing prothrombin into a conformation similar to the structure of ProTΔ146–167. PMID:24821807

  4. Make Time to Recharge: Growth and Renewal Play Key Roles in Sustaining School Leaders

    ERIC Educational Resources Information Center

    Drago-Severson, Ellie; Blum-DeStefano, Jessica

    2015-01-01

    Being a school leader in any role is hard, gratifying, and a gift of love. While it can be enormously satisfying to serve students, teachers, families, and school communities, leaders need to refill themselves in order to continue giving to others. This article highlights a learning-oriented model of leadership development and capacity building…

  5. Transdiagnostic factors across fibromyalgia and mental disorders: sleep disturbances may play a key role. A clinical review.

    PubMed

    Palagini, Laura; Carmassi, Claudia; Conversano, Ciro; Gesi, Camilla; Bazzichi, Laura; Giacomelli, Camillo; Dell'Osso, Liliana

    2016-01-01

    Sleep disturbances, affective disorders, pain and fatigue are often present in individuals affected by fibromyalgia (FM). The pathophysiology of FM is not yet well understood and, to date, no treatment has been proven to be fully effective in alleviating all symptoms. Adopting a transdiagnostic perspective could thus be useful for clinicians: treatment would target a transdiagnostic process across a range of disturbances, not just a single disorder. The aim of this review is to revise the available literature about the potential role of sleep disturbances as a transdiagnostic process in FM symptomatology and mood or anxiety disorders comorbidity. We are proposing a model under which sleep disturbances can play a central role. Because conditions of sleep loss are related to the activation of the stress system, including the activation of the inflammation system, we propose this mechanism as a key one: it can be shared by mental, sleep disturbances and pain in FM and it may explain, in part, the high levels of comorbidity between them. In this frame-work sleep disturbances may play a key role and be the target of therapeutic strategies across FM symptomatology and mental disorders. PMID:27157399

  6. Kalrn plays key roles within and outside of the nervous system

    PubMed Central

    2012-01-01

    Background The human KALRN gene, which encodes a complex, multifunctional Rho GDP/GTP exchange factor, has been linked to cardiovascular disease, psychiatric disorders and neurodegeneration. Examination of existing Kalrn knockout mouse models has focused only on neuronal phenotypes. However, Kalirin was first identified through its interaction with an enzyme involved in the synthesis and secretion of multiple bioactive peptides, and studies in C.elegans revealed roles for its orthologue in neurosecretion. Results We used a broad array of tests to evaluate the effects of ablating a single exon in the spectrin repeat region of Kalrn (KalSRKO/KO); transcripts encoding Kalrn isoforms containing only the second GEF domain can still be produced from the single remaining functional Kalrn promoter. As expected, KalSRKO/KO mice showed a decrease in anxiety-like behavior and a passive avoidance deficit. No changes were observed in prepulse inhibition of acoustic startle or tests of depression-like behavior. Growth rate, parturition and pituitary secretion of growth hormone and prolactin were deficient in the KalSRKO/KO mice. Based on the fact that a subset of Kalrn isoforms is expressed in mouse skeletal muscle and the observation that muscle function in C.elegans requires its Kalrn orthologue, KalSRKO/KO mice were evaluated in the rotarod and wire hang tests. KalSRKO/KO mice showed a profound decrease in neuromuscular function, with deficits apparent in KalSR+/KO mice; these deficits were not as marked when loss of Kalrn expression was restricted to the nervous system. Pre- and postsynaptic deficits in the neuromuscular junction were observed, along with alterations in sarcomere length. Conclusions Many of the widespread and diverse deficits observed both within and outside of the nervous system when expression of Kalrn is eliminated may reflect its role in secretory granule function and its expression outside of the nervous system. PMID:23116210

  7. Nitric oxide plays a key role in myelination in the developing brain.

    PubMed

    Olivier, Paul; Loron, Gauthier; Fontaine, Romain H; Pansiot, Julien; Dalous, Jérémie; Thi, Hoa Pham; Charriaut-Marlangue, Christiane; Thomas, Jean-Léon; Mercier, Jean-Christophe; Gressens, Pierre; Baud, Olivier

    2010-08-01

    Inhaled nitric oxide (iNO) is one of the most promising therapies used in neonates, but there is little information available about its effect on the developing brain. We explored the effects of both iNO and endogenous NO on developing white matter in rodents. Rat or mouse pups and their mothers were placed in a chamber containing 5 to 20 ppm of NO for 7 days after birth. Neonatal exposure to iNO was associated with a transient increase in central nervous system myelination in rats and C57BL/6 mice without any deleterious effects at low doses (5 ppm) or behavioral consequences in adulthood. Exposure to iNO was associated with a proliferative effect on immature oligodendrocytes and a subsequent promaturational effect. The role of endogenous NO in myelination was investigated in animals treated with the nitric oxides synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) in the neonatal period; this led to protracted myelination defects and subsequent behavioral deficits in adulthood. These effects were reversed by rescuing L-NAME-treated animals with iNO. Thus, we demonstrate considerable effect of both exogenous and endogenous NO on myelination in rodents. These data point to potential new avenues for neuroprotection in human perinatal brain damage. PMID:20613635

  8. Phytochelatins play a key role in arsenic accumulation and tolerance in the aquatic macrophyte Wolffia globosa.

    PubMed

    Zhang, Xin; Uroic, M Kalle; Xie, Wan-Ying; Zhu, Yong-Guan; Chen, Bao-Dong; McGrath, Steve P; Feldmann, Jörg; Zhao, Fang-Jie

    2012-06-01

    The rootless duckweed Wolffia globosa can accumulate and tolerate relatively large amounts of arsenic (As); however, the underlying mechanisms were unknown. W. globosa was exposed to different concentrations of arsenate with or without l-buthionine sulphoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase. Free thiol compounds and As(III)-thiol complexes were identified and quantified using HPLC - high resolution ICP-MS - accurate mass ESI-MS. Without BSO, 74% of the As accumulated in the duckweed was complexed with phytochelatins (PCs), with As(III)-PC(4) and As(III)-PC(3) being the main species. BSO was taken up by the duckweed and partly deaminated. The BSO treatment completely suppressed the synthesis of PCs and the formation of As(III)-PC complexes, and also inhibited the reduction of arsenate to arsenite. BSO markedly decreased both As accumulation and As tolerance in W. globosa. The results demonstrate an important role of PCs in detoxifying As and enabling As accumulation in W. globosa. PMID:22398017

  9. Swimming motility plays a key role in the stochastic dynamics of cell clumping

    NASA Astrophysics Data System (ADS)

    Qi, Xianghong; Nellas, Ricky B.; Byrn, Matthew W.; Russell, Matthew H.; Bible, Amber N.; Alexandre, Gladys; Shen, Tongye

    2013-04-01

    Dynamic cell-to-cell interactions are a prerequisite to many biological processes, including development and biofilm formation. Flagellum induced motility has been shown to modulate the initial cell-cell or cell-surface interaction and to contribute to the emergence of macroscopic patterns. While the role of swimming motility in surface colonization has been analyzed in some detail, a quantitative physical analysis of transient interactions between motile cells is lacking. We examined the Brownian dynamics of swimming cells in a crowded environment using a model of motorized adhesive tandem particles. Focusing on the motility and geometry of an exemplary motile bacterium Azospirillum brasilense, which is capable of transient cell-cell association (clumping), we constructed a physical model with proper parameters for the computer simulation of the clumping dynamics. By modulating mechanical interaction (‘stickiness’) between cells and swimming speed, we investigated how equilibrium and active features affect the clumping dynamics. We found that the modulation of active motion is required for the initial aggregation of cells to occur at a realistic time scale. Slowing down the rotation of flagellar motors (and thus swimming speeds) is correlated to the degree of clumping, which is consistent with the experimental results obtained for A. brasilense.

  10. ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes.

    PubMed

    Voon, Hsiao P J; Hughes, Jim R; Rode, Christina; De La Rosa-Velázquez, Inti A; Jenuwein, Thomas; Feil, Robert; Higgs, Douglas R; Gibbons, Richard J

    2015-04-21

    Histone H3.3 is a replication-independent histone variant, which replaces histones that are turned over throughout the entire cell cycle. H3.3 deposition at euchromatin is dependent on HIRA, whereas ATRX/Daxx deposits H3.3 at pericentric heterochromatin and telomeres. The role of H3.3 at heterochromatic regions is unknown, but mutations in the ATRX/Daxx/H3.3 pathway are linked to aberrant telomere lengthening in certain cancers. In this study, we show that ATRX-dependent deposition of H3.3 is not limited to pericentric heterochromatin and telomeres but also occurs at heterochromatic sites throughout the genome. Notably, ATRX/H3.3 specifically localizes to silenced imprinted alleles in mouse ESCs. ATRX KO cells failed to deposit H3.3 at these sites, leading to loss of the H3K9me3 heterochromatin modification, loss of repression, and aberrant allelic expression. We propose a model whereby ATRX-dependent deposition of H3.3 into heterochromatin is normally required to maintain the memory of silencing at imprinted loci. PMID:25865896

  11. Radial Clearance Found To Play a Key Role in the Performance of Compliant Foil Air Bearings

    NASA Technical Reports Server (NTRS)

    Radil, Kevin C.

    2003-01-01

    Compliant foil air bearings are at the forefront of the Oil-Free turbomachinery revolution, which supports gas turbine engines with hydrodynamic bearings that use air instead of oil as the working fluid. These types of bearings have been around for almost 50 years and have found a home in several commercial applications, such as in air cycle machines, turbocompressors, and microturbines, but are now being aggressively pursued for use in small and midrange aircraft gas turbine engines. Benefits include higher operating speeds and temperatures, lower maintenance costs, and greater reliability. The Oil-Free Turbomachinery team at the NASA Glenn Research Center is working to foster the transition of Oil-Free technology into gas turbine engines by performing in-house experiments on foil air bearings in order to gain a greater insight into their complex operating principles. A research program recently undertaken at Glenn focused on the concept of radial clearance and its influence on bearing performance. The tests were conducted on foil bearings with different radial clearances. As defined for a foil bearing, radial clearance is a measure of the small amount of shaft radial motion that is present from play that exists in the elastic support structure, such as between the top and bump foils and the bump foils and bearing shell (see the drawing). With an insufficient amount of radial clearance, the bearing imparts a high preload on the shaft, which when excessive, can reduce the loadcarrying capability of the bearing. On the other hand, systems using foil bearings with excessive radial clearance may experience rotordynamic instabilities because of low bearing preload. Therefore, without a more thorough understanding of radial clearance, it is difficult to accurately predict the performance of a given bearing design. The test program demonstrated that there is a direct correlation between radial clearance and the performance of foil air bearings. As shown in the graph, an

  12. [Importin-β1 plays a key role in the nucleocytoplasmic transportation process of MARVELD1].

    PubMed

    Wang, Z Y; Shi, M; Li, Y

    2015-01-01

    While MARVEL domain-containing protein 1 (MARVELD1) is widely expressed in normal tissue, its expression is decreased in tumor tissue. Importin-β1 is a kind of nucleocytoplasmic transport protein, which participates in protein transportation between the nucleus and cytoplasm. It has been known that MARVELD1 binds importin-β1. To define the biological functions of the binding between MARVELD1 and importin-β1, confocal laser scanning microscopy was applied to confirm the distribution of MARVELD1 in the cells when importin-β1, is knocked down, and the results show that MARVELD1's concentration is decreased in the nucleus and elevated in the cytoplasm. GST-pull down and western blot were applied to test the binding affinity between the normal importin-β1, and several truncations of MARVELD1, and the binding affinity between the normal MARVELD1 and several truncations of importin-β1. These results show that there exist several binding points between MARVELD1 and importin-β1. Basing on these results one can come to a conclusion that importin-β1 mediates the non-classical nucleocytoplasmic transportation of MARVELD1. It was also found that knockdown of importin-β1, leads to an increase in the total density of MARVELD1. Considering the abnormally reduced expression of MARVELD1 in tumor tissue, the results of this study will help gaining a better understanding of the roles of MARVELD1 in the signal network systems during tumorigenesis in cancer cells. PMID:26107903

  13. Hydrogen Sulfide Plays a Key Role in the Inhibitory Neurotransmission to the Pig Intravesical Ureter

    PubMed Central

    Fernandes, Vítor S.; Ribeiro, Ana S. F.; Martínez, Pilar; López-Oliva, María Elvira; Barahona, María Victoria; Orensanz, Luis M.; Martínez-Sáenz, Ana; Recio, Paz; Benedito, Sara; Bustamante, Salvador; García-Sacristán, Albino; Prieto, Dolores; Hernández, Medardo

    2014-01-01

    According to previous observations nitric oxide (NO), as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S) role in the neurogenic relaxation of the pig intravesical ureter. We have performed western blot and immunohistochemistry to study the expression of the H2S synthesis enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), measurement of enzymatic production of H2S and myographic studies for isometric force recording. Immunohistochemical assays showed a high CSE expression in the intravesical ureter muscular layer, as well as a strong CSE-immunoreactivity within nerve fibres distributed along smooth muscle bundles. CBS expression, however, was not consistently observed. On ureteral strips precontracted with thromboxane A2 analogue U46619, electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked frequency- and concentration-dependent relaxations. CSE inhibition with DL-propargylglycine (PPG) reduced EFS-elicited responses and a combined blockade of both CSE and NO synthase (NOS) with, respectively, PPG and NG-nitro-L-arginine (L-NOARG), greatly reduced such relaxations. Endogenous H2S production rate was reduced by PPG, rescued by addition of GYY4137 and was not changed by L-NOARG. EFS and GYY4137 relaxations were also reduced by capsaicin-sensitive primary afferents (CSPA) desensitization with capsaicin and blockade of ATP-dependent K+ (KATP) channels, transient receptor potential A1 (TRPA1), transient receptor potential vanilloid 1 (TRPV1), vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide (VIP/PACAP) and calcitonin gene-related peptide (CGRP) receptors with glibenclamide, HC030031, AMG9810, PACAP6–38 and CGRP8–37, respectively. These results suggest that H2S, synthesized by CSE, is involved in the inhibitory neurotransmission

  14. Heterologous induction of Ty1 retrotransposition: Reverse transcriptase plays a key role in initiation of the retrotransposition cycle

    SciTech Connect

    Reznik, N.L.; Kidgotko, O.V.; Zolotova, L.I.

    1995-12-01

    A new method was developed to study the mechanism of initiation of the retrotransposition cycle: retrotransposons of Drosophila melanogaster, gypsy, copia, and 17.6 were expressed in yeast under the control of strong yeast promoters. Expression of retrotransposons induced formation of viruslike particles (VLPs) associated with full-length Ty1 RNA and DNA sequences. This phenomenon was termed heterologous induction. When the gene for reverse transcriptase of human immunodeficiency virus (HIV) was expressed in yeast, the same results were obtained. These data allowed us to assume that the excess of active reverse transcriptase plays the key role in induction of transposition. Possible mechanisms of induction of Ty1 transposition by homologous and heterologous elements are discussed. 34 refs., 5 figs.

  15. ADP-glucose pyrophosphorylase gene plays a key role in the quality of corm and yield of cormels in gladiolus.

    PubMed

    Seng, Shanshan; Wu, Jian; Sui, Juanjuan; Wu, Chenyu; Zhong, Xionghui; Liu, Chen; Liu, Chao; Gong, Benhe; Zhang, Fengqin; He, Junna; Yi, Mingfang

    2016-05-20

    Starch is the main storage compound in underground organs like corms. ADP-glucose pyrophosphorylase (AGPase) plays a key role in regulating starch biosynthesis in storage organs and is likely one of the most important determinant of sink strength. Here, we identify an AGPase gene (GhAGPS1) from gladiolus. The highest transcriptional levels of GhAGPS1 were observed in cormels and corms. Transformation of GhAGPS1 into Arabidopsis rescued the phenotype of aps1 mutant. Silencing GhAGPS1 in gladiolus corms by virus-induced gene silencing (VIGS) decreased the transcriptional levels of two genes and starch content. Transmission electron microscopy analyses of leaf and corm sections confirmed that starch biosynthesis was inhibited. Corm weight and cormel number reduced significantly in the silenced plants. Taken together, these results indicate that inhibiting the expression of AGPase gene could impair starch synthesis, which results in the lowered corm quality and cormel yield in gladiolus. PMID:27107698

  16. The diaphanous Gene of Drosophila Interacts Antagonistically with multiple wing hairs and Plays a Key Role in Wing Hair Morphogenesis

    PubMed Central

    Lu, Qiuheng; Adler, Paul N.

    2015-01-01

    The Drosophila wing is covered by an array of distally pointing hairs that has served as a key model system for studying planar cell polarity (PCP). The adult cuticular hairs are formed in the pupae from cell extensions that contain extensive actin filaments and microtubules. The importance of the actin cytoskeleton for hair growth and morphogenesis is clear from the wide range of phenotypes seen in mutations in well-known actin regulators. Formin proteins promote the formation of long actin filaments of the sort thought to be important for hair growth. We report here that the formin encoding diaphanous (dia) gene plays a key role in hair morphogenesis. Both loss of function mutations and the expression of a constitutively active Dia led to cells forming both morphologically abnormal hairs and multiple hairs. The conserved frizzled (fz)/starry night (stan) PCP pathway functions to restrict hair initiation and activation of the cytoskeleton to the distal most part of wing cells. It also ensures the formation of a single hair per cell. Our data suggest that the localized inhibition of Dia activity may be part of this mechanism. We found the expression of constitutively active Dia greatly expands the region for activation of the cytoskeleton and that dia functions antagonistically with multiple wing hairs (mwh), the most downstream member of the fz/stan pathway. Further we established that purified fragments of Dia and Mwh could be co-immunoprecipitated suggesting the genetic interaction could reflect a direct physical interaction. PMID:25730111

  17. gga-miR-375 plays a key role in tumorigenesis post subgroup J Avian Leukosis Virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian leukosis is a neoplastic disease caused in part by subgroup J avian leukosis virus J (ALV-J). Micro ribonucleic acids (miRNAs) play pivotal oncogenic and tumour-suppressor roles in tumour development and progression. However, little is known about the potential role of miRNAs in avian leukosis...

  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. CCN2 plays a key role in extracellular matrix gene expression in severe hypertrophic cardiomyopathy and heart failure.

    PubMed

    Tsoutsman, Tatiana; Wang, Xiaoyu; Garchow, Kendra; Riser, Bruce; Twigg, Stephen; Semsarian, Christopher

    2013-09-01

    Hypertrophic cardiomyopathy (HCM) is the most common inherited primary myocardial disorder. HCM is characterized by interstitial fibrosis and excessive accumulation of extracellular matrix (ECM) proteins. Fibrosis in HCM has been associated with impaired cardiac function and heart failure, and has been considered a key substrate for ventricular arrhythmias and sudden death. The molecular triggers underpinning ECM production are not well established. We have previously developed a double-mutant mouse model of HCM that recapitulates the phenotype seen in humans with multiple mutations, including earlier onset of the disease, progression to a dilated phenotype, severe heart failure and premature mortality. The present study investigated the expression of ECM-encoding genes in severe HCM and heart failure. Significant upregulation of structural Fn1, regulatory Mmp14, Timp1, Serpin3A, SerpinE1, SerpineE2, Tgfβ1, and Tgfβ2; and matricellular Ccn2, Postn, Spp1, Thbs1, Thbs4, and Tnc was evident from the early, pre-phenotype stage. Non-myocytes expressed ECM genes at higher levels than cardiomyocytes in normal and diseased hearts. Synchronous increase of secreted CCN2 and TIMP1 plasma levels and decrease of MMP3 levels were observed in end-stage disease. CCN2 protein expression was increased from early disease in double-mutant hearts and played an important role in ECM responses. It was a powerful modulator of ECM regulatory (Timp1 and SerpinE1) and matricellular protein-encoding (Spp1, Thbs1, Thbs4 and Tnc) gene expression in cardiomyocytes when added exogenously in vitro. Modulation of CCN2 (CTGF, connective tissue growth factor) and associated early ECM changes may represent a new therapeutic target in the treatment and prevention of heart failure in HCM. PMID:23756156

  20. 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,…

  1. Calcineurin Plays Key Roles in the Dimorphic Transition and Virulence of the Human Pathogenic Zygomycete Mucor circinelloides

    PubMed Central

    Lee, Soo Chan; Li, Alicia; Calo, Silvia; Heitman, Joseph

    2013-01-01

    Many pathogenic fungi are dimorphic and switch between yeast and filamentous states. This switch alters host-microbe interactions and is critical for pathogenicity. However, in zygomycetes, whether dimorphism contributes to virulence is a central unanswered question. The pathogenic zygomycete Mucor circinelloides exhibits hyphal growth in aerobic conditions but switches to multi-budded yeast growth under anaerobic/high CO2 conditions. We found that in the presence of the calcineurin inhibitor FK506, Mucor exhibits exclusively multi-budded yeast growth. We also found that M. circinelloides encodes three calcineurin catalytic A subunits (CnaA, CnaB, and CnaC) and one calcineurin regulatory B subunit (CnbR). Mutations in the latch region of CnbR and in the FKBP12-FK506 binding domain of CnaA result in hyphal growth of Mucor in the presence of FK506. Disruption of the cnbR gene encoding the sole calcineurin B subunit necessary for calcineurin activity yielded mutants locked in permanent yeast phase growth. These findings reveal that the calcineurin pathway plays key roles in the dimorphic transition from yeast to hyphae. The cnbR yeast-locked mutants are less virulent than the wild-type strain in a heterologous host system, providing evidence that hyphae or the yeast-hyphal transition are linked to virulence. Protein kinase A activity (PKA) is elevated during yeast growth under anaerobic conditions, in the presence of FK506, or in the yeast-locked cnbR mutants, suggesting a novel connection between PKA and calcineurin. cnaA mutants lacking the CnaA catalytic subunit are hypersensitive to calcineurin inhibitors, display a hyphal polarity defect, and produce a mixture of yeast and hyphae in aerobic culture. The cnaA mutants also produce spores that are larger than wild-type, and spore size is correlated with virulence potential. Our results demonstrate that the calcineurin pathway orchestrates the yeast-hyphal and spore size dimorphic transitions that contribute to

  2. Subcellular Relocalization and Positive Selection Play Key Roles in the Retention of Duplicate Genes of Populus Class III Peroxidase Family.

    PubMed

    Ren, Lin-Ling; Liu, Yan-Jing; Liu, Hai-Jing; Qian, Ting-Ting; Qi, Li-Wang; Wang, Xiao-Ru; Zeng, Qing-Yin

    2014-06-16

    Gene duplication is the primary source of new genes and novel functions. Over the course of evolution, many duplicate genes lose their function and are eventually removed by deletion. However, some duplicates have persisted and evolved diverse functions. A particular challenge is to understand how this diversity arises and whether positive selection plays a role. In this study, we reconstructed the evolutionary history of the class III peroxidase (PRX) genes from the Populus trichocarpa genome. PRXs are plant-specific enzymes that play important roles in cell wall metabolism and in response to biotic and abiotic stresses. We found that two large tandem-arrayed clusters of PRXs evolved from an ancestral cell wall type PRX to vacuole type, followed by tandem duplications and subsequent functional specification. Substitution models identified seven positively selected sites in the vacuole PRXs. These positively selected sites showed significant effects on the biochemical functions of the enzymes. We also found that positive selection acts more frequently on residues adjacent to, rather than directly at, a critical active site of the enzyme, and on flexible regions rather than on rigid structural elements of the protein. Our study provides new insights into the adaptive molecular evolution of plant enzyme families. PMID:24934172

  3. Mesdc2 plays a key role in cell-surface expression of Lrp4 and postsynaptic specialization in myotubes.

    PubMed

    Hoshi, Taisuke; Tezuka, Tohru; Yokoyama, Kazumasa; Iemura, Shun-ichiro; Natsume, Tohru; Yamanashi, Yuji

    2013-11-29

    Low-density lipoprotein receptor-related protein 4 (Lrp4) is essential for pre- and post-synaptic specialization at the neuromuscular junction (NMJ), an indispensable synapse between a motor nerve and skeletal muscle. Muscle-specific receptor tyrosine kinase MuSK must form a complex with Lrp4 to organize postsynaptic specialization at NMJs. Here, we show that the chaperon Mesdc2 binds to the intracellular form of Lrp4 and promotes its glycosylation and cell-surface expression. Furthermore, knockdown of Mesdc2 suppresses cell-surface expression of Lrp4, activation of MuSK, and postsynaptic specialization in muscle cells. These results suggest that Mesdc2 plays an essential role in NMJ formation by promoting Lrp4 maturation. PMID:24140340

  4. Disturbance of oligodendrocyte function plays a key role in the pathogenesis of schizophrenia and major depressive disorder.

    PubMed

    Miyata, Shingo; Hattori, Tsuyoshi; Shimizu, Shoko; Ito, Akira; Tohyama, Masaya

    2015-01-01

    The major psychiatric disorders such as schizophrenia (SZ) and major depressive disorder (MDD) are thought to be multifactorial diseases related to both genetic and environmental factors. However, the genes responsible and the molecular mechanisms underlying the pathogenesis of SZ and MDD remain unclear. We previously reported that abnormalities of disrupted-in-Schizophrenia-1 (DISC1) and DISC1 binding zinc finger (DBZ) might cause major psychiatric disorders such as SZ. Interestingly, both DISC and DBZ have been further detected in oligodendrocytes and implicated in regulating oligodendrocyte differentiation. DISC1 negatively regulates the differentiation of oligodendrocytes, whereas DBZ plays a positive regulatory role in oligodendrocyte differentiation. We have reported that repeated stressful events, one of the major risk factors of MDD, can induce sustained upregulation of plasma corticosterone levels and serum/glucocorticoid regulated kinase 1 (Sgk1) mRNA expression in oligodendrocytes. Repeated stressful events can also activate the SGK1 cascade and cause excess arborization of oligodendrocyte processes, which is thought to be related to depressive-like symptoms. In this review, we discuss the expression of DISC1, DBZ, and SGK1 in oligodendrocytes, their roles in the regulation of oligodendrocyte function, possible interactions of DISC1 and DBZ in relation to SZ, and the activation of the SGK1 signaling cascade in relation to MDD. PMID:25705664

  5. Gga-miR-101-3p Plays a Key Role in Mycoplasma gallisepticum (HS Strain) Infection of Chicken.

    PubMed

    Chen, Jiao; Wang, Zaiwei; Bi, Dingren; Hou, Yue; Zhao, Yabo; Sun, Jianjun; Peng, Xiuli

    2015-01-01

    Mycoplasma gallisepticum (MG), one of the most pathogenic Mycoplasma, has caused tremendous economic loss in the poultry industry. Recently, increasing evidence has suggested that micro ribonucleic acids (miRNAs) are involved in microbial pathogenesis. However, little is known about potential roles of miRNAs in MG infection of chicken. In the present study, using miRNA Solexa sequencing we have found that gga-miR-101-3p was up-regulated in the lungs of MG-infected chicken embryos. Moreover, gga-miR-101-3p regulated expression of the host enhancer of zeste homolog 2 (EZH2) through binding to the 3' un-translated region (3'-UTR) of EZH2 gene. Over-expression of gga-miR-101-3p significantly inhibited EZH2 expression and hence inhibited proliferation of chicken embryonic fibroblast (DF-1 cells) by blocking the G1-to-S phase transition. Similar results were obtained in MG-infected chicken embryos and DF-1 cells, where gga-miR-101-3p was significantly up-regulated, while EZH2 was significantly down-regulated. This study reveals that gga-miR-101-3p plays an important role in MG infection through regulation of EZH2 expression and provides a new insight into the mechanisms of MG pathogenesis. PMID:26633386

  6. gga-miR-101-3p Plays a Key Role in Mycoplasma gallisepticum (HS Strain) Infection of Chicken

    PubMed Central

    Chen, Jiao; Wang, Zaiwei; Bi, Dingren; Hou, Yue; Zhao, Yabo; Sun, Jianjun; Peng, Xiuli

    2015-01-01

    Mycoplasma gallisepticum (MG), one of the most pathogenic Mycoplasma, has caused tremendous economic loss in the poultry industry. Recently, increasing evidence has suggested that micro ribonucleic acids (miRNAs) are involved in microbial pathogenesis. However, little is known about potential roles of miRNAs in MG infection of chicken. In the present study, using miRNA Solexa sequencing we have found that gga-miR-101-3p was up-regulated in the lungs of MG-infected chicken embryos. Moreover, gga-miR-101-3p regulated expression of the host enhancer of zeste homolog 2 (EZH2) through binding to the 3’ un-translated region (3’-UTR) of EZH2 gene. Over-expression of gga-miR-101-3p significantly inhibited EZH2 expression and hence inhibited proliferation of chicken embryonic fibroblast (DF-1 cells) by blocking the G1-to-S phase transition. Similar results were obtained in MG-infected chicken embryos and DF-1 cells, where gga-miR-101-3p was significantly up-regulated, while EZH2 was significantly down-regulated. This study reveals that gga-miR-101-3p plays an important role in MG infection through regulation of EZH2 expression and provides a new insight into the mechanisms of MG pathogenesis. PMID:26633386

  7. Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility

    SciTech Connect

    Lu, Renquan; Sun, Xinghui; Xiao, Ran; Zhou, Lei; Gao, Xiang; Guo, Lin

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer We generated stable transduced HE4 overexpression and knockdown cells. Black-Right-Pointing-Pointer HE4 was associated with EOC cell adhesion and motility. Black-Right-Pointing-Pointer HE4 might have some effects on activation of EGFR-MAPK signaling pathway. Black-Right-Pointing-Pointer HE4 play an important role in EOC tumorigenicity. -- Abstract: Human epididymis protein 4 (HE4) is a novel and specific biomarker for epithelial ovarian cancer (EOC). We previously demonstrated that serum HE4 levels were significantly elevated in the majority of EOC patients but not in subjects with benign disease or healthy controls. However, the precise mechanism of HE4 protein function is unknown. In this study, we generated HE4-overexpressing SKOV3 cells and found that stably transduced cells promoted cell adhesion and migration. Knockdown of HE4 expression was achieved by stable transfection of SKOV3 cells with a construct encoding a short hairpin DNA directed against the HE4 gene. Correspondingly, the proliferation and spreading ability of HE4-expressed cells were inhibited by HE4 suppression. Mechanistically, impaired EGFR and Erk1/2 phosphorylation were observed in cells with HE4 knockdown. The phosphorylation was restored when the knockdown cells were cultured in conditioned medium containing HE4. Moreover, in vivo tumorigenicity showed that HE4 suppression markedly inhibited the growth of tumors. This suggests that expression of HE4 is associated with cancer cell adhesion, migration and tumor growth, which can be related to its effects on the EGFR-MAPK signaling pathway. Our results provide evidence of the cellular and molecular mechanisms that may underlie the motility-promoting role of HE4 in EOC progression. The role of HE4 as a target for gene-based therapy might be considered in future studies.

  8. Endosomal MR1 Trafficking Plays a Key Role in Presentation of Mycobacterium tuberculosis Ligands to MAIT Cells

    PubMed Central

    Burr, Ansen; Grant, Wilmon F.; Canfield, Elizabeth T.; Sorensen, Michelle L.; Moita, Luis F.; Lewinsohn, David M.

    2016-01-01

    Mucosal-Associated Invariant T (MAIT) cells, present in high frequency in airway and other mucosal tissues, have Th1 effector capacity positioning them to play a critical role in the early immune response to intracellular pathogens, including Mycobacterium tuberculosis (Mtb). MR1 is a highly conserved Class I-like molecule that presents vitamin B metabolites to MAIT cells. The mechanisms for loading these ubiquitous small molecules are likely to be tightly regulated to prevent inappropriate MAIT cell activation. To define the intracellular localization of MR1, we analyzed the distribution of an MR1-GFP fusion protein in antigen presenting cells. We found that MR1 localized to endosomes and was translocated to the cell surface upon addition of 6-formyl pterin (6-FP). To understand the mechanisms by which MR1 antigens are presented, we used a lentiviral shRNA screen to identify trafficking molecules that are required for the presentation of Mtb antigen to HLA-diverse T cells. We identified Stx18, VAMP4, and Rab6 as trafficking molecules regulating MR1-dependent MAIT cell recognition of Mtb-infected cells. Stx18 but not VAMP4 or Rab6 knockdown also resulted in decreased 6-FP-dependent surface translocation of MR1 suggesting distinct pathways for loading of exogenous ligands and intracellular mycobacterially-derived ligands. We postulate that endosome-mediated trafficking of MR1 allows for selective sampling of the intracellular environment. PMID:27031111

  9. Endosomal MR1 Trafficking Plays a Key Role in Presentation of Mycobacterium tuberculosis Ligands to MAIT Cells.

    PubMed

    Harriff, Melanie J; Karamooz, Elham; Burr, Ansen; Grant, Wilmon F; Canfield, Elizabeth T; Sorensen, Michelle L; Moita, Luis F; Lewinsohn, David M

    2016-03-01

    Mucosal-Associated Invariant T (MAIT) cells, present in high frequency in airway and other mucosal tissues, have Th1 effector capacity positioning them to play a critical role in the early immune response to intracellular pathogens, including Mycobacterium tuberculosis (Mtb). MR1 is a highly conserved Class I-like molecule that presents vitamin B metabolites to MAIT cells. The mechanisms for loading these ubiquitous small molecules are likely to be tightly regulated to prevent inappropriate MAIT cell activation. To define the intracellular localization of MR1, we analyzed the distribution of an MR1-GFP fusion protein in antigen presenting cells. We found that MR1 localized to endosomes and was translocated to the cell surface upon addition of 6-formyl pterin (6-FP). To understand the mechanisms by which MR1 antigens are presented, we used a lentiviral shRNA screen to identify trafficking molecules that are required for the presentation of Mtb antigen to HLA-diverse T cells. We identified Stx18, VAMP4, and Rab6 as trafficking molecules regulating MR1-dependent MAIT cell recognition of Mtb-infected cells. Stx18 but not VAMP4 or Rab6 knockdown also resulted in decreased 6-FP-dependent surface translocation of MR1 suggesting distinct pathways for loading of exogenous ligands and intracellular mycobacterially-derived ligands. We postulate that endosome-mediated trafficking of MR1 allows for selective sampling of the intracellular environment. PMID:27031111

  10. Olanzapine-induced weight gain plays a key role in the potential cardiovascular risk: evidence from heart rate variability analysis

    PubMed Central

    Wang, Jun; Liu, Yan-song; Zhu, Wen-xian; Zhang, Fu-quan; Zhou, Zhen-he

    2014-01-01

    Patients with schizophrenia have a higher risk for cardiovascular disease (CVD) than the general population. Research has suggested that autonomic imbalance is a common pathway to increased morbidity and mortality for CVD. Heart rate variability (HRV) analysis is a non-invasive method that assesses autonomic imbalance, and low HRV is correlated with high cardiovascular risk. Olanzapine, a widely used antipsychotic drug, is considered to have good cardiac safety because of not causing significant corrected QT-interval (QTc) prolongation; however, it is still unclear whether olanzapine affects HRV. We recruited 83 patients with schizophrenia who were medication-free for at least 1 month and tested their HRV at the baseline and 4 weeks after treatment with olanzapine. We found that patients who had substantial weight gain (EWG) manifested significantly lower HRV than those who had non-substantial weight gain (NWG) and that HRV decrease was positively correlated to an increase in body mass index (BMI) and weight gain. Our results indicate that olanzapine-induced weight gain may play an important role in its potential cardiovascular risk. Since olanzapine has a very high potential for weight gain compared with other antipsychotics, further research is needed to explore its cardiovascular safety profile, specifically long-term cardiac safety. PMID:25487560

  11. The amide linker in nonpeptide neurotensin receptor ligands plays a key role in calcium signaling at the neurotensin receptor type 2.

    PubMed

    Thomas, James B; Giddings, Angela M; Olepu, Srinivas; Wiethe, Robert W; Warner, Keith R; Sarret, Philippe; Longpre, Jean-Michel; Runyon, Scott P; Gilmour, Brian P

    2015-01-01

    Compounds acting via the GPCR neurotensin receptor type 2 (NTS2) display analgesia in relevant preclinical models. The amide bond in nonpeptide NTS1 antagonists plays a central role in receptor recognition and molecular conformation. Using NTS2 FLIPR and binding assays, we found that it is also a key molecular structure for binding and calcium mobilization at NTS2. We found that reversed amides display a shift from agonist to antagonist activity and provided examples of the first competitive nonpeptide antagonists observed in the NTS2 FLIPR assay. These compounds will be valuable tools for determining the role of calcium signaling in vitro to NTS2 mediated analgesia. PMID:25881832

  12. Cooperative hydration effect causes thermal unfolding of proteins and water activity plays a key role in protein stability in solutions.

    PubMed

    Miyawaki, Osato; Dozen, Michiko; Hirota, Kaede

    2016-08-01

    The protein unfolding process observed in a narrow temperature range was clearly explained by evaluating the small difference in the enthalpy of hydrogen-bonding between amino acid residues and the hydration of amino acid residue separately. In aqueous solutions, the effect of cosolute on the protein stability is primarily dependent on water activity, aw, the role of which has been long neglected in the literature. The effect of aw on protein stability works as a power law so that a small change in aw is amplified substantially through the cooperative hydration effect. In the present approach, the role of hydrophobic interaction stands behind. This affects protein stability indirectly through the change in solution structure caused by the existence of cosolute. PMID:26896315

  13. Biosynthesis of the antimetabolite 6-thioguanine in Erwinia amylovora plays a key role in fire blight pathogenesis.

    PubMed

    Coyne, Sébastien; Chizzali, Cornelia; Khalil, Mohammed N A; Litomska, Agnieszka; Richter, Klaus; Beerhues, Ludger; Hertweck, Christian

    2013-09-27

    Sulfur for fire: The molecular basis for the biosynthesis of the antimetabolite 6-thioguanine (6TG) was unveiled in Erwinia amylovora, the causative agent of fire blight. Bioinformatics, heterologous pathway reconstitution in E. coli, and mutational analyses indicate that the protein YcfA mediates guanine thionation in analogy to 2-thiouridylase. Assays in planta and in cell cultures reveal for the first time a crucial role of 6TG in fire blight pathogenesis. PMID:24038828

  14. Nutritionists in industry can play a key role in helping to achieve Health of the Nation targets for nutrition.

    PubMed

    Kirk, T R; de Looy, A; Fletcher, R; Ruxton, C H

    2007-06-01

    Nutritionists working in food manufacturing and retailing are potentially in a more powerful position than any other professional group to contribute towards achieving the national targets for nutrition and the reduction of nutrition-related diseases, set out in The Health of the Nation (DoH, 1992) and in Scotland's Health, A Challenge to Us All (Scottish Office, 1993). The present paper sets out the details of this argument. First, a review is given of the functions and types of activities carried out by nutritionists in industry. Then a number of key practical ways in which nutritionists, through their activities and functions, can help towards achieving national targets for nutrition and nutrition-related diseases are described. Finally, suggestions are made about the knowledge, skills, and personal attributes needed by nutritionists who intend making successful careers in industry and who wish, at the same time, to contribute towards improving the health of the nation. PMID:17539871

  15. Sucrose in Cyanobacteria: From a Salt-Response Molecule to Play a Key Role in Nitrogen Fixation

    PubMed Central

    Kolman, María A.; Nishi, Carolina N.; Perez-Cenci, Macarena; Salerno, Graciela L.

    2015-01-01

    In the biosphere, sucrose is mainly synthesized in oxygenic photosynthetic organisms, such as cyanobacteria, green algae and land plants, as part of the carbon dioxide assimilation pathway. Even though its central position in the functional biology of plants is well documented, much less is known about the role of sucrose in cyanobacteria. In those prokaryotes, sucrose accumulation has been associated with salt acclimation, and considered as a compatible solute in low-salt tolerant strains. In the last years, functional characterizations of sucrose metabolizing enzymes, metabolic control analysis, cellular localization of gene expressions, and reverse genetic experiments have revealed that sucrose metabolism is crucial in the diazotrophic growth of heterocystic strains, and besides, that it can be connected to glycogen synthesis. This article briefly summarizes the current state of knowledge of sucrose physiological functions in modern cyanobacteria and how they might have evolved taking into account the phylogenetic analyses of sucrose enzymes. PMID:25569239

  16. Lateral Gene Transfer and Gene Duplication Played a Key Role in the Evolution of Mastigamoeba balamuthi Hydrogenosomes

    PubMed Central

    Nývltová, Eva; Stairs, Courtney W.; Hrdý, Ivan; Rídl, Jakub; Mach, Jan; Pačes, Jan; Roger, Andrew J.; Tachezy, Jan

    2015-01-01

    Lateral gene transfer (LGT) is an important mechanism of evolution for protists adapting to oxygen-poor environments. Specifically, modifications of energy metabolism in anaerobic forms of mitochondria (e.g., hydrogenosomes) are likely to have been associated with gene transfer from prokaryotes. An interesting question is whether the products of transferred genes were directly targeted into the ancestral organelle or initially operated in the cytosol and subsequently acquired organelle-targeting sequences. Here, we identified key enzymes of hydrogenosomal metabolism in the free-living anaerobic amoebozoan Mastigamoeba balamuthi and analyzed their cellular localizations, enzymatic activities, and evolutionary histories. Additionally, we characterized 1) several canonical mitochondrial components including respiratory complex II and the glycine cleavage system, 2) enzymes associated with anaerobic energy metabolism, including an unusual D-lactate dehydrogenase and acetyl CoA synthase, and 3) a sulfate activation pathway. Intriguingly, components of anaerobic energy metabolism are present in at least two gene copies. For each component, one copy possesses an mitochondrial targeting sequence (MTS), whereas the other lacks an MTS, yielding parallel cytosolic and hydrogenosomal extended glycolysis pathways. Experimentally, we confirmed that the organelle targeting of several proteins is fully dependent on the MTS. Phylogenetic analysis of all extended glycolysis components suggested that these components were acquired by LGT. We propose that the transformation from an ancestral organelle to a hydrogenosome in the M. balamuthi lineage involved the lateral acquisition of genes encoding extended glycolysis enzymes that initially operated in the cytosol and that established a parallel hydrogenosomal pathway after gene duplication and MTS acquisition. PMID:25573905

  17. Phospho-Bcl-xL(Ser62) plays a key role at DNA damage-induced G2 checkpoint

    PubMed Central

    Wang, Jianfang; Beauchemin, Myriam; Bertrand, Richard

    2012-01-01

    Accumulating evidence suggests that Bcl-xL, an anti-apoptotic member of the Bcl-2 family, also functions in cell cycle progression and cell cycle checkpoints. Analysis of a series of phosphorylation site mutants reveals that cells expressing Bcl-xL(Ser62Ala) mutant are less stable at the G2 checkpoint and enter mitosis more rapidly than cells expressing wild-type Bcl-xL or Bcl-xL phosphorylation site mutants, including Thr41Ala, Ser43Ala, Thr47Ala, Ser56Ala and Thr115Ala. Analysis of the dynamic phosphorylation and location of phospho-Bcl-xL(Ser62) in unperturbed, synchronized cells and during DNA damage-induced G2 arrest discloses that a pool of phospho-Bcl-xL(Ser62) accumulates into nucleolar structures in etoposide-exposed cells during G2 arrest. In a series of in vitro kinase assays, pharmacological inhibitors and specific siRNAs experiments, we found that Polo kinase 1 and MAPK9/JNK2 are major protein kinases involved in Bcl-xL(Ser62) phosphorylation and accumulation into nucleolar structures during the G2 checkpoint. In nucleoli, phospho-Bcl-xL(Ser62) binds to and co-localizes with Cdk1(cdc2), the key cyclin-dependent kinase required for entry into mitosis. These data indicate that during G2 checkpoint, phospho-Bcl-xL(Ser62) stabilizes G2 arrest by timely trapping of Cdk1(cdc2) in nucleolar structures to slow mitotic entry. It also highlights that DNA damage affects the dynamic composition of the nucleolus, which now emerges as a piece of the DNA damage response. PMID:22617334

  18. The Sigma Factor AlgU Plays a Key Role in Formation of Robust Biofilms by Nonmucoid Pseudomonas aeruginosa▿

    PubMed Central

    Bazire, Alexis; Shioya, Kouki; Soum-Soutéra, Emmanuelle; Bouffartigues, Emeline; Ryder, Cynthia; Guentas-Dombrowsky, Linda; Hémery, Gaëlle; Linossier, Isabelle; Chevalier, Sylvie; Wozniak, Daniel J.; Lesouhaitier, Olivier; Dufour, Alain

    2010-01-01

    The extracytoplasmic function sigma factor AlgU of Pseudomonas aeruginosa is responsible for alginate overproduction, leading to mucoidy and chronic infections of cystic fibrosis patients. We investigated here the role of AlgU in the formation of nonmucoid biofilms. The algU mutant of P. aeruginosa PAO1 (PAOU) showed a dramatic impairment in biofilm formation under dynamic conditions. PAOU was defective both in cell attachment to glass and in development of robust, shear-resistant biofilms. This was explained by an impaired production of extracellular matrix, specifically of the exopolysaccharide Psl, as revealed by microscopy and enzyme-linked immunosorbent assay. Complementing the algU mutation with a plasmid-borne algU gene restored wild-type phenotypes. Compared with that in PAO1, expression of the psl operon was reduced in the PAOU strain, and the biofilm formation ability of this strain was partially restored by inducing the transcription of the psl operon. Furthermore, expression of the lectin-encoding lecA and lecB genes was reduced in the PAOU strain. In agreement with the requirement of LecB for type IV pilus biogenesis, PAOU displayed impaired twitching motility. Collectively, these genetic downregulation events explain the biofilm formation defect of the PAOU mutant. Promoter mapping indicated that AlgU is probably not directly responsible for transcription of the psl operon and the lec genes, but AlgU is involved in the expression of the ppyR gene, whose product was reported to positively control psl expression. Expressing the ppyR gene in PAOU partially restored the formation of robust biofilms. PMID:20348252

  19. Root hairs play a key role in the endophytic colonization of olive roots by Pseudomonas spp. with biocontrol activity.

    PubMed

    Prieto, Pilar; Schilirò, Elisabetta; Maldonado-González, María Mercedes; Valderrama, Raquel; Barroso-Albarracín, Juan Bautista; Mercado-Blanco, Jesús

    2011-08-01

    The use of indigenous bacterial root endophytes with biocontrol activity against soil-borne phytopathogens is an environmentally-friendly and ecologically-efficient action within an integrated disease management framework. The earliest steps of olive root colonization by Pseudomonas fluorescens PICF7 and Pseudomonas putida PICP2, effective biocontrol agents (BCAs) against Verticillium wilt of olive (Olea europaea L.) caused by the fungus Verticillium dahliae Kleb., are here described. A gnotobiotic study system using in vitro propagated olive plants, differential fluorescent-protein tagging of bacteria, and confocal laser scanning microscopy analysis have been successfully used to examine olive roots-Pseudomonas spp. interactions at the single-cell level. In vivo simultaneous visualization of PICF7 and PICP2 cells on/in root tissues enabled to discard competition between the two bacterial strains during root colonization. Results demonstrated that both BCAs are able to endophytically colonized olive root tissues. Moreover, results suggest a pivotal role of root hairs in root colonization by both biocontrol Pseudomonas spp. However, colonization of root hairs appeared to be a highly specific event, and only a very low number of root hairs were effectively colonized by introduced bacteria. Strains PICF7 and PICP2 can simultaneously colonize the same root hair, demonstrating that early colonization of a given root hair by one strain did not hinder subsequent attachment and penetration by the other. Since many environmental factors can affect the number, anatomy, development, and physiology of root hairs, colonization competence and biocontrol effectiveness of BCAs may be greatly influenced by root hair's fitness. Finally, the in vitro study system here reported has shown to be a suitable tool to investigate colonization processes of woody plant roots by microorganisms with biocontrol potential. PMID:21347721

  20. Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson's Disease.

    PubMed

    Xu, Qi; Kanthasamy, Anumantha G; Jin, Huajun; Reddy, Manju B

    2016-01-01

    Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson's disease (PD). However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA) induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P < 0.0001) upregulated ferroportin 1 expression and significantly (P < 0.05) decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P < 0.05) and DNA fragmentation by 29% (P = 0.086) and increased cell viability by 22% (P < 0.05). In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P < 0.05) and intracellular iron by 28% (P < 0.01), indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1. PMID:27298749

  1. Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson's Disease

    PubMed Central

    Xu, Qi; Kanthasamy, Anumantha G.; Jin, Huajun; Reddy, Manju B.

    2016-01-01

    Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson's disease (PD). However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA) induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P < 0.0001) upregulated ferroportin 1 expression and significantly (P < 0.05) decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P < 0.05) and DNA fragmentation by 29% (P = 0.086) and increased cell viability by 22% (P < 0.05). In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P < 0.05) and intracellular iron by 28% (P < 0.01), indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1. PMID:27298749

  2. NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure.

    PubMed

    Chen, Liuji; Na, Ren; Boldt, Erin; Ran, Qitao

    2015-09-01

    Exposure to environmental toxins such as pesticides is implicated in increasing Alzheimer's disease risk. In this study, we investigated the long-term effects of paraquat exposure on cognition of Alzheimer's disease animal model APP/PS1 mice and wild-type (WT) mice. Our results showed that APP/PS1 mice had exacerbated cognition impairment and elevated Aβ levels at 5 months after paraquat exposure, and that WT mice had cognition impairment at 5 and 16 months after paraquat exposure. In addition, increased mitochondrial oxidative stress and augmented brain inflammation were observed in both paraquat-exposed APP/PS1 mice and WT mice. Interestingly, activation of NLRP3 inflammasome, which triggers inflammation in response to mitochondrial stress, was enhanced in paraquat-exposed mice. Moreover, transgenic mice overexpressing Prdx3, a key enzyme in detoxifying mitochondrial H2O2, had suppressed NLRP3 inflammasome activation, reduced brain inflammation, and attenuated cognition impairment after paraquat exposure. Together, our results indicate that NLRP3 inflammasome activation induced by mitochondrial reactive oxygen species plays a key role in mediating paraquat-induced long-term cognition decline by elevating brain inflammation. PMID:26119225

  3. The MqsRA Toxin-Antitoxin System from Xylella fastidiosa Plays a Key Role in Bacterial Fitness, Pathogenicity, and Persister Cell Formation.

    PubMed

    Merfa, Marcus V; Niza, Bárbara; Takita, Marco A; De Souza, Alessandra A

    2016-01-01

    Through the formation of persister cells, bacteria exhibit tolerance to multidrug and other environmental stresses without undergoing genetic changes. The toxin-antitoxin (TA) systems are involved in the formation of persister cells because they are able to induce cell dormancy. Among the TA systems, the MqsRA system has been observed to be highly induced in persister cells of Xylella fastidiosa (causal agent of citrus variegated chlorosis-CVC) activated by copper stress, and has been described in Escherichia coli as related to the formation of persister cells and biofilms. Thus, we evaluated the role of this TA system in X. fastidiosa by overexpressing the MqsR toxin, and verified that the toxin positively regulated biofilm formation and negatively cell movement, resulting in reduced pathogenicity in citrus plants. The overexpression of MqsR also increased the formation of persister cells under copper stress. Analysis of the gene and protein expression showed that this system likely has an autoregulation mechanism to express the toxin and antitoxin in the most beneficial ratio for the cell to oppose stress. Our results suggest that this TA system plays a key role in the adaptation and survival of X. fastidiosa and reveal new insights into the physiology of phytopathogen-host interactions. PMID:27375608

  4. The MqsRA Toxin-Antitoxin System from Xylella fastidiosa Plays a Key Role in Bacterial Fitness, Pathogenicity, and Persister Cell Formation

    PubMed Central

    Merfa, Marcus V.; Niza, Bárbara; Takita, Marco A.; De Souza, Alessandra A.

    2016-01-01

    Through the formation of persister cells, bacteria exhibit tolerance to multidrug and other environmental stresses without undergoing genetic changes. The toxin-antitoxin (TA) systems are involved in the formation of persister cells because they are able to induce cell dormancy. Among the TA systems, the MqsRA system has been observed to be highly induced in persister cells of Xylella fastidiosa (causal agent of citrus variegated chlorosis—CVC) activated by copper stress, and has been described in Escherichia coli as related to the formation of persister cells and biofilms. Thus, we evaluated the role of this TA system in X. fastidiosa by overexpressing the MqsR toxin, and verified that the toxin positively regulated biofilm formation and negatively cell movement, resulting in reduced pathogenicity in citrus plants. The overexpression of MqsR also increased the formation of persister cells under copper stress. Analysis of the gene and protein expression showed that this system likely has an autoregulation mechanism to express the toxin and antitoxin in the most beneficial ratio for the cell to oppose stress. Our results suggest that this TA system plays a key role in the adaptation and survival of X. fastidiosa and reveal new insights into the physiology of phytopathogen-host interactions. PMID:27375608

  5. CX3CL1/CX3CR1 Axis Plays a Key Role in Ischemia-Induced Oligodendrocyte Injury via p38MAPK Signaling Pathway.

    PubMed

    Wu, Xiao-Mei; Liu, Yong; Qian, Zhong-Ming; Luo, Qian-Qian; Ke, Ya

    2016-08-01

    Based on current knowledge on the role of the CX3CL1/CX3CR1 axis in the regulation of microglial activation and on the involvement of activated microglia in damaging oligodendrocytes, we hypothesized that CX3CL1/CX3CR1 axis is associated with the development of ischemic oligodendrocyte and white matter injury. We investigated the effects of CX3CL1, CX3CR1 shRNA, and p38MAPK inhibitor on the apoptosis, proliferation, and myelin proteolipid protein (PLP) expression in oligodendrocytes in co-cultures with BV2 microglia under ischemia. We demonstrated that CX3CL1 markedly increased the numbers of apoptotic oligodendrocytes, decreased PLP expression in oligodendrocytes, and inhibited the increased proliferation of oligodendrocytes induced by ischemia in co-cultures. All these effects of CX3CL1 were suppressed by pre-treatment of BV2 microglia with CX3CR1 shRNA to silence CX3CR1 expression or SB203580 to inhibit p38MAPK pathway. Our findings support that CX3CL1/CX3CR1 axis plays a key role in the development of ischemia-induced oligodendrocyte injury via p38MAPK signaling pathway. PMID:26189830

  6. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers

    PubMed Central

    Mani, Sendurai A.; Yang, Jing; Brooks, Mary; Schwaninger, Gunda; Zhou, Alicia; Miura, Naoyuki; Kutok, Jeffery L.; Hartwell, Kimberly; Richardson, Andrea L.; Weinberg, Robert A.

    2007-01-01

    The metastatic spread of epithelial cancer cells from the primary tumor to distant organs mimics the cell migrations that occur during embryogenesis. Using gene expression profiling, we have found that the FOXC2 transcription factor, which is involved in specifying mesenchymal cell fate during embryogenesis, is associated with the metastatic capabilities of cancer cells. FOXC2 expression is required for the ability of murine mammary carcinoma cells to metastasize to the lung, and overexpression of FOXC2 enhances the metastatic ability of mouse mammary carcinoma cells. We show that FOXC2 expression is induced in cells undergoing epithelial-mesenchymal transitions (EMTs) triggered by a number of signals, including TGF-β1 and several EMT-inducing transcription factors, such as Snail, Twist, and Goosecoid. FOXC2 specifically promotes mesenchymal differentiation during an EMT and may serve as a key mediator to orchestrate the mesenchymal component of the EMT program. Expression of FOXC2 is significantly correlated with the highly aggressive basal-like subtype of human breast cancers. These observations indicate that FOXC2 plays a central role in promoting invasion and metastasis and that it may prove to be a highly specific molecular marker for human basal-like breast cancers. PMID:17537911

  7. p38 MAPK Is Activated but Does Not Play a Key Role during Apoptosis Induction by Saturated Fatty Acid in Human Pancreatic β-Cells

    PubMed Central

    Šrámek, Jan; Němcová-Fürstová, Vlasta; Balušíková, Kamila; Daniel, Petr; Jelínek, Michael; James, Roger F.; Kovář, Jan

    2016-01-01

    Saturated stearic acid (SA) induces apoptosis in the human pancreatic β-cells NES2Y. However, the molecular mechanisms involved are unclear. We showed that apoptosis-inducing concentrations of SA activate the p38 MAPK signaling pathway in these cells. Therefore, we tested the role of p38 MAPK signaling pathway activation in apoptosis induction by SA in NES2Y cells. Crosstalk between p38 MAPK pathway activation and accompanying ERK pathway inhibition after SA application was also tested. The inhibition of p38 MAPK expression by siRNA silencing resulted in a decrease in MAPKAPK-2 activation after SA application, but it had no significant effect on cell viability or the level of phosphorylated ERK pathway members. The inhibition of p38 MAPK activity by the specific inhibitor SB202190 resulted in inhibition of MAPKAPK-2 activation and noticeable activation of ERK pathway members after SA treatment but in no significant effect on cell viability. p38 MAPK overexpression by plasmid transfection produced an increase in MAPKAPK-2 activation after SA exposure but no significant influence on cell viability or ERK pathway activation. The activation of p38 MAPK by the specific activator anisomycin resulted in significant activation of MAPKAPK-2. Concerning the effect on cell viability, application of the activator led to apoptosis induction similar to application of SA (PARP cleavage and caspase-7, -8, and -9 activation) and in inhibition of ERK pathway members. We demonstrated that apoptosis-inducing concentrations of SA activate the p38 MAPK signaling pathway and that this activation could be involved in apoptosis induction by SA in the human pancreatic β-cells NES2Y. However, this involvement does not seem to play a key role. Crosstalk between p38 MAPK pathway activation and ERK pathway inhibition in NES2Y cells seems likely. Thus, the ERK pathway inhibition by p38 MAPK activation does not also seem to be essential for SA-induced apoptosis. PMID:26861294

  8. Nitric Oxide Plays a Key Role in Ovariectomy-Induced Apoptosis in Anterior Pituitary: Interplay between Nitric Oxide Pathway and Estrogen.

    PubMed

    Ronchetti, Sonia A; Machiavelli, Leticia I; Quinteros, Fernanda A; Duvilanski, Beatriz H; Cabilla, Jimena P

    2016-01-01

    Changes in the estrogenic status produce deep changes in pituitary physiology, mainly because estrogens (E2) are one of the main regulators of pituitary cell population. Also, E2 negatively regulate pituitary neuronal nitric oxide synthase (nNOS) activity and expression and may thereby modulate the production of nitric oxide (NO), an important regulator of cell death and survival. Little is known about how ovary ablation affects anterior pituitary cell remodelling and molecular mechanisms that regulate this process have not yet been elucidated. In this work we used freshly dispersed anterior pituitaries as well as cell cultures from ovariectomized female rats in order to study whether E2 deficiency induces apoptosis in the anterior pituitary cells, the role of NO in this process and effects of E2 on the NO pathway. Our results showed that cell activity gradually decreases after ovariectomy (OVX) as a consequence of cell death, which is completely prevented by a pan-caspase inhibitor. Furthermore, there is an increase of fragmented nuclei and DNA cleavage thereby presenting the first direct evidence of the existence of apoptosis in the anterior pituitary gland after OVX. NO production and soluble guanylyl cyclase (sGC) expression in anterior pituitary cells increased concomitantly to the apoptosis. Inhibition of both, NO synthase (NOS) and sGC activities prevented the drop of cell viability after OVX, showing for the first time that increased NO levels and sGC activity observed post-OVX play a key role in the induction of apoptosis. Conversely, E2 and prolactin treatments decreased nNOS expression and activity in pituitary cells from OVX rats in a time- and E2 receptor-dependent manner, thus suggesting interplay between NO and E2 pathways in anterior pituitary. PMID:27611913

  9. Drastic reduction of sarcalumenin in Dp427 (dystrophin of 427 kDa)-deficient fibres indicates that abnormal calcium handling plays a key role in muscular dystrophy.

    PubMed Central

    Dowling, Paul; Doran, Philip; Ohlendieck, Kay

    2004-01-01

    Although the primary abnormality in dystrophin is the underlying cause for mdx (X-chromosome-linked muscular dystrophy), abnormal Ca2+ handling after sarcolemmal microrupturing appears to be the pathophysiological mechanism leading to muscle weakness. To develop novel pharmacological strategies for eliminating Ca2+-dependent proteolysis, it is crucial to determine the fate of Ca2+-handling proteins in dystrophin-deficient fibres. In the present study, we show that a key luminal Ca2+-binding protein SAR (sarcalumenin) is affected in mdx skeletal-muscle fibres. One- and two-dimensional immunoblot analyses revealed the relative expression of the 160 kDa SR (sarcoplasmic reticulum) protein to be approx. 70% lower in mdx fibres when compared with normal skeletal muscles. This drastic reduction in SAR was confirmed by immunofluorescence microscopy. Patchy internal labelling of SAR in dystrophic fibres suggests an abnormal formation of SAR domains. Differential co-immunoprecipitation experiments and chemical cross-linking demonstrated a tight linkage between SAR and the SERCA1 (sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase 1) isoform of the SR Ca2+-ATPase. However, the relative expression of the fast Ca2+ pump was not decreased in dystrophic membrane preparations. This implies that the reduction in SAR and calsequestrin-like proteins plays a central role in the previously reported impairment of Ca2+ buffering in the dystrophic SR [Culligan, Banville, Dowling and Ohlendieck (2002) J. Appl. Physiol. 92, 435-445]. Impaired Ca2+ shuttling between the Ca2+-uptake SERCA units and calsequestrin clusters via SAR, as well as an overall decreased luminal ion-binding capacity, might indirectly amplify the Ca2+-leak-channel-induced increase in cytosolic Ca2+ levels. This confirms the idea that abnormal Ca2+ cycling is involved in Ca2+-induced myonecrosis. Hence, manipulating disturbed Ca2+ handling might represent new modes of abolishing proteolytic degradation in muscular dystrophy

  10. Zinc-finger protein 91 plays a key role in LIGHT-induced activation of non-canonical NF-{kappa}B pathway

    SciTech Connect

    Jin, Hong Ri; Jin, Xuejun; Lee, Jung Joon

    2010-10-01

    Research highlights: {yields} LIGHT induces ZFP91expression and nuclear translocation of p65, p52, and RelB in LT{beta}R signaling. {yields} ZFP91 knock-down abolishes DNA-binding activity of p52 and RelB but not of p65. {yields} ZFP91 regulates LIGHT-induced stabilization and activation of NIK. {yields} ZFP91 is required for the expression of non-canonical NF-{kappa}B target genes. -- Abstract: LIGHT is a member of tumor necrosis factor (TNF) superfamily, and its function is mediated through lymphotoxin-{beta} receptor (LT{beta}R), which is known to play important roles in inflammatory and immune responses through activation of NF-{kappa}B signaling pathways. However, molecular mechanism of LT{beta}R ligation-induced NF-{kappa}B signaling remains incompletely understood. In this report we demonstrate that a novel zinc-finger protein 91 (ZFP91) is a critical regulator in LIGHT-induced activation of non-canonical NF-{kappa}B pathway. ZFP91 appears to be required for NF-{kappa}B2 (p100) processing to p52, nuclear translocation of p52 and RelB, and DNA-binding activity of NF-{kappa}B in LIGHT-induced activation of non-canonical NF-{kappa}B pathway. Furthermore, ZFP91 knock-down by RNA interference blocks the LIGHT-induced accumulation of NIK and p100 processing, as well as the expression of non-canonical NF-{kappa}B target genes. These data clearly indicate that ZFP91 is a key regulator in LIGHT-induced activation of non-canonical NF-{kappa}B pathway in LT{beta}R signaling.

  11. The Drosophila Broad-Complex plays a key role in controlling ecdysone-regulated gene expression at the onset of metamorphosis.

    PubMed

    Karim, F D; Guild, G M; Thummel, C S

    1993-07-01

    During Drosophila third instar larval development, one or more pulses of the steroid hormone ecdysone activate three temporally distinct sets of genes in the salivary glands, represented by puffs in the polytene chromosomes. The intermolt genes are induced first, in mid-third instar larvae; these genes encode a protein glue used by the animal to adhere itself to a solid substrate for metamorphosis. The intermolt genes are repressed at puparium formation as a high titer ecdysone pulse directly induces a small set of early regulatory genes. The early genes both repress their own expression and activate more than 100 late secondary-response genes. The Broad-Complex (BR-C) is an early ecdysone-inducible gene that encodes a family of DNA binding proteins defined by at least three lethal complementation groups: br, rbp, and l(1)2Bc. We have found that the BR-C is critical for the appropriate regulation of all three classes of ecdysone-inducible genes. Both rbp and l(1)2Bc are required for glue gene induction in mid-third instar larvae. In addition, the l(1)2Bc function is required for glue gene repression in prepupae; in l(1)2Bc mutants the glue genes are re-induced by the late prepupal ecdysone pulse, recapitulating a mid-third instar regulatory response at an inappropriate stage in development. The l(1)2Bc function is also required for the complete ecdysone induction of some early mRNAs (E74A, E75A, and BR-C) and efficient repression of most early mRNAs in prepupae. Like the intermolt secondary-response genes, the late secondary-response genes are absolutely dependent on rbp for their induction. An effect of l(1)2Bc mutations on late gene activity can also be detected, but is most likely a secondary consequence of the submaximal ecdysone-induction of a subset of early regulatory products. Our results indicate that the BR-C plays a key role in dictating the stage-specificity of the ecdysone response. In addition, the ecdysone-receptor protein complex alone is not

  12. 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…

  13. The tomato floral homeotic protein FBP1-like gene, SlGLO1, plays key roles in petal and stamen development.

    PubMed

    Guo, Xuhu; Hu, Zongli; Yin, Wencheng; Yu, Xiaohui; Zhu, Zhiguo; Zhang, Jianling; Chen, Guoping

    2016-01-01

    MADS-box transcription factors play important role in plant growth and development, especially floral organ identities. In our study, a MADS-box gene SlGLO1- tomato floral homeotic protein FBP1-like gene was isolated. Its tissue-specific expression profile analysis showed that SlGLO1 was highly expressed in petals and stamens. RNAi (RNA interference) repression of SlGLO1 resulted in floral organ abnormal phenotypes, including green petals with shorter size, and aberrant carpelloid stamens. SlGLO1-silenced lines are male sterile. Total chlorophyll content was increased and chlorophyll biosynthetic genes were significantly up-regulated in SlGLO1-silenced petals and stamens. Furthermore, B-class genes expression analysis indicated that the repressed function of SlGLO1 led to the enhanced expression of TAP3 and the down-regulation of TPI in the petals and stamens, while the expression of TM6 was reduced in petals and increased in stamens and carpels of SlGLO1-RNAi plants. Additionally, pollen grains of transgenic lines were aberrant and failed to germinate and tomato pollen-specific genes were down-regulated by more than 90% in SlGLO1-silenced lines. These results suggest that SlGLO1 plays important role in regulating plant floral organ and pollen development in tomato. PMID:26842499

  14. Subcellular Relocalization and Positive Selection Play Key Roles in the Retention of Duplicate Genes of Populus Class III Peroxidase Family[W][OPEN

    PubMed Central

    Ren, Lin-Ling; Liu, Yan-Jing; Liu, Hai-Jing; Qian, Ting-Ting; Qi, Li-Wang; Wang, Xiao-Ru; Zeng, Qing-Yin

    2014-01-01

    Gene duplication is the primary source of new genes and novel functions. Over the course of evolution, many duplicate genes lose their function and are eventually removed by deletion. However, some duplicates have persisted and evolved diverse functions. A particular challenge is to understand how this diversity arises and whether positive selection plays a role. In this study, we reconstructed the evolutionary history of the class III peroxidase (PRX) genes from the Populus trichocarpa genome. PRXs are plant-specific enzymes that play important roles in cell wall metabolism and in response to biotic and abiotic stresses. We found that two large tandem-arrayed clusters of PRXs evolved from an ancestral cell wall type PRX to vacuole type, followed by tandem duplications and subsequent functional specification. Substitution models identified seven positively selected sites in the vacuole PRXs. These positively selected sites showed significant effects on the biochemical functions of the enzymes. We also found that positive selection acts more frequently on residues adjacent to, rather than directly at, a critical active site of the enzyme, and on flexible regions rather than on rigid structural elements of the protein. Our study provides new insights into the adaptive molecular evolution of plant enzyme families. PMID:24934172

  15. The tomato floral homeotic protein FBP1-like gene, SlGLO1, plays key roles in petal and stamen development

    PubMed Central

    Guo, Xuhu; Hu, Zongli; Yin, Wencheng; Yu, Xiaohui; Zhu, Zhiguo; Zhang, Jianling; Chen, Guoping

    2016-01-01

    MADS-box transcription factors play important role in plant growth and development, especially floral organ identities. In our study, a MADS-box gene SlGLO1- tomato floral homeotic protein FBP1-like gene was isolated. Its tissue-specific expression profile analysis showed that SlGLO1 was highly expressed in petals and stamens. RNAi (RNA interference) repression of SlGLO1 resulted in floral organ abnormal phenotypes, including green petals with shorter size, and aberrant carpelloid stamens. SlGLO1-silenced lines are male sterile. Total chlorophyll content was increased and chlorophyll biosynthetic genes were significantly up-regulated in SlGLO1-silenced petals and stamens. Furthermore, B-class genes expression analysis indicated that the repressed function of SlGLO1 led to the enhanced expression of TAP3 and the down-regulation of TPI in the petals and stamens, while the expression of TM6 was reduced in petals and increased in stamens and carpels of SlGLO1-RNAi plants. Additionally, pollen grains of transgenic lines were aberrant and failed to germinate and tomato pollen-specific genes were down-regulated by more than 90% in SlGLO1-silenced lines. These results suggest that SlGLO1 plays important role in regulating plant floral organ and pollen development in tomato. PMID:26842499

  16. Key Roles in the Revolution of Work.

    ERIC Educational Resources Information Center

    Riverin-Simard, Danielle

    At the height of the work revolution and its great social challenges, career development and employment counseling specialists have essential key roles to play in order to support the socioeconomic growth of our community. This book suggests four pro-active key roles for the profession. This recommendation is based on research conducted over the…

  17. The Vaccine Candidate Substrate Binding Protein SBP2 Plays a Key Role in Arginine Uptake, Which Is Required for Growth of Moraxella catarrhalis

    PubMed Central

    Otsuka, Taketo; Kirkham, Charmaine; Brauer, Aimee; Koszelak-Rosenblum, Mary; Malkowski, Michael G.

    2015-01-01

    Moraxella catarrhalis is an exclusively human pathogen that is an important cause of otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. A vaccine to prevent M. catarrhalis infections would have an enormous global impact in reducing morbidity resulting from these infections. Substrate binding protein 2 (SBP2) of an ABC transporter system has recently been identified as a promising vaccine candidate antigen on the bacterial surface of M. catarrhalis. In this study, we showed that SBP1, -2, and -3 individually bind different basic amino acids with exquisite specificity. We engineered mutants that each expressed a single SBP from this gene cluster and showed in growth experiments that SBP1, -2, and -3 serve a nutritional function through acquisition of amino acids for the bacterium. SBP2 mediates uptake of arginine, a strict growth requirement of M. catarrhalis. Adherence and invasion assays demonstrated that SBP1 and SBP3 play a role in invasion of human respiratory epithelial cells, consistent with a nutritional role in intracellular survival in the human respiratory tract. This work demonstrates that the SBPs of an ABC transporter system function in the uptake of basic amino acids to support growth of M. catarrhalis. The critical role of SBP2 in arginine uptake may contribute to its potential as a vaccine antigen. PMID:26597985

  18. Genomic islands 1 and 2 play key roles in the evolution of extensively drug-resistant ST235 isolates of Pseudomonas aeruginosa

    PubMed Central

    Scott, Martin; Worden, Paul; Huntington, Peter; Hudson, Bernard; Karagiannis, Thomas; Charles, Ian G.; Djordjevic, Steven P.

    2016-01-01

    Pseudomonas aeruginosa are noscomially acquired, opportunistic pathogens that pose a major threat to the health of burns patients and the immunocompromised. We sequenced the genomes of P. aeruginosa isolates RNS_PA1, RNS_PA46 and RNS_PAE05, which displayed resistance to almost all frontline antibiotics, including gentamicin, piperacillin, timentin, meropenem, ceftazidime and colistin. We provide evidence that the isolates are representatives of P. aeruginosa sequence type (ST) 235 and carry Tn6162 and Tn6163 in genomic islands 1 (GI1) and 2 (GI2), respectively. GI1 disrupts the endA gene at precisely the same chromosomal location as in P. aeruginosa strain VR-143/97, of unknown ST, creating an identical CA direct repeat. The class 1 integron associated with Tn6163 in GI2 carries a blaGES-5–aacA4–gcuE15–aphA15 cassette array conferring resistance to carbapenems and aminoglycosides. GI2 is flanked by a 12 nt direct repeat motif, abuts a tRNA-gly gene, and encodes proteins with putative roles in integration, conjugative transfer as well as integrative conjugative element-specific proteins. This suggests that GI2 may have evolved from a novel integrative conjugative element. Our data provide further support to the hypothesis that genomic islands play an important role in de novo evolution of multiple antibiotic resistance phenotypes in P. aeruginosa. PMID:26962050

  19. Endocytic trafficking towards the vacuole plays a key role in the auxin receptor SCF(TIR)-independent mechanism of lateral root formation in A. thaliana.

    PubMed

    Pérez-Henríquez, Patricio; Raikhel, Natasha V; Norambuena, Lorena

    2012-11-01

    Plants' developmental plasticity plays a pivotal role in responding to environmental conditions. One of the most plastic plant organs is the root system. Different environmental stimuli such as nutrients and water deficiency may induce lateral root formation to compensate for a low level of water and/or nutrients. It has been shown that the hormone auxin tunes lateral root development and components for its signaling pathway have been identified. Using chemical biology, we discovered an Arabidopsis thaliana lateral root formation mechanism that is independent of the auxin receptor SCF(TIR). The bioactive compound Sortin2 increased lateral root occurrence by acting upstream from the morphological marker of lateral root primordium formation, the mitotic activity. The compound did not display auxin activity. At the cellular level, Sortin2 accelerated endosomal trafficking, resulting in increased trafficking of plasma membrane recycling proteins to the vacuole. Sortin2 affected Late endosome/PVC/MVB trafficking and morphology. Combining Sortin2 with well-known drugs showed that endocytic trafficking of Late E/PVC/MVB towards the vacuole is pivotal for Sortin2-induced SCF(TIR)-independent lateral root initiation. Our results revealed a distinctive role for endosomal trafficking in the promotion of lateral root formation via a process that does not rely on the auxin receptor complex SCF(TIR). PMID:22848095

  20. Genomic islands 1 and 2 play key roles in the evolution of extensively drug-resistant ST235 isolates of Pseudomonas aeruginosa.

    PubMed

    Roy Chowdhury, Piklu; Scott, Martin; Worden, Paul; Huntington, Peter; Hudson, Bernard; Karagiannis, Thomas; Charles, Ian G; Djordjevic, Steven P

    2016-03-01

    Pseudomonas aeruginosa are noscomially acquired, opportunistic pathogens that pose a major threat to the health of burns patients and the immunocompromised. We sequenced the genomes of P. aeruginosa isolates RNS_PA1, RNS_PA46 and RNS_PAE05, which displayed resistance to almost all frontline antibiotics, including gentamicin, piperacillin, timentin, meropenem, ceftazidime and colistin. We provide evidence that the isolates are representatives of P. aeruginosa sequence type (ST) 235 and carry Tn6162 and Tn6163 in genomic islands 1 (GI1) and 2 (GI2), respectively. GI1 disrupts the endA gene at precisely the same chromosomal location as in P. aeruginosa strain VR-143/97, of unknown ST, creating an identical CA direct repeat. The class 1 integron associated with Tn6163 in GI2 carries a blaGES-5-aacA4-gcuE15-aphA15 cassette array conferring resistance to carbapenems and aminoglycosides. GI2 is flanked by a 12 nt direct repeat motif, abuts a tRNA-gly gene, and encodes proteins with putative roles in integration, conjugative transfer as well as integrative conjugative element-specific proteins. This suggests that GI2 may have evolved from a novel integrative conjugative element. Our data provide further support to the hypothesis that genomic islands play an important role in de novo evolution of multiple antibiotic resistance phenotypes in P. aeruginosa. PMID:26962050

  1. Mechanisms of Mitochondrial Holocytochrome c Synthase and the Key Roles Played by Cysteines and Histidine of the Heme Attachment Site, Cys-XX-Cys-His*

    PubMed Central

    Babbitt, Shalon E.; San Francisco, Brian; Mendez, Deanna L.; Lukat-Rodgers, Gudrun S.; Rodgers, Kenton R.; Bretsnyder, Eric C.; Kranz, Robert G.

    2014-01-01

    Mitochondrial cytochrome c assembly requires the covalent attachment of heme by thioether bonds between heme vinyl groups and a conserved CXXCH motif of cytochrome c/c1. The enzyme holocytochrome c synthase (HCCS) binds heme and apocytochrome c substrate to catalyze this attachment, subsequently releasing holocytochrome c for proper folding to its native structure. We address mechanisms of assembly using a functional Escherichia coli recombinant system expressing human HCCS. Human cytochrome c variants with individual cysteine, histidine, double cysteine, and triple cysteine/histidine substitutions (of CXXCH) were co-purified with HCCS. Single and double mutants form a complex with HCCS but not the triple mutant. Resonance Raman and UV-visible spectroscopy support the proposal that heme puckering induced by both thioether bonds facilitate release of holocytochrome c from the complex. His-19 (of CXXCH) supplies the second axial ligand to heme in the complex, the first axial ligand was previously shown to be from HCCS residue His-154. Substitutions of His-19 in cytochrome c to seven other residues (Gly, Ala, Met, Arg, Lys, Cys, and Tyr) were used with various approaches to establish other roles played by His-19. Three roles for His-19 in HCCS-mediated assembly are suggested: (i) to provide the second axial ligand to the heme iron in preparation for covalent attachment; (ii) to spatially position the two cysteinyl sulfurs adjacent to the two heme vinyl groups for thioether formation; and (iii) to aid in release of the holocytochrome c from the HCCS active site. Only H19M is able to carry out these three roles, albeit at lower efficiencies than the natural His-19. PMID:25170082

  2. EsxA membrane-permeabilizing activity plays a key role in mycobacterial cytosolic translocation and virulence: effects of single-residue mutations at glutamine 5

    PubMed Central

    Zhang, Qi; Wang, Decheng; Jiang, Guozhong; Liu, Wei; Deng, Qing; Li, Xiujun; Qian, Wei; Ouellet, Hugues; Sun, Jianjun

    2016-01-01

    EsxA is required for virulence of Mycobacterium tuberculosis (Mtb) and plays an essential role in phagosome rupture and translocation to the cytosol of macrophages. Recent biochemical studies have demonstrated that EsxA is a membrane-permeabilizing protein. However, evidence that link EsxA membrane-permeabilizing activity to Mtb cytosolic translocation and virulence is lacking. Here we found that mutations at glutamine 5 (Q5) could up or down regulate EsxA membrane-permeabilizing activity. The mutation Q5K significantly diminished the membrane-permeabilizing activity, while Q5V enhanced the activity. By taking advantage of the single-residue mutations, we tested the effects of EsxA membrane-permeabilizing activity on mycobacterial virulence and cytosolic translocation using the esxA/esxB knockout strains of Mycobacterium marinum (Mm) and Mtb. Compared to wild type (WT), the Q5K mutant exhibited significantly attenuated virulence, evidenced by intracellular survival and cytotoxicity in mouse macrophages as well as infection of zebra fish embryos. The attenuated virulence of the Q5K mutant was correlated to the impaired cytosolic translocation. On the contrary, the Q5V mutant had a significantly increased cytosolic translocation and showed an overall increased virulence. This study provides convincing evidence that EsxA contributes to mycobacterial virulence with its membrane-permeabilizing activity that is required for cytosolic translocation. PMID:27600772

  3. Biogenesis of Fe/S proteins and pathogenicity: IscR plays a key role in allowing Erwinia chrysanthemi to adapt to hostile conditions.

    PubMed

    Rincon-Enriquez, Gabriel; Crété, Patrice; Barras, Frédéric; Py, Béatrice

    2008-03-01

    The Erwinia chrysanthemi genome is predicted to encode three systems, Nif, Isc and Suf, known to assist Fe/S cluster biogenesis and the CsdAE cysteine desulphurase. Single iscU, hscA and fdx mutants were found sensitive to paraquat and exhibited reduced virulence on both chicory leaves and Arabidopsis thaliana. Depletion of the whole Isc system led to a pleiotropic phenotype, including sensitivity to both paraquat and 2,2'-dipyridyl, auxotrophies for branched-chain amino acids, thiamine, nicotinic acid, and drastic alteration in virulence. IscR was able to suppress all of the phenotypes listed above in a sufC-dependent manner while depletion of the Isc system led to IscR-dependent activation of the suf operon. No virulence defects were found associated with csdA or nifS mutations. Surprisingly, we found that the sufC mutant was virulent against A. thaliana, whereas its virulence had been found altered in Saintpaulia. Collectively, these results lead us to propose that E. chrysanthemi possess the Fe/S biogenesis strategy suited to the physico-chemical conditions encountered in its host upon infection. In this view, the IscR regulator, which controls both Isc and Suf, is predicted to play a major role in the ability of E. chrysanthemi to colonize a wide array of different plants. PMID:18284573

  4. Genome-wide DNA methylation profiling by modified reduced representation bisulfite sequencing in Brassica rapa suggests that epigenetic modifications play a key role in polyploid genome evolution

    PubMed Central

    Chen, Xun; Ge, Xianhong; Wang, Jing; Tan, Chen; King, Graham J.; Liu, Kede

    2015-01-01

    Brassica rapa includes some of the most important vegetables worldwide as well as oilseed crops. The complete annotated genome sequence confirmed its paleohexaploid origins and provides opportunities for exploring the detailed process of polyploid genome evolution. We generated a genome-wide DNA methylation profile for B. rapa using a modified reduced representation bisulfite sequencing (RRBS) method. This sampling represented 2.24% of all CG loci (2.5 × 105), 2.16% CHG (2.7 × 105), and 1.68% CHH loci (1.05 × 105) (where H = A, T, or C). Our sampling of DNA methylation in B. rapa indicated that 52.4% of CG sites were present as 5mCG, with 31.8% of CHG and 8.3% of CHH. It was found that genic regions of single copy genes had significantly higher methylation compared to those of two or three copy genes. Differences in degree of genic DNA methylation were observed in a hierarchical relationship corresponding to the relative age of the three ancestral subgenomes, primarily accounted by single-copy genes. RNA-seq analysis revealed that overall the level of transcription was negatively correlated with mean gene methylation content and depended on copy number or was associated with the different subgenomes. These results provide new insights into the role epigenetic variation plays in polyploid genome evolution, and suggest an alternative mechanism for duplicate gene loss. PMID:26500672

  5. Cucumber ECERIFERUM1 (CsCER1), which influences the cuticle properties and drought tolerance of cucumber, plays a key role in VLC alkanes biosynthesis.

    PubMed

    Wang, Wenjiao; Zhang, Yan; Xu, Chong; Ren, Jiaojiao; Liu, Xiaofeng; Black, Kezia; Gai, Xinshuang; Wang, Qian; Ren, Huazhong

    2015-02-01

    Most land plants have a wax layer which covers their aerial parts to protect them from environmental stresses, such as drought, UV radiation, and pathogenic invasion. The wax biosynthesis has been well studied previously in Arabidopsis, but it still remains elusive in cucumber. Here, we isolated a CER1 homolog CsCER1 in cucumber, and we found that the expression of CsCER1 in the cucumber line 3401 which shows waxy fruit phenotype is much higher than that in the cucumber line 3413 which displays glossy fruit phenotype. Spatial and temporal expression analyses revealed that CsCER1 is specifically expressed in the epidermis where waxes are synthesized, and sub-cellular location showed that CsCER1 protein is localized to the endoplasmic reticulum. The expression of CsCER1 can be induced by low temperature, drought, salt stress and abscisic acid. In addition, abnormal expressions of CsCER1 in transgenic cucumber plants have dramatic effects on very-long-chain (VLC) alkanes biosynthesis, cuticle permeability, and drought resistance. Our data suggested that CsCER1 plays an important role in VLC alkanes biosynthesis in cucumber. PMID:25539982

  6. Genome-wide DNA methylation profiling by modified reduced representation bisulfite sequencing in Brassica rapa suggests that epigenetic modifications play a key role in polyploid genome evolution.

    PubMed

    Chen, Xun; Ge, Xianhong; Wang, Jing; Tan, Chen; King, Graham J; Liu, Kede

    2015-01-01

    Brassica rapa includes some of the most important vegetables worldwide as well as oilseed crops. The complete annotated genome sequence confirmed its paleohexaploid origins and provides opportunities for exploring the detailed process of polyploid genome evolution. We generated a genome-wide DNA methylation profile for B. rapa using a modified reduced representation bisulfite sequencing (RRBS) method. This sampling represented 2.24% of all CG loci (2.5 × 10(5)), 2.16% CHG (2.7 × 10(5)), and 1.68% CHH loci (1.05 × 10(5)) (where H = A, T, or C). Our sampling of DNA methylation in B. rapa indicated that 52.4% of CG sites were present as (5m)CG, with 31.8% of CHG and 8.3% of CHH. It was found that genic regions of single copy genes had significantly higher methylation compared to those of two or three copy genes. Differences in degree of genic DNA methylation were observed in a hierarchical relationship corresponding to the relative age of the three ancestral subgenomes, primarily accounted by single-copy genes. RNA-seq analysis revealed that overall the level of transcription was negatively correlated with mean gene methylation content and depended on copy number or was associated with the different subgenomes. These results provide new insights into the role epigenetic variation plays in polyploid genome evolution, and suggest an alternative mechanism for duplicate gene loss. PMID:26500672

  7. EsxA membrane-permeabilizing activity plays a key role in mycobacterial cytosolic translocation and virulence: effects of single-residue mutations at glutamine 5.

    PubMed

    Zhang, Qi; Wang, Decheng; Jiang, Guozhong; Liu, Wei; Deng, Qing; Li, Xiujun; Qian, Wei; Ouellet, Hugues; Sun, Jianjun

    2016-01-01

    EsxA is required for virulence of Mycobacterium tuberculosis (Mtb) and plays an essential role in phagosome rupture and translocation to the cytosol of macrophages. Recent biochemical studies have demonstrated that EsxA is a membrane-permeabilizing protein. However, evidence that link EsxA membrane-permeabilizing activity to Mtb cytosolic translocation and virulence is lacking. Here we found that mutations at glutamine 5 (Q5) could up or down regulate EsxA membrane-permeabilizing activity. The mutation Q5K significantly diminished the membrane-permeabilizing activity, while Q5V enhanced the activity. By taking advantage of the single-residue mutations, we tested the effects of EsxA membrane-permeabilizing activity on mycobacterial virulence and cytosolic translocation using the esxA/esxB knockout strains of Mycobacterium marinum (Mm) and Mtb. Compared to wild type (WT), the Q5K mutant exhibited significantly attenuated virulence, evidenced by intracellular survival and cytotoxicity in mouse macrophages as well as infection of zebra fish embryos. The attenuated virulence of the Q5K mutant was correlated to the impaired cytosolic translocation. On the contrary, the Q5V mutant had a significantly increased cytosolic translocation and showed an overall increased virulence. This study provides convincing evidence that EsxA contributes to mycobacterial virulence with its membrane-permeabilizing activity that is required for cytosolic translocation. PMID:27600772

  8. ATP-binding motifs play key roles in Krp1p, kinesin-related protein 1, function for bi-polar growth control in fission yeast

    SciTech Connect

    Rhee, Dong Keun; Cho, Bon A; Kim, Hyong Bai . E-mail: hbkim5212@hotmail.com

    2005-06-03

    Kinesin is a microtubule-based motor protein with various functions related to the cell growth and division. It has been reported that Krp1p, kinesin-related protein 1, which belongs to the kinesin heavy chain superfamily, localizes on microtubules and may play an important role in cytokinesis. However, the function of Krp1p has not been fully elucidated. In this study, we overexpressed an intact form and three different mutant forms of Krp1p in fission yeast constructed by site-directed mutagenesis in two ATP-binding motifs or by truncation of the leucine zipper-like motif (LZiP). We observed hyper-extended microtubules and the aberrant nuclear shape in Krp1p-overexpressed fission yeast. As a functional consequence, a point mutation of ATP-binding domain 1 (G89E) in Krp1p reversed the effect of Krp1p overexpression in fission yeast, whereas the specific mutation in ATP-binding domain 2 (G238E) resulted in the altered cell polarity. Additionally, truncation of the leucine zipper-like domain (LZiP) at the C-terminal of Krp1p showed a normal nuclear division. Taken together, we suggest that krp1p is involved in regulation of cell-polarized growth through ATP-binding motifs in fission yeast.

  9. Hydathode trichomes actively secreting water from leaves play a key role in the physiology and evolution of root-parasitic rhinanthoid Orobanchaceae

    PubMed Central

    Světlíková, Petra; Hájek, Tomáš; Těšitel, Jakub

    2015-01-01

    Background and Aims Root hemiparasites from the rhinanthoid clade of Orobanchaceae possess metabolically active glandular trichomes that have been suggested to function as hydathode trichomes actively secreting water, a process that may facilitate resource acquisition from the host plant’s root xylem. However, no direct evidence relating the trichomes to water secretion exists, and carbon budgets associated with this energy-demanding process have not been determined. Methods Macro- and microscopic observations of the leaves of hemiparasitic Rhinanthus alectorolophus were conducted and night-time gas exchange was measured. Correlations were examined among the intensity of guttation, respiration and transpiration, and analysis of these correlations allowed the carbon budget of the trichome activity to be quantified. We examined the intensity of guttation, respiration and transpiration, correlations among which indicate active water secretion. Key Results Guttation was observed on the leaves of 50 % of the young, non-flowering plants that were examined, and microscopic observations revealed water secretion from the glandular trichomes present on the abaxial leaf side. Night-time rates of respiration and transpiration and the presence of guttation drops were positively correlated, which is a clear indicator of hydathode trichome activity. Subsequent physiological measurements on older, flowering plants indicated neither intense guttation nor the presence of correlations, which suggests that the peak activity of hydathodes is in the juvenile stage. Conclusions This study provides the first unequivocal evidence for the physiological role of the hydathode trichomes in active water secretion in the rhinanthoid Orobanchaceae. Depending on the concentration of organic elements calculated to be in the host xylem sap, the direct effect of water secretion on carbon balance ranges from close to neutral to positive. However, it is likely to be positive in the xylem-only feeding

  10. 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

  11. The key factor limiting plant growth in cold and humid alpine areas also plays a dominant role in plant carbon isotope discrimination

    PubMed Central

    Xu, Meng; Wang, Guoan; Li, Xiaoliang; Cai, Xiaobu; Li, Xiaolin; Christie, Peter; Zhang, Junling

    2015-01-01

    Many environmental factors affect carbon isotope discrimination in plants, yet the predominant factor influencing this process is generally assumed to be the key growth-limiting factor. However, to our knowledge this hypothesis has not been confirmed. We therefore determined the carbon isotope composition (δ13C) of plants growing in two cold and humid mountain regions where temperature is considered to be the key growth-limiting factor. Mean annual temperature (MAT) showed a significant impact on variation in carbon isotope discrimination value (Δ) irrespective of study area or plant functional type with either partial correlation or regression analysis, but the correlation between Δ and soil water content (SWC) was usually not significant. In multiple stepwise regression analysis, MAT was either the first or the only variable selected into the prediction model of Δ against MAT and SWC, indicating that the effect of temperature on carbon isotope discrimination was predominant. The results therefore provide evidence that the key growth-limiting factor is also crucial for plant carbon isotope discrimination. Changes in leaf morphology, water viscosity and carboxylation efficiency with temperature may be responsible for the observed positive correlation between Δ and temperature. PMID:26579188

  12. Indigenous organophosphate-degrading (opd) plasmid pCMS1 of Brevundimonasdiminuta is self-transmissible and plays a key role in horizontal mobility of the opd gene.

    PubMed

    Pandeeti, Emmanuel Vijay Paul; Chakka, Deviprasanna; Pandey, Jay Prakash; Siddavattam, Dayananda

    2011-05-01

    A fosmid library of the 66kb indigenous organophosphate-degrading (opd) plasmid pCMS1 of Brevundimonas diminuta was tagged with mini-transposon EZTn5 , to determine its sequence using transposon-specific primers. The sequence revealed the presence of a number of tra genes suggesting their role in conjugal transfer of pCMS1. Consistent with the presence of the tra genes, the B. diminuta plasmid, pCMS1::tet, generated by replacing the opd gene with opd::tet, served as a donor for transferring pCMS1::tet into recipient strain Pseudomonas putida. The self-transmissibility of the opd-containing plasmid pCMS1 and the existence of identical opd genes on otherwise dissimilar plasmids suggests a probable role of indigenous opd plasmids like pCMS1 in transferring the opd gene among soil bacteria. PMID:21354204

  13. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action.

    PubMed

    Currie, Richard A; Peffer, Richard C; Goetz, Amber K; Omiecinski, Curtis J; Goodman, Jay I

    2014-07-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

  14. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    PubMed Central

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

  15. Orphan nuclear receptor oestrogen-related receptor γ (ERRγ) plays a key role in hepatic cannabinoid receptor type 1-mediated induction of CYP7A1 gene expression.

    PubMed

    Zhang, Yaochen; Kim, Don-Kyu; Lee, Ji-Min; Park, Seung Bum; Jeong, Won-Il; Kim, Seong Heon; Lee, In-Kyu; Lee, Chul-Ho; Chiang, John Y L; Choi, Hueng-Sik

    2015-09-01

    Bile acids are primarily synthesized from cholesterol in the liver and have important roles in dietary lipid absorption and cholesterol homoeostasis. Detailed roles of the orphan nuclear receptors regulating cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis, have not yet been fully elucidated. In the present study, we report that oestrogen-related receptor γ (ERRγ) is a novel transcriptional regulator of CYP7A1 expression. Activation of cannabinoid receptor type 1 (CB1 receptor) signalling induced ERRγ-mediated transcription of the CYP7A1 gene. Overexpression of ERRγ increased CYP7A1 expression in vitro and in vivo, whereas knockdown of ERRγ attenuated CYP7A1 expression. Deletion analysis of the CYP7A1 gene promoter and a ChIP assay revealed an ERRγ-binding site on the CYP7A1 gene promoter. Small heterodimer partner (SHP) inhibited the transcriptional activity of ERRγ and thus regulated CYP7A1 expression. Overexpression of ERRγ led to increased bile acid levels, whereas an inverse agonist of ERRγ, GSK5182, reduced CYP7A1 expression and bile acid synthesis. Finally, GSK5182 significantly reduced hepatic CB1 receptor-mediated induction of CYP7A1 expression and bile acid synthesis in alcohol-treated mice. These results provide the molecular mechanism linking ERRγ and bile acid metabolism. PMID:26348907

  16. The ZntA-like NpunR4017 plays a key role in maintaining homeostatic levels of zinc in Nostoc punctiforme.

    PubMed

    Hudek, L; Bräu, L; Michalczyk, A A; Neilan, B A; Meeks, J C; Ackland, M L

    2015-12-01

    Analysis of cellular response to zinc exposure provides insights into how organisms maintain homeostatic levels of zinc that are essential, while avoiding potentially toxic cytosolic levels. Using the cyanobacterium Nostoc punctiforme as a model, qRT-PCR analyses established a profile of the changes in relative mRNA levels of the ZntA-like zinc efflux transporter NpunR4017 in response to extracellular zinc. In cells treated with 18 μM of zinc for 1 h, NpunR4017 mRNA levels increased by up to 1300 % above basal levels. The accumulation and retention of radiolabelled (65)Zn by NpunR4107-deficient and overexpressing strains were compared to wild-type levels. Disruption of NpunR4017 resulted in a significant increase in zinc accumulation up to 24 % greater than the wild type, while cells overexpressing NpunR4107 accumulated 22 % less than the wild type. Accumulation of (65)Zn in ZntA(-) Escherichia coli overexpressing NpunR4017 was reduced by up to 21 %, indicating the capacity for NpunR4017 to compensate for the loss of ZntA. These findings establish the newly identified NpunR4017 as a zinc efflux transporter and a key transporter for maintaining zinc homeostasis in N. punctiforme. PMID:26290176

  17. Mass Spectrometry-based Workflow for Accurate Quantification of Escherichia coli Enzymes: How Proteomics Can Play a Key Role in Metabolic Engineering*

    PubMed Central

    Trauchessec, Mathieu; Jaquinod, Michel; Bonvalot, Aline; Brun, Virginie; Bruley, Christophe; Ropers, Delphine; de Jong, Hidde; Garin, Jérôme; Bestel-Corre, Gwenaëlle; Ferro, Myriam

    2014-01-01

    Metabolic engineering aims to design high performance microbial strains producing compounds of interest. This requires systems-level understanding; genome-scale models have therefore been developed to predict metabolic fluxes. However, multi-omics data including genomics, transcriptomics, fluxomics, and proteomics may be required to model the metabolism of potential cell factories. Recent technological advances to quantitative proteomics have made mass spectrometry-based quantitative assays an interesting alternative to more traditional immuno-affinity based approaches. This has improved specificity and multiplexing capabilities. In this study, we developed a quantification workflow to analyze enzymes involved in central metabolism in Escherichia coli (E. coli). This workflow combined full-length isotopically labeled standards with selected reaction monitoring analysis. First, full-length 15N labeled standards were produced and calibrated to ensure accurate measurements. Liquid chromatography conditions were then optimized for reproducibility and multiplexing capabilities over a single 30-min liquid chromatography-MS analysis. This workflow was used to accurately quantify 22 enzymes involved in E. coli central metabolism in a wild-type reference strain and two derived strains, optimized for higher NADPH production. In combination with measurements of metabolic fluxes, proteomics data can be used to assess different levels of regulation, in particular enzyme abundance and catalytic rate. This provides information that can be used to design specific strains used in biotechnology. In addition, accurate measurement of absolute enzyme concentrations is key to the development of predictive kinetic models in the context of metabolic engineering. PMID:24482123

  18. Conserved Epigenetic Mechanisms Could Play a Key Role in Regulation of Photosynthesis and Development-Related Genes during Needle Development of Pinus radiata

    PubMed Central

    Meijón, Mónica; Escandón, Mónica; Cañal, María Jesús

    2015-01-01

    Needle maturation is a complex process that involves cell growth, differentiation and tissue remodelling towards the acquisition of full physiological competence. Leaf induction mechanisms are well known; however, those underlying the acquisition of physiological competence are still poorly understood, especially in conifers. We studied the specific epigenetic regulation of genes defining organ function (PrRBCS and PrRBCA) and competence and stress response (PrCSDP2 and PrSHMT4) during three stages of needle development and one de-differentiated control. Gene-specific changes in DNA methylation and histone were analysed by bisulfite sequencing and chromatin immunoprecipitation (ChIP). The expression of PrRBCA and PrRBCS increased during needle maturation and was associated with the progressive loss of H3K9me3, H3K27me3 and the increase in AcH4. The maturation-related silencing of PrSHMT4 was correlated with increased H3K9me3 levels, and the repression of PrCSDP2, to the interplay between AcH4, H3K27me3, H3K9me3 and specific DNA methylation. The employ of HAT and HDAC inhibitors led to a further determination of the role of histone acetylation in the regulation of our target genes. The integration of these results with high-throughput analyses in Arabidopsis thaliana and Populus trichocarpa suggests that the specific epigenetic mechanisms that regulate photosynthetic genes are conserved between the analysed species. PMID:25965766

  19. 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…

  20. bHLH-PAS family transcription factor methoprene-tolerant plays a key role in JH action in preventing the premature development of adult structures during larval-pupal metamorphosis

    PubMed Central

    Parthasarathy, R.; Tan, Anjiang; Palli, Subba R.

    2008-01-01

    The biological actions of juvenile hormones are well studied; they regulate almost all aspects of an insect’s life. However, the molecular actions of these hormones are not well understood. Recent studies in the red flour beetle, Tribolium castaneum, demonstrated the utility of this insect as a model system to study JH action. These studies confirmed that the bHLH-PAS family transcription factor, methoprene-tolerant (TcMet,) plays a key role in JH action during larval stages. In this study, we investigated the role of TcMet in JH action during larval-pupal metamorphosis. The phenotypes of TcMet RNAi insects shared similarity with the phenotypes of some allatectomized lepidopteran larvae that were attempting to undergo precocious larval-pupal metamorphosis. Knocking-down TcMet during the final instar also disrupted larval-pupal ecdysis, resulting in the development of adultoid underneath the larval skin. However, the loss of TcMet did not completely block remodeling of internal tissues such as midgut. T. castaneum larvae injected with TcMet dsRNA demonstrated a resistance to a JH analog (JHA), hydroprene, irrespective of time and route of application. Knocking-down TcMet also caused down regulation of JH-response genes, JHE and Kr-h1 suggesting that TcMet might be involved in the expression of these genes. Based on the phenotype, gene expression, and JHA action studies in TcMet RNAi insects, this study concludes that Met plays a key role in JH action for preventing the premature development of adult structures during larval-pupal metamorphosis. PMID:18450431

  1. 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…

  2. 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…

  3. 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…

  4. Identification of an arginine residue in the dual coenzyme-specific glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides that plays a key role in binding NADP+ but not NAD+.

    PubMed

    Levy, H R; Vought, V E; Yin, X; Adams, M J

    1996-02-01

    Glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides can utilize either NADP or NAD as coenzyme. The enzyme's three-dimensional structure has been solved (Rowland et al., 1994, Structure 2, 1073-1087) and shown to contain a conventional nucleotide binding domain. NADP+ was modeled into the structure by superimposing the beta alpha beta domain and that of coenzyme-bound 6-phosphogluconate dehydrogenase (Adams et al., 1994, Structure 2, 651-658), enabling us to identify Arg-46 as a potentially important residue for NADP+ binding. Using site-directed mutagenesis, we constructed mutant enzymes in which Arg-46 was replaced by glutamine (R46Q) and alanine (R46A) and examined their kinetic properties. The principal effects in these mutant enzymes were that the Km and Ki values for NADP+ increased by 2 to 3 orders of magnitude over those of the wild-type enzyme. No other kinetic constant was altered more than 6.5-fold. Changing this single amino acid leads to mutant glucose-6-phosphate dehydrogenases with coenzyme specificities that favor NAD+, whereas the wild-type enzyme prefers NADP+ as coenzyme. These results confirm that Arg-46 plays a key role in NADP+ binding by contributing a positively charged planar residue that interacts primarily with the 2'-adenosine phosphate. The Arg residue corresponding to Arg-46 in L. mesenteroides glucose-6-phosphate dehydrogenase is conserved in all glucose-6-phosphate dehydrogenases and, presumably, plays the same role in all these enzymes. PMID:8579362

  5. 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…

  6. 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)

  7. 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'…

  8. 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…

  9. 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…

  10. Key roles of aquaporins in tumor biology.

    PubMed

    Papadopoulos, Marios C; Saadoun, Samira

    2015-10-01

    Aquaporins are protein channels that facilitate the flow of water across plasma cell membranes in response to osmotic gradients. This review summarizes the evidence that aquaporins play key roles in tumor biology including tumor-associated edema, tumor cell migration, tumor proliferation and tumor angiogenesis. Aquaporin inhibitors may thus be a novel class of anti-tumor agents. However, attempts to produce small molecule aquaporin inhibitors have been largely unsuccessful. Recently, monoclonal human IgG antibodies against extracellular aquaporin-4 domains have become available and could be engineered to kill aquaporin-4 over-expressing cells in the malignant brain tumor glioblastoma. We conclude this review by discussing future directions in aquaporin tumor research. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. PMID:25204262

  11. "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…

  12. 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

  13. 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

  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. The oxidoreductase DsbA plays a key role in the ability of the Crohn's disease-associated adherent-invasive Escherichia coli strain LF82 to resist macrophage killing.

    PubMed

    Bringer, Marie-Agnès; Rolhion, Nathalie; Glasser, Anne-Lise; Darfeuille-Michaud, Arlette

    2007-07-01

    Adherent-invasive Escherichia coli (AIEC) isolated from Crohn's disease patients is able to adhere to and invade intestinal epithelial cells and to replicate in mature phagolysosomes within macrophages. Here, we show that the dsbA gene, encoding a periplasmic oxidoreductase, was required for AIEC strain LF82 to adhere to intestinal epithelial cells and to survive within macrophages. The LF82-DeltadsbA mutant did not express flagella and, probably as a consequence of this, did not express type 1 pili. The role of DsbA in adhesion is restricted to the loss of flagella and type 1 pili, as forced contact between bacteria and cells and induced expression of type 1 pili restored the wild-type phenotype. In contrast, the dsbA gene is essential for AIEC LF82 bacteria to survive within macrophages, irrespective of the loss of flagella and type 1 pilus expression, and the survival ability of LF82-DeltadsbA was as low as that of the nonpathogenic E. coli K-12, which was efficiently killed by macrophages. We also provide evidence that the dsbA gene is needed for LF82 bacteria to grow and survive in an acidic and nutrient-poor medium that partly mimics the harsh environment of the phagocytic vacuole. In addition, under such stress conditions dsbA transcription is highly up-regulated. Finally, the CpxRA signaling pathway does not play a role in regulation of dsbA expression in AIEC LF82 bacteria under conditions similar to those of mature phagolysosomes. PMID:17449627

  16. 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…

  17. 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…

  18. 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…

  19. 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)

  20. 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…

  1. Separation processes: Playing a critical role

    SciTech Connect

    Humphrey, J.L.

    1995-10-01

    Separation processes are the main cog in the manufacturing well of the chemical process industries (CPI). They are used for such essential chores as removal of contaminants from raw materials, recovery and purification of primary products, and elimination of contaminants from effluent water and air streams. This article provides an overview of key separation processes, highlights recent commercial developments, and provides insights on expected new developments. It focuses o the core processes for fluid mixture separations--distillation, extraction, adsorption, membranes, and their hybrid systems. Other important processes, such as crystallization and fluid/particle separations, are left for others to cover. 40 refs., 8 figs., 4 tabs.

  2. 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

  3. 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…

  4. 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…

  5. 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.

  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. 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…

  8. 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…

  9. 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…

  10. 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…

  11. 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)

  12. 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…

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. "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…

  19. 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…

  20. 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

  1. Landsat plays a key role in reducing hunger on earth

    USGS Publications Warehouse

    U.S. Geological Survey

    2016-01-01

    The United Nations’ Department of Economic and Social Affairs predicts 9.7 billion people will sit down every day to the global dinner table by 2050. If this prediction is correct, the world is going to need more crops, more livestock, and more efficient agricultural practices.

  2. GIS plays key role in NYC Rescue and Relief Operation

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    New York City, Sept. 17—The posters of missing loved ones are pasted onto New York City walls and street signs six days after 2 hijacked commercial airlines destroyed the World Trade Center in lower Manhattan on September 11. Several miles uptown from “ground zero,” heightened security hovers around the city's Office of Emergency Management rescue and relief command center, an around-the-clock operation. Police, firefighters, military, officials with the Federal Emergency Management Agency, communications technicians, and a beehive of others work in controlled chaos in this cavernous, convention center-sized hall, lined with computers and adorned with several American flags.After the original command center at 7 World Trade Center collapsed to rubble as an after-effect of the plane strikes, city officials scrambled to recreate it. Alan Leidner, director of New York's citywide geographic information systems (GIS), and who is with the Department of Information Technology and Telecommunications, knew that maps would be an integral component of the rescue and relief efforts. Maps provide emergency workers and others with accurate and detailed scientific data in the form of visual aids upon which they can make informed decisions.

  3. 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…

  4. ``Plug and play'' quantum key distribution system with differential phase shift

    NASA Astrophysics Data System (ADS)

    Zhou, Chunyuan; Wu, Guang; Chen, Xiuliang; Zeng, Heping

    2003-09-01

    We propose a "plug and play" scheme for the long-distance fiber-based cryptosystem based on the differential phase shift quantum key distribution, where any birefringence effects and polarization-dependent losses in the transmission fiber are automatically compensated by using a Faraday mirror. This system not only has stable performance but also creates keys 8/3 times more efficiently than the conventional cryptosystem based on the BB84 protocol.

  5. 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)

  6. 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 ...

  7. 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...

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. "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…

  14. 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…

  15. 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

  16. 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…

  17. 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…

  18. (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.

  19. 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

  20. 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

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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)

  8. 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…

  9. 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…

  10. 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…

  11. 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…

  12. 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)

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. 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

  20. 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)

  1. 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…

  2. 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…

  3. Plug-and-play measurement-device-independent quantum key distribution

    NASA Astrophysics Data System (ADS)

    Choi, Yujun; Kwon, Osung; Woo, Minki; Oh, Kyunghwan; Han, Sang-Wook; Kim, Yong-Su; Moon, Sung

    2016-03-01

    Quantum key distribution (QKD) guarantees unconditional communication security based on the laws of quantum physics. However, practical QKD suffers from a number of quantum hackings due to the device imperfections. From the security standpoint, measurement-device-independent quantum key distribution (MDI-QKD) is in the limelight since it eliminates all the possible loopholes in detection. Due to active control units for mode matching between the photons from remote parties, however, the implementation of MDI-QKD is highly impractical. In this paper, we propose a method to resolve the mode matching problem while minimizing the use of active control units. By introducing the plug-and-play (P&P) concept into MDI-QKD, the indistinguishability in spectral and polarization modes between photons can naturally be guaranteed. We show the feasibility of P&P MDI-QKD with a proof-of-principle experiment.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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…

  9. 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…

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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)

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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)

  6. Agroecology: the key role of arbuscular mycorrhizas in ecosystem services.

    PubMed

    Gianinazzi, Silvio; Gollotte, Armelle; Binet, Marie-Noëlle; van Tuinen, Diederik; Redecker, Dirk; Wipf, Daniel

    2010-11-01

    The beneficial effects of arbuscular mycorrhizal (AM) fungi on plant performance and soil health are essential for the sustainable management of agricultural ecosystems. Nevertheless, since the 'first green revolution', less attention has been given to beneficial soil microorganisms in general and to AM fungi in particular. Human society benefits from a multitude of resources and processes from natural and managed ecosystems, to which AM make a crucial contribution. These resources and processes, which are called ecosystem services, include products like food and processes like nutrient transfer. Many people have been under the illusion that these ecosystem services are free, invulnerable and infinitely available; taken for granted as public benefits, they lack a formal market and are traditionally absent from society's balance sheet. In 1997, a team of researchers from the USA, Argentina and the Netherlands put an average price tag of US $33 trillion a year on these fundamental ecosystem services. The present review highlights the key role that the AM symbiosis can play as an ecosystem service provider to guarantee plant productivity and quality in emerging systems of sustainable agriculture. The appropriate management of ecosystem services rendered by AM will impact on natural resource conservation and utilisation with an obvious net gain for human society. PMID:20697748

  7. 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…

  8. 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

  9. Investigating the Evolution of Key Member Roles in Socio-Technical Networks--Introducing the Composite Role Framework

    ERIC Educational Resources Information Center

    Lid, Viil

    2013-01-01

    The vitality of socio-technical networks, like online communities and social networks, is predominantly dependent upon active member participation. In most socio-technical networks a minority of members participate more than others and thus play key roles that sustain the value of the network. The overarching objective of this study was to extend…

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  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. 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…

  20. 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…

  1. 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…

  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. Patient advocacy in the USA: key communication role functions.

    PubMed

    Martin, Donald R; Tipton, Bryan K

    2007-09-01

    Researchers have long documented the importance of patient advocacy programs as a means of providing customer service in health-care organizations. Yet, while effective communication is often acknowledged as key to effective patient advocacy, knowledge of the specific communication role functions enacted by patient advocates remains limited, as does our understanding of the function of patient advocacy at the organizational level. This qualitative investigation not only provides a typology of communication roles enacted by patient advocates while solving problems on behalf of patients and their family members, but also integrates scholarly research on "boundary-spanning" as a means of theoretically contextualizing the advocacy role at the organizational level. PMID:17688476

  6. Where Do the Children Play? A Manual for Latch Key Child Development Programs.

    ERIC Educational Resources Information Center

    YMCA of Metropolitan Portland, OR.

    This manual outlines the goals, guidelines, and requirements of Y.M.C.A. Latch Key Child Development Programs, which provide before- and after-school day care services for children who otherwise might be at home with no adult supervision. Included is information on how to begin a program, enrollment procedures, facilities, space utilization, daily…

  7. 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

  8. 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…

  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. 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

  12. 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…

  13. Building the Education Pipeline: Why Boards Must Play a Role

    ERIC Educational Resources Information Center

    Reed, Charles B.

    2010-01-01

    Working with K-12 schools is a valuable way for institutions and their boards to cultivate college-ready students and equip them with a sense of purpose and direction when they arrive on campus. Key elements to preparing young students for higher education include communicating expectations clearly and consistently, reaching out to underserved…

  14. Mutations in metabolic pathways, what role does genetic background play?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ornithine transcarbamylase (OTC) is a key enzyme for the synthesis of urea and the endogenous synthesis of arginine. OTC is present in hepatocytes and enterocytes and catalyzes the synthesis of citrulline. Although the spf-ash mutation results in a reduction in enzyme abundance, ureagenesis is maint...

  15. Psychopathology in Adolescence: Does Development Play a Role?

    ERIC Educational Resources Information Center

    Petersen, Anne C.; Ebata, Aaron T.

    Thos paper discusses myths about adolescent psychopathology, including the beliefs that psychopathology is a normal state in adolescence; that adolescents grow out of their psychopathology; and that with regard to psychopathology, adolescents are either like adults or like children. Key features of adolescent development are summarized, the life…

  16. 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…

  17. 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.

  18. The Influence of an Educational Course on Language Expression and Treatment of Gaming Addiction for Massive Multiplayer Online Role-Playing Game (MMORPG) Players

    ERIC Educational Resources Information Center

    Kim, Pyoung Won; Kim, Seo Young; Shim, Miseon; Im, Chang-Hwan; Shon, Young-Min

    2013-01-01

    Addiction to Massive Multiple Online Role-Playing Games (MMORPGs) among juveniles has become a serious problem in Korea and has led to legislation prohibiting juveniles from playing games after midnight. One key factor in gaming addiction is the so-called narrative, or story, gamers create for themselves while playing. This study investigated how…

  19. Key roles of necroptotic factors in promoting tumor growth

    PubMed Central

    Liu, Xinjian; Zhou, Min; Mei, Ling; Ruan, Jiaying; Hu, Qian; Peng, Jing; Su, Hang; Liao, Hong; Liu, Shanling; Liu, WeiPing; Wang, He; Huang, Qian; Li, Fang; Li, Chuan-Yuan

    2016-01-01

    Necroptotic factors are generally assumed to play a positive role in tumor therapy by eliminating damaged tumor cells. Here we show that, contrary to expectation, necroptotic factors RIPK1, RIPK3, and MLKL promote tumor growth. We demonstrate that genetic knockout of necroptotic genes RIPK1, RIPK3, or MLKL in cancer cells significantly attenuated their abilities to grow in an anchorage-independent manner. In addition, they exhibited significantly enhanced radiosensitivity. The knockout cells also showed greatly reduced ability to form tumors in mice. Moreover, necrosulfonamide (NSA), a previously identified chemical inhibitor of necroptosis, could significantly delay tumor growth in a xenograft model. Mechanistically, we show that necroptoic factors play a significant role in maintaining the activity of NF-κB. Finally, we found that high levels of phosphorylated MLKL in human esophageal and colon cancers are associated with poor overall survival. Taken together, we conclude that pro-necroptic factors such as RIPK1, RIPK3, and MLKL may play a role in supporting tumor growth, and MLKL may be a promising target for cancer treatment. PMID:26959742

  20. Key roles of necroptotic factors in promoting tumor growth.

    PubMed

    Liu, Xinjian; Zhou, Min; Mei, Ling; Ruan, Jiaying; Hu, Qian; Peng, Jing; Su, Hang; Liao, Hong; Liu, Shanling; Liu, WeiPing; Wang, He; Huang, Qian; Li, Fang; Li, Chuan-Yuan

    2016-04-19

    Necroptotic factors are generally assumed to play a positive role in tumor therapy by eliminating damaged tumor cells. Here we show that, contrary to expectation, necroptotic factors RIPK1, RIPK3, and MLKL promote tumor growth. We demonstrate that genetic knockout of necroptotic genes RIPK1, RIPK3, or MLKL in cancer cells significantly attenuated their abilities to grow in an anchorage-independent manner. In addition, they exhibited significantly enhanced radiosensitivity. The knockout cells also showed greatly reduced ability to form tumors in mice. Moreover, necrosulfonamide (NSA), a previously identified chemical inhibitor of necroptosis, could significantly delay tumor growth in a xenograft model. Mechanistically, we show that necroptoic factors play a significant role in maintaining the activity of NF-κB. Finally, we found that high levels of phosphorylated MLKL in human esophageal and colon cancers are associated with poor overall survival. Taken together, we conclude that pro-necroptic factors such as RIPK1, RIPK3, and MLKL may play a role in supporting tumor growth, and MLKL may be a promising target for cancer treatment. PMID:26959742

  1. 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…

  2. Vascular growth factors play critical roles in kidney glomeruli.

    PubMed

    Gnudi, Luigi; Benedetti, Sara; Woolf, Adrian S; Long, David A

    2015-12-01

    Kidney glomeruli ultrafilter blood to generate urine and they are dysfunctional in a variety of kidney diseases. There are two key vascular growth factor families implicated in glomerular biology and function, namely the vascular endothelial growth factors (VEGFs) and the angiopoietins (Angpt). We present examples showing not only how these molecules help generate and maintain healthy glomeruli but also how they drive disease when their expression is dysregulated. Finally, we review how manipulating VEGF and Angpt signalling may be used to treat glomerular disease. PMID:26561594

  3. 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.

  4. 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

  5. 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

  6. 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.…

  7. 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)

  8. 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

  9. 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

  10. Natural fracture characterization: A key to success in an exploration play, Converse County, Wyoming

    SciTech Connect

    Parks, S.L.; Gale, M.S.; Bradley, P.J.; Mount, V.S.

    1996-06-01

    Numerous vertical wells drilled in the southern Powder River basin have encountered fractured, tight, overpressured, Cretaceous hydrocarbon reservoirs. These reservoirs demonstrate enhanced productivity and ultimate recovery with little to no water production. Effective exploration and development of these reservoirs includes a systematic approach to characterization and prediction of the fracture system. Surface mapping within Cretaceous units along the southern and western margins of the basin revealed multiple fracture sets related to both regional and local tectonic events. A pre-Laramide regional fracture set oriented at approximately N70{degrees}E is dominant over the mapped 500 square mile area. This set displays a consistent frequency, direction, height. and morphology both in the surface and subsurface. Fractures in early Tertiary rocks within the basin are unidirectionally oriented along a WNW azimuth, a direction also found in the Cretaceous units. Vaster Resources, Inc. is actively exploring fractured reservoirs in the Powder River basin with horizontal wells targeting the Niobrara and Frontier formations. Integration of the detailed surface outcrop studies with regional cross-sections, Landsat lineament analysis, FMS log data, 2D multicomponent/multisource shear wave seismic, and borehole breakouts (to determine present day stress) have been used to successfully predict the orientation, frequency, and degree of openness of the subsurface fracture system. The consistency of the fracture system and its positive impact on reservoir productivity significantly enhance the prospectiveness of Cretaceous plays throughout the southern Powder River basin.