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  1. Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites

    PubMed Central

    Rajendran, Esther; Hapuarachchi, Sanduni V.; Miller, Catherine M.; Fairweather, Stephen J.; Cai, Yeping; Smith, Nicholas C.; Cockburn, Ian A.; Bröer, Stefan; Kirk, Kiaran; van Dooren, Giel G.

    2017-01-01

    Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. The identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. Here we demonstrate that members of an apicomplexan-specific protein family—the Novel Putative Transporters (NPTs)—play key roles in the uptake of cationic amino acids. We show that an NPT from Toxoplasma gondii (TgNPT1) is a selective arginine transporter that is essential for parasite survival and virulence. We also demonstrate that a homologue of TgNPT1 from the malaria parasite Plasmodium berghei (PbNPT1), shown previously to be essential for the sexual gametocyte stage of the parasite, is a cationic amino acid transporter. This reveals a role for cationic amino acid scavenging in gametocyte biology. Our study demonstrates a critical role for amino acid transporters in the survival, virulence and life cycle progression of these parasites. PMID:28205520

  2. Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites.

    PubMed

    Rajendran, Esther; Hapuarachchi, Sanduni V; Miller, Catherine M; Fairweather, Stephen J; Cai, Yeping; Smith, Nicholas C; Cockburn, Ian A; Bröer, Stefan; Kirk, Kiaran; van Dooren, Giel G

    2017-02-16

    Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. The identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. Here we demonstrate that members of an apicomplexan-specific protein family-the Novel Putative Transporters (NPTs)-play key roles in the uptake of cationic amino acids. We show that an NPT from Toxoplasma gondii (TgNPT1) is a selective arginine transporter that is essential for parasite survival and virulence. We also demonstrate that a homologue of TgNPT1 from the malaria parasite Plasmodium berghei (PbNPT1), shown previously to be essential for the sexual gametocyte stage of the parasite, is a cationic amino acid transporter. This reveals a role for cationic amino acid scavenging in gametocyte biology. Our study demonstrates a critical role for amino acid transporters in the survival, virulence and life cycle progression of these parasites.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Endoplasmic Reticulum Stress Plays a Key Role in the Pathogenesis of Diabetic Peripheral Neuropathy

    PubMed Central

    Lupachyk, Sergey; Watcho, Pierre; Stavniichuk, Roman; Shevalye, Hanna; Obrosova, Irina G.

    2013-01-01

    Endoplasmic reticulum stress resulting from abnormal folding of newly synthesized proteins impairs metabolism, transcriptional regulation, and gene expression, and it is a key mechanism of cell injury. Endoplasmic reticulum stress plays an important role in cardiovascular and neurodegenerative diseases, cancer, and diabetes. We evaluated the role for this phenomenon in diabetic peripheral neuropathy. Endoplasmic reticulum stress manifest in upregulation of multiple components of unfolded protein response was identified in neural tissues (sciatic nerve, spinal cord) of streptozotocin diabetic rats and mice. A chemical chaperone, trimethylamine oxide, administered for 12 weeks after induction of diabetes (110 mg⋅kg−1⋅d−1, a prevention paradigm) attenuated endoplasmic reticulum stress, peripheral nerve dysfunction, intraepidermal nerve fiber loss, and sciatic nerve and spinal cord oxidative-nitrative stress in streptozotocin diabetic rats. Similar effects on diabetes-induced endoplasmic reticulum stress and peripheral nerve dysfunction were observed with a structurally unrelated chemical chaperone, 4-phenylbutyric acid (100 mg⋅kg−1⋅d−1, intraperitoneal). CCAAT/enhancer-binding protein homologous protein (CHOP)−/− mice made diabetic with streptozotocin displayed less severe sciatic nerve oxidative-nitrative stress and peripheral neuropathy than the wild-type (C57Bl6/J) mice. Neither chemical chaperones nor CHOP gene deficiency reduced diabetic hyperglycemia. Our findings reveal an important role of endoplasmic reticulum stress in the development of diabetic peripheral neuropathy and identify a potential new therapeutic target. PMID:23364451

  8. The stringent response plays a key role in Bacillus subtilis survival of fatty acid starvation.

    PubMed

    Pulschen, André A; Sastre, Diego E; Machinandiarena, Federico; Crotta Asis, Agostina; Albanesi, Daniela; de Mendoza, Diego; Gueiros-Filho, Frederico J

    2017-02-01

    The stringent response is a universal adaptive mechanism to protect bacteria from nutritional and environmental stresses. The role of the stringent response during lipid starvation has been studied only in Gram-negative bacteria. Here, we report that the stringent response also plays a crucial role in the adaptation of the model Gram-positive Bacillus subtilis to fatty acid starvation. B. subtilis lacking all three (p)ppGpp-synthetases (RelBs , RelP and RelQ) or bearing a RelBs variant that no longer synthesizes (p)ppGpp suffer extreme loss of viability on lipid starvation. Loss of viability is paralleled by perturbation of membrane integrity and function, with collapse of membrane potential as the likely cause of death. Although no increment of (p)ppGpp could be detected in lipid starved B. subtilis, we observed a substantial increase in the GTP/ATP ratio of strains incapable of synthesizing (p)ppGpp. Artificially lowering GTP with decoyinine rescued viability of such strains, confirming observations that low intracellular GTP is important for survival of nutritional stresses. Altogether, our results show that activation of the stringent response by lipid starvation is a broadly conserved response of bacteria and that a key role of (p)ppGpp is to couple biosynthetic processes that become detrimental if uncoordinated.

  9. Quantitative proteomics reveals that peroxidases play key roles in post-flooding recovery in soybean roots.

    PubMed

    Khan, Mudassar Nawaz; Sakata, Katsumi; Hiraga, Susumu; Komatsu, Setsuko

    2014-12-05

    Soybean is an important legume crop that exhibits markedly reduced growth and yields under flooding conditions. To unravel the mechanisms involved in recovery after flooding in soybean root, gel-free proteomic analysis was performed. Morphological analysis revealed that growth suppression was more severe with increased flooding duration. Out of a total of 1645 and 1707 identified proteins, 73 and 21 proteins were changed significantly during the recovery stage following 2 and 4 days flooding, respectively. Based on the proteomic, clustering, and in silico protein-protein interaction analyses, six key enzymes were analyzed at the mRNA level. Lipoxygenase 1, which was increased at the protein level during the recovery period, was steadily down-regulated at the mRNA level. The peroxidase superfamily protein continuously increased in abundance during the course of recovery and was up-regulated at the mRNA level. HAD acid phosphatase was decreased at the protein level and down-regulated at the transcript level, while isoflavone reductase and an unknown protein were increased at both the protein and mRNA levels. Consistent with these findings, the enzymatic activity of peroxidase was decreased under flooding stress but increased significantly during the recovery sage. These results suggest that peroxidases might play key roles in post-flooding recovery in soybean roots through the scavenging of toxic radicals.

  10. Synaptojanin-1 plays a key role in astrogliogenesis: possible relevance for Down’s syndrome

    PubMed Central

    Herrera, Federico; Chen, Qi; Fischer, Wolfgang H.; Maher, Pamela; Schubert, David

    2009-01-01

    There is increasing interest in gliogenesis as the relevance of glia to both brain development and pathology becomes better understood. However, little is known about this process. The use of multidimensional protein identification technology (MudPIT) to identify changes in phosphoprotein levels in rat neural precursor cells treated with cytokines or retinoic acid showed that phosphorylation of the catalytic subunit of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K p110α) and dephosphorylation of the inositol phosphatase synaptojanin-1 were common to the gliogenic stimuli. While PI3K was found to be involved in both neuro- and astrogliogenesis, synaptojanin-1 was specifically involved in astrogliogenesis of neural precursor cells. The role of synaptojanin-1 in astrogliogenesis was further confirmed by analysis of neuron- and glia-specific markers in synaptojanin-1 knockout mouse brain. Additional experiments showed that the Sac1-like phosphatase domain of synaptojanin-1 is the responsible for the observed astrogliogenic effect. Our results strongly indicate that phosphatidylinositol metabolism plays a key role in astrogliogenesis. The relevance of our findings for Down’s syndrome pathology is discussed. PMID:19282871

  11. The nonstructural proteins of Nipah virus play a key role in pathogenicity in experimentally infected animals.

    PubMed

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

    2010-09-15

    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.

  12. PP2C family members play key roles in regulation of cell survival and apoptosis.

    PubMed

    Tamura, Shinri; Toriumi, Shinnosuke; Saito, Jun-Ichi; Awano, Kenjiro; Kudo, Tada-Aki; Kobayashi, Takayasu

    2006-07-01

    Although unlimited proliferation of cancer cells is supported by multiple signaling pathways involved in the regulation of proliferation, survival, and apoptosis, the molecular mechanisms coordinating these different pathways to promote the proliferation and survival of cancer cells have remained unclear. SAPK and integrin-ILK signaling pathways play key roles in the promotion of apoptosis and cell proliferation/survival, respectively. Studies of TNFalpha- and H2O2-induced apoptosis revealed that ASK1, a component of the SAPK system, mediates the TNFalpha and H2O2 signaling of apoptosis. ASK1 is activated by autophosphorylation of a specific threonine residue (T845) following TNFalpha stimulation. Our recent studies indicate that PP2Cepsilon, a member of the PP2C family, associates with and inactivates ASK1 by dephosphorylating T845. In contrast, PP2Cdelta/ILKAP, a second PP2C family member, activates ASK1 by enhancing cellular phosphorylation of T845. PP2Cdelta/ILKAP also forms a complex with ILK1 to inhibit the GSK3beta-mediated integrin-ILK1 signaling in vivo, inhibiting cell cycle progression. These observations raise the possibility that PP2Cdelta/ILKAP acts to control the cross-talk between integrin-induced and TNFalpha-induced signaling pathways, inhibiting the former and stimulating the latter, thereby inhibiting proliferation and survival and promoting the apoptosis of cancer cells.

  13. Epidermal CD147 expression plays a key role in IL-22-induced psoriatic dermatitis

    PubMed Central

    Peng, Cong; Zhang, ShengXi; Lei, Li; Zhang, Xu; Jia, Xuekun; Luo, Zhongling; Huang, Xiaoyan; Kuang, Yanhong; Zeng, Weiqi; Su, Juan; Chen, Xiang

    2017-01-01

    Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and terminal differentiation. Interleukin-22 (IL-22) and the transcription factor Stat3 play pivotal roles in the pathogenesis of psoriasis. CD147 is a transmembrane glycosylation protein that belongs to the immunoglobulin superfamily. Our previous studies have shown that CD147 is a marker of high keratinocyte proliferation and poor keratinocyte differentiation as well as a psoriasis susceptibility gene. The current study demonstrates that CD147 is highly expressed in psoriatic skin lesions. Specific CD147 over-expression in the epidermis of K5-promoter transgenic mice promotes imiquimod (IMQ)-induced psoriasis-like inflammation characterized by acanthosis, granular layer loss and inflammatory cell infiltration. We also found that IL-22 increases CD147 transcription in vitro and in vivo and that Stat3 binds directly to the CD147 promoter between positions −854 and −440, suggesting that CD147 expression is up-regulated in patients with psoriasis through Stat3 activation. In addition, CD147 knockdown dramatically blocks IL-22-mediated Stat3 activation as well as IL-22-induced cytokine, chemokine and antimicrobial factor expression. Together, these findings show that CD147 is a novel and key mediator of IL-22-induced psoriatic alterations in the epidermis and might be a therapeutic target in patients with psoriasis. PMID:28272440

  14. Hepatocyte growth factor plays a key role in insulin resistance-associated compensatory mechanisms.

    PubMed

    Araújo, Tiago G; Oliveira, Alexandre G; Carvalho, Bruno M; Guadagnini, Dioze; Protzek, André O P; Carvalheira, Jose B C; Boschero, Antonio C; Saad, Mario J A

    2012-12-01

    Insulin resistance is present in obesity and in type 2 diabetes and is associated with islet cell hyperplasia and hyperinsulinemia, but the driving forces behind this compensatory mechanism are incompletely understood. Previous data have suggested the involvement of an unknown circulating insulin resistance-related β-cell growth factor. In this context, looking for candidates to be a circulating factor, we realized that hepatocyte growth factor (HGF) is a strong candidate as a link between insulin resistance and increased mass of islets/hyperinsulinemia. Our approach aimed to show a possible cause-effect relationship between increase in circulating HGF levels and compensatory islet hyperplasia/hyperinsulinemia by showing the strength of the association, whether or not is a dose-dependent response, the temporality, consistency, plausibility, and reversibility of the association. In this regard, our data showed: 1) a strong and consistent correlation between HGF and the compensatory mechanism in three animal models of insulin resistance; 2) HGF increases β-cell mass in a dose-dependent manner; 3) blocking HGF shuts down the compensatory mechanisms; and 4) an increase in HGF levels seems to precede the compensatory response associated with insulin resistance, indicating that these events occur in a sequential mode. Additionally, blockages of HGF receptor (Met) worsen the impaired insulin-induced insulin signaling in liver of diet-induced obesity rats. Overall, our data indicate that HGF is a growth factor playing a key role in islet mass increase and hyperinsulinemia in diet-induced obesity rats and suggest that the HGF-Met axis may have a role on insulin signaling in the liver.

  15. Supporting Children and Families: Communities, Schools, Employers Play Key Roles. Growing Up Well. Focus on Prevention.

    ERIC Educational Resources Information Center

    Barthauer, Linda; Halfon, Neal

    This report, eighth and last in a series, discusses the important role community groups and leaders, schools, and employers play in providing children and parents support and encouragement. It reports the opinions of California adults, expressed in a survey conducted by the California Center for Health Improvement (CCHI), about a variety of issues…

  16. Bromodomain Protein Brd4 Plays a Key Role in Merkel Cell Polyomavirus DNA Replication

    PubMed Central

    Wang, Xin; Li, Jing; Schowalter, Rachel M.; Jiao, Jing; Buck, Christopher B.; You, Jianxin

    2012-01-01

    Merkel cell polyomavirus (MCV or MCPyV) is the first human polyomavirus to be definitively linked to cancer. The mechanisms of MCV-induced oncogenesis and much of MCV biology are largely unexplored. In this study, we demonstrate that bromodomain protein 4 (Brd4) interacts with MCV large T antigen (LT) and plays a critical role in viral DNA replication. Brd4 knockdown inhibits MCV replication, which can be rescued by recombinant Brd4. Brd4 colocalizes with the MCV LT/replication origin complex in the nucleus and recruits replication factor C (RFC) to the viral replication sites. A dominant negative inhibitor of the Brd4-MCV LT interaction can dissociate Brd4 and RFC from the viral replication complex and abrogate MCV replication. Furthermore, obstructing the physiologic interaction between Brd4 and host chromatin with the chemical compound JQ1(+) leads to enhanced MCV DNA replication, demonstrating that the role of Brd4 in MCV replication is distinct from its role in chromatin-associated transcriptional regulation. Our findings demonstrate mechanistic details of the MCV replication machinery; providing novel insight to elucidate the life cycle of this newly discovered oncogenic DNA virus. PMID:23144621

  17. Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis

    PubMed Central

    Xie, Wanqing; Zhou, Lijiang; Li, Shan; Hui, Tianqian; Chen, Di

    2015-01-01

    Spondyloarthritis (SpA) is a group of diseases consisting of psoriatic arthritis (PsA), reactive arthritis, arthritis related to inflammatory bowel disease (a subgroup of juvenile idiopathic arthritis), and ankylosing spondylitis (the prototype of SpA). Axial bone formation and the combination of concurrent erosion and new bone formation are specific characteristics of SpA disease. The use of anti-proinflammatory cytokines, such as inhibitors of tumor necrosis factor α (TNF-α), appears to be the greatest advance in the treatment of SpA over the past 20 years. However, TNF-α blockers do not halt new bone formation. Recent clinical observations and animal studies demonstrate that Wnt signaling proteins and natural Wnt inhibitors, such as DKK1 and sclerostin, are likely to play important roles in the process of ankylosis in SpA, and could potentially serve as therapeutic targets for the treatment of SpA. PMID:26629686

  18. Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis.

    PubMed

    Xie, Wanqing; Zhou, Lijiang; Li, Shan; Hui, Tianqian; Chen, Di

    2016-01-01

    Spondyloarthritis (SpA) is a group of diseases consisting of psoriatic arthritis (PsA), reactive arthritis, arthritis related to inflammatory bowel disease (a subgroup of juvenile idiopathic arthritis), and ankylosing spondylitis (the prototype of SpA). Axial bone formation and the combination of concurrent erosion and new bone formation are specific characteristics of SpA disease. The use of antiproinflammatory cytokines, such as inhibitors of tumor necrosis factor α (TNF-α), appears to be the greatest advance in the treatment of SpA over the past 20 years. However, TNF-α blockers do not halt new bone formation. Recent clinical observations and animal studies demonstrate that Wnt signaling proteins and natural Wnt inhibitors, such as DKK1 and sclerostin, are likely to play important roles in the process of ankylosis in SpA, and could potentially serve as therapeutic targets for the treatment of SpA.

  19. Cell wall composition plays a key role on sensitivity of filamentous fungi to chitosan.

    PubMed

    Aranda-Martinez, Almudena; Lopez-Moya, Federico; Lopez-Llorca, Luis Vicente

    2016-10-01

    Chitosan antifungal activity has been reported for both filamentous fungi and yeast. Previous studies have shown fungal plasma membrane as main chitosan target. However, the role of the fungal cell wall (CW) in their response to chitosan is unknown. We show that cell wall regeneration in Neurospora crassa (chitosan sensitive) protoplasts protects them from chitosan damage. Caspofungin, a β-1,3-glucan synthase inhibitor, showed a synergistic antifungal effect with chitosan for N. crassa but not for Pochonia chlamydosporia, a biocontrol fungus resistant to chitosan. Chitosan significantly repressed N. crassa genes involved in β-1,3-glucan synthesis (fks) and elongation (gel-1) but the chitin synthase gene (chs-1) did not present changes in its expression. N. crassa cell wall deletion strains related to β-1,3-glucan elongation (Δgel-1 and Δgel-2) were more sensitive to chitosan than wild type (wt). On the contrary, chitin synthase deletion strain (Δchs-1) showed the same sensitivity to chitosan than wt. The mycelium of P. chlamydosporia showed a higher (ca. twofold) β-1,3-glucan/chitin ratio than that of N. crassa. Taken together, our results indicate that cell wall composition plays an important role on -sensitivity of filamentous fungi to chitosan.

  20. Parental provisioning behaviour plays a key role in linking personality with reproductive success.

    PubMed

    Mutzel, A; Dingemanse, N J; Araya-Ajoy, Y G; Kempenaers, B

    2013-08-07

    Repeatable behavioural traits ('personality') have been shown to covary with fitness, but it remains poorly understood how such behaviour-fitness relationships come about. We applied a multivariate approach to reveal the mechanistic pathways by which variation in exploratory and aggressive behaviour is translated into variation in reproductive success in a natural population of blue tits, Cyanistes caeruleus. Using path analysis, we demonstrate a key role for provisioning behaviour in mediating the link between personality and reproductive success (number of fledged offspring). Aggressive males fed their nestlings at lower rates than less aggressive individuals. At the same time, their low parental investment was associated with increased female effort, thereby positively affecting fledgling production. Whereas male exploratory behaviour was unrelated to provisioning behaviour and reproductive success, fast-exploring females fed their offspring at higher rates and initiated breeding earlier, thus increasing reproductive success. Our findings provide strong support for specific mechanistic pathways linking components of behavioural syndromes to reproductive success. Importantly, relationships between behavioural phenotypes and reproductive success were obscured when considering simple bivariate relationships, underlining the importance of adopting multivariate views and statistical tools as path analysis to the study of behavioural evolution.

  1. 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

  2. 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.

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

    PubMed Central

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

    2015-01-01

    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

  4. A FILAMENTOUS FLOWER orthologue plays a key role in leaf patterning in opium poppy.

    PubMed

    Vosnakis, Nikolaos; Maiden, Afiqah; Kourmpetli, Sofia; Hands, Philip; Sharples, Donna; Drea, Sinéad

    2012-11-01

    The plant-specific YABBY genes were initially defined by their roles in determining abaxial/adaxial cell fate in lateral organs of eudicots, and repressing meristematic genes in differentiating tissues such as leaves. In Arabidopsis thaliana FILAMENTOUS FLOWER (FIL) is also required for inflorescence and floral meristem establishment and flower development in a pathway involving the floral transition and identity genes. Here we describe the characterization of a FIL orthologue from the basal eudicot, Papaver somniferum (the opium poppy), and demonstrate a role for the gene in patterning the highly lobed leaf of the poppy. Silencing of PapsFIL using viral-induced gene silencing resulted in leaves of reduced laminar area, more pronounced margin serration and, in some cases, leaf bifurcation. In contrast, the gene does not appear to affect the development of the flower, and these variations in function are discussed in relation to its taxonomic position as a basal eudicot and its determinate growth habit.

  5. Domain a' of protein disulfide isomerase plays key role in inhibiting alpha-synuclein fibril formation.

    PubMed

    Cheng, Han; Wang, Lei; Wang, Chih-chen

    2010-07-01

    alpha-Synuclein (alpha Syn) is the main component of Lewy bodies formed in midbrain dopaminergic neurons which is a pathological characteristic of Parkinson's disease. It has been recently showed to induce endoplasmic reticulum (ER) stress and impair ER functions. However, the mechanism of how ER responds to alpha Syn toxicity is poorly understood. In the present study, we found that protein disulfide isomerase (PDI), a stress protein abundant in ER, effectively inhibits alpha Syn fibril formation in vitro. In PDI molecule with a structure of abb'xa'c, domain a' was found to be essential and sufficient for PDI to inhibit alpha Syn fibril formation. PDI was further found to be more avid for binding with intermediate species formed during alpha Syn fibril formation, and the binding was more intensive in the later lag phase. Our results provide new insight into the role of PDI in protecting ER from the deleterious effects of misfolded protein accumulation in many neurodegenerative diseases.

  6. Elevated Nicotianamine Levels in Arabidopsis halleri Roots Play a Key Role in Zinc Hyperaccumulation[W

    PubMed Central

    Deinlein, Ulrich; Weber, Michael; Schmidt, Holger; Rensch, Stefan; Trampczynska, Aleksandra; Hansen, Thomas H.; Husted, Søren; Schjoerring, Jan K.; Talke, Ina N.; Krämer, Ute; Clemens, Stephan

    2012-01-01

    Zn deficiency is among the leading health risk factors in developing countries. Breeding of Zn-enriched crops is expected to be facilitated by molecular dissection of plant Zn hyperaccumulation (i.e., the ability of certain plants to accumulate Zn to levels >100-fold higher than normal plants). The model hyperaccumulators Arabidopsis halleri and Noccaea caerulescens share elevated nicotianamine synthase (NAS) expression relative to nonaccumulators among a core of alterations in metal homeostasis. Suppression of Ah-NAS2 by RNA interference (RNAi) resulted in strongly reduced root nicotianamine (NA) accumulation and a concomitant decrease in root-to-shoot translocation of Zn. Speciation analysis by size-exclusion chromatography coupled to inductively coupled plasma mass spectrometry showed that the dominating Zn ligands in roots were NA and thiols. In NAS2-RNAi plants, a marked increase in Zn-thiol species was observed. Wild-type A. halleri plants cultivated on their native soil showed elemental profiles very similar to those found in field samples. Leaf Zn concentrations in NAS2-RNAi lines, however, did not reach the Zn hyperaccumulation threshold. Leaf Cd accumulation was also significantly reduced. These results demonstrate a role for NAS2 in Zn hyperaccumulation also under near-natural conditions. We propose that NA forms complexes with Zn(II) in root cells and facilitates symplastic passage of Zn(II) toward the xylem. PMID:22374395

  7. 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

  8. p38 mitogen-activated protein kinase plays a key role in regulating MAPKAPK2 expression

    SciTech Connect

    Sudo, Tatsuhiko . E-mail: sudo@riken.jp; Kawai, Kayoko; Matsuzaki, Hiroshi; Osada, Hiroyuki

    2005-11-18

    One of three major families of the mitogen-activated kinases (MAPK), p38 as well as JNK, has been shown to transduce extracellular stress stimuli into cellular responses by phospho-relay cascades. Among p38 families, p38{alpha} is a widely characterized isoform and the biological phenomena are explained by its kinase activity regulating functions of its downstream substrates. However, its specific contributions to each phenomenon are yet not fully elucidated. For better understanding of the role of MAPKs, especially p38{alpha}, we utilized newly established mouse fibroblast cell lines originated from a p38{alpha} null mouse, namely, a parental cell line without p38{alpha} gene locus, knockout of p38{alpha} (KOP), Zeosin-resistant (ZKOP), revertant of p38{alpha} (RKOP), and Exip revertant (EKOP). EKOP is smaller in size but grows faster than the others. Although comparable amounts of ERK and JNK are expressed in each cell line, ERK is highly phosphorylated in EKOP even in normal culture conditions. Serum stimulation after serum starvation led to ERK phosphorylation in RKOP and ZKOP, but not in EKOP as much. On the contrary, relative phosphorylation level of JNK to total JNK in response to UV was low in RKOP. And its phosphorylation as well as total JNK is slightly lower in EKOP. RKOP is less sensitive to UV irradiation as judged by the survival rate. Stress response upon UV or sorbitol stimuli, leading to mitogen activate protein kinase activated kinase 2 (MAPKAPK2) phosphorylation, was only observed in RKOP. Further experiments reveal that MAPKAPK2 expression is largely suppressed in ZKOP and EKOP. Its expression was recovered by re-introduction of p38{alpha}. The loss of MAPKAPK2 expression accompanied by the defect of p38{alpha} is confirmed in an embryonic extract prepared from p38{alpha} null mice. These data demonstrate that p38 signal pathway is regulated not only by phosphorylation but also by modulation of the expression of its component. Together, we have

  9. 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

  10. Hydrogen sulfide plays a key role in the inhibitory neurotransmission to the pig intravesical ureter.

    PubMed

    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 to

  11. 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.

  12. mRNA translation during oocyte maturation plays a key role in development of primordial germ cells in Xenopus embryos.

    PubMed

    Zeynali, Bahman; Dixon, Keith E

    2004-09-01

    It is believed that cytoplasmic localization in the egg is necessary for development of primordial germ cells (PGCs) in Xenopus embryos. In this study, we sought to determine if translation of maternal mRNA during oocyte maturation is involved in the development of PGCs. Donor oocytes were collected from both stimulated (those who receive gonadotropin) and unstimulated females, artificially matured and fertilized using a host transfer technique. Using chloramphenicol (50 microM and 500 microM RNA), RNA translation was inhibited during oocyte maturation. Our results showed that in unstimulated embryos treated with 50 microM chloramphenicol, there was a significant reduction in the number of PGCs reaching genital ridges. In stimulated embryos, however, the number of PGCs was unchanged unless a higher concentration (500 microM) of chloramphenicol was used. From these results it is suggested that maternal mRNA translation during oocyte maturation plays a key role in development of PGCs.

  13. The ORCA2 transcription factor plays a key role in regulation of the terpenoid indole alkaloid pathway

    PubMed Central

    2013-01-01

    Background The terpenoid indole alkaloid (TIA) pathway leads to the production of pharmaceutically important drugs, such as the anticancer compounds vinblastine and vincristine. Unfortunately, these drugs are produced in trace amounts, causing them to be very costly. To increase production of these drugs, an improved understanding of the TIA regulatory pathway is needed. Towards this end, transgenic Catharanthus roseus hairy roots that overexpress the ORCA2 TIA transcriptional activator were generated and characterized. Results Transcriptional profiling experiments revealed that overexpression of ORCA2 results in altered expression of key genes from the indole and terpenoid pathways, which produce precursors for the TIA pathway, and from the TIA pathway itself. In addition, metabolite-profiling experiments revealed that overexpression of ORCA2 significantly affects the levels of several TIA metabolites. ORCA2 overexpression also causes significant increases in transcript levels of several TIA regulators, including TIA transcriptional repressors. Conclusions Results presented here indicate that ORCA2 plays a critical role in regulation of TIA metabolism. ORCA2 regulates expression of key genes from both feeder pathways, as well as the genes (STR and SGD) encoding the enzymes that catalyze the first two steps in TIA biosynthesis. ORCA2 may play an especially important role in regulation of the downstream branches of the TIA pathway, as it regulates four out of five genes characterized from this part of the pathway. Regulation of TIA transcriptional repressors by ORCA2 may provide a mechanism whereby increases in TIA metabolite levels in response to external stimuli are transient and limited in magnitude. PMID:24099172

  14. 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

  15. Oral macrophage-like cells play a key role in tolerance induction following sublingual immunotherapy of asthmatic mice.

    PubMed

    Mascarell, L; Saint-Lu, N; Moussu, H; Zimmer, A; Louise, A; Lone, Y; Ladant, D; Leclerc, C; Tourdot, S; Van Overtvelt, L; Moingeon, P

    2011-11-01

    Sublingual allergen-specific immunotherapy (SLIT) is a safe and efficacious treatment for type 1 respiratory allergies. Herein, we investigated the key subset(s) of antigen-presenting cells (APCs) involved in antigen/allergen capture and tolerance induction during SLIT. Following sublingual administration, fluorochrome-labeled ovalbumin (OVA) is predominantly captured by oral CD11b⁺CD11c⁻ cells that migrate to cervical lymph nodes (CLNs) and present the antigen to naive CD4⁺ T cells. Conditional depletion with diphtheria toxin of CD11b⁺, but not CD11c⁺ cells, in oral tissues impairs CD4⁺ T-cell priming in CLNs. In mice with established asthma to OVA, specific targeting of the antigen to oral CD11b⁺ cells using the adenylate cyclase vector system reduces airway hyperresponsiveness (AHR), eosinophil recruitment in bronchoalveolar lavages (BALs), and specific Th2 responses in CLNs and lungs. Oral CD11b⁺CD11c⁻ cells resemble tolerogenic macrophages found in the lamina propria (LP) of the small intestine in that they express the mannose receptor CD206, as well as class-2 retinaldehyde dehydrogenase (RALDH2), and they support the differentiation of interferon-γ/interleukin-10 (IFNγ/IL-10)-producing Foxp3⁺ CD4⁺ regulatory T cells. Thus, among the various APC subsets present in oral tissues of mice, macrophage-like cells play a key role in tolerance induction following SLIT.

  16. Clusterin in the protein corona plays a key role in the stealth effect of nanoparticles against phagocytes.

    PubMed

    Aoyama, Michihiko; Hata, Katsutomo; Higashisaka, Kazuma; Nagano, Kazuya; Yoshioka, Yasuo; Tsutsumi, Yasuo

    2016-10-28

    In biological fluids, nanoparticles interact with biological components such as proteins, and a layer called the "protein corona" forms around the nanoparticles. It is believed that the composition of the protein corona affects the cellular uptake and in vivo biodistribution of nanoparticles; however, the key proteins of the protein corona that control the biological fate of nanoparticles remain unclear. Recently, it was reported that clusterin binding to pegylated nanoparticles is important for the stealth effect of pegylated nanoparticles in phagocytes. However, the effect of clusterin on non-pegylated nanoparticles is unknown, although it is known that clusterin is present in the protein corona of non-pegylated nanoparticles. Here, we assessed the stealth effect of clusterin in the corona of non-pegylated silver nanoparticles and silica nanoparticles. We found that serum- and plasma-protein corona inhibited the cellular uptake of silver nanoparticles and silica nanoparticles in phagocytes and that the plasma-protein corona showed a greater stealth effect compared with the serum-protein corona. Clusterin was present in both the serum- and plasma-protein corona, but was present at a higher level in the plasma-protein corona than in the serum-protein corona. Clusterin binding to silver nanoparticles and silica nanoparticles suppressed the cellular uptake of nanoparticles in human macrophage-like cells (THP-1 cells). Although further studies are required to determine how clusterin suppresses non-specific cellular uptake in phagocytes, our data suggest that clusterin plays a key role in the stealth effect of not only pegylated nanoparticles but also non-pegylated nanoparticles.

  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.

  20. First Chinese public hospital wins Joint Commission International accreditation: the Health Information Department played a key role in the process.

    PubMed

    Shaffer, Audrey; Jun, Cheng Li

    2008-07-01

    Sir Run Run Shaw Hospital in Hangzhou, China spent five years preparing for a Joint Commission International accreditation survey. In March 2007 it became the first public hospital on the Chinese mainland to attain international accreditation. The Health Information Department, managed according to Western standards, played an integral role in preparing the hospital for the survey.

  1. 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,…

  2. Upregulation of NOXA by 10-Hydroxycamptothecin plays a key role in inducing fibroblasts apoptosis and reducing epidural fibrosis

    PubMed Central

    Li, Xiaolei; He, Jun

    2017-01-01

    demonstrate that upregulation of NOXA by HCPT plays a key role in inducing fibroblast apoptosis and in reducing epidural fibrosis. These findings might provide a potential therapeutic target for preventing epidural fibrosis following laminectomy. PMID:28097065

  3. 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

  4. Caveolin-1 plays a key role in the oleanolic acid-induced apoptosis of HL-60 cells.

    PubMed

    Ma, Wei; Wang, Di-Di; Li, Li; Feng, Yu-Kuan; Gu, Hong-Mei; Zhu, Gui-Ming; Piao, Jin-Hua; Yang, Yu; Gao, Xu; Zhang, Peng-Xia

    2014-07-01

    Our previous study found that caveolin-1 (CAV-1) protein expression is upregulated during oleanolic acid (OA)-induced inhibition of proliferation and promotion of apoptosis in HL-60 cells. CAV-1 is the main structural protein component of caveolae, playing important roles in tumorigenesis and tumor development. It has been shown that cav-1 expression is lower in leukemia cancer cell lines SUP-B15, HL-60, THP-1 and K562 and in chronic lymphocytic leukemia primary (CLP) cells when compared with normal white blood cells, with the lowest cav-1 expression level found in HL-60 cells. To study the effects of cav-1 in HL-60 cells and the effects of cav-1 overexpression on OA drug efficacy, cav-1 was overexpressed in HL-60 cells using lentiviral-mediated transfection combined with OA treatment. The results showed that cav-1 overexpression inhibited HL-60 cell proliferation, promoted apoptosis, arrested the cell cycle in the G1 phase and inhibited activation of the PI3K/AKT/mTOR signaling pathway. Overexpression of CAV-1 also increased HL-60 cell sensitivity to OA. To further verify whether OA affects HL-60 cells via the activation of downstream signaling pathways by CAV-1, cav-1 gene expression was silenced using RNAi, and the cells were treated with OA to examine its efficacy. The results showed that after cav-1 silencing, OA had little effect on cell activity, apoptosis, the cell cycle and phosphorylation of HL-60 cells. This study is the first to show that CAV-1 plays a crucial role in the effects of OA on HL-60 cells.

  5. 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.

  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. An intrinsically disordered region of RPN10 plays a key role in restricting ubiquitin chain elongation in RPN10 monoubiquitination.

    PubMed

    Puig-Sàrries, Pilar; Bijlmakers, Marie-José; Zuin, Alice; Bichmann, Anne; Pons, Miquel; Crosas, Bernat

    2015-08-01

    Despite being a common mechanism in eukaryotes, the process by which protein monoubiquitination is produced and regulated in vivo is not completely understood. We present here the analysis of the process of monoubiquitination of the proteasomal subunit Rpn10 (regulatory particle non-ATPase 10), involved in the recruitment of polyubiquitinated substrates. Rpn10 is monoubiquitinated in vivo by the Nedd4 (neural precursor cell expressed developmentally down-regulated 4) enzyme Rsp5 (reverses SPT-phenotype protein 5) and this modification impairs the interaction of Rpn10 with substrates, having a regulatory effect on proteasome function. Remarkably, a disordered region near the ubiquitin-interacting motif of Rpn10 plays a role in the restriction of the polyubiquitin extension activity of Rsp5. Mutations in this disordered region promote ubiquitin chain extension of Rpn10. Thus, our work sheds light on the molecular basis and the functional relevance of a type of monoubiquitination that is driven by the substrate. Moreover, we uncover a putative role for disordered regions in modulating ubiquitin-protein ligation.

  8. Disturbance of Oligodendrocyte Function Plays a Key Role in the Pathogenesis of Schizophrenia and Major Depressive Disorder

    PubMed Central

    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

  9. 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.

  10. The TvLEGU-1, a Legumain-Like Cysteine Proteinase, Plays a Key Role in Trichomonas vaginalis Cytoadherence

    PubMed Central

    Rendón-Gandarilla, Francisco Javier; Ramón-Luing, Lucero de los Angeles; Ortega-López, Jaime; Rosa de Andrade, Ivone; Benchimol, Marlene; Arroyo, Rossana

    2013-01-01

    The goal of this paper was to characterize a Trichomonas vaginalis cysteine proteinase (CP) legumain-1 (TvLEGU-1) and determine its potential role as a virulence factor during T. vaginalis infection. A 30-kDa band, which migrates in three protein spots (pI~6.3, ~6.5, and ~6.7) with a different type and level of phosphorylation, was identified as TvLEGU-1 by one- and two-dimensional Western blot (WB) assays, using a protease-rich trichomonad extract and polyclonal antibodies produced against the recombinant TvLEGU-1 (anti-TvLEGU-1r). Its identification was confirmed by mass spectrometry. Immunofluorescence, cell binding, and WB assays showed that TvLEGU-1 is upregulated by iron at the protein level, localized on the trichomonad surface and in lysosomes and Golgi complex, bound to the surface of HeLa cells, and was found in vaginal secretions. Additionally, the IgG and Fab fractions of the anti-TvLEGU-1r antibody inhibited trichomonal cytoadherence up to 45%. Moreover, the Aza-Peptidyl Michael Acceptor that inhibited legumain proteolytic activity in live parasites also reduced levels of trichomonal cytoadherence up to 80%. In conclusion, our data show that the proteolytic activity of TvLEGU-1 is necessary for trichomonal adherence. Thus, TvLEGU-1 is a novel virulence factor upregulated by iron. This is the first report that a legumain-like CP plays a role in a pathogen cytoadherence. PMID:23509742

  11. IgG receptor FcγRIIB plays a key role in obesity-induced hypertension.

    PubMed

    Sundgren, Nathan C; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D; Tanigaki, Keiji; Yuhanna, Ivan S; Chambliss, Ken L; Mineo, Chieko; Shaul, Philip W

    2015-02-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that FcγRIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that FcγRIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas FcγRIIB(+/+) mice developed obesity-induced hypertension, FcγRIIB(-/-) mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; FcγRIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet-fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting FcγRIIB may potentially offer new means to treat hypertension in obese individuals.

  12. The Preferential Infection of Astrocytes by Enterovirus 71 Plays a Key Role in the Viral Neurogenic Pathogenesis

    PubMed Central

    Feng, Min; Guo, Sujie; Fan, Shengtao; Zeng, Xiaofeng; Zhang, Ying; Liao, Yun; Wang, Jianbin; Zhao, Ting; Wang, Lichun; Che, Yanchun; Wang, Jingjing; Ma, Na; Liu, Longding; Yue, Lei; Li, Qihan

    2016-01-01

    The pathological manifestations of fatal cases of human hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) are characterized by inflammatory damage to the central nervous system (CNS). Here, the dynamic distribution of EV71 in the CNS and the subsequent pathological characteristics within different regions of neonatal rhesus macaque brain tissue were studied using a chimeric EV71 expressing green fluorescence protein. The results were compared with brain tissue obtained from the autopsies of deceased EV71-infected HFMD patients. These observations suggested that the virus was prevalent in areas around the blood vessels and nerve nuclei in the brain stem and showed a preference for astrocytes in the CNS. Interestingly, infected astrocytes within the in vivo and in vitro human and macaque systems exhibited increased expression of excitatory neurotransmitters and cytokines that also stimulated the neuronal secretion of the excitatory neurotransmitters noradrenalin and adrenalin, and this process most likely plays a role in the pathophysiological events that occur during EV71 infection. PMID:28066727

  13. The mitochondrial Na+/Ca2+ exchanger plays a key role in the control of cytosolic Ca2+ oscillations.

    PubMed

    Hernández-SanMiguel, Esther; Vay, Laura; Santo-Domingo, Jaime; Lobatón, Carmen D; Moreno, Alfredo; Montero, Mayte; Alvarez, Javier

    2006-07-01

    There is increasing evidence that mitochondria play an important role in the control of cytosolic Ca2+ signaling. We show here that the main mitochondrial Ca2+-exit pathway, the mitochondrial Na+/Ca2+ exchanger, controls the pattern of cytosolic Ca2+ oscillations in non-excitable cells. In HeLa cells, the inhibitor of the mitochondrial Na+/Ca2+ exchanger CGP37157 changed the pattern of the oscillations induced by histamine from a high-frequency irregular one to a lower frequency baseline spike type, surprisingly with little changes in the average Ca2+ values of a large cell population. In human fibroblasts, CGP37157 increased the frequency of the baseline oscillations in cells having spontaneous activity and induced the generation of oscillations in cells without spontaneous activity. This effect was dose-dependent, disappeared when the inhibitor was washed out and was not mimicked by mitochondrial depolarization. CGP37157 increased mitochondrial [Ca2+] and ATP production in histamine-stimulated HeLa cells, but the effect on ATP production was only transient. CGP37157 also activated histamine-induced Ca2+ release from the endoplasmic reticulum and increased the size of the cytosolic Ca2+ peak induced by histamine in HeLa cells. Our results suggest that the mitochondrial Na+/Ca2+ exchanger directly modulates inositol 1,4,5-trisphosphate-induced Ca2+ release and in that way controls cytosolic Ca2+ oscillations.

  14. Rho plays a key role in TGF-β1-induced proliferation and cytoskeleton rearrangement of human periodontal ligament cells.

    PubMed

    Wang, Li; Wang, Tingle; Song, Meng; Pan, Jinsong

    2014-02-01

    Human periodontal ligament cells (hPDLCs) form specialised connective tissues that influence the lifespan of the tooth. Periodontal disease is a chronic infectious disease of the periodontal supporting tissues caused by a variety of factors, particularly the loss of hPDLCs. Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine known to play an important role in periodontal disease, but little is known about the effects of TGF-β1 on human PDL cells. To determine how TGF-β1 mediates the changes in hPDLCs, we characterised the effects of TGF-β1 treatment on hPDLCs. We then elucidated the signalling pathway that mediates these effects. Serum-starved hPDLCs were incubated with 10ng/mL TGF-β1, and their proliferation was examined using the Cell Counting Kit-8, while their morphological changes were examined by phase-contrast microscopy. F-actin reorganisation was visualised by phalloidin staining and confocal microscopy. Protein expression was analysed by western blotting. We found that TGF-β1 treatment induced proliferation and cytoskeletal reorganisation, decreased Rho-GDIa protein expression, activated ROCK protein expression, and increased the phosphorylation of LIM kinase and cofilin. Proliferation and cytoskeletal rearrangement were suppressed by pre-treatment with the ROCK inhibitor Y-27632; additionally, expression of ROCK protein and phosphorylation of LIM kinase and cofilin were decreased by Y-27632, while Rho-GDIa knockdown by targeted siRNA transfection causes opposite effects. Therefore, we propose that TGF-β1 induces proliferation and cytoskeletal rearrangement in hPDLCs via Rho GTPase-dependent pathways that modulate ROCK, LIM kinase, and cofilin activity.

  15. How the bioanalytical scientist plays a key role in interdisciplinary project teams in the development of biotherapeutics - a reflection of the European Bioanalysis Forum.

    PubMed

    Dudal, Sherri; Staack, Roland F; Stoellner, Daniela; Fjording, Marianne Scheel; Vieser, Eva; Pascual, Marie-Hélène; Brudny-Kloeppel, Margarete; Golob, Michaela

    2014-05-01

    The bioanalytical scientist plays a key role in the project team for the drug development of biotherapeutics from the discovery to the marketing phase. Information from the project team members is required for assay development and sample analysis during the discovery, preclinical and clinical phases of the project and input is needed from the bioanalytical scientist to help data interpretation. The European Bioanalysis Forum target team 20 discussed many of the gaps in information and communication between the bioanalytical scientist and project team members as a base for providing a perspective on the bioanalytical scientist's role and interactions within the project team.

  16. 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.

  17. 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.

  18. The Interrelationship between Abscisic Acid and Reactive Oxygen Species Plays a Key Role in Barley Seed Dormancy and Germination

    PubMed Central

    Ishibashi, Yushi; Aoki, Nozomi; Kasa, Shinsuke; Sakamoto, Masatsugu; Kai, Kyohei; Tomokiyo, Reisa; Watabe, Gaku; Yuasa, Takashi; Iwaya-Inoue, Mari

    2017-01-01

    Seed dormancy is one of the adaptive responses in the plant life cycle and an important agronomic trait. Reactive oxygen species (ROS) release seed dormancy and promote seed germination in several cereal crops; however, the key regulatory mechanism of ROS-mediated seed dormancy and germination remains controversial. Here, we focused on the relationship between hydrogen peroxide (a ROS) and abscisic acid (ABA) in dormant and non-dormant barley seeds. The hydrogen peroxide (H2O2) level produced in barley seed embryos after imbibition was higher in non-dormant seeds than in dormant seeds. H2O2 regulated the ABA content in the embryos through ABA-8′-hydroxylase, an ABA catabolic enzyme. Moreover, compared with non-dormant seeds, in dormant seeds the activity of NADPH oxidase, which produces ROS, was lower, whereas the activity of catalase, which is a H2O2 scavenging enzyme, was higher, as was the expression of HvCAT2. Furthermore, precocious germination of isolated immature embryos was suppressed by the transient introduction of HvCAT2 driven by the maize (Zea mays) ubiquitin promoter. HvCAT2 expression was regulated through an ABA-responsive transcription factor (HvABI5) induced by ABA. These results suggest that the changing of balance between ABA and ROS is active in barley seed embryos after imbibition and regulates barley seed dormancy and germination. PMID:28377774

  19. The Interrelationship between Abscisic Acid and Reactive Oxygen Species Plays a Key Role in Barley Seed Dormancy and Germination.

    PubMed

    Ishibashi, Yushi; Aoki, Nozomi; Kasa, Shinsuke; Sakamoto, Masatsugu; Kai, Kyohei; Tomokiyo, Reisa; Watabe, Gaku; Yuasa, Takashi; Iwaya-Inoue, Mari

    2017-01-01

    Seed dormancy is one of the adaptive responses in the plant life cycle and an important agronomic trait. Reactive oxygen species (ROS) release seed dormancy and promote seed germination in several cereal crops; however, the key regulatory mechanism of ROS-mediated seed dormancy and germination remains controversial. Here, we focused on the relationship between hydrogen peroxide (a ROS) and abscisic acid (ABA) in dormant and non-dormant barley seeds. The hydrogen peroxide (H2O2) level produced in barley seed embryos after imbibition was higher in non-dormant seeds than in dormant seeds. H2O2 regulated the ABA content in the embryos through ABA-8'-hydroxylase, an ABA catabolic enzyme. Moreover, compared with non-dormant seeds, in dormant seeds the activity of NADPH oxidase, which produces ROS, was lower, whereas the activity of catalase, which is a H2O2 scavenging enzyme, was higher, as was the expression of HvCAT2. Furthermore, precocious germination of isolated immature embryos was suppressed by the transient introduction of HvCAT2 driven by the maize (Zea mays) ubiquitin promoter. HvCAT2 expression was regulated through an ABA-responsive transcription factor (HvABI5) induced by ABA. These results suggest that the changing of balance between ABA and ROS is active in barley seed embryos after imbibition and regulates barley seed dormancy and germination.

  20. 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

  1. Disruption of Endothelial Cell Homeostasis Plays a Key Role in the Early Pathogenesis of Coronary Artery Abnormalities in Kawasaki Disease

    PubMed Central

    Ueno, Kentaro; Ninomiya, Yumiko; Hazeki, Daisuke; Masuda, Kiminori; Nomura, Yuichi; Kawano, Yoshifumi

    2017-01-01

    Disruption of endothelial cell homeostasis may be associated with the pathogenesis of coronary artery abnormalities (CAA) in Kawasaki disease (KD). We sought to clarify the poorly understood pathogenic role of endothelial cell survival and death in KD vasculitis. Human umbilical vein endothelial cells (HUVECs) stimulated with sera from KD patients, compared with sera from patients with bacterial infections, exhibited significant increases in cytotoxicity, high mobility group box protein 1 (HMGB-1), and caspase-3/7 and a decrease in phosphorylated Akt/Akt (pAkt/Akt) ratios. HUVECs stimulated with sera from KD patients treated with immunoglobulin (IG) showed significantly decreased cytotoxicity, HMGB-1, and caspase-3/7 levels and increased pAkt/Akt ratios, as compared with results for untreated HUVECs (P < 0.001, P = 0.008, P = 0.040, and P < 0.001, respectively). In HUVECs stimulated with sera from KD patients, the increased cytotoxicity levels and the suppression of increased pAkt/Akt ratios after subsequent IG treatment were closely related to the development of CAA (P = 0.002 and P = 0.035). Our data reveal that shifting the balance toward cell death rather than survival appears to perturb endothelial cell homeostasis and is closely related to the development of CAA. The cytoprotective effects of IG treatment appear to ameliorate endothelial cell homeostasis. PMID:28255175

  2. Non-photochemical Quenching Plays a Key Role in Light Acclimation of Rice Plants Differing in Leaf Color

    PubMed Central

    Zhao, Xia; Chen, Tingting; Feng, Baohua; Zhang, Caixia; Peng, Shaobing; Zhang, Xiufu; Fu, Guanfu; Tao, Longxing

    2017-01-01

    Non-photochemical quenching (NPQ) is an important photoprotective mechanism in rice; however, little is known regarding its role in the photosynthetic response of rice plants with differing in leaf color to different irradiances. In this study, two rice genotypes containing different chlorophyll contents, namely Zhefu802 (high chlorophyll) and Chl-8 (low chlorophyll), were subjected to moderate or high levels of light intensity at the 6-leaf stage. Chl-8 possessed a lower chlorophyll content and higher chlorophyll a:b ratio compared with Zhefu802, while Pn, Fv/Fm, and ΦPSII contents were higher in Chl-8. Further results indicated that no significant differences were observed in the activities of Rubisco, Mg2+-ATPase, and Ca2+-ATPase between these genotypes. This suggested that no significant difference in the capacity for CO2 assimilation exists between Zhe802 and Chl-8. Additionally, no significant differences in stomatal limitation were observed between the genotypes. Interestingly, higher NPQ and energy quenching (qE), as well as lower photoinhibitory quenching (qI) and production of reactive oxygen species (ROS) was observed in Chl-8 compared with Zhefu802 under both moderate and high light treatments. This indicated that NPQ could improve photosynthesis in rice under both moderate and high light intensities, particularly the latter, whereby NPQ alleviates photodamage by reducing ROS production. Both zeaxanthin content and the expression of PsbS1 were associated with the induction of NPQ under moderate light, while only zeaxanthin was associated with NPQ induction under high light. In summary, NPQ could improve photosynthesis in rice under moderate light and alleviate photodamage under high light via a decrease in ROS generation. PMID:28119700

  3. Non-photochemical Quenching Plays a Key Role in Light Acclimation of Rice Plants Differing in Leaf Color.

    PubMed

    Zhao, Xia; Chen, Tingting; Feng, Baohua; Zhang, Caixia; Peng, Shaobing; Zhang, Xiufu; Fu, Guanfu; Tao, Longxing

    2016-01-01

    Non-photochemical quenching (NPQ) is an important photoprotective mechanism in rice; however, little is known regarding its role in the photosynthetic response of rice plants with differing in leaf color to different irradiances. In this study, two rice genotypes containing different chlorophyll contents, namely Zhefu802 (high chlorophyll) and Chl-8 (low chlorophyll), were subjected to moderate or high levels of light intensity at the 6-leaf stage. Chl-8 possessed a lower chlorophyll content and higher chlorophyll a:b ratio compared with Zhefu802, while Pn, Fv/Fm, and ΦPSII contents were higher in Chl-8. Further results indicated that no significant differences were observed in the activities of Rubisco, Mg(2+)-ATPase, and Ca(2+)-ATPase between these genotypes. This suggested that no significant difference in the capacity for CO2 assimilation exists between Zhe802 and Chl-8. Additionally, no significant differences in stomatal limitation were observed between the genotypes. Interestingly, higher NPQ and energy quenching (qE), as well as lower photoinhibitory quenching (qI) and production of reactive oxygen species (ROS) was observed in Chl-8 compared with Zhefu802 under both moderate and high light treatments. This indicated that NPQ could improve photosynthesis in rice under both moderate and high light intensities, particularly the latter, whereby NPQ alleviates photodamage by reducing ROS production. Both zeaxanthin content and the expression of PsbS1 were associated with the induction of NPQ under moderate light, while only zeaxanthin was associated with NPQ induction under high light. In summary, NPQ could improve photosynthesis in rice under moderate light and alleviate photodamage under high light via a decrease in ROS generation.

  4. The iron-induced cysteine proteinase TvCP4 plays a key role in Trichomonas vaginalis haemolysis.

    PubMed

    Cárdenas-Guerra, Rosa Elena; Arroyo, Rossana; Rosa de Andrade, Ivone; Benchimol, Marlene; Ortega-López, Jaime

    2013-11-01

    Trichomonas vaginalis has multiple proteinases, mainly of the cysteine type (CPs), including a 34 kDa precursor cathepsin L-like CP dubbed TvCP4. TvCP4 is an iron-up-regulated CP. The goal of this work was to identify the role of TvCP4 in the virulence of T. vaginalis. We cloned, expressed, and purified the recombinant mature enzyme region of TvCP4 (TvCP4r) to produce a rabbit polyclonal antibody (α-TvCP4r). This antibody reacted with a ∼24 kDa protein band in total protein extracts that could correspond to the mature enzyme. By two-dimensional western blot assays TvCP4 corresponded to three protein spots of ∼24 kDa with pI values of ∼6.7, 6.9, and 7.0 and two spots of ∼22 and ∼21 kDa with a pI of 6.9, as confirmed by mass spectrometry. As expected, a higher amount of TvCP4 was detected in cytoplasmic vesicles, lysosomes, and on the surface of iron-rich parasites when compared with normal and iron-depleted parasites. The α-TvCP4r antibody protected human erythrocytes from trichomonal lysis. Additionally, TvCP4 is expressed during infection and is part of the released products detected in vaginal fluids of patients with trichomonosis. Thus, data show that TvCP4 is an iron-induced CP that participates in T. vaginalis haemolysis.

  5. B cells play key roles in th2-type airway immune responses in mice exposed to natural airborne allergens.

    PubMed

    Drake, Li Yin; Iijima, Koji; Hara, Kenichiro; Kobayashi, Takao; Kephart, Gail M; Kita, Hirohito

    2015-01-01

    Humans are frequently exposed to various airborne allergens. In addition to producing antibodies, B cells participate in immune responses via various mechanisms. The roles of B cells in allergic airway inflammation and asthma have been controversial. We examined the functional importance of B cells in a mouse model of asthma, in which mice were exposed repeatedly to common airborne allergens. Naïve wild-type BALB/c mice or B cell-deficient JH-/- mice were exposed intranasally to a cocktail of allergen extracts, including Alternaria, Aspergillus, and house dust mite, every other day for two weeks. Ovalbumin was included in the cocktail to monitor the T cell immune response. Airway inflammation, lung pathology, and airway reactivity were analyzed. The airway exposure of naïve wild type mice to airborne allergens induced robust eosinophilic airway inflammation, increased the levels of Th2 cytokines and chemokines in the lung, and increased the reactivity to inhaled methacholine. These pathological changes and immune responses were attenuated in B cell-deficient JH-/- mice. The allergen-induced expansion of CD4+ T cells was impaired in the lungs and draining lymph nodes of JH-/- mice. Furthermore, lymphocytes from JH-/- mice failed to produce Th2 cytokines in response to ovalbumin re-stimulation in vitro. Our results suggest that B cells are required for the optimal development of Th2-type immune responses and airway inflammation when exposed to common airborne allergens. The therapeutic targeting of B cells may be beneficial to treat asthma in certain patients.

  6. Stathmin, a new target of PRL-3 identified by proteomic methods, plays a key role in progression and metastasis of colorectal cancer.

    PubMed

    Zheng, Ping; Liu, Yong-Xia; Chen, Lin; Liu, Xun-Hua; Xiao, Zheng-Quan; Zhao, Liang; Li, Guang-Qiu; Zhou, Jun; Ding, Yan-Qing; Li, Jian-Ming

    2010-10-01

    To better understand the role of PRL-3 in progression and metastasis of colorectal cancer (CRC), we searched for PRL-3 associated proteins using proteomic methods. We identified 39 PRL-3 associated proteins based on proteomic strategy. Stathmin, a key oncoprotein, was proved to be a new PRL-3 associated protein. Notably, co-immunoprecipitation assays in both endogenous CRC cell lines and CRC tissues indicated that PRL-3 could interact with stathmin. And, both stathmin and PRL-3 contributed to microtubule (MT) destabilization of CRC cells. Moreover, gain-of-function and loss-of-function analyses revealed that stathmin promoted proliferation, cell adhesion, and migration of human CRC cells. Immunohistochemical analysis of 149 colorectal tumor samples showed that overexpression of stathmin was strongly correlated with tumor differentiation (P = 0.035), tumor invasion (P = 0.024), lymph node status (P < 0.001), Dukes classification (P < 0.001), and TNM staging (P < 0.001) of CRC patients. Univariate and multivariate survival analyses further supported that overexpression of stathmin protein was a potential independent poor prognostic factor for CRC. Our results reveal many PRL-3 associated proteins for the first time. The oncoprotein stathmin plays a key role in CRC as a new target of PRL-3. Interaction between PRL-3 and stathmin leads to MT destabilization of CRC cells, which contributes to progression and metastasis of CRC.

  7. Mast cells play a key role in Th2 cytokine-dependent asthma model through production of adhesion molecules by liberation of TNF-α.

    PubMed

    Chai, Ok Hee; Han, Eui-Hyeog; Lee, Hern-Ku; Song, Chang Ho

    2011-01-31

    Mast cells are well recognized as key cells in allergic reactions, such as asthma and allergic airway diseases. However, the effects of mast cells and TNF-α on T-helper type 2 (Th2) cytokine-dependent asthma are not clearly understood. Therefore, an aim of this study was to investigate the role of mast cells on Th2 cytokine-dependent airway hyperresponsiveness and inflammation. We used genetically mast cell-deficient WBB6F1/J-Kitw/Kitw-v (W/Wv), congenic normal WBB6F1/J-Kit+/Kit+ (+/+), and mast cell-reconstituted W/Wv mouse models of allergic asthma to investigate the role of mast cells in Th2 cytokine-dependent asthma induced by ovalbumin (OVA). And we investigated whether the intratracheal injection of TNF-α directly induce the expression of ICAM-1 and VCAM-1 in W/Wv mice. This study, with OVA-sensitized and OVA-challenged mice, revealed the following typical histopathologic features of allergic diseases: increased inflammatory cells of the airway, airway hyperresponsiveness, and increased levels of TNF-α, intercellular adhesion molecule (ICAM)-1, and vascular cellular adhesion molecule (VCAM)-1. However, the histopathologic features and levels of ICAM-1 and VCAM-1 proteins in W/Wv mice after OVA challenges were significantly inhibited. Moreover, mast cell-reconstituted W/Wv mice showed restoration of histopathologic features and recovery of ICAM-1 and VCAM-1 protein levels that were similar to those found in +/+ mice. Intratracheal administration of TNF-α resulted in increased ICAM-1 and VCAM-1 protein levels in W/Wv mice. These results suggest that mast cells play a key role in a Th2 cytokine-dependent asthma model through production of adhesion molecules, including ICAM-1 and VCAM-1, by liberation of TNF-α.

  8. 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.

  9. 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

  10. GDP-D-mannose 3,5-epimerase (GME) plays a key role at the intersection of ascorbate and non-cellulosic cell-wall biosynthesis in tomato.

    PubMed

    Gilbert, Louise; Alhagdow, Moftah; Nunes-Nesi, Adriano; Quemener, Bernard; Guillon, Fabienne; Bouchet, Brigitte; Faurobert, Mireille; Gouble, Barbara; Page, David; Garcia, Virginie; Petit, Johann; Stevens, Rebecca; Causse, Mathilde; Fernie, Alisdair R; Lahaye, Marc; Rothan, Christophe; Baldet, Pierre

    2009-11-01

    The GDP-D-mannose 3,5-epimerase (GME, EC 5.1.3.18), which converts GDP-d-mannose to GDP-l-galactose, is generally considered to be a central enzyme of the major ascorbate biosynthesis pathway in higher plants, but experimental evidence for its role in planta is lacking. Using transgenic tomato lines that were RNAi-silenced for GME, we confirmed that GME does indeed play a key role in the regulation of ascorbate biosynthesis in plants. In addition, the transgenic tomato lines exhibited growth defects affecting both cell division and cell expansion. A further remarkable feature of the transgenic plants was their fragility and loss of fruit firmness. Analysis of the cell-wall composition of leaves and developing fruit revealed that the cell-wall monosaccharide content was altered in the transgenic lines, especially those directly linked to GME activity, such as mannose and galactose. In agreement with this, immunocytochemical analyses showed an increase of mannan labelling in stem and fruit walls and of rhamnogalacturonan labelling in the stem alone. The results of MALDI-TOF fingerprinting of mannanase cleavage products of the cell wall suggested synthesis of specific mannan structures with modified degrees of substitution by acetate in the transgenic lines. When considered together, these findings indicate an intimate linkage between ascorbate and non-cellulosic cell-wall polysaccharide biosynthesis in plants, a fact that helps to explain the common factors in seemingly unrelated traits such as fruit firmness and ascorbate content.

  11. Analysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation

    PubMed Central

    Barría, María Inés; González, Angel; Vera-Otarola, Jorge; León, Ursula; Vollrath, Valeska; Marsac, Delphine; Monasterio, Octavio; Pérez-Acle, Tomás; Soza, Alejandro; López-Lastra, Marcelo

    2009-01-01

    The HCV internal ribosome entry site (IRES) spans a region of ∼340 nt that encompasses most of the 5′ untranslated region (5′UTR) of the viral mRNA and the first 24–40 nt of the core-coding region. To investigate the implication of altering the primary sequence of the 5′UTR on IRES activity, naturally occurring variants of the 5′UTR were isolated from clinical samples and analyzed. The impact of the identified mutations on translation was evaluated in the context of RLuc/FLuc bicistronic RNAs. Results show that depending on their location within the RNA structure, these naturally occurring mutations cause a range of effects on IRES activity. However, mutations within subdomain IIId hinder HCV IRES-mediated translation. In an attempt to explain these data, the dynamic behavior of the subdomain IIId was analyzed by means of molecular dynamics (MD) simulations. Despite the loss of function, MD simulations predicted that mutant G266A/G268U possesses a structure similar to the wt-RNA. This prediction was validated by analyzing the secondary structure of the isolated IIId RNAs by circular dichroism spectroscopy in the presence or absence of Mg2+ ions. These data strongly suggest that the primary sequence of subdomain IIId plays a key role in HCV IRES-mediated translation. PMID:19106142

  12. Somatic variation plays a key role in the evolution of the Vf gene family residing in the Vf locus that confers resistance to apple scab disease.

    PubMed

    Xu, Mingliang; Korban, Schuyler S

    2004-07-01

    A cluster of four receptor-like genes has been previously identified in the Vf locus of the crabapple Malus floribunda clone 821 that confers resistance to five races of the fungal pathogen Venturia inaequalis, the casual agent of apple scab disease. Pairwise comparisons of the four Vf paralogs in both promoter and coding regions reveal their timeline evolutionary history. The four Vf paralogs have evolved from four ancient Vf members resulting from two sequential duplication events of a single Vf progenitor initially present in the Malus genome. The coding sequences of the four Vf paralogs are characterized with high numbers of unique polymorphic nucleotides, a number of short duplications/deletions, various deletions of complete LRR copy units, and a casual insert of a transposon-like element. Significant high ratios of nonsynonymous to synonymous substitutions, Ka/Ks, are observed in the putative ligand binding residues in the LRR domains. No sequence exchange between the four Vf paralogs is observed. Compared with promoter regions, only nucleotide substitutions are dramatically elevated in the coding regions. The results presented in this study strongly indicate that the Vf locus is under strong and steady horizontal selective pressures imposed by the fungal pathogen V. inaequalis, and divergent selection on somatic variations plays a key role in shaping the resistance specificity.

  13. 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

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

    PubMed Central

    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

  15. Hyperthermal Intact Molecular Ions Play Key Role in Retention of ATRP Surface Initiation Capability of Plasma Polymer Films from Ethyl α-Bromoisobutyrate.

    PubMed

    Saboohi, Solmaz; Coad, Bryan R; Michelmore, Andrew; Short, Robert D; Griesser, Hans J

    2016-06-29

    We report a systematic study of the plasma polymerization of ethyl α-bromoisobutyrate (EBIB) to produce thin film coatings capable of serving as ATRP initiation surfaces, for which they must contain α-bromoisobutyryl functional groups. In the deposition of polymeric coatings by plasma polymerization there generally occurs considerable fragmentation of precursor ("monomer") molecules in the plasma; and the retention of larger structural elements is challenging, particularly when they are inherently chemically labile. Empirical principles such as low plasma power and low pressure are usually utilized. However, we show that the α-bromoisobutyryl structural moiety is labile in a plasma gas phase and in low pressure plasma conditions, below the collisional threshold, there is little retention. At higher pressure, in contrast, fragmentation of this structural motif appears to be reduced substantially, and coatings useful for ATRP initiation were obtained. Mass spectrometry analysis of the composition of the plasma phase revealed that the desired structural moiety can be retained through the plasma, if the plasma conditions are steered toward ions of the precursor molecule. Whereas at low pressure the plasma polymer assembles mainly from various neutral (radical) fragments, at higher pressure the deposition occurs from hyperthermal ions, among which the protonated intact molecular ion is the most abundant. At higher pressure, a substantial population of ions has low kinetic energy, leading to "soft landing" and thus less fragmentation. This study demonstrates that relatively complex structural motifs in precursor molecules can be retained in plasma polymerization if the chemical and physical processes occurring in the plasma phase are elucidated and controlled such that desirable larger structural elements play a key role in the film deposition.

  16. 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.

  17. 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…

  18. G-protein-coupled bile acid receptor plays a key role in bile acid metabolism and fasting-induced hepatic steatosis in mice.

    PubMed

    Donepudi, Ajay C; Boehme, Shannon; Li, Feng; Chiang, John Y L

    2017-03-01

    Bile acids are signaling molecules that play a critical role in regulation of hepatic metabolic homeostasis by activating nuclear farnesoid X receptor (Fxr) and membrane G-protein-coupled receptor (Takeda G-protein-coupled receptor 5; Tgr5). The role of FXR in regulation of bile acid synthesis and hepatic metabolism has been studied extensively. However, the role of TGR5 in hepatic metabolism has not been explored. The liver plays a central role in lipid metabolism, and impaired response to fasting and feeding contributes to steatosis and nonalcoholic fatty liver and obesity. We have performed a detailed analysis of gallbladder bile acid and lipid metabolism in Tgr5(-/-) mice in both free-fed and fasted conditions. Lipid profiles of serum, liver and adipose tissues, bile acid composition, energy metabolism, and messenger RNA and protein expression of the genes involved in lipid metabolism were analyzed. Results showed that deficiency of the Tgr5 gene in mice alleviated fasting-induced hepatic lipid accumulation. Expression of liver oxysterol 7α-hydroxylase in the alternative bile acid synthesis pathway was reduced. Analysis of gallbladder bile acid composition showed marked increase of taurocholic acid and decrease of tauro-α and β-muricholic acid in Tgr5(-/-) mice. Tgr5(-/-) mice had increased hepatic fatty acid oxidation rate and decreased hepatic fatty acid uptake. Interestingly, fasting induction of fibroblast growth factor 21 in liver was attenuated. In addition, fasted Tgr5(-/-) mice had increased activation of hepatic growth hormone-signal transducer and activator of transcription 5 (GH-Stat5) signaling compared to wild-type mice.

  19. Methyl-CpG-binding protein MBD2 plays a key role in maintenance and spread of DNA methylation at CpG islands and shores in cancer.

    PubMed

    Stirzaker, C; Song, J Z; Ng, W; Du, Q; Armstrong, N J; Locke, W J; Statham, A L; French, H; Pidsley, R; Valdes-Mora, F; Zotenko, E; Clark, S J

    2017-03-01

    Cancer is characterised by DNA hypermethylation and gene silencing of CpG island-associated promoters, including tumour-suppressor genes. The methyl-CpG-binding domain (MBD) family of proteins bind to methylated DNA and can aid in the mediation of gene silencing through interaction with histone deacetylases and histone methyltransferases. However, the mechanisms responsible for eliciting CpG island hypermethylation in cancer, and the potential role that MBD proteins play in modulation of the methylome remain unclear. Our previous work demonstrated that MBD2 preferentially binds to the hypermethylated GSTP1 promoter CpG island in prostate cancer cells. Here, we use functional genetic approaches to investigate if MBD2 plays an active role in reshaping the DNA methylation landscape at this locus and genome-wide. First, we show that loss of MBD2 results in inhibition of both maintenance and spread of de novo methylation of a transfected construct containing the GSTP1 promoter CpG island in prostate cancer cells and Mbd2-/- mouse fibroblasts. De novo methylation was rescued by transient expression of Mbd2 in Mbd2-/- cells. Second, we show that MBD2 depletion triggers significant hypomethylation genome-wide in prostate cancer cells with concomitant loss of MBD2 binding at promoter and enhancer regulatory regions. Finally, CpG islands and shores that become hypomethylated after MBD2 depletion in LNCaP cancer cells show significant hypermethylation in clinical prostate cancer samples, highlighting a potential active role of MBD2 in promoting cancer-specific hypermethylation. Importantly, co-immunoprecipiation of MBD2 shows that MBD2 associates with DNA methyltransferase enzymes 1 and 3A. Together our results demonstrate that MBD2 has a critical role in 'rewriting' the cancer methylome at specific regulatory regions.

  20. 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

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

    PubMed Central

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

    2010-01-01

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

  2. 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

  3. Isc1p Plays a Key Role in Hydrogen Peroxide Resistance and Chronological Lifespan through Modulation of Iron Levels and Apoptosis

    PubMed Central

    Almeida, Teresa; Marques, Marta; Mojzita, Dominik; Amorim, Maria A.; Silva, Rui D.; Almeida, Bruno; Rodrigues, Pedro; Ludovico, Paula; Hohmann, Stefan; Moradas-Ferreira, Pedro; Côrte-Real, Manuela

    2008-01-01

    The inositolphosphosphingolipid phospholipase C (Isc1p) of Saccharomyces cerevisiae belongs to the family of neutral sphingomyelinases that generates the bioactive sphingolipid ceramide. In this work the role of Isc1p in oxidative stress resistance and chronological lifespan was investigated. Loss of Isc1p resulted in a higher sensitivity to hydrogen peroxide that was associated with an increase in oxidative stress markers, namely intracellular oxidation, protein carbonylation, and lipid peroxidation. Microarray analysis showed that Isc1p deficiency up-regulated the iron regulon leading to increased levels of iron, which is known to catalyze the production of the highly reactive hydroxyl radicals via the Fenton reaction. In agreement, iron chelation suppressed hydrogen peroxide sensitivity of isc1Δ mutants. Cells lacking Isc1p also displayed a shortened chronological lifespan associated with oxidative stress markers and aging of parental cells was correlated with a decrease in Isc1p activity. The analysis of DNA fragmentation and caspase-like activity showed that Isc1p deficiency increased apoptotic cell death associated with oxidative stress and aging. Furthermore, deletion of Yca1p metacaspase suppressed the oxidative stress sensitivity and premature aging phenotypes of isc1Δ mutants. These results indicate that Isc1p plays an important role in the regulation of cellular redox homeostasis, through modulation of iron levels, and of apoptosis. PMID:18162582

  4. 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

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

    2014-10-17

    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.

  5. 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

  6. 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

  7. OsLEA3-2, an Abiotic Stress Induced Gene of Rice Plays a Key Role in Salt and Drought Tolerance

    PubMed Central

    Duan, Jianli; Cai, Weiming

    2012-01-01

    Late embryogenesis abundant (LEA) proteins are involved in tolerance to drought, cold and high salinity in many different organisms. In this report, a LEA protein producing full-length gene OsLEA3-2 was identified in rice (Oryza sativa) using the Rapid Amplification of cDNA Ends (RACE) method. OsLEA3-2 was found to be only expressed in the embryo and can be induced by abiotic stresses. The coding protein localizes to the nucleus and overexpression of OsLEA3-2 in yeast improved growth performance compared with control under salt- and osmotic-stress conditions. OsLEA3-2 was also inserted into pHB vector and overexpressed in Arabidopsis and rice. The transgenic Arabidopsis seedlings showed better growth on MS media supplemented with 150 mM mannitol or 100 mM NaCl as compared with wild type plants. The transgenic rice also showed significantly stronger growth performance than control under salinity or osmotic stress conditions and were able to recover after 20 days of drought stress. In vitro analysis showed that OsLEA3-2 was able to protect LDH from aggregation on freezing and inactivation on desiccation. These results indicated that OsLEA3-2 plays an important role in tolerance to abiotic stresses. PMID:23024799

  8. 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

  9. 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.

  10. Endoplasmic reticulum stress-induced neuronal inflammatory response and apoptosis likely plays a key role in the development of diabetic encephalopathy

    PubMed Central

    Wang, Zhouguang; Huang, Yan; Cheng, Yi; Tan, Yi; Wu, Fenzan; Wu, Jiamin; Shi, Hongxue; Zhang, Hongyu; Yu, Xichong; Gao, Hongchang; Lin, Li; Cai, Jun; Zhang, Jinsan; Li, Xiaokun; Cai, Lu; Xiao, Jian

    2016-01-01

    We assumed that diabetic encephalopathy (DEP) may be induced by endoplasmic reticulum (ER)-mediated inflammation and apoptosis in central nervous system. To test this notion, here we investigated the neuronal ER stress and associated inflammation and apoptosis in a type 2 diabetes model induced with high-fat diet/streptozotocin in Sprague-Dawley rats. Elevated expressions of ER stress markers, including glucose-regulated protein 78 (GRP78), activating transcription factor-6 (ATF-6), X-box binding protein-1 (XBP-1), and C/EBP homologous protein, and phosphor-Jun N-terminal kinase (p-JNK) were evident in the hippocampus CA1 of diabetic rats. These changes were also accompanied with the activation of NF-κB and the increased levels of inflammatory cytokines, tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6). Mechanistic study with in vitro cultured hippocampus neurons exposed to high glucose (HG), which induced a diabetes-like effects, shown by increased ER stress, JNK and NF-κB activation, and inflammatory response. Inhibition of ER stress by 4-phenylbutyrate (4-PBA) or blockade of JNK activity by specific inhibitor or transfection of DN-JNK attenuated HG-induced inflammation and associated apoptosis. To validate the in vitro finding, in vivo application of 4-PBA resulted in a significant reduction of diabetes-induced neuronal ER stress, inflammation and cell death, leading to the prevention of DEP. These results suggest that diabetes-induced neuronal ER stress plays the critical role for diabetes-induced neuronal inflammation and cell death, leading to the development of DEP. PMID:27793043

  11. 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

  12. Psychiatrists' Perceptions of Role-Playing Games.

    PubMed

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

    2015-09-01

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

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

    PubMed

    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 (δ(13)C) 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.

  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

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

    2014-07-03

    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.

  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 Central

    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

    2017-01-01

    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. 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.

  17. Tomato Glutamate Decarboxylase Genes SlGAD2 and SlGAD3 Play Key Roles in Regulating γ-Aminobutyric Acid Levels in Tomato (Solanum lycopersicum).

    PubMed

    Takayama, Mariko; Koike, Satoshi; Kusano, Miyako; Matsukura, Chiaki; Saito, Kazuki; Ariizumi, Tohru; Ezura, Hiroshi

    2015-08-01

    Tomato (Solanum lycopersicum) can accumulate relatively high levels of γ-aminobutyric acid (GABA) during fruit development. However, the molecular mechanism underlying GABA accumulation and its physiological function in tomato fruits remain elusive. We previously identified three tomato genes (SlGAD1, SlGAD2 and SlGAD3) encoding glutamate decarboxylase (GAD), likely the key enzyme for GABA biosynthesis in tomato fruits. In this study, we generated transgenic tomato plants in which each SlGAD was suppressed and those in which all three SlGADs were simultaneously suppressed. A significant decrease in GABA levels, i.e. 50-81% compared with wild-type (WT) levels, was observed in mature green (MG) fruits of the SlGAD2-suppressed lines, while a more drastic reduction (up to <10% of WT levels) was observed in the SlGAD3- and triple SlGAD-suppressed lines. These findings suggest that both SlGAD2 and SlGAD3 expression are crucial for GABA biosynthesis in tomato fruits. The importance of SlGAD3 expression was also confirmed by generating transgenic tomato plants that over-expressed SlGAD3. The MG and red fruits of the over-expressing transgenic lines contained higher levels of GABA (2.7- to 5.2-fold) than those of the WT. We also determined that strong down-regulation of the SlGADs had little effect on overall plant growth, fruit development or primary fruit metabolism under normal growth conditions.

  18. Arabidopsis EMBRYOMAKER encoding an AP2 domain transcription factor plays a key role in developmental change from vegetative to embryonic phase.

    PubMed

    Tsuwamoto, Ryo; Yokoi, Shuji; Takahata, Yoshihito

    2010-07-01

    Although several types of plant cells retain the competence to enter into embryonic development without fertilization, the molecular mechanism(s) underlying ectopic embryogenesis is largely unknown. To gain insight into this mechanism, in a previous study we identified 136 ESTs specifically expressed in microspore embryogenesis of Brassica napus. Here, we describe the characterization of the Arabidopsis EMBRYOMAKER (EMK) gene, which is homologous to one of the identified Brassica ESTs (BnGemb-58) and encodes an AP2 domain transcription factor. The AtEMK was expressed in developing and mature embryos, but its rapid disappearance occurred during germination. After germination, the expression of AtEMK was found in the root apical meristem and the distal parts of cotyledons. Although a mutant lacking AtEMK exhibited no distinctive defects in the embryo, ectopic expression of AtEMK induced embryo-like structures from cotyledons. The embryo-like structures contained high concentration of lipids, expressed several embryo-specific genes, and could convert into independent plants, indicating that the structures are somatic embryos. In vitro culture, AtEMK enhanced the efficiency of somatic embryogenesis. Furthermore, ectopic expression of AtEMK caused the formation of trichomes on cotyledons, dedifferentiated several tissues into calli, and retarded root development, demonstrating that AtEMK is harmful for the normal development of plants after germination. From these results, we conclude that the AtEMK is a key player to maintain embryonic identity, and the rapid disappearance of AtEMK expression during germination is essential for the developmental transition between the embryonic and vegetative phases in plants.

  19. [A Study of the relationship between craniofacial morphology and the occlusion in lacteal dentition: occipital remodeling specificities and basicranial individual features that play an occlusal key role].

    PubMed

    Deshayes, Marie-Josèphe; Deshayes, Julie

    2013-03-01

    Before performing any procedure or initiating early intervention on children in lacteal dentition, it is crucial to closely investigate a few key elements of the cranial base of the child. A first step of diagnostics is needed - the classification of the dysharmony ie its squelettal and/or functional element - before we prescribe a major orthopedic treatment or just stop dysfunctions using simple functional appliances. To confront these constraints of diagnostic, a set of 243 children in the lacteal dentition was examined. Our clinical expertise made it possible to select cephalometric measurements that would be supposedly linked with the type of skeletal dysharmony (based on cranial and facial osseous landmarks located on the profile-view of a digital tele-X-ray). The occlusal classification takes into account occlusal criteria and the design of the masticatory function. Statistical analysis (namely linear discriminant analysis of cephalometric variables) indicates that in lacteal dentition, some cranial architectural features have preferred links with specific occlusions. We noticed that the amplitude of basicranial "flexure" (hence the sphenoidal angle) is influenced by the occipital remodeling: the ontogenic process of flexion of the base and the amplitude of closure of the sphenoid angle are under controlled by the remodeling of the occipital bone in three main modalities. Correlations exist between these groups and the facial equilibrium, like a forward or backward position of the chin. The important clinical deduction is that the masticatory function in lacteal dentition is organized by architectural constraints that arise from the remodeling of the cranial base; the squelettal effect of dysfunctions is certainly specific to each type of dysfunction, nonetheless it also depends on the architectural uniqueness of the cranial base.

  20. Yeast RAD2, a homolog of human XPG, plays a key role in the regulation of the cell cycle and actin dynamics

    PubMed Central

    Kang, Mi-Sun; Yu, Sung-Lim; Kim, Ho-Yeol; Gorospe, Choco Michael; Choi, Byung Hyune; Lee, Sung Haeng; Lee, Sung-Keun

    2014-01-01

    Summary Mutations in the human XPG gene cause Cockayne syndrome (CS) and xeroderma pigmentosum (XP). Transcription defects have been suggested as the fundamental cause of CS; however, defining CS as a transcription syndrome is inconclusive. In particular, the function of XPG in transcription has not been clearly demonstrated. Here, we provide evidence for the involvement of RAD2, the Saccharomyces cerevisiae counterpart of XPG, in cell cycle regulation and efficient actin assembly following ultraviolet irradiation. RAD2 C-terminal deletion, which resembles the XPG mutation found in XPG/CS cells, caused cell growth arrest, the cell cycle stalling, a defective α-factor response, shortened lifespan, cell polarity defect, and misregulated actin-dynamics after DNA damage. Overexpression of the C-terminal 65 amino acids of Rad2p was sufficient to induce hyper-cell polarization. In addition, RAD2 genetically interacts with TPM1 during cell polarization. These results provide insights into the role of RAD2 in post-UV irradiation cell cycle regulation and actin assembly, which may be an underlying cause of XPG/CS. PMID:24326185

  1. Variation in the dopamine D2 receptor gene plays a key role in human pain and its modulation by transcranial magnetic stimulation.

    PubMed

    Jääskeläinen, Satu K; Lindholm, Pauliina; Valmunen, Tanja; Pesonen, Ullamari; Taiminen, Tero; Virtanen, Arja; Lamusuo, Salla; Forssell, Heli; Hagelberg, Nora; Hietala, Jarmo; Pertovaara, Antti

    2014-10-01

    We tested whether variation of the dopamine D2 receptor (DRD2) gene contributes to individual differences in thermal pain sensitivity and analgesic efficacy of repetitive transcranial magnetic stimulation (rTMS) in healthy subjects (n=29) or susceptibility to neuropathic pain in patients with neurophysiologically confirmed diagnosis (n=16). Thermal sensitivity of healthy subjects was assessed before and after navigated rTMS provided to the S1/M1 cortex. All subjects were genotyped for the DRD2 gene 957C>T and catechol-O-methyltransferase (COMT) protein Val158Met polymorphisms. In healthy subjects, 957C>T influenced both innocuous and noxious thermal detection thresholds that were lowest in 957TT homozygotes (P values from .0277 to .0462). rTMS to S1 cortex had analgesic effect only in 957TT homozygote genotype (P=.0086). In patients, prevalence of 957TT homozygote genotype was higher than in a healthy Finnish population (50% vs 27%; P=.0191). Patients with 957TT genotype reported more severe pain than patients with other genotypes (P=.0351). COMT Val158Met polymorphism was not independently associated with the studied variables. Genetic regulation of DRD2 function by 957C>T polymorphism thus seems to influence thermal and pain sensitivity, its modulation by rTMS, and susceptibility to neuropathic pain. This indicates a central role for the dopamine system and DRD2 in pain and analgesia. This may have clinical implications regarding individualized selection of patients for rTMS treatment and assessment of risks for neuropathic pain.

  2. 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…

  3. Ordinal Position in Role Play Practice.

    ERIC Educational Resources Information Center

    Robinson, Sharon E.; Cabianca, William A.

    Although the effectiveness of role play and its vicarious learning experiences for counselor training is well documented, little research has focused on the impact of the order of playing the roles on skill development. To investigate the effect of ordinal position, 36 beginning counseling students, 24 female and 12 male, with a median age of 30,…

  4. 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…

  5. 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…

  6. Role-Playing in Counselor Student Development

    ERIC Educational Resources Information Center

    Osborn, Debra; Costas, Lisa

    2013-01-01

    This study examined how role-plays impacted 27 counseling students' overall skills as measured by instructor ratings and self-ratings during practice triads in a microskills course. A Mann-Whitney U nonparametric test revealed no significant difference for scripted versus personal concerns role-plays. Students indicated a strong belief that…

  7. Solving the Plagiary Puzzle with Role Plays.

    ERIC Educational Resources Information Center

    Moder, Carol Lynn; Halleck, Gene B.

    1995-01-01

    Presents exercises and role plays designed to help English-as-a-Second-Language (ESL) students enrolled in or bound for American universities understand plagiarism and the need to properly document essays and term papers. (five references) (MDM)

  8. 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…

  9. Some Roles Children Play in Their Families

    ERIC Educational Resources Information Center

    Rollins, Nancy; And Others

    1973-01-01

    A child patient may play one of several fixed roles in the family. As scapegoat, his shortcomings are emphasized; as baby, his dependence, weakness, and immaturity are rewarded; as pet, love and praise, some undeserved, are won; and, as peacemaker, he must promote peace at the cost of suppressing his own feelings. (ST)

  10. "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…

  11. 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.

  12. Key questions for conducting role delineation research.

    PubMed

    Taub, Alyson; Gilmore, Gary D; Olsen, Larry K; Connell, Dave

    2011-06-01

    Role delineation research for the verification of professional competencies is essential in many professions to promote quality assurance and support capacity building and workforce development. In this article, guidance is provided about key aspects of role delineation research. The information contained in this article focuses on 13 key questions within three selected research phases when attempting to identify and verify the roles that are inherent within any given profession. The major sections in the paper include planning the research, collecting and analyzing the data, interpreting findings, and considering the future. Recommendations and examples related to each of the important questions are provided to assist others undertaking role delineation research.

  13. 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…

  14. A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions

    PubMed Central

    Shimizu, Kiminori; Paul, Sanjoy; Ohba, Ayumi; Gonoi, Tohru; Watanabe, Akira; Gomi, Katsuya

    2017-01-01

    Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans. This fungal-specific Zn2-Cys6 type transcription factor AtrR was found to regulate expression of the genes related to ergosterol biosynthesis, including cyp51A that encodes a target protein of azoles. The atrR deletion mutant showed impaired growth under hypoxic conditions and attenuation of virulence in murine infection model for aspergillosis. These results were similar to the phenotypes for a mutant strain lacking SrbA that is also a direct regulator for the cyp51A gene. Notably, AtrR was responsible for the expression of cdr1B that encodes an ABC transporter related to azole resistance, whereas SrbA was not involved in the regulation. Chromatin immunoprecipitation assays indicated that AtrR directly bound both the cyp51A and cdr1B promoters. In the clinically isolated itraconazole resistant strain that harbors a mutant Cyp51A (G54E), deletion of the atrR gene resulted in a hypersensitivity to the azole drugs. Together, our results revealed that AtrR plays a pivotal role in a novel azole resistance mechanism by co-regulating the drug target (Cyp51A) and putative drug efflux pump (Cdr1B). PMID:28052140

  15. Data Generation through Role-Play: Assessing Oral Proficiency

    ERIC Educational Resources Information Center

    Halleck, Gene

    2007-01-01

    This study analyzes the use of role-play as an elicitation device for the evaluation of a nonnative speaker's oral language. In this analysis of role-play as a methodology to generate data for assessment purposes, the study examines the role that interlocutors play in two types of interactions. It raises questions about the validity and…

  16. Middle Leadership: A Key Role of Numeracy Reform

    ERIC Educational Resources Information Center

    Jorgensen, Robyn

    2016-01-01

    This paper reports on a large national project that explored successful numeracy practices in remote and very remote schools. While there have been a number of significant findings, the middle leader has been identified as a key role in the development of successful numeracy/mathematics practices in schools. The middle leader plays a critical role…

  17. Reality and Second-Language Role-Play.

    ERIC Educational Resources Information Center

    Piper, David; Piper, Terry

    1983-01-01

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

  18. Role-Playing for Different Viewpoints.

    ERIC Educational Resources Information Center

    Duncombe, Sydney; Heikkinen, Michael H.

    1990-01-01

    Presents a teaching technique in which the instructor alternately dons hats that represent opposing viewpoints. Discusses the educational value of the hat technique in teaching politics and government. Explains the role of students in the exercise and provides a students' evaluation of the technique. Maintains the technique makes abstract concepts…

  19. 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…

  20. Breaking Frame in a Role-Play Simulation: A Language Socialization Perspective

    ERIC Educational Resources Information Center

    Schick, Laurie

    2008-01-01

    This article uses key concepts developed in frame analysis and language socialization theories to reconceptualize role-play simulation as socialization practice. The reconceptualization includes (a) an effort to explain an unexpected response to a role-play simulation on the topic of bullying and (b) a discussion regarding how this explanation…

  1. 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…

  2. 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…

  3. The ubiquitin C-terminal hydrolase L1 (UCH-L1) C terminus plays a key role in protein stability, but its farnesylation is not required for membrane association in primary neurons.

    PubMed

    Bishop, Paul; Rubin, Philip; Thomson, Andrew R; Rocca, Dan; Henley, Jeremy M

    2014-12-26

    Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is highly expressed in neurons. A possible role for UCH-L1 in neurodegeneration has been highlighted because of its presence in Lewy bodies associated with Parkinson disease and neurofibrillary tangles observed in Alzheimer disease. UCH-L1 exists in two forms in neurons, a soluble cytoplasmic form (UCH-L1(C)) and a membrane-associated form (UCH-L1(M)). Alzheimer brains show reduced levels of soluble UCH-L1(C) correlating with the formation of UCH-L1-immunoreactive tau tangles, whereas UCH-L1(M) has been implicated in α-synuclein dysfunction. Given these reports of divergent roles, we investigated the properties of UCH-L1 membrane association. Surprisingly, our results indicate that UCH-L1 does not partition to the membrane in the cultured cell lines we tested. Furthermore, in primary cultured neurons, a proportion of UCH-L1(M) does partition to the membrane, but, contrary to a previous report, this does not require farnesylation. Deletion of the four C-terminal residues caused the loss of protein solubility, abrogation of substrate binding, increased cell death, and an abnormal intracellular distribution, consistent with protein dysfunction and aggregation. These data indicate that UCH-L1 is differently processed in neurons compared with clonal cell lines and that farnesylation does not account for the membrane association in neurons.

  4. 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…

  5. 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…

  6. Is Role Playing an Effective EFL Teaching Technique?

    ERIC Educational Resources Information Center

    Smith, Frances L.

    The literature on role-playing as a classroom instructional technique for English as a second language has addressed its benefits in improved acquisition of language or linguistic skills, communicative skills, cross-cultural skills, and interpersonal skills. However, promoters of role-playing may have set their goals too high and may be wasting…

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. The Use of Role Play in the Training of Hypnotherapy.

    ERIC Educational Resources Information Center

    Sanders, Shirley

    A model has been developed for using role play in the supervision and training of hypnotherapy. Specific techniques can be role played by trainee and supervisor which can enable the trainee to develop skill and confidence in the use of hypnotic techniques. Hypnotic induction, listening, observing and providing feedback, relaxation,…

  12. 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…

  13. Role-Playing in an English Conversation Lesson

    ERIC Educational Resources Information Center

    Menne, Saxon

    1977-01-01

    Describes a role-play exercise in which several groups, of varying ability and of six members each, acted out a crime story, with the help of written information. Preparation included vocabulary and pronunciation exercises. After performance, errors were corrected and the play performed again, with roles re-distributed. (IFS/WGA)

  14. Master's Students' Experiences in a Multicultural Counseling Role-Play

    ERIC Educational Resources Information Center

    Rapisarda, Clarrice; Jencius, Marty; McGlothlin, Jason

    2011-01-01

    This study examined the experiences of master's students in regard to their participation in a multicultural role-play and review process (Jencius "et al." 2004). Whereas the literature has supported the use of role-plays as a multicultural training technique (Alvarez and Miville 2003; Vazquez and Garcia-Vazquez 2003), there is a distinct lack of…

  15. Role-Playing for Inhibited Students in Paternal Communities.

    ERIC Educational Resources Information Center

    Al-Saadat, Abdullah I.; Afifi, Elhami A.

    1997-01-01

    Highlights classroom role playing in Saudi Arabian classrooms as a psychological aid that fosters self-confidence in inhibited, timid, hesitant, and passive students and relieves them of their paternal communicative limitations. Proposes an overall strategy for role-playing as an effective communicative activity that teachers can exploit to help…

  16. Teaching Language Realistically: Role Play Is the Thing.

    ERIC Educational Resources Information Center

    Salies, Tania Gastao

    Role-playing is proposed as an ideal technique to teach language because it prepares learners for the unpredictable nature of real-life communication, teaches appropriate language use, and boosts self-confidence. Theories that have paved the way for the current communicative approach to language teaching are reviewed, role-playing is defined, and…

  17. Grammar J, as in Jazzing Around: The Roles "Play" Plays in Style.

    ERIC Educational Resources Information Center

    Ostrom, Hans

    This paper asks what role "play" plays in writing and how it can help a writer, whatever dread, boredom, skill, or ethnicity he/she brings to writing. Some of the ideas in the paper come from Africa, courtesy of Robert Farris Thompson. In his "philosophy of discourse" discussed in the paper, Thompson speaks of the "big…

  18. The Play's the Thing: Teachers' Roles in Children's Play. Early Childhood Education Series. 2nd Edition

    ERIC Educational Resources Information Center

    Jones, Elizabeth; Reynolds, Gretchen

    2011-01-01

    Responding to current debates on the place of play in schools, the authors have extensively revised their groundbreaking book. They explain how and why play is a critical part of children's development, as well as the central role adults have to promote it. This classic textbook and popular practitioner resource offers systematic descriptions and…

  19. Functional analysis of the new barley gene HvKu80 indicates that it plays a key role in double-strand DNA break repair and telomere length regulation.

    PubMed

    Stolarek, Magdalena; Gruszka, Damian; Braszewska-Zalewska, Agnieszka; Maluszynski, Mirosław

    2015-11-01

    Genotoxic stress causes a reduced stability of the plant genome and has a detrimental effect on plant growth and productivity. Double-strand breaks (DSBs) are the most harmful of all DNA lesions because they cause the loss of genetic information on both strands of the DNA helix. In the presented study the coding and genomic sequences of the HvKu80 gene were determined. A mutational analysis of two fragments of HvKu80 using TILLING (Targeting Induced Local Lesions IN Genomes) allowed 12 mutations to be detected, which resulted in identification of 11 alleles. Multidirectional analyses demonstrated that the HvKu80 gene is involved in the elimination of DSBs in Hordeum vulgare. The barley mutants carrying the identified ku80.c and ku80.j alleles accumulated bleomycin-induced DSBs to a much greater extent than the parent cultivar 'Sebastian'. The altered reaction of the mutants to DSB-inducing agent and the kinetics of DNA repair in these genotypes are associated with a lower expression level of the mutated gene. The study also demonstrated the significant role of the HvKu80 gene in the regulation of telomere length in barley.

  20. Qualitative Evaluation of a Role Play Bullying Simulation.

    PubMed

    Gillespie, Gordon L; Brown, Kathryn; Grubb, Paula; Shay, Amy; Montoya, Karen

    Bullying against nurses is becoming a pervasive problem. In this article, a role play simulation designed for undergraduate nursing students is described. In addition, the evaluation findings from a subsample of students who participated in a role play simulation addressing bullying behaviors are reported. Focus group sessions were completed with a subset of eight students who participated in the intervention. Sessions were audiorecorded, transcribed verbatim, and analyzed using Colaizzi's procedural steps for qualitative analysis. Themes derived from the data were "The Experience of Being Bullied", "Implementation of the Program", "Desired Outcome of the Program", and "Context of Bullying in the Nursing Profession". Role play simulation was an effective and active learning strategy to diffuse education on bullying in nursing practice. Bullying in nursing was identified as a problem worthy of incorporation into the undergraduate nursing curriculum. To further enhance the learning experience with role play simulation, adequate briefing instructions, opportunity to opt out of the role play, and comprehensive debriefing are essential.

  1. Role playing: applications in hostage and crisis negotiation skills training.

    PubMed

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

    2008-03-01

    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 resolve high-risk and often volatile situations in a peaceful, nonviolent manner when possible. The purpose of this paper is to (a) describe development and validation of a role-play test specifically geared toward law enforcement negotiators, (b) present different role-play formats that have been incorporated in law enforcement negotiation training, and (c) discuss limitations and considerations in use of these instruments. Suggestions for directions that future efforts in this area might take are offered. The heuristic value of role playing in crisis management, counterterrorism, and emergency and mass casualty disaster training exercises is also underscored.

  2. 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.

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

    USGS Publications Warehouse

    ,

    2016-08-24

    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.

  4. 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.

  5. Local neurons play key roles in the mammalian olfactory bulb.

    PubMed

    Saghatelyan, Armen; Carleton, Alan; Lagier, Samuel; de Chevigny, Antoine; Lledo, Pierre-Marie

    2003-01-01

    Over the past few decades, research exploring how the brain perceives, discriminates, and recognizes odorant molecules has received a growing interest. Today, olfaction is no longer considered a matter of poetry. Chemical senses entered the biological era when an increasing number of scientists started to elucidate the early stages of the olfactory pathway. A combination of genetic, biochemical, cellular, electrophysiological and behavioral methods has provided a picture of how odor information is processed in the olfactory system as it moves from the periphery to higher areas of the brain. Our group is exploring the physiology of the main olfactory bulb, the first processing relay in the mammalian brain. From different electrophysiological approaches, we are attempting to understand the cellular rules that contribute to the synaptic transmission and plasticity at this central relay. How olfactory sensory inputs, originating from the olfactory epithelium located in the nasal cavity, are encoded in the main olfactory bulb remains a crucial question for understanding odor processing. More importantly, the persistence of a high level of neurogenesis continuously supplying the adult olfactory bulb with newborn local neurons provides an attractive model to investigate how basic olfactory functions are maintained when a large proportion of local neurons are continuously renewed. For this purpose, we summarize the current ideas concerning the molecular mechanisms and organizational strategies used by the olfactory system to encode and process information in the main olfactory bulb. We discuss the degree of sensitivity of the bulbar neuronal network activity to the persistence of this high level of neurogenesis that is modulated by sensory experience. Finally, it is worth mentioning that analyzing the molecular mechanisms and organizational strategies used by the olfactory system to transduce, encode, and process odorant information in the olfactory bulb should aid in understanding the general neural mechanisms involved in both sensory perception and memory. Due to space constraints, this review focuses exclusively on the olfactory systems of vertebrates and primarily those of mammals.

  6. 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…

  7. DOES DISSOLVED INORGANIC CARBON PLAY A ROLE IN ARSENIC MOBILIZATION?

    EPA Science Inventory

    Recent experimental results provide evidence that dissolved inorganic carbon plays a direct role in mobilizing arsenic in anoxic aquatic environments. This hypothesis is partially supported by observed correlations between elevated levels of arsenic and alkalinity in a ground wa...

  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 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...

  10. 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

  11. "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…

  12. Straw Castles: A Role-Play in Group Dynamics.

    ERIC Educational Resources Information Center

    Barron, Jennie

    1993-01-01

    Describes a learning activity that allows participants to role play both dysfunctional and constructive roles during a group task, illustrating how group success depends on the attitudes and actions of its members. Includes instructions for the learning activity, questions for debriefing, and follow-up activities. (LP)

  13. 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…

  14. 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…

  15. Power Plays: Children's Constructions of Gender and Power in Role Plays.

    ERIC Educational Resources Information Center

    Francis, Becky

    1997-01-01

    Investigates whether primary school girls took up powerful positions in role-play groups and how these children were positioned through gender discourses during their interaction. Analysis suggests that children's constructions of gender appear potentially to empower boys and disempower girls in interaction. It suggests that discourse analysis can…

  16. Contrasting Roles of Dopamine and Noradrenaline in the Motivational Properties of Social Play Behavior in Rats

    PubMed Central

    Achterberg, E J Marijke; van Kerkhof, Linda W M; Servadio, Michela; van Swieten, Maaike M H; Houwing, Danielle J; Aalderink, Mandy; Driel, Nina V; Trezza, Viviana; Vanderschuren, Louk J M J

    2016-01-01

    Social play behavior, abundant in the young of most mammalian species, is thought to be important for social and cognitive development. Social play is highly rewarding, and as such, the expression of social play depends on its pleasurable and motivational properties. Since the motivational properties of social play have only sporadically been investigated, we developed a setup in which rats responded for social play under a progressive ratio schedule of reinforcement. Dopaminergic neurotransmission plays a key role in incentive motivational processes, and both dopamine and noradrenaline have been implicated in the modulation of social play behavior. Therefore, we investigated the role of dopamine and noradrenaline in the motivation for social play. Treatment with the psychostimulant drugs methylphenidate and cocaine increased responding for social play, but suppressed its expression during reinforced play periods. The dopamine reuptake inhibitor GBR-12909 increased responding for social play, but did not affect its expression, whereas the noradrenaline reuptake inhibitor atomoxetine decreased responding for social play as well as its expression. The effects of methylphenidate and cocaine on responding for social play, but not their play-suppressant effects, were blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. In contrast, pretreatment with the α2-adrenoceptor antagonist RX821002 prevented the play-suppressant effect of methylphenidate, but left its effect on responding for social play unaltered. In sum, the present study introduces a novel method to study the incentive motivational properties of social play behavior in rats. Using this paradigm, we demonstrate dissociable roles for dopamine and noradrenaline in social play behavior: dopamine stimulates the motivation for social play, whereas noradrenaline negatively modulates the motivation for social play behavior and its expression. PMID:26174597

  17. 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).

  18. Teachers' roles in supporting children's literacy development through play.

    PubMed

    Saracho, Olivia N

    2002-04-01

    This study focused on the roles five kindergarten teachers assumed to promote literacy. Data were collected through systematic videotaped observations during the children's play periods. Saracho's analysis of the transcriptions in identifying the roles of the teachers suggested teachers' roles in the children's literacy-play include director of instructions (instructing students to follow directions and learn concepts), transition director (directing students to make smooth transitions), supporter of learning (acknowledging and praising students' work to promote learning), storyteller (reading or telling a story and encouraging children to respond), and instructional guide (providing instructional guidance for learning).

  19. Qualitative Evaluation of a Role Play Bullying Simulation

    PubMed Central

    Gillespie, Gordon L.; Brown, Kathryn; Grubb, Paula; Shay, Amy; Montoya, Karen

    2015-01-01

    Bullying against nurses is becoming a pervasive problem. In this article, a role play simulation designed for undergraduate nursing students is described. In addition, the evaluation findings from a subsample of students who participated in a role play simulation addressing bullying behaviors are reported. Focus group sessions were completed with a subset of eight students who participated in the intervention. Sessions were audiorecorded, transcribed verbatim, and analyzed using Colaizzi’s procedural steps for qualitative analysis. Themes derived from the data were “The Experience of Being Bullied”, “Implementation of the Program”, “Desired Outcome of the Program”, and “Context of Bullying in the Nursing Profession”. Role play simulation was an effective and active learning strategy to diffuse education on bullying in nursing practice. Bullying in nursing was identified as a problem worthy of incorporation into the undergraduate nursing curriculum. To further enhance the learning experience with role play simulation, adequate briefing instructions, opportunity to opt out of the role play, and comprehensive debriefing are essential. PMID:26504502

  20. Role-Playing in Analytical Chemistry: The Alumni Speak

    NASA Astrophysics Data System (ADS)

    Jackson, Paul T.; Walters, John P.

    2000-08-01

    Cooperative learning constructs take a variety of forms. Over the last 15 years, one such pedagogical structure, role-playing, has been used in the analytical chemistry curriculum at St. Olaf College. A long-term assessment of this teaching method was conducted through use of a survey distributed to alumni graduating between 1987 and 1997. The graduates overwhelmingly indicated that the use of role-playing had a positive impact on their careers as well as their lives. Furthermore, many non-achievement learning outcomes attributed to cooperative learning experiences were reinforced through the survey response. Role-playing created an effective environment in which to develop communication and collaborative skills in addition to the technical skills that are essential to analytical chemistry. These results support continued evolutionary development of this teaching method.

  1. Role-playing in the problem-based learning class.

    PubMed

    Chan, Zenobia C Y

    2012-01-01

    Learning and teaching have been conceptualized and executed in many styles, such as self-learning, peer learning, and interaction between the learner and mentor. Today, openness to alternative ideas and embracing innovative approaches in nursing education are encouraged in order to meet students' learning interests and needs, and to address ever-changing healthcare requests. Problem-based learning has been widely adopted in nursing education, with various positive effects on students' learning, such as motivated learning, team work, problem-solving skills and critical thinking. Role-plays have been demonstrated as an effective learning strategy that includes an active and experiential feature that facilitates students' autonomy in their health-related learning. However, there is a lack of discussion of whether and how role-play can be used in problem-based learning (PBL). This paper shows the development of a classroom-based innovation using role-play in the PBL class for higher diploma year-one nurse students (a total of 20 students, five per group). This paper consists of five sections: a) the literature on PBL and nurse education, and role-plays as the innovation; b) the PBL case scenario with the illustration of the two role-play scripts, c) student evaluation on role-play in the PBL class; d) discussions on both achievements and limitations of this innovation, and e) the conclusion. It is hoped that this paper will be an example to other nurse educators who are keen on exploring interactive and student-driven learning and teaching strategies in the PBL class.

  2. Patient care simulations: role playing to enhance clinical understanding.

    PubMed

    Comer, Shirley K

    2005-01-01

    Role-play techniques can serve as an effective substitute for, and supplement to, simulation technology when teaching clinical nursing skills. They provide risk-free opportunities to practice clinical skills and develop clinical judgment. A two-phase patient care simulation, performed in real time, is described. Students are presented with a scenario and work cooperatively in role-playing appropriate care, with one student using a prepared script to assume the role of patient. The class functions as a resource for four students who assume the nursing role. Students reported increased understanding of course material as a result of participation in the clinical simulation scenario. Faculty observed a decreased failure rate on the corresponding course examination.

  3. 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…

  4. 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…

  5. 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)

  6. Role-Playing a Legend in Virtual Reality.

    ERIC Educational Resources Information Center

    Ge, Xun; Lee, Jack; Yamashiro, Kelly A.

    2003-01-01

    Reports a case study of thirteen college students engaging in a role-play activity of a Maui legend in a virtual reality environment. Immersed in the authentic cultural environment, the students not only interacted with the environment and each other, but recreated the legend based on their interpretation of the culture. (CAK)

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. Negotiate Your Future: Web-Based Role Play

    ERIC Educational Resources Information Center

    Ahamer, Gilbert

    2004-01-01

    An original concept for a Web-based role play "SurfingGlobalChange" is proposed on the basis of multi-year interdisciplinary teaching experience and constructivist pedagogy. Underlying didactic orientation is towards self-guided learning, acquiring socially compatible "competence to act" in a globalised world, self-optimising social procedures…

  12. 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…

  13. 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…

  14. 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…

  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. Classroom "Role-Playing": A Basic Blueprint for Performance.

    ERIC Educational Resources Information Center

    Ratliff, Gerald Lee

    Dynamic classroom role-playing for junior and senior high school classes in literature and acting is an essential ingredient in cultivating characterization and interpretation if a student is to learn the technical skills of performance. Although no simple classroom performance blueprint exists for predicting the degree of success a student…

  17. 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)

  18. 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…

  19. 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…

  20. 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…

  1. 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.

  2. 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)

  3. 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…

  4. 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…

  5. 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.

  6. Shedding the Ego: Drama-Based Role-Play and Identity in Distance Language Tuition

    ERIC Educational Resources Information Center

    Brash, Barbel; Warnecke, Sylvia

    2009-01-01

    In this article, the authors attempt to answer the following questions: How do we understand role-play? How are role-play and identity linked? What are the purposes, benefits and challenges of role-play as a teaching tool? What are the roles of students and teachers in role-play? What does role-play add to telephone tutorials and online…

  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. 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

  9. 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.

  10. 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.

  11. Hemoglobin S-nitrosylation plays an essential role in cardioprotection

    PubMed Central

    Zhang, Rongli; Hess, Douglas T.; Reynolds, James D.; Stamler, Jonathan S.

    2016-01-01

    Homeostatic control of tissue oxygenation is achieved largely through changes in blood flow that are regulated by the classic physiological response of hypoxic vasodilation. The role of nitric oxide (NO) in the control of blood flow is a central tenet of cardiovascular biology. However, extensive evidence now indicates that hypoxic vasodilation entails S-nitrosothiol–based (SNO-based) vasoactivity (rather than NO per se) and that this activity is conveyed substantially by the βCys93 residue in hemoglobin. Thus, tissue oxygenation in the respiratory cycle is dependent on S-nitrosohemoglobin. This perspective predicts that red blood cells (RBCs) may play an important but previously undescribed role in cardioprotection. Here, we have found that cardiac injury and mortality in models of myocardial infarction and heart failure were greatly enhanced in mice lacking βCys93 S-nitrosylation. In addition, βCys93 mutant mice exhibited adaptive collateralization of cardiac vasculature that mitigated ischemic injury and predicted outcomes after myocardial infarction. Enhanced myopathic injury and mortality across different etiologies in the absence of βCys93 confirm the central cardiovascular role of RBC-derived SNO-based vasoactivity and point to a potential locus of therapeutic intervention. Our findings also suggest the possibility that RBCs may play a previously unappreciated role in heart disease. PMID:27841756

  12. 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.

  13. Basophil-derived IL-4 plays versatile roles in immunity.

    PubMed

    Yamanishi, Yoshinori; Karasuyama, Hajime

    2016-09-01

    Recent studies demonstrated that basophils play crucial and non-redundant roles in the immune system, in spite of the fact that they are the rarest granulocytes and represent less than 1 % of peripheral blood leukocytes. In response to various stimuli, basophils release effector molecules stored in their cytoplasmic granules, including chemical mediators and proteases, and also secrete cytokines and chemokines. In this review, we will focus on the physiological and pathological roles of basophil-derived IL-4. Basophils can readily produce large quantities of IL-4 and are therefore the important source of IL-4. Basophil-derived IL-4 has been shown to regulate other immune cells, including T cells, B cells, group 2 innate lymphoid cells, monocytes, and macrophages. It also acts on non-hematopoietic cells such as fibroblasts and endothelial cells. Those cells stimulated with basophil-derived IL-4 contribute to the positive or negative regulation of a variety of immune responses in health and disease, including protection against parasitic and bacterial infections, allergy, and autoimmune diseases. Thus, basophil-derived IL-4 plays versatile roles in immunity.

  14. Experimental asymmetric plug-and-play measurement-device-independent quantum key distribution

    NASA Astrophysics Data System (ADS)

    Tang, Guang-Zhao; Sun, Shi-Hai; Xu, Feihu; Chen, Huan; Li, Chun-Yan; Liang, Lin-Mei

    2016-09-01

    Measurement-device-independent quantum key distribution (MDI-QKD) is immune to all security loopholes on detection. Previous experiments on MDI-QKD required spatially separated signal lasers and complicated stabilization systems. In this paper, we perform a proof-of-principle experimental demonstration of plug-and-play MDI-QKD over an asymmetric channel setting with a single signal laser in which the whole system is automatically stabilized in spectrum, polarization, arrival time, and phase reference. Both the signal laser and the single-photon detectors are in the possession of a common server. A passive timing-calibration technique is applied to ensure the precise and stable overlap of signal pulses. The results pave the way for the realization of a quantum network in which the users only need the encoding devices.

  15. 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…

  16. 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.

  17. 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.

  18. 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.

  19. Cerebellar vermis plays a causal role in visual motion discrimination.

    PubMed

    Cattaneo, Zaira; Renzi, Chiara; Casali, Stefano; Silvanto, Juha; Vecchi, Tomaso; Papagno, Costanza; D'Angelo, Egidio

    2014-09-01

    Cerebellar patients have been found to show deficits in visual motion discrimination, suggesting that the cerebellum may play a role in visual sensory processing beyond mediating motor control. Here we show that triple-pulse online transcranial magnetic stimulation (TMS) over cerebellar vermis but not over the cerebellar hemispheres significantly impaired motion discrimination. Critically, the interference caused by vermis TMS on motion discrimination did not depend on an indirect effect of TMS over nearby visual areas, as demonstrated by a control experiment in which TMS over V1 but not over cerebellar vermis significantly impaired orientation discrimination. These findings demonstrate the causal role of the cerebellar vermis in visual motion processing in neurologically normal participants.

  20. GPR56 Plays Varying Roles in Endogenous Cancer Progression

    PubMed Central

    Xu, Lei; Begum, Shahinoor; Barry, Marc; Crowley, Denise; Yang, Liquan; Bronson, Roderick T.; Hynes, Richard O.

    2011-01-01

    GPR56, a non-classical adhesion receptor, was previously reported to suppress tumor growth and metastasis in xenograft models using human melanoma cell lines. To understand whether GPR56 plays similar roles in the development of endogenous tumors, we analyzed cancer progression in Gpr56−/− mice using a variety of transgenic cancer models. Our results showed that GPR56 suppressed prostate cancer progression in the TRAMP model on a mixed genetic background, similar to its roles in progression of melanoma xenografts. However, its roles in other cancer types appeared to be complex. It had marginal effects on tumor onset of mammary tumors in the MMTV-PyMT model, but had no effects on subsequent tumor progression in either the MMTV-PyMT mice or the melanoma model, Ink4a/Arf−/− tyr-Hras. These results indicate diverse roles of GPR56 in cancer progression and provide the first genetic evidence for the involvement of an adhesion GPCR in endogenous cancer development. PMID:20333450

  1. PDGFRα plays a crucial role in connective tissue remodeling.

    PubMed

    Horikawa, Shinjiro; Ishii, Yoko; Hamashima, Takeru; Yamamoto, Seiji; Mori, Hisashi; Fujimori, Toshihiko; Shen, Jie; Inoue, Ran; Nishizono, Hirofumi; Itoh, Hiroshi; Majima, Masataka; Abraham, David; Miyawaki, Toshio; Sasahara, Masakiyo

    2015-12-07

    Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate the distinctive role of PDGF receptor-α (PDGFRα) in this process. In the present study, the Pdgfra gene was systemically inactivated in adult mouse (α-KO mouse), and the role of PDGFRα was examined in the subcutaneously implanted sponge matrices. PDGFRα expressed in the fibroblasts of Pdgfra-preserving control mice (Flox mice), was significantly reduced in the sponges in α-KO mice. Neovascularized areas were largely suppressed in the α-KO mice than in the Flox mice, whereas the other parameters related to the blood vessels and endothelial cells were similar. The deposition of collagen and fibronectin and the expression of collagen 1a1 and 3a1 genes were significantly reduced in α-KO mice. There was a significantly decrease in the number and dividing fibroblasts in the α-KO mice, and those of macrophages were similar between the two genotypes. Hepatocyte growth factor (Hgf) gene expression was suppressed in Pdgfra-inactivated fibroblasts and connective tissue. The findings implicate the role of PDGFRα-dependent ECM and HGF production in fibroblasts that promotes the remodeling of connective tissue and suggest that PDGFRα may be a relevant target to regulate connective tissue remodeling.

  2. FGF plays a subtle role in oligodendrocyte maintenance in vivo.

    PubMed

    Harari, D; Finkelstein, D; Bernard, O

    1997-08-15

    Numerous in vitro studies indicate that fibroblast growth factors (FGFs) play a role in both the development and maintenance of oligodendrocytes. Addition of FGF to mature oligodendrocytes in culture was reported to downregulate the expression of genes encoding proteins of the myelin sheath and to induce a loss of myelin compaction. In this study, a model was developed to functionally block FGF signaling in oligodendrocytes in vivo, by generating transgenic mice expressing a dominant-negative FGF receptor (FGFR1), under the control of the myelin basic protein (MBP) promoter. To demonstrate the effectiveness of this model, truncated FGFR1 was first overexpressed in an FGF-responsive cell line in vitro. It was confirmed that FGF-signalling was blocked in these cells. Subsequently, five independent transgenic lines ("MBP-FRD") were generated. Three lines expressing the highest level of the transgene were further studied. Initial investigation by Western blot and light microscopic analyses revealed no apparent alterations in myelination of the MBP-FRD mouse brains. However, ultrastructural analysis of myelinated optic nerve fibres from two independent MBP-FRD lines revealed a significant increase in myelin thickness as a function of fibre diameter for both transgenic lines (13% and 16% increase). This increase in myelin thickness was not accompanied by alterations in myelin compaction. These results support the idea that FGF signaling in oligodendrocytes plays a role in the modulation of axon myelination in vivo.

  3. [Vascular depression in the elderly. Does inflammation play a role?].

    PubMed

    Viscogliosi, Giovanni; Andreozzi, Paola; Chiriac, Iulia Maria; Ettorre, Evaristo; Vulcano, Achiropita; Servello, Adriana; Marigliano, Benedetta; Marigliano, Vincenzo

    2011-06-01

    Vascular depression in the elderly. Does inflammation play a role?Depression is the most common comorbidity in the elderly, and it is a major determinant of disability. The late-onset depression in highly associated to cardiovascular disease. Depressive symptoms may follow vascular brain damage, especially when mood regulating areas are affected. However depression is strongly associated to vascular disease even when there is no manifest brain damage. Recently great attention has been given to chronic inflammation, both related to depression and vascular disease. Both experimental and clinical evidence shows that a rise in the concentrations of proinflammatory cytokines and glucocorticoids in depressed patients is associated with defect in serotonergic function. Chronic inflammation may underlie many forms of depression associated with vascular disease and metabolic syndrome. The importance of the inflammation hypothesis of depression lies is that psychotropic drugs may have central anti-inflammatory action, and that new generation of central anti-inflammatory drugs may be useful in depression treatment.

  4. The role thermal physiology plays in species invasion.

    PubMed

    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.

  5. 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

  6. Different roles played by periostin splice variants in retinal neovascularization.

    PubMed

    Nakama, Takahito; Yoshida, Shigeo; Ishikawa, Keijiro; Kobayashi, Yoshiyuki; Abe, Takaya; Kiyonari, Hiroshi; Shioi, Go; Katsuragi, Naruto; Ishibashi, Tatsuro; Morishita, Ryuichi; Taniyama, Yoshiaki

    2016-12-01

    Retinal neovascularization (NV) due to retinal ischemia is one of the major causes of vision reduction in patients with different types of retinal diseases although anti-vascular endothelial growth factor (anti-VEGF) therapy can partially reduce the size of the retinal NV. We recently reported that periostin plays an important role in the development of NV and the formation of preretinal fibrovascular membranes, but the role of the splice variants of periostin on retinal NV has not been determined. We examined the expressions of periostin splice variants in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of periostin splice variants on retinal NV using periostin knock out mice, and the effects of anti-periostin antibodies on retinal NV. Our results showed that the expressions of the periostin splice variants were increased in ischemic retinas. The degree of increase of periostin lacking exon 17 was the highest among the periostin splice variants examined. Both genetic ablation of periostin exons 17 and 21 and antibodies for periostin exons 17 and 21 affected preretinal pathological NV. Inhibition of exon 17 of periostin had the greatest effect in reducing preretinal pathological NV. These findings suggest a causal link between periostin splice variants and retinal NV, and an intravitreal injection of antibody for exon 17 and exon 21 of periostin should be considered to inhibit preretinal pathological NV.

  7. 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

  8. 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.

  9. Do Demodex mites play a role in pterygium development?

    PubMed

    Tarkowski, Witold; Moneta-Wielgoś, Joanna; Młocicki, Daniel

    2017-01-01

    Numerous reports point to Demodex mites as the aetiology of certain eye and skin conditions, hence it is highly probable that infestation with these mites may also play a role in the aetiology and pathogenesis of pterygium. Therefore here we present a hypothesis: whether the presence of Demodex mites in eyelash hair follicles significantly correlates with the presence of pterygia, which could point to a potential role of these mites in the development of such lesions. We present preliminary data for supporting this hypothesis. These results were collected from a group of 69 subjects, including 39 with pterygium. Subjects were studied for the presence of Demodex folliculorum and/or D. brevis within eyelash follicles. The sample was defined as positive if at least one parasite, larva or egg were present. Preliminary statistical analyses were performed, and indicated a significant relationship between Demodex mite infestation and the presence of pterygium (p<0.05). This suggests that demodicosis could be one of the factors causing pterygium and significantly contribute to its development. Subjects who had both pterygium and Demodex infestation formed a dominant group. The proportion of subjects with both pterygia and Demodex presence is high at 93.33%, while the proportion of subjects without pterygia who have mites is low at 20.51%. Aforementioned results support our working hypothesis that infestation with Demodex mites may result in pterygium development and therefore patients diagnosed with pterygium should be assessed for the presence of Demodex to verify our preliminary results. In the present paper, we discuss potential influence of Demodex on conjunctiva and propose a hypothetical pathological mechanism linking the development of pterygia with demodicosis.

  10. 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

  11. Does inadequate sleep play a role in vulnerability to obesity?

    PubMed Central

    Knutson, Kristen L.

    2011-01-01

    The prevalence of obesity is increasing rapidly worldwide, which is cause for concern because obesity increases the risk of cardiovascular disease and diabetes, reduces life expectancy and impairs quality of life. A better understanding of the risk factors for obesity is therefore a critical global health concern and human biologists can play an important role in identifying these risk factors in various populations. The objective of this review is to present the evidence that inadequate sleep may be a novel risk factor associated with increased vulnerability to obesity and associated cardiometabolic disease. Experimental studies have found that short-term sleep restriction is associated with impaired glucose metabolism, dysregulation of appetite and increased blood pressure. Observational studies have observed cross-sectional associations between short sleep duration (generally <6 hours per night) and increased body mass index or obesity, prevalent diabetes and prevalent hypertension. Some studies also reported an association between self-reported long sleep duration (generally >8 hours per night) and cardiometabolic disease. A few prospective studies have found a significant increased risk of weight gain, incident diabetes and incident hypertension associated with inadequate sleep. Given the potential link between inadequate sleep and obesity, a critical next step is to identify the social, cultural and environmental determinants of sleep, which would help to identify vulnerable populations. Future human biology research should consider variation in sleep characteristics among different populations and determine whether the associations between sleep and obesity observed in Western populations persist elsewhere. PMID:22275135

  12. 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.

  13. Significant roles played by IL-10 in Chlamydia infections.

    PubMed

    Hakimi, Hamid; Zare-Bidaki, Mohammad; Zainodini, Nahid; Assar, Shokrollah; Arababadi, Mohammad Kazemi

    2014-06-01

    Chlamydia species are obligate intracellular parasites which cause usually asymptomatic genital tract infections and also are associated with several complications. Previous studies demonstrated that immune responses to Chlamydia species are different and the diseases will be limited to some cases. Additionally, Chlamydia species are able to modulate immune responses via regulating expression of some immune system molecules including cytokines. IL-10, as the main anti-inflammatory cytokine, plays important roles in the induction of immune-tolerance against self-antigen and also immune-homeostasis after microbe elimination. Furthermore, it has been documented that ectopic expression of IL-10 is associated with several chronic infectious diseases. Therefore, it can be hypothesized that changes in the regulation of this cytokine can be associated with infection with several species of Chlamydia and their associated complications. This review collected the recent information regarding the association and relationship of IL-10 with Chlamydia infections. Another aim of this review article is to address recent data regarding the association of genetic variations (polymorphisms) of IL-10 and Chlamydia infections.

  14. Does inadequate sleep play a role in vulnerability to obesity?

    PubMed

    Knutson, Kristen L

    2012-01-01

    The prevalence of obesity is increasing rapidly worldwide, which is cause for concern because obesity increases the risk of cardiovascular disease and diabetes, reduces life expectancy, and impairs quality of life. A better understanding of the risk factors for obesity is therefore a critical global health concern, and human biologists can play an important role in identifying these risk factors in various populations. The objective of this review is to present the evidence that inadequate sleep may be a novel risk factor associated with increased vulnerability to obesity and associated cardiometabolic disease. Experimental studies have found that short-term sleep restriction is associated with impaired glucose metabolism, dysregulation of appetite, and increased blood pressure. Observational studies have observed cross-sectional associations between short sleep duration (generally <6 h per night) and increased body mass index or obesity, prevalent diabetes, and prevalent hypertension. Some studies also reported an association between self-reported long sleep duration (generally >8 h per night) and cardiometabolic disease. A few prospective studies have found a significant increased risk of weight gain, incident diabetes, and incident hypertension associated with inadequate sleep. Given the potential link between inadequate sleep and obesity, a critical next step is to identify the social, cultural, and environmental determinants of sleep, which would help to identify vulnerable populations. Future human biology research should consider variation in sleep characteristics among different populations and determine whether the associations between sleep and obesity observed in Western populations persist elsewhere.

  15. Playing with Fear: Children's Play and Its Role in Expressing Fears.

    ERIC Educational Resources Information Center

    Heibeck, Tracy H.

    Preschool children's fears of animals and the dark were investigated in an effort to examine how preschoolers use play as a medium for expressing fearful emotions. A total of 48 children participated in the study. Interviews with parents were used to identify 12 preschoolers who were anxious about the dark and 12 who were anxious about dogs; 24…

  16. 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…

  17. Exploring the Potential of Role Play in Higher Education: Development of a Typology and Teacher Guidelines

    ERIC Educational Resources Information Center

    Rao, Deepa; Stupans, Ieva

    2012-01-01

    Role-play, in which learners act out roles in case scenarios, appears to be used across a broad range of discipline areas to address learning across the cognitive, psychomotor and affective domains. This paper describes the development of a prospective typology of role-play learning opportunities derived from role-play scenarios used at one large…

  18. Water Tectonics: Evidence That Hydration Plays a Role in Tectonism

    NASA Astrophysics Data System (ADS)

    Lowry, A. R.; Schutt, D.; Perez-Gussinye, M.; Buehler, J. S.; Berry, M. A.; Ma, X.; Ravat, D.

    2015-12-01

    Several new observations provide evidence that water may play a more important role in tectonism than previously realized. Among these, • Thermodynamical modeling suggests that hydration promotes crustal mineral assemblages with lowered vP/vS and decreased density. This sheds new light on the significance of low crustal vP/vS measured in the western U.S. Cordillera from joint inversion of EarthScope USArray receiver functions and gravity. vP/vS, previously interpreted in terms of quartz abundance, is strikingly low throughout the highest-elevation regions of the western Cordillera. • Rheological modeling of flexural rigidity measurements also can be used to map water variations, primarily in the uppermost mantle. Mantle hydration estimated from flexural rigidity exhibits very similar spatial distribution to crustal hydration inferred from vP/vS, with the notable exception that the Wyoming craton has dry mantle lithosphere but a hydrous crust. • In hydrated lithosphere of the high-elevation western U.S. Cordillera, Moho temperatures estimated from Pn velocities are systematically colder than predictions by simple geothermal models of surface heat flow. These differences can only be reconciled by invoking a previously unrecognized advective term in the deep thermal transfer. • New and improved estimates of magnetic bottom are much deeper than the depth of the magnetite Curie temperature in some apparently hydrous lithosphere (notably, east of the Siletzia accreted terrane). This may indicate exotic magnetic mineralogies thought to occur only under hydrous conditions. Lithospheric hydration may be driven either by dehydration of subducted slab or by entrainment of water into upwellings passing through the mantle transition zone. Conceptualizing hydration as a large-scale process accompanied by increased buoyancy and decreased ductile strength, coupled with widespread changes in mineralogy, mass and energy transfer may help to illuminate many otherwise

  19. 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.

  20. Role of Education in Rural Development: A Key Factor for Developing Countries.

    ERIC Educational Resources Information Center

    Navaratnam, Kathiravelu K.

    Relevent, locally-controlled educational programs play key roles in rural development in developing nations. Education has a desirable controlling influence over development of the rural individual, family, community, and society, leading to reduced poverty, income equity, and controlled unemployment. The failure of trickle-down development and…

  1. Does IGF-1 play a role in the biology of endometrial cancer?

    PubMed

    Majchrzak-Baczmańska, Dominika; Malinowski, Andrzej

    2016-01-01

    Insulin-like growth factor 1 (IGF-1) is a mitogen which plays a key role in regulating cell proliferation, differentiation, and apoptosis. It belongs to the family of proteins also composed of insulin-like growth factor 2 (IGF-2), two types of membrane receptors (IGF-1R and IGF-2R), 6 binding proteins (IGFBP 1-6), hydrolyzing proteases, and reactive molecules binding proteins, which regulate the activity of growth factors. Disturbances in the functioning of IGFBP/IGF/1GF1R can lead to induction of carcinogenesis, which has been demonstrated in breast, prostate or colon cancers. Findings evaluating the role of IGF-1 in endometrial cancer biology are ambiguous and contradictory. Therefore, in the present study, we analyzed the role of IGF-1 in the process of carcinogenesis of endometrial cancer, based on the available literature.

  2. Key role of succinate dehydrogenase in insulin-induced inactivation of protein tyrosine phosphatases.

    PubMed

    Pomytkin, I A; Kolesova, O E

    2002-06-01

    We studied the role of mitochondria in insulin-induced inactivation of protein tyrosine phosphatases in the liver. The mitochondrial respiratory chain is an insulin-sensitive source of H(2)O(2)that acts as a physiological inhibitor of protein tyrosine phosphatases. Succinate dehydrogenase plays a key role in insulin-stimulated generation of H(2)O(2)and inactivation of liver protein tyrosine phosphatases.

  3. Expressions of Critical Thinking in Role-Playing Simulations: Comparisons across Roles

    ERIC Educational Resources Information Center

    Ertmer, Peggy A.; Strobel, Johannes; Cheng, Xi; Chen, Xiaojun; Kim, Hannah; Olesova, Larissa; Sadaf, Ayesha; Tomory, Annette

    2010-01-01

    The development of critical thinking is crucial in professional education to augment the capabilities of pre-professional students. One method for enhancing critical thinking is participation in role-playing simulation-based scenarios where students work together to resolve a potentially real situation. In this study, undergraduate nursing…

  4. 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…

  5. 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…

  6. Role-Playing Rhetoric of Science Pedagogy and the Study of Medical Ethics.

    ERIC Educational Resources Information Center

    Mitchell, Gordon

    This essay blends practical reflection on current efforts to develop a role-playing curriculum at the University of Pittsburgh with a theoretical investigation of role-playing as a pedagogic technique. This paper examines educational literature on role-playing pedagogy as the topic is treated in a variety of academic fields including medicine,…

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  8. 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…

  9. 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.

  10. 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…

  11. 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...

  12. 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…

  13. 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

  14. Hepatic Glucocorticoid Receptor Plays a Greater Role Than Adipose GR in Metabolic Syndrome Despite Renal Compensation.

    PubMed

    Bose, Sandip K; Hutson, Irina; Harris, Charles A

    2016-12-01

    Exogenous glucocorticoid administration results in hyperglycemia, insulin resistance, hepatic dyslipidemia, and hypertension, a constellation of findings known as Cushing's syndrome. These effects are mediated by the glucocorticoid receptor (GR). Because GR activation in liver and adipose has been implicated in metabolic syndrome (MS), we wanted to determine the role of GR in these tissues in the development of MS. Because GR knockout (KO) mice (whole-body KO) exhibit perinatal lethality due to respiratory failure, we generated tissue-specific (liver or adipose) GRKO mice using cre-lox technology. Real-time PCR analysis of liver mRNA from dexamethasone-treated wildtype (WT) and liver GRKO mice indicated that hepatic GR regulates the expression of key genes involved in gluconeogenesis and glycogen metabolism. Interestingly, we have observed that liver-specific deletion of GR resulted in a significant increase in mRNA expression of key genes involved in gluconeogenesis and glycogen metabolism in kidney tissue, indicating a compensatory mechanism to maintain glucose homeostasis. We have also observed that GR plays an important role in regulating the mRNA expression of key genes involved in lipid metabolism. Liver GRKO mice demonstrated decreased fat mass and liver glycogen content compared with WT mice administered dexamethasone for 2 weeks. Adipose-specific deletion of GR did not alter glucose tolerance or insulin sensitivity of adipose GRKO mice compared with WT mice administrated dexamethasone. This indicates that liver GR might be more important in development of MS in dexamethasone-treated mice, whereas adipose GR plays a little role in these paradigms.

  15. 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…

  16. 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.

  17. 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.

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  20. 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.

  1. Mitochondrial genetic background plays a role in increasing risk to asthma.

    PubMed

    Zifa, Emily; Daniil, Zoe; Skoumi, Eleutheria; Stavrou, Maria; Papadimitriou, Kostantinos; Terzenidou, Marini; Kostikas, Konstantinos; Bagiatis, Vasileios; Gourgoulianis, Konstantinos I; Mamuris, Zissis

    2012-04-01

    A number of studies suggest that mitochondrial dysfunction plays a role in the pathogenesis of asthma. To shed light for the first time on the role of the mitochondrial genome in the etiology of asthma we analyzed the mitochondrial tRNA genes and part of their flanking regions in patients with asthma compared with a set of healthy controls. We found a total of 10 mutations in 56 out of 76 asthmatic patients. Four of these mutations were not found in the control group, five were observed at a significantly lower frequency in controls, but none of the combinations of mutations detected in asthma patients was observed in the controls. Furthermore, we observed that 27.6% of the asthma patients (vs. 4% of the controls) belonged to the haplogroup U (Fisher test P = 0.00) and a positive significant correlation was found between the occurrence of the haplogroup U and the severity of the disease (Fisher test P = 0.02). Whereas further studies in larger cohorts are needed to confirm these observations we suggest that the mitochondrial genetic background plays a key role in asthma development.

  2. Parkin Plays a Role in Sporadic Parkinson’s Disease

    PubMed Central

    Dawson, Ted M.; Dawson, Valina L.

    2014-01-01

    Background Parkinson’s Disease (PD) is a chronic progressive neurologic disorder, which affects approximately one million men and women in the U.S. alone. PD represents a heterogeneous disorder with common clinical manifestations and for the most part common neuropathological findings. Objective This short article reviews the role of the ubiquitin E3 ligase in sporadic PD. Methods The role of parkin in sporadic PD was reviewed by querying PubMed Results Parkin is inactivated in sporadic PD via S-nitrosylation, oxidative and dopaminergic stress, and phosphorylation by the stress activated kinase, c-Abl leading to the accumulation of AIMP2 and PARIS (ZNF746). Conclusion Strategies aimed at maintaining parkin in a catalytically active state or interfering with toxicity of AIMP2 and PARIS (ZNF746) offer new therapeutic opportunities. PMID:24029689

  3. Does inflammation play a role in kava hepatotoxicity?

    PubMed

    Zhang, Lillian Yuan; Rowe, Anthony; Ramzan, Iqbal

    2011-04-01

    The pathophysiology of kava hepatotoxicity remains inconclusive. There is circumstantial evidence for the roles of toxic metabolites, inhibition of cyclooxygenase (COX) enzymes and depletion of liver glutathione. Pharmacogenomic effects are likely, particularly for Cytochrome P450 genes. Experimental and clinical cases of hepatotoxicity show evidence of hepatitis. The question remains whether this inflammation is caused by components of kava directly, or indirectly due to the downstream effects.

  4. What Roles Can Scientists Play in Public Discourse?

    NASA Astrophysics Data System (ADS)

    Oppenheimer, Michael

    2011-04-01

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

  5. 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

  6. 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.

  7. MicroRNAs play critical roles during plant development and in response to abiotic stresses

    PubMed Central

    de Lima, Júlio César; Loss-Morais, Guilherme; Margis, Rogerio

    2012-01-01

    MicroRNAs (miRNAs) have been identified as key molecules in regulatory networks. The fine-tuning role of miRNAs in addition to the regulatory role of transcription factors has shown that molecular events during development are tightly regulated. In addition, several miRNAs play crucial roles in the response to abiotic stress induced by drought, salinity, low temperatures, and metals such as aluminium. Interestingly, several miRNAs have overlapping roles with regard to development, stress responses, and nutrient homeostasis. Moreover, in response to the same abiotic stresses, different expression patterns for some conserved miRNA families among different plant species revealed different metabolic adjustments. The use of deep sequencing technologies for the characterisation of miRNA frequency and the identification of new miRNAs adds complexity to regulatory networks in plants. In this review, we consider the regulatory role of miRNAs in plant development and abiotic stresses, as well as the impact of deep sequencing technologies on the generation of miRNA data. PMID:23412556

  8. MicroRNAs play critical roles during plant development and in response to abiotic stresses.

    PubMed

    de Lima, Júlio César; Loss-Morais, Guilherme; Margis, Rogerio

    2012-12-01

    MicroRNAs (miRNAs) have been identified as key molecules in regulatory networks. The fine-tuning role of miRNAs in addition to the regulatory role of transcription factors has shown that molecular events during development are tightly regulated. In addition, several miRNAs play crucial roles in the response to abiotic stress induced by drought, salinity, low temperatures, and metals such as aluminium. Interestingly, several miRNAs have overlapping roles with regard to development, stress responses, and nutrient homeostasis. Moreover, in response to the same abiotic stresses, different expression patterns for some conserved miRNA families among different plant species revealed different metabolic adjustments. The use of deep sequencing technologies for the characterisation of miRNA frequency and the identification of new miRNAs adds complexity to regulatory networks in plants. In this review, we consider the regulatory role of miRNAs in plant development and abiotic stresses, as well as the impact of deep sequencing technologies on the generation of miRNA data.

  9. Key players and team play: anaerobic microbial communities in hydrocarbon-contaminated aquifers.

    PubMed

    Kleinsteuber, Sabine; Schleinitz, Kathleen M; Vogt, Carsten

    2012-05-01

    Biodegradation of anthropogenic pollutants in shallow aquifers is an important microbial ecosystem service which is mainly brought about by indigenous anaerobic microorganisms. For the management of contaminated sites, risk assessment and control of natural attenuation, the assessment of in situ biodegradation and the underlying microbial processes is essential. The development of novel molecular methods, "omics" approaches, and high-throughput techniques has revealed new insight into complex microbial communities and their functions in anoxic environmental systems. This review summarizes recent advances in the application of molecular methods to study anaerobic microbial communities in contaminated terrestrial subsurface ecosystems. We focus on current approaches to analyze composition, dynamics, and functional diversity of subsurface communities, to link identity to activity and metabolic function, and to identify the ecophysiological role of not yet cultured microbes and syntrophic consortia. We discuss recent molecular surveys of contaminated sites from an ecological viewpoint regarding degrader ecotypes, abiotic factors shaping anaerobic communities, and biotic interactions underpinning the importance of microbial cooperation for microbial ecosystem services such as contaminant degradation.

  10. Dachshund homologues play a conserved role in islet cell development

    PubMed Central

    Kalousova, Anna; Mavropoulos, Anastasia; Adams, Bruce A.; Nekrep, Nada; Li, Zhongmei; Krauss, Stephan; Stainier, Didier Y.; German, Michael S.

    2010-01-01

    All metazoans use insulin to control energy metabolism, but they secrete it from different cells: neurons in the central nervous system in invertebrates and endocrine cells in the gut or pancreas in vertebrates. Despite their origins in different germ layers, all of these insulin-producing cells share common functional features and gene expression patterns. In this study, we tested the role in insulin-producing cells of the vertebrate homologues of Dachshund, a transcriptional regulator that marks the earliest committed progenitors of the neural insulin-producing cells in Drosophila. Both zebrafish and mice expressed a single dominant Dachshund homologue in the pancreatic endocrine lineage, and in both species loss of this homologue reduced the numbers of all islet cell types including the insulin-producing β-cells. In mice, Dach1 gene deletion left pancreatic progenitor cells unaltered, but blocked the perinatal burst of proliferation of differentiated β-cells that normally generates most of the β-cell mass. In β-cells, Dach1 bound to the promoter of the cell cycle inhibitor p27Kip1, which constrains β-cell proliferation. Taken together, these data demonstrate a conserved role for Dachshund homologues in the production of insulin-producing cells. PMID:20869363

  11. Lysophosphatidylcholine plays critical role in allergic airway disease manifestation

    PubMed Central

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

    2016-01-01

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

  12. Early influences and childhood development. Does helicobacter play a role?

    PubMed

    Lee, Adrian

    2007-11-01

    In the late 1960s, Rene Dubos showed that a variety of nutritional stress in utero or in early infancy could have dramatic impact on childhood development that was irreversible. This included detectable changes in the brain. Since that time, iron deficiency anemia (IDA) has been identified as one of the major nutritional stresses that leads to permanent behavioral changes in both experimental animals and humans resulting in poorer cognitive, motor, and social-emotional function. It has been proposed that these changes play an important part in the inter-generational transmission of poverty. More recently, it is becoming clear that Helicobacter pylori causes IDA in populations on an iron-limiting diet. The main thesis of this article is that H. pylori infection may indeed have an impact on childhood development and that much more research is needed in this area as intervention via immunization or antimicrobial therapy in populations in the developing world may have major positive benefits via cure of IDA and prevention of brain damage in the young.

  13. Autophagic Recycling Plays a Central Role in Maize Nitrogen Remobilization

    PubMed Central

    Chung, Taijoon; Pennington, Janice G.; Federico, Maria L.; Kaeppler, Heidi F.; Kaeppler, Shawn M.

    2015-01-01

    Autophagy is a primary route for nutrient recycling in plants by which superfluous or damaged cytoplasmic material and organelles are encapsulated and delivered to the vacuole for breakdown. Central to autophagy is a conjugation pathway that attaches AUTOPHAGY-RELATED8 (ATG8) to phosphatidylethanolamine, which then coats emerging autophagic membranes and helps with cargo recruitment, vesicle enclosure, and subsequent vesicle docking with the tonoplast. A key component in ATG8 function is ATG12, which promotes lipidation upon its attachment to ATG5. Here, we fully defined the maize (Zea mays) ATG system transcriptionally and characterized it genetically through atg12 mutants that block ATG8 modification. atg12 plants have compromised autophagic transport as determined by localization of a YFP-ATG8 reporter and its vacuolar cleavage during nitrogen or fixed-carbon starvation. Phenotypic analyses showed that atg12 plants are phenotypically normal and fertile when grown under nutrient-rich conditions. However, when nitrogen-starved, seedling growth is severely arrested, and as the plants mature, they show enhanced leaf senescence and stunted ear development. Nitrogen partitioning studies revealed that remobilization is impaired in atg12 plants, which significantly decreases seed yield and nitrogen-harvest index. Together, our studies demonstrate that autophagy, while nonessential, becomes critical during nitrogen stress and severely impacts maize productivity under suboptimal field conditions. PMID:25944100

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  15. Can lenalidomide play a role in the management of scleritis?

    PubMed

    Al-Jafar, Hassan A; Abul, Nadia; Kumar, Niranjan; Al-Awadhi, Adel

    2013-06-18

    Lenalidomide is an immunomodulatory agent that was approved for the treatment of a monoclonal bone marrow disorders, myelodysplastic syndrome del(5q)(MDS del(5q)), in 2005; the drug was subsequently also approved for the treatment of refractory multiple myeloma, a bone marrow malignancy of the B-lymphocyte lineage. The purpose of this study is to report a case of MDS del(5q) in a female patient, which was most likely secondary to the immunosuppressive drugs that the patient was taking for scleritis. After lenalidomide treatment, the patient's haematological symptoms rapidly resolved and she became transfusion independent, with normal haemoglobin levels. This medication also helped control her dependence on high doses of oral prednisolone. The patient continued to receive treatment with low-dose lenalidomide, and her scleritis has been in long-term remission for 3 years. A larger prospective study can further define the role of lenalidomide in the management of scleritis.

  16. Can lenalidomide play a role in the management of scleritis?

    PubMed Central

    Al-Jafar, Hassan A; Abul, Nadia; Kumar, Niranjan; Al-Awadhi, Adel

    2013-01-01

    Lenalidomide is an immunomodulatory agent that was approved for the treatment of a monoclonal bone marrow disorders, myelodysplastic syndrome del(5q)(MDS del(5q)), in 2005; the drug was subsequently also approved for the treatment of refractory multiple myeloma, a bone marrow malignancy of the B-lymphocyte lineage. The purpose of this study is to report a case of MDS del(5q) in a female patient, which was most likely secondary to the immunosuppressive drugs that the patient was taking for scleritis. After lenalidomide treatment, the patient's haematological symptoms rapidly resolved and she became transfusion independent, with normal haemoglobin levels. This medication also helped control her dependence on high doses of oral prednisolone. The patient continued to receive treatment with low-dose lenalidomide, and her scleritis has been in long-term remission for 3 years. A larger prospective study can further define the role of lenalidomide in the management of scleritis. PMID:23780766

  17. Etiology of Sarcoidosis: Does Infection Play a Role?

    PubMed Central

    Saidha, Shiv; Sotirchos, Elias S.; Eckstein, Christopher

    2012-01-01

    Sarcoidosis is a granulomatous inflammatory disorder of unclear etiology, which is known to affect multiple organ systems including the lungs, heart, skin, central nervous system, and eyes, among others. For this reason, sarcoidosis represents a systemic medical disorder that is clinically relevant to multiple medical sub-specialties. Despite extensive research, the etiology of sarcoidosis has yet to be elucidated, although most evidence supports that the pathogenetic mechanism of sarcoidosis is an aberrant immune response, driven by an unidentified antigen (or antigens) in genetically susceptible individuals. Multiple candidate etiologic agents, including microbial organisms and environmental agents, have been investigated, but study results are inconclusive. In this review, we describe the known histologic and immunologic features of sarcoidosis and discuss the evidence supporting a role for infectious processes in the pathogenesis of sarcoidosis. PMID:22461752

  18. [Anticholinergics for overactive bladder: does subtype selectivity play a role?].

    PubMed

    Michel, M C; Barendrecht, M M; Oelke, M

    2006-07-01

    Anticholinergics act in the treatment of overactive bladder by blocking muscarinic receptors of which five subtypes exist. Their desired effects occur via M(3) receptors, but a role for M(2) receptors is being discussed. Adverse effects such as dry mouth and constipation occur also via M(3) receptors, but M(2) and M(1) receptors can mediate side effects in the heart or on cognitive function, respectively. Therefore, an M(3)-selective drug such as darifenacin could theoretically be less effective but also have fewer cardiac or central nervous side effects. However, the limited available clinical data do not support a smaller efficacy or better general tolerability. The lack of adverse effects on cognitive function is well documented for darifenacin, but it cannot yet be determined definitively whether this discriminates it from other modern anticholinergics.

  19. Adam12 plays a role during uterine decidualization in mice.

    PubMed

    Zhang, Li; Guo, Weixiang; Chen, Qi; Fan, Xiujun; Zhang, Ying; Duan, Enkui

    2009-12-01

    In mouse, decidualization is characterized by the proliferation of stromal cells and their differentiation into specialized type of cells (decidual cells) with polyploidy, surrounding the implanting blastocyst. However, the mechanisms involved in these processes remain poorly understood. Using multiple approaches, we have examined the role of Adam12 in decidualization during early pregnancy in mice. Adam12 is spatiotemporally expressed in decidualizing stromal cells in intact pregnant females and in pseudopregnant mice undergoing artificially induced decidualization. In the ovariectomized mouse uterus, the expression of Adam12 is upregulated after progesterone treatment, which is primarily mediated by nuclear progesterone receptor. In a stromal cell culture model, the expression of Adam12 gradually rises with the progression of stromal decidualization, whereas the attenuated expression of Adam12 after siRNA knockdown significantly blocks the progression of decidualization. Our study suggests that Adam12 is involved in promoting uterine decidualization during pregnancy.

  20. Aspartate oxidase plays an important role in Arabidopsis stomatal immunity.

    PubMed

    Macho, Alberto P; Boutrot, Freddy; Rathjen, John P; Zipfel, Cyril

    2012-08-01

    Perception of pathogen-associated molecular patterns (PAMPs), such as bacterial flagellin (or the peptide flg22), by surface-localized receptors activates defense responses and subsequent immunity. In a previous forward-genetic screen aimed at the identification of Arabidopsis (Arabidopsis thaliana) flagellin-insensitive (fin) mutants, we isolated fin4, which is severely affected in flg22-triggered reactive oxygen species (ROS) bursts. Here, we report that FIN4 encodes the chloroplastic enzyme ASPARTATE OXIDASE (AO), which catalyzes the first irreversible step in the de novo biosynthesis of NAD. Genetic studies on the role of NAD have been hindered so far by the lethality of null mutants in NAD biosynthetic enzymes. Using newly identified knockdown fin alleles, we found that AO is required for the ROS burst mediated by the NADPH oxidase RBOHD triggered by the perception of several unrelated PAMPs. AO is also required for RBOHD-dependent stomatal closure. However, full AO activity is not required for flg22-induced responses that are RBOHD independent. Interestingly, although the fin4 mutation dramatically affects RBOHD function, it does not affect functions carried out by other members of the RBOH family, such as RBOHC and RBOHF. Finally, we determined that AO is required for stomatal immunity against the bacterium Pseudomonas syringae. Altogether, our work reveals a novel specific requirement for AO activity in PAMP-triggered RBOHD-dependent ROS burst and stomatal immunity. In addition, the availability of viable mutants for the chloroplastic enzyme AO will enable future detailed studies on the role of NAD metabolism in different cellular processes, including immunity, in Arabidopsis.

  1. Efficacy of role play in concert with lecture to enhance student learning of immunology.

    PubMed

    Elliott, Samantha L

    2010-01-01

    Despite numerous reports that active learning increases student understanding, many barriers still exist that prevent faculty from shedding the traditional passive lecture and adopting active learning strategies in the classroom. This study looks at the use of role play as an active learning technique to convey new material, or as reinforcement to traditional lecture. A pre- and post-test survey was utilized to determine student learning gains, along with an anonymous survey to determine student attitudes about role play. Student learning gains are similar regardless of class size, role-playing participation or learning style, and reflect an increase in lower order cognition. Attitudes and learning gains indicate role play is preferable as a reinforcement technique, although the order does not matter if both lecture and role play are utilized to convey information. These data provide insight into the best practices of role-playing implementation in concert with traditional lecture format.

  2. Role-play and the Industrial Revolution: an STS approach to the teaching of steam engines

    NASA Astrophysics Data System (ADS)

    Sabka, Diego; Pereira de Pereira, Alexsandro; Lima Junior, Paulo

    2016-11-01

    Role-play is an interesting, although underexplored, way of teaching physics in high school. This paper presents a science-technology-society (STS) approach to the teaching of heat engines based on a role-play of the Industrial Revolution. Enacting the role-play, students are presented not only to scientific concepts, but also to the social and technological controversies of industrial development.

  3. Do microglia play a role in sex differences in TBI?

    PubMed

    Caplan, Henry W; Cox, Charles S; Bedi, Supinder S

    2017-01-02

    Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality for both males and females and is, thus, a major focus of current study. Although the overall death rate of TBI for males is roughly three times higher than that for females, males have been disproportionately represented in clinical and preclinical studies. Gender differences are known to exist in many neurologic disorders, such as multiple sclerosis and stroke, and differences appear to exist in TBI. Furthermore, it is known that microglia have sexually dimorphic roles in CNS development and other neurologic conditions; however, most animal studies of microglia and TBI have focused on male subjects. Microglia are a current target of many preclinical and clinical therapeutic trials for TBI. Understanding the relationship among sex, sex hormones, and microglia is critical to truly understanding the pathophysiology of TBI. However, the evidence for sex differences in TBI centers mainly on sex hormones, and evidenced-based conclusions are often contradictory. In an attempt to review the current literature, it is apparent that sex differences likely exist, but the contradictory nature and magnitude of such differences in the existing literature does not allow definite conclusions to be drawn, except that more investigation of this issue is necessary. © 2016 Wiley Periodicals, Inc.

  4. Maintenance of polymorphic females: do parasites play a role?

    PubMed

    Sánchez-Guillén, R A; Martínez-Zamilpa, S M J; Jiménez-Cortés, J G; Forbes, M R L; Córdoba-Aguilar, A

    2013-01-01

    The role of parasites in explaining maintenance of polymorphism is an unexplored research avenue. In odonates, female-limited color polymorphism (one female morph mimicking the conspecific male and one or more gynochromatic morphs) is widespread. Here we investigated whether parasitism contributes to color polymorphism maintenance by studying six species of female dimorphic damselflies using large databases of field-collected animals. We predicted that androchrome females (male mimics) would be more intensively parasitized than gynochrome females which is, according to previous studies, counterbalanced by the advantages of the former when evading male harassment compared to gynochrome females. Here we show that in Ischnura denticollis and Enallagma novahispaniae, androchrome females suffer from a higher degree of parasitism than gynochromatic females, and contrary to prediction, than males. Thus, our study has detected a correlation between color polymorphism and parasitic burden in odonates. This leads us to hypothesize that natural selection, via parasite pressure, can explain in part how androchrome and gynochrome female color morphs can be maintained. Both morphs may cope with parasites in a different way: given that androchrome females are more heavily parasitized, they may pay a higher fecundity costs, in comparison to gynochrome females.

  5. IFT46 plays an essential role in cilia development

    PubMed Central

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

    2015-01-01

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

  6. Radiology Education of Physician Extenders: What Role Should Radiologists Play?

    PubMed

    RiChard, Jamie L; Liu, Benjamin P; Casalino, David D; Russell, Eric J; Horowitz, Jeanne M

    2017-02-08

    As physician extenders (PEs) enter the medical community in large numbers, they have an increasing impact on imaging utilization and imaging-based procedures. Physician assistants (PAs) and nurse practitioners (NPs) have an advanced level of education and some practice autonomously. However, PA and NP programs are not required to provide any basic radiology education. For PEs who did receive basic radiology education during their graduate program, the curriculum is nonstandard and there is a wide variation. PEs working in primary care and nonradiology specialties place imaging orders, review report findings, and answer patient questions. Other PEs working within radiology practices operate as liaisons with patients in diagnostic radiology or perform an increasing number of interventional procedures. Basic radiology education in formal PE certificate programs as well as on-the-job education about radiology may benefit patients, radiologists, and the health-care system. What role, if any, should the radiologist assume for educating PE students and practicing PAs and NPs? This review analyzes the benefits and drawbacks of radiologists educating PEs.

  7. [Activities and authors. Role playing in health education].

    PubMed

    de Araújo, E G; Nunes, M M

    1996-01-01

    One the forms that the capitalism met for perpetuate his ideology was through of scholastic institution and do this, your set doctrinaire. This space orderly frequently oppose teachers and students, where the practice is enforce through of foregoing scheme. At sphere of health, this scheme repeatedly, because the conception of health /disease nap works of health teach the subordinate population and the culture is transmit for health, basically on advice and norm for the people with process of culpability for theirs diseases. We would like at this work report our experience with the Pedagogic Psychodrama of ROMANA (1987), at raising your demands referring informations about Firsts Aids with teenagers matriculation on course for patrol at slum of Rocinha(R.J.), where the datas were analysis quality of discourse. The utilization of a methodology don't exclude the station context if subject of apprenticeship, contribute for understand your role and commitment with the transformation personal and collective, we hope contribute with Nursing, teach possibilities, pedagogic and creatives for humanization the Education at Health.

  8. The ULT trxG factors play a role in arabidopsis fertilization

    PubMed Central

    Monfared, Mona M; Fletcher, Jennifer C

    2014-01-01

    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 decisions and cellular differentiation in plants, relatively little is known about the functions of plant trxG factors. We recently determined the biological roles for the ULT1 and ULT2 trxG genes during Arabidopsis vegetative and reproductive development. Our study revealed that ULT1 and ULT2 genes have overlapping activities in regulating Arabidopsis shoot and floral stem cell activity, and that they have a redundant function in establishing the apical-basal polarity axis of the gynoecium. Here we present data that ult1 and ult1 ult2 siliques contain a significant proportion of aborted ovules, supporting an additional role for ULT1 in Arabidopsis fertility. Our results add to the number of plant developmental processes that are regulated by trxG activity. PMID:25531183

  9. Symbiotic bacteria of helminths: what role may they play in ecosystems under anthropogenic stress?

    PubMed

    Morley, N J

    2016-11-01

    Symbiotic bacteria are a common feature of many animals, particularly invertebrates, from both aquatic and terrestrial habitats. These bacteria have increasingly been recognized as performing an important role in maintaining invertebrate health. Both ecto- and endoparasitic helminths have also been found to harbour a range of bacterial species which provide a similar function. The part symbiotic bacteria play in sustaining homeostasis of free-living invertebrates exposed to anthropogenic pressure (climate change, pollution), and the consequences to invertebrate populations when their symbionts succumb to poor environmental conditions, are increasingly important areas of research. Helminths are also susceptible to environmental stress and their symbiotic bacteria may be a key aspect of their responses to deteriorating conditions. This article summarizes the ecophysiological relationship helminths have with symbiotic bacteria and the role they play in maintaining a healthy parasite and the relevance of specific changes that occur in free-living invertebrate-bacteria interactions under anthropogenic pressure to helminths and their bacterial communities. It also discusses the importance of understanding the mechanistic sensitivity of helminth-bacteria relationships to environmental stress for comprehending the responses of parasites to challenging conditions.

  10. An evaluation of the role played by remote sensing technology following the World Trade Center attack

    NASA Astrophysics Data System (ADS)

    Huyck, Charles K.; Adams, Beverley J.; Kehrlein, David I.

    2003-06-01

    Remote sensing technology has been widely recognized for contributing to emergency response efforts after the World Trade Center attack on September 11th, 2001. The need to coordinate activities in the midst of a dense, yet relatively small area, made the combination of imagery and mapped data strategically useful. This paper reviews the role played by aerial photography, satellite imagery, and LIDAR data at Ground Zero. It examines how emergency managers utilized these datasets, and identifies significant problems that were encountered. It goes on to explore additional ways in which imagery could have been used, while presenting recommendations for more effective use in future disasters and Homeland Security applications. To plan adequately for future events, it was important to capture knowledge from individuals who responded to the World Trade Center attack. In recognition, interviews with key emergency management and geographic information system (GIS) personnel provide the basis of this paper. Successful techniques should not be forgotten, or serious problems dismissed. Although widely used after September 11th, it is important to recognize that with better planning, remote sensing and GIS could have played an even greater role. Together with a data acquisition timeline, an expanded discussion of these issues is available in the MCEER/NSF report “Emergency Response in the Wake of the World Trade Center Attack; The Remote Sensing Perspective” (Huyck and Adams, 2002)

  11. Phytochromes play a role in phototropism and gravitropism in Arabidopsis roots

    NASA Astrophysics Data System (ADS)

    Correll, Melanie J.; Coveney, Katrina M.; Raines, Steven V.; Mullen, Jack L.; Hangarter, Roger P.; Kiss, John Z.

    2003-05-01

    Phototropism as well as gravitropism plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. Phytochrome A (phyA) and phyB mediate the positive red-light-based photoresponse in roots since single mutants (and the double phyAB mutant) were severely impaired in this response. In blue-light-based negative phototropism, phyA and phyAB (but not phyB) were inhibited in the response relative to the WT. In root gravitropism, phyB and phyAB (but not phyA) were inhibited in the response compared to the WT. The differences observed in tropistic responses were not due to growth limitations since the growth rates among all the mutants tested were not significantly different from that of the WT. Thus, our study shows that the blue-light and red-light systems interact in roots and that phytochrome plays a key role in plant development by integrating multiple environmental stimuli.

  12. Phytochromes play a role in phototropism and gravitropism in Arabidopsis roots

    NASA Technical Reports Server (NTRS)

    Correll, Melanie J.; Coveney, Katrina M.; Raines, Steven V.; Mullen, Jack L.; Hangarter, Roger P.; Kiss, John Z.

    2003-01-01

    Phototropism as well as gravitropism plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. Phytochrome A (phyA) and phyB mediate the positive red-light-based photoresponse in roots since single mutants (and the double phyAB mutant) were severely impaired in this response. In blue-light-based negative phototropism, phyA and phyAB (but not phyB) were inhibited in the response relative to the WT. In root gravitropism, phyB and phyAB (but not phyA) were inhibited in the response compared to the WT. The differences observed in tropistic responses were not due to growth limitations since the growth rates among all the mutants tested were not significantly different from that of the WT. Thus, our study shows that the blue-light and red-light systems interact in roots and that phytochrome plays a key role in plant development by integrating multiple environmental stimuli. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

  13. Intragenic CpG islands play important roles in bivalent chromatin assembly of developmental genes.

    PubMed

    Lee, Sun-Min; Lee, Jungwoo; Noh, Kyung-Min; Choi, Won-Young; Jeon, Sejin; Oh, Goo Taeg; Kim-Ha, Jeongsil; Jin, Yoonhee; Cho, Seung-Woo; Kim, Young-Joon

    2017-03-07

    CpG, 5'-C-phosphate-G-3', islands (CGIs) have long been known for their association with enhancers, silencers, and promoters, and for their epigenetic signatures. They are maintained in embryonic stem cells (ESCs) in a poised but inactive state via the formation of bivalent chromatin containing both active and repressive marks. CGIs also occur within coding sequences, where their functional role has remained obscure. Intragenic CGIs (iCGIs) are largely absent from housekeeping genes, but they are found in all genes associated with organ development and cell lineage control. In this paper, we investigated the epigenetic status of iCGIs and found that they too reside in bivalent chromatin in ESCs. Cell type-specific DNA methylation of iCGIs in differentiated cells was linked to the loss of both the H3K4me3 and H3K27me3 marks, and disruption of physical interaction with promoter regions, resulting in transcriptional activation of key regulators of differentiation such as PAXs, HOXs, and WNTs. The differential epigenetic modification of iCGIs appears to be mediated by cell type-specific transcription factors distinct from those bound by promoter, and these transcription factors may be involved in the hypermethylation of iCGIs upon cell differentiation. iCGIs thus play a key role in the cell type-specific regulation of transcription.

  14. Multilayered Regulation of Ethylene Induction Plays a Positive Role in Arabidopsis Resistance against Pseudomonas syringae.

    PubMed

    Guan, Rongxia; Su, Jianbin; Meng, Xiangzong; Li, Sen; Liu, Yidong; Xu, Juan; Zhang, Shuqun

    2015-09-01

    Ethylene, a key phytohormone involved in plant-pathogen interaction, plays a positive role in plant resistance against fungal pathogens. However, its function in plant bacterial resistance remains unclear. Here, we report a detailed analysis of ethylene induction in Arabidopsis (Arabidopsis thaliana) in response to Pseudomonas syringae pv tomato DC3000 (Pst). Ethylene biosynthesis is highly induced in both pathogen/microbe-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity (ETI), and the induction is potentiated by salicylic acid (SA) pretreatment. In addition, Pst actively suppresses PAMP-triggered ethylene induction in a type III secretion system-dependent manner. SA potentiation of ethylene induction is dependent mostly on MITOGEN-ACTIVATED PROTEIN KINASE6 (MPK6) and MPK3 and their downstream ACS2 and ACS6, two type I isoforms of 1-aminocyclopropane-1-carboxylic acid synthases (ACSs). ACS7, a type III ACS whose expression is enhanced by SA pretreatment, is also involved. Pst expressing the avrRpt2 effector gene (Pst-avrRpt2), which is capable of triggering ETI, induces a higher level of ethylene production, and the elevated portion is dependent on SALICYLIC ACID INDUCTION DEFICIENT2 and NONEXPRESSER OF PATHOGENESIS-RELATED GENE1, two key players in SA biosynthesis and signaling. High-order ACS mutants with reduced ethylene induction are more susceptible to both Pst and Pst-avrRpt2, demonstrating a positive role of ethylene in plant bacterial resistance mediated by both PAMP-triggered immunity and ETI.

  15. The Sirt6 gene: Does it play a role in tooth development?

    PubMed Central

    Liao, Xueyang; Feng, Bo; Zhang, Demao; Liu, Peng; Zhou, Xuedong; Li, Ruimin; Ye, Ling

    2017-01-01

    Dental Mesenchymal Cells (DMCs) are known to play a role in tooth development as well as in the repair and regeneration of dental tissue. A large number of signaling molecules regulate the proliferation and differentiation of DMC, though the underlying mechanisms are still not fully understood. Sirtuin-6 (SIRT6), a key regulator of aging, can exert an impact on embryonic stem cell (ESC) differentiation. The experimental deletion of Sirt6 in mouse bone marrow cells has been found to have an inhibiting impact on the bone mineral density and the osteogenic differentiation of these cells. The possible role of Sirt6 in tooth development, however, has at present remained largely unexplored. In the present study, we found that SIRT6 had no effect on tooth development before birth. However, Sirt6 gene deletion in knockout mice did have two post-natal impacts: a delay in tooth eruption and sluggishness in the development of dental roots. We propose an explanation of the possible molecular basis of the changes observed in Sirt6-/- mice. SIRT6 is expressed in mouse odontoblasts. Sirt6 deletion enhanced the proliferation of DMCs, as well as their capacity for adipogenic differentiation. On the other hand, it inhibited their capacity for in vitro osteogenic/chondrogenic differentiation. Further studies suggested that other factors may mediate the role of Sirt6 in odontogenesis. These include the nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase (p38-MAPK), extracellular regulated MAP kinase (ERK) pathways and the mitochondrial energy. We demonstrated that Sirt6 plays a role in tooth root formation and confirmed that SIRT6 is necessary for DMC differentiation as well as for the development of the tooth root and for eventual tooth eruption. These results establish a new link between SIRT6 and tooth development. PMID:28355287

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

    NASA Astrophysics Data System (ADS)

    Heise Kofoed, Mikkel

    2006-11-01

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

  17. Intraparietal regions play a material general role in working memory: evidence supporting an internal attentional role

    PubMed Central

    Killebrew, Kyle; Mruczek, Ryan; Berryhill, Marian E.

    2015-01-01

    Determining the role of intraparietal sulcus (IPS) regions in working memory (WM) remains a topic of considerable interest and lack of clarity. One group of hypotheses, the internal attention view, proposes that the IPS plays a material general role in maintaining information in WM. An alternative viewpoint, the pure storage account, proposes that the IPS in each hemisphere maintains material specific (e.g., left – phonological; right – visuospatial) information. Yet, adjudication between competing theoretical perspectives is complicated by divergent findings from different methodologies and their use of different paradigms, perhaps most notably between functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). For example, fMRI studies typically use full field stimulus presentations and report bilateral IPS activation, whereas EEG studies direct attention to a single hemifield and report a contralateral bias in both hemispheres. Here, we addressed this question by applying a regions-of-interest fMRI approach to elucidate IPS contributions to WM. Importantly, we manipulated stimulus type (verbal, visuospatial) and the cued hemifield to assess the degree to which IPS activations reflect stimulus specific or stimulus general processing consistent with the pure storage or internal attention hypotheses. These data revealed significant contralateral bias along regions IPS0-5 regardless of stimulus type. Also present was a weaker stimulus-based bias apparent in stronger left lateralized activations for verbal stimuli and stronger right lateralized activations for visuospatial stimuli. However, there was no consistent stimulus-based lateralization of activity. Thus, despite the observation of stimulus-based modulation of spatial lateralization this pattern was bilateral. As such, although it is quantitatively underspecified, our results are overall more consistent with an internal attention view that the IPS plays a material general role in

  18. Canadian Early Childhood Educators' Perceptions of Young Children's Gender-Role Play and Cultural Identity

    ERIC Educational Resources Information Center

    Servos, Jennifer E.; Dewar, Brandy A.; Bosacki, Sandra L.; Coplan, Robert J.

    2016-01-01

    This article investigates early childhood educators' perceptions of children's gender-role play and the impact their cultural background plays in their gender identity and play behaviors. Through qualitative in-depth interviews, early childhood educators in Canada (n = 40) were asked questions relating to their experiences with children from…

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

    ERIC Educational Resources Information Center

    Eggleston, Noel C.

    1978-01-01

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

  20. Mars Colony: Using Role-Play as a Pedagogical Approach to Teaching Science

    ERIC Educational Resources Information Center

    Dolenc, Nathan; Wood, Aja; Soldan, Katie; Tai, Robert H.

    2016-01-01

    In this article, the authors discuss role-play as a pedagogical strategy to engage kindergarten and first-grade students in science and engineering. They present a five-part Mars colony lesson that they developed for a blended class, during which students role-play a space-exploration story that enables them to gain a firsthand perspective of what…

  1. The Great Evolution Trial: Use of Role-Play in the Classroom.

    ERIC Educational Resources Information Center

    Duveen, Jonathan; Solomon, Joan

    1994-01-01

    Provides both the pedagogic and scientific thinking that guided the construction of a classroom role play called "The Great Evolution Debate," which is about the publication of Darwin's "The Origin of Species." Provides tentative findings regarding learning from role playing. (ZWH)

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

    Samalot-Rivera, Amaury

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Howes, Elaine V.; Cruz, Barbara C.

    2009-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    ERIC Educational Resources Information Center

    Shen, Lin; Suwanthep, Jitpanat

    2011-01-01

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

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

    ERIC Educational Resources Information Center

    Cruz, Barbara C.; Murthy, Shalini A.

    2006-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    ERIC Educational Resources Information Center

    Belova, Nadja; Eilks, Ingo; Feierabend, Timo

    2015-01-01

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

  11. Enhancing Role-Play Activities with Pocket Camcorder Technology: Strategies for Counselor-Educators

    ERIC Educational Resources Information Center

    Walter, Sara Meghan; Thanasiu, Page L.

    2011-01-01

    Counselor-educators can benefit from specific guidelines and creative suggestions when implementing role-play and technology-related teaching strategies in counseling training programs. Therefore, the purpose of this article is to: (a) discuss the use of role-play and video recording in counselor education; (b) introduce counselor-educators to…

  12. What Happens When Students Do Simulation-role-play in Science?

    ERIC Educational Resources Information Center

    Aubusson, Peter; Fogwill, Stephen; Perkovic, Linda; Barr, Rajender

    1997-01-01

    Results of this study suggest that simulation-role-play allows students to demonstrate their understanding, explore their views, and develop deeper understanding of phenomena. The technique was especially beneficial to students who prefer learning kinesthetically. Suggests a strategy for using analogical analysis in simulation-role-play. Contains…

  13. Tutor Scaffolding Styles of Dilemma Solving in Network-Based Role-Play

    ERIC Educational Resources Information Center

    Pata, Kai; Sarapuu, Tago; Lehtinen, Erno

    2005-01-01

    This study investigated tutoring during collaborative role-play dealing with environmental dilemmas in a synchronous network environment. The relationships of different tutor scaffolding styles with students' discourse acts and their decision-making variables were studied. A role-play with a jigsaw design was developed using the model of real-life…

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

    ERIC Educational Resources Information Center

    Kraus, Rachel

    2008-01-01

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

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

    ERIC Educational Resources Information Center

    Craft, Judy; Ainscough, Louise

    2015-01-01

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

  16. mTOR Complex 1 Plays Critical Roles in Hematopoiesis and Pten-Loss-Evoked Leukemogenesis

    PubMed Central

    Kalaitzidis, Demetrios; Sykes, Stephen M.; Wang, Zhu; Punt, Natalie; Tang, Yuefeng; Ragu, Christine; Sinha, Amit U.; Lane, Steven W.; Souza, Amanda L.; Clish, Clary B.; Anastasiou, Dimitrios; Gilliland, D. Gary; Scadden, David T.; Guertin, David A.; Armstrong, Scott A.

    2013-01-01

    SUMMARY The mammalian target of rapamycin (mTOR)-pathway serves as a key sensor of cellular-energetic state, and functions to maintain tissue homeostasis. Hyperactivation of the mTOR pathway impairs hematopoietic stem cell (HSC) function and is associated with leukemogenesis. However, the roles of the unique mTOR complexes (mTORCs) in hematopoeisis and leukemogenesis have not been adequately elucidated. We deleted the mTORC1 component, Raptor (regulatory-associated protein of mTOR), in mouse HSC and its loss causes a non-lethal phenotype characterized by pancytopenia, splenomegaly, and the accumulation of monocytoid cells. Furthermore, Raptor is required for HSC regeneration, and plays largely non-redundant roles with Rictor (rapamycin-insensitive companion of mTOR), in these processes. Ablation of Raptor also significantly extends survival of mice in models of leukemogenesis evoked by Pten deficiency. These data delineate critical roles for mTORC1 in hematopoietic function and leukemogenesis, and inform clinical strategies based on chronic mTORC1 inhibition. PMID:22958934

  17. Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing.

    PubMed

    Becherel, Olivier J; Yeo, Abrey J; Stellati, Alissa; Heng, Evelyn Y H; Luff, John; Suraweera, Amila M; Woods, Rick; Fleming, Jean; Carrie, Dianne; McKinney, Kristine; Xu, Xiaoling; Deng, Chuxia; Lavin, Martin F

    2013-04-01

    Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2), plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossing-over in homologous recombination and in meiotic sex chromosome inactivation (MSCI). Disruption of the Setx gene caused persistence of DNA double-strand breaks, a defect in disassembly of Rad51 filaments, accumulation of DNA:RNA hybrids (R-loops), and ultimately a failure of crossing-over. Senataxin localised to the XY body in a Brca1-dependent manner, and in its absence there was incomplete localisation of DNA damage response proteins to the XY chromosomes and ATR was retained on the axial elements of these chromosomes, failing to diffuse out into chromatin. Furthermore persistence of RNA polymerase II activity, altered ubH2A distribution, and abnormal XY-linked gene expression in Setx⁻/⁻ revealed an essential role for senataxin in MSCI. These data support key roles for senataxin in coordinating meiotic crossing-over with transcription and in gene silencing to protect the integrity of the genome.

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

    ERIC Educational Resources Information Center

    Kim, Yongho; Kellogg, David

    2007-01-01

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

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

    PubMed

    Doorn, Neelke; Kroesen, J Otto

    2013-12-01

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

  20. Informatic analysis for hidden pulse attack exploiting spectral characteristics of optics in plug-and-play quantum key distribution system

    NASA Astrophysics Data System (ADS)

    Ko, Heasin; Lim, Kyongchun; Oh, Junsang; Rhee, June-Koo Kevin

    2016-10-01

    Quantum channel loopholes due to imperfect implementations of practical devices expose quantum key distribution (QKD) systems to potential eavesdropping attacks. Even though QKD systems are implemented with optical devices that are highly selective on spectral characteristics, information theory-based analysis about a pertinent attack strategy built with a reasonable framework exploiting it has never been clarified. This paper proposes a new type of trojan horse attack called hidden pulse attack that can be applied in a plug-and-play QKD system, using general and optimal attack strategies that can extract quantum information from phase-disturbed quantum states of eavesdropper's hidden pulses. It exploits spectral characteristics of a photodiode used in a plug-and-play QKD system in order to probe modulation states of photon qubits. We analyze the security performance of the decoy-state BB84 QKD system under the optimal hidden pulse attack model that shows enormous performance degradation in terms of both secret key rate and transmission distance.

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

    SciTech Connect

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

    2009-12-01

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

  2. Role of auditory feedback in the control of successive keystrokes during piano playing

    PubMed Central

    Soechting, John F.

    2011-01-01

    The purpose of this study was to elucidate the role of auditory feedback derived from one keystroke in the control of the rhythmicity and velocity of successive keystrokes during piano playing. We examined the effects of transient auditory perturbations with respect to the pitch, loudness, and timing of one tone on subsequent keystrokes while six pianists played short excerpts from three simple musical pieces having different tempi (“event rates”). Immediately after a delay in tone production, the inter-keystroke interval became shorter. This compensatory action depended on the tempo, being most prominent at the medium tempo. This indicates that temporal information provided by auditory feedback is utilized to regulate the timing of movement elements produced in a sequence. We also found that the keystroke velocity changed after the timing, pitch, or loudness of a tone was altered, although the response differed depending on the type of perturbation. While delaying the timing or altering the pitch led to an increase in the velocity, altering the loudness changed the velocity in an inconsistent manner. Furthermore, perturbing a tone elicited by the right hand also affected the rhythmicity and velocity of keystrokes with the left hand, indicating that bimanual coordination of tone production was maintained. Finally, altering the pitch sometimes resulted in striking an incorrect key, mostly in the slow piece, emphasizing the importance of pitch information for accurate planning and execution of sequential piano keystrokes. PMID:20521031

  3. Key role of hydrodynamic interactions in colloidal gelation.

    PubMed

    Furukawa, Akira; Tanaka, Hajime

    2010-06-18

    Colloidal gelation is caused by the formation of a percolated network of colloidal particles suspended in a liquid. Thus far the major transport process leading to gelation has been believed to be the brownian diffusion of particles. Contrary to this common belief, we reveal by numerical simulations that many-body hydrodynamic interactions between colloidal particles also play an essential role in gelation: They significantly promote gelation, or lower the colloid volume fraction threshold for percolation, as compared to their absence. We find that the incompressible nature of a liquid component and the resulting self-organization of hydrodynamic flow with a transverse (rotational) character are responsible for this enhancement of network-forming ability.

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

    PubMed

    Mackay Yarnal, Careen

    2006-01-01

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

  5. Key role of 5-HT3 receptors in the nucleus tractus solitarii in cardiovagal stress reactivity.

    PubMed

    Sévoz-Couche, Caroline; Brouillard, Charly

    2017-03-01

    Serotonin plays a modulatory role in central control of the autonomic nervous system (ANS). The nucleus tractus solitarii (NTS) in the medulla is an area of viscerosomatic integration innervated by both central and peripheral serotonergic fibers. Influences from different origins therefore trigger the release of serotonin into the NTS and exert multiple influences on the ANS. This major influence on the ANS is also mediated by activation of several receptors in the NTS. In particular, the NTS is the central zone with the highest density of serotonin3 (5-HT3) receptors. In this review, we present evidence that 5-HT3 receptors in the NTS play a key role in one of the crucial homeostatic responses to acute and chronic stress: inhibitory modulation of the parasympathetic component of the ANS. The possible functional interactions of 5-HT3 receptors with GABAA and NK1 receptors in the NTS are also discussed.

  6. NADPH oxidase plays a crucial role in the activation of pancreatic stellate cells.

    PubMed

    Masamune, Atsushi; Watanabe, Takashi; Kikuta, Kazuhiro; Satoh, Kennichi; Shimosegawa, Tooru

    2008-01-01

    Activated pancreatic stellate cells (PSCs) play an important role in pancreatic fibrosis and inflammation, where oxidative stress is implicated in the pathogenesis. NADPH oxidase might be a source of reactive oxygen species (ROS) in the injured pancreas. This study aimed to clarify the expression and regulation of cell functions by NADPH oxidase in PSCs. PSCs were isolated from rat and human pancreas tissues. Expression of NADPH oxidase was assessed by reverse transcription-PCR and immunostaining. Intracellular ROS production was assessed using 2',7'-dichlorofluorescin diacetate. The effects of diphenylene iodonium (DPI) and apocynin, inhibitors of NADPH oxidase, on key parameters of PSC activation were evaluated in vitro. In vivo, DPI (at 1 mg.kg body wt(-1).day(-1)) was administered in drinking water to 10-wk-old male Wistar Bonn/Kobori rats for 10 wk and to rats with chronic pancreatitis induced by dibutyltin dichloride (DBTC). PSCs expressed key components of NADPH oxidase (p22(phox), p47(phox), NOX1, gp91(phox)/NOX2, NOX4, and NOX activator 1). PDGF-BB, IL-1beta, and angiotensin II induced ROS production, which was abolished by DPI and apocynin. DPI inhibited PDGF-induced proliferation, IL-1beta-induced chemokine production, and expression of alpha-smooth muscle actin and collagen. DPI inhibited transformation of freshly isolated cells to a myofibroblast-like phenotype. In addition, DPI inhibited the development of pancreatic fibrosis in Wistar Bonn/Kobori rats and in rats with DBTC-induced chronic pancreatitis. In conclusion, PSCs express NADPH oxidase to generate ROS, which mediates key cell functions and activation of PSCs. NADPH oxidase might be a potential target for the treatment of pancreatic fibrosis.

  7. Eight proteins play critical roles in RCC with bone metastasis via mitochondrial dysfunction.

    PubMed

    Wang, Jiang; Zhao, Xiaolin; Qi, Jun; Yang, Caihong; Cheng, Hao; Ren, Ye; Huang, Lei

    2015-08-01

    Most kidney cancers are renal cell carcinomas (RCC). RCC lacks early warning signs and 70 % of patients with RCC develop metastases. Among them, 50 % of patients having skeletal metastases developed a dismal survival of less than 10 % at 5 years. Therefore, exploring the key driving proteins and pathways involved in RCC bone metastasis could benefit patients' therapy and prolong their survival. We examined the difference between the OS-RC-2 cells and the OS-RC-2-BM5 cells (subpopulation from OS-RC-2) of RCC with proteomics. Then we employed Western-blot, immunohistochemistry and the clinical database (oncomine) to screen and verify the key proteins and then we analyzed the functions and the related pathways of selected key proteins with system biology approaches. Our proteomic data revealed 26 significant changed spots (fold change <0.5 and >1.9, P < 0.05) between two cells. The Western blotting results validated for these identified spots were consistent with the proteomics'. From the public clinical database, 23 out of 26 proteins were connected with RCC metastases and 9 out of 23 with survival time directly (P < 0.05). Finally, only 8 out of 9 proteins had significantly positive results in tissues of RCC patients with bone metastasis compared with primary tumor (P < 0.05). System biology analyzing results showed these eight proteins mainly distributed in oxidative phosphorylation which indicates that mitochondria dysfunction played the critical role to regulate cells metastasis. Our article used a variety of experimental techniques to find eight proteins which abnormally regulated mitochondrial function to achieve a successful induction for RCC metastasis to bone.

  8. What roles do middle managers play in implementation of innovative practices?

    PubMed Central

    Engle, Ryann L.; Lopez, Emily R.; Gormley, Katelyn E.; Chan, Jeffrey A.; Charns, Martin P.; Lukas, Carol VanDeusen

    2017-01-01

    Background: Middle managers play key roles in hospitals as the bridge between senior leaders and frontline staff. Yet relatively little research has focused on their role in implementing new practices. Purpose: The aim of this study was to expand the understanding of middle managers’ influence in organizations by looking at their activities through the lens of two complementary conceptual frameworks. Methodology/Approach: We analyzed qualitative data from 17 Veterans Affairs Medical Centers with high and low potential to change organizational practices. We analyzed 98 interviews with staff ranging from senior leaders to frontline staff to identify themes within an a priori framework reflecting middle manager activities. Findings: Analyses yielded 14 emergent themes that allowed us to classify specific expressions of middle manager commitment to implementation of innovative practices (e.g., facilitate improvement innovation, garner staff buy-in). In comparing middle manager behaviors in high and low change potential sites, we found that most emergent themes were present in both groups. However, the activities and interactions described differed between the groups. Practice Implications: Middle managers can use the promising strategies identified by our analyses to guide and improve their effectiveness in implementing new practices. These strategies can also inform senior leaders striving to guide middle managers in those efforts. PMID:26488239

  9. Neurospora COP9 signalosome integrity plays major roles for hyphal growth, conidial development, and circadian function.

    PubMed

    Zhou, Zhipeng; Wang, Ying; Cai, Gaihong; He, Qun

    2012-01-01

    The COP9 signalosome (CSN) is a highly conserved multifunctional complex that has two major biochemical roles: cleaving NEDD8 from cullin proteins and maintaining the stability of CRL components. We used mutation analysis to confirm that the JAMM domain of the CSN-5 subunit is responsible for NEDD8 cleavage from cullin proteins in Neurospora crassa. Point mutations of key residues in the metal-binding motif (EX(n)HXHX(10)D) of the CSN-5 JAMM domain disrupted CSN deneddylation activity without interfering with assembly of the CSN complex or interactions between CSN and cullin proteins. Surprisingly, CSN-5 with a mutated JAMM domain partially rescued the phenotypic defects observed in a csn-5 mutant. We found that, even without its deneddylation activity, the CSN can partially maintain the stability of the SCF(FWD-1) complex and partially restore the degradation of the circadian clock protein FREQUENCY (FRQ) in vivo. Furthermore, we showed that CSN containing mutant CSN-5 efficiently prevents degradation of the substrate receptors of CRLs. Finally, we found that deletion of the CAND1 ortholog in N. crassa had little effect on the conidiation circadian rhythm. Our results suggest that CSN integrity plays major roles in hyphal growth, conidial development, and circadian function in N. crassa.

  10. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis

    PubMed Central

    Tsai, Wei-Chih; Hsu, Sheng-Da; Hsu, Chu-Sui; Lai, Tsung-Ching; Chen, Shu-Jen; Shen, Roger; Huang, Yi; Chen, Hua-Chien; Lee, Chien-Hsin; Tsai, Ting-Fen; Hsu, Ming-Ta; Wu, Jaw-Ching; Huang, Hsien-Da; Shiao, Ming-Shi; Hsiao, Michael; Tsou, Ann-Ping

    2012-01-01

    MicroRNA-122 (miR-122), which accounts for 70% of the liver’s total miRNAs, plays a pivotal role in the liver. However, its intrinsic physiological roles remain largely undetermined. We demonstrated that mice lacking the gene encoding miR-122a (Mir122a) are viable but develop temporally controlled steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). These mice exhibited a striking disparity in HCC incidence based on sex, with a male-to-female ratio of 3.9:1, which recapitulates the disease incidence in humans. Impaired expression of microsomal triglyceride transfer protein (MTTP) contributed to steatosis, which was reversed by in vivo restoration of Mttp expression. We found that hepatic fibrosis onset can be partially attributed to the action of a miR-122a target, the Klf6 transcript. In addition, Mir122a–/– livers exhibited disruptions in a range of pathways, many of which closely resemble the disruptions found in human HCC. Importantly, the reexpression of miR-122a reduced disease manifestation and tumor incidence in Mir122a–/– mice. This study demonstrates that mice with a targeted deletion of the Mir122a gene possess several key phenotypes of human liver diseases, which provides a rationale for the development of a unique therapy for the treatment of chronic liver disease and HCC. PMID:22820290

  11. FACT plays a major role in histone dynamics affecting VSG expression site control in Trypanosoma brucei.

    PubMed

    Denninger, Viola; Rudenko, Gloria

    2014-11-01

    Chromatin remodelling is involved in the transcriptional regulation of the RNA polymerase I transcribed variant surface glycoprotein (VSG) expression sites (ESs) of Trypanosoma brucei. We show that the T. brucei FACT complex contains the Pob3 and Spt16 subunits, and plays a key role in ES silencing. We see an inverse correlation between transcription and condensed chromatin, whereby FACT knockdown results in ES derepression and more open chromatin around silent ES promoters. Derepressed ESs show increased sensitivity to micrococcal nuclease (MNase) digestion, and a decrease in histones at silent ES promoters but not telomeres. In contrast, FACT knockdown results in more histones at the active ES, correlated with transcription shut-down. ES promoters are derepressed in cells stalled at the G2/M cell cycle stage after knockdown of FACT, but not in G2/M cells stalled after knockdown of cyclin 6. This argues that the observed ES derepression is a direct consequence of histone chaperone activity by FACT at the G2/M cell cycle stage which could affect transcription elongation, rather than an indirect consequence of a cell cycle checkpoint. These experiments highlight the role of the FACT complex in cell cycle-specific chromatin remodelling within VSG ESs.

  12. The Many Roles We Play: Perceptions of the Role of Psychology Lecturers According to Staff and Students

    ERIC Educational Resources Information Center

    Coyne, Sarah M.

    2007-01-01

    Lecturers in psychology have many different roles that they must play. It is often very difficult to know what roles are the most important and which to focus on. This study assessed the perceived importance of seven different roles lecturers undertake according to psychology lecturers and students. Results indicated that assessor, course planner,…

  13. Bringing the U.S. Senate to Your Classroom: A Role Play Activity.

    ERIC Educational Resources Information Center

    Hack, Ken

    1989-01-01

    Advocates role playing for teaching a unit on the legislative branch of government. Students were divided into political parties, sat on committees, and produced legislation. Concludes that experiencing the governmental process enhances citizen participation. (GG)

  14. For Kids with Kidney Disease, Race May Play Role in Outcomes

    MedlinePlus

    ... gov/news/fullstory_162794.html For Kids With Kidney Disease, Race May Play Role in Outcomes Risk of ... chronic kidney failure. All had been treated for kidney disease with either dialysis or transplants between 1995 and ...

  15. Exercise and Drinking May Play a Role in Vision Impairment Risk

    MedlinePlus

    ... May Play a Role in Vision Impairment Risk Mar. 20, 2014 In 2020, the number of people ... 2004;122:477–85. Related Stories Drusen Diagnosis Mar 01, 2017 Stargardt Disease Symptoms Mar 01, 2017 ...

  16. Problematic usage among highly-engaged players of massively multiplayer online role playing games.

    PubMed

    Peters, Christopher S; Malesky, L Alvin

    2008-08-01

    One popular facet of Internet gaming is the massively multiplayer online role playing game (MMORPG). Some individuals spend so much time playing these games that it creates problems in their lives. This study focused on players of World of Warcraft. Factor analysis revealed one factor related to problematic usage, which was correlated with amount of time played, and personality characteristics of agreeableness, conscientiousness, neuroticism, and extraversion.

  17. FtsH11 Proteases play a critical role in high temperature stress tolerance in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    FtsHs (Filamentous temperature sensitive H), ATP-dependent zinc metalloproteases of the AAA-superfamily, play essential roles in the turn over of thylakoid proteins damaged by high light stress during photosynthesis. Here, we show that FtsH11, one of the 12 FtsH members in Arabidopsis, plays critic...

  18. Learner Interaction in a Massively Multiplayer Online Role Playing Game (MMORPG): A Sociocultural Discourse Analysis

    ERIC Educational Resources Information Center

    Peterson, Mark

    2012-01-01

    This exploratory study investigates the linguistic and social interaction of four intermediate EFL learners during game play in a massively multiplayer online role playing game (MMORPG). Twelve illustrative episodes drawn from the participants' text chat, collected in four 70-minute sessions held over a one-month period, are analyzed from a…

  19. Exploring Kindergarten Teachers' Views and Roles Regarding Children's Outdoor Play Environments in Oman

    ERIC Educational Resources Information Center

    Ihmeideh, Fathi M.; Al-Qaryouti, Ibrahim A.

    2016-01-01

    The purpose of this study was to explore kindergarten teachers' views and roles regarding outdoor play environments in Omani kindergartens. Thirty kindergarten teachers from 15 private kindergartens were observed and interviewed. The results indicated that teachers recognize the importance of outdoor play in children's development and learning.…

  20. What Can Students Learn in an Extended Role-Play Simulation on Technology and Society?

    ERIC Educational Resources Information Center

    Loui, Michael C.

    2009-01-01

    In a small course on technology and society, students participated in an extended role-play simulation for two weeks. Each student played a different adult character in a fictional community, which faces technological decisions in three scenarios set in the near future. The three scenarios involved stem cell research, nanotechnology, and privacy.…

  1. Using Analogy Role-Play Activity in an Undergraduate Biology Classroom to Show Central Dogma Revision

    ERIC Educational Resources Information Center

    Takemura, Masaharu; Kurabayashi, Mario

    2014-01-01

    For the study of biology in an undergraduate classroom, a classroom exercise was developed: an analogy role-play to learn mechanisms of gene transcription and protein translation (central dogma). To develop the central dogma role-play exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress hanger, and amino acids using Lego®…

  2. Links between dissociation and role play in a nonclinical sample of preschool children.

    PubMed

    Carlson, Stephanie M; Tahiroglu, Deniz; Taylor, Marjorie

    2008-01-01

    Children's role play activities are included in symptom checklists of dissociative disorders, yet little is known about the potential relation between individual differences in role play and dissociative behaviors in normative development. This issue was examined in a study of 147 children aged 3 and 4 from a nonclinical population. Parents completed the Child Dissociative Checklist (CDC; F. W. Putnam, K. Helmers, & P. K. Trickett, 1993) and a questionnaire about their child's role play, fears, behavior problems, and dreams. Children were also interviewed about these same items. Dissociation was significantly related to parent report of fears, problem behaviors, and nightmares. These results are consistent with the view that CDC scores reflect some degree of difficulty in children's lives. Children who engaged in role play, particularly children with imaginary companions, scored higher on the CDC than other children. However, role play was not related to the measures of fears or problem behaviors. The results suggest that a distinction between pathological and nonpathological dissociation is warranted, with role play activities being more closely linked to the latter. Measurement of dissociation in preschoolers is discussed.

  3. The role of key features in predator recognition by untrained birds.

    PubMed

    Beránková, Jana; Veselý, Petr; Sýkorová, Jana; Fuchs, Roman

    2014-07-01

    The most important role in the recognition and categorization of predators (as well as other animals) is usually attributed to so-called key features. Under laboratory conditions, we tested the role of yellow eyes (specific for the genus Accipiter in European raptors) and hooked beak (common for all European birds of prey) in the recognition of the sparrowhawk (Accipiter nisus) by untrained great tits (Parus major) caught in the wild. Using wooden dummies, we interchanged either one of these potential key features or the body of the sparrowhawk (predator) and domestic pigeon (harmless bird). The tested tits showed three types of behaviour in the presence of the dummies: fear, interest without fear, and lack of interest. Eye interchange lowered fear of the sparrowhawk, but did not cause fear of the pigeon. Beak interchange did not lower fear of the sparrowhawk. Eye interchange caused increased interest in both species. Thus, a specific sparrowhawk feature is necessary for correct sparrowhawk dummy recognition but a general raptor feature is not. On the other hand, a specific sparrowhawk feature on a pigeon dummy is not enough to prompt sparrowhawk recognition. Thus, key features play an important, but not exclusive, role in predator recognition. An increased interest in some of the modified dummies implies that the tits have a general concept of a sparrowhawk. The individual variability in behaviour of tits is discussed.

  4. Following instructions in a virtual school: Does working memory play a role?

    PubMed

    Jaroslawska, Agnieszka J; Gathercole, Susan E; Logie, Matthew R; Holmes, Joni

    2016-05-01

    Accumulating evidence that working memory supports the ability to follow instructions has so far been restricted to experimental paradigms that have greatly simplified the practical demands of performing actions to instructions in everyday tasks. The aim of the present study was to investigate whether working memory is involved in maintaining information over the longer periods of time that are more typical of everyday situations that require performing instructions to command. Forty-two children 7-11 years of age completed assessments of working memory, a real-world following-instructions task employing 3-D objects, and two new computerized instruction-following tasks involving navigation around a virtual school to complete a sequence of practical spoken commands. One task involved performing actions in a single classroom, and the other, performing actions in multiple locations in a virtual school building. Verbal working memory was closely linked with all three following-instructions paradigms, but with greater association to the virtual than to the real-world tasks. These results indicate that verbal working memory plays a key role in following instructions over extended periods of activity.

  5. Developmental programming of obesity and insulin resistance: does mitochondrial dysfunction in oocytes play a role?

    PubMed

    Turner, Nigel; Robker, Rebecca L

    2015-01-01

    Insulin resistance is a key defect associated with obesity, type 2 diabetes and other metabolic diseases. While a number of factors have been suggested to cause defects in insulin action, there is a very strong association between inappropriate lipid deposition in insulin target tissues and the development of insulin resistance. In recent times, a large number of studies have reported changes in markers of mitochondrial metabolism in insulin-resistant individuals, leading to the theory that defects in mitochondrial substrate oxidation are responsible for the buildup of lipid intermediates and the development of insulin resistance. The primary support for the mitochondrial theory of insulin resistance comes from studies in skeletal muscle; however, there is recent evidence in murine models that mitochondrial dysfunction in oocytes may also play a role. Oocytes from obese or insulin-resistant mice have been shown to exhibit abnormalities in many different mitochondrial parameters, including mitochondrial morphology and membrane potential. Here we review the findings regarding the link between mitochondrial dysfunction and insulin resistance, and propose that abnormalities in mitochondrial metabolism in oocytes may predispose to the development of obesity and insulin resistance and thus contribute to the inter-generational programming of metabolic disease.

  6. Glutamine synthetase in the phloem plays a major role in controlling proline production

    PubMed Central

    Brugiere, N; Dubois, F; Limami, AM; Lelandais, M; Roux, Y; Sangwan, RS; Hirel, B

    1999-01-01

    To inhibit expression specifically in the phloem, a 274-bp fragment of a cDNA (Gln1-5) encoding cytosolic glutamine synthetase (GS1) from tobacco was placed in the antisense orientation downstream of the cytosolic Cu/Zn superoxide dismutase promoter of Nicotiana plumbaginifolia. After Agrobacterium-mediated transformation, two transgenic N. tabacum lines exhibiting reduced levels of GS1 mRNA and GS activity in midribs, stems, and roots were obtained. Immunogold labeling experiments allowed us to verify that the GS protein content was markedly decreased in the phloem companion cells of transformed plants. Moreover, a general decrease in proline content in the transgenic plants in comparison with wild-type tobacco was observed when plants were forced to assimilate large amounts of ammonium. In contrast, no major changes in the concentration of amino acids used for nitrogen transport were apparent. A (15)NH(4)(+)-labeling kinetic over a 48-hr period confirmed that in leaves of transgenic plants, the decrease in proline production was directly related to glutamine availability. After 2 weeks of salt treatment, the transgenic plants had a pronounced stress phenotype, consisting of wilting and bleaching in the older leaves. We conclude that GS in the phloem plays a major role in regulating proline production consistent with the function of proline as a nitrogen source and as a key metabolite synthesized in response to water stress. PMID:10521528

  7. A Minor Subset of Super Elongation Complexes Plays a Predominant Role in Reversing HIV-1 Latency.

    PubMed

    Li, Zichong; Lu, Huasong; Zhou, Qiang

    2016-02-01

    Promoter-proximal pausing by RNA polymerase II (Pol II) is a key rate-limiting step in HIV-1 transcription and latency reversal. The viral Tat protein recruits human super elongation complexes (SECs) to paused Pol II to overcome this restriction. Despite the recent progress in understanding the functions of different subsets of SECs in controlling cellular and Tat-activated HIV transcription, little is known about the SEC subtypes that help reverse viral latency in CD4(+) T cells. Here, we used the CRISPR-Cas9 genome-editing tool to knock out the gene encoding the SEC subunit ELL2, AFF1, or AFF4 in Jurkat/2D10 cells, a well-characterized HIV-1 latency model. Depletion of these proteins drastically reduced spontaneous and drug-induced latency reversal by suppressing HIV-1 transcriptional elongation. Surprisingly, a low-abundance subset of SECs containing ELL2 and AFF1 was found to play a predominant role in cooperating with Tat to reverse latency. By increasing the cellular level/activity of these Tat-friendly SECs, we could potently activate latent HIV-1 without using any drugs. These results implicate the ELL2/AFF1-SECs as an important target in the future design of a combinatorial therapeutic approach to purge latent HIV-1.

  8. A Minor Subset of Super Elongation Complexes Plays a Predominant Role in Reversing HIV-1 Latency

    PubMed Central

    Li, Zichong; Lu, Huasong

    2016-01-01

    Promoter-proximal pausing by RNA polymerase II (Pol II) is a key rate-limiting step in HIV-1 transcription and latency reversal. The viral Tat protein recruits human super elongation complexes (SECs) to paused Pol II to overcome this restriction. Despite the recent progress in understanding the functions of different subsets of SECs in controlling cellular and Tat-activated HIV transcription, little is known about the SEC subtypes that help reverse viral latency in CD4+ T cells. Here, we used the CRISPR-Cas9 genome-editing tool to knock out the gene encoding the SEC subunit ELL2, AFF1, or AFF4 in Jurkat/2D10 cells, a well-characterized HIV-1 latency model. Depletion of these proteins drastically reduced spontaneous and drug-induced latency reversal by suppressing HIV-1 transcriptional elongation. Surprisingly, a low-abundance subset of SECs containing ELL2 and AFF1 was found to play a predominant role in cooperating with Tat to reverse latency. By increasing the cellular level/activity of these Tat-friendly SECs, we could potently activate latent HIV-1 without using any drugs. These results implicate the ELL2/AFF1-SECs as an important target in the future design of a combinatorial therapeutic approach to purge latent HIV-1. PMID:26830226

  9. NEUTROPHILS PLAY A CRITICAL ROLE IN THE DEVELOPMENT OF LPS-INDUCED AIRWAY DISEASE

    EPA Science Inventory

    ETD-02-045 (GAVETT) GPRA # 10108

    Neutrophils Play a Critical Role in the Development of LPS-Induced Airway Disease.
    Jordan D. Savov, Stephen H. Gavett*, David M. Brass, Daniel L. Costa*, and David A. Schwartz

    ABSTRACT
    We investigated the role of neutrophils...

  10. Reflecting on Role Play in Geographic Education: The Case of the Banana War

    ERIC Educational Resources Information Center

    Kurtz, Hilda E.

    2004-01-01

    Debates over the nature and extent of globalization raise many issues to be addressed in a geographic education. In this paper, I briefly review case method instruction and role-play as teaching strategies suitable for material on globalization and other geographic subject matter, and then sketch an overview of an undergraduate geography role-play…

  11. Psychometric Characteristics of Role-Play Assessments of Social Skill in Schizophrenia

    ERIC Educational Resources Information Center

    Bellack, Alan S.; Brown, Clayton H.; Thomas-Lohrman, Shannon

    2006-01-01

    There is an extensive literature documenting that people with schizophrenia have marked impairments in social role functioning and social skill. One of the most widely employed strategies for assessing social skill has been role-play tests: simulated social interactions that are videotaped for subsequent behavioral coding. There has been…

  12. Using Social Networking for Online Role-Plays to Develop Students' Argumentative Strategies

    ERIC Educational Resources Information Center

    Beach, Richard; Doerr-Stevens, Candance

    2011-01-01

    Social networking sites may include argumentative writing about particular issues in which participants adopt competing perspective and discourses on those issues. This study examined roles and discourses adopted by high school students participating in an online role-play conducted on a Ning platform regarding their school's Internet policies on…

  13. Key Role of CRF in the Skin Stress Response System

    PubMed Central

    Zmijewski, Michal A.; Zbytek, Blazej; Tobin, Desmond J.; Theoharides, Theoharis C.; Rivier, Jean

    2013-01-01

    The discovery of corticotropin-releasing factor (CRF) or CRH defining the upper regulatory arm of the hypothalamic-pituitary-adrenal (HPA) axis, along with the identification of the corresponding receptors (CRFRs 1 and 2), represents a milestone in our understanding of central mechanisms regulating body and local homeostasis. We focused on the CRF-led signaling systems in the skin and offer a model for regulation of peripheral homeostasis based on the interaction of CRF and the structurally related urocortins with corresponding receptors and the resulting direct or indirect phenotypic effects that include regulation of epidermal barrier function, skin immune, pigmentary, adnexal, and dermal functions necessary to maintain local and systemic homeostasis. The regulatory modes of action include the classical CRF-led cutaneous equivalent of the central HPA axis, the expression and function of CRF and related peptides, and the stimulation of pro-opiomelanocortin peptides or cytokines. The key regulatory role is assigned to the CRFR-1α receptor, with other isoforms having modulatory effects. CRF can be released from sensory nerves and immune cells in response to emotional and environmental stressors. The expression sequence of peptides includes urocortin/CRF→pro-opiomelanocortin→ACTH, MSH, and β-endorphin. Expression of these peptides and of CRFR-1α is environmentally regulated, and their dysfunction can lead to skin and systemic diseases. Environmentally stressed skin can activate both the central and local HPA axis through either sensory nerves or humoral factors to turn on homeostatic responses counteracting cutaneous and systemic environmental damage. CRF and CRFR-1 may constitute novel targets through the use of specific agonists or antagonists, especially for therapy of skin diseases that worsen with stress, such as atopic dermatitis and psoriasis. PMID:23939821

  14. Key role of CRF in the skin stress response system.

    PubMed

    Slominski, Andrzej T; Zmijewski, Michal A; Zbytek, Blazej; Tobin, Desmond J; Theoharides, Theoharis C; Rivier, Jean

    2013-12-01

    The discovery of corticotropin-releasing factor (CRF) or CRH defining the upper regulatory arm of the hypothalamic-pituitary-adrenal (HPA) axis, along with the identification of the corresponding receptors (CRFRs 1 and 2), represents a milestone in our understanding of central mechanisms regulating body and local homeostasis. We focused on the CRF-led signaling systems in the skin and offer a model for regulation of peripheral homeostasis based on the interaction of CRF and the structurally related urocortins with corresponding receptors and the resulting direct or indirect phenotypic effects that include regulation of epidermal barrier function, skin immune, pigmentary, adnexal, and dermal functions necessary to maintain local and systemic homeostasis. The regulatory modes of action include the classical CRF-led cutaneous equivalent of the central HPA axis, the expression and function of CRF and related peptides, and the stimulation of pro-opiomelanocortin peptides or cytokines. The key regulatory role is assigned to the CRFR-1α receptor, with other isoforms having modulatory effects. CRF can be released from sensory nerves and immune cells in response to emotional and environmental stressors. The expression sequence of peptides includes urocortin/CRF→pro-opiomelanocortin→ACTH, MSH, and β-endorphin. Expression of these peptides and of CRFR-1α is environmentally regulated, and their dysfunction can lead to skin and systemic diseases. Environmentally stressed skin can activate both the central and local HPA axis through either sensory nerves or humoral factors to turn on homeostatic responses counteracting cutaneous and systemic environmental damage. CRF and CRFR-1 may constitute novel targets through the use of specific agonists or antagonists, especially for therapy of skin diseases that worsen with stress, such as atopic dermatitis and psoriasis.

  15. Autophagy plays an important role in protecting Pacific oysters from OsHV-1 and Vibrio aestuarianus infections.

    PubMed

    Moreau, Pierrick; Moreau, Kevin; Segarra, Amélie; Tourbiez, Delphine; Travers, Marie-Agnès; Rubinsztein, David C; Renault, Tristan

    2015-01-01

    Recent mass mortality outbreaks around the world in Pacific oysters, Crassostrea gigas, have seriously affected the aquaculture economy. Although the causes for these mortality outbreaks appear complex, infectious agents are involved. Two pathogens are associated with mass mortality outbreaks, the virus ostreid herpesvirus 1 (OsHV-1) and the bacterium Vibrio aestuarianus. Here we describe the interactions between these 2 pathogens and autophagy, a conserved intracellular pathway playing a key role in innate immunity. We show for the first time that autophagy pathway is present and functional in Pacific oysters and plays an important role to protect animals from infections. This study contributes to better understand the innate immune system of Pacific oysters.

  16. Intra-myocellular fatty acid metabolism plays a critical role in mediating responses to dietary restriction in Drosophila melanogaster

    PubMed Central

    Katewa, Subhash D.; Demontis, Fabio; Kolipinski, Marysia; Hubbard, Allan; Gill, Matthew S.; Perrimon, Norbert; Melov, Simon; Kapahi, Pankaj

    2012-01-01

    Summary Changes in fat content have been associated with dietary restriction (DR), but whether they play a causal role in mediating various responses to DR remains unknown. We demonstrate that upon DR, Drosophila melanogaster shift their metabolism towards increasing both fatty acid synthesis and breakdown, which is required for various responses to DR. Inhibition of fatty acid synthesis or oxidation genes specifically in the muscle tissue inhibited lifespan extension upon DR. Furthermore, DR enhances spontaneous activity of flies which was found to be dependent on the enhanced fatty acid metabolism. This increase in activity was found to be at least partially required for the lifespan extension upon DR. Over-expression of adipokinetic hormone (dAKH), the functional ortholog of glucagon, enhances fat metabolism, spontaneous activity and lifespan. Together, these results suggest that enhanced fat metabolism in the muscle and physical activity play a key role in the protective effects of DR. PMID:22768842

  17. Autophagy plays an important role in protecting Pacific oysters from OsHV-1 and Vibrio aestuarianus infections

    PubMed Central

    Moreau, Pierrick; Moreau, Kevin; Segarra, Amélie; Tourbiez, Delphine; Travers, Marie-Agnès; Rubinsztein, David C; Renault, Tristan

    2015-01-01

    Recent mass mortality outbreaks around the world in Pacific oysters, Crassostrea gigas, have seriously affected the aquaculture economy. Although the causes for these mortality outbreaks appear complex, infectious agents are involved. Two pathogens are associated with mass mortality outbreaks, the virus ostreid herpesvirus 1 (OsHV-1) and the bacterium Vibrio aestuarianus. Here we describe the interactions between these 2 pathogens and autophagy, a conserved intracellular pathway playing a key role in innate immunity. We show for the first time that autophagy pathway is present and functional in Pacific oysters and plays an important role to protect animals from infections. This study contributes to better understand the innate immune system of Pacific oysters. PMID:25714877

  18. Role-play as an educational tool in medication communication skills: Students’ perspectives

    PubMed Central

    Lavanya, S. H.; Kalpana, L.; Veena, R. M.; Bharath Kumar, V. D.

    2016-01-01

    Objectives: Medication communication skills are vital aspects of patient care that may influence treatment outcomes. However, traditional pharmacology curriculum deals with imparting factual information, with little emphasis on patient communication. The current study aims to explore students’ perceptions of role-play as an educational tool in acquiring communication skills and to ascertain the need of role-play for their future clinical practice. Materials and Methods: This questionnaire-based study was done in 2nd professional MBBS students. A consolidated concept of six training cases, focusing on major communication issues related to medication prescription in pharmacology, were developed for peer-role-play sessions for 2nd professional MBBS (n = 122) students. Structured scripts with specific emphasis on prescription medication communication and checklists for feedback were developed. Prevalidated questionnaires measured the quantitative aspects of role-plays in relation to their relevance as teaching–learning tool, perceived benefits of sessions, and their importance for future use. Statistical Analysis: Data analysis was performed using descriptive statistics. Results: The role-play concept was well appreciated and considered an effective means for acquiring medication communication skills. The structured feedback by peers and faculty was well received by many. Over 90% of the students reported immense confidence in communicating therapy details, namely, drug name, purpose, mechanism, dosing details, and precautions. Majority reported a better retention of pharmacology concepts and preferred more such sessions. Conclusions: Most students consider peer-role-play as an indispensable tool to acquire effective communication skills regarding drug therapy. By virtue of providing experiential learning opportunities and its feasibility of implementation, role-play sessions justify inclusion in undergraduate medical curricula. PMID:28031605

  19. Toy-playing behavior, sex-role orientation, spatial ability, and science achievement

    NASA Astrophysics Data System (ADS)

    Tracy, Dyanne M.

    The purpose of this correlational study was to examine the possible relationships among children's extracurricular toy-playing habits, sex-role orientations, spatial abilities, and science achievement. Data were gathered from 282 midwestern, suburban, fifth-grade students. It was found that boys had significantly higher spatial skills than girls. No significant differences in spatial ability were found among students with different sex-role orientations. No significant differences in science achievement were found between girls and boys, or among students with the four different sex-role orientations. Students who had high spatial ability also had significantly higher science achievement scores than students with low spatial ability. Femininely oriented boys who reported low playing in the two-dimensional, gross-body-movement, and proportional-arrangement toy categories scored significantly higher on the test of science achievement than girls with the same sex-role and toy-playing behavior.

  20. Characterizing the role benthos plays in large coastal seas and estuaries: A modular approach

    USGS Publications Warehouse

    Tenore, K.R.; Zajac, R.N.; Terwin, J.; Andrade, F.; Blanton, J.; Boynton, W.; Carey, D.; Diaz, R.; Holland, Austin F.; Lopez-Jamar, E.; Montagna, P.; Nichols, F.; Rosenberg, R.; Queiroga, H.; Sprung, M.; Whitlatch, R.B.

    2006-01-01

    Ecologists studying coastal and estuarine benthic communities have long taken a macroecological view, by relating benthic community patterns to environmental factors across several spatial scales. Although many general ecological patterns have been established, often a significant amount of the spatial and temporal variation in soft-sediment communities within and among systems remains unexplained. Here we propose a framework that may aid in unraveling the complex influence of environmental factors associated with the different components of coastal systems (i.e. the terrestrial and benthic landscapes, and the hydrological seascape) on benthic communities, and use this information to assess the role played by benthos in coastal ecosystems. A primary component of the approach is the recognition of system modules (e.g. marshes, dendritic systems, tidal rivers, enclosed basins, open bays, lagoons). The modules may differentially interact with key forcing functions (e.g. temperature, salinity, currents) that influence system processes and in turn benthic responses and functions. Modules may also constrain benthic characteristics and related processes within certain ecological boundaries and help explain their overall spatio-temporal variation. We present an example of how benthic community characteristics are related to the modular structure of 14 coastal seas and estuaries, and show that benthic functional group composition is significantly related to the modular structure of these systems. We also propose a framework for exploring the role of benthic communities in coastal systems using this modular approach and offer predictions of how benthic communities may vary depending on the modular composition and characteristics of a coastal system. ?? 2006 Elsevier B.V. All rights reserved.

  1. Analyzing Members' Motivations to Participate in Role-Playing and Self-Expression Based Virtual Communities

    NASA Astrophysics Data System (ADS)

    Lee, Young Eun; Saharia, Aditya

    With the rapid growth of computer mediated communication technologies in the last two decades, various types of virtual communities have emerged. Some communities provide a role playing arena, enabled by avatars, while others provide an arena for expressing and promoting detailed personal profiles to enhance their offline social networks. Due to different focus of these virtual communities, different factors motivate members to participate in these communities. In this study, we examine differences in members’ motivations to participate in role-playing versus self-expression based virtual communities. To achieve this goal, we apply the Wang and Fesenmaier (2004) framework, which explains members’ participation in terms of their functional, social, psychological, and hedonic needs. The primary contributions of this study are two folds: First, it demonstrates differences between role-playing and self-expression based communities. Second, it provides a comprehensive framework describing members’ motivation to participate in virtual communities.

  2. Roles of temperamental arousal and gender-segregated play in young children's social adjustment.

    PubMed

    Fabes, R A; Shepard, S A; Guthrie, I K; Martin, C L

    1997-07-01

    The hypothesis that gender differences in children's adjustment is partially influenced by differences in temperament and interactions with same-sex peers was examined. Fifty-seven predominantly White, middle-class preschoolers (29 boys and 28 girls, M age = 54.5 months) participated. Measures were taken of children's arousability, problem behaviors, and tendencies to play with same-sex peers. A semester later, children's peer status was assessed. Analyses revealed that arousability and same-sex peer play interacted to predict problem behaviors. For boys high in arousability, play with same-sex peers increased problem behaviors. In contrast, arousable girls who played with other girls were relatively unlikely to show problem behaviors. Moreover, the interaction of arousability and same-sex peer play predicted boys' (but not girls') peer status, and this relation was partially mediated by problem behaviors. The role of gender-related processes is discussed.

  3. Overstimulation of the inhibitory nervous system plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

    PubMed Central

    Tuk, Bert

    2016-01-01

    Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity. PMID:27547379

  4. Using virtual worlds for role play simulation in child and adolescent psychiatry: an evaluation study

    PubMed Central

    Vallance, Aaron K.; Hemani, Ashish; Fernandez, Victoria; Livingstone, Daniel; McCusker, Kerri; Toro-Troconis, Maria

    2014-01-01

    Aims and method To develop and evaluate a novel teaching session on clinical assessment using role play simulation. Teaching and research sessions occurred sequentially in computer laboratories. Ten medical students were divided into two online small-group teaching sessions. Students role-played as clinician avatars and the teacher played a suicidal adolescent avatar. Questionnaire and focus-group methodology evaluated participants’ attitudes to the learning experience. Quantitative data were analysed using SPSS, qualitative data through nominal-group and thematic analyses. Results Participants reported improvements in psychiatric skills/knowledge, expressing less anxiety and more enjoyment than role-playing face to face. Data demonstrated a positive relationship between simulator fidelity and perceived utility. Some participants expressed concern about added value over other learning methods and non-verbal communication. Clinical implications The study shows that virtual worlds can successfully host role play simulation, valued by students as a useful learning method. The potential for distance learning would allow delivery irrespective of geographical distance and boundaries. PMID:25285217

  5. Senior veterinary students' perceptions of using role play to learn communication skills.

    PubMed

    Brandt, Jennifer C; Bateman, Shane W

    2006-01-01

    Recent studies of veterinary practice have suggested a correlation between well-developed communication skills and job satisfaction, career retention, customer satisfaction, decreased lawsuits, and financial remuneration for veterinarians. Veterinary educators are under growing pressure to teach functional communication skills to veterinary students; however, the methods employed have not been well evaluated. In this study we have evaluated veterinary student's attitudes to learning communication skills by participating in role play. The study indicates that experiential learning modalities such as role play are perceived as effective by students, despite reluctance to participate and some discomfort surrounding participation.

  6. Key role of striatal cholinergic interneurons in processes leading to arrest of motor stereotypies.

    PubMed

    Aliane, Verena; Pérez, Sylvie; Bohren, Yohann; Deniau, Jean-Michel; Kemel, Marie-Louise

    2011-01-01

    Motor stereotypy is a key symptom of various disorders such as Tourette's syndrome and punding. Administration of nicotine or cholinesterase inhibitors is effective in treating some of these symptoms. However, the role of cholinergic transmission in motor stereotypy remains unknown. During strong cocaine-induced motor stereotypy, we showed earlier that increased dopamine release results in decreased acetylcholine release in the territory of the dorsal striatum related to the prefrontal cortex. Here, we investigated the role of striatal cholinergic transmission in the arrest of motor stereotypy. Analysis of N-methyl-d-aspartic acid-evoked release of dopamine and acetylcholine during declining intensity of motor stereotypy revealed a dissociation between dopamine and acetylcholine release. Whereas dopamine release remained increased, the inhibition of acetylcholine release decreased, mirroring the time course of motor stereotypy. Furthermore, pharmacological treatments restoring striatal acetylcholine release (raclopride, dopamine D2 antagonist; intraperitoneal or local injection in prefrontal territory of the dorsal striatum) rapidly stopped motor stereotypy. In contrast, pharmacological treatments that blocked the post-synaptic effects of acetylcholine (scopolamine, muscarinic antagonist; intraperitoneal or striatal local injection) or induced degeneration of cholinergic interneurons (AF64A, cholinergic toxin) in the prefrontal territory of the dorsal striatum robustly prolonged the duration of strong motor stereotypy. Thus, we propose that restoration of cholinergic transmission in the prefrontal territory of the dorsal striatum plays a key role in the arrest of motor stereotypy.

  7. Skills Development Using Role-Play in a First-Year Pharmacy Practice Course

    PubMed Central

    2011-01-01

    Objectives. To evaluate the usefulness of a role-play model in developing students’ patient-care skills in a first-year undergraduate pharmacy practice course. Design. A role-play model was developed and implemented in workshops across 2 semesters of a year-long course. Students performed different roles, including that of a pharmacist and a patient, and documented case notes in a single interaction. Assessment. Student perceptions of the usefulness of the approach in acquiring skills were measured by surveying students during both semesters. All student assessments (N=130 in semester1; N=129 in semester 2) also were analyzed for skills in verbal communication, information gathering, counselling and making recommendations, and accurately documenting information. A majority of students found the approach useful in developing skills. An analysis of student assessments revealed that role-playing was not as effective in building skills related to accurate documentation as it was in other areas of patient care. Conclusions. Role play is useful for developing patient-care skills in communication and information gathering but not for documentation of case notes. PMID:21829258

  8. Academic detailing can play a key role in assessing and implementing comparative effectiveness research findings.

    PubMed

    Fischer, Michael A; Avorn, Jerry

    2012-10-01

    Comparative effectiveness research evaluates the relative effectiveness, safety, and value of competing treatment options in clinically realistic settings. Such evaluations can be methodologically complex and difficult to interpret. There will be a growing need for critical evaluation of comparative effectiveness studies to assess the adequacy of their design and to put new information into a broader context. Equally important, this knowledge will have to be communicated to clinicians in a way that will actually change practice. We identify three challenges to effective dissemination of comparative effectiveness research findings: the difficulty of interpreting comparative effectiveness research data, the need for trusted sources of information, and the challenge of turning research results into clinical action. We suggest that academic detailing-direct outreach education that gives clinicians an accurate and unbiased synthesis of the best evidence for practice in a given clinical area-can translate comparative effectiveness research findings into actions that improve health care decision making and patient outcomes.

  9. Tetraspanin CD151 plays a key role in skin squamous cell carcinoma

    PubMed Central

    Li, Qinglin; Yang, Xiuwei H.; Xu, Fenghui; Sharma, Chandan; Wang, Hong-Xing; Knoblich, Konstantin; Rabinovitz, Isaac; Granter, Scott R.; Hemler, Martin E.

    2012-01-01

    Here we provide the first evidence that tetraspanin CD151 can support de novo carcinogenesis. During two-stage mouse skin chemical carcinogenesis, CD151 reduces tumor lag time and increases incidence, multiplicity, size, and progression to malignant squamous cell carcinoma (SCC), while supporting both cell survival during tumor initiation and cell proliferation during the promotion phase. In human skin SCC, CD151 expression is selectively elevated compared to other skin cancer types. CD151 support of keratinocyte survival and proliferation may depend on activation of transcription factor STAT3, a regulator of cell proliferation and apoptosis. CD151 also supports PKCα-α6β4 integrin association and PKC-dependent β4 S1424 phosphorylation, while regulating α6β4 distribution. CD151-PKCα effects on integrin β4 phosphorylation and subcellular localization are consistent with epithelial disruption to a less polarized, more invasive state. CD151 ablation, while minimally affecting normal cell and normal mouse functions, markedly sensitized mouse skin and epidermoid cells to chemicals/drugs including DMBA (mutagen) and camptothecin (topoisomerase inhibitor), as well as to agents targeting EGFR, PKC, Jak2/Tyk2, and STAT3. Hence, CD151 ‘co-targeting’ may be therapeutically beneficial. These findings not only support CD151 as a potential tumor target, but also should apply to other cancers utilizing CD151-laminin-binding integrin complexes. PMID:22824799

  10. Symmetry plays a key role in the erasing of patterned surface features

    SciTech Connect

    Benzaquen, Michael; Salez, Thomas; Raphaël, Elie; Ilton, Mark; Massa, Michael V.; Fowler, Paul; Dalnoki-Veress, Kari

    2015-08-03

    We report on how the relaxation of patterns prepared on a thin film can be controlled by manipulating the symmetry of the initial shape. The validity of a lubrication theory for the capillary-driven relaxation of surface profiles is verified by atomic force microscopy measurements, performed on films that were patterned using focused laser spike annealing. In particular, we observe that the shape of the surface profile at late times is entirely determined by the initial symmetry of the perturbation, in agreement with the theory. The results have relevance in the dynamical control of topographic perturbations for nanolithography and high density memory storage.

  11. ISFET pH Sensitivity: Counter-Ions Play a Key Role

    NASA Astrophysics Data System (ADS)

    Parizi, Kokab B.; Xu, Xiaoqing; Pal, Ashish; Hu, Xiaolin; Wong, H. S. Philip

    2017-02-01

    The Field Effect sensors are broadly used for detecting various target analytes in chemical and biological solutions. We report the conditions under which the pH sensitivity of an Ion Sensitive Field Effect transistor (ISFET) sensor can be significantly enhanced. Our theory and simulations show that by using pH buffer solutions containing counter-ions that are beyond a specific size, the sensor shows significantly higher sensitivity which can exceed the Nernst limit. We validate the theory by measuring the pH response of an extended gate ISFET pH sensor. The consistency and reproducibility of the measurement results have been recorded in hysteresis free and stable operations. Different conditions have been tested to confirm the accuracy and validity of our experiment results such as using different solutions, various oxide dielectrics as the sensing layer and off-the-shelf versus IC fabricated transistors as the basis of the ISFET sensor.

  12. Conformational change of Dishevelled plays a key regulatory role in the Wnt signaling pathways

    PubMed Central

    Lee, Ho-Jin; Shi, De-Li; Zheng, Jie J

    2015-01-01

    The intracellular signaling molecule Dishevelled (Dvl) mediates canonical and non-canonical Wnt signaling via its PDZ domain. Different pathways diverge at this point by a mechanism that remains unclear. Here we show that the peptide-binding pocket of the Dvl PDZ domain can be occupied by Dvl's own highly conserved C-terminus, inducing a closed conformation. In Xenopus, Wnt-regulated convergent extension (CE) is readily affected by Dvl mutants unable to form the closed conformation than by wild-type Dvl. We also demonstrate that while Dvl cooperates with other Wnt pathway elements to activate canonical Wnt signaling, the open conformation of Dvl more effectively activates Jun N-terminal kinase (JNK). These results suggest that together with other players in the Wnt signaling pathway, the conformational change of Dvl regulates Wnt stimulated JNK activity in the non-canonical Wnt signaling. DOI: http://dx.doi.org/10.7554/eLife.08142.001 PMID:26297804

  13. Controllers and Pilots Play a Key Role in Runway Safety Initiatives Through Real-Time Simulation

    NASA Technical Reports Server (NTRS)

    Madson, Mike; Bender, Kim

    2004-01-01

    A new and innovative way to evaluate runway safety initiatives for airports is through the use of interactive real-time simulation. The National Aeronautics and Space Administration (NASA) operates an integrated suite of simulators that can give both pilots and tower controllers the ability to simultaneously "try out" ideas in the safety of virtual reality. In February of 2003, the FAA conducted a demonstration in the NASA facilities for Dallas/Fort Worth International Airport (DFW) of a concept to reduce runway crossings and enhance the efficiency of the airport. Currently DFW experiences about 1,700 runway crossings per day, which contribute to arrival and departure delays and the potential for runway incursions. The proposed concept included the addition of new perimeter taxiways on the East and West sides of the airport. Through use of NASA's unique simulation capabilities, DFW controllers and commercial pilots provided expert feedback on the safety and operational implications by directly experiencing the proposed changes. Overall, the data collected from the participants and the simulators demonstrated that the concept would improve operations at DFW, if implemented. Improvements were observed in many areas including departure rates, taxi duration, runway crossings, and controller and pilot communications.

  14. Where mother knows best. In Cambodia's highlands, women play a key role.

    PubMed

    1993-09-22

    Phnom Penh businessmen wanted to convert a hillside near Ban Lung, the provincial capital of Ratanakiri in northeast Cambodia, into a resort for senior government officials and businessmen. The resort was to lead treks into the hills so the men could stare at the topless women of the Khmer Loeu tribes. The tribes' views on marriage, sex, birth control, abortion, and courtship are quite progressive. Until just recently, unmarried daughters lived in small houses connected to the family house so they could have sexual relationships with prospective mates. The custom stopped because many of the women conceived before marriage and many of the fathers were married men. Nevertheless, young women still have as much sexual freedom as do young men. Neither punishment nor disgrace befall unmarried pregnant women. If a married man impregnates a woman, he pays her family with 4 buffalo, some pigs, a few chickens, and rice wine. If the man is single and does not want to marry the pregnant woman, he reimburses her and attends to her throughout the pregnancy. Childbirth ends his obligation. Women may divorce an abusive husband. Any man that abuses a woman, married or not, is severely punished. Only women can make decisions about childbirth. They often induce abortion after having 4-5 children, generally using herbs. Women are spiritual healers. Priestesses are the only medium through which ancestral spirits impart blessings and messages to tribe members. these powers affect male and female relations greatly. Women rise at 4 am to do chores. They usually make breakfast and clean the house before boys awake. Women and the tribe value men, largely because few survived the Khmer Rouge massacres. Khmer Loeu women are beginning to want to be like other women, such as wearing shirts. These modern attitudes are more likely to change the tribe's culture than did the widespread killing by the Khmer Rouge in the 1970s.

  15. Maintenance Rehearsal: The Key to the Role Attention Plays in Storage and Forgetting

    ERIC Educational Resources Information Center

    McFarlane, Kimberley A.; Humphreys, Michael S.

    2012-01-01

    Research with the maintenance-rehearsal paradigm, in which word pairs are rehearsed as distractor material during a series of digit recall trials, has previously indicated that low frequency and new word pairs capture attention to a greater degree than high frequency and old word pairs. This impacts delayed recognition of the pairs and interferes…

  16. Beyond the brochure. Administrators play key role in positioning the practice, aligning marketing with mission.

    PubMed

    Redling, Bob

    2007-04-01

    Marketing doesn't start and stop with a glossy brochure, a display ad in the local Yellow Pages or a Web site. Those are merely tactics that a medical group practice might use to position its physicians' services in the community. Marketing and planning support a medical group's mission and vision--and its strategic plan. The adminstrator must demonstrate this connection to physicians and educate them about what marketing really is.

  17. Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains

    PubMed Central

    Ulianov, Sergey V.; Khrameeva, Ekaterina E.; Gavrilov, Alexey A.; Flyamer, Ilya M.; Kos, Pavel; Mikhaleva, Elena A.; Penin, Aleksey A.; Logacheva, Maria D.; Imakaev, Maxim V.; Chertovich, Alexander; Gelfand, Mikhail S.; Shevelyov, Yuri Y.; Razin, Sergey V.

    2016-01-01

    Recent advances enabled by the Hi-C technique have unraveled many principles of chromosomal folding that were subsequently linked to disease and gene regulation. In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. Mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principles of TAD folding in Drosophila melanogaster, we performed Hi-C and poly(A)+ RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e., the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predicts TAD boundaries much worse than active chromatin marks do. Interestingly, inter-TADs correspond to decompacted inter-bands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin. We propose the mechanism of TAD self-assembly based on the ability of nucleosomes from inactive chromatin to aggregate, and lack of this ability in acetylated nucleosomal arrays. Finally, we test this hypothesis by polymer simulations and find that TAD partitioning may be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin. PMID:26518482

  18. Catalase plays a key role in salt stress acclimation induced by hydrogen peroxide pretreatment in maize.

    PubMed

    Gondim, Franklin Aragão; Gomes-Filho, Enéas; Costa, José Hélio; Mendes Alencar, Nara Lídia; Prisco, José Tarquinio

    2012-07-01

    Pretreatment in plants is recognized as a valuable strategy to stimulate plant defenses, leading to better plant development. This study evaluated the effects of H₂O₂ leaf spraying pretreatment on plant growth and investigated the antioxidative mechanisms involved in the response of maize plants to salt stress. It was found that salinity reduced maize seedling growth when compared to control conditions, and H₂O₂ foliar spraying was effective in minimizing this effect. Analysis of the antioxidative enzymes catalase (EC 1.11.1.6), guaiacol peroxidase (EC 1.11.1.7), ascorbate peroxidase (EC 1.11.1.1) and superoxide dismutase (EC 1.15.1.1) revealed that H₂O₂ spraying increased antioxidant enzyme activities. Catalase (CAT) was the most responsive of these enzymes to H₂O₂, with higher activity early (48 h) in the treatment, while guaiacol peroxidase (GPX) and ascorbate peroxidase (APX) were responsive only at later stages (240 h) of treatment. Increased CAT activity appears linked to gene expression regulation. Lower malondialdehyde levels were detected in plants with higher CAT activity, which may result from the protective function of this enzyme. Overall, we can conclude that pretreatment with H₂O₂ leaf spraying was able to reduce the deleterious effects of salinity on seedling growth and lipid peroxidation. These responses could be attributed to the ability of H₂O₂ to induce antioxidant defenses, especially CAT activity.

  19. Radial glial cells play a key role in echinoderm neural regeneration

    PubMed Central

    2013-01-01

    Background Unlike the mammalian central nervous system (CNS), the CNS of echinoderms is capable of fast and efficient regeneration following injury and constitutes one of the most promising model systems that can provide important insights into evolution of the cellular and molecular events involved in neural repair in deuterostomes. So far, the cellular mechanisms of neural regeneration in echinoderm remained obscure. In this study we show that radial glial cells are the main source of new cells in the regenerating radial nerve cord in these animals. Results We demonstrate that radial glial cells of the sea cucumber Holothuria glaberrima react to injury by dedifferentiation. Both glia and neurons undergo programmed cell death in the lesioned CNS, but it is the dedifferentiated glial subpopulation in the vicinity of the injury that accounts for the vast majority of cell divisions. Glial outgrowth leads to formation of a tubular scaffold at the growing tip, which is later populated by neural elements. Most importantly, radial glial cells themselves give rise to new neurons. At least some of the newly produced neurons survive for more than 4 months and express neuronal markers typical of the mature echinoderm CNS. Conclusions A hypothesis is formulated that CNS regeneration via activation of radial glial cells may represent a common capacity of the Deuterostomia, which is not invoked spontaneously in higher vertebrates, whose adult CNS does not retain radial glial cells. Potential implications for biomedical research aimed at finding the cure for human CNS injuries are discussed. PMID:23597108

  20. Technology Plays a Key Role in Preparing Students for the World beyond Graduation. Best Practices Newsletter

    ERIC Educational Resources Information Center

    Southern Regional Education Board (SREB), 2013

    2013-01-01

    Many teachers use the Internet and other electronic and web-based resources to engage students in meaningful assignments for independent learning, greater ownership of learning and better preparation for college and careers. The technology practices should align with the new college- and career-readiness standards (CCRS). They also should enhance…

  1. ERK Signaling Pathway Plays a Key Role in Baicalin Protection Against Acetaminophen-Induced Liver Injury.

    PubMed

    Liao, Chia-Chih; Day, Yuan-Ji; Lee, Hung-Chen; Liou, Jiin-Tarng; Chou, An-Hsun; Liu, Fu-Chao

    2017-01-01

    Acetaminophen (APAP) overdose causes hepatocytes necrosis and acute liver failure. Baicalin (BA), a major flavonoid of Scutellariae radix, has potent hepatoprotective properties in traditional medicine. In the present study, we investigated the protective effects of BA on a APAP-induced liver injury in a mouse model. The mice received an intraperitoneal hepatotoxic dose of APAP (300[Formula: see text]mg/kg) and after 30[Formula: see text]min, were treated with BA at concentrations of 0, 15, 30, or 60[Formula: see text]mg/kg. After 16[Formula: see text]h of treatment, the mice were sacrificed for further analysis. APAP administration significantly elevated the serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity when compared with control animals. Baicalin treatment significantly attenuated the elevation of liver ALT levels, as well as hepatic MPO activity in a dose- dependent manner (15-60[Formula: see text]mg/kg) in APAP-treated mice. The strongest beneficial effects of BA were seen at a dose of 30[Formula: see text]mg/kg. BA treatment at 30[Formula: see text]mg/kg after APAP overdose reduced elevated hepatic cytokine (TNF-[Formula: see text] and IL-6) levels, and macrophage recruitment around the area of hepatotoxicity in immunohistochemical staining. Significantly, BA treatment can also decrease hepatic phosphorylated extracellular signal-regulated kinase (ERK) expression, which is induced by APAP overdose. Our data suggests that baicalin treatment can effectively attenuate APAP-induced liver injury by down-regulating the ERK signaling pathway and its downstream effectors of inflammatory responses. These results support that baicalin is a potential hepatoprotective agent.

  2. ISFET pH Sensitivity: Counter-Ions Play a Key Role

    PubMed Central

    Parizi, Kokab B.; Xu, Xiaoqing; Pal, Ashish; Hu, Xiaolin; Wong, H. S. Philip

    2017-01-01

    The Field Effect sensors are broadly used for detecting various target analytes in chemical and biological solutions. We report the conditions under which the pH sensitivity of an Ion Sensitive Field Effect transistor (ISFET) sensor can be significantly enhanced. Our theory and simulations show that by using pH buffer solutions containing counter-ions that are beyond a specific size, the sensor shows significantly higher sensitivity which can exceed the Nernst limit. We validate the theory by measuring the pH response of an extended gate ISFET pH sensor. The consistency and reproducibility of the measurement results have been recorded in hysteresis free and stable operations. Different conditions have been tested to confirm the accuracy and validity of our experiment results such as using different solutions, various oxide dielectrics as the sensing layer and off-the-shelf versus IC fabricated transistors as the basis of the ISFET sensor. PMID:28150700

  3. Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains.

    PubMed

    Ulianov, Sergey V; Khrameeva, Ekaterina E; Gavrilov, Alexey A; Flyamer, Ilya M; Kos, Pavel; Mikhaleva, Elena A; Penin, Aleksey A; Logacheva, Maria D; Imakaev, Maxim V; Chertovich, Alexander; Gelfand, Mikhail S; Shevelyov, Yuri Y; Razin, Sergey V

    2016-01-01

    Recent advances enabled by the Hi-C technique have unraveled many principles of chromosomal folding that were subsequently linked to disease and gene regulation. In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. Mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principles of TAD folding in Drosophila melanogaster, we performed Hi-C and poly(A)(+) RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e., the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predicts TAD boundaries much worse than active chromatin marks do. Interestingly, inter-TADs correspond to decompacted inter-bands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin. We propose the mechanism of TAD self-assembly based on the ability of nucleosomes from inactive chromatin to aggregate, and lack of this ability in acetylated nucleosomal arrays. Finally, we test this hypothesis by polymer simulations and find that TAD partitioning may be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin.

  4. Hexokinase 2, Glycogen Synthase and Phosphorylase Play a Key Role in Muscle Glycogen Supercompensation

    PubMed Central

    Irimia, José M.; Rovira, Jordi; Nielsen, Jakob N.; Guerrero, Mario; Wojtaszewski, Jørgen F. P.; Cussó, Roser

    2012-01-01

    Background Glycogen-depleting exercise can lead to supercompensation of muscle glycogen stores, but the biochemical mechanisms of this phenomenon are still not completely understood. Methods Using chronic low-frequency stimulation (CLFS) as an exercise model, the tibialis anterior muscle of rabbits was stimulated for either 1 or 24 hours, inducing a reduction in glycogen of 90% and 50% respectively. Glycogen recovery was subsequently monitored during 24 hours of rest. Results In muscles stimulated for 1 hour, glycogen recovered basal levels during the rest period. However, in those stimulated for 24 hours, glycogen was supercompensated and its levels remained 50% higher than basal levels after 6 hours of rest, although the newly synthesized glycogen had fewer branches. This increase in glycogen correlated with an increase in hexokinase-2 expression and activity, a reduction in the glycogen phosphorylase activity ratio and an increase in the glycogen synthase activity ratio, due to dephosphorylation of site 3a, even in the presence of elevated glycogen stores. During supercompensation there was also an increase in 5′-AMP-activated protein kinase phosphorylation, correlating with a stable reduction in ATP and total purine nucleotide levels. Conclusions Glycogen supercompensation requires a coordinated chain of events at two levels in the context of decreased cell energy balance: First, an increase in the glucose phosphorylation capacity of the muscle and secondly, control of the enzymes directly involved in the synthesis and degradation of the glycogen molecule. However, supercompensated glycogen has fewer branches. PMID:22860128

  5. Histone H1 plays a role in heterochromatin formation and VSG expression site silencing in Trypanosoma brucei.

    PubMed

    Povelones, Megan L; Gluenz, Eva; Dembek, Marcin; Gull, Keith; Rudenko, Gloria

    2012-01-01

    The African sleeping sickness parasite Trypanosoma brucei evades the host immune system through antigenic variation of its variant surface glycoprotein (VSG) coat. Although the T. brucei genome contains ∼1500 VSGs, only one VSG is expressed at a time from one of about 15 subtelomeric VSG expression sites (ESs). For antigenic variation to work, not only must the vast VSG repertoire be kept silent in a genome that is mainly constitutively transcribed, but the frequency of VSG switching must be strictly controlled. Recently it has become clear that chromatin plays a key role in silencing inactive ESs, thereby ensuring monoallelic expression of VSG. We investigated the role of the linker histone H1 in chromatin organization and ES regulation in T. brucei. T. brucei histone H1 proteins have a different domain structure to H1 proteins in higher eukaryotes. However, we show that they play a key role in the maintenance of higher order chromatin structure in bloodstream form T. brucei as visualised by electron microscopy. In addition, depletion of histone H1 results in chromatin becoming generally more accessible to endonucleases in bloodstream but not in insect form T. brucei. The effect on chromatin following H1 knock-down in bloodstream form T. brucei is particularly evident at transcriptionally silent ES promoters, leading to 6-8 fold derepression of these promoters. T. brucei histone H1 therefore appears to be important for the maintenance of repressed chromatin in bloodstream form T. brucei. In particular H1 plays a role in downregulating silent ESs, arguing that H1-mediated chromatin functions in antigenic variation in T. brucei.

  6. γδ T Cells Play a Protective Role in Chikungunya Virus-Induced Disease

    PubMed Central

    Ferris, Martin T.; Whitmore, Alan C.; Montgomery, Stephanie A.; Thurlow, Lance R.; McGee, Charles E.; Rodriguez, Carlos A.; Lim, Jean K.; Heise, Mark T.

    2015-01-01

    ABSTRACT Chikungunya virus (CHIKV) is an alphavirus responsible for causing epidemic outbreaks of polyarthralgia in humans. Because CHIKV is initially introduced via the skin, where γδ T cells are prevalent, we evaluated the response of these cells to CHIKV infection. CHIKV infection led to a significant increase in γδ T cells in the infected foot and draining lymph node that was associated with the production of proinflammatory cytokines and chemokines in C57BL/6J mice. γδ T cell−/− mice demonstrated exacerbated CHIKV disease characterized by less weight gain and greater foot swelling than occurred in wild-type mice, as well as a transient increase in monocytes and altered cytokine/chemokine expression in the foot. Histologically, γδ T cell−/− mice had increased inflammation-mediated oxidative damage in the ipsilateral foot and ankle joint compared to wild-type mice which was independent of differences in CHIKV replication. These results suggest that γδ T cells play a protective role in limiting the CHIKV-induced inflammatory response and subsequent tissue and joint damage. IMPORTANCE Recent epidemics, including the 2004 to 2007 outbreak and the spread of CHIKV to naive populations in the Caribbean and Central and South America with resultant cases imported into the United States, have highlighted the capacity of CHIKV to cause explosive epidemics where the virus can spread to millions of people and rapidly move into new areas. These studies identified γδ T cells as important to both recruitment of key inflammatory cell populations and dampening the tissue injury due to oxidative stress. Given the importance of these cells in the early response to CHIKV, this information may inform the development of CHIKV vaccines and therapeutics. PMID:26491151

  7. Psychotherapy with a 3-Year-Old Child: The Role of Play in the Unfolding Process

    PubMed Central

    Salcuni, Silvia; Di Riso, Daniela; Mabilia, Diana; Lis, Adriana

    2017-01-01

    Few studies have investigated the outcomes and process of psychodynamic psychotherapies with children. Among the limited number of studies, some only paid attention to play and verbal production, as they are fundamental aspects in assessing the psychotherapy process. This paper focuses on an empirical investigation of a 3-year, once-a-week psychodynamic psychotherapy carried out with a 3-year-old girl. A process-outcome design was implemented to evaluate play and verbal discourse in in the initial, middle, and final parts of 30 psychotherapy sessions. Repeated measurements of standardized play categories (the Play Category System and the Affect in Play Scale—Preschool version) and verbal discourse (Verbal Production) were analyzed. To increase the clinical validity of the study, data from the assessment phase and vignettes from the sessions were reported to deepen the patient’s picture during the unfolding therapy process. Parent reports before and after the therapy were also included. Empirically measured changes in play and verbal production were fundamental in evaluating the young patient’s psychotherapy process. Verbal production and discourse ability progressively increased and took the place of play, which instead became more symbolic. Developmental issues as well as psychotherapy’s influence on the patient’s change, were discussed in relation to the role of play in enhancing the development of verbal dialog and the expression of the child’s emotions, needs, and desires. PMID:28101070

  8. Experiencing the Elicitation of User Requirements and Recording Them in Use Case Diagrams through Role-Play

    ERIC Educational Resources Information Center

    Costain, Gay; McKenna, Brad

    2011-01-01

    This paper describes a role-play exercise used in a second-year tertiary Systems Analysis and Design course, and the quantitative and qualitative analysis of the students' responses to a survey that solicited their perceptions of that role-play experience. The role-play involved students in eliciting user requirements from customers during a Joint…

  9. To What Extent Might Role Play Be a Useful Tool for Learning Mathematics?

    ERIC Educational Resources Information Center

    Williams, Helen

    2012-01-01

    To most children in primary school role-play is just something you do, and something you enjoy. It is part-and-parcel of being at school, part of the normal classroom activity. So, why can it not just be a normal part of learning mathematics? Can we study learners "in role", and make judgments about what they learn, and how they learn? This is the…

  10. From board to bedside – training the communication competences of medical students with role plays

    PubMed Central

    2014-01-01

    Background Role plays and standardized patients are often used in medical education and have proven to be effective tools for enhancing the communication skills of medical students. Most course concepts need additional time and teaching staff, and there are only a few studies about role plays in the preclinical segment. Methods We developed a highly consolidated concept for the curricular course of 2nd-year medical students, including ten role plays about five subjects: anamnesis, shared decision making, prevention, breaking bad news, and so-called “difficult interactions”. Before the course, all students were asked about their expectations and attitudes toward the course. After the course, all students rated the course, their individual learning progress, whether their expectations had been fulfilled, and re-evaluated their attitudes. Questionnaires were self-report measures and had a quantitative and a short qualitative section and were analyzed with descriptive statistics. Group differences (sex, age, role played) were evaluated with t tests at a Bonferonni-corrected significance level of p = .03 and the non-parametric U-tests. Results Implementing this practical course concept is possible without incurring additional costs. This paper not only shows how that can be done but also provides 5 examples of role scripts for different training subjects. The course concept was highly appreciated by the students. More than 75% felt that they had learned important communication techniques and would be better able to handle difficult situations. Playing the doctor’s role was felt to be more useful than playing the patient’s role. Women admitted a higher degree of shyness in the beginning and gave higher ratings to their learning progress than men. Students’ most frequent wish in the qualitative analysis was to be able to play the doctor’s role at least once. The students’ answers showed a differentiated pattern, thus suggesting that the influence of

  11. The Evolution of Musical Diversity: The Key Role of Vertical Transmission

    PubMed Central

    Le Bomin, Sylvie; Lecointre, Guillaume; Heyer, Evelyne

    2016-01-01

    Music, like languages, is one of the key components of our culture, yet musical evolution is still poorly known. Numerous studies using computational methods derived from evolutionary biology have been successfully applied to varied subset of linguistic data. One of the major drawback regarding musical studies is the lack of suitable coded musical data that can be analysed using such evolutionary tools. Here we present for the first time an original set of musical data coded in a way that enables construction of trees classically used in evolutionary approaches. Using phylogenetic methods, we test two competing theories on musical evolution: vertical versus horizontal transmission. We show that, contrary to what is currently believed, vertical transmission plays a key role in shaping musical diversity. The signal of vertical transmission is particularly strong for intrinsic musical characters such as metrics, rhythm, and melody. Our findings reveal some of the evolutionary mechanisms at play for explaining musical diversity and open a new field of investigation in musical evolution. PMID:27027305

  12. Principals' Perceptions and Experiences of the Role Parents Play in School Governing Bodies in Rural Areas

    ERIC Educational Resources Information Center

    Hartell, Cycil; Dippenaar, Hanlie; Moen, Melanie; Dladla, Themba

    2016-01-01

    This study investigated the perceptions and experiences of rural school principals in South Africa of the role that parents in the school governing bodies (SGBs) play in improving school management and governance. The study reports on a literature review as well as on the empirical investigation, which was based on a qualitative research paradigm.…

  13. Describing Roles that Gay-Straight Alliances Play in Schools: From Individual Support to School Change

    ERIC Educational Resources Information Center

    Griffin, Pat; Lee, Camille; Waugh, Jeffrey; Beyer, Chad

    2004-01-01

    Based on a broader qualitative study of organizational level changes in schools participating in Massachusetts' Safe Schools Program, the authors describe four roles that GSAs played in the twenty-two schools: counseling and support; "safe" space; primary vehicle for raising awareness, increasing visibility, and educating about LGBT…

  14. Trading Spaces: An Educator's Ethnographic Exploration of Adolescents' Digital Role-Play

    ERIC Educational Resources Information Center

    Haynes-Moore, Stacy

    2015-01-01

    In this work, the author examines a digital role-play in which participants composed an alternate version of "The Hunger Games" (Collins, 2008). Participants imagined characters and posted more than 400 scenes in the online collaboration. The author draws upon ethnographic methods (Merriam, 2009) to describe her participant-observer…

  15. Understanding Bullying: Using Role-Play with 12-Year-Old Boys in Cyprus

    ERIC Educational Resources Information Center

    Kaloyirou, Chrystalla; Lindsay, Geoff

    2014-01-01

    This study examines the use of role-play in order to investigate bullies' intentions, feelings and perceptions through identification and projection. The study was conducted with nine 12-year-old boys that presented high levels of bullying behaviour, according to their teachers and peers, from three state primary schools in Nicosia, Cyprus, with…

  16. The Roles That Librarians and Libraries Play in Distance Education Settings

    ERIC Educational Resources Information Center

    Corbett, Amanda; Brown, Abbie

    2015-01-01

    This article explores the literature that focuses on the various roles librarians and libraries play in distance education settings. Learners visit libraries either in person or via networked computing technology to ask for help with their online courses. Questions range from how to upload a document with a learning management system, to how to…

  17. Role-Play Game-Enhanced English for a Specific-Purpose Vocabulary-Acquisition Framework

    ERIC Educational Resources Information Center

    Lu, Fang-Chen; Chang, Ben

    2016-01-01

    With the advantages of an engaged and authentic role-play game (RPG), this study aims to develop an RPG-enhanced English for specific purposes (ESP) vocabulary-acquisition framework, providing teachers and students a systematic way to incorporate RPG into ESP learning. The framework is composed of five parts: goal, three-level vocabulary sets, RPG…

  18. Group Dynamics in a Discussion Group for Older Adults: Does Gender Play a Role?

    ERIC Educational Resources Information Center

    de Medeiros, Kate; Harris-Trovato, Dana; Bradley, Evelyn; Gaines, Jean; Parrish, John

    2007-01-01

    Lifelong learning programs continue to grow in span and scope. Few studies, however, have investigated how older adults themselves participate in group learning. The central question explored in our study was as follows: Does gender play a role in group dynamics for older adults? Two groups of volunteers (age 62 to 96 years) enrolled in a 16-week…

  19. Teachers' Roles in Infants' Play and Its Changing Nature in a Dynamic Group Care Context

    ERIC Educational Resources Information Center

    Jung, Jeesun

    2013-01-01

    Using a qualitative research approach, this article explores teachers' roles in infants' play and its changing nature in an infant group care setting. Three infant teachers in a child care center were followed over three months. Observations, interviews, ongoing conversations, emails, and reflective notes were used as data sources. Findings…

  20. Using Role-Play to Enhance Foodborne Illness Crisis Management Capacity in the Produce Industry

    ERIC Educational Resources Information Center

    Kreske, Audrey; Ducharme, Diane; Gunter, Chris; Phister, Trevor

    2013-01-01

    Foodborne illness outbreaks have measurable public health effects and often lead to negative produce industry impacts. Reducing loss following a crisis event requires a management plan, although many fresh produce industry members don't have one. Evidence-based workshops using a role-play simulated outbreak were delivered to impact crisis…

  1. Sustainability and Science Learning: Perceptions from 8th Grade Students Involved with a Role Playing Activity

    ERIC Educational Resources Information Center

    Freire, Sofia; Baptista, Mónica; Freire, Ana

    2016-01-01

    Raising awareness about sustainability is an urgent need and as such education for sustainability has gained relevancy for the last decades. It is acknowledged that science education can work as an important context for educating for sustainability. The goal of the present paper is to describe a role-playing activity about the construction of a…

  2. A Role-Play to Illustrate the Energy Changes Occurring in an Exothermic Reaction.

    ERIC Educational Resources Information Center

    Tyas, Toby; Cabot, John

    1999-01-01

    Describes a role-play activity designed to help students understand the energy changes involved in an exothermic reaction by modeling the concepts of bond-breaking takes in energy, activation energy, temperature rise, and bond breaking gives out energy. (WRM)

  3. Using a Role-Play Video to Convey Expectations about Academic Integrity

    ERIC Educational Resources Information Center

    Bullard, Lisa G.; Melvin, Adam T.

    2011-01-01

    We have developed an instructional video that uses role-play to illustrate the differences between acceptable behavior and cheating on assignments. Since we began showing it in an introductory chemical engineering course, the average number of confirmed instances of cheating decreased slightly, but the average percentage of students who were…

  4. Parenting Talent: A Qualitative Investigation of the Roles Parents Play in Talent Development

    ERIC Educational Resources Information Center

    Witte, Amanda L.; Kiewra, Kenneth A.; Kasson, Sarah C.; Perry, Kyle R.

    2015-01-01

    Previous research has linked talent development to four factors--early experience, coaching, practice, and motivation. In addition to these factors, contemporary talent experts suggest that parents play a critical role in talent development. The purpose of the present study was to uncover parents' in-time perspectives on the talent development…

  5. The Evolution and Evaluation of an Online Role Play through Design-Based Research

    ERIC Educational Resources Information Center

    Beckmann, Elizabeth A.; Mahanty, Sango

    2016-01-01

    This paper presents selected findings from a 5-year design-based research case study of the evolution of an online role play that allows postgraduate students to explore the complexities inherent in land rights negotiations between indigenous peoples and others. In the context of Laurillard's (2002) conversational framework and a design-based…

  6. Student Voices about the Role Feedback Plays in the Enhancement of Their Learning

    ERIC Educational Resources Information Center

    Plank, Christine; Dixon, Helen; Ward, Gillian

    2014-01-01

    If feedback is to be framed as purposeful dialogue then both students and teachers have significant roles to play. Students must be willing and able to provide feedback to teachers not only about their learning needs but also about the teaching they experience. In turn, teachers must create the conditions that support active student learning and…

  7. What Do Students Learn from a Role-Play Simulation of an International Negotiation?

    ERIC Educational Resources Information Center

    Schnurr, Matthew A.; De Santo, Elizabeth M.; Green, Amanda D.

    2014-01-01

    This article uses pre- and post-surveys to assess learning outcomes associated with a role-play simulation set within a fictionalized extension of the Convention on Biological Diversity. Quantitative and qualitative data suggest that the simulation increased student appreciation of the complexity of international negotiation, but decreased student…

  8. Choices and Chances: The Sociology Role-Playing Game--The Sociological Imagination in Practice

    ERIC Educational Resources Information Center

    Simpson, Joseph M.; Elias, Vicky L.

    2011-01-01

    This article introduces a sociology role-playing game (RPG) used to demonstrate the broad range of social forces, institutions, and structures in a semester-long series of in-class and homework assignments. RPGs and other simulation games have been frequently suggested as a useful teaching methodology because of their unique ability to allow…

  9. Exploring Game Experiences and Game Leadership in Massively Multiplayer Online Role-Playing Games

    ERIC Educational Resources Information Center

    Jang, YeiBeech; Ryu, SeoungHo

    2011-01-01

    This study explored the in-game experiences of massively multiplayer online role-playing game (MMORPG) players focusing on game leadership and offline leadership. MMORPGs have enormous potential to provide gameplayers with rich social experiences through various interactions along with social activities such as joining a game community, team play…

  10. Excessive Use of Massively Multi-Player Online Role-Playing Games: A Pilot Study

    ERIC Educational Resources Information Center

    Hussain, Zaheer; Griffiths, Mark D.

    2009-01-01

    Massively multiplayer online role-playing games (MMORPGs) are one of the most interesting innovations in the area of online computer gaming. This pilot study set out to examine the psychological and social effects of online gaming using an online questionnaire with particular reference to excessive and "dependent" online gaming. A self-selecting…

  11. Role-Playing Game Based Assessment to Fractional Concept in Second Grade Mathematics

    ERIC Educational Resources Information Center

    Chiu, Fu-Yuan; Hsieh, Mei-Ling

    2017-01-01

    This study developed a set of Role-playing game (RPG), which was used to explore whether significant differences exist in academic performance and learning attitudes between RPG-based assessment and traditional lectures. This study also investigated the satisfaction of students toward the RPG scenario. Research participants included 100 second…

  12. Learning Strategies and Learner Attitudes in the Massively Multiplayer Online Role-Playing Game Cube World

    ERIC Educational Resources Information Center

    Goh, Shu Li

    2016-01-01

    The rapid progress of technology has revolutionized learning and in the field of computer assisted language learning, the use of digital games has expanded significantly. One type of game that has been attracting interest is massively multiplayer online role-playing games (henceforth MMORPGs). Recent research has drawn attention to the potential…

  13. Designing After-School Learning Using the Massively Multiplayer Online Role-Playing Game

    ERIC Educational Resources Information Center

    King, Elizabeth M.

    2015-01-01

    Digital games have become popular for engaging students in a range of learning goals, both in the classroom and the after-school space. In this article, I discuss a specific genre of video game, the massively multiplayer online role-playing game (MMO), which has been identified as a dynamic environment for encountering 21st-century workplace…

  14. Role-Playing Games for Capacity Building in Water and Land Management: Some Brazilian Experiences

    ERIC Educational Resources Information Center

    Camargo, Maria Eugenia; Jacobi, Pedro Roberto; Ducrot, Raphaele

    2007-01-01

    Role-playing games in natural resource management are currently being tested as research, training, and intervention tools all over the world. Various studies point out their potential to deal with complex issues and to contribute to training processes. The objective of this contribution is to analyze the limits and potentialities of this tool for…

  15. Using Massively Multiplayer Online Role-Playing Games for Online Learning

    ERIC Educational Resources Information Center

    Childress, Marcus D.; Braswell, Ray

    2006-01-01

    This article addresses the use of a massively multiplayer online role-playing game (MMORPG) to foster communication and interaction and to facilitate cooperative learning in an online course. The authors delineate the definition and history of massively multiplayer online games (MMOGs), and describe current uses of MMORPGs in education, including…

  16. Student Perceptions of a Role-Playing Simulation in an Introductory International Relations Course

    ERIC Educational Resources Information Center

    Giovanello, Sean P.; Kirk, Jason A.; Kromer, Mileah K.

    2013-01-01

    An emerging assumption in undergraduate political science education is that role-playing simulations are an effective teaching tool. While previous studies have addressed the pedagogical advantages of simulations as compared to more traditional teaching techniques, less attention has been paid to student perceptions of these simulations. This…

  17. Rapid changes in cellular immunity following a confrontational role-play stressor.

    PubMed

    Naliboff, B D; Solomon, G F; Gilmore, S L; Fahey, J L; Benton, D; Pine, J

    1995-09-01

    Recent laboratory studies have shown several immune system changes consistently associated with brief stress including increases in circulating natural killer (NK) cell numbers, increases in NK cell cytotoxicity (NKCC), increases in suppressor cytotoxic (CD8) T cell numbers, and decreases in the in vitro proliferative response to mitogen stimulation. In the present study, we use a confrontational role-play, which brings out responses varying from assertion to capitulation and examine the psychological, behavioral, physiological, and immune system responses to this task compared to a resting control task. Compared to the control condition, the brief confrontational role-play led to significant subjective and physiological arousal and increases in circulating NK (CD16, CD56) as well as large granular lymphocyte (CD57) cells and suppressor/cytotoxic T cells (CD8). There were also significant relationships between stress-related increases in the cardiovascular measures and the numbers of circulating NK cells. These findings support sympathetic nervous system activation as a primary mechanism for increases in NK cell numbers under challenge. These role-play results are generally consistent with those from other laboratory tasks such as mental arithmetic. However, in contrast to previously examined brief stressors, the role-play led to decreased NKCC adjusted for percentage of NK cells. This apparent differential change in NK cytotoxicity across different types of activating experimental tasks points to the importance of examining dimensions of the behavioral and emotional response to challenge or threat in addition to that of autonomic arousal.

  18. "Try Walking in Our Shoes": Teaching Acculturation and Related Cultural Adjustment Processes through Role-Play

    ERIC Educational Resources Information Center

    Zamboanga, Byron L.; Ham, Lindsay S.; Tomaso, Cara C.; Audley, Shannon; Pole, Nnamdi

    2016-01-01

    In this article, we describe several role-playing exercises on acculturation and relevant cultural adjustment processes that we incorporated into Tomcho and Foel's classroom activity on acculturation, and we report data that examine subsequent changes in students' responses on pretest and posttest measures shortly after the activity and present…

  19. Using analogy role-play activity in an undergraduate biology classroom to show central dogma revision.

    PubMed

    Takemura, Masaharu; Kurabayashi, Mario

    2014-01-01

    For the study of biology in an undergraduate classroom, a classroom exercise was developed: an analogy role-play to learn mechanisms of gene transcription and protein translation (central dogma). To develop the central dogma role-play exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress hanger, and amino acids using Lego® blocks (Lego System A/S, Denmark). Students were studying in the course of mathematics, physics, or chemistry, so biology was not among their usual studies. In this exercise, students perform the central dogma role-play and respectively act out nuclear matrix proteins, a transcription factor, an RNA polymerase II, an mRNA transport protein, nuclear pore proteins, a large ribosomal subunit, a small ribosomal subunit, and several amino-acyl tRNA synthetases. Questionnaire results obtained after the activity show that this central dogma role-play analogy holds student interest in the practical molecular biological processes of transcription and translation.

  20. Researching Travel Behavior and Adaptability: Using a Virtual Reality Role-Playing Game

    ERIC Educational Resources Information Center

    Watcharasukarn, Montira; Krumdieck, Susan; Green, Richard; Dantas, Andre

    2011-01-01

    This article describes a virtual reality role-playing game that was developed as a survey tool to collect travel behavior data and explore and monitor travel behavior adaptation. The Advanced Energy and Material Systems Laboratory has designed, developed a prototype, and tested such a game platform survey tool, called Travel Activity Constraint…

  1. Building Fictional Ethos: Analysing the Rhetorical Strategies of Persona Design for Online Role Play

    ERIC Educational Resources Information Center

    Doerr-Stevens, Candance

    2011-01-01

    This article presents a qualitative case study that uses discourse and social semiotic analysis methods in order to examine the rhetorical construction of fictional personas within an online role play used for learning in the college classroom. Of special focus are the differing patterns of semiotic resource use (for example, language and…

  2. Unsavory Problems at Tasty's: A Role-Play about Whistle-Blowing

    ERIC Educational Resources Information Center

    Comer, Debra R.; Vega, Gina

    2006-01-01

    This article presents a role-play exercise to make the topic of whistle-blowing personally salient to undergraduates. Students identify with the prospective whistle-blower, whose decision affects several stakeholders. The protagonist merely suspects her manager of stealing, until she hears concrete evidence of his thefts from her assistant…

  3. What Are the Roles that Children's Drawings Play in Inquiry of Science Concepts?

    ERIC Educational Resources Information Center

    Chang, Ni

    2012-01-01

    This study was designed to identify the roles that drawing played in the process of children's acquisition of science concepts. Seventy pre-service teachers through four semesters from a Midwest University in the USA developed lesson plans on science concepts and then taught them to 70 young children ages 4-7, respectively. This experience was…

  4. Students as "Humans Chromosomes" in Role-Playing Mitosis and Meiosis

    ERIC Educational Resources Information Center

    Chinnici, Joseph P.; Yue, Joyce W.; Torres, Kieron M.

    2004-01-01

    Students often find it challenging to understand mitosis and meiosis and determine their processes. To develop an easier way to understand these terms, students are asked to role-play mitosis and meiosis and students themselves act as human chromosomes, which help students to learn differences between mitosis and meiosis.

  5. Enhancing Information Systems Auditing Knowledge with Role-Playing Game: An Experimental Investigation

    ERIC Educational Resources Information Center

    Wongpinunwatana, Nitaya

    2013-01-01

    This study examined the use and effect of a role-playing game on learners' ability in information systems audit. The study is based on experimental research. Information systems control and audit case study and video had been developed. A total of 75 graduate students undertaking a Master's degree in accounting participated in the experiment. The…

  6. A Role-Play Game to Facilitate the Development of Students' Reflective Internet Skills

    ERIC Educational Resources Information Center

    Admiraal, Wilfried

    2015-01-01

    Although adolescents are currently the most frequent users of the Internet, many youngsters still have difficulties with a critical, reflective, and responsible use of the Internet. A study was carried out on teaching with a digital role-play game to increase students' reflective Internet skills. In this game, students had to promote a fictional…

  7. The Ethanol Project: Exploring Alternative Energy with Role-Play and Writing

    ERIC Educational Resources Information Center

    Winter, Julia

    2013-01-01

    This article describes a project that includes a two-week series of researching, essay writing, and speaking lessons exploring the broader implications of using ethanol as a fuel. The author, a chemistry teacher, describes how she uses a senate hearing discussion of ethanol fuel subsidies as the forum for a role-play. The four components of the…

  8. Can Pesticide Delivery Methods Play a Role in Sustainable Pest Management?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Conventional insecticides continue to play an important role in greenhouse pest management programs. Penetrating a dense plant canopy can be difficult with a handgun, and there is some evidence that boom sprayers or broadcast applications result in a more uniform deposition than handguns. A large-...

  9. Teacher's Skill Improvement by Role-Play and Simulations on Collaborative Educational Virtual Worlds

    ERIC Educational Resources Information Center

    Lorenzo, Carlos-Miguel

    2014-01-01

    This study looked at teachers' role-play and simulations in order to increase teachers' skills in psycho-pedagogical support on educational virtual worlds. We put forward a proposal to encourage the use of 3D scenarios where teachers can improve their skills for situations of cultural and ethical concerns that require a high level…

  10. E-Drama: Facilitating Online Role-Play Using an AI Actor and Emotionally Expressive Characters

    ERIC Educational Resources Information Center

    Zhang, Li; Gillies, Marco; Dhaliwal, Kulwant; Gower, Amanda; Robertson, Dale; Crabtree, Barry

    2009-01-01

    This paper describes a multi-user role-playing environment, referred to as "e-drama", which enables groups of people to converse online, in scenario driven virtual environments. The starting point of this research, is an existing application known as "edrama", a 2D graphical environment in which users are represented by static…

  11. Health Education in Practice. Let's Party: Teaching Responsible Alcohol Consumption Through Role Play.

    ERIC Educational Resources Information Center

    Lyde, Adrian R.; Temple, Mark A.

    1998-01-01

    Role play can teach college students responsible alcohol consumption behavior. The paper presents a technique to help students develop skills and attitudes that lead to responsible alcohol use behaviors. The technique models appropriate behaviors for party hosts, helps students put knowledge into action, and lets students explore the potential…

  12. Role Playing and Incentives in the Modification of the Social Interaction of Chronic Psychiatric Patients

    ERIC Educational Resources Information Center

    Doty, David Warren

    1975-01-01

    This article studied the relative and combined effectiveness of role playing and monetary incentives to increase the social interaction and responsiveness of chronic male psychiatric patients. Trend analyses of ward data and experimental findings consistently indicated significant positive changes at posttreatment for only those groups receiving…

  13. "Abolitionism under Attack:" A Role-Playing Simulation in American History.

    ERIC Educational Resources Information Center

    Bennett, Paul W.

    1986-01-01

    This one-week role-playing exercise for senior high school students simulates a street trial centering on the issue of slavery in the years before the American Civil War. A leading figure in the abolitionist movement is forced to confront her opponents in a face-to-face encounter. (RM)

  14. Understanding Collectivism and Female Genital Cutting through a Family Role-Playing Exercise

    ERIC Educational Resources Information Center

    Miller, Carol

    2014-01-01

    This study is a test of the effectiveness of a classroom role-playing exercise used to increase the understanding of cultural practices with which many Midwestern college students are uncomfortable. I employed a pre-test/post-test comparison group design. Students enrolled in two sections of a general education global issues course (N = 56) were…

  15. Developing Adolescents' Resistance to Sexual Coercion through Role-Playing Activities in a Virtual World

    ERIC Educational Resources Information Center

    McGinn, Marion; Arnedillo-Sánchez, Inmaculada

    2015-01-01

    This paper explores the use of a three dimensional virtual world (3-DVW) to delivery assertiveness training to young adolescents. The case study aims to understand how a sense of presence in VWs facilitates and affect the performance of students role-playing activities to enhance their ability to resist sexual coercion. The results indicate that a…

  16. Colleges Could Play Crucial Role in Halting Spread of AIDS Epidemic, Public-Health Officials Say.

    ERIC Educational Resources Information Center

    Biemiller, Lawrence

    1987-01-01

    Public-health specialists say colleges and universities could play a crucial role in halting the spread of AIDS by educating all their students about the disease and how to avoid becoming infected with the virus that causes it. Reaching minority groups and drug users, and "safe sex" kits are discussed. (MLW)

  17. Informal Workplace Communication--What Roles Can Microblogging Play in It?

    ERIC Educational Resources Information Center

    Zhao, Dejin

    2012-01-01

    Informal communication, e.g., unplanned "water-cooler" conversations, has been suggested to play important roles in collaborative work and organizational innovation. It provides opportunities among employees for exchanging work-relevant information, initiating potential collaboration, maintaining awareness of workplace context; and…

  18. Role-Playing Simulation as a Communication Tool in Community Dialogue: Karkonosze Mountains Case Study

    ERIC Educational Resources Information Center

    Krolikowska, Karolina; Kronenberg, Jakub; Maliszewska, Karolina; Sendzimir, Jan; Magnuszewski, Piotr; Dunajski, Andrzej; Slodka, Anna

    2007-01-01

    This article describes a process of role-playing simulation (RPS) as it was used during an educational exercise in community dialogue in the Karkonosze Mountains region of southwest Poland. Over the past decade Karkonosze National Park, a regional tourist magnet, has provided an excellent example of environmental conflict emerging from the…

  19. Using Role-Play to Foster Transformational and Social Action Multiculturalism in the ESL Classroom

    ERIC Educational Resources Information Center

    Gordon, Tatiana

    2012-01-01

    This article discusses the use of role-play as an effective strategy for enhancing the quality of multicultural curricula in the English as a second language (ESL) classroom. The author critiques the use of the simplistic additive approach to multicultural instruction and furthers the work of those theorists who advocate the use of the more…

  20. (Re)considering the Role "Familismo" Plays in Latina/o High School Students' College Choices

    ERIC Educational Resources Information Center

    Martinez, Melissa A.

    2013-01-01

    This qualitative study examines the role "familismo" (Marín & Marín, 1991) played in 20 Latina/o high school seniors' college choices. "Familismo" is the tendency to hold the wants and needs of family in higher regard than one's own and has been considered a common trait of Latina/o families. Interviews with students and…

  1. Enhance Learning on Software Project Management through a Role-Play Game in a Virtual World

    ERIC Educational Resources Information Center

    Maratou, Vicky; Chatzidaki, Eleni; Xenos, Michalis

    2016-01-01

    This article presents a role-play game for software project management (SPM) in a three-dimensional online multiuser virtual world. The Opensimulator platform is used for the creation of an immersive virtual environment that facilitates students' collaboration and realistic interaction, in order to manage unexpected events occurring during the…

  2. Female Superintendents in California and the Role That Mentoring and Networking Have Played in Their Success

    ERIC Educational Resources Information Center

    Dudek, Vicky

    2012-01-01

    This study examined the role that mentoring, formal networking, and informal networking have played in the lives of women who have obtained the position of superintendent in the state of California. The researcher explored the access that female administrators had to mentors and networks, followed by the perceived benefits they received when they…

  3. Simulation Games and Role Playing. Social Studies for the Elementary School. Proficiency Module #6.

    ERIC Educational Resources Information Center

    Bagley, Earl G.; Pierfy, David A.

    Designed as part of a series to develop teaching strategies for the elementary curriculum, this module focuses on simulation games and role playing as two important teaching devices. The first part describes games and simulation; and factors that should be considered in selecting, using, and debriefing games in the classroom. Exercises to test…

  4. General Federation of Women's Clubs: A Role Playing Exercise for Studying the Progressive Era.

    ERIC Educational Resources Information Center

    Barker, Sherman

    1986-01-01

    Provides an example of a role-playing exercise which takes place as a result of an imaginary caucus of women's groups meeting in the fall of 1912. The purpose of the caucus is to determine which of four presidential candidates--Woodrow Wilson, Theodore Roosevelt, William Howard Taft, and Eugene Debs--will receive the endorsement of the women's…

  5. Understanding Our Environment: Challenge. Clear Water Challenge: A Role Play Activity.

    ERIC Educational Resources Information Center

    Lieblich, Suzanne, Ed.

    Part of the Understanding Our Environment project that is designed to engage students in investigating specific environmental problems through concrete activity and direct experience, this unit contains a role-play activity in the form of a public inquiry into the cause of a fish kill on a river that runs through the fictional town of Oakwood. A…

  6. Solutions-Focused Role Play: Its Use in Training Peer Helpers

    ERIC Educational Resources Information Center

    Beale, Andrew V.; Hall, Kimberly R.

    2005-01-01

    Solutions-focused role play provides students with structured opportunities to transfer what they have learned to authentic situations they are likely to encounter as peer helpers. Rather than coming up with a single way to solve a problem, students are encouraged to explore multiple possible solutions. Peer training programs have traditionally…

  7. The Role the Collegiate American Marketing Association Plays in Professional and Entrepreneurial Skill Development

    ERIC Educational Resources Information Center

    Peltier, James W.; Scovotti, Carol; Pointer, Lucille

    2008-01-01

    Professional student organizations offer members a wide range of learning opportunities for applied marketing experiences. Little research exists in the marketing education literature on the role student organizations play in preparing their members for life beyond school. Understanding what students seek as members of such organizations and how…

  8. Early school competence: the roles of sex-segregated play and effortful control.

    PubMed

    Fabes, Richard A; Martin, Carol Lynn; Hanish, Laura D; Anders, Mary C; Madden-Derdich, Debra A

    2003-09-01

    The purpose of this research was to examine the role that young children's same-sex peer interactions play in influencing early school competence. The authors also examined the degree to which effortful control (EC) moderated these relations. The same-sex play preferences of 98 young children (50 boys and 48 girls; mean age = 54.77 months) were observed during the fall semester. At the end of the fall semester, one set of teachers reported on children's EC, and at the end of the following springsemester, another set reported on children's school competence (social, academic, and perceptual-motor). Results revealed that EC moderated the relations of children's same-sex play to their school competence. These patterns differed for boys and girls such that same-sex play was positively related to school outcomes for boys high in EC and for girls low in EC.

  9. Interaction with the game and motivation among players of massively multiplayer online role-playing games.

    PubMed

    Fuster, Héctor; Carbonell, Xavier; Chamarro, Andrés; Oberst, Ursula

    2013-01-01

    Knowledge about users interacting with Massively Multiplayer Online Role-Playing Games (MMORPG) is fundamental in order to prevent their potential negative effects on behavior. For this reason, the present study analyzed the relationship between styles of play and motivations. An online questionnaire asking for socio-demographic details, playing style, characteristics of the game played and motivations for playing, was answered by 430 Spanish-speaking MMORPG players (45.1% males). The identified profile for players, far away from the stereotype of an adolescent, consisted in a person who mainly plays on PvP (Player versus Player) servers, choosing the type of game according to his experience. Regarding motivations, they were interested in relating with other players through the game (Socialization), in discovering the game's possibilities and development of its adventures (Exploration), to a lesser extent in leadership and prestige (Achievement) and, lastly, identification with an avatar and escape from reality (Dissociation). Although part of the reason for playing was escapism and/or stress relief, the main motivation had a social nature. We conclude that MMORPG offer an attractive environment for a broad spectrum of people, and we have not been able to confirm the stereotype of a loner avoiding reality, taking refuge in games.

  10. Developing Children's Views of the Nature of Science Through Role Play

    NASA Astrophysics Data System (ADS)

    Cakici, Yilmaz; Bayir, Eylem

    2012-05-01

    The purpose of this study is to investigate the effect of using role play (portraying a scientist's life story) on the children's views of the nature of science (NOS). The study was carried out at the Children's University of Trakya in Turkey during the summer of 2010. The participants consisted of 18 children, aged 10-11. They met for 10 days for approximately 3 h per day. All children completed the pre- and post-tests including 16 open-ended questions in order to reveal changes in their views of the NOS prior to and at the completion of the role-play activities. The results revealed that the children had more informed views of the target NOS aspects in comparison with their views prior to the role-play activities. A large majority of the children (around 80-85%) started out with naive conceptions of the target NOS aspects. Following the role-play activities portraying scientists' lives, there was a 40-45% positive change in children's views of the tentative, empirical and creative/imaginative aspect of the NOS, and a 50-60% positive change in their views regarding the subjective/theory-laden and social-cultural embeddedness of science. The most substantial change occurred in their views concerning scientific method, with a shift of 72%. The percentage of informed views on images of scientists showed diversity. Overall results indicate that role-play/drama-oriented activities portraying scientist's life stories could be used as one of the exciting, informative and constructive ways of developing understanding of the NOS among children.

  11. Key roles for the small leucine-rich proteoglycans in renal and pulmonary pathophysiology

    PubMed Central

    Nastase, Madalina V.; Iozzo, Renato V.; Schaefer, Liliana

    2014-01-01

    Background Small leucine-rich proteoglycans (SLRPs) are molecules that have signaling roles in a multitude of biological processes. In this respect, SLRPs play key roles in the evolution of a variety of diseases throughout the human body. Scope of Review We will critically review current developments in the roles of SLRPs in several types of disease of the kidney and lungs. Particular emphasis will be given to the roles of decorin and biglycan, the best characterized members of the SLRP gene family. Major Conclusions In both renal and pulmonary disorders, SLRPs are essential elements that regulate several pathophysiological processes including fibrosis, inflammation and tumor progression. Decorin has remarkable antifibrotic and antitumorigenic properties and is considered a valuable potential treatment of these diseases. Biglycan can modulate inflammatory processes in lung and renal inflammation and is a potential target in the treatment of inflammatory conditions. General significance SLRPs can serve as either treatment targets or as potential treatment in renal or lung disease. PMID:24508120

  12. Role Modeling and Role Playing: A Manual for Vocational Development and Employment Agencies.

    ERIC Educational Resources Information Center

    Bertcher, Harvey; And Others

    This project investigated two major areas: (1) ways in which social science research and employment agency experience could be melded so as to make practical knowledge available to these agencies, and (2) ways of convincing employment agencies to use this knowledge. The manual resulting from the investigation focuses on role modeling and role…

  13. Social Roles, Role-Playing, and Education: On the High School as Prison

    ERIC Educational Resources Information Center

    Haney, Craig; Zimbardo, Philip G.

    1973-01-01

    A description and discussion of an experiment which placed normal college males into a prison-like environment related the term "prison" to any environment restricting human freedom, and explored the control of behavior by situations and roles with reference to educational settings, specifically the high school. (Author/KM)

  14. The Acceleration of the Universe in the Light of Supernovae: The Key Role of CTIO

    NASA Astrophysics Data System (ADS)

    Hamuy, M.; Suntzeff, N. B.

    2015-05-01

    The discovery of acceleration and dark energy arguably constitutes the most revolutionary discovery in astrophysics in recent years. The Cerro Tololo Inter-American Observatory (CTIO) played a key role in this amazing discovery through three systematic surveys organized by staff astronomers: the “Tololo Supernova Program“ (1986-2000), the Calán/Tololo Project (1989-1993), and the “High-Z Supernova Search Team” (1994-1998). CTIO's state of the art instruments also were fundamental in the independent discovery of acceleration by the “Supernova Cosmology Project” (1992-1999). Here I summarize the work on supernovae carried out from CTIO that led to the discovery of acceleration and dark energy and provide a brief historical summary on the use of Type Ia supernovae in cosmology in order to provide context for the CTIO contribution.

  15. Computer-supported games and role plays in teaching water management

    NASA Astrophysics Data System (ADS)

    Hoekstra, A. Y.

    2012-02-01

    There is an increasing demand for an interdisciplinary approach in teaching water management. Computer-supported games and role plays offer the potential of creating an environment in which different disciplines come together and in which students are challenged to develop integrated understanding. Two examples are discussed. The River Basin Game is a common-pool resource game in which participants experience the risk of over-abstractions of water in a river basin and learn how this risk relates to the complexity of the system, the conflict between individual and group optimum and the difficulty to come to good cooperation. The Globalization of Water Role Play makes participants familiar with the global dimension of water management by letting them experience how national governments can integrate considerations of water scarcity and domestic water productivities into decisions on international trade in commodities like food, cotton and bio-energy. The two examples illustrate that plays inspire participants to think about the functioning of systems as a whole and to develop good cooperative courses of action, whereby both uncertainties about the system and the presence of different values and perspectives among participants play a role.

  16. Computer-supported games and role plays in teaching water management

    NASA Astrophysics Data System (ADS)

    Hoekstra, A. Y.

    2012-08-01

    There is an increasing demand for an interdisciplinary approach in teaching water management. Computer-supported games and role plays offer the potential of creating an environment in which different disciplines come together and in which students are challenged to develop integrated understanding. Two examples are discussed. The River Basin Game is a common-pool resource game in which participants experience the risk of over-abstractions of water in a river basin and learn how this risk relates to the complexity of the system, the conflict between individual and group optimums and the difficulty in achieving good cooperation. The Globalization of Water Role Play makes participants familiar with the global dimension of water management by letting them experience how national governments can integrate considerations of water scarcity and domestic water productivities into decisions on international trade in commodities like food, cotton and bio-energy. The two examples illustrate that play sessions inspire participants to think about the functioning of systems as a whole and to develop good cooperative courses of action, whereby both uncertainties about the system and the presence of different values and perspectives among participants play a role.

  17. Clinical Intuition at Play

    ERIC Educational Resources Information Center

    Marks-Tarlow, Terry

    2014-01-01

    A clinical psychologist and consulting psychotherapist discusses how elements of play, inherent in the intuition required in analysis, can provide a cornerstone for serious therapeutic work. She argues that many aspects of play--its key roles in human development, individual growth, and personal creativity, among others--can help therapists and…

  18. Chronic hyperglicemia and nitric oxide bioavailability play a pivotal role in pro-atherogenic vascular modifications

    PubMed Central

    De Filippis, Elena Anna

    2007-01-01

    Diabetes is associated with accelerated atherosclerosis and macrovascular complications are a major cause of morbidity and mortality in this disease. Although our understanding of vascular pathology has lately greatly improved, the mechanism(s) underlying enhanced atherosclerosis in diabetes remain unclear. Endothelial cell dysfunction is emerging as a key component in the pathophysiology of cardiovascular abnormalities associated with diabetes. Although it has been established that endothelium plays a critical role in overall homeostasis of the vessels, vascular smooth muscle cells (vSMC) in the arterial intima have a relevant part in the development of atherosclerosis in diabetes. However, high glucose induced alterations in vSMC behaviour are not fully characterized. Several studies have reported that impaired nitric oxide (NO) synthesis and/or actions are often present in diabetes and endothelial dysfunction. Furthermore, although endothelial cells are by far the main site of vascular NO synthesis, vSMC do express nitric oxyde synthases (NOSs) and NO synthesis in vSMC might be important in vessel’s function. Although it is known that vSMC contribute to vascular pathology in diabetes by their change from a quiescent state to an activated proliferative and migratory phenotype (termed phenotypic modulation), whether this altered phenotypic modulation might also involve alterations in the nitrergic systems is still controversial. Our recent data indicate that, in vivo, chronic hyperglycemia might induce an increased number of vSMC proliferative clones which persist in culture and are associated with increased eNOS expression and activity. However, upregulation of eNOS and increased NO synthesis occur in the presence of a marked concomitant increase of O2− production. Since NO bioavailabilty might not be increased in high glucose stimulated vSMC, it is tempting to hypothesize that the proliferative phenotype observed in cells from diabetic rats is associated

  19. Chronic hyperglicemia and nitric oxide bioavailability play a pivotal role in pro-atherogenic vascular modifications.

    PubMed

    Pandolfi, Assunta; De Filippis, Elena Anna

    2007-11-01

    Diabetes is associated with accelerated atherosclerosis and macrovascular complications are a major cause of morbidity and mortality in this disease. Although our understanding of vascular pathology has lately greatly improved, the mechanism(s) underlying enhanced atherosclerosis in diabetes remain unclear. Endothelial cell dysfunction is emerging as a key component in the pathophysiology of cardiovascular abnormalities associated with diabetes. Although it has been established that endothelium plays a critical role in overall homeostasis of the vessels, vascular smooth muscle cells (vSMC) in the arterial intima have a relevant part in the development of atherosclerosis in diabetes. However, high glucose induced alterations in vSMC behaviour are not fully characterized. Several studies have reported that impaired nitric oxide (NO) synthesis and/or actions are often present in diabetes and endothelial dysfunction. Furthermore, although endothelial cells are by far the main site of vascular NO synthesis, vSMC do express nitric oxyde synthases (NOSs) and NO synthesis in vSMC might be important in vessel's function. Although it is known that vSMC contribute to vascular pathology in diabetes by their change from a quiescent state to an activated proliferative and migratory phenotype (termed phenotypic modulation), whether this altered phenotypic modulation might also involve alterations in the nitrergic systems is still controversial. Our recent data indicate that, in vivo, chronic hyperglycemia might induce an increased number of vSMC proliferative clones which persist in culture and are associated with increased eNOS expression and activity. However, upregulation of eNOS and increased NO synthesis occur in the presence of a marked concomitant increase of O(2-) production. Since NO bioavailabilty might not be increased in high glucose stimulated vSMC, it is tempting to hypothesize that the proliferative phenotype observed in cells from diabetic rats is associated with

  20. The apelinergic system: the role played in human physiology and pathology and potential therapeutic applications.

    PubMed

    Ladeiras-Lopes, Ricardo; Ferreira-Martins, João; Leite-Moreira, Adelino F

    2008-05-01

    Apelin is a recently discovered peptide, identified as an endogenous ligand of receptor APJ. Apelin and receptor APJ are expressed in a wide variety of tissues including heart, brain, kidneys and lungs. Their interaction may have relevant pathophysiologic effects in those tissues. In fact, the last decade has been rich in illustrating the possible roles played by apelin in human physiology, namely as a regulating peptide of cardiovascular, hypothalamus-hypophysis, gastrointestinal, and immune systems. The possible involvement of apelin in the pathogenesis of high prevalence conditions and comorbidities - such as hypertension, heart failure, and Diabetes Mellitus Type 2 (T2DM) - rank it as a likely therapeutic target to be investigated in the future. The present paper is an overview of apelin physiologic effects and presents the possible role played by this peptide in the pathogenesis of a number of conditions as well as the therapeutic implications that might, therefore, be investigated.

  1. The integral nuclear membrane protein nurim plays a role in the suppression of apoptosis.

    PubMed

    Chen, H; Chen, K; Chen, J; Cheng, H; Zhou, R

    2012-12-01

    As an essential component of eukaryotic cells, the nuclear envelope (NE) plays a crucial role in many physiological processes. At present, a few membrane proteins from NE have been functionally characterized. To determine whether the inner nuclear membrane (INM) protein Nurim is expressed in cancer cells with evidence of apoptosis, we identified three isoforms of this protein that are specific for human testicular seminoma and are generated by alternative splicing. We observed that Nurim is expressed in a broad range of cancer types and that its expression level is correlated with a higher tumor grade. Biochemical analysis showed that Nurim b, like a, is tightly bound to the nuclear envelope. Furthermore, knockdown using miR-Nurim resulted in an abnormal shape change of the nuclear envelope. Notably, Nurim knockdown obviously increased apoptosis induced by ultraviolet in HeLa cells. Together, these findings implicate that the INM protein Nurim plays an important role in the suppression of apoptosis.

  2. Role-play using SBAR technique to improve observed communication skills in senior nursing students.

    PubMed

    Kesten, Karen S

    2011-02-01

    Patients in the care of clinically expert professionals suffer medical errors with alarming frequency. The Joint Commission's National Patient Safety Goals strives to improve the effectiveness of communication among caregivers by recommending the implementation of a standardized tool known as SBAR (Situation, Background, Assessment, and Recommendation). This experimental study evaluated data from undergraduate nursing students (N = 115) on their performance using a standardized communication tool SBAR. The mean performance scores of the didactic plus role-play students were significantly higher than those who had didactic instruction alone (t = -2.6, p = 0.005). Findings suggest role-play may have a place in teaching communication skills in nursing schools as well as continuing education and training in hospitals and other health care settings. Interdisciplinary communication training may provide even more effective learning. The link between effective communication and improved patient outcomes also should be studied.

  3. Direct interaction with the public: making it a "serious game" with role playing

    NASA Astrophysics Data System (ADS)

    Vercelli, Samuela; Lombardi, Salvatore; Jones, David; Pearce, Jonathan; Persoglia, Sergio; De Vittor, Cinzia; Gemeni, Vassiliki; Svendsen Skriung, Camilla; Bigi, Sabina; Franzese, Carmela; Riley, Nick; McConnell, Brian; Volpi, Valentina; Donda, Federica

    2014-05-01

    Researchers have an important role in the societal process of understanding and evaluating new technologies, but their role is often undermined by the lack of appropriate contexts where a constructive dialogue can take place, thus leading to awareness of issues and correct perception of scientific data. In the case of geoscience the problem can be even harsher, due to the often limited education on the subject, complexity of the imaginative relationship with the underground, lack of social shared representations of key geological features. This contribution reports about an interactive session organised during the 2012 ESOF - European Science Open Forum http://esof2012.org/ for the FP7 project RISCS - 'Research into Impacts and Safety in CO2 Storage' http://www.riscs-co2.eu/ and in collaboration with the FP7 project CGS Europe http://www.cgseurope.net/ . The session saw the participation of about 100 people. The RISCS project is a European project which has explored the potential environmental impacts of the geological storage of CO2, as a technology for abating CO2 emissions. The session was meant to introduce the participants to the information produced within the RISCS project on possible impacts of CO2 on onshore and offshore ecosystems and human population. The objective was to experiment a process for facilitating, through dialogue and self-discovery, an understanding of the particular issues that need to be considered when evaluating the potential impacts of CO2 storage. It was also an opportunity to test an innovative and original format for science communication, aimed at involving a large group of participants in interactive activities with experts, based on the Role Playing Game pattern. The structure of the workshop included an exploration of participants' questions on and interest in CCS impacts, small group interaction with researchers and a final feed-back from each group to the plenary. Each group of about 10 participants was provided the

  4. A Quantitative Content Analysis of Leveled Vocabulary Embedded within Massively Multiplayer Online Role-Playing Games (MMORPGs)

    ERIC Educational Resources Information Center

    Haas, Leslie

    2012-01-01

    This content analysis examined levels of vocabulary within massively multiplayer online role-playing games (MMORPGs). A total of six MMORPGs were studied; three were pay-to-play (P2P), and three were free-to-play (F2P). Sixty hours of game play (10 hours per game) provided the researcher with 50,240 embedded vocabulary words. Each MMORPG was…

  5. IRE1/bZIP60-Mediated Unfolded Protein Response Plays Distinct Roles in Plant Immunity and Abiotic Stress Responses

    PubMed Central

    Blanco, Francisca; Boatwright, Jon Lucas; Moreno, Ignacio; Jordan, Melissa R.; Chen, Yani; Brandizzi, Federica; Dong, Xinnian

    2012-01-01

    Endoplasmic reticulum (ER)-mediated protein secretion and quality control have been shown to play an important role in immune responses in both animals and plants. In mammals, the ER membrane-located IRE1 kinase/endoribonuclease, a key regulator of unfolded protein response (UPR), is required for plasma cell development to accommodate massive secretion of immunoglobulins. Plant cells can secrete the so-called pathogenesis-related (PR) proteins with antimicrobial activities upon pathogen challenge. However, whether IRE1 plays any role in plant immunity is not known. Arabidopsis thaliana has two copies of IRE1, IRE1a and IRE1b. Here, we show that both IRE1a and IRE1b are transcriptionally induced during chemically-induced ER stress, bacterial pathogen infection and treatment with the immune signal salicylic acid (SA). However, we found that IRE1a plays a predominant role in the secretion of PR proteins upon SA treatment. Consequently, the ire1a mutant plants show enhanced susceptibility to a bacterial pathogen and are deficient in establishing systemic acquired resistance (SAR), whereas ire1b is unaffected in these responses. We further demonstrate that the immune deficiency in ire1a is due to a defect in SA- and pathogen-triggered, IRE1-mediated cytoplasmic splicing of the bZIP60 mRNA, which encodes a transcription factor involved in the expression of UPR-responsive genes. Consistently, IRE1a is preferentially required for bZIP60 splicing upon pathogen infection, while IRE1b plays a major role in bZIP60 processing upon Tunicamycin (Tm)-induced stress. We also show that SA-dependent induction of UPR-responsive genes is altered in the bzip60 mutant resulting in a moderate susceptibility to a bacterial pathogen. These results indicate that the IRE1/bZIP60 branch of UPR is a part of the plant response to pathogens for which the two Arabidopsis IRE1 isoforms play only partially overlapping roles and that IRE1 has both bZIP60-dependent and bZIP60-independent functions in

  6. New insights into an old story: pollen ROS also play a role in hay fever.

    PubMed

    Speranza, Anna; Scoccianti, Valeria

    2012-08-01

    Reactive oxygen species (ROS) can exhibit negative and benign traits. In plants, ROS levels increase markedly during periods of environmental stress, and defense against pathogen attack. ROS form naturally as a by-product of normal oxygen metabolism, and evenly play an essential role in cell growth. The short ROS lifespan makes them ideal molecules to act in cell signaling, a role they share in both plants and animals. A particular plant organism, the pollen grain, may closely interact with human mucosa and an allergic inflammatory response often results. Pollen grain ROS represent a first, crucial signal which primes and magnifies a cascade of events in the allergic response.

  7. Playable Stories: Making Programming and 3D Role-Playing Game Design Personally and Socially Relevant

    ERIC Educational Resources Information Center

    Ingram-Goble, Adam

    2013-01-01

    This is an exploratory design study of a novel system for learning programming and 3D role-playing game design as tools for social change. This study was conducted at two sites. Participants in the study were ages 9-14 and worked for up to 15 hours with the platform to learn how to program and design video games with personally or socially…

  8. The Key Roles in the Informal Organization: A Network Analysis Perspective

    ERIC Educational Resources Information Center

    de Toni, Alberto F.; Nonino, Fabio

    2010-01-01

    Purpose: The purpose of this paper is to identify the key roles embedded in the informal organizational structure (informal networks) and to outline their contribution in the companies' performance. A major objective of the research is to find and characterize a new key informal role that synthesises problem solving, expertise, and accessibility…

  9. Facebook Role Play Addiction – A Comorbidity with Multiple Compulsive–Impulsive Spectrum Disorders

    PubMed Central

    Nathan, Deeepa; Shukla, Lekhansh; Kandasamy, Arun; Benegal, Vivek

    2016-01-01

    Background Problematic Internet use (PIU) is an emerging entity with varied contents. Behavioral addictions have high comorbidity of attention deficit hyperactivity disorder and obsessive–compulsive spectrum disorders. Social networking site (SNS) addiction and role playing game (RPG) addiction are traditionally studied as separate entities. We present a case with excessive Internet use, with a particular focus on phenomenology and psychiatric comorbidities. Case presentation Fifteen-year-old girl with childhood onset attention deficit disorder, obsessive–compulsive disorder, adolescent onset trichotillomania, and disturbed family environment presented with excessive Facebook use. Main online activity was creating profiles in names of mainstream fictional characters and assuming their identity (background, linguistic attributes, etc.). This was a group activity with significant socialization in the virtual world. Craving, salience, withdrawal, mood modification, and conflict were clearly elucidated and significant social and occupational dysfunction was evident. Discussion This case highlights various vulnerability and sociofamilial factors contributing to behavioral addiction. It also highlights the presence of untreated comorbidities in such cases. The difference from contemporary RPGs and uniqueness of role playing on SNS is discussed. SNS role playing as a separate genre of PIU and its potential to reach epidemic proportions are discussed. Conclusions Individuals with temperamental vulnerability are likely to develop behavioral addictions. Identification and management of comorbid conditions are important. The content of PIU continues to evolve and needs further study. PMID:27156380

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

    PubMed Central

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

    2016-01-01

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

  11. Role-play simulations for climate change adaptation education and engagement

    NASA Astrophysics Data System (ADS)

    Rumore, Danya; Schenk, Todd; Susskind, Lawrence

    2016-08-01

    In order to effectively adapt to climate change, public officials and other stakeholders need to rapidly enhance their understanding of local risks and their ability to collaboratively and adaptively respond to them. We argue that science-based role-play simulation exercises -- a type of 'serious game' involving face-to-face mock decision-making -- have considerable potential as education and engagement tools for enhancing readiness to adapt. Prior research suggests role-play simulations and other serious games can foster public learning and encourage collective action in public policy-making contexts. However, the effectiveness of such exercises in the context of climate change adaptation education and engagement has heretofore been underexplored. We share results from two research projects that demonstrate the effectiveness of role-play simulations in cultivating climate change adaptation literacy, enhancing collaborative capacity and facilitating social learning. Based on our findings, we suggest such exercises should be more widely embraced as part of adaptation professionals' education and engagement toolkits.

  12. Facebook Role Play Addiction - A Comorbidity with Multiple Compulsive-Impulsive Spectrum Disorders.

    PubMed

    Nathan, Deeepa; Shukla, Lekhansh; Kandasamy, Arun; Benegal, Vivek

    2016-06-01

    Background Problematic Internet use (PIU) is an emerging entity with varied contents. Behavioral addictions have high comorbidity of attention deficit hyperactivity disorder and obsessive-compulsive spectrum disorders. Social networking site (SNS) addiction and role playing game (RPG) addiction are traditionally studied as separate entities. We present a case with excessive Internet use, with a particular focus on phenomenology and psychiatric comorbidities. Case presentation Fifteen-year-old girl with childhood onset attention deficit disorder, obsessive-compulsive disorder, adolescent onset trichotillomania, and disturbed family environment presented with excessive Facebook use. Main online activity was creating profiles in names of mainstream fictional characters and assuming their identity (background, linguistic attributes, etc.). This was a group activity with significant socialization in the virtual world. Craving, salience, withdrawal, mood modification, and conflict were clearly elucidated and significant social and occupational dysfunction was evident. Discussion This case highlights various vulnerability and sociofamilial factors contributing to behavioral addiction. It also highlights the presence of untreated comorbidities in such cases. The difference from contemporary RPGs and uniqueness of role playing on SNS is discussed. SNS role playing as a separate genre of PIU and its potential to reach epidemic proportions are discussed. Conclusions Individuals with temperamental vulnerability are likely to develop behavioral addictions. Identification and management of comorbid conditions are important. The content of PIU continues to evolve and needs further study.

  13. Understanding protein synthesis: a role-play approach in large undergraduate human anatomy and physiology classes.

    PubMed

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

    2009-06-01

    This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section presented with a traditional lecture served as the control group. A pretest/posttest assessment and a survey were administered to both sections and used in data analysis. In addition, overall test scores and item analysis were examined. The analysis revealed that participants in both groups improved significantly from pretest to posttest, but there were no significant differences between the groups in posttest scores. Neither group showed a significant change from posttest to the exam. However, there was a moderate positive effect on engagement and satisfaction survey questions from being in the study group (based on 255 total surveys returned by both groups). The role-play activity was at least as effective as the lecture in terms of student performance on the above-mentioned assessments. In addition, it proved successful in engaging students in the learning process and increasing their satisfaction.

  14. Use of interactive theater and role play to develop medical students' skills in breaking bad news.

    PubMed

    Skye, Eric P; Wagenschutz, Heather; Steiger, Jeffrey A; Kumagai, Arno K

    2014-12-01

    Creative arts have been increasingly implemented in medical education. This study investigated the use of interactive theater and role play with professional actors in teaching breaking bad news to medical students. The objectives were to explore the contexts, approaches, experiences, and reactions in giving and receiving bad news. Second-year medical students participated in a required educational session that utilized interactive theater which helps students learn about the issues of breaking bad news to a patient with cancer. Following the interactive theater piece, professional actors provided students role play experiences in small groups with breaking bad news. Anonymous evaluation surveys were given out to all second-year medical students at the conclusion of the breaking bad news session. Surveys contained quantitative and qualitative responses. Three years of evaluations were analyzed. A total of 451 (88 %) students completed the evaluations. Comments were thematically analyzed. Ninety-four percent agreed that the theater piece prompted reflection on patient-provider communications, and 89 % agreed that it stimulated discussion on complex issues with breaking bad news. The two most common themes in student comments concerned the importance of realism in the theater piece, and the value of experiencing multiple perspectives. Use of professional actors during the role play exercises enhances the realism and pushed the students out of their own "comfort zones" in ways that may more closely approximate real life clinical situations. Interactive theater can be a potentially powerful tool to teach breaking bad news during medical school.

  15. GPs have key role in managing motor neurone disease.

    PubMed

    Orrell, Richard W

    2011-09-01

    Motor neurone disease (MND) is a rapidly progressive neurodegenerative condition. It affects people of all ages, but is more common with increasing age (especially over 50 years) and men are affected twice as often as women. The causes remain unknown, although around 5% of cases have a genetic basis. Survival is usually only three to five years from diagnosis. MND affects both upper and lower motor neurones, with variable contributions. The nerve involvement in MND usually has a focal onset, is asymmetrical, but tends to spread to adjacent regions of the body. If the affected region is in the legs, a common presenting feature is tripping, falls or foot drop. If it is in the arms there may be difficulty with fine tasks such as fastening buttons, or raising an arm, and if the cranial nerves are affected there may be slurring of speech, or difficulty swallowing. Key to the diagnosis is evidence of progression, and this may lead to some delay in considering and also confirming the diagnosis. When examining the patient, evidence of more widespread neuromuscular involvement should be looked for. In a patient with foot drop, and fasciculation of the tongue, MND would be a likely diagnosis. Upper motor neurone involvement may be readily determined by examining the reflexes. Brisk reflexes, in the arms, legs or jaw, in the context of features of lower motor neurone denervation are highly suggestive of MND. Suspicion of MND should lead to referral for a neurology opinion. The most useful investigation is likely to be EMG with nerve conduction studies, and probably MRI scan of relevant areas. Blood tests are arranged to screen for any other causative condition. Riluzole is a disease modifying drug licensed to extend the life of patients with MND. There is no treatment that will reverse, or halt, progression of the disease.

  16. A Key Role for Inhibins in Dendritic Cell Maturation and Function.

    PubMed

    Olguín-Alor, Roxana; de la Fuente-Granada, Marisol; Bonifaz, Laura C; Antonio-Herrera, Laura; García-Zepeda, Eduardo A; Soldevila, Gloria

    2016-01-01

    Inhibins are members of the TGFβ superfamily, which regulate many cellular processes including differentiation, proliferation, survival and apoptosis. Although initially described as hormones regulating the hypothalamus-pituitary-gonadal axis, based on their ability to antagonize Activins, our group has recently reported that they play a role in thymocyte differentiation and survival, as well as in thymic stromal cell maturation and nTreg generation. Here, we used Inhibin knock out mice (Inhα-/-) to investigate the role of Inhibins in peripheral dendritic cell maturation and function. We first demonstrated that LPS treated Inhα+/+ bone marrow derived dendritic cells (BMDC) were capable to produce significant levels of Inhibin A. Interestingly, Inhα-/- BMDC showed reduced MHCII and CD86 upregulation and increased PD-L1 expression in response to LPS compared to Inhα+/+, which correlated with reduced ability to induce proliferation of allogeneic T cells. The "semi-mature" phenotype displayed by Inhα-/- mBMDC correlated with increased levels of IL-10 and slightly decreased IL-6 production after LPS stimulation. In addition, Inhα-/- mBMDC showed impaired migration towards CCL19 and CCL21, assessed by in vitro chemotaxis and in vivo competitive homing experiments, despite their normal CCR7 expression. Furthermore, in vivo LPS-induced DC maturation was also diminished in Inhα-/- mice, specially within the LC (CD207+ CD11b+ CD103-) subpopulation. Finally, analysis of delayed type hypersensitivity responses in Inhα-/- mice, showed reduced ear swelling as a result of reduced cellular infiltration in the skin, correlating with impaired homing of CD207+ DCs to the draining lymph nodes. In summary, our data demonstrate for the first time that Inhibins play a key role in peripheral DC maturation and function, regulating the balance between immunity and tolerance.

  17. Key Role for Efflux in the Preservative Susceptibility and Adaptive Resistance of Burkholderia cepacia Complex Bacteria

    PubMed Central

    Rushton, Laura; Sass, Andrea; Baldwin, Adam; Dowson, Christopher G.; Donoghue, Denise

    2013-01-01

    Bacteria from the Burkholderia cepacia complex (Bcc) are encountered as industrial contaminants, and little is known about the species involved or their mechanisms of preservative resistance. Multilocus sequence typing (MLST) revealed that multiple Bcc species may cause contamination, with B. lata (n = 17) and B. cenocepacia (n = 11) dominant within the collection examined. At the strain level, 11 of the 31 industrial sequence types identified had also been recovered from either natural environments or clinical infections. Minimal inhibitory (MIC) and minimum bactericidal (MBC) preservative concentrations varied across 83 selected Bcc strains, with industrial strains demonstrating increased tolerance for dimethylol dimethyl hydantoin (DMDMH). Benzisothiazolinone (BIT), DMDMH, methylisothiazolinone (MIT), a blend of 3:1 methylisothiazolinone-chloromethylisothiazolinone (M-CMIT), methyl paraben (MP), and phenoxyethanol (PH), were all effective anti-Bcc preservatives; benzethonium chloride (BC) and sodium benzoate (SB) were least effective. Since B. lata was the dominant industrial Bcc species, the type strain, 383T (LMG 22485T), was used to study preservative tolerance. Strain 383 developed stable preservative tolerance for M-CMIT, MIT, BIT, and BC, which resulted in preservative cross-resistance and altered antibiotic susceptibility, motility, and biofilm formation. Transcriptomic analysis of the B. lata 383 M-CMIT-adapted strain demonstrated that efflux played a key role in its M-CMIT tolerance and elevated fluoroquinolone resistance. The role of efflux was corroborated using the inhibitor l-Phe-Arg-β-napthylamide, which reduced the MICs of M-CMIT and ciprofloxacin. In summary, intrinsic preservative tolerance and stable adaptive changes, such as enhanced efflux, play a role in the ability of Bcc bacteria to cause industrial contamination. PMID:23587949

  18. A Key Role for Inhibins in Dendritic Cell Maturation and Function

    PubMed Central

    Olguín-Alor, Roxana; de la Fuente-Granada, Marisol; Bonifaz, Laura C.; Antonio-Herrera, Laura; García-Zepeda, Eduardo A.; Soldevila, Gloria

    2016-01-01

    Inhibins are members of the TGFβ superfamily, which regulate many cellular processes including differentiation, proliferation, survival and apoptosis. Although initially described as hormones regulating the hypothalamus-pituitary-gonadal axis, based on their ability to antagonize Activins, our group has recently reported that they play a role in thymocyte differentiation and survival, as well as in thymic stromal cell maturation and nTreg generation. Here, we used Inhibin knock out mice (Inhα-/-) to investigate the role of Inhibins in peripheral dendritic cell maturation and function. We first demonstrated that LPS treated Inhα+/+ bone marrow derived dendritic cells (BMDC) were capable to produce significant levels of Inhibin A. Interestingly, Inhα-/- BMDC showed reduced MHCII and CD86 upregulation and increased PD-L1 expression in response to LPS compared to Inhα+/+, which correlated with reduced ability to induce proliferation of allogeneic T cells. The “semi-mature” phenotype displayed by Inhα-/- mBMDC correlated with increased levels of IL-10 and slightly decreased IL-6 production after LPS stimulation. In addition, Inhα-/- mBMDC showed impaired migration towards CCL19 and CCL21, assessed by in vitro chemotaxis and in vivo competitive homing experiments, despite their normal CCR7 expression. Furthermore, in vivo LPS-induced DC maturation was also diminished in Inhα-/- mice, specially within the LC (CD207+ CD11b+ CD103-) subpopulation. Finally, analysis of delayed type hypersensitivity responses in Inhα-/- mice, showed reduced ear swelling as a result of reduced cellular infiltration in the skin, correlating with impaired homing of CD207+ DCs to the draining lymph nodes. In summary, our data demonstrate for the first time that Inhibins play a key role in peripheral DC maturation and function, regulating the balance between immunity and tolerance. PMID:27936218

  19. Designing Online Role Plays with a Focus on Story Development to Support Engagement and Critical Learning for Higher Education Students

    ERIC Educational Resources Information Center

    Dracup, Mary

    2012-01-01

    Online role plays, as they are designed for use in higher education in Australia and internationally, are active and authentic learning activities (Wills, Leigh & Ip, 2011). In online role plays, students take a character role in developing a story that serves as a metaphor for real-life experience in order to develop a potentially wide range…

  20. Bacterial microcompartment assembly: The key role of encapsulation peptides

    DOE PAGES

    Aussignargues, Clément; Paasch, Bradley C.; Gonzalez-Esquer, Raul; ...

    2015-06-23

    Bacterial microcompartments (BMCs) are proteinaceous organelles used by a broad range of bacteria to segregate and optimize metabolic reactions. Their functions are diverse, and can be divided into anabolic (carboxysome) and catabolic (metabolosomes) processes, depending on their cargo enzymes. The assembly pathway for the β-carboxysome has been characterized, revealing that biogenesis proceeds from the inside out. The enzymes coalesce into a procarboxysome, followed by encapsulation in a protein shell that is recruited to the procarboxysome by a short (~17 amino acids) extension on the C-terminus of one of the encapsulated proteins. A similar extension is also found on the N-more » or C-termini of a subset of metabolosome core enzymes. These encapsulation peptides (EPs) are characterized by a primary structure predicted to form an amphipathic α-helix that interacts with shell proteins. In this study, we review the features, function and widespread occurrence of EPs among metabolosomes, and propose an expanded role for EPs in the assembly of diverse BMCs.« less

  1. Bacterial microcompartment assembly: The key role of encapsulation peptides

    SciTech Connect

    Aussignargues, Clément; Paasch, Bradley C.; Gonzalez-Esquer, Raul; Erbilgin, Onur; Kerfeld, Cheryl A.

    2015-06-23

    Bacterial microcompartments (BMCs) are proteinaceous organelles used by a broad range of bacteria to segregate and optimize metabolic reactions. Their functions are diverse, and can be divided into anabolic (carboxysome) and catabolic (metabolosomes) processes, depending on their cargo enzymes. The assembly pathway for the β-carboxysome has been characterized, revealing that biogenesis proceeds from the inside out. The enzymes coalesce into a procarboxysome, followed by encapsulation in a protein shell that is recruited to the procarboxysome by a short (~17 amino acids) extension on the C-terminus of one of the encapsulated proteins. A similar extension is also found on the N- or C-termini of a subset of metabolosome core enzymes. These encapsulation peptides (EPs) are characterized by a primary structure predicted to form an amphipathic α-helix that interacts with shell proteins. In this study, we review the features, function and widespread occurrence of EPs among metabolosomes, and propose an expanded role for EPs in the assembly of diverse BMCs.

  2. The key role of eyewitnesses in rapid earthquake impact assessment

    NASA Astrophysics Data System (ADS)

    Bossu, Rémy; Steed, Robert; Mazet-Roux, Gilles; Roussel, Frédéric; Etivant, Caroline

    2014-05-01

    published after validation. Quake Catcher Networks (QCN) where a cheap USB MEMS motion sensors transform a PC in a seismic station are being deployed in Thessaloniki and Patras (Greece) in collaboration with Stanford University and the USGS. Flashsourcing is also used which is the analysis in real time of traffic surges observed on EMSC's earthquake information website; these surges are caused by the natural convergence of eyewitnesses who rush to the Internet to investigate the cause of the shaking that they have just felt. Within 5 minutes and independently of any seismic data, this detects felt earthquakes, maps the felt area and can detect the presence of damage. We will also explain the roles of social networks in optimising data collection and how citizen involvement has changed our earthquake information services.

  3. IL-10 Plays Opposing Roles during Staphylococcus aureus Systemic and Localized Infections

    PubMed Central

    Leech, John M.; Lacey, Keenan A.; Mulcahy, Michelle E.; Medina, Eva

    2017-01-01

    IL-10 is a potent anti-inflammatory mediator that plays a crucial role in limiting host immunopathology during bacterial infections by controlling effector T cell activation. Staphylococcus aureus has previously been shown to manipulate the IL-10 response as a mechanism of immune evasion during chronic systemic and biofilm models of infection. In the present study, we demonstrate divergent roles for IL-10 depending on the site of infection. During acute systemic S. aureus infection, IL-10 plays an important protective role and is required to prevent bacterial dissemination and host morbidity by controlling effector T cells and the associated downstream hyperactivation of inflammatory phagocytes, which are capable of host tissue damage. CD19+CD11b+CD5+ B1a regulatory cells were shown to rapidly express IL-10 in a TLR2-dependent manner in response to S. aureus, and adoptive transfer of B1a cells was protective during acute systemic infection in IL-10–deficient hosts. In contrast, during localized s.c. infection, IL-10 production plays a detrimental role by facilitating bacterial persistence via the same mechanism of controlling proinflammatory T cell responses. Our findings demonstrate that induction of IL-10 has a major influence on disease outcome during acute S. aureus infection. Too much IL-10 at one end of the scale may suppress otherwise protective T cell responses, thus facilitating persistence of the bacteria, and at the other end, too little IL-10 may tend toward fatal host-mediated pathology through excessive activation of T cells and associated phagocyte-mediated damage. PMID:28167629

  4. Serious Simulation Role-Playing Games for Transformative Climate Change Education: "World Climate" and "Future Climate"

    NASA Astrophysics Data System (ADS)

    Rooney-Varga, J. N.; Sterman, J.; Sawin, E.; Jones, A.; Merhi, H.; Hunt, C.

    2012-12-01

    Climate change, its mitigation, and adaption to its impacts are among the greatest challenges of our times. Despite the importance of societal decisions in determining climate change outcomes, flawed mental models about climate change remain widespread, are often deeply entrenched, and present significant barriers to understanding and decision-making around climate change. Here, we describe two simulation role-playing games that combine active, affective, and analytical learning to enable shifts of deeply held conceptions about climate change. The games, World Climate and Future Climate, use a state-of-the-art decision support simulation, C-ROADS (Climate Rapid Overview and Decision Support) to provide users with immediate feedback on the outcomes of their mitigation strategies at the national level, including global greenhouse gas (GHG) emissions and concentrations, mean temperature changes, sea level rise, and ocean acidification. C-ROADS outcomes are consistent with the atmosphere-ocean general circulation models (AOGCMS), such as those used by the IPCC, but runs in less than one second on ordinary laptops, providing immediate feedback to participants on the consequences of their proposed policies. Both World Climate and Future Climate role-playing games provide immersive, situated learning experiences that motivate active engagement with climate science and policy. In World Climate, participants play the role of United Nations climate treaty negotiators. Participant emissions reductions proposals are continually assessed through interactive exploration of the best available science through C-ROADS. Future Climate focuses on time delays in the climate and energy systems. Participants play the roles of three generations: today's policymakers, today's youth, and 'just born.' The game unfolds in three rounds 25 simulated years apart. In the first round, only today's policymakers make decisions; In the next round, the young become the policymakers and inherit the

  5. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

    SciTech Connect

    Du, Fengxia; Zhang, Minjie; Li, Xiaohua; Yang, Caiyun; Meng, Hao; Wang, Dong; Chang, Shuang; Xu, Ye; Price, Brendan; Sun, Yingli

    2014-10-03

    Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after DNA repair. - Abstract: The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.

  6. Cholesterol plays a larger role during Mycobacterium tuberculosis in vitro dormancy and reactivation than previously suspected.

    PubMed

    Soto-Ramirez, Maria D; Aguilar-Ayala, Diana A; Garcia-Morales, Lazaro; Rodriguez-Peredo, Sofia M; Badillo-Lopez, Claudia; Rios-Muñiz, Diana E; Meza-Segura, Mario A; Rivera-Morales, Gelen Y; Leon-Solis, Lizbel; Cerna-Cortes, Jorge F; Rivera-Gutierrez, Sandra; Helguera-Repetto, Addy C; Gonzalez-Y-Merchand, Jorge A

    2017-03-01

    It is known that cholesterol plays a key role for Mycobacterium tuberculosis (Mtb) adaptation and survival within the host, thus contributing to the establishment of dormancy. It has been extensively demonstrated that fatty acids are the main energy source of Mtb during infection and dormancy, and it has been proposed that these molecules are implicated in reactivation of bacilli from a dormant state. We used in vitro models to analyze Mtb gene expression during dormancy and reactivation when fatty acids and cholesterol are the unique carbon source in the media. Our results suggest that cholesterol might function as a signal to trigger Mtb expression of some genes required for stress protection earlier than the one induced by fatty acids alone, indicating that cholesterol is very favorable for its development. This process is so conducive that cholesterol-adapted bacilli can reactivate their growth after NRP2 dormancy state even 10 min post ventilation. Thus, we hypothesize that cholesterol is not only involved in Mtb dormancy but that it also plays a critical role for favorable and almost immediate reactivation from an in vitro long-lasting dormant state induced by hypoxia.

  7. Is Avian Malaria Playing a Role in Native Bird Declines in New Zealand? Testing Hypotheses along an Elevational Gradient

    PubMed Central

    Poulin, Robert; Tompkins, Daniel M.

    2016-01-01

    The mosquito-borne disease avian malaria (Plasmodium spp.) has impacted both captive populations and wild individuals of native New Zealand bird species. However, whether or not it is a cause of concern to their wild populations is still unclear. In Hawaii, the disease has been a major factor in the population declines of some native forest bird species, often limiting their elevational distribution due to an inverse relationship between force of infection and elevation. While studies have investigated latitudinal patterns of infection in New Zealand, elevational patterns are unexplored. To address this, a survey was conducted in Nelson Lakes National Park, a site experiencing native bird declines in which disease has been suggested as playing a role, to investigate whether there is a similar inverse relationship in New Zealand. Results from blood samples (n = 436) collected over three seasons across a broad elevational range (650–1400 m) support there being such a relationship. In addition, an overall higher prevalence in non-native (14.1%) versus native birds (1.7%) may indicate differential impacts on these two groups, while particularly high prevalence in non-native Turdus spp. supports previous suggestions that they are key reservoir hosts for the disease. Overall, these findings add weight to the hypothesis that avian malaria is playing a role in ongoing declines of native New Zealand birds. PMID:27802326

  8. Constrained by Our Connections: White Matter's Key Role in Interindividual Variability in Visual Working Memory Capacity

    PubMed Central

    Golestani, Ali M.; Miles, Laura; Babb, James; Castellanos, F. Xavier; Malaspina, Dolores

    2014-01-01

    Visual working memory (VWM) plays an essential role in many perceptual and higher-order cognitive processes. Despite its reliance on a broad network of brain regions, VWM has a capacity limited to a few objects. This capacity varies substantially across individuals and relates closely to measures of overall cognitive function (Luck and Vogel, 2013). The mechanisms underlying these properties are not completely understood, although the amplitude of neural signal oscillations (Vogel and Machizawa, 2004) and brain activation in specific cortical regions (Todd and Marois, 2004) have been implicated. Variability in VWM performance may also reflect variability in white matter structural properties. However, data based primarily on diffusion tensor imaging approaches remain inconclusive. Here, we investigate the relationship between white matter and VWM capacity in human subjects using an advanced diffusion imaging technique, diffusion kurtosis imaging. Diffusion kurtosis imaging provides several novel quantitative white mater metrics, among them the axonal water fraction (faxon), an index of axonal density and caliber. Our results show that 59% of individual variability in VWM capacity may be explained by variations in faxon within a widely distributed network of white matter tracts. Increased faxon associates with increased VWM capacity. An additional 12% in VWM capacity variance may be explained by diffusion properties of the extra-axonal space. These data demonstrate, for the first time, the key role of white matter in limiting VWM capacity in the healthy adult brain and suggest that white matter may represent an important therapeutic target in disorders of impaired VWM and cognition. PMID:25378158

  9. Key roles of the Broad-Complex gene in insect embryogenesis.

    PubMed

    Piulachs, Maria-Dolors; Pagone, Viviana; Bellés, Xavier

    2010-06-01

    The Broad-Complex (BR-C) is a primary response gene in the ecdysteroid signaling pathway which encodes a family of transcription factors that play a key role in metamorphic processes. With the aim of studying the possible functions of BR-C in the embryogenesis of a short germ band insect, we cloned BR-C cDNAs in the cockroach Blattella germanica (BgBR-C) and obtained the full coding region of six BR-C isoforms (Z1-Z6) of which, Z1-Z5 have homologous sequences in other insects, whereas Z6 is new. Temporal-expression patterns indicate that BgBR-C isoforms are present throughout the embryogenesis of B. germanica, although with weak fluctuations. Silencing all BgBR-C isoforms in the embryo through parental RNAi elicited a diversity of phenotypes. These phenotypes suggest roles for BgBR-C in different embryogenesis processes of B. germanica, mainly in the formation of the germ band, in the transition from 30% to 35% of total development, when the amnion and serosa rupture and the secondary dorsal organ is formed, and in the hatching process, which involves neural, endocrine and muscular coordination.

  10. Leu1 plays a role in iron metabolism and is required for virulence in Cryptococcus neoformans.

    PubMed

    Do, Eunsoo; Hu, Guanggan; Caza, Mélissa; Oliveira, Debora; Kronstad, James W; Jung, Won Hee

    2015-02-01

    Amino acid biosynthetic pathways that are absent in mammals are considered an attractive target for antifungal therapy. Leucine biosynthesis is one such target pathway, consisting of a five-step conversion process starting from the valine precursor 2-keto-isovalerate. Isopropylmalate dehydrogenase (Leu1) is an Fe-S cluster protein that is required for leucine biosynthesis in the model fungus Saccharomyces cerevisiae. The human pathogenic fungus Cryptococcus neoformans possesses an ortholog of S. cerevisiae Leu1, and our previous transcriptome data showed that the expression of LEU1 is regulated by iron availability. In this study, we characterized the role of Leu1 in iron homeostasis and the virulence of C. neoformans. We found that deletion of LEU1 caused leucine auxotrophy and that Leu1 may play a role in the mitochondrial-cytoplasmic Fe-S cluster balance. Whereas cytoplasmic Fe-S protein levels were not affected, mitochondrial Fe-S proteins were up-regulated in the leu1 mutant, suggesting that Leu1 mainly influences mitochondrial iron metabolism. The leu1 mutant also displayed increased sensitivity to oxidative stress and cell wall/membrane disrupting agents, which may have been caused by mitochondrial dysfunction. Furthermore, the leu1 mutant was deficient in capsule formation and showed attenuated virulence in a mouse inhalation model of cryptococcosis. Overall, our results indicate that Leu1 plays a role in iron metabolism and is required for virulence in C. neoformans.

  11. NHE8 plays an important role in mucosal protection via its effect on bacterial adhesion

    PubMed Central

    Liu, Chang; Xu, Hua; Zhang, Bo; Johansson, Malin E. V.; Li, Jing; Hansson, Gunnar C.

    2013-01-01

    The Na+/H+ exchanger NHE8 is expressed on the apical membrane of intestinal epithelial cells and is particularly abundant in the colon. Our previous study showed that Muc2 expression was significantly reduced in NHE8-knockout (NHE8−/−) mice, suggesting that NHE8 plays a role in mucosal protection in the colon. The current study confirms and extends our studies on the role of NHE8 in mucosal protection. The number of bacteria attached on the distal colon was significantly increased in NHE8−/− mice compared with their wild-type littermates. As expected, IL-4 expression was markedly increased in NHE8−/− mice compared with wild-type mice. Immunohistochemistry showed disorganization in the mucin layer of NHE8−/− mice, suggesting a possible direct bacteria-epithelia interaction. Furthermore, NHE8−/− mice were susceptible to dextran sodium sulfate-induced mucosal injury. In wild-type mice, dextran sodium sulfate treatment inhibited colonic NHE8 expression. In Caco-2 cells, the absence of NHE8 expression resulted in higher adhesion rates of Salmonella typhimurium but not Lactobacillus plantarum. Similarly, in vivo, S. typhimurium adhesion rate was increased in NHE8−/− mice compared with wild-type mice. Our study suggests that NHE8 plays important roles in protecting intestinal epithelia from infectious bacterial adherence. PMID:23657568

  12. May bacterial or pancreatic proteases play a critical role in inflammatory bowel disease?

    PubMed

    Qin, Xiaofa

    2014-09-21

    In a recent review paper, Carroll and Maharshak discussed a critical role of enteric bacterial proteases in the pathogenesis of inflammatory bowel disease (IBD). I take a great interest in this paper as I also suspected proteases, not from the bacteria, but those originated from the pancreas that failed to be inactivated in the lower gut due to a reduction in gut bacteria, may have played a critical role in the pathogenesis of IBD, which was first published more than a decade ago and discussed again in more detail in a recent paper published in this journal. Antibiotics may result in a big reduction in gut bacteria and bacterial proteases, but multiple studies demonstrated dramatic increased of pancreatic proteases like trypsin and chymotrypsin in the feces of animals or patients treated with antibiotics. Multiple large-scale studies also demonstrated use of antibiotics caused an increase but not decrease in the risk of developing IBD, suggesting impaired inactivation and degradation of pancreatic proteases may have played a more critical role in the pathogenesis of IBD.

  13. Sebox plays an important role during the early mouse oogenesis in vitro.

    PubMed

    Moreno, Dafne Linda; Salazar, Zayil; Betancourt, Miguel; Casas, Eduardo; Ducolomb, Yvonne; González, Cristina; Bonilla, Edmundo

    2014-02-01

    Oogenesis is a highly complex process that requires the exquisite temporal and spatial regulation of gene expression at multiple levels. Skin-embryo-brain-oocyte homeobox (Sebox) gene encodes a transcription factor that is highly expressed in germinal vesicle stage oocytes and that plays an essential role in early embryogenesis at the 2-cell stage in the mouse. As Sebox is also expressed in mouse fetal ovaries, the aim of the present study was to study its role during the early oogenesis in vitro. Expression of Sebox was low in 15.5 to 17.5 days post coitum (dpc) ovaries, showed a peak at 18.5 dpc and then its expression decreased dramatically in newborn ovaries. Sebox expression was efficiently knocked down (>80%) in fetal mouse ovary explants in culture using RNAi technology. When fetal ovary explants were transfected with Sebox-specific RNAi, the number of oocytes at germinal vesicle stage and showing a diameter of 40-70 μm was decreased significantly to 75% after 7 days of culture relative to the negative control, and to 22.4% after 10 days of culture, thus indicating that Sebox plays an important role in the early oogenesis in mice.

  14. p21 induction plays a dual role in anti-cancer activity of ursolic acid

    PubMed Central

    Zhang, Xudong; Song, Xinhua; Yin, Shutao; Zhao, Chong; Fan, Lihong

    2015-01-01

    Previous studies have shown that induction of G1 arrest and apoptosis by ursolic acid is associated with up-regulation of cyclin-dependent kinase inhibitor (CDKI) protein p21 in multiple types of cancer cells. However, the functional role of p21 induction in G1 cell cycle arrest and apoptosis, and the mechanisms of p21 induction by ursolic acid have not been critically addressed. In the current study, we demonstrated that p21 played a mediator role in G1 cell cycle arrest by ursolic acid, whereas p21-mediated up-regulation of Mcl-1 compromised apoptotic effect of ursolic acid. These results suggest that p21 induction plays a dual role in the anti-cancer activity of ursolic acid in terms of cell cycle and apoptosis regulation. p21 induction by ursolic acid was attributed to p53 transcriptional activation. Moreover, we found that ursolic acid was able to inhibit murine double minute-2 protein (MDM2) and T-LAK cell-originated protein kinase (TOPK), the two negative regulator of p53, which in turn contributed to ursolic acid-induced p53 activation. Our findings provided novel insights into understanding of the mechanisms involved in cell cycle arrest and apoptosis induction in response to ursolic acid exposure. PMID:26582056

  15. Does psychosocial stress play a role in the exacerbation of psoriasis?

    PubMed

    Hunter, H J A; Griffiths, C E M; Kleyn, C E

    2013-11-01

    It is widely accepted that psychosocial stress can result from the daily strains of living with a diagnosis of psoriasis. There is now an evolving body of work to suggest that psychosocial stress may also play a role in the exacerbation of psoriasis. We discuss the historical evidence supporting a temporal relationship between psychosocial stress and the exacerbation of psoriasis. The underlying pathophysiological mechanisms by which this occurs are largely unknown, but current evidence points towards a role for nerve-related factors, namely their interaction with mast cells and the potentiation of neurogenic inflammation in this regard. It is also likely that the physiological stress response in patients with psoriasis differs from that in healthy individuals, as evidenced by alterations in the hypothalamic-pituitary-adrenal axis and sympathetic-adrenal-medullary system function. Psychological stress results in a redistribution of leucocytes with increased trafficking of inflammatory cells into the skin, which may exacerbate psoriasis. Langerhans cells play a role in the stress response of normal skin; their function in the stress response of patients with psoriasis is open to speculation. We discuss the influence of stress reactivity in patients with psoriasis and the impact of stress reduction strategies in the management of psoriasis. Finally, we suggest potentially fruitful areas for future research.

  16. Mitochondria play an important role in the cell proliferation suppressing activity of berberine

    PubMed Central

    Yan, Xiao-Jin; Yu, Xuan; Wang, Xin-Pei; Jiang, Jing-Fei; Yuan, Zhi-Yi; Lu, Xi; Lei, Fan; Xing, Dong-Ming

    2017-01-01

    After being studied for approximately a century, berberine (BBR) has been found to act on various targets and pathways. A great challenge in the pharmacological analysis of BBR at present is to identify which target(s) plays a decisive role. In the study described herein, a rescue experiment was designed to show the important role of mitochondria in BBR activity. A toxic dose of BBR was applied to inhibit cell proliferation and mitochondrial activity, then α-ketobutyrate (AKB), an analogue of pyruvate that serves only as an electron receptor of NADH, was proven to partially restore cell proliferation. However, mitochondrial morphology damage and TCA cycle suppression were not recovered by AKB. As the AKB just help to regenerate NAD+, which is make up for part function of mitochondrial, the recovered cell proliferation stands for the contribution of mitochondria to the activity of BBR. Our results also indicate that BBR suppresses tumour growth and reduces energy charge and mitochondrial DNA (mtDNA) copy number in a HepG2 xenograft model. In summary, our study suggests that mitochondria play an important role in BBR activity regarding tumour cell proliferation and metabolism. PMID:28181523

  17. Leu1 plays a role in iron metabolism and is required for virulence in Cryptococcus neoformans

    PubMed Central

    Do, Eunsoo; Hu, Guanggan; Caza, Mélissa; Oliveira, Debora; Kronstad, James W.; Jung, Won Hee

    2015-01-01

    Amino acid biosynthetic pathways that are absent in mammals are considered an attractive target for antifungal therapy. Leucine biosynthesis is one such target pathway, consisting of a five-step conversion process starting from the valine precursor 2-keto-isovalerate. Isopropylmalate dehydrogenase (Leu1) is an Fe-S cluster protein that is required for leucine biosynthesis in the model fungus Saccharomyces cerevisiae. The human pathogenic fungus Cryptococcus neoformans possesses an ortholog of S. cerevisiae Leu1, and our previous transcriptome data showed that the expression of LEU1 is regulated by iron availability. In this study, we characterized the role of Leu1 in iron homeostasis and the virulence of C. neoformans. We found that deletion of LEU1 caused leucine auxotrophy and that Leu1 may play a role in the mitochondrial-cytoplasmic Fe-S cluster balance. Whereas cytoplasmic Fe-S protein levels were not affected, mitochondrial Fe-S proteins were up- regulated in the leu1 mutant, suggesting that Leu1 mainly influences mitochondrial iron metabolism. The leu1 mutant also displayed increased sensitivity to oxidative stress and cell wall/membrane disrupting agents, which may have been caused by mitochondrial dysfunction. Furthermore, the leu1 mutant was deficient in capsule formation and showed attenuated virulence in a mouse inhalation model of cryptococcosis. Overall, our results indicate that Leu1 plays a role in iron metabolism and is required for virulence in C. neoformans. PMID:25554701

  18. Cadherin2 (N-cadherin) plays an essential role in zebrafish cardiovascular development

    PubMed Central

    Bagatto, Brian; Francl, Jessie; Liu, Bei; Liu, Qin

    2006-01-01

    Background Cadherins are cell surface adhesion molecules that play important roles in development of vertebrate tissues and organs. We studied cadherin2 expression in developing zebrafish heart using in situ hybridization and immunocytochemical methods, and we found that cadherin2 was strongly expressed by the myocardium of the embryonic zebrafish. To gain insight into cadherin2 role in the formation and function of the heart, we analyzed cardiac differentiation and performance in a cadherin2 mutant, glass onion (glo). Results We found that the cadherin2 mutant had enlarged pericardial cavity, disorganized atrium and ventricle, and reduced expression of a ventricular specific marker vmhc. Individual myocardiocytes in the glo mutant embryos became round shaped and loosely aggregated. In vivo measurements of cardiac performance revealed that the mutant heart had significantly reduced heart rate, stroke volume and cardiac output compared to control embryos. Formation of the embryonic vascular system in the glo mutants was also affected. Conclusion Our results suggest that cadherin2 plays an essential role in zebrafish cardiovascular development. Although the exact mechanisms remain unknown as to the formation of the enlarged pericardium and reduced peripheral blood flow, it is clear that myocardiocyte differentiation and physiological cardiovascular performance is impaired when cadherin2 function is disrupted. PMID:16719917

  19. mTORC1 and mTORC2 play different roles in regulating cardiomyocyte differentiation from embryonic stem cells.

    PubMed

    Zheng, Bei; Wang, Jiadan; Tang, Leilei; Shi, Jiana; Zhu, Danyan

    2017-01-01

    Mammalian target of rapamycin (mTOR) is a serine/threonine kinase and functions through two distinct complexes, mTOR complex 1 (mTORC1) and complex 2 (mTORC2), with their key components Raptor and Rictor, to play crucial roles in cellular survival and growth. However, the roles of mTORC1 and mTORC2 in regulating cardiomyocyte differentiation from mouse embryonic stem (mES) cells are not clear. In this study, we performed Raptor or Rictor knockdown experiments to investigate the roles of mTORC1 and mTORC2 in cardiomyocyte differentiation. Ablation of Raptor markedly increased the number of cardiomyocytes derived from mES cells with well-organized myofilaments. Expression levels of brachyury (mesoderm protein), Nkx2.5 (cardiac progenitor cell protein), and α-Actinin (cardiomyocyte marker) were increased in Raptor knockdown cells. In contrast, loss of Rictor prevented cardiomyocyte differentiation. The dual ablation of Raptor and Rictor also decreased the number of cardiomyocytes. The two complexes exerted a regulatory mechanism in such a manner that knockdown of Raptor/mTORC1 resulted in a decreased phosphorylation of Rictor (Thr1135), which subsequently activated Rictor/mTORC2 in the differentiation of mES cells into cardiomyocytes. In conclusion, mTORC1 and mTORC2 played different roles in cardiomyocyte differentiation from mES cells in vitro. The activation of Rictor/mTORC2 was critical for facilitating cardiomyocyte differentiation from mES cells. Thus, this complex may be a promising target for regulating myocardial differentiation from embryonic stem cells or induced pluripotent stem cells.

  20. The MAT locus genes play different roles in sexual reproduction and pathogenesis in Fusarium graminearum.

    PubMed

    Zheng, Qian; Hou, Rui; Juanyu; Zhang; Ma, Jiwen; Wu, Zhongshou; Wang, Guanghui; Wang, Chenfang; Xu, Jin-Rong

    2013-01-01

    Sexual reproduction plays a critical role in the infection cycle of Fusarium graminearum because ascospores are the primary inoculum. As a homothallic ascomycete, F. graminearum contains both the MAT1-1 and MAT1-2-1 loci in the genome. To better understand their functions and regulations in sexual reproduction and pathogenesis, in this study we assayed the expression, interactions, and mutant phenotypes of individual MAT locus genes. Whereas the expression of MAT1-1-1 and MAT12-1 rapidly increased after perithecial induction and began to decline after 1 day post-perithecial induction (dpi), the expression of MAT1-1-2 and MAT1-1-3 peaked at 4 dpi. MAT1-1-2 and MAT1-1-3 had a similar expression profile and likely are controlled by a bidirectional promoter. Although none of the MAT locus genes were essential for perithecium formation, all of them were required for ascosporogenesis in self-crosses. In outcrosses, the mat11-1-2 and mat11-1-3 mutants were fertile but the mat1-1-1 and mat1-2-1 mutants displayed male- and female-specific defects, respectively. The mat1-2-1 mutant was reduced in FgSO expression and hyphal fusion. Mat1-1-2 interacted with all other MAT locus transcription factors, suggesting that they may form a protein complex during sexual reproduction. Mat1-1-1 also interacted with FgMcm1, which may play a role in controlling cell identity and sexual development. Interestingly, the mat1-1-1 and mat1-2-1 mutants were reduced in virulence in corn stalk rot assays although none of the MAT locus genes was important for wheat infection. The MAT1-1-1 and MAT1-2-1 genes may play a host-specific role in colonization of corn stalks.

  1. Role playing to train elementary teachers to use a classroom management “skill package”1

    PubMed Central

    Jones, Fredric H.; Eimers, Robert C.

    1975-01-01

    Two teachers who led regular third-grade classrooms in a suburban elementary school were trained via role-playing to use a broad range of social skills in dealing with group behavioral management in the classroom. Teacher training reduced disruptive student behavior during both seat work and group discussions in both classrooms. A measure of student productivity during arithmetic period in one classroom showed significant gains in arithmetic problems correct per day for the middle and bottom thirds of the class, with the bottom third increasing by 76%. PMID:16795507

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

    Cancer.gov

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

  3. Neutrophil extracellular Taps play an important role in clearance of Streptococcus suis in vivo.

    PubMed

    Zhao, Jianqing; Lin, Lan; Fu, Lei; Han, Li; Zhang, Anding

    2016-04-01

    Streptococcus suis infection induces formation of neutrophil extracellular traps (NETs) in vitro; however, the contribution of NETs-mediated killing to the pathogenesis of S. suis in vivo is yet to be elicited. The findings of the present study indicated that extracellular DNA fiber can be induced in a murine model in response to S. suis infection. A nuclease that destroys their structure was used to evaluate the role of NETs on S. suis infection. Treatment with nuclease resulted in a greater bacteria load and higher serum TNF-α concentrations in response to S. suis infection, indicating that NETs structure played an essential role in S. suis clearance and inflammation. Furthermore, nuclease treatment resulted in more severe clinical signs during and higher mortality from S. suis infection. These findings indicated that NETs structure contributes to protection against S. suis infection.

  4. Argumentation with restricted linguistic ability: performing a role play with aphasia or in a second language.

    PubMed

    Ahlsén, Elisabeth

    2005-01-01

    The main objective of this study is to illustrate how adaptation to linguistic limitations takes place in a specific activity and is affected by factors pertaining to the social activity or the individuals. A man with aphasia is compared to an adult immigrant L2 learner. An argumentative role play was video-recorded, transcribed and analysed. Both subjects have a very limited vocabulary and produce short utterances. The L2 learner often uses words that are semantically related to the target word, while the subject with aphasia uses more general and vague words, like pronouns, in combination with adverbs and set phrases. Both subjects use gesturing as strategy, and it is suggested that the semantic specificity of words as well as gestures is important in determining the role of gesture. Apart from gesture, he L2 learner uses mainly simplification and appeal strategies, while the subject with aphasia uses mainly fluency and sociolinguistic strategies.

  5. Do nonlinearities play a significant role in short term, beat-to-beat variability?

    NASA Technical Reports Server (NTRS)

    Choi, H. G.; Mukkamala, R.; Moody, G. B.; Mark, R. G.

    2001-01-01

    Numerous studies of short-term beat-to-beat variability in cardiovascular signals have not resolved the debate about the completeness of linear analysis techniques. This aim of this paper is to evaluate further the role of nonlinearities in short-term, beat-to-beat variability. We compared linear autoregressive moving average (ARMA) and nonlinear neural network (NN) models for predicting instantaneous heart rate (HR) and mean arterial blood pressure (BP) from past HR and BP. To evaluate these models, we used HR and BP time series from the MIMIC database. Experimental results indicate that NN-based nonlinearities do not play a significant role and suggest that ARMA linear analysis techniques provide adequate characterization of the system dynamics responsible for generating short-term, beat-to-beat variability.

  6. LKR/SDH Plays Important Roles throughout the Tick Life Cycle Including a Long Starvation Period

    PubMed Central

    Battur, Banzragch; Boldbaatar, Damdinsuren; Umemiya-Shirafuji, Rika; Liao, Min; Battsetseg, Badgar; Taylor, DeMar; Baymbaa, Badarch; Fujisaki, Kozo

    2009-01-01

    Background Lysine-ketoglutarate reductase/saccharopine dehydrogenase (LKR/SDH) is a bifunctional enzyme catalyzing the first two steps of lysine catabolism in plants and mammals. However, to date, the properties of the lysine degradation pathway and biological functions of LKR/SDH have been very little described in arthropods such as ticks. Methodology/Principal Findings We isolated and characterized the gene encoding lysine-ketoglutarate reductase (LKR, EC 1.5.1.8) and saccharopine dehydrogenase (SDH, EC 1.5.1.9) from a tick, Haemaphysalis longicornis, cDNA library that encodes a bifunctional polypeptide bearing domains similar to the plant and mammalian LKR/SDH enzymes. Expression of LKR/SDH was detected in all developmental stages, indicating an important role throughout the tick life cycle, including a long period of starvation after detachment from the host. The LKR/SDH mRNA transcripts were more abundant in unfed and starved ticks than in fed and engorged ticks, suggesting that tick LKR/SDH are important for the starved tick. Gene silencing of LKR/SDH by RNAi indicated that the tick LKR/SDH plays an integral role in the osmotic regulation of water balance and development of eggs in ovary of engorged females. Conclusions/Significance Transcription analysis and gene silencing of LKR/SDH indicated that tick LKR/SDH enzyme plays not only important roles in egg production, reproduction and development of the tick, but also in carbon, nitrogen and water balance, crucial physiological processes for the survival of ticks. This is the first report on the role of LKR/SDH in osmotic regulation in animals including vertebrate and arthropods. PMID:19774086

  7. T helper 17 cells play a critical pathogenic role in lung cancer

    PubMed Central

    Chang, Seon Hee; Mirabolfathinejad, Seyedeh Golsar; Katta, Harshadadevi; Cumpian, Amber M.; Gong, Lei; Caetano, Mauricio S.; Moghaddam, Seyed Javad; Dong, Chen

    2014-01-01

    Lung cancer development is associated with extensive pulmonary inflammation. In addition, the linkage between chronic obstructive pulmonary disease (COPD) and lung cancer has been demonstrated in population-based studies. IL-17–producing CD4 helper T cells (Th17 cells) play a critical role in promoting chronic tissue inflammation. Although Th17 cells are found in human COPD and lung cancer, their role is not understood. We have thus used a mouse model of lung cancer, in which an oncogenic form of K-ras (K-rasG12D), frequently found in human lung cancer, is restrictedly expressed in lung epithelial cells [via Clara cell secretory protein (CCSPcre)]. In this model, Th17 and Treg but not Th1 cells were found enriched at the tumor tissues. When CCSPcre/K-rasG12D mice were weekly challenged with a lysate of nontypeable Haemophilus influenza (NTHi), which induces COPD-type inflammation and accelerates the tumor growth, they showed greatly enhanced Th17 cell infiltration in the lung tissues. Lack of IL-17, but not IL-17F, resulted in a significant reduction in lung tumor numbers in CCSPcre/K-rasG12D mice and also those treated with NTHi. Absence of IL-17 not only resulted in reduction of tumor cell proliferation and angiogenesis, but also decreased the expression of proinflammatory mediators and reduced recruitment of myeloid cells. Depletion of Gr-1+CD11b+ myeloid cells in CCSPcre/K-rasG12D mice suppressed tumor growth in lung, indicating Gr-1+CD11b+ myeloid cells recruited by IL-17 play a protumor role. Taken together, our data demonstrate a critical role for Th17 cell-mediated inflammation in lung tumorigenesis and suggest a novel way for prevention and treatment of this disease. PMID:24706787

  8. Autocrine regulation of interferon gamma in mesenchymal stem cells plays a role in early osteoblastogenesis.

    PubMed

    Duque, Gustavo; Huang, Dao Chao; Macoritto, Michael; Rivas, Daniel; Yang, Xian Fang; Ste-Marie, Louis Georges; Kremer, Richard

    2009-03-01

    Interferon (IFN)gamma is a strong inhibitor of osteoclast differentiation and activity. However, its role in osteoblastogenesis has not been carefully examined. Using microarray expression analysis, we found that several IFNgamma-inducible genes were upregulated during early phases of osteoblast differentiation of human mesenchymal stem cells (hMSCs). We therefore hypothesized that IFNgamma may play a role in this process. We first observed a strong and transient increase in IFNgamma production following hMSC induction to differentiate into osteoblasts. We next blocked this endogenous production using a knockdown approach with small interfering RNA and observed a strong inhibition of hMSC differentiation into osteoblasts with a concomitant decrease in Runx2, a factor indispensable for osteoblast development. Additionally, exogenous addition of IFNgamma accelerated hMSC differentiation into osteoblasts in a dose-dependent manner and induced higher levels of Runx2 expression during the early phase of differentiation. We next examined IFNgamma signaling in vivo in IFNgamma receptor 1 knockout (IFNgammaR1(-/-)) mice. Compared with their wild-type littermates, IFNgammaR1(-/-) mice exhibited a reduction in bone mineral density. As in the in vitro experiments, MSCs obtained from IFNgammaR1(-/-) mice showed a lower capacity to differentiate into osteoblasts. In summary, we demonstrate that the presence of IFNgamma plays an important role during the commitment of MSCs into the osteoblastic lineage both in vitro and in vivo, and that this process can be accelerated by exogenous addition of IFNgamma. These data therefore support a new role for IFNgamma as an autocrine regulator of hMSC differentiation and as a potential new target of bone-forming cells in vivo.

  9. The Key Role of Nitrogenated Aromatics in Interstellar and Planetary Evolution and the Formation of Life

    NASA Astrophysics Data System (ADS)

    Bakes, Emma

    2004-05-01

    Nitrogenated heterocyclics can dominate the chemistry and thermodynamics of key regions, from interstellar clouds to planetary atmospheres. A nitrogenated hydrocarbon haze around a planet, or a moon such as Titan, dominates its temperature, atmospheric circulation and climate control. Photochemistry plays a key role in the structure and evolution of the haze. A detailed knowledge of haze photochemistry provides a deeper understanding of the global properties of the planet. It can also provide information about primitive terrestrial atmospheric chemistry on early Earth. Pyrrolysis of Titan tholin, a laboratory simulated atmospheric haze contains over 100 identified products, including aliphatic hydrocarbons, aromatic hydrocarbons, nitriles, amines, pyrroles (e.g. coenzymes), pyrazines (molecules which function in the earthy tastes and smells of food), pyridines (e.g. cofactors) and pyrimidines (RNA and DNA building blocks) (Khare et al. 1984). Heterocyclic molecules such as those synthesized in a reducing haze have played an important role in the evolution of life. Most coenzymes and vitamins contain a central heterocyclic ring which is necessary to fulfill the biological function of the coenzyme. This observation has spawned the idea that coenzymes were formed early in the history of life and may have been present during the prebiotic period of terrestrial evolution. Could they have originated as a product of atmospheric gas phase chemistry in the reducing, nitrogenated atmosphere of early Earth? Nucleic acids are composed of three different building blocks, namely a sugar, a phosphate and an organic base which may be either a purine or a pyrimidine. These three building blocks form a nucleotide, the basic building block of nucleic acids. RNA contains a ribose sugar and the purines are adenine and guanine, while the pyrimidines are cytosine and uracil. The production of these building blocks is the first step towards the ``RNA World''. These structures are

  10. Contextual Differences in Parent-Child Play: Implications for Children's Gender Role Development.

    ERIC Educational Resources Information Center

    Lindsey, Eric W.; Mize, Jacquelyn

    2001-01-01

    Videotaped parent-child play behaviors of preschool children in pretend and physical play sessions, noting children's play with same-sex peers. Context influenced gender differentiated patterns of parent-child play behavior. Girls engaged in more pretend play, and boys were engaged in more physical play with peers. Parents contributed to…

  11. World of Wordcraft: Foreign Language Grammar and Composition Taught as a Term-Long Role-Playing Game

    ERIC Educational Resources Information Center

    Gellar-Goad, T. H. M.

    2015-01-01

    This article outlines an innovative approach to the instruction of foreign languages: a term-long role-playing game in the style of tabletop role-playing games such as "Dungeons & Dragons." Students adopt personas, avatars, or "player characters" and take them through adventures, exploration, puzzles, and fights with…

  12. Staff Training for Business Process Improvement: The Benefit of Role-Plays in the Case of KreditSim

    ERIC Educational Resources Information Center

    Borner, Rene; Moormann, Jurgen; Wang, Minhong

    2012-01-01

    Purpose: The paper aims to explore staff's experience with role-plays using the example of training bank employees in Six Sigma as a major methodology for business process improvement. Design/methodology/approach: The research is based on a case study. A role-play, KreditSim, is used to simulate a loan approval process that has to be improved by…

  13. The Assessment of Elaborated Role-Play in Young Children: Invisible Friends, Personified Objects, and Pretend Identities

    ERIC Educational Resources Information Center

    Taylor, Marjorie; Sachet, Alison B.; Maring, Bayta L.; Mannering, Anne M.

    2013-01-01

    Role-play (i.e., pretending in which children imagine and act out the part of another individual) was assessed with child interviews and parent questionnaires about invisible friends, personified objects, and pretend identities in a sample of 208 young children. Children who engaged in role-play did not differ from other children in age or…

  14. Teaching Social Communication Skills Using a Cool versus Not Cool Procedure plus Role-Playing and a Social Skills Taxonomy

    ERIC Educational Resources Information Center

    Leaf, Justin B.; Taubman, Mitchell; Milne, Christine; Dale, Stephanie; Leaf, Jeremy; Townley-Cochran, Donna; Tsuji, Kathleen; Kassardjian, Alyne; Alcalay, Aditt; Leaf, Ronald; McEachin, John

    2016-01-01

    We utilized a cool versus not cool procedure plus role-playing to teach social communication skills to three individuals diagnosed with autism spectrum disorder. The cool versus not cool procedure plus role-playing consisted of the researcher randomly demonstrating the behavior correctly (cool) two times and the behavior incorrectly (not cool) two…

  15. Effects of a single-session assertiveness music therapy role playing protocol for psychiatric inpatients.

    PubMed

    Silverman, Michael J

    2011-01-01

    The purpose of this study was to implement and measure the effectiveness of a single-session assertiveness music therapy role playing protocol for psychiatric inpatients. Participants (N=133) were randomly assigned by group to one of three conditions: (a) Assertiveness Music Therapy, (b) No Music Assertiveness, or (c) Music No Assertiveness. Participants in both assertiveness conditions role played a number of different commonly occurring scenarios at an inpatient psychiatric facility and in the community. There were no significant between-group differences in posttest quality of life, locus of control, or other subscales. However, participants in both assertiveness conditions tended to have slightly higher internal locus of control and overall quality of life scores than participants in the music no assertiveness condition. Additionally, the assertiveness music therapy condition had higher attendance rates than the other conditions. A higher percentage of participants from both the assertiveness music therapy and music no assertiveness conditions indicated they thought their session was the most helpful/therapeutic group therapy session in which they had participated; this was not the case for the assertiveness no music condition. Future research is warranted to measure the effects of protocols that can help psychiatric patients generalize skills learned in treatment.

  16. Osterix plays a critical role in BMP4-induced promoter activity of connexin43.

    PubMed

    Han, Younho; Cho, Dong Hyeok; Chung, Dong Jin; Lee, Kwang Youl

    2016-09-16

    Osterix is an essential transcription factor for osteogenesis and is expressed in osteoblasts. Although Osterix has been shown to be induced by bone morphogenetic protein 4, the molecular mechanism underlying Osterix function during osteoblast differentiation remains unclear. Connexin43 (Cx43) is the most abundant gap junction protein in bone cells and plays a critical role in osteoblast differentiation. However, little is known about the functional interactions between Osterix and the Cx43 promoter. In the present study, we investigated the relationship between Osterix and Cx43 in HEK293 and C2C12 cells. Cx43 expression was significantly repressed by the addition of shRNA against Osterix, whereas overexpression of Osterix resulted in enhanced Cx43 expression. Furthermore, Osterix directly occupied the promoter region of Cx43 and subsequently increased Cx43 promoter activity in a dose-dependent manner. In addition, phosphorylation of the Ser76 and Ser80 residues in Osterix were found to be critical for its activity on the Cx43 promoter. Our results suggest that Osterix plays an important role in increasing bone morphogenetic protein 4-induced Cx43 activity.

  17. Myocardin marks the earliest cardiac gene expression and plays an important role in heart development.

    PubMed

    Chen, Jian-Fu; Wang, Shusheng; Wu, Qiulian; Cao, Dongsun; Nguyen, Thiha; Chen, Yiping; Wang, Da-Zhi

    2008-10-01

    Myocardin belongs to the SAP domain family of transcription factors and is expressed specifically in cardiac and smooth muscle during embryogenesis and in adulthood. Myocardin functions as a transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression. However, the in vivo function of myocardin during cardiogenesis is not completely understood. Here we clone myocardin from chick embryonic hearts and show that myocardin protein sequences are highly conserved cross species. Detailed studies of chick myocardin expression reveal that myocardin is expressed in cardiac and smooth muscle lineage during early embryogenesis, similar to that found in mouse. Interestingly, the expression of myocardin in the heart was found enriched in the outflow tract and the sinoatrial segments shortly after the formation of linear heart tube. Such expression pattern is also maintained in later developing embryos, suggesting that myocardin may play a unique role in the formation of those cardiac modules. Similar to its mouse counterpart, chick myocardin is able to activate cardiac and smooth muscle promoter reporter genes and induce smooth muscle gene expression in nonmuscle cells. Ectopic overexpression of myocardin enlarged the embryonic chick heart. Conversely, repression of the endogenous chick myocardin using antisense oligonucleotides or a dominant negative mutant form of myocardin inhibited cardiogenesis. Together, our data place myocardin as one of the earliest cardiac marker genes for cardiogenesis and support the idea that myocardin plays an essential role in cardiac gene expression and cardiogenesis.

  18. Lysosomal integral membrane protein Sidt2 plays a vital role in insulin secretion.

    PubMed

    Gao, Jialin; Yu, Cui; Xiong, Qianyin; Zhang, Yao; Wang, Lizhuo

    2015-01-01

    Abnormal insulin secretion results in impaired glucose tolerance and is one of the causal factors in the etiology of type 2 diabetes mellitus. Sidt2, a lysosomal integral membrane protein, plays a critical role in insulin secretion. Here, we further investigate its regulation in insulin secretion. We show that Sidt2(-/-) mice exhibit weight loss, decreased postnatal survival rate with aging, increased fasting glucose and impaired glucose tolerance. After loading high levels of glucose in their diet, Sidt2(-/-) mice produce notably lower insulin levels at the first-phase secretion compared with Sidt2(+/+) mice. Consistent with the in vivo study, INS-1 cells treated with Sidt2 siRNA produced less insulin when loaded with 16.7 mM of glucose. Only 2 of the 13 genes, synap1 and synap3 which encode soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, showed significantly decreased expression in Sidt2(-/-) mice. In conclusion, Sdit2 may play a vital role in the regulation of insulin secretion via two SNARE proteins synap1 and syanp3.

  19. Do As I Say: Using Communication Role-Plays to Assess Sexual Assertiveness Following an Intervention.

    PubMed

    Mercer Kollar, Laura M; Davis, Teaniese L; Monahan, Jennifer L; Samp, Jennifer A; Coles, Valerie B; Bradley, Erin L P; Sales, Jessica McDermott; Comer, Sarah K; Worley, Timothy; Rose, Eve; DiClemente, Ralph J

    2016-12-01

    Sexual risk reduction interventions are often ineffective for women who drink alcohol. The present study examines whether an alcohol-related sexual risk reduction intervention successfully trains women to increase assertive communication behaviors and decrease aggressive communication behaviors. Women demonstrated their communication skills during interactive role-plays with male role-play partners. Young, unmarried, and nonpregnant African American women (N = 228, ages 18-24) reporting unprotected vaginal or anal sex and greater than three alcoholic drinks in the past 90 days were randomly assigned to a control, a sexual risk reduction, or a sexual and alcohol risk reduction (NLITEN) condition. Women in the NLITEN condition significantly increased assertive communication behavior compared to women in the control condition, yet use of aggressive communicative behaviors was unchanged. These data suggest assertive communication training is an efficacious component of a sexual and alcohol risk reduction intervention. Public health practitioners and health educators may benefit from group motivational enhancement therapy (GMET) training and adding a GMET module to existing sexual health risk reduction interventions. Future research should examine GMET's efficacy in combination with other evidence-based interventions within other populations and examine talking over and interrupting one's sexual partner as an assertive communication behavior within sexual health contexts.

  20. The kidneys play a central role in the clearance of rhGH in rats.

    PubMed

    Vestergaard, Bill; Thygesen, Peter; Kreilgaard, Mads; Fels, Johannes Josef; Lykkesfeldt, Jens; Agersø, Henrik

    2016-04-30

    The kidneys are thought to play an important role in the clearance of recombinant human growth hormone (rhGH), but the relative importance is not clear. Obtaining knowledge of clearance pathway is an important prerequisite for the development of new long acting growth hormone analogues targeted at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rhGH in non-anesthetized rats, anesthetized rats and in nephrectomized anesthetized rats. Clearance in non-anesthetized rats was 290 ml/h/kg. This was reduced to 185 ml/h/kg by anesthesia and further reduced to 18 ml/h/kg by nephrectomy. As nephrectomy was able to reduce clearance with 90%, we conclude that renal clearance plays a pivotal role in the elimination of rhGH in rats.