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  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. 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)

  3. Abscisic acid uridine diphosphate glucosyltransferases play a crucial role in abscisic acid homeostasis in Arabidopsis.

    PubMed

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

    2014-05-01

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

  4. Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells.

    PubMed

    Saitoh, Sayaka; Maruyama, Takeshi; Yako, Yuta; Kajita, Mihoko; Fujioka, Yoichiro; Ohba, Yusuke; Kasai, Nobuhiro; Sugama, Natsu; Kon, Shunsuke; Ishikawa, Susumu; Hayashi, Takashi; Yamazaki, Tomohiro; Tada, Masazumi; Fujita, Yasuyuki

    2017-03-21

    Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have elucidated the functional involvement of endocytosis in the elimination of RasV12-transformed cells. First, we show that Rab5, a crucial regulator of endocytosis, is accumulated in RasV12-transformed cells that are surrounded by normal epithelial cells, which is accompanied by up-regulation of clathrin-dependent endocytosis. Addition of chlorpromazine or coexpression of a dominant-negative mutant of Rab5 suppresses apical extrusion of RasV12 cells from the epithelium. We also show in zebrafish embryos that Rab5 plays an important role in the elimination of transformed cells from the enveloping layer epithelium. In addition, Rab5-mediated endocytosis of E-cadherin is enhanced at the boundary between normal and RasV12 cells. Rab5 functions upstream of epithelial protein lost in neoplasm (EPLIN), which plays a positive role in apical extrusion of RasV12 cells by regulating protein kinase A. Furthermore, we have revealed that epithelial defense against cancer (EDAC) from normal epithelial cells substantially impacts on Rab5 accumulation in the neighboring transformed cells. This report demonstrates that Rab5-mediated endocytosis is a crucial regulator for the competitive interaction between normal and transformed epithelial cells in mammals.

  5. Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient.

    PubMed

    Shimojima, Masaya; Yuasa, Shinsuke; Motoda, Chikaaki; Yozu, Gakuto; Nagai, Toshihiro; Ito, Shogo; Lachmann, Mark; Kashimura, Shin; Takei, Makoto; Kusumoto, Dai; Kunitomi, Akira; Hayashiji, Nozomi; Seki, Tomohisa; Tohyama, Shugo; Hashimoto, Hisayuki; Kodaira, Masaki; Egashira, Toru; Hayashi, Kenshi; Nakanishi, Chiaki; Sakata, Kenji; Yamagishi, Masakazu; Fukuda, Keiichi

    2017-03-14

    Alteration of the nuclear Ca(2+) transient is an early event in cardiac remodeling. Regulation of the nuclear Ca(2+) transient is partly independent of the cytosolic Ca(2+) transient in cardiomyocytes. One nuclear membrane protein, emerin, is encoded by EMD, and an EMD mutation causes Emery-Dreifuss muscular dystrophy (EDMD). It remains unclear whether emerin is involved in nuclear Ca(2+) homeostasis. The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca(2+) transient. The cardiac hypertrophic stimuli increased the nuclear area, decreased nuclear invagination, and increased the half-decay time of the nuclear Ca(2+) transient in cardiomyocytes. Emd knockdown cardiomyocytes showed similar properties after hypertrophic stimuli. The EDMD-iPS cell-derived cardiomyocytes showed increased nuclear area, decreased nuclear invagination, and increased half-decay time of the nuclear Ca(2+) transient. An autopsied heart from a patient with EDMD also showed increased nuclear area and decreased nuclear invagination. These data suggest that Emerin plays a crucial role in nuclear structure and in the nuclear Ca(2+) transient. Thus, emerin and the nuclear Ca(2+) transient are possible therapeutic targets in heart failure and EDMD.

  6. Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient

    PubMed Central

    Shimojima, Masaya; Yuasa, Shinsuke; Motoda, Chikaaki; Yozu, Gakuto; Nagai, Toshihiro; Ito, Shogo; Lachmann, Mark; Kashimura, Shin; Takei, Makoto; Kusumoto, Dai; Kunitomi, Akira; Hayashiji, Nozomi; Seki, Tomohisa; Tohyama, Shugo; Hashimoto, Hisayuki; Kodaira, Masaki; Egashira, Toru; Hayashi, Kenshi; Nakanishi, Chiaki; Sakata, Kenji; Yamagishi, Masakazu; Fukuda, Keiichi

    2017-01-01

    Alteration of the nuclear Ca2+ transient is an early event in cardiac remodeling. Regulation of the nuclear Ca2+ transient is partly independent of the cytosolic Ca2+ transient in cardiomyocytes. One nuclear membrane protein, emerin, is encoded by EMD, and an EMD mutation causes Emery-Dreifuss muscular dystrophy (EDMD). It remains unclear whether emerin is involved in nuclear Ca2+ homeostasis. The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca2+ transient. The cardiac hypertrophic stimuli increased the nuclear area, decreased nuclear invagination, and increased the half-decay time of the nuclear Ca2+ transient in cardiomyocytes. Emd knockdown cardiomyocytes showed similar properties after hypertrophic stimuli. The EDMD-iPS cell-derived cardiomyocytes showed increased nuclear area, decreased nuclear invagination, and increased half-decay time of the nuclear Ca2+ transient. An autopsied heart from a patient with EDMD also showed increased nuclear area and decreased nuclear invagination. These data suggest that Emerin plays a crucial role in nuclear structure and in the nuclear Ca2+ transient. Thus, emerin and the nuclear Ca2+ transient are possible therapeutic targets in heart failure and EDMD. PMID:28290476

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

    PubMed Central

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

    2016-01-01

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

  8. SIRT1 may play a crucial role in overload induced hypertrophy of skeletal muscle.

    PubMed

    Koltai, Erika; Bori, Zoltán; Chabert, Clovis; Dubouchaud, Hervé; Naito, Hisashi; Machida, Shuichi; Davies, Kelvin Ja; Murlasits, Zsolt; Fry, Andrew C; Boldogh, Istvan; Radak, Zsolt

    2017-03-02

    Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well-studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus, and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in SIRT1 content and activity (P < 0.001). SIRT1-regulated Akt, eNOS, GLUT4 levels were also induced in hypertrophied muscles, and SIRT1 levels correlated with muscle mass, paired box protein 7 (Pax7), proliferating cell nuclear antigen (PCNA) and nicotinamide phosphoribosyltransferase (Nampt) levels. Alternatively, decreased FOXO1 and increased K48 polyubiquitination also suggest that SIRT1 could also be involved in the catabolic process of hypertrophy. Furthermore, increased levels of K63 and muscle RING finger 2 (MuRF2) protein could also be important enhancers of muscle mass. We report here that the levels of miR1 and miR133a decrease in hypertrophy and negatively correlate with muscle mass, SIRT1, and Nampt levels. Our results reveal a strong agreement between SIRT1 levels and activity, SIRT1 regulated pathways, and overload-induced hypertrophy. These findings, along with the well-known regulatory roles that SIRT1 plays in modulating both anabolic and catabolic pathways, allow us to propose the hypothesis that SIRT1 may actually play a crucial causal role in overload induced hypertrophy of skeletal muscle. This hypothesis will now require rigorous direct and functional testing. This article is protected by copyright. All rights reserved.

  9. ING2 (inhibitor of growth protein-2) plays a crucial role in preimplantation development.

    PubMed

    Zhou, Lin; Wang, Pei; Zhang, Juanjuan; Heng, Boon Chin; Tong, Guo Qing

    2016-02-01

    ING2 (inhibitor of growth protein-2) is a member of the ING-gene family and participates in diverse cellular processes involving tumor suppression, DNA repair, cell cycle regulation, and cellular senescence. As a subunit of the Sin3 histone deacetylase complex co-repressor complex, ING2 binds to H3K4me3 to regulate chromatin modification and gene expression. Additionally, ING2 recruits histone methyltransferase (HMT) activity for gene repression, which is independent of the HDAC class I or II pathway. However, the physiological function of ING2 in mouse preimplantation embryo development has not yet been characterized previously. The expression, localization and function of ING2 during preimplantation development were investigated in this study. We showed increasing expression of ING2 within the nucleus from the 4-cell embryo stage onwards; and that down-regulation of ING2 expression by endoribonuclease-prepared small interfering RNA (esiRNA) microinjection results in developmental arrest during the morula to blastocyst transition. Embryonic cells microinjected with ING2-specific esiRNA exhibited decreased blastulation rate compared to the negative control. Further investigation of the underlying mechanism indicated that down-regulation of ING2 significantly increased expression of p21, whilst decreasing expression of HDAC1. These results suggest that ING2 may play a crucial role in the process of preimplantation embryo development through chromatin regulation.

  10. Decorin induced by progesterone plays a crucial role in suppressing endometriosis.

    PubMed

    Ono, Yoshihiro Joshua; Terai, Yoshito; Tanabe, Akiko; Hayashi, Atsushi; Hayashi, Masami; Yamashita, Yoshiki; Kyo, Satoru; Ohmichi, Masahide

    2014-11-01

    Dienogest, a synthetic progestin, has been shown to be effective against endometriosis, although it is still unclear as to how it affects the ectopic endometrial cells. Decorin has been shown to be a powerful endogenous tumor repressor acting in a paracrine fashion to limit tumor growth. Our objectives were to examine the direct effects of progesterone and dienogest on the in vitro proliferation of the human ectopic endometrial epithelial and stromal cell lines, and evaluate as to how decorin contributes to this effect. We also examined DCN mRNA expression in 50 endometriosis patients. The growth of both cell lines was inhibited in a dose-dependent manner by both decorin and dienogest. Using a chromatin immunoprecipitation assay, it was noted that progesterone and dienogest directly induced the binding of the decorin promoter in the EMOsis cc/TERT cells (immortalized human ovarian epithelial cells) and CRL-4003 cells (immortalized human endometrial stromal cells). Progesterone and dienogest also led to significant induced cell cycle arrest via decorin by promoting production of p21 in both cell lines in a dose-dependent manner. Decorin also suppressed the expression of MET in both cell lines. We confirmed that DCN mRNA expression in patients treated with dienogest was higher than that in the control group. In conclusion, decorin induced by dienogest appears to play a crucial role in suppressing endometriosis by exerting anti-proliferative effects and inducing cell cycle arrest via the production of p21 human ectopic endometrial cells and eutopic endometrial stromal cells.

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

    PubMed

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

    2011-12-01

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

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

    PubMed Central

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

    2004-01-01

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

  13. Muscarinic cholinergic receptor (M2) plays a crucial role in the development of myopia in mice.

    PubMed

    Barathi, Veluchamy A; Kwan, Jia Lin; Tan, Queenie S W; Weon, Sung Rhan; Seet, Li Fong; Goh, Liang Kee; Vithana, Eranga N; Beuerman, Roger W

    2013-09-01

    Myopia is a huge public health problem worldwide, reaching the highest incidence in Asia. Identification of susceptible genes is crucial for understanding the biological basis of myopia. In this paper, we have identified and characterized a functional myopia-associated gene using a specific mouse-knockout model. Mice lacking the muscarinic cholinergic receptor gene (M2; also known as Chrm2) were less susceptible to lens-induced myopia compared with wild-type mice, which showed significantly increased axial length and vitreous chamber depth when undergoing experimental induction of myopia. The key findings of this present study are that the sclera of M2 mutant mice has higher expression of collagen type I and lower expression of collagen type V than do wild-type mice and mice that are mutant for other muscarinic subtypes, and, therefore, M2 mutant mice were resistant to the development of experimental myopia. Pharmacological blockade of M2 muscarinic receptor proteins retarded myopia progression in the mouse. These results suggest for the first time a role of M2 in growth-related changes in extracellular matrix genes during myopia development in a mammalian model. M2 receptor antagonists might thus provide a targeted therapeutic approach to the management of this refractive error.

  14. The ovarian hormone estradiol plays a crucial role in the control of food intake in females

    PubMed Central

    Eckel, Lisa A.

    2011-01-01

    Despite a strong male bias in both basic and clinical research, it is becoming increasingly accepted that the ovarian hormone estradiol plays an important role in the control of food intake in females. Estradiol’s feeding inhibitory effect occurs in a variety of species, including women, but the underlying mechanism has been studied most extensively in rats and mice. Accordingly, much of the data reviewed here is derived from the rodent literature. Adult female rats display a robust decrease in food intake during estrus and ovariectomy promotes hyperphagia and weight gain, both of which can be prevented by a physiological regimen of estradiol treatment. Behavioral analyses have demonstrated that the feeding inhibitory effect of estradiol is mediated entirely by a decrease in meal size. In rats, estradiol appears to exert this action indirectly via interactions with peptide and neurotransmitter systems implicated in the direct control of meal size. Here, I summarize research examining the neurobiological mechanism underlying estradiol’s anorexigenic effect. Central estrogen receptors (ERs) have been implicated and activation of one ER subtype in particular, ERα, appears both sufficient and necessary for the estrogenic control of food intake. Future studies are necessary to identify the critical brain areas and intracellular signaling pathways responsible for estradiol’s anorexigenic effect. A clearer understanding of the estrogenic control of food intake is prerequisite to elucidating the biological factors that contribute to obesity and eating disorders, both of which are more prevalent in women, compared to men. PMID:21530561

  15. Olfactory receptor accessory proteins play crucial roles in receptor function and gene choice

    PubMed Central

    Sharma, Ruchira; Ishimaru, Yoshiro; Davison, Ian; Ikegami, Kentaro; Chien, Ming-Shan; You, Helena; Chi, Quiyi; Kubota, Momoka; Yohda, Masafumi; Ehlers, Michael; Matsunami, Hiroaki

    2017-01-01

    Each of the olfactory sensory neurons (OSNs) chooses to express a single G protein-coupled olfactory receptor (OR) from a pool of hundreds. Here, we show the receptor transporting protein (RTP) family members play a dual role in both normal OR trafficking and determining OR gene choice probabilities. Rtp1 and Rtp2 double knockout mice (RTP1,2DKO) show OR trafficking defects and decreased OSN activation. Surprisingly, we discovered a small subset of the ORs are expressed in larger numbers of OSNs despite the presence of fewer total OSNs in RTP1,2DKO. Unlike typical ORs, some overrepresented ORs show robust cell surface expression in heterologous cells without the co-expression of RTPs. We present a model in which developing OSNs exhibit unstable OR expression until they choose to express an OR that exits the ER or undergo cell death. Our study sheds light on the new link between OR protein trafficking and OR transcriptional regulation. DOI: http://dx.doi.org/10.7554/eLife.21895.001 PMID:28262096

  16. 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.

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

    PubMed

    Avenanti, Alessio; Urgesi, Cosimo

    2011-06-01

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

  18. Erythrocyte membrane sulfatide plays a crucial role in the adhesion of sickle erythrocytes to endothelium.

    PubMed

    Zhou, Z; Thiagarajan, P; Udden, M; Lòpez, J A; Guchhait, P

    2011-06-01

    Enhanced adhesion of sickle erythrocytes to the vascular endothelium and subendothelial matrix is fundamental to the development of vascular occlusion in sickle cell disease. Erythrocyte membrane sulfatide is implicated in the pathogenesis of vasoocclusive crises in sickle cell disease (SCD) patients. Because previous evidence linking sulfatide to cell adhesion has largely been circumstantial due to a lack of reagents that specifically target sulfatide, we used two sulfatide-specific strategies to address the role of erythrocyte membrane sulfatide in sickle cell adhesion to the vascular endothelium: a single-chain fragment variable chain (scFv) antibody against sulfatide as well as cerebroside sulfotransferase-deficient mice incapable of synthesising sulfatide. The sickle erythrocytes from mice and humans adhered at a greater extent and at higher shear stresses to activated endothelium than normal erythrocytes, and approximately 60% of the adhesion was prevented by the anti-sulfatide scFv. Similarly, the extent of adhesion of sulfatide-deficient erythrocytes was lower than normal erythrocytes. These findings suggest an important role for membrane sulfatide in sickle cell disease pathophysiology.

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

    PubMed Central

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

    2015-01-01

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

  20. Rice WRKY45 plays a crucial role in benzothiadiazole-inducible blast resistance.

    PubMed

    Shimono, Masaki; Sugano, Shoji; Nakayama, Akira; Jiang, Chang-Jie; Ono, Kazuko; Toki, Seiichi; Takatsuji, Hiroshi

    2007-06-01

    Benzothiadiazole (BTH) is a so-called plant activator and protects plants from diseases by activating the salicylic acid (SA) signaling pathway. By microarray screening, we identified BTH- and SA-inducible WRKY transcription factor (TF) genes that were upregulated within 3 h after BTH treatment. Overexpression of one of them, WRKY45, in rice (Oryza sativa) markedly enhanced resistance to rice blast fungus. RNA interference-mediated knockdown of WRKY45 compromised BTH-inducible resistance to blast disease, indicating that it is essential for BTH-induced defense responses. In a transient expression system, WRKY45 activated reporter gene transcription through W-boxes. Epistasis analysis suggested that WRKY45 acts in the SA signaling pathway independently of NH1, a rice ortholog of Arabidopsis thaliana NPR1, which distinguishes WRKY45 from known Arabidopsis WRKY TFs. Two defense-related genes, encoding a glutathione S-transferase and a cytochrome P450, were found to be regulated downstream of WRKY45 but were not regulated by NH1, consistent with the apparent independence of the WRKY45- and NH1-dependent pathways. Defense gene expression in WRKY45-overexpressed rice plants varied with growth conditions, suggesting that some environmental factor(s) acts downstream of WRKY45 transcription. We propose a role for WRKY45 in BTH-induced and SA-mediated defense signaling in rice and its potential utility in improving disease resistance of rice, an importance food resource worldwide.

  1. The Guanine-Nucleotide Exchange Factor SGEF Plays a Crucial Role in the Formation of Atherosclerosis

    PubMed Central

    Kroon, Jeffrey; Welch, Christopher; Bakker, Erik N.; Matlung, Hanke L.; van den Berg, Timo K.; Sharek, Lisa; Doerschuk, Claire; Hahn, Klaus; Burridge, Keith

    2013-01-01

    The passage of leukocytes across the endothelium and into arterial walls is a critical step in the development of atherosclerosis. Previously, we showed in vitro that the RhoG guanine nucleotide exchange factor SGEF (Arhgef26) contributes to the formation of ICAM-1-induced endothelial docking structures that facilitate leukocyte transendothelial migration. To further explore the in vivo role of this protein during inflammation, we generated SGEF-deficient mice. When crossed with ApoE null mice and fed a Western diet, mice lacking SGEF showed a significant decrease in the formation of atherosclerosis in multiple aortic areas. A fluorescent biosensor revealed local activation of RhoG around bead-clustered ICAM-1 in mouse aortic endothelial cells. Notably, this activation was decreased in cells from SGEF-deficient aortas compared to wild type. In addition, scanning electron microscopy of intimal surfaces of SGEF−/− mouse aortas revealed reduced docking structures around beads that were coated with ICAM-1 antibody. Similarly, under conditions of flow, these beads adhered less stably to the luminal surface of carotid arteries from SGEF−/− mice. Taken together, these results show for the first time that a Rho-GEF, namely SGEF, contributes to the formation of atherosclerosis by promoting endothelial docking structures and thereby retention of leukocytes at athero-prone sites of inflammation experiencing high shear flow. SGEF may therefore provide a novel therapeutic target for inhibiting the development of atherosclerosis. PMID:23372835

  2. Prenatal myonuclei play a crucial role in skeletal muscle hypertrophy in rodents.

    PubMed

    Kawano, Fuminori; Ono, Yusuke; Fujita, Ryo; Watanabe, Atsuya; Masuzawa, Ryo; Shibata, Kazuhiro; Hasegawa, Shunsuke; Nakata, Ken; Nakai, Naoya

    2017-03-01

    Multinucleated muscle fibers are formed by the fusion of myogenic progenitor cells during embryonic and fetal myogenesis. However, the role of prenatally incorporated myonuclei in the skeletal muscle fibers of adult animals is poorly understood. We demonstrated, using muscle-specific reporter mice, that the prenatal myonuclei remained in the adult soleus muscle, although cardiotoxin injection caused the loss of prenatal myonuclei. Overloading by the tendon transection of synergists failed to induce compensatory hypertrophy in regenerated soleus muscle fibers of adult rats, whereas unloading by tail suspension normally induced the fiber atrophy. Loss of hypertrophying function correlated with the lowered histone acetylation at the transcription start site of Igf1r gene, which was one of the genes that did not respond to the overloading. These parameters were improved by the transplantation of cells harvested from the juvenile soleus muscles of neonatal rats in association with enhanced histone acetylation of Igf1r gene. These results indicated that the presence of prenatal myonuclei was closely related to the status of histone acetylation, which could regulate the responsiveness of muscle fibers to physiological stimuli.

  3. Bromovirus movement protein genes play a crucial role in host specificity.

    PubMed Central

    Mise, K; Allison, R F; Janda, M; Ahlquist, P

    1993-01-01

    Monocot-adapted brome mosaic virus (BMV) and dicot-adapted cowpea chlorotic mottle virus (CCMV) are closely related bromoviruses with tripartite RNA genomes. Although RNAs 1 and 2 together are sufficient for RNA replication in protoplasts, systemic infection also requires RNA3, which encodes the coat protein and the nonstructural 3a movement protein. We have previously shown with bromoviral reassortants that host specificity determinants in both viruses are encoded by RNA3 as well as by RNA1 and/or RNA2. Here, to test their possible role in host specificity, the 3a movement protein genes were precisely exchanged between BMV and CCMV. The hybrid viruses, but not 3a deletion mutants, systemically infected Nicotiana benthamiana, a permissive host for both parental viruses. The hybrids thus retain basic competence for replication, packaging, cell-to-cell spread, and long-distance (vascular) spread. However, the hybrids failed to systemically infect either barley or cowpea, selective hosts for parental viruses. Thus, the 3a gene and/or its encoded 3a protein contributes to host specificity of both monocot- and dicot-adapted bromoviruses. Tests of inoculated cowpea leaves showed that the spread of the CCMV hybrid containing the BMV 3a gene was blocked at a very early stage of infection. Moreover, the BMV hybrid containing the CCMV 3a gene appeared to spread farther than wt BMV in inoculated cowpea leaves. Several pseudorevertants directing systemic infection in cowpea leaves were obtained from plants inoculated with the CCMV(BMV 3a) hybrid, suggesting that the number of mutations required to adapt the hybrid to dicots is small. Images PMID:7682628

  4. Thioredoxins Play a Crucial Role in Dynamic Acclimation of Photosynthesis in Fluctuating Light.

    PubMed

    Thormählen, Ina; Zupok, Arkadius; Rescher, Josephin; Leger, Jochen; Weissenberger, Stefan; Groysman, Julia; Orwat, Anne; Chatel-Innocenti, Gilles; Issakidis-Bourguet, Emmanuelle; Armbruster, Ute; Geigenberger, Peter

    2017-01-09

    Sunlight represents the energy source for photosynthesis and plant growth. When growing in the field, plant photosynthesis has to manage strong fluctuations in light intensities. Regulation based on the thioredoxin (Trx) system is believed to ensure light-responsive control of photosynthetic reactions in the chloroplast. However, direct evidence for a role of this system in regulating dynamic acclimation of photosynthesis in fluctuating conditions is largely lacking. In this report we show that the ferredoxin-dependent Trxs m1 and m2 as well as the NADPH-dependent NTRC are both indispensable for photosynthetic acclimation in fluctuating light intensities. Arabidopsis mutants with combined deficiency in Trxs m1 and m2 show wild-type growth and photosynthesis under constant light condition, while photosynthetic parameters are strongly modified in rapidly alternating high and low light. Two independent trxm1m2 mutants show lower photosynthetic efficiency in high light, but surprisingly significantly higher photosynthetic efficiency in low light. Our data suggest that a main target of Trx m1 and m2 is the NADP-malate dehydrogenase involved in export of excess reductive power from the chloroplast. The decreased photosynthetic efficiency in the high-light peaks may thus be explained by a reduced capacity of the trxm1m2 mutants in the rapid light activation of this enzyme. In the ntrc mutant, dynamic responses of non-photochemical quenching of excitation energy and plastoquinone reduction state both were strongly attenuated in fluctuating light intensities, leading to a massive decrease in PSII quantum efficiency and a specific decrease in plant growth under these conditions. This is likely due to the decreased ability of the ntrc mutant to control the stromal NADP(H) redox poise. Taken together, our results indicate that NTRC is indispensable in ensuring the full range of dynamic responses of photosynthesis to optimize photosynthesis and maintain growth in fluctuating

  5. The alternative sigma factor σ(B) plays a crucial role in adaptive strategies of Clostridium difficile during gut infection.

    PubMed

    Kint, Nicolas; Janoir, Claire; Monot, Marc; Hoys, Sandra; Soutourina, Olga; Dupuy, Bruno; Martin-Verstraete, Isabelle

    2017-02-15

    Clostridium difficile is a major cause of diarrhoea associated with antibiotherapy. Exposed to stresses in the gut, C. difficile can survive by inducing protection, detoxification and repair systems. In several firmicutes, most of these systems are controlled by the general stress response involving σ(B) . In this work, we studied the role of σ(B) in the physiopathology of C. difficile. We showed that the survival of the sigB mutant during the stationary phase was reduced. Using a transcriptome analysis, we showed that σ(B) controls the expression of ∼25% of genes including genes involved in sporulation, metabolism, cell surface biogenesis and the management of stresses. By contrast, σ(B) does not control toxin gene expression. In agreement with the up-regulation of sporulation genes, the sporulation efficiency is higher in the sigB mutant than in the wild-type strain. sigB inactivation also led to increased sensitivity to acidification, cationic antimicrobial peptides, nitric oxide and ROS. In addition, we showed for the first time that σ(B) also plays a crucial role in oxygen tolerance in this strict anaerobe. Finally, we demonstrated that the fitness of colonisation by the sigB mutant is greatly affected in a dixenic mouse model of colonisation when compared to the wild-type strain.

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

    PubMed

    Nichols, Buford L; Quezada-Calvillo, Roberto; Robayo-Torres, Claudia C; Ao, Zihua; Hamaker, Bruce R; Butte, Nancy F; Marini, Juan; Jahoor, Farook; Sterchi, Erwin E

    2009-04-01

    Starch is the major source of food glucose and its digestion requires small intestinal alpha-glucosidic activities provided by the 2 soluble amylases and 4 enzymes bound to the mucosal surface of enterocytes. Two of these mucosal activities are associated with sucrase-isomaltase complex, while another 2 are named maltase-glucoamylase (Mgam) in mice. Because the role of Mgam in alpha-glucogenic digestion of starch is not well understood, the Mgam gene was ablated in mice to determine its role in the digestion of diets with a high content of normal corn starch (CS) and resulting glucose homeostasis. Four days of unrestricted ingestion of CS increased intestinal alpha-glucosidic activities in wild-type (WT) mice but did not affect the activities of Mgam-null mice. The blood glucose responses to CS ingestion did not differ between null and WT mice; however, insulinemic responses elicited in WT mice by CS consumption were undetectable in null mice. Studies of the metabolic route followed by glucose derived from intestinal digestion of (13)C-labeled and amylase-predigested algal starch performed by gastric infusion showed that, in null mice, the capacity for starch digestion and its contribution to blood glucose was reduced by 40% compared with WT mice. The reduced alpha-glucogenesis of null mice was most probably compensated for by increased hepatic gluconeogenesis, maintaining prandial glucose concentration and total flux at levels comparable to those of WT mice. In conclusion, mucosal alpha-glucogenic activity of Mgam plays a crucial role in the regulation of prandial glucose homeostasis.

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

    PubMed Central

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

    2016-01-01

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

  8. α1-Tubulin FaTuA1 plays crucial roles in vegetative growth and conidiation in Fusarium asiaticum.

    PubMed

    Hu, Weiqun; Zhang, Xiaoping; Chen, Xiang; Zheng, Jingwu; Yin, Yanni; Ma, Zhonghua

    2015-04-01

    The filamentous ascomycete Fusarium asiaticum contains two homologous genes FaTUA1 and FaTUA2 encoding α-tubulins. In this study, we found that FaTUA2 was dispensable for vegetative growth and sporulation in F. asiaticum. The deletion of FaTUA1 however led to dramatically reduced mycelial growth, twisted hyphae and abnormal nuclei in apical cells of hyphae. The FaTUA1 deletion mutant (ΔFaTuA1-5) also showed a significant decrease in conidiation, and produced abnormal conidia. Pathogenicity assays showed that ΔFaTuA1-5 exhibited decreased virulence on wheat head. Unexpectedly, the deletion of FaTUA1 led to resistance to high temperatures. In addition, ΔFaTuA2 showed increased sensitivity to carbendazim. Furthermore, increased FaTUA2 expression in ΔFaTuA1-5 partially restored the defects of the mutant in mycelial growth, conidial production and virulence, vice versa, increased FaTUA1 expression in the FaTUA2 deletion mutant also partially relieved the defect of the mutant in the delay of conidial germination. Taken together, these results indicate that FaTuA1 plays crucial roles in vegetative growth and development, and the functions of FaTuA1 and FaTuA2 are partially interchangeable in F. asiaticum.

  9. Intestinal Na+, K+, 2Cl- cotransporter 2 plays a crucial role in hyperosmotic transitions of a euryhaline teleost.

    PubMed

    Esbaugh, Andrew J; Cutler, Brett

    2016-11-01

    Euryhaline fishes, such as the red drum (Sciaenops ocellatus), must quickly transition between hyperosmotic and hypoosmotic physiological strategies. When freshwater individuals transition to seawater they are exposed to increased diffusive water loss and ion gain. To maintain osmoregulatory balance these animals must drink and absorb seawater through the intestine, followed by ion excretion at the gills. The ability of fishes to transition between strategies can limit the magnitude of osmotic shock that can be tolerated. Here, we demonstrate that red drum can tolerate direct transfer from freshwater to full-strength seawater with marginal impacts on osmotic balance, as indicated by plasma and muscle ion concentration, as well as muscle water. Seawater transition is concurrent with a significant increase in intestinal fluid volume. Typical patterns of osmoregulatory plasticity were observed in the gill with increased expression of nkcc1 and cftr Expression changes in the anterior intestine were observed after 24 h for nkcc2 with smaller and later responses observed for slc26a3, slc26a6, and nbc Immunofluorescence staining demonstrated similar patterns of NKCC localization in freshwater and seawater intestines; however, reduced basolateral staining of V-type ATPase was observed in seawater. Electrophysiological preparations demonstrated that seawater fish had increased absorptive current in the anterior intestine, which was significantly reduced in the presence of 10 μmol/L bumetanide. Overall, these results suggest that nkcc2 plays a crucial role during hyperosmotic transitions, and may be a more important complement to the well-known bicarbonate secretion pathway than generally considered.

  10. Natural allelic variations of TCS1 play a crucial role in caffeine biosynthesis of tea plant and its related species.

    PubMed

    Jin, Ji-Qiang; Yao, Ming-Zhe; Ma, Chun-Lei; Ma, Jian-Qiang; Chen, Liang

    2016-03-01

    Tea caffeine synthase 1 (TCS1) is an enzyme that catalyzes the methylation of N-3 and N-1 and considered to be the most critical enzyme in the caffeine biosynthetic pathway of tea plant. This study shows that TCS1 has six types of allelic variations, namely, TCS1a, TCS1b, TCS1c, TCS1d, TCS1e, and TCS1f, with a 252 bp insertion/deletion mutation in the 5'-untranslated region. Among tea plant and its related species, TCS1a is the predominant allele, and TCS1b-f are the rare alleles that mainly appear in few wild germplasms. The full-length cDNA sequences of three new alleles, namely, TCS1d, TCS1e, and TCS1f, were isolated from specific germplasms, and all of recombinant proteins have higher caffeine synthase (CS, EC 2.1.1.160) activity than theobromine synthase (TS, EC 2.1.1.159). Amino acid residue 269 is responsible for the difference in TCS activity and substrate recognition, which was demonstrated by using site-directed mutagenesis experiments. Furthermore, natural variations in TCS1 change the transcription levels. There are two molecular mechanisms controlling the caffeine biosynthesis in low-caffeine-accumulating tea germplasms, i.e., TCS1 allele with low transcription level or its encoded protein with only TS activity. Allelic variations of TCS1 play a crucial role in caffeine biosynthesis. Taken together, our work provides valuable foundation for a comprehensive understanding of the mechanism of caffeine biosynthesis in section Thea plants and useful guidance for effective breeding.

  11. Gβ-like CpcB plays a crucial role for growth and development of Aspergillus nidulans and Aspergillus fumigatus.

    PubMed

    Kong, Qing; Wang, Long; Liu, Zengran; Kwon, Nak-Jung; Kim, Sun Chang; Yu, Jae-Hyuk

    2013-01-01

    Growth, development, virulence and secondary metabolism in fungi are governed by heterotrimeric G proteins (G proteins). A Gβ-like protein called Gib2 has been shown to function as an atypical Gβ in Gpa1-cAMP signaling in Cryptococcus neoformans. We found that the previously reported CpcB (cross pathway control B) protein is the ortholog of Gib2 in Aspergillus nidulans and Aspergillus fumigatus. In this report, we further characterize the roles of CpcB in governing growth, development and toxigenesis in the two aspergilli. The deletion of cpcB results in severely impaired cellular growth, delayed spore germination, and defective asexual sporulation (conidiation) in both aspergilli. Moreover, CpcB is necessary for proper expression of the key developmental activator brlA during initiation and progression of conidiation in A. nidulans and A. fumigatus. Somewhat in accordance with the previous study, the absence of cpcB results in the formation of fewer, but not micro-, cleistothecia in A. nidulans in the presence of wild type veA, an essential activator of sexual development. However, the cpcB deletion mutant cleistothecia contain no ascospores, validating that CpcB is required for progression and completion of sexual fruiting including ascosporogenesis. Furthermore, unlike the canonical GβSfaD, CpcB is not needed for the biosynthesis of the mycotoxin sterigmatocystin (ST) as the cpcB null mutant produced reduced amount of ST with unaltered STC gene expression. However, in A. fumigatus, the deletion of cpcB results in the blockage of gliotoxin (GT) production. Further genetic analyses in A. nidulans indicate that CpcB may play a central role in vegetative growth, which might be independent of FadA- and GanB-mediated signaling. A speculative model summarizing the roles of CpcB in conjunction with SfaD in A. nidulans is presented.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-04

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

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

    PubMed Central

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

    2016-01-01

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

  15. Peripheral blood mononuclear cell traffic plays a crucial role in mother-to-infant transmission of hepatitis B virus.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Hübner, Patrick P.; Khan, Serajul I.

    2015-01-01

    Although anatomically well described, the functional role of the mammalian efferent vestibular system (EVS) remains unclear. Unlike in fish and reptiles, the mammalian EVS does not seem to play a role in modulation of primary afferent activity in anticipation of active head movements. However, it could play a role in modulating long-term mechanisms requiring plasticity such as vestibular adaptation. We measured the efficacy of vestibuloocular reflex (VOR) adaptation in α9-knockout mice. These mice carry a missense mutation of the gene encoding the α9 nicotinic acetylcholine receptor (nAChR) subunit. The α9 nAChR subunit is expressed in the vestibular and auditory periphery, and its loss of function could compromise peripheral input from the predominantly cholinergic EVS. We measured the VOR gain (eye velocity/head velocity) in 26 α9-knockout mice and 27 cba129 control mice. Mice were randomly assigned to one of three groups: gain-increase adaptation (1.5×), gain-decrease adaptation (0.5×), or no adaptation (baseline, 1×). After adaptation training (horizontal rotations at 0.5 Hz with peak velocity 20°/s), we measured the sinusoidal (0.2–10 Hz, 20–100°/s) and transient (1,500–6,000°/s2) VOR in complete darkness. α9-Knockout mice had significantly lower baseline gains compared with control mice. This difference increased with stimulus frequency (∼5% <1 Hz to ∼25% >1 Hz). Moreover, vestibular adaptation (difference in VOR gain of gain-increase and gain-decrease adaptation groups as % of gain increase) was significantly reduced in α9-knockout mice (17%) compared with control mice (53%), a reduction of ∼70%. Our results show that the loss of α9 nAChRs moderately affects the VOR but severely affects VOR adaptation, suggesting that the EVS plays a crucial role in vestibular plasticity. PMID:26424577

  17. Nse1, Nse2, and a Novel Subunit of the Smc5-Smc6 Complex, Nse3, Play a Crucial Role in Meiosis

    PubMed Central

    Pebernard, Stephanie; McDonald, W. Hayes; Pavlova, Yelena; Yates, John R.; Boddy, Michael N.

    2004-01-01

    The structural maintenance of chromosomes (SMC) family of proteins play key roles in the organization, packaging, and repair of chromosomes. Cohesin (Smc1+3) holds replicated sister chromatids together until mitosis, condensin (Smc2+4) acts in chromosome condensation, and Smc5+6 performs currently enigmatic roles in DNA repair and chromatin structure. The SMC heterodimers must associate with non-SMC subunits to perform their functions. Using both biochemical and genetic methods, we have isolated a novel subunit of the Smc5+6 complex, Nse3. Nse3 is an essential nuclear protein that is required for normal mitotic chromosome segregation and cellular resistance to a number of genotoxic agents. Epistasis with Rhp51 (Rad51) suggests that like Smc5+6, Nse3 functions in the homologous recombination based repair of DNA damage. We previously identified two non-SMC subunits of Smc5+6 called Nse1 and Nse2. Analysis of nse1-1, nse2-1, and nse3-1 mutants demonstrates that they are crucial for meiosis. The Nse1 mutant displays meiotic DNA segregation and homologous recombination defects. Spore viability is reduced by nse2-1 and nse3-1, without affecting interhomolog recombination. Finally, genetic interactions shared by the nse mutants suggest that the Smc5+6 complex is important for replication fork stability. PMID:15331764

  18. Identification of residues in a hydrophilic loop of the Papaver rhoeas S protein that play a crucial role in recognition of incompatible pollen.

    PubMed Central

    Kakeda, K; Jordan, N D; Conner, A; Ride, J P; Franklin-Tong, V E; Franklin, F C

    1998-01-01

    The self-incompatibility response involves S allele-specific recognition between stigmatic S proteins and incompatible pollen. This response results in pollen inhibition. Defining the amino acid residues within the stigmatic S proteins that participate in S allele-specific inhibition of incompatible pollen is essential for the elucidation of the molecular basis of the self-incompatibility response. We have constructed mutant derivatives of the S1 protein from Papaver rhoeas by using site-directed mutagenesis and have tested their biological activity. This has enabled us to identify amino acid residues in the stigmatic S proteins of P. rhoeas that are required for S-specific inhibition of incompatible pollen. We report here the identification of several amino acid residues in the predicted hydrophilic loop 6 of the P. rhoeas stigmatic S1 protein that are involved in the inhibition of S1 pollen. Mutation of the only hypervariable amino acid, which is situated in this loop, resulted in the complete loss of ability of the S protein to inhibit S1 pollen. This clearly demonstrates that this residue plays a crucial role in pollen recognition and may also participate in defining allelic specificity. We have also established the importance of highly conserved amino acids adjacent to this hypervariable site. Our studies demonstrate that both variable and conserved amino acids in the region of the S protein corresponding to surface loop 6 are key elements that play a role in the recognition and inhibition of incompatible pollen in the pollen-pistil self-incompatibility reaction. PMID:9761798

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

    SciTech Connect

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

    2012-08-03

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

  20. The conserved cis-Pro39 residue plays a crucial role in the proper positioning of the catalytic base Asp38 in ketosteroid isomerase from Comamonas testosteroni.

    PubMed Central

    Nam, Gyu Hyun; Cha, Sun-Shin; Yun, Young Sung; Oh, Yun Hee; Hong, Bee Hak; Lee, Heung-Soo; Choi, Kwan Yong

    2003-01-01

    KSI (ketosteroid isomerase) from Comamonas testosteroni is a homodimeric enzyme that catalyses the allylic isomerization of Delta5-3-ketosteroids to their conjugated Delta4-isomers at a reaction rate equivalent to the diffusion-controlled limit. Based on the structural analysis of KSI at a high resolution, the conserved cis-Pro39 residue was proposed to be involved in the proper positioning of Asp38, a critical catalytic residue, since the residue was found not only to be structurally associated with Asp38, but also to confer a structural rigidity on the local active-site geometry consisting of Asp38, Pro39, Val40, Gly41 and Ser42 at the flexible loop between b-strands B1 and B2. In order to investigate the structural role of the conserved cis-Pro39 residue near the active site of KSI, Pro39 was replaced with alanine or glycine. The free energy of activation for the P39A and P39G mutants increased by 10.5 and 16.7 kJ/mol (2.5 and 4.0 kcal/mol) respectively, while DG(U)H2O (the free-energy change for unfolding in the absence of urea at 25.00+/-0.02 degrees C) decreased by 31.0 and 35.6 kJ/mol (7.4 and 8.5 kcal/mol) respectively, compared with the wild-type enzyme. The crystal structure of the P39A mutant in complex with d-equilenin [d-1,3,5(10),6,8-estrapentaen-3-ol-17-one], a reaction intermediate analogue, determined at 2.3 A (0.23 nm) resolution revealed that the P39A mutation significantly disrupted the proper orientations of both d-equilenin and Asp38, as well as the local active-site geometry near Asp38, which resulted in substantial decreases in the activity and stability of KSI. Upon binding 1-anilinonaphthalene-8-sulphonic acid, the fluorescence intensities of the P39A and P39G mutants were increased drastically, with maximum wavelengths blue-shifted upon binding, indicating that the mutations might alter the hydrophobic active site of KSI. Taken together, our results demonstrate that the conserved cis-Pro39 residue plays a crucial role in the proper

  1. A functional cyclic AMP response element plays a crucial role in neuroendocrine cell type-specific expression of the secretory granule protein chromogranin A.

    PubMed Central

    Wu, H; Mahata, S K; Mahata, M; Webster, N J; Parmer, R J; O'Connor, D T

    1995-01-01

    specificity of the promoter. The functional activity of the CRE site was confirmed through studies of the endogenous chromogranin A gene. Northern mRNA analysis showed that expression of the endogenous chromogranin A gene was stimulated seven- to eightfold by cAMP in PC12 cells, whereas no induction occurred in the NIH3T3 cells. Similar cAMP induction was obtained with the transfected chromogranin A promoter in PC12 cells, and abolition of the CRE site (by deletion or point mutation) eliminated the induction. Thus, the CRE site in the chromogranin A proximal promoter is functional and plays a crucial, indeed indispensable, role in neuroendocrine-specific expression of the gene. These results also provide insight into transcriptional mechanisms governing acquisition of the neuroendocrine secretory phenotype. Images PMID:7615829

  2. Bovine papillomavirus type 2 infects the urinary bladder of water buffalo (Bubalus bubalis) and plays a crucial role in bubaline urothelial carcinogenesis.

    PubMed

    Roperto, Sante; Russo, Valeria; Ozkul, Ayhan; Sepici-Dincel, Aylin; Maiolino, Paola; Borzacchiello, Giuseppe; Marcus, Ioan; Esposito, Iolanda; Riccardi, Marita Georgia; Roperto, Franco

    2013-02-01

    Bovine papillomavirus type 2 (BPV-2) has been shown to infect and play a role in urinary bladder carcinogenesis of buffaloes grazed on pastures with ferns from the Marmara and Black Sea Regions of Turkey. BPV-2 DNA has been found in both neoplastic and non-neoplastic lesions of the urinary bladder. Furthermore, this virus may be a normal inhabitant of the urinary bladder since BPV-2 DNA has also been detected in clinically normal buffaloes. The viral activation by fern immunosuppressant or carcinogen may trigger the urothelial cell transformation. The E5 oncoprotein was solely detected in urothelial tumours and appeared to be co-localized with the overexpressed and phosphorylated platelet derived growth factor (PDGF) β receptor in a double-colour immunofluorescence assay. Our results indicate that the E5-PDGF β receptor interaction also occurs in spontaneous tumours of the bubaline urinary bladder, revealing an additional role of BPV-2 in bladder carcinogenesis of buffaloes.

  3. Zebrafish foxc1a plays a crucial role in early somitogenesis by restricting the expression of aldh1a2 directly.

    PubMed

    Li, Jingyun; Yue, Yunyun; Dong, Xiaohua; Jia, Wenshuang; Li, Kui; Liang, Dong; Dong, Zhangji; Wang, Xiaoxiao; Nan, Xiaoxi; Zhang, Qinxin; Zhao, Qingshun

    2015-04-17

    Foxc1a is a member of the forkhead transcription factors. It plays an essential role in zebrafish somitogenesis. However, little is known about the molecular mechanisms underlying its controlling somitogenesis. To uncover how foxc1a regulates zebrafish somitogenesis, we generated foxc1a knock-out zebrafish using TALEN (transcription activator-like effector nuclease) technology. The foxc1a null embryos exhibited defective somites at early development. Analyses on the expressions of the key genes that control processes of somitogenesis revealed that foxc1a controlled early somitogenesis by regulating the expression of myod1. In the somites of foxc1a knock-out embryos, expressions of fgf8a and deltaC were abolished, whereas the expression of aldh1a2 (responsible for providing retinoic acid signaling) was significantly increased. Once the increased retinoic acid level in the foxc1a null embryos was reduced by knocking down aldh1a2, the reduced expression of myod1 was partially rescued by resuming expressions of fgf8a and deltaC in the somites of the mutant embryos. Moreover, a chromatin immunoprecipitation assay on zebrafish embryos revealed that Foxc1a bound aldh1a2 promoter directly. On the other hand, neither knocking down fgf8a nor inhibiting Notch signaling affected the expression of aldh1a2, although knocking down fgf8a reduced expression of deltaC in the somites of zebrafish embryos at early somitogenesis and vice versa. Taken together, our results demonstrate that foxc1a plays an essential role in early somitogenesis by controlling Fgf and Notch signaling through restricting the expression of aldh1a2 in paraxial mesoderm directly.

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

    PubMed

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

    2016-05-20

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

  5. CD4⁺ T cells play a crucial role for lenalidomide in vivo anti-tumor activity in murine multiple myeloma.

    PubMed

    Zhang, Liang; Bi, Enguang; Hong, Sungyoul; Qian, Jianfei; Zheng, Chengyun; Wang, Michael; Yi, Qing

    2015-11-03

    Lenalidomide modulates the host immune response against myeloma via multiple actions. Although these effects have been elucidated in vitro, the central action of lenalidomide-mediated anti-myeloma immune response in vivo is not clear. To investigate its immune action in vivo, we selected the murine myeloma cell line 5TGM1, which is resistant to direct tumoricidal effects of lenalidomide in vitro and in immunodeficient mice, but sensitive to lenalidomide treatment in 5TGM1-bearing immunocompetent mice. Depletion of CD4+ T cells, but not NK cells, B cells, or CD8+ T cells, deprived lenalidomide of its therapeutic effects on 5TGM1-bearing immunocompetent mice. Lenalidomide significantly increased the numbers of IFN-γ-secreting CD4+ and CD8+ T cells but had no effects on NK cells and B cells in this mouse model. Lenalidomide slightly decreased the number of CD25+Foxp3+ T cells but increased perforin expression in CD8+ T cells in vivo. Using this mouse model for investigation of anti-tumor immune action of lenalidomide, we demonstrated that lenalidomide facilitated a type-1 anti-tumor immune response in vivo. The CD4+ T cell subset may play a critical role in the lenalidomide-mediated anti-myeloma immune response in vivo.

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

    PubMed Central

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

    2016-01-01

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

  7. The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease

    PubMed Central

    Kereïche, Sami; Kováčik, Lubomír; Bednár, Jan; Pevala, Vladimír; Kunová, Nina; Ondrovičová, Gabriela; Bauer, Jacob; Ambro, Ľuboš; Bellová, Jana; Kutejová, Eva; Raška, Ivan

    2016-01-01

    Lon is an essential, multitasking AAA+ protease regulating many cellular processes in species across all kingdoms of life. Altered expression levels of the human mitochondrial Lon protease (hLon) are linked to serious diseases including myopathies, paraplegia, and cancer. Here, we present the first 3D structure of full-length hLon using cryo-electron microscopy. hLon has a unique three-dimensional structure, in which the proteolytic and ATP-binding domains (AP-domain) form a hexameric chamber, while the N-terminal domain is arranged as a trimer of dimers. These two domains are linked by a narrow trimeric channel composed likely of coiled-coil helices. In the presence of AMP-PNP, the AP-domain has a closed-ring conformation and its N-terminal entry gate appears closed, but in ADP binding, it switches to a lock-washer conformation and its N-terminal gate opens, which is accompanied by a rearrangement of the N-terminal domain. We have also found that both the enzymatic activities and the 3D structure of a hLon mutant lacking the first 156 amino acids are severely disturbed, showing that hLon’s N-terminal domains are crucial for the overall structure of the hLon, maintaining a conformation allowing its proper functioning. PMID:27632940

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

    PubMed Central

    2009-01-01

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

  9. Tuning the nature and stability of self-assemblies formed by ester benzene 1,3,5-tricarboxamides: the crucial role played by the substituents.

    PubMed

    Desmarchelier, Alaric; Alvarenga, Bruno Giordano; Caumes, Xavier; Dubreucq, Ludovic; Troufflard, Claire; Tessier, Martine; Vanthuyne, Nicolas; Idé, Julien; Maistriaux, Thomas; Beljonne, David; Brocorens, Patrick; Lazzaroni, Roberto; Raynal, Matthieu; Bouteiller, Laurent

    2016-09-20

    As the benzene 1,3,5-tricarboxamide (BTA) moiety is commonly used as the central assembling unit for the construction of functionalized supramolecular architectures, strategies to tailor the nature and stability of BTA assemblies are needed. The assembly properties of a library of structurally simple BTAs derived from amino dodecyl esters (ester BTAs, 13 members) have been studied, either in the bulk or in cyclohexane solutions, by means of a series of analytical methods (NMR, DSC, POM, FT-IR, UV-Vis, CD, ITC, high-sensitivity DSC, SANS). Two types of hydrogen-bonded species have been identified and characterized: the expected amide-bonded helical rods (or stacks) that are structurally similar to those formed by BTAs with simple alkyl side chains (alkyl BTAs), and ester-bonded dimers in which the BTAs are connected by means of hydrogen bonds linking the amide N-H and the ester C[double bond, length as m-dash]O. MM/MD calculations coupled with simulations of CD spectra allow for the precise determination of the molecular arrangement and of the hydrogen bond pattern of these dimers. Our study points out the crucial influence of the substituent attached on the amino-ester α-carbon on the relative stability of the rod-like versus dimeric assemblies. By varying this substituent, one can precisely tune the nature of the dominant hydrogen-bonded species (stacks or dimers) in the neat compounds and in cyclohexane over a wide range of temperatures and concentrations. In the neat BTAs, stacks are stable up to 213 °C and dimers above 180 °C whilst in cyclohexane stacks form at c* > 3 × 10(-5) M at 20 °C and dimers are stable up to 80 °C at 7 × 10(-6) M. Ester BTAs that assemble into stacks form a liquid-crystalline phase and yield gels or viscous solutions in cyclohexane, demonstrating the importance of controlling the structure of these assemblies. Our systematic study of these structurally similar ester BTAs also allows for a better understanding of how a single atom

  10. Dickkopf homolog 3 (DKK3) plays a crucial role upstream of WNT/β-CATENIN signaling for Sertoli cell mediated regulation of spermatogenesis.

    PubMed

    Das, Deepika Sharma; Wadhwa, Neerja; Kunj, Neetu; Sarda, Kanchan; Pradhan, Bhola Shankar; Majumdar, Subeer S

    2013-01-01

    Testicular Sertoli cells (Sc) are main somatic component of seminiferous tubules that govern the differentiation of germ cells (Gc) and provide them physical support. Sc are the target of follicle stimulating hormone (FSH) and testosterone (T) which are known to regulate spermatogenesis. FSH and T levels in human and sub-human male primates remain high during infancy (4-6 months post birth), similar to those during puberty. Subsequently, juvenile phase is marked with low levels of these hormones. In spite of prolonged hormonal exposure, spermatogenesis is not discerned during infancy unlike that during puberty. Situation during infancy is similar to certain idiopathic male infertility, where prolonged hormone supplementation fails to initiate spermatogenesis. In our quest to determine non hormonal causes of idiopathic infertility which may reside within the Sc, we investigated the association between spermatogenesis and Sc specific gene(s) expressed differentially during puberty and infancy. Although products of several genes may be necessary for quantitatively normal spermatogenesis, one needs to investigate their roles one by one. Differential display and real time PCR analysis revealed higher expression of a known tumor suppressor, Dickkopf homolog 3 (DKK3), by pubertal monkey Sc as compared to infant Sc. To evaluate role of DKK3 in spermatogenesis, we generated DKK3 knock down mice (DKDM) using shRNA construct targeted to DKK3. In testis of adult DKDM, expression of DKK3 mRNA and protein were significantly (p<0.05) low and was associated with elevated WNT-4/β-CATENIN activity. Elevated β-CATENIN activity is known to restrict Sc maturation. Abundant expression of infant Sc marker, Mullerian inhibiting substance (MIS), in the testes of adult DKDM confirmed lack of Sc maturation in DKDM. Gc differentiation and fertility was severely compromised in DKDM. This is the first report of role of DKK3 in the testis and DKK3 mediated regulation of spermatogenesis via WNT

  11. Transient receptor potential vanilloid 1 - a polymodal nociceptive receptor - plays a crucial role in formaldehyde-induced skin inflammation in mice.

    PubMed

    Usuda, Haruki; Endo, Takumi; Shimouchi, Ayumi; Saito, Asaka; Tominaga, Makoto; Yamashita, Hirotaka; Nagai, Hiroichi; Inagaki, Naoki; Tanaka, Hiroyuki

    2012-01-01

    Formaldehyde (FA) is irritating to the skin and is the main cause of sick building syndrome. However, the cutaneous reaction induced by long-term FA exposure has not been fully investigated. In our previous study, we demonstrated that repeated painting of 2% - 10% FA on mouse ears caused marked ear swelling and increased mRNA expression of transient receptor potential vanilloid 1 (TRPV1) and neurotrophins in the ear. TRPV1 is reported to be involved in neurogenic inflammation; therefore, in the present study, we investigated the role of TRPV1 in FA-induced skin inflammation using TRPV1 gene-knockout mice. Mice were painted with 5% FA once a week for 5 weeks, and ear swelling and mRNA expression were investigated. Ear swelling and increased expression of neurotrophins mRNA by FA provocation in wild-type mice were attenuated by disruption of the TRPV1 gene. Furthermore, painting with a threshold dose of capsaicin, which does not induce ear swelling in intact mice, caused marked ear swelling after painting the ear 5 times with FA, indicating that inflamed tissues after FA application are hypersensitive to various ligands of TRPV1 in mice. These results demonstrated that neurogenic inflammation via TRPV1 and neurotrophins could be involved in FA-induced dermatitis.

  12. Induction of heme oxygenase-1 by Na+-H+ exchanger 1 protein plays a crucial role in imatinib-resistant chronic myeloid leukemia cells.

    PubMed

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

    2015-05-15

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

  13. Colleges Play Crucial Role in Military's Restructuring

    ERIC Educational Resources Information Center

    Fischer, Karin

    2009-01-01

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

  14. 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)

  15. 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,…

  16. The crucial role of recess in school.

    PubMed

    Murray, Robert; Ramstetter, Catherine

    2013-01-01

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

  17. The crucial role of cholangiocytes in cholangiopathies.

    PubMed

    Park, Seon Mee

    2012-07-01

    Cholangiopathies are diseases involving the intrahepatic biliary tree. They appear to involve, chronic inflammation of the bile ducts, which can lead to the development of bile duct cholestasis, proliferation/ductopenia, biliary fibrosis, and malignant transformation. Sustained stimulatory insults to biliary epithelial cells can induce a ductular reaction, which has a key role in the initiation and progression of cholangiopathies. The epithelial-mesenchymal interaction between reactive cholangiocytes and mesenchymal cells with the inflammatory infiltrates plays a major role in this pathogenesis. Cytokines, chemokines, growth factors and morphogens mediate these interactions in an autocrine or paracrine manner. The main hepatic myofibroblasts (MFs) in cholangiopathies originate from portal fibroblasts. Hepatic stellate cells and fibrocytes also transform into MFs. Whether cholangiocytes or hepatocytes are a source of MFs via the epithelial-mesenchymal transition (EMT) remains a matter of controversy. Although there have been numerous indirect findings supporting the theory of a cholangiocyte EMT in human tissues, recent studies using lineage tracing methods have demonstrated strong evidence against the EMT. Understanding the pathogenic mechanisms involved in cholangiopathies can allow for better-targeted anti-fibrotic therapies in animal models. Before anti-fibrotic therapies can translate into clinical trials, improved monitoring of the fibrotic progression of cholangiopathies and an accurate assessment regarding the effectiveness of the proposed treatments must be achieved.

  18. The Crucial Role of Cholangiocytes in Cholangiopathies

    PubMed Central

    2012-01-01

    Cholangiopathies are diseases involving the intrahepatic biliary tree. They appear to involve, chronic inflammation of the bile ducts, which can lead to the development of bile duct cholestasis, proliferation/ductopenia, biliary fibrosis, and malignant transformation. Sustained stimulatory insults to biliary epithelial cells can induce a ductular reaction, which has a key role in the initiation and progression of cholangiopathies. The epithelial-mesenchymal interaction between reactive cholangiocytes and mesenchymal cells with the inflammatory infiltrates plays a major role in this pathogenesis. Cytokines, chemokines, growth factors and morphogens mediate these interactions in an autocrine or paracrine manner. The main hepatic myofibroblasts (MFs) in cholangiopathies originate from portal fibroblasts. Hepatic stellate cells and fibrocytes also transform into MFs. Whether cholangiocytes or hepatocytes are a source of MFs via the epithelial-mesenchymal transition (EMT) remains a matter of controversy. Although there have been numerous indirect findings supporting the theory of a cholangiocyte EMT in human tissues, recent studies using lineage tracing methods have demonstrated strong evidence against the EMT. Understanding the pathogenic mechanisms involved in cholangiopathies can allow for better-targeted anti-fibrotic therapies in animal models. Before anti-fibrotic therapies can translate into clinical trials, improved monitoring of the fibrotic progression of cholangiopathies and an accurate assessment regarding the effectiveness of the proposed treatments must be achieved. PMID:22844556

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

    PubMed Central

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

    2016-01-01

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

  20. Motivation: Its Crucial Role in Language Learning.

    ERIC Educational Resources Information Center

    Finocchiaro, Mary

    The role of motivation in second language learning is explored. Motivation involves positive learner and teacher attitudes which must be sustained through every stage of the learning process. Factors that influence motivation are described, including: teaching methodology, understanding meanings of words, mastery, objectives, classroom techniques,…

  1. The Crucial Role of Recess in Schools

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  2. The Arabidopsis U11/U12-65K is an indispensible component of minor spliceosome and plays a crucial role in U12 intron splicing and plant development.

    PubMed

    Jung, Hyun Ju; Kang, Hunseung

    2014-06-01

    The U12-dependent introns have been identified in a wide range of eukaryotes and are removed from precursor-mRNAs by U12 intron-specific minor spliceosome. Although several proteins unique to minor spliceosome have been identified, the nature of their effect on U12 intron splicing as well as plant growth and development remain largely unknown. Here, we characterized the functional role of an U12-type spliceosomal protein, U11/U12-65K in Arabidopsis thaliana. The transgenic knockdown plants generated by artificial miRNA-mediated silencing strategy exhibited severe defect in growth and development, such as severely arrested primary inflorescence stems, serrated leaves, and the formation of many rosette leaves after bolting. RNA sequencing and reverse transcription polymerase chain reaction (RT-PCR) analyses revealed that splicing of 198 out of the 234 previously predicted U12 intron-containing genes and 32 previously unidentified U12 introns was impaired in u11/u12-65k mutant. Moreover, the U11/U12-65K mutation affected alternative splicing, as well as U12 intron splicing, of many introns. Microarray analysis revealed that the genes involved in cell wall biogenesis and function, plant development, and metabolic processes are differentially expressed in the mutant plants. U11/U12-65K protein bound specifically to U12 small nuclear RNA (snRNA), which is necessary for branch-point site recognition. Taken together, these results provide clear evidence that U11/U12-65K is an indispensible component of minor spliceosome and involved in U12 intron splicing and alternative splicing of many introns, which is crucial for plant development.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  4. Crucial Role of Vitamin D in the Musculoskeletal System

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-01

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

  6. A crucial role for spatial distribution in bacterial quorum sensing

    PubMed Central

    Gao, Meng; Zheng, Huizhen; Ren, Ying; Lou, Ruyun; Wu, Fan; Yu, Weiting; Liu, Xiudong; Ma, Xiaojun

    2016-01-01

    Quorum sensing (QS) is a process that enables bacteria to communicate using secreted signaling molecules, and then makes a population of bacteria to regulate gene expression collectively and control behavior on a community-wide scale. Theoretical studies of efficiency sensing have suggested that both mass-transfer performance in the local environment and the spatial distribution of cells are key factors affecting QS. Here, an experimental model based on hydrogel microcapsules with a three-dimensional structure was established to investigate the influence of the spatial distribution of cells on bacterial QS. Vibrio harveyi cells formed different spatial distributions in the microcapsules, i.e., they formed cell aggregates with different structures and sizes. The cell aggregates displayed stronger QS than did unaggregated cells even when equal numbers of cells were present. Large aggregates (LA) of cells, with a size of approximately 25 μm, restricted many more autoinducers (AIs) than did small aggregates (SA), with a size of approximately 10 μm, thus demonstrating that aggregate size significantly affects QS. These findings provide a powerful demonstration of the fact that the spatial distribution of cells plays a crucial role in bacterial QS. PMID:27698391

  7. Island Cotton Enhanced Disease Susceptibility 1 Gene Encoding a Lipase-Like Protein Plays a Crucial Role in Response to Verticillium dahliae by Regulating the SA Level and H2O2 Accumulation

    PubMed Central

    Yan, Zhang; Xingfen, Wang; Wei, Rong; Jun, Yang; Zhiying, Ma

    2016-01-01

    Cotton is one of the most economically important crops, but most cultivated varieties lack adequate innate immunity or resistance to Verticillium wilt. This results in serious losses to both yield and fiber quality. To identify the genetic resources for innate immunity and understand the pathways for pathogen defenses in this crop, here we focus on orthologs of the central Arabidopsis thaliana defense regulator Enhanced Disease Susceptibility 1 (EDS1). The full-length cDNA of GbEDS1 was obtained by screening the full-length cDNA library of Gossypium barbadense combining with RACE strategy. Its open reading frame is 1848 bp long, encoding 615 amino acid residues. Sequence analysis showed that GbEDS1 contains a conserved N-terminal lipase domain and an EDS1-specific KNEDT motif. Expression profiling indicated that the gene is induced by Verticillium dahliae as well as salicylic acid (SA) treatment. Subcellular localization assays revealed that GbEDS1 is located in the cell cytoplasm and nucleus. Overexpression of GbEDS1 in Arabidopsis dramatically up-regulated SA and H2O2 production, resulting in enhanced disease resistance to V. dahliae. Silencing of GbEDS1 in G. barbadense significantly decreased SA and H2O2 accumulation, leading to the cotton more susceptibility. Moreover, combining the gene expression results from transgenic Arabidopsis and silenced-GbEDS1 cotton, it indicated that GbEDS1 could activate GbNDR1 and GbBAK1 expression. These findings not only broaden our knowledge about the biological role of GbEDS1, but also provide new insights into the defense mechanisms of GbEDS1 against V. dahliae in cotton. PMID:28018374

  8. AKT plays a crucial role in gastric cancer

    PubMed Central

    SASAKI, TAKAMITSU; YAMASHITA, YUICHI; KUNIYASU, HIROKI

    2015-01-01

    The AKT protein is involved in the phosphatidylinositol-3 kinase signaling pathway and is a vital regulator of survival, proliferation and differentiation in various types of cells. Helicobacter pylori infection induces epithelial cell proliferation and oxidative stress in chronic gastritis. These alterations lead to telomere shortening, resulting in the activation of telomerase. AKT, in particular, is activated by H. pylori-induced inflammation. AKT then promotes the expression of human telomerase reverse transcriptase, which encodes a catalytic subunit of telomerase, and induces telomerase activity, an essential component of the process of carcinogenesis. AKT activation is increased in gastric mucosa with carcinogenic properties and is associated with the low survival of patients with gastric cancer. The findings of the present study suggest that AKT is pivotal in gastric carcinogenesis and progression. PMID:26622541

  9. STIM and ORAI proteins: crucial roles in hallmarks of cancer.

    PubMed

    Fiorio Pla, A; Kondratska, K; Prevarskaya, N

    2016-04-01

    Intracellular Ca(2+) signals play a central role in several cellular processes; therefore it is not surprising that altered Ca(2+) homeostasis regulatory mechanisms lead to a variety of severe pathologies, including cancer. Stromal interaction molecules (STIM) and ORAI proteins have been identified as critical components of Ca(2+) entry in both store-dependent (SOCE mechanism) and independent by intracellular store depletion and have been implicated in several cellular functions. In recent years, both STIMs and ORAIs have emerged as possible molecular targets for cancer therapeutics. In this review we focus on the role of STIM and ORAI proteins in cancer progression. In particular we analyze their role in the different hallmarks of cancer, which represent the organizing principle that describes the complex multistep process of neoplastic diseases.

  10. Crucial role of astrocytes in temporal lobe epilepsy.

    PubMed

    Steinhäuser, C; Grunnet, M; Carmignoto, G

    2016-05-26

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

  11. 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.

  12. Rhizobium-legume symbioses: the crucial role of plant immunity.

    PubMed

    Gourion, Benjamin; Berrabah, Fathi; Ratet, Pascal; Stacey, Gary

    2015-03-01

    New research results have significantly revised our understanding of the rhizobium-legume infection process. For example, Nod factors (NFs), previously thought to be absolutely essential for this symbiosis, were shown to be dispensable under particular conditions. Similarly, an NF receptor, previously considered to be solely involved in symbiosis, was shown to function during plant pathogen infections. Indeed, there is a growing realization that plant innate immunity is a crucial component in the establishment and maintenance of symbiosis. We review here the factors involved in the suppression of plant immunity during rhizobium-legume symbiosis, and we attempt to place this information into context with the most recent and sometimes surprising research results.

  13. Restaurant Role-Play in Psychology

    ERIC Educational Resources Information Center

    Borya, Anthony

    2013-01-01

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

  14. The crucial role of plant mitochondria in orchestrating drought tolerance

    PubMed Central

    Atkin, Owen K.; Macherel, David

    2009-01-01

    Background Around the world, the frequency and intensity of droughts is increasing as a result of global climate change, with important consequences for the growth and survival of agricultural and native plant species. Understanding how plants respond to water stress is thus crucial for predicting the impacts of climate change on the crop productivity and ecosystem functioning. In contrast to the large number of studies assessing drought impacts on photosynthesis, relatively little attention has been devoted to understanding how mitochondrial respiratory metabolism is altered under water stress conditions. Scope This review provides an overview of the impacts of water stress on mitochondrial respiration (R), combining studies at the whole-plant, individual organ, cellular and organelle levels. To establish whether there are clear patterns in the response of in vivo R to water stress, a wide range of root, leaf and whole-plant studies are reviewed. It is shown that water stress almost always inhibits R in actively growing roots and whole plants. However, in fully expanded, mature leaves the response is more variable, with water stress reducing R in near two-thirds of reported studies, with most of the remainder showing no change. Only a few studies reported increases in leaf R under severe water stress conditions. The mechanisms responsible for these variable responses are discussed. Importantly, the fact is highlighted that irrespective of whether drought increases or decreases respiration, overall the changes in R are minor compared with the large decreases in photosynthetic carbon gain in response to drought. Based on recent work highlighting the link between chloroplast and mitochondrial functions in leaves, we propose a model by which mitochondrial R enables survival and rapid recovery of productivity under water stress conditions. Finally, the effects of water stress on mitochondrial function, protein abundance and overall metabolism are reviewed. PMID

  15. Crucial Role of Hyaluronan in Neointimal Formation after Vascular Injury

    PubMed Central

    Kashima, Yuichiro; Takahashi, Masafumi; Shiba, Yuji; Itano, Naoki; Izawa, Atsushi; Koyama, Jun; Nakayama, Jun; Taniguchi, Shun'ichiro; Kimata, Koji; Ikeda, Uichi

    2013-01-01

    Background Hyaluronan (HA) is a primary component of the extracellular matrix of cells, and it is involved in the pathogenesis of atherosclerosis. The purpose of this study was to investigate the role of HA in neointimal formation after vascular injury and determine its tissue-specific role in vascular smooth muscle cells (VSMCs) by using a cre-lox conditional transgenic (cTg) strategy. Methods and Results HA was found to be expressed in neointimal lesions in humans with atherosclerosis and after wire-mediated vascular injury in mice. Inhibition of HA synthesis using 4-methylumbelliferone markedly inhibited neointimal formation after injury. In vitro experiments revealed that low-molecular-weight HA (LMW-HA) induced VSMC activation, including migration, proliferation, and production of inflammatory cytokines, and reactive oxygen species (ROS). The migration and proliferation of VSMCs were mediated by the CD44/RhoA and CD44/ERK1/2 pathways, respectively. Because HA synthase 2 (HAS2) is predominantly expressed in injured arteries, we generated cTg mice that overexpress the murine HAS2 gene specifically in VSMCs (cHAS2/CreSM22α mice) and showed that HA overexpression markedly enhanced neointimal formation after cuff-mediated vascular injury. Further, HA-overexpressing VSMCs isolated from cHAS2/CreSM22α mice showed augmented migration, proliferation, and production of inflammatory cytokines and ROS. Conclusion VSMC-derived HA promotes neointimal formation after vascular injury, and HA may be a potential therapeutic target for cardiovascular disease. PMID:23484050

  16. 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,…

  17. 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…

  18. 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…

  19. 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…

  20. IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy.

    PubMed

    Cayrol, Corinne; Girard, Jean-Philippe

    2014-12-01

    IL-33 is a nuclear cytokine from the IL-1 family constitutively expressed in epithelial barrier tissues and lymphoid organs, which plays important roles in type-2 innate immunity and human asthma. Recent studies indicate that IL-33 induces production of large amounts of IL-5 and IL-13 by group 2 innate lymphoid cells (ILC2s), for initiation of allergic inflammation shortly after exposure to allergens or infection with parasites or viruses. IL-33 appears to function as an alarmin (alarm signal) rapidly released from producing cells upon cellular damage or cellular stress. In this review, we discuss the cellular sources, mode of action and regulation of IL-33, and we highlight its crucial roles in vivo with particular emphasis on results obtained using IL33-deficient mice.

  1. 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)

  2. 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…

  3. 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)

  4. 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…

  5. PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis

    PubMed Central

    Hirabayashi, Tetsuya; Anjo, Tatsuki; Kaneko, Arisa; Senoo, Yuuya; Shibata, Akitaka; Takama, Hiroyuki; Yokoyama, Kohei; Nishito, Yasumasa; Ono, Tomio; Taya, Choji; Muramatsu, Kazuaki; Fukami, Kiyoko; Muñoz-Garcia, Agustí; Brash, Alan R.; Ikeda, Kazutaka; Arita, Makoto; Akiyama, Masashi; Murakami, Makoto

    2017-01-01

    Mutations in patatin-like phospholipase domain-containing 1 (PNPLA1) cause autosomal recessive congenital ichthyosis, but the mechanism involved remains unclear. Here we show that PNPLA1, an enzyme expressed in differentiated keratinocytes, plays a crucial role in the biosynthesis of ω-O-acylceramide, a lipid component essential for skin barrier. Global or keratinocyte-specific Pnpla1-deficient neonates die due to epidermal permeability barrier defects with severe transepidermal water loss, decreased intercellular lipid lamellae in the stratum corneum, and aberrant keratinocyte differentiation. In Pnpla1−/− epidermis, unique linoleate-containing lipids including acylceramides, acylglucosylceramides and (O-acyl)-ω-hydroxy fatty acids are almost absent with reciprocal increases in their putative precursors, indicating that PNPLA1 catalyses the ω-O-esterification with linoleic acid to form acylceramides. Moreover, acylceramide supplementation partially rescues the altered differentiation of Pnpla1−/− keratinocytes. Our findings provide valuable insight into the skin barrier formation and ichthyosis development, and may contribute to novel therapeutic strategies for treatment of epidermal barrier defects. PMID:28248300

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

    ERIC Educational Resources Information Center

    Camp, Sharon L., Ed.; And Others

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

  7. Crucial yet divergent roles of mitochondrial redox state in skeletal muscle vs. brown adipose tissue energetics.

    PubMed

    Mailloux, Ryan J; Adjeitey, Cyril Nii-Klu; Xuan, Jian Ying; Harper, Mary-Ellen

    2012-01-01

    Reduced glutathione (GSH) is the major determinant of redox balance in mitochondria and as such is fundamental in the control of cellular bioenergetics. GSH is also the most important nonprotein antioxidant molecule in cells. Surprisingly, the effect of redox environment has never been examined in skeletal muscle and brown adipose tissue (BAT), two tissues that have exceptional dynamic range and that are relevant to the development of obesity and related diseases. Here, we show that the redox environment plays crucial, yet divergent, roles in modulating mitochondrial bioenergetics in skeletal muscle and BAT. Skeletal muscle mitochondria were found to naturally have a highly reduced environment (GSH/GSSG≈46), and this was associated with fairly high (∼40%) rates of state 4 (nonphosphorylating) respiration and decreased reactive oxygen species (ROS) emission. The deglutathionylation of uncoupling protein 3 (UCP3) following an increase in the reductive potential of mitochondria results in a further increase in nonphosphorylating respiration (∼20% in situ). BAT mitochondria were found to have a much more oxidized status (GSH/GSSG≈13) and had basal reactive oxygen species emission that was higher (∼250% increase in ROS generation) than that in skeletal muscle mitochondria. When redox status was subsequently increased (i.e., more reduced), UCP1-mediated uncoupling was more sensitive to GDP inhibition. Surprisingly, BAT was found to be devoid of glutaredoxin-2 (Grx2) expression, while there was abundant expression in skeletal muscle. Taken together, these findings reveal the importance of redox environment in controlling bioenergetic functions in both tissues, and the highly unique characteristics of BAT in this regard.

  8. "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…

  9. Crucial role of interferon-gamma and stimulated macrophages in cardiovascular disease.

    PubMed

    Schroecksnadel, Katharina; Frick, Barbara; Winkler, Christiana; Fuchs, Dietmar

    2006-07-01

    Inflammation and immune activation are crucially involved in the pathogenesis of atherosclerosis and cardiovascular disease. Accordingly, markers of inflammation such as fibrinogen, ferritin, C-reactive protein or neopterin are found in patients with vascular diseases, correlating strongly with the extent of disease and predicting disease progression. Neopterin formation by human monocyte-derived macrophages and dendritic cells is induced by the pro-inflammatory cytokine interferon-gamma, which is released by activated T-lymphocytes. Human macrophages are centrally involved in plaque formation, and interferon-gamma and macrophages are also of importance in the development of oxidative stress for antimicrobial and antitumoural defence within the cell-mediated immune response. Interferon-gamma also stimulates the enzyme indoleamine-2,3-dioxygenase, which degrades tryptophan to kynurenine. Again, macrophages are the most important cell type executing this enzyme reaction, but also other cells like dendritic cells, endothelial cells or fibroblasts can contribute to the depletion of tryptophan. Likewise, enhanced tryptophan degradation was reported in patients with coronary heart disease and was found to correlate with enhanced neopterin formation. In chronic diseases such as in cardiovascular disease, biochemical reactions induced by interferon-gamma may have detrimental consequences for host cells. In concert with other pro-inflammatory cytokines, interferon-gamma is the most important trigger for the formation and release of reactive oxygen species (ROS). Chronic ROS-production leads to the depletion of antioxidants like vitamin C and E and glutathione, with a consequence that oxidative stress develop. Oxidative stress plays a major role in the atherogenesis and progression of cardiovascular disease, and it may also account for the irreversible oxidation of other oxidation-sensitive substances like B-vitamins (e.g. folic acid and B12). They are essential cofactors in

  10. 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.

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

    ERIC Educational Resources Information Center

    Graham, Kerrie Lewis

    2010-01-01

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

  12. Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification.

    PubMed

    Ohhata, Tatsuya; Hoki, Yuko; Sasaki, Hiroyuki; Sado, Takashi

    2008-01-01

    Expression of Xist, which triggers X inactivation, is negatively regulated in cis by an antisense gene, Tsix, transcribed along the entire Xist gene. We recently demonstrated that Tsix silences Xist through modification of the chromatin structure in the Xist promoter region. This finding prompted us to investigate the role of antisense transcription across the Xist promoter in Tsix-mediated silencing. Here, we prematurely terminated Tsix transcription before the Xist promoter and addressed its effect on Xist silencing in mouse embryos. We found that although 93% of the region encoding Tsix was transcribed, truncation of Tsix abolished the antisense regulation of Xist. This resulted in a failure to establish the repressive chromatin configuration at the Xist promoter on the mutated X, including DNA methylation and repressive histone modifications, especially in extraembryonic tissues. These results suggest a crucial role for antisense transcription across the Xist promoter in Xist silencing.

  13. 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…

  14. 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…

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-08-21

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

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    2015-08-21

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  20. GLUT1‐mediated glucose uptake plays a crucial role during Plasmodium hepatic infection

    PubMed Central

    Meireles, Patrícia; Sales‐Dias, Joana; Andrade, Carolina M.; Mello‐Vieira, João; Mancio‐Silva, Liliana; Simas, J. Pedro; Staines, Henry M.

    2016-01-01

    Summary Intracellular pathogens have evolved mechanisms to ensure their survival and development inside their host cells. Here, we show that glucose is a pivotal modulator of hepatic infection by the rodent malaria parasite Plasmodium berghei and that glucose uptake via the GLUT1 transporter is specifically enhanced in P. berghei‐infected cells. We further show that ATP levels of cells containing developing parasites are decreased, which is known to enhance membrane GLUT1 activity. In addition, GLUT1 molecules are translocated to the membrane of the hepatic cell, increasing glucose uptake at later stages of infection. Chemical inhibition of GLUT1 activity leads to a decrease in glucose uptake and the consequent impairment of hepatic infection, both in vitro and in vivo. Our results reveal that changes in GLUT1 conformation and cellular localization seem to be part of an adaptive host response to maintain adequate cellular nutrition and energy levels, ensuring host cell survival and supporting P. berghei hepatic development. PMID:27404888

  1. 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)

  2. Crucial Role of Viral Reactivation in the Development of Severe Drug Eruptions: a Comprehensive Review.

    PubMed

    Shiohara, Tetsuo; Ushigome, Yukiko; Kano, Yoko; Takahashi, Ryo

    2015-10-01

    A growing number of cells, mediators, and pathways have been implicated in severe drug eruptions. Fifteen years ago, we published landmark studies that sparked the current advances in our understanding of the role of viral reactivations in severe drug eruptions. Viral reactivations then became critically important as diagnostic tools, but how precisely they participated in the pathogenesis remained less well-defined. The question of whether viral reactivations are pathogenic or are instead as epiphenomenon of severe tissue damage has plagued the field of drug allergy for some decades. Recent evidence points to a crucial role for tissue-resident memory T (TRM) cells in immune protection against viral infections. Yet immune protection against viral infections is but one side of a coin, the other side of which comprises effector cells capable of mediating severe immunopathology: Once drug antigen is cross-recognized by these T cells, they could be activated to kill surrounding epidermal cells, resulting in drug-induced tissue damage. Such TRM cells could persistently reside in the skin lesions of fixed drug eruptions (FDE) and are most likely a major cell type responsible for the development of FDE. We also discuss the role of regulatory T (Treg) cells in the setting of drug allergy, in which herpesviruses are reactivated in sequence. Although many details of the complicated interactions among viruses, anti-viral immune responses, TRM cells, and Treg cells remain to be elucidated, we review the current status of this rapidly advancing field.

  3. 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…

  4. 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…

  5. Crucial role of vHNF1 in vertebrate hepatic specification.

    PubMed

    Lokmane, Ludmilla; Haumaitre, Cécile; Garcia-Villalba, Pilar; Anselme, Isabelle; Schneider-Maunoury, Sylvie; Cereghini, Silvia

    2008-08-01

    Mouse liver induction occurs via the acquisition of ventral endoderm competence to respond to inductive signals from adjacent mesoderm, followed by hepatic specification. Little is known about the regulatory circuit involved in these processes. Through the analysis of vHnf1 (Hnf1b)-deficient embryos, generated by tetraploid embryo complementation, we demonstrate that lack of vHNF1 leads to defective hepatic bud formation and abnormal gut regionalization. Thickening of the ventral hepatic endoderm and expression of known hepatic genes do not occur. At earlier stages, hepatic specification of vHnf1-/- ventral endoderm is disrupted. More importantly, mutant ventral endoderm cultured in vitro loses its responsiveness to inductive FGF signals and fails to induce the hepatic-specification genes albumin and transthyretin. Analysis of liver induction in zebrafish indicates a conserved role of vHNF1 in vertebrates. Our results reveal the crucial role of vHNF1 at the earliest steps of liver induction: the acquisition of endoderm competence and the hepatic specification.

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

    SciTech Connect

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

    2010-06-10

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

  7. 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…

  8. 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…

  9. A crucial role for the putative Arabidopsis topoisomerase VI in plant growth and development

    PubMed Central

    Yin, Yanhai; Cheong, Hyeonsook; Friedrichsen, Danielle; Zhao, Yunde; Hu, Jianping; Mora-Garcia, Santiago; Chory, Joanne

    2002-01-01

    Plant steroid hormones, brassinosteroids (BRs), play important roles throughout plant growth and development. Plants defective in BR biosynthesis or perception display cell elongation defects and severe dwarfism. Two dwarf mutants named bin3 and bin5 with identical phenotypes to each other display some characteristics of BR mutants and are partially insensitive to exogenously applied BRs. In the dark, bin3 or bin5 seedlings are de-etiolated with short hypocotyls and open cotyledons. Light-grown mutant plants are dwarfs with short petioles, epinastic leaves, short inflorescence stems, and reduced apical dominance. We cloned BIN3 and BIN5 and show that BIN5 is one of three putative Arabidopsis SPO11 homologs (AtSPO11-3) that also shares significant homology to archaebacterial topoisomerase VI (TOP6) subunit A, whereas BIN3 represents a putative eukaryotic homolog of TOP6B. The pleiotropic dwarf phenotypes of bin5 establish that, unlike all of the other SPO11 homologs that are involved in meiosis, BIN5/AtSPO11-3 plays a major role during somatic development. Furthermore, microarray analysis of the expression of about 5500 genes in bin3 or bin5 mutants indicates that about 321 genes are down-regulated in both of the mutants, including 18 of 30 BR-induced genes. These results suggest that BIN3 and BIN5 may constitute an Arabidopsis topoisomerase VI that modulates expression of many genes, including those regulated by BRs. PMID:12119417

  10. 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.

  11. 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…

  12. 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…

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. 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,…

  19. 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…

  20. 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)

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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…

  6. 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.

  7. 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.

  8. 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.

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

    PubMed Central

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

    2016-01-01

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

  10. Approximate Bayesian Computation Reveals the Crucial Role of Oceanic Islands for the Assembly of Continental Biodiversity.

    PubMed

    Patiño, Jairo; Carine, Mark; Mardulyn, Patrick; Devos, Nicolas; Mateo, Rubén G; González-Mancebo, Juana M; Shaw, A Jonathan; Vanderpoorten, Alain

    2015-07-01

    The perceived low levels of genetic diversity, poor interspecific competitive and defensive ability, and loss of dispersal capacities of insular lineages have driven the view that oceanic islands are evolutionary dead ends. Focusing on the Atlantic bryophyte flora distributed across the archipelagos of the Azores, Madeira, the Canary Islands, Western Europe, and northwestern Africa, we used an integrative approach with species distribution modeling and population genetic analyses based on approximate Bayesian computation to determine whether this view applies to organisms with inherent high dispersal capacities. Genetic diversity was found to be higher in island than in continental populations, contributing to mounting evidence that, contrary to theoretical expectations, island populations are not necessarily genetically depauperate. Patterns of genetic variation among island and continental populations consistently fitted those simulated under a scenario of de novo foundation of continental populations from insular ancestors better than those expected if islands would represent a sink or a refugium of continental biodiversity. We, suggest that the northeastern Atlantic archipelagos have played a key role as a stepping stone for transoceanic migrants. Our results challenge the traditional notion that oceanic islands are the end of the colonization road and illustrate the significant role of oceanic islands as reservoirs of novel biodiversity for the assembly of continental floras.

  11. 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…

  12. A Computational Approach to Studying Protein Folding Problems Considering the Crucial Role of the Intracellular Environment.

    PubMed

    González-Pérez, Pedro P; Orta, Daniel J; Peña, Irving; Flores, Eduardo C; Ramírez, José U; Beltrán, Hiram I; Alas, Salomón J

    2017-02-08

    Intracellular protein folding (PF) is performed in a highly inhomogeneous, crowded, and correlated environment. Due to this inherent complexity, the study and understanding of PF phenomena is a fundamental issue in the field of computational systems biology. In particular, it is important to use a modeled medium that accurately reflects PF in natural systems. In the current study, we present a simulation wherein PF is carried out within an inhomogeneous modeled medium. Simulation resources included a two-dimensional hydrophobic-polar (HP) model, evolutionary algorithms, and the dual site-bond model. The dual site-bond model was used to develop an environment where HP beads could be folded. Our modeled medium included correlation lengths and fractal-like behavior, which were selected according to HP sequence lengths to induce folding in a crowded environment. Analysis of three benchmark HP sequences showed that the modeled inhomogeneous space played an important role in deeper energy folding and obtained better performance and convergence compared with homogeneous environments. Our computational approach also demonstrated that our correlated network provided a better space for PF. Thus, our approach represents a major advancement in PF simulations, not only for folding but also for understanding functional chemical structure and physicochemical properties of proteins in crowded molecular systems, which normally occur in nature.

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

    PubMed

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

    1992-04-01

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

  14. 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...

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  16. 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.

  17. 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

  18. "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…

  19. 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)

  20. 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…

  1. 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…

  2. 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…

  3. 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).

  4. 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).

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

    SciTech Connect

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

    2013-12-15

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  7. 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

  8. Crucial role of zebrafish prox1 in hypothalamic catecholaminergic neurons development

    PubMed Central

    Pistocchi, Anna; Gaudenzi, Germano; Carra, Silvia; Bresciani, Erica; Del Giacco, Luca; Cotelli, Franco

    2008-01-01

    Background Prox1, the vertebrate homolog of prospero in Drosophila melanogaster, is a divergent homeogene that regulates cell proliferation, fate determination and differentiation during vertebrate embryonic development. Results Here we report that, in zebrafish, prox1 is widely expressed in several districts of the Central Nervous System (CNS). Specifically, we evidenced prox1 expression in a group of neurons, already positive for otp1, located in the hypothalamus at the level of the posterior tuberculum (PT). Prox1 knock-down determines the severe loss of hypothalamic catecholaminergic (CA) neurons, identified by tyrosine hydroxylase (TH) expression, and the synergistic prox1/otp1 overexpression induces the appearance of hypothalamic supernumerary TH-positive neurons and ectopic TH-positive cells on the yolk epitelium. Conclusion Our findings indicate that prox1 activity is crucial for the proper development of the otp1-positive hypothalamic neuronal precursors to their terminal CA phenotype. PMID:18331627

  9. 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.

  10. 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.

  11. 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.

  12. Crucial roles of reactive chemical species in modification of respiratory syncytial virus by nitrogen gas plasma.

    PubMed

    Sakudo, Akikazu; Toyokawa, Yoichi; Imanishi, Yuichiro; Murakami, Tomoyuki

    2017-05-01

    The exact mechanisms by which nanoparticles, especially those composed of soft materials, are modified by gas plasma remain unclear. Here, we used respiratory syncytial virus (RSV), which has a diameter of 80-350nm, as a model system to identify important factors for gas plasma modification of nanoparticles composed of soft materials. Nitrogen gas plasma, generated by applying a short high-voltage pulse using a static induction (SI) thyristor power supply produced reactive chemical species (RCS) and caused virus inactivation. The plasma treatment altered the viral genomic RNA, while treatment with a relatively low concentration of hydrogen peroxide, which is a neutral chemical species among RCS, effectively inactivated the virus. Furthermore, a zero dimensional kinetic global model of the reaction scheme during gas plasma generation identified the production of various RCS, including neutral chemical species. Our findings suggest the nitrogen gas plasma generates RCS, including neutral species that damage the viral genomic RNA, leading to virus inactivation. Thus, RCS generated by gas plasma appears to be crucial for virus inactivation, suggesting this may constitute an important factor in terms of the efficient modification of nanoparticles composed of soft materials.

  13. Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease

    PubMed Central

    Scaldaferri, Franco; Sans, Miquel; Vetrano, Stefania; Graziani, Cristina; De Cristofaro, Raimondo; Gerlitz, Bruce; Repici, Alessandro; Arena, Vincenzo; Malesci, Alberto; Panes, Julian; Grinnell, Brian W.; Danese, Silvio

    2007-01-01

    Endothelial protein C receptor (EPCR) and thrombomodulin (TM) are expressed at high levels in the resting microvasculature and convert protein C (PC) into its activated form, which is a potent anticoagulant and antiinflammatory molecule. Here we provide evidence that in Crohn disease (CD) and ulcerative colitis (UC), the 2 major forms of inflammatory bowel disease (IBD), there was loss of expression of endothelial EPCR and TM, which in turns caused impairment of PC activation by the inflamed mucosal microvasculature. In isolated human intestinal endothelial cells, administration of recombinant activated PC had a potent antiinflammatory effect, as demonstrated by downregulated cytokine-dependent cell adhesion molecule expression and chemokine production as well as inhibited leukocyte adhesion. In vivo, administration of activated PC was therapeutically effective in ameliorating experimental colitis as evidenced by reduced weight loss, disease activity index, and histological colitis scores as well as inhibited leukocyte adhesion to the inflamed intestinal vessels. The results suggest that the PC pathway represents a new system crucially involved in governing intestinal homeostasis mediated by the mucosal microvasculature. Restoring the PC pathway may represent a new therapeutic approach to suppress intestinal inflammation in IBD. PMID:17557119

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

    SciTech Connect

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

    1992-10-01

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

  15. Crucial role of interlayer distance for antiferromagnet-induced perpendicular magnetic anisotropy

    NASA Astrophysics Data System (ADS)

    Wang, Bo-Yao; Lin, Po-Han; Tsai, Ming-Shian; Shih, Chun-Wei; Lee, Meng-Ju; Huang, Chun-Wei; Jih, Nae-Yeou; Cheng, Pei-Yu; Wei, Der-Hsin

    2015-12-01

    Antiferromagnetic (AFM) thin films were recently proposed to be an alternative to conventional materials for achieving perpendicular magnetic anisotropy (PMA) in ferromagnetic thin films, because AFM thin films exhibit an advantage of flexible control. Here, we report that antiferromagnet-induced PMA is highly sensitive to interfacial moments of AFM thin films as well as the magnetic interaction of such moments with volume moments, determined according to the vertical interlayer distance. Magnetic hysteresis loops and x-ray magnetic domain imaging revealed the establishment of perpendicular magnetization on face-centered tetragonal (fct)-like Mn/Co/Ni films when covered with monolayered Mn films. A cover of Mn films that exhibit contracted fct- [vertical-to-in-plane lattice constant ratio (c /a )=0.95 ] and expanded fct-like (c /a =1.05 ) structures at different thickness levels induced in-plane magnetic anisotropy and PMA in Co/Ni films, respectively, confirming that the interlayer distance is a crucial parameter for establishing perpendicular magnetization.

  16. p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis.

    PubMed

    Su, Xiaohua; Chakravarti, Deepavali; Flores, Elsa R

    2013-02-01

    The role of p63 in cancer has been an area of intense debate and controversy. Is TP63 (which encodes p63) a tumour suppressor gene or an oncogene? This debate is partly due to the complexity of the gene. There are several p63 isoforms - some with tumour suppressive functions and others with oncogenic functions. In this Opinion article, we focus on the recent advances in understanding p63 biology and its roles in cancer. In this regard, we discuss the role of p63 in multiple stem cell compartments, ageing, in the response to DNA damage and in DNA repair. Finally, we highlight the importance of understanding the interactions between all three p53 family members and the potential impact of this knowledge on cancer therapy and regenerative medicine.

  17. 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…

  18. 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…

  19. 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)

  20. 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)

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  2. 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…

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. 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)

  12. 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…

  13. 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…

  14. 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…

  15. 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.

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

    ERIC Educational Resources Information Center

    Dychkowski, Linda

    2000-01-01

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

  17. Modeling plasma-based CO2 conversion: crucial role of the dissociation cross section

    NASA Astrophysics Data System (ADS)

    Bogaerts, Annemie; Wang, Weizong; Berthelot, Antonin; Guerra, Vasco

    2016-10-01

    Plasma-based CO2 conversion is gaining increasing interest worldwide. A large research effort is devoted to improving the energy efficiency. For this purpose, it is very important to understand the underlying mechanisms of the CO2 conversion. The latter can be obtained by computer modeling, describing in detail the behavior of the various plasma species and all relevant chemical processes. However, the accuracy of the modeling results critically depends on the accuracy of the assumed input data, like cross sections. This is especially true for the cross section of electron impact dissociation, as the latter process is believed to proceed through electron impact excitation, but it is not clear from the literature which excitation channels effectively lead to dissociation. Therefore, the present paper discusses the effect of different electron impact dissociation cross sections reported in the literature on the calculated CO2 conversion, for a dielectric barrier discharge (DBD) and a microwave (MW) plasma. Comparison is made to experimental data for the DBD case, to elucidate which cross section might be the most realistic. This comparison reveals that the cross sections proposed by Itikawa and by Polak and Slovetsky both seem to underestimate the CO2 conversion. The cross sections recommended by Phelps with thresholds of 7 eV and 10.5 eV yield a CO2 conversion only slightly lower than the experimental data, but the sum of both cross sections overestimates the values, indicating that these cross sections represent dissociation, but most probably also include other (pure excitation) channels. Our calculations indicate that the choice of the electron impact dissociation cross section is crucial for the DBD, where this process is the dominant mechanism for CO2 conversion. In the MW plasma, it is only significant at pressures up to 100 mbar, while it is of minor importance for higher pressures, when dissociation proceeds mainly through collisions of CO2 with heavy

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

    NASA Astrophysics Data System (ADS)

    Renard, Francois

    2015-04-01

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

  19. Introduction: MicroRNAs in human reproduction: small molecules with crucial regulatory roles.

    PubMed

    Imbar, Tal; Galliano, Daniela; Pellicer, Antonio; Laufer, Neri

    2014-06-01

    MicroRNAs constitute a large family of approximately 21-nucleotide-long, noncoding RNAs. They emerged more than 20 years ago as key posttranscriptional regulators of gene expression. The regulatory role of these small RNA molecules has recently begun to be explored in the human reproductive system. In this issue's Views and Reviews, the authors present the current knowledge regarding the involvement of microRNAs in several aspects of human reproduction and discuss its future implications for clinical practice.

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

    PubMed

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

    2008-06-09

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

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

    PubMed Central

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

    2016-01-01

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

  2. 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.

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

    PubMed

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

    2015-10-01

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

  4. The Crucial Role of Zona Pellucida in Cryopreservation of Oocytes by Vitrification

    PubMed Central

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

    2015-01-01

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

  5. 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…

  6. The beginnings of psychoanalytic supervision: the crucial role of Max Eitingon.

    PubMed

    Watkins, C Edward

    2013-09-01

    Psychoanalytic supervision is moving well into its 2nd century of theory, practice, and (to a limited extent) research. In this paper, I take a look at the pioneering first efforts to define psychoanalytic supervision and its importance to the psychoanalytic education process. Max Eitingon, the "almost forgotten man" of psychoanalysis, looms large in any such consideration. His writings or organizational reports were seemingly the first psychoanalytic published material to address the following supervision issues: rationale, screening, notes, responsibility, supervisee learning/personality issues, and the extent and length of supervision itself. Although Eitingon never wrote formally on supervision, his pioneering work in the area has continued to echo across the decades and can still be seen reflected in contemporary supervision practice. I also recognize the role of Karen Horney-one of the founders of the Berlin Institute and Poliklinik, friend of Eitingon, and active, vital participant in Eitingon's efforts-in contributing to and shaping the beginnings of psychoanalytic education.

  7. Brain stimulation reveals crucial role of overcoming self-centeredness in self-control

    PubMed Central

    Soutschek, Alexander; Ruff, Christian C.; Strombach, Tina; Kalenscher, Tobias; Tobler, Philippe N.

    2016-01-01

    Neurobiological models of self-control predominantly focus on the role of prefrontal brain mechanisms involved in emotion regulation and impulse control. We provide evidence for an entirely different neural mechanism that promotes self-control by overcoming bias for the present self, a mechanism previously thought to be mainly important for interpersonal decision-making. In two separate studies, we show that disruptive transcranial magnetic stimulation (TMS) of the temporo-parietal junction—a brain region involved in overcoming one’s self-centered perspective—increases the discounting of delayed and prosocial rewards. This effect of TMS on temporal and social discounting is accompanied by deficits in perspective-taking and does not reflect altered spatial reorienting and number recognition. Our findings substantiate a fundamental commonality between the domains of self-control and social decision-making and highlight a novel aspect of the neurocognitive processes involved in self-control. PMID:27774513

  8. 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…

  9. Crucial role of calbindin-D28k in the pathogenesis of Alzheimer's disease mouse model.

    PubMed

    Kook, S-Y; Jeong, H; Kang, M J; Park, R; Shin, H J; Han, S-H; Son, S M; Song, H; Baik, S H; Moon, M; Yi, E C; Hwang, D; Mook-Jung, I

    2014-10-01

    Calbindin-D28k (CB), one of the major calcium-binding and buffering proteins, has a critical role in preventing a neuronal death as well as maintaining calcium homeostasis. Although marked reductions of CB expression have been observed in the brains of mice and humans with Alzheimer disease (AD), it is unknown whether these changes contribute to AD-related dysfunction. To determine the pathogenic importance of CB depletions in AD models, we crossed 5 familial AD mutations (5XFAD; Tg) mice with CB knock-out (CBKO) mice and generated a novel line CBKO·5XFAD (CBKOTg) mice. We first identified the change of signaling pathways and differentially expressed proteins globally by removing CB in Tg mice using mass spectrometry and antibody microarray. Immunohistochemistry showed that CBKOTg mice had significant neuronal loss in the subiculum area without changing the magnitude (number) of amyloid β-peptide (Aβ) plaques deposition and elicited significant apoptotic features and mitochondrial dysfunction compared with Tg mice. Moreover, CBKOTg mice reduced levels of phosphorylated mitogen-activated protein kinase (extracellular signal-regulated kinase) 1/2 and cAMP response element-binding protein at Ser-133 and synaptic molecules such as N-methyl-D-aspartate receptor 1 (NMDA receptor 1), NMDA receptor 2A, PSD-95 and synaptophysin in the subiculum compared with Tg mice. Importantly, this is the first experimental evidence that removal of CB from amyloid precursor protein/presenilin transgenic mice aggravates AD pathogenesis, suggesting that CB has a critical role in AD pathogenesis.

  10. 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.

  11. Crucial role for prion protein membrane anchoring in the neuroinvasion and neural spread of prion infection.

    PubMed

    Klingeborn, Mikael; Race, Brent; Meade-White, Kimberly D; Rosenke, Rebecca; Striebel, James F; Chesebro, Bruce

    2011-02-01

    In nature prion diseases are usually transmitted by extracerebral prion infection, but clinical disease results only after invasion of the central nervous system (CNS). Prion protein (PrP), a host-encoded glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein, is necessary for prion infection and disease. Here, we investigated the role of the anchoring of PrP on prion neuroinvasion by studying various inoculation routes in mice expressing either anchored or anchorless PrP. In control mice with anchored PrP, intracerebral or sciatic nerve inoculation resulted in rapid CNS neuroinvasion and clinical disease (154 to 156 days), and after tongue, ocular, intravenous, or intraperitoneal inoculation, CNS neuroinvasion was only slightly slower (193 to 231 days). In contrast, in anchorless PrP mice, these routes resulted in slow and infrequent CNS neuroinvasion. Only intracerebral inoculation caused brain PrPres, a protease-resistant isoform of PrP, and disease in both types of mice. Thus, anchored PrP was an essential component for the rapid neural spread and CNS neuroinvasion of prion infection.

  12. A Crucial Role of CXCL14 for Promoting Regulatory T Cells Activation in Stroke

    PubMed Central

    Lee, Hsu-Tung; Liu, Shih-Ping; Lin, Chen-Huan; Lee, Sophie Wei; Hsu, Chung Y.; Sytwu, Huey-Kang; Hsieh, Chia-Hung; Shyu, Woei-Cherng

    2017-01-01

    Inflammatory processes have a detrimental role in the pathophysiology of ischemic stroke. However, little is known about the endogenous anti-inflammatory mechanisms in ischemic brain. Here, we identify CXCL14 as a critical mediator of these mechanisms. CXCL14 levels were upregulated in the ischemic brains of humans and rodents. Moreover, hypoxia inducible factor-1α (HIF-1α) drives hypoxia- or cerebral ischemia (CI)-dependent CXCL14 expression via directly binding to the CXCL14 promoter. Depletion of CXCL14 inhibited the accumulation of immature dendritic cells (iDC) or regulatory T cells (Treg) and increased the infarct volume, whereas the supplementation of CXCL14 had the opposite effects. CXCL14 promoted the adhesion, migration, and homing of circulating CD11c+ iDC to the ischemic tissue via the upregulation of the cellular prion protein (PrPC), PECAM-1, and MMPs. The accumulation of Treg in ischemic areas of the brain was mediated through a cooperative effect of CXCL14 and iDC-secreted IL-2-induced Treg differentiation. Interestingly, CXCL14 largely promoted IL-2-induced Treg differentiation. These findings indicate that CXCL14 is a critical immunomodulator involved in the stroke-induced inflammatory reaction. Passive CXCL14 supplementation provides a tractable path for clinical translation in the improvement of stroke-induced neuroinflammation. PMID:28382159

  13. Crucial roles of TNFAIP8 protein in regulating apoptosis and Listeria infection.

    PubMed

    Porturas, Thomas P; Sun, Honghong; Buchlis, George; Lou, Yunwei; Liang, Xiaohong; Cathopoulis, Terry; Fayngerts, Svetlana; Johnson, Derek S; Wang, Zhaojun; Chen, Youhai H

    2015-06-15

    TNF-α-induced protein 8 (TNFAIP8 or TIPE) is a newly described regulator of cancer and infection. However, its precise roles and mechanisms of actions are not well understood. We report in this article that TNFAIP8 regulates Listeria monocytogenes infection by controlling pathogen invasion and host cell apoptosis in a RAC1 GTPase-dependent manner. TNFAIP8-knockout mice were resistant to lethal L. monocytogenes infection and had reduced bacterial load in the liver and spleen. TNFAIP8 knockdown in murine liver HEPA1-6 cells increased apoptosis, reduced bacterial invasion into cells, and resulted in dysregulated RAC1 activation. TNFAIP8 could translocate to plasma membrane and preferentially associate with activated RAC1-GTP. The combined effect of reduced bacterial invasion and increased sensitivity to TNF-α-induced clearance likely protected the TNFAIP8-knockout mice from lethal listeriosis. Thus, by controlling bacterial invasion and the death of infected cells through RAC1, TNFAIP8 regulates the pathogenesis of L. monocytogenes infection.

  14. Crucial roles of TNFAIP8 protein in regulating apoptosis and Listeria infection

    PubMed Central

    Porturas, Thomas P.; Sun, Honghong; Buchlis, George; Lou, Yunwei; Liang, Xiaohong; Cathopoulis, Terry; Fayngerts, Svetlana; Johnson, Derek S.; Wang, Zhaojun; Chen, Youhai H.

    2015-01-01

    TNFα-induced protein 8 (TNFAIP8 or TIPE) is a newly described regulator of cancer and infection. However, its precise roles and mechanisms of actions are not well understood. We report here that TNFAIP8 regulates Listeria monocytogenes infection by controlling pathogen invasion and host cell apoptosis in a RAC1 GTPase-dependent manner. TNFAIP8 knockout mice were found to be resistant to lethal L. monocytogenes infection and had reduced bacterial load in the liver and spleen. TNFAIP8-knockdown in murine liver HEPA1-6 cells increased apoptosis, reduced bacterial invasion into cells, and resulted in dysregulated RAC1 activation. TNFAIP8 could translocate to plasma membrane and preferentially associate with activated GTP-RAC1. The combined effect of reduced bacterial invasion and increased sensitivity to TNFα-induced clearance likely protected the TNFAIP8 knockout mice from lethal listeriosis. Thus, by controlling bacterial invasion and the death of infected cells through RAC1, TNFAIP8 regulates the pathogenesis of L. monocytogenes infection. PMID:25948813

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

    PubMed

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

    2012-01-01

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

  16. 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

  17. 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.

  18. 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.

  19. ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc.

    PubMed

    Zhang, C; Zhang, S; Zhang, Z; He, J; Xu, Y; Liu, S

    2014-12-04

    Rho-associated kinase (ROCK) has an essential role in governing cell morphology and motility, and increased ROCK activity contributes to cancer cell invasion and metastasis. Burgeoning data suggest that ROCK is also involved in the growth regulation of tumor cells. However, thus far, the molecular mechanisms responsible for ROCK-governed tumor cell growth have not been clearly elucidated. Here we showed that inhibition of ROCK kinase activity, either by a selective ROCK inhibitor Y27632 or by specific ROCK small interfering RNA (siRNA) molecules, attenuated not only motility but also the proliferation of PC3 prostate cancer cells in vitro and in vivo. Importantly, mechanistic investigation revealed that ROCK endowed cancer cells with tumorigenic capability, mainly by targeting c-Myc. ROCK could increase the transcriptional activity of c-Myc by promoting c-Myc protein stability, and ROCK inhibition reduced c-Myc-mediated expression of mRNA targets (such as HSPC111) and microRNA targets (such as miR-17-92 cluster). We provided evidence demonstrating that ROCK1 directly interacted with and phosphorylated c-Myc, resulting in stabilization of the protein and activation of its transcriptional activity. Suppression of ROCK-c-Myc downstream molecules, such as c-Myc-regulated miR-17, also impaired tumor cell growth in vitro and in vivo. In addition, c-Myc was shown to exert a positive feedback regulation on ROCK by increasing RhoA mRNA expression. Therefore, inhibition of ROCK and its stimulated signaling might prove to be a promising strategy for restraining tumor progression in prostate cancer.

  20. Crucial role of copper in detection of metal-coordinating odorants.

    PubMed

    Duan, Xufang; Block, Eric; Li, Zhen; Connelly, Timothy; Zhang, Jian; Huang, Zhimin; Su, Xubo; Pan, Yi; Wu, Lifang; Chi, Qiuyi; Thomas, Siji; Zhang, Shaozhong; Ma, Minghong; Matsunami, Hiroaki; Chen, Guo-Qiang; Zhuang, Hanyi

    2012-02-28

    Odorant receptors (ORs) in olfactory sensory neurons (OSNs) mediate detection of volatile odorants. Divalent sulfur compounds, such as thiols and thioethers, are extremely potent odorants. We identify a mouse OR, MOR244-3, robustly responding to (methylthio)methanethiol (MeSCH(2)SH; MTMT) in heterologous cells. Found specifically in male mouse urine, strong-smelling MTMT [human threshold 100 parts per billion (ppb)] is a semiochemical that attracts female mice. Nonadjacent thiol and thioether groups in MTMT suggest involvement of a chelated metal complex in MOR244-3 activation. Metal ion involvement in thiol-OR interactions was previously proposed, but whether these ions change thiol-mediated OR activation remained unknown. We show that copper ion among all metal ions tested is required for robust activation of MOR244-3 toward ppb levels of MTMT, structurally related sulfur compounds, and other metal-coordinating odorants (e.g., strong-smelling trans-cyclooctene) among >125 compounds tested. Copper chelator (tetraethylenepentamine, TEPA) addition abolishes the response of MOR244-3 to MTMT. Histidine 105, located in the third transmembrane domain near the extracellular side, is proposed to serve as a copper-coordinating residue mediating interaction with the MTMT-copper complex. Electrophysiological recordings of the OSNs in the septal organ, abundantly expressing MOR244-3, revealed neurons responding to MTMT. Addition of copper ion and chelator TEPA respectively enhanced and reduced the response of some MTMT-responding neurons, demonstrating the physiological relevance of copper ion in olfaction. In a behavioral context, an olfactory discrimination assay showed that mice injected with TEPA failed to discriminate MTMT. This report establishes the role of metal ions in mammalian odor detection by ORs.

  1. Crucial role of copper in detection of metal-coordinating odorants

    PubMed Central

    Duan, Xufang; Block, Eric; Li, Zhen; Connelly, Timothy; Zhang, Jian; Huang, Zhimin; Su, Xubo; Pan, Yi; Wu, Lifang; Chi, Qiuyi; Thomas, Siji; Zhang, Shaozhong; Ma, Minghong; Matsunami, Hiroaki; Chen, Guo-Qiang; Zhuang, Hanyi

    2012-01-01

    Odorant receptors (ORs) in olfactory sensory neurons (OSNs) mediate detection of volatile odorants. Divalent sulfur compounds, such as thiols and thioethers, are extremely potent odorants. We identify a mouse OR, MOR244-3, robustly responding to (methylthio)methanethiol (MeSCH2SH; MTMT) in heterologous cells. Found specifically in male mouse urine, strong-smelling MTMT [human threshold 100 parts per billion (ppb)] is a semiochemical that attracts female mice. Nonadjacent thiol and thioether groups in MTMT suggest involvement of a chelated metal complex in MOR244-3 activation. Metal ion involvement in thiol–OR interactions was previously proposed, but whether these ions change thiol-mediated OR activation remained unknown. We show that copper ion among all metal ions tested is required for robust activation of MOR244-3 toward ppb levels of MTMT, structurally related sulfur compounds, and other metal-coordinating odorants (e.g., strong-smelling trans-cyclooctene) among >125 compounds tested. Copper chelator (tetraethylenepentamine, TEPA) addition abolishes the response of MOR244-3 to MTMT. Histidine 105, located in the third transmembrane domain near the extracellular side, is proposed to serve as a copper-coordinating residue mediating interaction with the MTMT–copper complex. Electrophysiological recordings of the OSNs in the septal organ, abundantly expressing MOR244-3, revealed neurons responding to MTMT. Addition of copper ion and chelator TEPA respectively enhanced and reduced the response of some MTMT-responding neurons, demonstrating the physiological relevance of copper ion in olfaction. In a behavioral context, an olfactory discrimination assay showed that mice injected with TEPA failed to discriminate MTMT. This report establishes the role of metal ions in mammalian odor detection by ORs. PMID:22328155

  2. A crucial role of nitric oxide in acute lung injury secondary to the acute necrotizing pancreatitis.

    PubMed

    Cheng, Shi; Yan, Wen-Mao; Yang, Bin; Shi, Jing-dong; Song, Mao-min; Zhao, Yuqian

    2010-04-01

    To investigate the role of nitric oxide (NO) in acute lung inflammation and injury secondary to acute necrotizing pancreatitis (ANP), 5% sodium taurocholate was retrogradely injected into the biliopancreatic duct of rats to ANP model. These ANP rats were given L-Arginine (L-Arg, 100 mg/kg), L-NAME (10 mg/kg), or their combination by intraperitoneal injection 30 min prior to ANP induction. At 1, 3, 6, and 12 hours after ANP induction, lung NO production, and inducible NO synthase (iNOS) expression were measured. Lung histopathological changes, bronchoalveolar lavage (BAL) protein concentration, proinflammatory mediators tumor necrotic factor alpha (TNF-alpha), and lung tissue myeloperoxidase (MPO) activity were examined. Results showed that NO production and iNOS mRNA expression in alveolar macrophages (AMs) were significantly increased along with significant increases in lung histological abnormalities and BAL proteins in the ANP group, all of which were further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These markers were slightly attenuated by pretreatment with combination of L-Arg + L-NAME, suggesting that NO is required for initiating the acute lung damage in ANP rats, and also that L-Arg-enhanced lung injury is mediated by its NO generation rather than its direct effect. MPO activity and TNF-alpha expression in lung were upregulated in the ANP rats and further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These results suggest that overproduction of NO mediated by iNOS in the lung is required for the acute lung inflammation and damage secondary to ANP.

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  4. 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

  5. Strength of hydrogen bond network takes crucial roles in the dissociation process of inhibitors from the HIV-1 protease binding pocket.

    PubMed

    Li, Dechang; Ji, Baohua; Hwang, Keh-Chih; Huang, Yonggang

    2011-04-29

    To understand the underlying mechanisms of significant differences in dissociation rate constant among different inhibitors for HIV-1 protease, we performed steered molecular dynamics (SMD) simulations to analyze the entire dissociation processes of inhibitors from the binding pocket of protease at atomistic details. We found that the strength of hydrogen bond network between inhibitor and the protease takes crucial roles in the dissociation process. We showed that the hydrogen bond network in the cyclic urea inhibitors AHA001/XK263 is less stable than that of the approved inhibitor ABT538 because of their large differences in the structures of the networks. In the cyclic urea inhibitor bound complex, the hydrogen bonds often distribute at the flap tips and the active site. In contrast, there are additional accessorial hydrogen bonds formed at the lateral sides of the flaps and the active site in the ABT538 bound complex, which take crucial roles in stabilizing the hydrogen bond network. In addition, the water molecule W301 also plays important roles in stabilizing the hydrogen bond network through its flexible movement by acting as a collision buffer and helping the rebinding of hydrogen bonds at the flap tips. Because of its high stability, the hydrogen bond network of ABT538 complex can work together with the hydrophobic clusters to resist the dissociation, resulting in much lower dissociation rate constant than those of cyclic urea inhibitor complexes. This study may provide useful guidelines for design of novel potent inhibitors with optimized interactions.

  6. 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.

  7. 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.

  8. The crucial role of vitamin C and its transporter (SVCT2) in bone marrow stromal cell autophagy and apoptosis

    PubMed Central

    Sangani, Rajnikumar; Periyasamy-Thandavan, Sudharsan; Pathania, Rajneesh; Ahmad, Saif; Kutiyanawalla, Ammar; Kolhe, Ravindra; Bhattacharyya, Maryka H.; Chutkan, Norman; Hunter, Monte; Hill, William D.; Hamrick, Mark; Isales, Carlos; Fulzele, Sadanand

    2016-01-01

    Vitamin C is an antioxidant that plays a vital role in various biological processes including bone formation. Previously, we reported that vitamin C is transported into bone marrow stromal cells (BMSCs) through the sodium dependent Vitamin C Transporter 2 (SVCT2) and this transporter plays an important role in osteogenic differentiation. Furthermore, this transporter is regulated by oxidative stress. To date, however, the exact role of vitamin C and its transporter (SVCT2) in ROS regulated autophagy and apoptosis in BMSCs is poorly understood. In the present study, we observed that oxidative stress decreased survival of BMSCs in a dose-dependent manner and induced growth arrest in the G1 phase of the cell cycle. These effects were accompanied by the induction of autophagy, confirmed by P62 and LC3B protein level and punctate GFP–LC3B distribution. The supplementation of vitamin C significantly rescued the BMSCs from oxidative stress by regulating autophagy. Knockdown of the SVCT2 transporter in BMSCs synergistically decreased cell survival even under low oxidative stress conditions. Also, supplementing vitamin C failed to rescue cells from stress. Our results reveal that the SVCT2 transporter plays a vital role in the mechanism of BMSC survival under stress conditions. Altogether, this study has given new insight into the role of the SVCT2 transporter in oxidative stress related autophagy and apoptosis in BMSCs. PMID:26210298

  9. 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).

  10. 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…

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. [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.

  18. 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.

  19. The role thermal physiology plays in species invasion

    PubMed Central

    Kelley, Amanda L.

    2014-01-01

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

  20. Inflammatory monocytes and NK cells play a crucial role in DNAM-1–dependent control of cytomegalovirus infection

    PubMed Central

    Kaynan, Noa; Jordan, Stefan; Messerle, Martin; Mandelboim, Ofer

    2016-01-01

    The poliovirus receptor (PVR) is a ubiquitously expressed glycoprotein involved in cellular adhesion and immune response. It engages the activating receptor DNAX accessory molecule (DNAM)-1, the inhibitory receptor TIGIT, and the CD96 receptor with both activating and inhibitory functions. Human cytomegalovirus (HCMV) down-regulates PVR expression, but the significance of this viral function in vivo remains unknown. Here, we demonstrate that mouse CMV (MCMV) also down-regulates the surface PVR. The m20.1 protein of MCMV retains PVR in the endoplasmic reticulum and promotes its degradation. A MCMV mutant lacking the PVR inhibitor was attenuated in normal mice but not in mice lacking DNAM-1. This attenuation was partially reversed by NK cell depletion, whereas the simultaneous depletion of mononuclear phagocytes abolished the virus control. This effect was associated with the increased expression of DNAM-1, whereas TIGIT and CD96 were absent on these cells. An increased level of proinflammatory cytokines in sera of mice infected with the virus lacking the m20.1 and an increased production of iNOS by inflammatory monocytes was observed. Blocking of CCL2 or the inhibition of iNOS significantly increased titer of the virus lacking m20.1. In this study, we have demonstrated that inflammatory monocytes, together with NK cells, are essential in the early control of CMV through the DNAM-1–PVR pathway. PMID:27503073

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

    PubMed Central

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

    2014-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. A novel protein C-phycocyanin plays a crucial role in the hypocholesterolemic action of Spirulina platensis concentrate in rats.

    PubMed

    Nagaoka, Satoshi; Shimizu, Kazuo; Kaneko, Hideki; Shibayama, Fumi; Morikawa, Kensei; Kanamaru, Yoshihiro; Otsuka, Ayako; Hirahashi, Tomohiro; Kato, Toshimitsu

    2005-10-01

    This study was designed to clarify the mechanisms of the hypocholesterolemic action of Spirulina platensis concentrate (SPC) and identify the novel hypocholesterolemic protein derived from SPC. We investigated the effects of casein or SPC on the solubility of cholesterol, taurocholate binding capacity in vitro, cholesterol absorption in Caco-2 cells, and cholesterol metabolism in rats for 10 d. We also evaluated the effects of SPC, C-phycocyanin (PHY), and PHY residue on cholesterol metabolism in rats fed a high-cholesterol diet for 5 d, and SPC or SPC-acetone extract for 10 d. SPC had a significantly greater bile acid-binding capacity than casein in vitro. Micellar cholesterol solubility and cholesterol uptake by Caco-2 cells was significantly lower in the presence of SPC compared with casein. Fecal excretion of cholesterol and bile acids was significantly greater in rats fed the SPC-supplemented diet than in those fed the casein control diet. Serum and liver cholesterol concentrations were significantly lower in rats fed SPC than in those fed casein. Thus, the hypocholesterolemic action of SPC may involve the inhibition of both jejunal cholesterol absorption and ileal bile acid reabsorption. Although no studies to date have found a hypocholesterolemic protein among the algal proteins, we report here the discovery of a hypocholesterolemic effect in the novel protein C-phycocyanin. This study provides the first direct evidence that PHY, a novel hypocholesterolemic protein derived from Spirulina platensis, can powerfully influence serum cholesterol concentrations and impart a stronger hypocholesterolemic activity than SPC in animals.

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

    PubMed Central

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

    2017-01-01

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

  5. The endothelin B receptor plays a crucial role for the adhesion of neutrophils to the endothelium in sickle cell disease.

    PubMed

    Koehl, Bérengère; Nivoit, Pierre; El Nemer, Wassim; Lenoir, Olivia; Hermand, Patricia; Pereira, Catia; Brousse, Valentine; Guyonnet, Léa; Ghinatti, Giulia; Benkerrou, Malika; Colin, Yves; Le Van Kim, Caroline; Tharaux, Pierre-Louis

    2017-04-06

    Although the primary origin of sickle cell disease is a hemoglobin disorder, several cell types contribute considerably to the physiopathology of the disease. The adhesion of neutrophils to activated endothelium is critical in sickle cell disease pathophysiology and the targeting of neutrophils and their interactions with endothelium represent important opportunities for new therapeutics. We focused on endothelin-1, a mediator involved in neutrophil activation and recruitment in tissues, and we investigated the involvement of the endothelin receptors in interaction of neutrophils with endothelial cells. We used fluorescence intravital microscopy analyses of the microcirculation in sickle mice and quantitative microfluidic fluorescence microscopy of human blood. Both experiments on mouse model and patients indicate that blocking endothelin receptors, particularly ETB receptor highly influences neutrophils recruitment under inflammatory conditions in sickle cell disease. We show that human neutrophils display functional ETB receptors with calcium signaling capability leading to increased adhesion to the endothelium, through action on both endothelial cells and neutrophils. ETB intact function was also found to be required for TNFα-dependent upregulation of CD11b on neutrophils. Furthermore, we confirmed that human neutrophils synthesize endothelin-1 that may be involved in autocrine and paracrine pathophysiological actions. Thus, the endothelin-ETB axis should be considered as a cytokine-like potent pro-inflammatory pathway in sickle cell disease. Blockade of endothelin receptor, including ETB, may provide major benefits for preventing or treating vaso-occlusive crises of sickle cell patients.

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

    PubMed

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

    2011-05-01

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

  7. Autoinducer-2 plays a crucial role in gut colonization and probiotic functionality of Bifidobacterium breve UCC2003.

    PubMed

    Christiaen, Steven E A; O'Connell Motherway, Mary; Bottacini, Francesca; Lanigan, Noreen; Casey, Pat G; Huys, Geert; Nelis, Hans J; van Sinderen, Douwe; Coenye, Tom

    2014-01-01

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

  8. 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

  9. 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.

  10. Auxin-binding pocket of ABP1 is crucial for its gain-of-function cellular and developmental roles.

    PubMed

    Grones, Peter; Chen, Xu; Simon, Sibu; Kaufmann, Walter A; De Rycke, Riet; Nodzyński, Tomasz; Zažímalová, Eva; Friml, Jiří

    2015-08-01

    The plant hormone auxin is a key regulator of plant growth and development. Auxin levels are sensed and interpreted by distinct receptor systems that activate a broad range of cellular responses. The Auxin-Binding Protein1 (ABP1) that has been identified based on its ability to bind auxin with high affinity is a prime candidate for the extracellular receptor responsible for mediating a range of auxin effects, in particular, the fast non-transcriptional ones. Contradictory genetic studies suggested prominent or no importance of ABP1 in many developmental processes. However, how crucial the role of auxin binding to ABP1 is for its functions has not been addressed. Here, we show that the auxin-binding pocket of ABP1 is essential for its gain-of-function cellular and developmental roles. In total, 16 different abp1 mutants were prepared that possessed substitutions in the metal core or in the hydrophobic amino acids of the auxin-binding pocket as well as neutral mutations. Their analysis revealed that an intact auxin-binding pocket is a prerequisite for ABP1 to activate downstream components of the ABP1 signalling pathway, such as Rho of Plants (ROPs) and to mediate the clathrin association with membranes for endocytosis regulation. In planta analyses demonstrated the importance of the auxin binding pocket for all known ABP1-mediated postembryonic developmental processes, including morphology of leaf epidermal cells, root growth and root meristem activity, and vascular tissue differentiation. Taken together, these findings suggest that auxin binding to ABP1 is central to its function, supporting the role of ABP1 as auxin receptor.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. Crucial role of the Rap G protein signal in Notch activation and leukemogenicity of T-cell acute lymphoblastic leukemia.

    PubMed

    Doi, Keiko; Imai, Takahiko; Kressler, Christopher; Yagita, Hideo; Agata, Yasutoshi; Vooijs, Marc; Hamazaki, Yoko; Inoue, Joe; Minato, Nagahiro

    2015-01-23

    The Rap G protein signal regulates Notch activation in early thymic progenitor cells, and deregulated Rap activation (Rap(high)) results in the development of Notch-dependent T-cell acute lymphoblastic leukemia (T-ALL). We demonstrate that the Rap signal is required for the proliferation and leukemogenesis of established Notch-dependent T-ALL cell lines. Attenuation of the Rap signal by the expression of a dominant-negative Rap1A17 or Rap1GAP, Sipa1, in a T-ALL cell line resulted in the reduced Notch processing at site 2 due to impaired maturation of Adam10. Inhibition of the Rap1 prenylation with a geranylgeranyl transferase inhibitor abrogated its membrane-anchoring to Golgi-network and caused reduced proprotein convertase activity required for Adam10 maturation. Exogenous expression of a mature form of Adam10 overcame the Sipa1-induced inhibition of T-ALL cell proliferation. T-ALL cell lines expressed Notch ligands in a Notch-signal dependent manner, which contributed to the cell-autonomous Notch activation. Although the initial thymic blast cells barely expressed Notch ligands during the T-ALL development from Rap(high) hematopoietic progenitors in vivo, the ligands were clearly expressed in the T-ALL cells invading extrathymic vital organs. These results reveal a crucial role of the Rap signal in the Notch-dependent T-ALL development and the progression.

  18. Activating KIRs exert a crucial role on relapse and overall survival after HLA-identical sibling transplantation.

    PubMed

    Schellekens, Jennifer; Rozemuller, Erik H; Petersen, Eefke J; van den Tweel, Jan G; Verdonck, Leo F; Tilanus, Marcel G J

    2008-04-01

    Recognition of HLA-C molecules by killer cell immunoglobulin-like receptors (KIRs) is an important mechanism in the regulation of natural killer (NK) cell activity. Eradication of residual leukaemic cells by alloreactive donor NK cells after haematopoietic stem cell transplantation (HSCT) fulfils a crucial role in the control of relapse. This retrospective study evaluates 83 patients and their related donors. All individuals were typed at low-resolution level to determine their HLA repertoire. KIR genotyping data were obtained by the use of sequence-specific oligonucleotide (SSO) analysis. All data were combined with patient and donor characteristics and post-transplant clinical data. A higher overall survival was seen when KIR2DS1 in the donor was mismatched with the HLA-C group 2 ligand in the patient (p=0.03). The number of activating KIRs either in the patient or in the donor was significantly correlated with the occurrence of relapse (p=0.003 and p=0.02, respectively). In addition, the presence of KIR2DS5 in the patient alone or in both the patient and donor was significantly correlated with the occurrence of relapse (p=0.004 and p=0.005, respectively). In conclusion, significant correlations were found for activating KIRs with overall survival and relapse.

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2016-01-01

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

  1. The physiatrists' crucial role in the development and implementation of a longitudinal musculoskeletal physical examination curriculum in a medical school.

    PubMed

    Newcomer, Karen L; Laskowski, Edward R; Grande, Joseph P; Dyrbye, Liselotte N

    2013-01-01

    The musculoskeletal physical examination (MSK PE) is a critical clinical skill that should be mastered by all medical students. The authors believe that physiatrists should have a crucial role in undergraduate musculoskeletal education. This article outlines the successful integration of an MSK PE curriculum taught by physiatrists into the first 2 yrs of medical school. During year 1, a basic MSK PE is taught concomitantly with the human anatomy course and focuses on anatomical correlation with physical examination maneuvers. In year 2, the MSK PE is taught concomitantly with the musculoskeletal didactic block. Special musculoskeletal tests, basic neurologic evaluation, and case correlation are also added to expand on the examination skills learned in the first year. At the end of the second year and before beginning third-year clinical rotations, students take a practical test to demonstrate their competency in the MSK PE. The authors believe that an important component of their MSK PE educational sessions is a low student-to-instructor ratio (4:1), with ample hands-on supervision of physical examination skills practice. Residents in the Department of Physical Medicine and Rehabilitation assist with the teaching. With their intensive training and clinical experience in musculoskeletal medicine, physiatric staff and residents are ideal faculty for teaching the MSK PE. The authors are hopeful that this article encourages other physiatrists to construct similar programs aimed to develop MSK PE skills in medical students.

  2. Cytosolic phospholipase A2 α has a crucial role in the pathogenesis of DSS-induced colitis in mice.

    PubMed

    Rosengarten, Marina; Hadad, Nurit; Solomonov, Yulia; Lamprecht, Sergio; Levy, Rachel

    2016-02-01

    Colitis, an inflammation of the colon, is a well-characterized massive tissue injury. Cytosolic phospholipase A2 α (cPLA2 α) upregulation plays an important role in the development of several inflammatory diseases. The aim of the present study was to define the role of cPLA2 α upregulation in the development of colitis. We used a mouse model of dextran sulfate sodium induced colitis. Immunoblotting analysis showed that cPLA2 α and NF-κB were upregulated and activated in the colon from day 2 of colitis induction. This molecular event preceded the development of the disease, as determined by Disease Activity Index score, body weight, colon length, and the expression of colonic inflammatory markers, including neutrophil infiltration detected by myeloperoxidase and by NIMP-R14, ICAM-1, COX-2, iNOS upregulation and LTB4 and TNF-α secretion. Prevention of cPLA2 α upregulation and activity in the colon by i.v. administration of specific antisense oligonucleotides against cPLA2 α 1 day prior and every day of exposure to dextran sulfate sodium significantly impeded the development of the disease and prevented NF-κB activation, neutrophils infiltration into the colonic mucosa, and expression of proinflammatory proteins in the colon. Our results demonstrate a critical role of cPLA2 α upregulation in inflammation and development of murine colitis.

  3. Long-range effects in anion-π interactions: their crucial role in the inhibition mechanism of Mycobacterium tuberculosis malate synthase.

    PubMed

    Bauzá, Antonio; Quiñonero, David; Deyà, Pere M; Frontera, Antonio

    2014-06-02

    The glyoxylate shunt is an anaplerotic bypass of the traditional Krebs cycle. It plays a prominent role in Mycobacterium tuberculosis virulence, so it can be exploited for the development of antitubercular therapeutics. The shunt involves two enzymes: isocitrate lyase (ICL) and malate synthase (GlcB). The shunt bypasses two steps of the tricarboxylic acid cycle, allowing the incorporation of carbon, and thus, refilling oxaloacetate under carbon-limiting conditions. The targeting of ICL is complicated; however, GlcB, which accommodates the pantothenate tail of acetyl-CoA in the active site, is easier to target. A catalytic Mg(2+) unit is located at the bottom of the cavity, and plays a very important role. Recently, the development of effective antituberculosis drugs based on phenyldiketo acids (PDKAs) has been reported. Interestingly, all the crystal structures of GlcB-inhibitor complexes exhibit close contact between the carboxylate of Asp633 and the face of the aromatic ring of the inhibitor. Remarkably, the replacement of the phenyl ring in PDKA by aliphatic moieties yields inactive inhibitors, suggesting that the aromatic moiety is crucial for inhibition. However, the aromatic ring of PDKA is not electron-deficient, and consequently, the anion-π interaction is expected to be very weak (dominated only by polarization effects). Herein, through a combination analysis of the recent X-ray structures of GlcB-PDKA complexes retrieved from the protein data bank (PDB) and computational ab initio studies (RI-MP2/def2-TZVP level of theory), we demonstrate the prominent role of the Mg(2+) ion in the active site, which promotes long-range enhancement of the anion-π interaction.

  4. 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…

  5. 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…

  6. 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

  7. 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.

  8. Memo has a novel role in S1P signaling and is [corrected] crucial for vascular development.

    PubMed

    Kondo, Shunya; Bottos, Alessia; Allegood, Jeremy C; Masson, Regis; Maurer, Francisca G; Genoud, Christel; Kaeser, Patrick; Huwiler, Andrea; Murakami, Masato; Spiegel, Sarah; Hynes, Nancy E

    2014-01-01

    Memo is a conserved protein that was identified as an essential mediator of tumor cell motility induced by receptor tyrosine kinase activation. Here we show that Memo null mouse embryonic fibroblasts (MEFs) are impaired in PDGF-induced migration and this is due to a defect in sphingosine-1-phosphate (S1P) signaling. S1P is a bioactive phospholipid produced in response to multiple stimuli, which regulates many cellular processes. S1P is secreted to the extracellular milieu where it exerts its function by binding a family of G-protein coupled receptors (S1PRs), causing their activation in an autocrine or paracrine manner. The process, termed cell-autonomous S1PR signaling, plays a role in survival and migration. Indeed, PDGF uses cell-autonomous S1PR signaling to promote cell migration; we show here that this S1P pathway requires Memo. Using vascular endothelial cells (HUVECs) with Memo knock-down we show that their survival in conditions of serum-starvation is impaired. Furthermore, Memo loss in HUVECs causes a reduction of junctional VE-cadherin and an increase in sprout formation. Each of these phenotypes is rescued by S1P or S1P agonist addition, showing that Memo also plays an important role in cell-autonomous S1PR signaling in endothelial cells. We also produced conventional and endothelial cell-specific conditional Memo knock-out mouse strains and show that Memo is essential for embryonic development. Starting at E13.5 embryos of both strains display bleeding and other vascular problems, some of the phenotypes that have been described in mouse strains lacking S1PRs. The essential role of Memo in embryonic vascular development may be due in part to alterations in S1P signaling. Taken together our results show that Memo has a novel role in the S1P pathway and that Memo is needed to promote cell-autonomous S1PR activation.

  9. 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

  10. 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.

  11. 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

  12. Crucial role of cytoskeleton reorganization in the negative inotropic effect of chromogranin A-derived peptides in eel and frog hearts.

    PubMed

    Mazza, Rosa; Mannarino, Cinzia; Imbrogno, Sandra; Barbieri, Sandra Francesca; Adamo, Cristina; Angelone, Tommaso; Corti, Angelo; Tota, Bruno

    2007-02-01

    Vasostatins (VSs), i.e. the main biologically active peptides generated by the proteolytic processing of chromogranin A (CGA) N-terminus, exert negative inotropism in vertebrate hearts. Here, using isolated working eel (Anguilla anguilla) and frog (Rana esculenta) heart preparations, we have studied the role of the cytoskeleton in the VSs-mediated inotropic response. In both eel and frog hearts, VSs-mediated-negative inotropy was abolished by treatment with inhibitors of cytoskeleton reorganization, such as cytochalasin-D (eel: 10 nM; frog: 1 nM), an inhibitor of actin polymerisation, wortmannin (0.01 nM), an inhibitor of PI3-kinase (PI3-K)/protein kinase B (Akt) signal-transduction cascade, butanedione 2-monoxime (BDM) (eel: 100 nM; frog: 10 nM), an antagonist of myosin ATPase, and N-(6-aminohexil)-5-chloro-1-naphthalenesulfonamide (W7) (eel: 100 nM; frog: 1 nM), a calcium-calmodulin antagonist. These results demonstrate that changes in cytoskeletal dynamics play a crucial role in the negative inotropic influence of VSs on eel and frog hearts.

  13. Membrane organization of virus and target cell plays a role in HIV entry.

    PubMed

    Dumas, Fabrice; Preira, Pascal; Salomé, Laurence

    2014-12-01

    The initial steps of the Human Immunodeficiency Virus (HIV) replication cycle play a crucial role that arbitrates viral tropism and infection efficiency. Before the release of its genome into the host cell cytoplasm, viruses operate a complex sequence of events that take place at the plasma membrane of the target cell. The first step is the binding of the HIV protein envelope (Env) to the cellular receptor CD4. This triggers conformational changes of the gp120 viral protein that allow its interaction with a co-receptor that can be either CCR5 or CXCR4, defining the tropism of the virus entering the cell. This sequential interaction finally drives the fusion of the viral and host cell membrane or to the endocytosis of the viruses. Here, we discuss how the membrane composition and organization of both the virus and the target cell can affect these steps and thus influence the capability of the viruses to infect cells.

  14. Activity-dependent regulation of release probability at excitatory hippocampal synapses: a crucial role of FMRP in neurotransmission

    PubMed Central

    Wang, Xiao-Sheng; Peng, Chun-Zi; Cai, Wei-Jun; Xia, Jian; Jin, Daozhong; Dai, Yuqiao; Luo, Xue-Gang; Klyachko, Vitaly A.; Deng, Pan-Yue

    2014-01-01

    Transcriptional silencing of the Fmr1 gene encoding fragile X mental retardation protein (FMRP) causes Fragile X Syndrome (FXS), the most common form of inherited intellectual disability and the leading genetic cause of autism. FMRP has been suggested to play important roles in regulating neurotransmission and short-term synaptic plasticity at excitatory hippocampal and cortical synapses. However, the origins and the mechanisms of these FMRP actions remain incompletely understood, and the role of FMRP in regulating synaptic release probability and presynaptic function remains debated. Here we used variance-mean analysis and peak scaled nonstationary variance analysis to examine changes in both pre- and postsynaptic parameters during repetitive activity at excitatory CA3-CA1 hippocampal synapses in a mouse model of FXS. Our analyses revealed that loss of FMRP did not affect the basal release probability or basal synaptic transmission, but caused an abnormally elevated release probability specifically during repetitive activity. These abnormalities were not accompanied by changes in EPSC kinetics, quantal size or postsynaptic AMPA receptor conductance. Our results thus indicate that FMRP regulates neurotransmission at excitatory hippocampal synapses specifically during repetitive activity via modulation of release probability in a presynaptic manner. Our study suggests that FMRP function in regulating neurotransmitter release is an activity-dependent phenomenon that may contribute to the pathophysiology of FXS. PMID:24646437

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

    PubMed Central

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

    2016-01-01

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

  16. 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…

  17. 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,…

  18. 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…

  19. 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…

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

    SciTech Connect

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

    2015-10-28

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

  1. Importance of pH homeostasis in metabolic health and diseases: crucial role of membrane proton transport.

    PubMed

    Aoi, Wataru; Marunaka, Yoshinori

    2014-01-01

    Protons dissociated from organic acids in cells are partly buffered. If not, they are transported to the extracellular fluid through the plasma membrane and buffered in circulation or excreted in urine and expiration gas. Several transporters including monocarboxylate transporters and Na(+)/H(+) exchanger play an important role in uptake and output of protons across plasma membranes in cells of metabolic tissues including skeletal muscle and the liver. They also contribute to maintenance of the physiological pH of body fluid. Therefore, impairment of these transporters causes dysfunction of cells, diseases, and a decrease in physical performance associated with abnormal pH. Additionally, it is known that fluid pH in the interstitial space of metabolic tissues is easily changed due to little pH buffering capacitance in interstitial fluids and a reduction in the interstitial fluid pH may mediate the onset of insulin resistance unlike blood containing pH buffers such as Hb (hemoglobin) and albumin. In contrast, habitual exercise and dietary intervention regulate expression/activity of transporters and maintain body fluid pH, which could partly explain the positive effect of healthy lifestyle on disease prognosis.

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

    PubMed

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

    2015-10-28

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

  3. Identification of the silkworm quail gene reveals a crucial role of a receptor guanylyl cyclase in larval pigmentation.

    PubMed

    Yuasa, Masashi; Kiuchi, Takashi; Banno, Yutaka; Katsuma, Susumu; Shimada, Toru

    2016-01-01

    Diverse color patterns on the integument of lepidopteran larvae play important roles in their survival through camouflage, mimicry, sexual signaling, and aposematism. In the silkworm Bombyx mori, many color pattern variations have been preserved in inbred strains making them a good model for elucidating the molecular mechanisms that underlie color pattern formation. In this study, we focused on the silkworm quail (q) mutant, which exhibits abnormalities in multiple pigment biosynthesis pathways. Positional cloning of the q gene revealed that disruption of a guanylyl cyclase gene, BmGC-I, is responsible for its abnormal pigmentation. In q mutants, we identified a 16-bp deletion in the BmGC-I transcript, resulting in the production of a premature stop codon. Knockout of the BmGC-I gene resulted in the q-like abnormal pigmentation, thereby demonstrating that the BmGC-I gene is involved in the pigment biosynthesis pathway in the integument. Moreover, quantitative reverse transcription polymerase chain reaction showed that BmGC-I was strongly expressed in the fourth instar on day 2. Our results suggest that BmGC-I deficiency affects the pigment biosynthesis pathway, which supports the involvement of guanylyl cyclase in larval coloration.

  4. 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

  5. Crucial roles of Robo proteins in midline crossing of cerebellofugal axons and lack of their up-regulation after midline crossing

    PubMed Central

    Tamada, Atsushi; Kumada, Tatsuro; Zhu, Yan; Matsumoto, Tomoko; Hatanaka, Yumiko; Muguruma, Keiko; Chen, Zhe; Tanabe, Yasuto; Torigoe, Makio; Yamauchi, Kenta; Oyama, Hiroshi; Nishida, Kazuhiko; Murakami, Fujio

    2008-01-01

    Background Robo1, Robo2 and Rig-1 (Robo3), members of the Robo protein family, are candidate receptors for the chemorepellents Slit and are known to play a crucial role in commissural axon guidance in the spinal cord. However, their roles at other axial levels remain unknown. Here we examine expression of Robo proteins by cerebellofugal (CF) commissural axons in the rostral hindbrain and investigate their roles in CF axon pathfinding by analysing Robo knockout mice. Results We analysed the expression of Robo proteins by CF axons originating from deep cerebellar neurons in rodent embryos, focusing on developmental stages of their midline crossing and post-crossing navigation. At the stage of CF axon midline crossing, mRNAs of Robo1 and Robo2 are expressed in the nuclear transitory zone of the cerebellum, where the primordium of the deep cerebellar nuclei are located, supporting the notion that CF axons express Robo1 and Robo2. Indeed, immunohistochemical analysis of CF axons labelled by electroporation to deep cerebellar nuclei neurons indicates that Robo1 protein, and possibly also Robo2 protein, is expressed by CF axons crossing the midline. However, weak or no expression of these proteins is found on the longitudinal portion of CF axons. In Robo1/2 double knockout mice, many CF axons reach the midline but fail to exit it. We find that CF axons express Rig-1 (Robo3) before they reach the midline but not after the longitudinal turn. Consistent with this in vivo observation, axons elicited from a cerebellar explant in co-culture with a floor plate explant express Rig-1. In Rig-1 deficient mouse embryos, CF axons appear to project ipsilaterally without reaching the midline. Conclusion These results indicate that Robo1, Robo2 or both are required for midline exit of CF axons. In contrast, Rig-1 is required for their approach to the midline. However, post-crossing up-regulation of these proteins, which plays an important role in spinal commissural axon guidance, does

  6. 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…

  7. 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.

  8. 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…

  9. 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…

  10. Salt gradient driven ion transport in solid-state nanopores: the crucial role of reservoir geometry and size.

    PubMed

    Lin, Chih-Yuan; Chen, Fu; Yeh, Li-Hsien; Hsu, Jyh-Ping

    2016-11-21

    Modern applications of nanotechnology such as salinity gradient power and ionic diodes usually involve the transport of ionic species in a system comprising a nanopore connecting two large reservoirs. The charge properties on the nanopore surface plays a key role, and they need to be estimated by fitting a mathematical model for the system to measurable quantities such as ionic current or conductance. This model can also be used to simulate the system behavior under various conditions. However, the large difference between the linear size of a nanopore and that of a reservoir makes relevant analyses difficult. Considering numerical efforts, the impact of the computational domain for the reservoir geometry and size on the system behavior is almost always overlooked in previous studies, where the computational domain for a reservoir is often assumed to have a relatively small size. Taking salinity gradient ionic current as an example, we show for the first time that the performance of a reservoir-nanopore-reservoir system is influenced appreciably by the computational domain for the reservoir geometry and size, especially when a voltage bias is not applied. Using the reported experimental data for the osmotic current in a single boron nitride nanopore, we show that its surface charge density can be estimated realistically by choosing an appropriate computational domain for reservoir geometry and size. Numerical simulation also reveals that choosing appropriate reservoir geometry and size is necessary; otherwise, the results obtained might be unreliable, or even misleading. To avoid this, we suggest that for the nanopore with the pore length smaller than 1000 nm, the size of the computational domain of a reservoir, (length × radius), with equal length and radius, should exceed 800 × 800 nm.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-04-01

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

  13. 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)

  14. 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

  15. 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.

  16. 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…

  17. Crucial role of membrane potential in heat stress-induced overproduction of reactive oxygen species in avian skeletal muscle mitochondria.

    PubMed

    Kikusato, Motoi; Toyomizu, Masaaki

    2013-01-01

    Heat stress is an environmental factor that causes oxidative stress. We found previously that acute heat stress stimulates the production of reactive oxygen species (ROS) in the skeletal muscle mitochondria of birds, and that this was accompanied by an increase of the mitochondrial membrane potential (ΔΨ) due to increased substrate oxidation by the electron transport chain. We also showed that avian uncoupling protein (avUCP) expression is decreased by the heat exposure. The present study clarifies whether ΔΨ is a major determinant of the overproduction of ROS due to acute heat stress, and if the decrease in avUCP expression is responsible for the elevation in ΔΨ. Control (24°C) and acute heat-stressed (34°C for 12 h) birds exhibited increased succinate-driven mitochondrial ROS production as indicated by an elevation of ΔΨ, with this increase being significantly higher in the heat-stressed group compared with the control group. In glutamate/malate-energized mitochondria, no difference in the ROS production between the groups was observed, though the mitochondrial ΔΨ was significantly higher in the heat-stressed groups compared with the control group. Furthermore, mitochondria energized with either succinate/glutamate or succinate/malate showed increased ROS production and ΔΨ in the heat-stressed group compared with mitochondria from the control group. These results suggest that succinate oxidation could play an important role in the heat stress-induced overproduction of mitochondrial ROS in skeletal muscle. In agreement with the notion of a decrease in avUCP expression in response to heat stress, proton leak, which was likely mediated by UCP (that part which is GDP-inhibited and arachidonic acid-sensitive), was reduced in the heat-exposed group. We suggest that the acute heat stress-induced overproduction of mitochondrial ROS may depend on ΔΨ, which may in turn result not only from increased substrate oxidation but also from a decrease in the

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

    DOE PAGES

    Young, Jenna; Chung, Daehwan; Bomble, Yannick J.; ...

    2014-10-09

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

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

    SciTech Connect

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

    2014-10-09

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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-21

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

  7. 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

  8. 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

  9. 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

  10. 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.

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

    PubMed Central

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

    1990-01-01

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

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  13. Does seed size and surface anatomy play role in combating phytotoxicity of nanoparticles?

    PubMed

    Jain, Navin; Bhargava, Arpit; Pareek, Vikram; Sayeed Akhtar, Mohd; Panwar, Jitendra

    2017-03-01

    Rapid utilization of nano-based products will inevitably release nanoparticles into the environment with unidentified consequences. Plants, being an integral part of ecosystem play a vital role in the incorporation of nanoparticles in food chain and thus, need to be critically assessed. The present study assesses the comparative phytotoxicity of nanoparticle, bulk and ionic forms of zinc at different concentrations on selected plant species with varying seed size and surface anatomy. ZnO nanoparticles were chosen in view of their wide spread use in cosmetics and health care products, which allow their direct release in the environment. The impact on germination rate, shoot & root length and vigour index were evaluated. A concentration dependent inhibition of seed germination as well as seedling length was observed in all the tested plants. Due to the presence of thick cuticle on testa and root, pearl millet (xerophytic plant) was found to be relatively less sensitive to ZnO nanoparticles as compared to wheat and tomato (mesophytic plants) with normal cuticle layer. No correlation was observed between nanoparticles toxicity and seed size. The results indicated that variations in surface anatomy of seeds play a crucial role in determining the phytotoxicity of nanoparticles. The present findings significantly contribute to assess potential consequences of nanoparticle release in environment particularly with major emphasis on plant systems. It is the first report which suggests that variations observed in phytotoxicity of nanoparticles is mainly due to the predominant differences in size and surface anatomy of tested plant seeds and root architecture. Effect of various concentrations of nano ZnO, bulk ZnO and zinc sulphate on the growth of pearl millet (A), tomato (B) and wheat (C) seedlings.

  14. 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.

  15. 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

  16. 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

  17. [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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. [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.

  7. 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

  8. 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.

  9. Inwardly rectifying K+ (Kir) channels in Drosophila. A crucial role of cellular milieu factors Kir channel function.

    PubMed

    Döring, Frank; Wischmeyer, Erhard; Kühnlein, Ronald P; Jäckle, Herbert; Karschin, Andreas

    2002-07-12

    Three cDNAs encoding inwardly rectifying potassium (Kir) channels were isolated from Drosophila melanogaster. The protein sequences of Drosophila KirI (dKirI) and dKirII are moderately (<44%) and dKirIII sequence is weakly (<27%) identical to human Kir channel subunits. During fly development, five dKir channel transcripts derived from three genes are differentially expressed. Whole mount in situ hybridizations revealed dKirI transcripts absent from embryos, but dKirII and dKirIII are expressed in the embryonic hind gut and in Malpighian tubules, respectively, thus covering the entire osmoregulatory system of the developing fly. In the head of adult flies, predominantly dKirII transcripts were detected. When expressed in Xenopus oocytes, dKir channel activity was only observed after amino acid substitutions in their cytosolic tails (e.g. exchange of a unique valine in the NH(2) terminus). In contrast, heterologous expression of wild type dKirI and dKirII in Drosophila S2 cells readily evoked typical inwardly rectifying K(+) currents, which were weakly sensitive to Ba(2+). Thus, the specific milieu of insect cells provides a crucial cellular environment for proper function of dKir channels.

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

    SciTech Connect

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

    1992-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-05-10

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

  13. 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

  14. 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…

  15. Crucial Role for Neuronal Nitric Oxide Synthase in Early Microcirculatory Derangement and Recipient Survival following Murine Pancreas Transplantation

    PubMed Central

    Cardini, Benno; Watschinger, Katrin; Hermann, Martin; Obrist, Peter; Oberhuber, Rupert; Brandacher, Gerald; Chuaiphichai, Surawee; Channon, Keith M.; Pratschke, Johann; Maglione, Manuel; Werner, Ernst R.

    2014-01-01

    Objective Aim of this study was to identify the nitric oxide synthase (NOS) isoform involved in early microcirculatory derangements following solid organ transplantation. Background Tetrahydrobiopterin donor treatment has been shown to specifically attenuate these derangements following pancreas transplantation, and tetrahydrobiopterin-mediated protective effects to rely on its NOS-cofactor activity, rather than on its antioxidant capacity. However, the NOS-isoform mainly involved in this process has still to be defined. Methods Using a murine pancreas transplantation model, grafts lacking one of the three NOS-isoforms were compared to grafts from wild-type controls. Donors were treated with either tetrahydrobiopterin or remained untreated. All grafts were subjected to 16 h cold ischemia time and transplanted into wild-type recipients. Following 4 h graft reperfusion, microcirculation was analysed by confocal intravital fluorescence microscopy. Recipient survival was monitored for 50 days. Results Transplantation of the pancreas from untreated wild-type donor mice resulted in microcirculatory damage of the transplanted graft and no recipient survived more than 72 h. Transplanting grafts from untreated donor mice lacking either endothelial or inducible NOS led to similar outcomes. In contrast, donor treatment with tetrahydrobiopterin prevented microcirculatory breakdown enabling long-term survival. Sole exception was transplantation of grafts from untreated donor mice lacking neuronal NOS. It resulted in intact microvascular structure and long-term recipient survival, either if donor mice were untreated or treated with tetrahydrobiopterin. Conclusion We demonstrate for the first time the crucial involvement of neuronal NOS in early microcirculatory derangements following solid organ transplantation. In this model, protective effects of tetrahydrobiopterin are mediated by targeting this isoform. PMID:25389974

  16. 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…

  17. 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…

  18. 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…

  19. 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)

  20. 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…

  1. 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…

  2. 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.

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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…

  14. The fundamental contribution of Robert A. Good to the discovery of the crucial role of thymus in mammalian immunity

    PubMed Central

    Ribatti, Domenico

    2006-01-01

    Robert Alan Good was a pioneer in the field of immunodeficiency diseases. He and his colleagues defined the cellular basis and functional consequences of many of the inherited immunodeficiency diseases. His was one of the groups that discovered the pivotal role of the thymus in the immune system development and defined the separate development of the thymus-dependent and bursa-dependent lymphoid cell lineages and their responsibilities in cell-mediated and humoral immunity. PMID:17067308

  15. A Crucial Role for p90RSK-Mediated Reduction of ERK5 Transcriptional Activity in Endothelial Dysfunction and Atherosclerosis

    PubMed Central

    Le, Nhat-Tu; Heo, Kyung-Sun; Takei, Yuichiro; Lee, Hakjoo; Woo, Chang-Hoon; Chang, Eugene; McClain, Carolyn; Hurley, Cheryl; Wang, Xin; Li, Faqian; Xu, Haodong; Morrell, Craig; Sullivan, Mark A.; Cohen, Michael S.; Serafimova, Iana M.; Taunton, Jack; Fujiwara, Keigi; Abe, Jun-ichi

    2013-01-01

    Background Diabetes mellitus (DM) is a major risk factor for cardiovascular mortality by increasing endothelial cell (EC) dysfunction and subsequently accelerating atherosclerosis. Extracellular-signal regulated kinase 5 (ERK5) is activated by steady laminar flow and regulates EC function by increasing eNOS expression and inhibiting EC inflammation. However, the role and regulatory mechanisms of ERK5 in EC dysfunction and atherosclerosis are poorly understood. Here, we report the critical role of the p90 ribosomal S6 kinase (p90RSK)/ERK5 complex in EC dysfunction in DM and atherosclerosis. Methods and Results Inducible EC-specific ERK5 knockout (ERK5-EKO) mice showed increased leukocyte rolling and impaired vessel reactivity. To examine the role of endothelial ERK5 in atherosclerosis, we used inducible ERK5-EKO-LDLR−/− mice and observed increased plaque formation. When activated, p90RSK associated with ERK5, and this association inhibited ERK5 transcriptional activity and up-regulated VCAM-1 expression. In addition, p90RSK directly phosphorylated ERK5 S496 and reduced eNOS expression. p90RSK activity was increased in diabetic mouse vessels, and FMK-MEA, a specific p90RSK inhibitor, ameliorated EC-leukocyte recruitment and diminished vascular reactivity in DM mice. Interestingly, in ERK-EKO mice, increased leukocyte rolling and impaired vessel reactivity were resistant to the beneficial effects of FMK-MEA, suggesting a critical role for endothelial ERK5 in mediating the salutary effects of FMK-MEA on endothelial dysfunction. FMK-MEA also inhibited atherosclerosis formation in ApoE−/− mice. Conclusions Our study highlights the importance of the p90RSK/ERK5 module as a critical mediator of EC dysfunction in DM and atherosclerosis formation, thus revealing a potential new target for therapeutic intervention. PMID:23243209

  16. 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…

  17. 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.

  18. The crucial role of calcium interacting with soil pH in enhanced biodegradation of metam-sodium.

    PubMed

    Warton, Ben; Matthiessen, John N

    2005-09-01

    Enhanced biodegradation of soil-applied pesticides has long been correlated with soil pH above ca 6.5-7.5, but the possibility of confounding or interdependence with calcium, given that soil calcium concentration increases exponentially as pH rises above that range, has not previously been studied. Enhanced biodegradation of the broad-spectrum biocide metam-sodium was readily induced de novo in a naturally acid sandy soil (pH 4.2 measured in 0.01 M CaCl2) by multiple treatments, but only when the pH and calcium concentration were raised simultaneously using calcium carbonate (lime). Enhanced biodegradation was not induced when soil pH alone was raised with magnesium carbonate, nor when calcium alone was raised using calcium chloride. In limed sand treated monthly for 12 months, the degradation rate increased to where dissipation was complete within 24 h of application after the fifth metam-sodium treatment at pH 7.8 and after the eighth metam-sodium treatment at pH 6.8. Pesticide concentration was reduced, but not eliminated, at pH 5.8 and was unchanged at pH 4.8. When metam-sodium was applied bi- and tri-monthly, the degradation rate also increased when soil pH was raised with calcium carbonate, but to a lesser extent than with monthly applications. In an acid loam soil amended to the same pH values with calcium carbonate and treated monthly, there was no correlation between soil pH or calcium concentration and degradation. The results reveal the crucial interdependence of pH and calcium concentration in enhancement of biodegradation of soil-applied pesticides, but confirm that the phenomenon ultimately depends on interaction with soil type and frequency of application factors, all of which probably together act to affect the abundance, composition and activity of the soil microbial biomass.

  19. BACE2 plays a role in the insulin receptor trafficking in pancreatic ß-cells.

    PubMed

    Casas, Silvia; Casini, Paola; Piquer, Sandra; Altirriba, Jordi; Soty, Maud; Cadavez, Lisa; Gomis, Ramon; Novials, Anna

    2010-12-01

    BACE1 (β-site amyloidogenic cleavage of precursor protein-cleaving enzyme 1) is a β-secretase protein that plays a central role in the production of the β-amyloid peptide in the brain and is thought to be involved in the Alzheimer's pathogenesis. In type 2 diabetes, amyloid deposition within the pancreatic islets is a pathophysiological hallmark, making crucial the study in the pancreas of BACE1 and its homologous BACE2 to understand the pathological mechanisms of this disease. The objectives of the present study were to characterize the localization of BACE proteins in human pancreas and determine their function. High levels of BACE enzymatic activity were detected in human pancreas. In normal human pancreas, BACE1 was observed in endocrine as well as in exocrine pancreas, whereas BACE2 expression was restricted to β-cells. Intracellular analysis using immunofluorescence showed colocalization of BACE1 with insulin and BACE2 with clathrin-coated vesicles of the plasma membrane in MIN6 cells. When BACE1 and -2 were pharmacologically inhibited, BACE1 localization was not altered, whereas BACE2 content in clathrin-coated vesicles was increased. Insulin internalization rate was reduced, insulin receptor β-subunit (IRβ) expression was decreased at the plasma membrane and increased in the Golgi apparatus, and a significant reduction in insulin gene expression was detected. Similar results were obtained after specific BACE2 silencing in MIN6 cells. All these data point to a role for BACE2 in the IRβ trafficking and insulin signaling. In conclusion, BACE2 is hereby presented as an important enzyme in β-cell function.

  20. 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.

  1. The Academic Librarian: Buying Into, Playing Out, and Resisting the Teacher Role in Higher Education

    ERIC Educational Resources Information Center

    Austin, Trevor; Bhandol, Janine

    2013-01-01

    This article reports the findings of a small-scale study in a UK university. The research investigated how academic librarians experienced the processes of becoming a teacher. As more librarians are drawn into a teaching role, understanding these developments becomes crucial. A narrative approach revealed the challenges faced as they participated…

  2. Pore helices play a dynamic role as integrators of domain motion during Kv11.1 channel inactivation gating.

    PubMed

    Perry, Matthew D; Ng, Chai Ann; Vandenberg, Jamie I

    2013-04-19

    Proteins that form ion-selective pores in the membrane of cells are integral to many rapid signaling processes, including regulating the rhythm of the heartbeat. In potassium channels, the selectivity filter is critical for both endowing an exquisite selectivity for potassium ions, as well as for controlling the flow of ions through the pore. Subtle rearrangements in the complex hydrogen-bond network that link the selectivity filter to the surrounding pore helices differentiate conducting (open) from nonconducting (inactivated) conformations of the channel. Recent studies suggest that beyond the selectivity filter, inactivation involves widespread rearrangements of the channel protein. Here, we use rate equilibrium free energy relationship analysis to probe the structural changes that occur during selectivity filter gating in Kv11.1 channels, at near atomic resolution. We show that the pore helix plays a crucial dynamic role as a bidirectional interface during selectivity filter gating. We also define the molecular bases of the energetic coupling between the pore helix and outer helix of the pore domain that occurs early in the transition from open to inactivated states, as well as the coupling between the pore helix and inner helix late in the transition. Our data demonstrate that the pore helices are more than just static structural elements supporting the integrity of the selectivity filter; instead they play a crucial dynamic role during selectivity filter gating.

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

    PubMed Central

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

    2015-01-01

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

  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. Focused screening of mitochondrial metabolism reveals a crucial role for a tumor suppressor Hbp1 in ovarian reserve

    PubMed Central

    Dong, Z; Huang, M; Liu, Z; Xie, P; Dong, Y; Wu, X; Qu, Z; Shen, B; Huang, X; Zhang, T; Li, J; Liu, J; Yanase, T; Zhou, C; Xu, Y

    2016-01-01

    Granulosa cells (GCs) are tightly associated with fertility and the fate of ovarian follicles. Mitochondria are the central executers of apoptosis. However, the genetic basis underlying mitochondrial modulation in GCs during the ovarian development is poorly understood. Here, CRISPR/Cas9-mediated genetic screening was used to identify genes conferring mitochondrial metabolism in human GCs. The results uncovered roles for several tumor suppressors, including HBP1, in the augmentation of mitochondrial function. Focused analysis revealed that high-mobility group (HMG)-box transcription factor 1 (Hbp1) levels regulate mitochondrial biogenesis, which is associated with global changes in transcription including Tfam. The systemic or granulosa-specific but not oocyte-specific ablation of Hbp1 promoted follicle growth and oocyte production, and is associated with the reduced apoptotic signals in mouse GCs. Consistent with increased mitochondrial function and attenuated GC apoptosis, the regulation of Hbp1 conferred substantial protection of ovarian reserve. Thus, the results of the present study provide a critical target to understand the control of the reproductive lifespan. PMID:27206316

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Roth, Stephan V.

    2016-10-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. Plasmin-induced procoagulant effects in the blood coagulation: a crucial role of coagulation factors V and VIII.

    PubMed

    Ogiwara, Kenichi; Nogami, Keiji; Nishiya, Katsumi; Shima, Midori

    2010-09-01

    Plasminogen activators provide effective treatment for patients with acute myocardial infarction. However, paradoxical elevation of thrombin activity associated with failure of clot lysis and recurrent thrombosis has been reported. Generation of thrombin in these circumstances appears to be owing to plasmin (Plm)-induced activation of factor (F) XII. Plm catalyzes proteolysis of several coagulant factors, but the roles of these factors on Plm-mediated procoagulant activity remain to be determined. Recently developed global coagulation assays were used in this investigation. Rotational thromboelastometry using whole blood, clot waveform analysis and thrombin generation tests using plasma, showed that Plm (> or =125 nmol/l) shortened the clotting times in similar dose-dependent manners. In particular, the thrombin generation test, which was unaffected by products of fibrinolysis, revealed the enhanced coagulation with an approximately two-fold increase of peak level of thrombin generation. Studies using alpha2-antiplasmin-deficient plasma revealed that much lower dose of Plm (> or =16 nmol/l) actually contributed to enhancing thrombin generation. The shortening of clotting time could be observed even in the presence of corn trypsin inhibitor, supporting that Plm exerted the procoagulant activity independently of FXII. In addition, using specific coagulation-deficient plasmas, the clot waveform analysis showed that Plm did not shorten the clotting time in only FV-deficient or FVIII-deficient plasma in prothrombin time-based or activated partial thromboplastin time-based assay, respectively. Our results indicated that Plm did possess procoagulant activity in the blood coagulation, and this effect was likely attributed by multicoagulation factors, dependent on FV and/or FVIII.

  10. Crucial Roles of Systemic and Tissue Lipid Peroxidation Levels and Anti-Oxidant Defences Following Contrast Agent Application

    PubMed Central

    Sitar, Gungor; Kucuk, Mehmet; Erinc Sitar, Mustafa; Yasar, Ozgur; Aydin, Seval; Yanar, Karolin; Cakatay, Ufuk; Buyukpınarbasili, Nur

    2016-01-01

    Background One of the most important side effects of contrast pharmaceutical agents, which are used very common in routine radiology practice, is contrast induced nephropathy. Even ischemia, oxidative stress and osmolality related cytotoxic effects are considered, the molecular mechanisms underlying this pathology have not been identified completely yet. Objectives The aim of the current study was to reveal the role of oxidative stress and antioxidant enzymatic defence mechanisms in the aetiopathogenesis of contrast-induced nephropathy. We also studied possible alleviating effects of N-acetylcysteine (NAC), a potent antioxidant, to obtain extra information regarding the molecular mechanisms underlying this pathology. Materials and Methods This is an clinical-experimental study, This study was conducted of Istanbul/Turkey between September 15, 2012 and April 15, 2013. Three groups of male rats were randomly set up as a control group (C), a 100 mg/kg intraperitoneal NAC + 7 mL/kg contrast agent group (N + CIN) and a 7 mL/kg intraperitoneal contrast agent group (CIN). They were placed in individual metabolic cages 48 hours after agent administration to obtain 24-hour urine samples. Renal function tests (albumin, urea, creatinine, total protein) were conducted, oxidative stress parameters (Cu, Zn superoxide dismutase activity - Cu, Zn-SOD; advanced oxidation protein products - AOPP; protein carbonyls - PCO; total thiol groups - T-SH; and lipid hydroperoxides -LHP) were measured and tissues were analysed histopathologically. Results Compared with the control group, groups CIN and N + CIN had significantly higher urea and LHP levels (P < 0.05 and P < 0.001, respectively) and significantly lower Cu, Zn-SOD activity and creatinine clearance (P < 0.05). There was no statistically significant difference between the groups in PCO or AOPP levels despite differences in descriptive statistics. Conclusions Contrast-agent-induced nephropathic changes are more closely related to

  11. A crucial role for the ubiquitously expressed transcription factor Sp1 at early stages of hematopoietic specification

    PubMed Central

    Gilmour, Jane; Assi, Salam A.; Jaegle, Ulrike; Kulu, Divine; van de Werken, Harmen; Clarke, Deborah; Westhead, David R.; Philipsen, Sjaak; Bonifer, Constanze

    2014-01-01

    Mammalian development is regulated by the interplay of tissue-specific and ubiquitously expressed transcription factors, such as Sp1. Sp1 knockout mice die in utero with multiple phenotypic aberrations, but the underlying molecular mechanism of this differentiation failure has been elusive. Here, we have used conditional knockout mice as well as the differentiation of mouse ES cells as a model with which to address this issue. To this end, we examined differentiation potential, global gene expression patterns and Sp1 target regions in Sp1 wild-type and Sp1-deficient cells representing different stages of hematopoiesis. Sp1−/− cells progress through most embryonic stages of blood cell development but cannot complete terminal differentiation. This failure to fully differentiate is not seen when Sp1 is knocked out at later developmental stages. For most Sp1 target and non-target genes, gene expression is unaffected by Sp1 inactivation. However, Cdx genes and multiple Hox genes are stage-specific targets of Sp1 and are downregulated at an early stage. As a consequence, expression of genes involved in hematopoietic specification is progressively deregulated. Our work demonstrates that the early absence of active Sp1 sets a cascade in motion that culminates in a failure of terminal hematopoietic differentiation and emphasizes the role of ubiquitously expressed transcription factors for tissue-specific gene regulation. In addition, our global side-by-side analysis of the response of the transcriptional network to perturbation sheds a new light on the regulatory hierarchy of hematopoietic specification. PMID:24850855

  12. Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion

    PubMed Central

    2010-01-01

    Background The formation of metastasis is the most common cause of death in patients with lung cancer. A major implement to understand the molecular mechanisms involved in lung cancer metastasis has been the lack of suitable models to address it. In this study, we aimed at establishing a highly metastatic model of human lung cancer and characterizing its metastatic properties and underlying mechanisms. Methods The human lung adeno-carcinoma SPC-A-1 cell line was used as parental cells for developing of highly metastatic cells by in vivo selection in NOD/SCID mice. After three rounds of selection, a new SPC-A-1sci cell line was established from pulmonary metastatic lesions. Subsequently, the metastatic properties of this cell line were analyzed, including optical imaging of in vivo metastasis, immunofluorescence and immunohistochemical analysis of several epithelial mesenchymal transition (EMT) makers and trans-well migration and invasion assays. Finally, the functional roles of fibronectin in the invasive and metastatic potentials of SPC-A-1sci cells were determined by shRNA analysis. Results A spontaneously pulmonary metastatic model of human lung adeno-carcinoma was established in NOD/SCID mice, from which a new lung cancer cell line, designated SPC-A-1sci, was isolated. Initially, the highly metastatic behavior of this cell line was validated by optical imaging in mice models. Further analyses showed that this cell line exhibit phenotypic and molecular alterations consistent with EMT. Compared with its parent cell line SPC-A-1, SPC-A-1sci was more aggressive in vitro, including increased potentials for cell spreading, migration and invasion. Importantly, fibronectin, a mesenchymal maker of EMT, was found to be highly expressed in SPC-A-1sci cells and down-regulation of it can decrease the in vitro and in vivo metastatic abilities of this cell line. Conclusions We have successfully established a new human lung cancer cell line with highly metastatic potentials

  13. Subequatorial cytoplasm plays an important role in ectoderm patterning in the sea urchin embryo.

    PubMed

    Kominami, Tetsuya; Akagawa, Megumi; Takata, Hiromi

    2006-02-01

    To gain information on the process of ectoderm patterning, the animal halves of sea urchin embryos were isolated at various stages, and their morphology was examined when control embryos developed into pluteus larvae. The animal halves separated at the 8-cell stage developed into 'dauerblastula', without showing any conspicuous ectoderm differentiation. In contrast, some of the animal halves isolated at the 60-cell stage (after the sixth cleavage) formed a ciliated band and oral opening, suggesting that some patterning signal was transmitted from the vegetal to animal hemisphere during early cleavage. Further patterning of the animal hemisphere did not seem to occur until hatching, since both the animal halves isolated at the 60-cell stage and hatching stage showed the same degree of ectoderm patterning. After hatching, the later animal halves were isolated, the more patterned ectoderm they formed. The animal halves isolated just prior to gastrulation differentiated well-patterned ectoderm. It is of note, however, that the level of separation was a more crucial factor than the timing of separation; even the animal fragments of newly hatched embryos differentiated well-patterned ectoderm if they had been separated at a subequatorial level. This suggests that the signal for ectoderm patterning is transmitted over the equator after hatching, and once the cells in the supra-equatorial region receive the signal, they, in turn, can transmit the signal upwardly. Interestingly, if the third cleavage plane was shifted toward the vegetal pole, the isolated animal pole-side fragments developed into 'embryoids' with fully patterned ectoderm. These results indicate that not the micromere descendants but the subequatorial cytoplasm plays an important role in ectoderm patterning.

  14. 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,…

  15. The crucial role of chelate-chelate stacking interactions in the crystal structure of a square planar copper(II) complex

    NASA Astrophysics Data System (ADS)

    Jana, Subrata; Khan, Samim; Bauzá, Antonio; Frontera, Antonio; Chattopadhyay, Shouvik

    2017-01-01

    A square planar copper(II) complex has been synthesized and characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction study. The X-ray structure of the complex is used to analyze the crucial role of the π-interactions in the solid state. The complex also shows significant hydrogen-bonding interactions. Moreover, we have evaluated energetically both interactions by means of high level DFT calculations (BP86-D3/def2-TZVP) and characterized them using the Bader's theory of "atoms-in-molecules".

  16. 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)

  17. 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 ...

  18. 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 ...

  19. 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.

  20. Evaluating the impact of role-playing simulations on global competency in an online transnational engineering course

    NASA Astrophysics Data System (ADS)

    Wold, Kari

    Successfully interacting with those from different cultures is essential to excel in any field, particularly when global, transnational collaborations in the workplace are increasingly common. However, many higher education students in engineering are not explicitly taught how to display the global competency skills desired by future employers. To display global competency skills means students must be able to visibly respect and recognize differences among those from different cultures. Global competency also means students must be able to show they can adjust their behaviors and integrate others' ideas when working with those with cultural backgrounds other than their own. While these skills are now deemed essential for future engineers, many institutions are struggling with determining which strategies and activities are universally effective to allow students to practice the global competency skills now crucial for success. Immersing engineering students in interactive role-playing simulations in transnational environments is one way institutions are encouraging students to illustrate and develop global competency skills. Role-playing simulations in transnational education provide environments where students adopt roles, interact with other students, and together explore and address realistic global problems. However, no studies have addressed whether or how role-playing simulations can help develop global competency in transnational engineering courses, students' perceptions regarding whether they change their abilities to display global competency in those environments, and their perspectives the effectiveness of using role-playing simulations for this purpose. To address this gap, this study assesses the impact of two subsequent role-playing simulations involving nuclear energy policy in a transnational course involving engineering students from the University of Virginia in Charlottesville, Virginia, and from Technische Universitat Dortmund in Dortmund

  1. 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...

  2. 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…

  3. 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.…

  4. 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.…

  5. 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®…

  6. 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.

  7. An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways.

    PubMed

    Deuis, Jennifer R; Zimmermann, Katharina; Romanovsky, Andrej A; Possani, Lourival D; Cabot, Peter J; Lewis, Richard J; Vetter, Irina

    2013-09-01

    Cold allodynia, pain in response to cooling, occurs during or within hours of oxaliplatin infusion and is thought to arise from a direct effect of oxaliplatin on peripheral sensory neurons. To characterize the pathophysiological mechanisms underlying acute oxaliplatin-induced cold allodynia, we established a new intraplantar oxaliplatin mouse model that rapidly developed long-lasting cold allodynia mediated entirely through tetrodotoxin-sensitive Nav pathways. Using selective inhibitors and knockout animals, we found that Nav1.6 was the key isoform involved, while thermosensitive transient receptor potential channels were not involved. Consistent with a crucial role for delayed-rectifier potassium channels in excitability in response to cold, intraplantar administration of the K(+)-channel blocker 4-aminopyridine mimicked oxaliplatin-induced cold allodynia and was also inhibited by Nav1.6 blockers. Intraplantar injection of the Nav1.6 activator Cn2 elicited spontaneous pain, mechanical allodynia, and enhanced 4-aminopyridine-induced cold allodynia. These findings provide behavioural evidence for a crucial role of Nav1.6 in multiple peripheral pain pathways including cold allodynia.

  8. 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...

  9. 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…

  10. 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...

  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. Why play an active role? A qualitative examination of lay citizens' main motives for participation in health promotion.

    PubMed

    Fienieg, Barbara; Nierkens, Vera; Tonkens, Evelien; Plochg, Thomas; Stronks, Karien

    2012-09-01

    While active participation is regarded essential in health promotion worldwide, its application proves to be challenging. Notably, participants' experiences are infrequently studied, and it is largely unknown why lay citizens would want to play an active role in promoting the health of the community they belong to. Aiming to produce practical insights to further the application of the participation principle, this qualitative study examined participants' driving motives in a diverse array of health promotion undertakings. Six projects in The Netherlands were used as case studies, including a community-project promoting mental health, peer education against harmful substance use, a health support group, health policy development, physical activity and healthy life style courses. The study involved 24 participants, who played a variety of active roles. Semi-structured interviews were conducted, transcribed verbatim and subjected to content analysis. We found four main motives driving lay citizens in their active participation in health promotion projects: 'purposeful action', 'personal development', 'exemplary status' and 'service and reciprocity'. The motives reflected crucially distinct personal desires in the participation process, namely to produce tangible results, to experience advancements for oneself, to gain personal recognition as a role model and to have or maintain valued relationships. The implications of the findings are discussed for researchers and professionals in health promotion.

  14. 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

  15. 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.

  16. The Pepper Lipoxygenase CaLOX1 Plays a Role in Osmotic, Drought and High Salinity Stress Response.

    PubMed

    Lim, Chae Woo; Han, Sang-Wook; Hwang, In Sun; Kim, Dae Sung; Hwang, Byung Kook; Lee, Sung Chul

    2015-05-01

    In plants, lipoxygenases (LOXs) are involved in various physiological processes, including defense responses to biotic and abiotic stresses. Our previous study had shown that the pepper 9-LOX gene, CaLOX1, plays a crucial role in cell death due to pathogen infection. Here, the function of CaLOX1 in response to osmotic, drought and high salinity stress was examined using CaLOX1-overexpressing (CaLOX1-OX) Arabidopsis plants. Changes in the temporal expression pattern of the CaLOX1 gene were observed when pepper leaves were treated with drought and high salinity, but not when treated with ABA, the primary hormone in response to drought stress. During seed germination and seedling development, CaLOX1-OX plants were more tolerant to ABA, mannitol and high salinity than wild-type plants. In contrast, expression of the ABA-responsive marker genes RAB18 and RD29B was higher in CaLOX1-OX Arabidopsis plants than in wild-type plants. In response to high salinity, CaLOX1-OX plants exhibited enhanced tolerance, compared with the wild type, which was accompanied by decreased accumulation of H2O2 and high levels of RD20, RD29A, RD29B and P5CS gene expression. Similarly, CaLOX1-OX plants were also more tolerant than wild-type plants to severe drought stress. H2O2 production and the relative increase in lipid peroxidation were lower, and the expression of COR15A, DREB2A, RD20, RD29A and RD29B was higher in CaLOX1-OX plants, relative to wild-type plants. Taken together, our results indicate that CaLOX1 plays a crucial role in plant stress responses by modulating the expression of ABA- and stress-responsive marker genes, lipid peroxidation and H2O2 production.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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…

  4. 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…

  5. 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

  6. Real-Time Imaging of Interactions of Neutrophils with Cryptococcus neoformans Demonstrates a Crucial Role of Complement C5a-C5aR Signaling.

    PubMed

    Sun, Donglei; Zhang, Mingshun; Liu, Gongguan; Wu, Hui; Zhu, Xiaoping; Zhou, Hong; Shi, Meiqing

    2015-10-26

    Neutrophils have been shown to efficiently kill Cryptococcus neoformans, a causative agent of meningoencephalitis. Here, using live-cell imaging, we characterize the dynamic interactions of neutrophils with C. neoformans and the underlying mechanisms in real time. Neutrophils were directly seen to chase C. neoformans cells and then rapidly internalize them. Complement C5a-C5aR signaling guided neutrophils to migrate to the yeast cells, resulting in optimal phagocytosis and subsequent killing of the organisms. The addition of recombinant complement C5a enhanced neutrophil movement but did not induce chemotaxis, suggesting that the C5a gradient is crucial. Incubation with C. neoformans resulted in enhanced activation of Erk and p38 mitogen-activated protein (MAP) kinases (MAPKs) in neutrophils. Inhibition of the p38 MAPK pathway, but not the Erk pathway, significantly impaired neutrophil migration and its subsequent killing of C. neoformans. Deficiency of CD11b or blocking of CD11b did not affect the migration of neutrophils toward C. neoformans but almost completely abolished phagocytosis and killing of the organisms by neutrophils. C5a-C5aR signaling induced enhanced surface expression of CD11b. Interestingly, the original surface expression of CD11b was essential and sufficient for neutrophils to attach to C. neoformans but was unable to mediate phagocytosis. In contrast, the enhanced surface expression of CD11b induced by C5a-C5aR signaling was essential for neutrophil phagocytosis and subsequent killing of yeast cells. Collectively, this is the first report of the dynamic interactions of neutrophils with C. neoformans, demonstrating a crucial role of C5a-C5aR signaling in neutrophil killing of C. neoformans in real time.

  7. Real-Time Imaging of Interactions of Neutrophils with Cryptococcus neoformans Demonstrates a Crucial Role of Complement C5a-C5aR Signaling

    PubMed Central

    Sun, Donglei; Zhang, Mingshun; Liu, Gongguan; Wu, Hui; Zhu, Xiaoping; Zhou, Hong

    2015-01-01

    Neutrophils have been shown to efficiently kill Cryptococcus neoformans, a causative agent of meningoencephalitis. Here, using live-cell imaging, we characterize the dynamic interactions of neutrophils with C. neoformans and the underlying mechanisms in real time. Neutrophils were directly seen to chase C. neoformans cells and then rapidly internalize them. Complement C5a-C5aR signaling guided neutrophils to migrate to the yeast cells, resulting in optimal phagocytosis and subsequent killing of the organisms. The addition of recombinant complement C5a enhanced neutrophil movement but did not induce chemotaxis, suggesting that the C5a gradient is crucial. Incubation with C. neoformans resulted in enhanced activation of Erk and p38 mitogen-activated protein (MAP) kinases (MAPKs) in neutrophils. Inhibition of the p38 MAPK pathway, but not the Erk pathway, significantly impaired neutrophil migration and its subsequent killing of C. neoformans. Deficiency of CD11b or blocking of CD11b did not affect the migration of neutrophils toward C. neoformans but almost completely abolished phagocytosis and killing of the organisms by neutrophils. C5a-C5aR signaling induced enhanced surface expression of CD11b. Interestingly, the original surface expression of CD11b was essential and sufficient for neutrophils to attach to C. neoformans but was unable to mediate phagocytosis. In contrast, the enhanced surface expression of CD11b induced by C5a-C5aR signaling was essential for neutrophil phagocytosis and subsequent killing of yeast cells. Collectively, this is the first report of the dynamic interactions of neutrophils with C. neoformans, demonstrating a crucial role of C5a-C5aR signaling in neutrophil killing of C. neoformans in real time. PMID:26502909

  8. 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.…

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. 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)

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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…

  14. 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.

  15. "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…

  16. 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.

  17. 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…

  18. 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…

  19. 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…

  20. 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…

  1. 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.

  2. 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…

  3. 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…

  4. 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…

  5. 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-...

  6. 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…

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

    ERIC Educational Resources Information Center

    Lorenzo, Carlos-Miguel

    2014-01-01

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

  8. 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…

  9. 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…

  10. 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…

  11. "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)

  12. 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…

  13. 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…

  14. 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…

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  16. 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…

  17. (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…

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. 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…

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

    ERIC Educational Resources Information Center

    Beale, Andrew V.; Hall, Kimberly R.

    2005-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. The crucial role of Φ- and K-segments in the in vitro functionality of Vitis vinifera dehydrin DHN1a.

    PubMed

    Rosales, Raquel; Romero, Irene; Escribano, Ma Isabel; Merodio, Carmen; Sanchez-Ballesta, Ma Teresa

    2014-12-01

    Dehydrins (DHNs), group II LEA (Late Embryogenesis Abundant) proteins, are among the most commonly observed proteins which accumulate in plants in response to cold and any other environmental factors, causing the dehydration of cells. In previous studies, we isolated a YSK2-type VvcDHN1a gene from table grapes (Vitis vinifera cv. Cardinal) which presented two spliced variants (the spliced, DHN1a_s and the unspliced, DHN1a_u). Their expression was induced by low temperature storage and CO2, although with different accumulation patterns. DHN1a_u codifies for a truncated YS protein lacking Ф- and K-segments, which might affect its functionality. In this work, we expressed both DHN1a_s and DHN1a_u recombinant proteins in Escherichia coli. We carried out a number of in vitro assays to analyze the implications that Ф- and K-segments have in the protective role of VvcDHN1 against different abiotic stresses and their antifungal activity against the fungal pathogen Botrytis cinerea. Our results showed that unlike DHN1a_u, DHN1a_s has a potent cryoprotective effect on lactate dehydrogenase activity, protects malate dehydrogenase against dehydration and partially inhibits B. cinerea growth. Moreover, the DHN1a promoter presented cis-regulatory elements related to cold and drought, as well as biotic stress-related elements. We also observed that both spliced variants interact weakly with DNA, suggesting that K-segments are not involved in DNA binding. Overall, this work highlights the crucial role of Ф- and K-segments in DHNs function in plant response to abiotic stress showing for the first time, the potential role of the V. vinifera DHN1a_s in the protection against freezing and dehydration as well as inhibiting B. cinerea growth.

  10. 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…

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

    ERIC Educational Resources Information Center

    Haney, Craig; Zimbardo, Philip G.

    1973-01-01

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

  12. Does mineralocorticoid receptor play a vital role in the development of depressive disorder?

    PubMed

    Chen, Jiao; Wang, Zhen-Zhen; Zhang, Shuai; Zuo, Wei; Chen, Nai-Hong

    2016-05-01

    Depression is a leading cause of disability worldwide. However, the biological and molecular mechanisms underlying this disease remain unclear. Stress, a disposing factor in the development of depression, leads to hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoids release. Glucocorticoids at physiological concentrations activate two types of steroid receptors including the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). During the past decades, lots of studies have confirmed the role of GR in depression. An increasing number of studies, in recent years, indicate that abnormal function of MR is also a crucial component of the pathophysiology of depression. Thus, this review summarizes the role of MR in the HPA axis dysregulation, inflammation, decreased neurogenesis and stress-related behaviors in depression. All of which will provide more information about MR in depression.

  13. Do advanced glycation end-products play a role in malaria susceptibility?

    PubMed Central

    Traoré, Karim; Arama, Charles; Médebielle, Maurice; Doumbo, Ogobara; Picot, Stéphane

    2016-01-01

    There are growing data supporting the differences in susceptibility to malaria described between sympatric populations with different lifestyles. Evidence has also been growing for some time that nutritional status and the host’s metabolism are part of the complex mechanisms underlying these differences. The role of dietary advanced glycation end-products (AGEs) in the modulation of immune responses (innate and adaptive responses) and chronic oxidative stress has been established. But less is known about AGE implication in naturally acquired immunity and susceptibility to malaria. Since inflammatory immune responses and oxidative events have been demonstrated as the hallmark of malaria infection, it seems crucial to investigate the role of AGE in susceptibility or resistance to malaria. This review provides new insight into the relationship between nutrition, metabolic disorders, and infections, and how this may influence the mechanisms of susceptibility or resistance to malaria in endemic areas. PMID:27012162

  14. 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.

  15. 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.

  16. A crucial role for DOK1 in PDGF-BB-stimulated glioma cell invasion through p130Cas and Rap1 signalling.

    PubMed

    Barrett, Angela; Evans, Ian M; Frolov, Antonina; Britton, Gary; Pellet-Many, Caroline; Yamaji, Maiko; Mehta, Vedanta; Bandopadhyay, Rina; Li, Ningning; Brandner, Sebastian; Zachary, Ian C; Frankel, Paul

    2014-06-15

    DOK1 regulates platelet-derived growth factor (PDGF)-BB-stimulated glioma cell motility. Mechanisms regulating tumour cell motility are essential for invasion and metastasis. We report here that PDGF-BB-mediated glioma cell invasion and migration are dependent on the adaptor protein downstream of kinase 1 (DOK1). DOK1 is expressed in several glioma cell lines and in tumour biopsies from high-grade gliomas. DOK1 becomes tyrosine phosphorylated upon PDGF-BB stimulation of human glioma cells. Knockdown of DOK1 or expression of a DOK1 mutant (DOK1FF) containing Phe in place of Tyr at residues 362 and 398, resulted in inhibition of both the PDGF-BB-induced tyrosine phosphorylation of p130Cas (also known as BCAR1) and the activation of Rap1. DOK1 colocalises with tyrosine phosphorylated p130Cas at the cell membrane of PDGF-BB-treated cells. Expression of a non-tyrosine-phosphorylatable substrate domain mutant of p130Cas (p130Cas15F) inhibited PDGF-BB-mediated Rap1 activation. Knockdown of DOK1 and Rap1 inhibited PDGF-BB-induced chemotactic cell migration, and knockdown of DOK1 and Rap1 and expression of DOK1FF inhibited PDGF-mediated three-dimensional (3D) spheroid invasion. These data show a crucial role for DOK1 in the regulation of PDGF-BB-mediated tumour cell motility through a p130Cas-Rap1 signalling pathway. [Corrected

  17. Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb.

    PubMed

    Matsumoto, Kazu; Li, Yingcui; Jakuba, Caroline; Sugiyama, Yoshinori; Sayo, Tetsuya; Okuno, Misako; Dealy, Caroline N; Toole, Bryan P; Takeda, Junji; Yamaguchi, Yu; Kosher, Robert A

    2009-08-01

    The glycosaminoglycan hyaluronan (HA) is a structural component of extracellular matrices and also interacts with cell surface receptors to directly influence cell behavior. To explore functions of HA in limb skeletal development, we conditionally inactivated the gene for HA synthase 2, Has2, in limb bud mesoderm using mice that harbor a floxed allele of Has2 and mice carrying a limb mesoderm-specific Prx1-Cre transgene. The skeletal elements of Has2-deficient limbs are severely shortened, indicating that HA is essential for normal longitudinal growth of all limb skeletal elements. Proximal phalanges are duplicated in Has2 mutant limbs indicating an involvement of HA in patterning specific portions of the digits. The growth plates of Has2-deficient skeletal elements are severely abnormal and disorganized, with a decrease in the deposition of aggrecan in the matrix and a disruption in normal columnar cellular relationships. Furthermore, there is a striking reduction in the number of hypertrophic chondrocytes and in the expression domains of markers of hypertrophic differentiation in the mutant growth plates, indicating that HA is necessary for the normal progression of chondrocyte maturation. In addition, secondary ossification centers do not form in the central regions of Has2 mutant growth plates owing to a failure of hypertrophic differentiation. In addition to skeletal defects, the formation of synovial joint cavities is defective in Has2-deficient limbs. Taken together, our results demonstrate that HA has a crucial role in skeletal growth, patterning, chondrocyte maturation and synovial joint formation in the developing limb.

  18. Crucial roles of sucrose and microRNA399 in systemic signaling of P deficiency: a tale of two team players?

    PubMed

    Liu, Junqi; Vance, Carroll P

    2010-12-01

    MicroRNAs (miRNAs) have been recognized as important regulators in plant response to nutrient deficiencies. Of particular interest is the discovery that miR399 functions systemically in the maintenance of phosphate (Pi) homeostasis in response to external Pi fluctuation. Recent studies have further implicated both miR399 and sugars (mainly sucrose) as potential signal molecules in the shoot-to-root communication of phosphorus (P) status. Given that both miR399 and sucrose are transported via the phloem, their potential interaction (or cross-talk) along the signaling pathway is especially appealing for further exploration. In this mini-review, we highlight recent progress in unraveling crucial roles of both sucrose and miR399 in P-deficiency signaling. In particular, we further discuss recent findings that photosynthetic carbon (C) assimilation and subsequent partitioning, by overriding signaling of low external Pi, act as checkpoints upstream of miR399 for the onset of a systemic P-deficiency status.

  19. Polarization of IRON-REGULATED TRANSPORTER 1 (IRT1) to the plant-soil interface plays crucial role in metal homeostasis.

    PubMed

    Barberon, Marie; Dubeaux, Guillaume; Kolb, Cornelia; Isono, Erika; Zelazny, Enric; Vert, Grégory

    2014-06-03

    In plants, the controlled absorption of soil nutrients by root epidermal cells is critical for growth and development. IRON-REGULATED TRANSPORTER 1 (IRT1) is the main root transporter taking up iron from the soil and is also the main entry route in plants for potentially toxic metals such as manganese, zinc, cobalt, and cadmium. Previous work demonstrated that the IRT1 protein localizes to early endosomes/trans-Golgi network (EE/TGN) and is constitutively endocytosed through a monoubiquitin- and clathrin-dependent mechanism. Here, we show that the availability of secondary non-iron metal substrates of IRT1 (Zn, Mn, and Co) controls the localization of IRT1 between the outer polar domain of the plasma membrane and EE/TGN in root epidermal cells. We also identify FYVE1, a phosphatidylinositol-3-phosphate-binding protein recruited to late endosomes, as an important regulator of IRT1-dependent metal transport and metal homeostasis in plants. FYVE1 controls IRT1 recycling to the plasma membrane and impacts the polar delivery of this transporter to the outer plasma membrane domain. This work establishes a functional link between the dynamics and the lateral polarity of IRT1 and the transport of its substrates, and identifies a molecular mechanism driving polar localization of a cell surface protein in plants.

  20. Polarization of IRON-REGULATED TRANSPORTER 1 (IRT1) to the plant-soil interface plays crucial role in metal homeostasis

    PubMed Central

    Barberon, Marie; Dubeaux, Guillaume; Kolb, Cornelia; Isono, Erika; Zelazny, Enric; Vert, Grégory

    2014-01-01

    In plants, the controlled absorption of soil nutrients by root epidermal cells is critical for growth and development. IRON-REGULATED TRANSPORTER 1 (IRT1) is the main root transporter taking up iron from the soil and is also the main entry route in plants for potentially toxic metals such as manganese, zinc, cobalt, and cadmium. Previous work demonstrated that the IRT1 protein localizes to early endosomes/trans-Golgi network (EE/TGN) and is constitutively endocytosed through a monoubiquitin- and clathrin-dependent mechanism. Here, we show that the availability of secondary non-iron metal substrates of IRT1 (Zn, Mn, and Co) controls the localization of IRT1 between the outer polar domain of the plasma membrane and EE/TGN in root epidermal cells. We also identify FYVE1, a phosphatidylinositol-3-phosphate-binding protein recruited to late endosomes, as an important regulator of IRT1-dependent metal transport and metal homeostasis in plants. FYVE1 controls IRT1 recycling to the plasma membrane and impacts the polar delivery of this transporter to the outer plasma membrane domain. This work establishes a functional link between the dynamics and the lateral polarity of IRT1 and the transport of its substrates, and identifies a molecular mechanism driving polar localization of a cell surface protein in plants. PMID:24843126

  1. Eyes of the Storm: Can Fusion Centers Play a Crucial Role During the Response Phase of Natural Disasters Through Collaborative Relationships With Emergency Operations Centers?

    DTIC Science & Technology

    2014-09-01

    sector infrastructure owner/operators. The consortium was able to identify gas stations, banks, restaurants , pharmacies, and hotels that were open for...a state of heavy reliance on interconnectivity through technology and modern conveniences . This reality can strain resources in a steady state

  2. Prolactin receptor-associated protein/17beta-hydroxysteroid dehydrogenase type 7 gene (Hsd17b7) plays a crucial role in embryonic development and fetal survival.

    PubMed

    Shehu, Aurora; Mao, Jifang; Gibori, Gil B; Halperin, Julia; Le, Jamie; Devi, Y Sangeeta; Merrill, Bradley; Kiyokawa, Hiroaki; Gibori, Geula

    2008-10-01

    Our laboratory has previously cloned and purified a protein named PRAP (prolactin receptor-associated protein) that was shown to be a novel 17beta-hydroxysteroid dehydrogenase (HSD) enzyme with dual activity. This enzyme, renamed HSD17B7 or PRAP/17beta-HSD7, converts estrone to estradiol and is also involved in cholesterol biosynthesis. The major site of its expression is the corpus luteum of a great number of species including rodents and humans. To examine the functional significance of HSD17B7 in pregnancy, we generated a knockout mouse model with targeted deletions of exons 1-4 of this gene. We anticipated a mouse with a severe fertility defect due to its inability to regulate estrogen levels during pregnancy. The heterozygous mutant mice are normal in their development and gross anatomy. The females cycle normally, and both male and female are fertile with normal litter size. To our surprise, the breeding of heterozygous mice yielded no viable HSD17B7 null mice. However, we found HSD17B7 null embryo alive in utero on d 8.5 and d 9.5. By d 10.5, the fetuses grow and suffer from severe brain malformation and heart defect. Because the brain depends on in situ cholesterol biosynthesis for its development beginning at d 10, the major cause of fetal death appears to be due to the cholesterol synthetic activity of this enzyme. By ablating HSD17B7 function, we have uncovered, in vivo, an important requirement for this enzyme during fetal development.

  3. Serotonin in peripheral blood reflects oxidative stress and plays a crucial role in atherosclerosis: Novel insights toward holistic anti-atherothrombotic strategy.

    PubMed

    Sugiura, Tomonori; Dohi, Yasuaki; Yamashita, Sumiyo; Hirowatari, Yuji; Fujii, Satoshi; Ohte, Nobuyuki

    2016-03-01

    We enrolled 132 outpatients with cardiovascular risk factors to evaluate the serotonin levels in platelet-poor plasma (PPP) and whole blood (WB). PPP serotonin levels and PPP/WB serotonin ratio were significantly correlated with levels of oxidative stress measured by derivative reactive oxygen metabolites (d-ROM). Twenty-five subjects were revealed to have stable coronary artery disease (CAD), and the levels CRP, d-ROM, and PPP/WB serotonin ratio were significantly higher in subjects with CAD than in those without CAD. Logistic regression analysis performed with the endpoint of having CAD revealed that the PPP/WB serotonin ratio was independently associated with CAD (odds ratio 3.37, 95% confidence interval 1.04-10.9, P = 0.04). Receiver operating characteristic (ROC) curve analyses to discriminate subjects with CAD from those without CAD indicated that combining PPP/WB serotonin ratio and d-ROM improved diagnostic utility. Targeting the serotonin-oxidative stress axis as part of a holistic anti-atherothrombotic strategy could be beneficial for patients with atherosclerosis.

  4. E-/P-selectins and colon carcinoma metastasis: first in vivo evidence for their crucial role in a clinically relevant model of spontaneous metastasis formation in the lung

    PubMed Central

    Köhler, S; Ullrich, S; Richter, U; Schumacher, U

    2009-01-01

    Background: Interactions of endothelial selectins with tumour cell glycoconjugates have been shown to have a major role in tumour cell dissemination in previous experiments. However, experiments validating this observation were limited in value, as ‘metastases' in these experiments were artificially induced by i.v. injection rather than developed spontaneously as in true metastases. Methods: Endothelial (E) and platelet (P)-selectin-deficient severe combined immunodeficient (scid) mice were generated and human HT 29 colon cancer cells were subcutaneously inoculated in these mice and in wild-type scid mice. Tumour growth, spontaneous metastasis formation in the lung and adherence of HT29 cells to E- and P-selectin under flow were determined. Results: The number of metastases decreased by 84% in E- and P-selectin-deficient scid mice, compared with wild-type scid mice. The remaining 16% metastases in the E- and P-selectin-deficient scid mice grew within the pulmonary artery and not in the alveolar septae as they did in wild-type scid mice. Flow experiments indicate that tumour cells roll and tether on an E- and P-selectin matrix similar to leukocytes; however, firm adhesion is mainly mediated in E-selectin. Conclusion: Our results indicate that E- and P-selectins have a crucial role in spontaneous metastasis formation. As the human HT 29 colon cancer cells are positive for the lectin Helix pomatia agglutinin (HPA), which identified the metastatic phenotype in earlier clinical studies, these results are of particular clinical relevance. PMID:20010946

  5. CREB-mediated synaptogenesis and neurogenesis is crucial for the role of 5-HT1a receptors in modulating anxiety behaviors

    PubMed Central

    Zhang, Jing; Cai, Cheng-Yun; Wu, Hai-Yin; Zhu, Li-Juan; Luo, Chun-Xia; Zhu, Dong-Ya

    2016-01-01

    Serotonin 1a-receptor (5-HT1aR) has been specifically implicated in the pathogenesis of anxiety. However, the mechanism underlying the role of 5-HT1aR in anxiety remains poorly understood. Here we show in mice that the transcription factor cAMP response element binding protein (CREB) in the hippocampus functions as an effector of 5-HT1aR in modulating anxiety-related behaviors. We generated recombinant lentivirus LV-CREB133-GFP expressing a dominant negative CREB which could not be phosphorylated at Ser133 to specifically reduce CREB activity, and LV-VP16-CREB-GFP expressing a constitutively active fusion protein VP16-CREB which could be phosphorylated by itself to specifically enhance CREB activity. LV-CREB133-GFP neutralized 5-HT1aR agonist-induced up-regulation of synapse density, spine density, dendrite complexity, neurogenesis, and the expression of synapsin and spinophilin, two well-characterized synaptic proteins, and abolished the anxiolytic effect of 5-HT1aR agonist; whereas LV-VP16-CREB-GFP rescued the 5-HT1aR antagonist-induced down-regulation of synapse density, spine density, dendrite complexity, neurogenesis and synapsin and spinophilin expression, and reversed the anxiogenic effect of 5-HT1aR antagonist. The deletion of neurogenesis by irradiation or the diminution of synaptogenesis by knockdown of synapsin expression abolished the anxiolytic effects of both CREB and 5-HT1aR activation. These findings suggest that CREB-mediated hippoacampus structural plasticity is crucial for the role of 5-HT1aR in modulating anxiety-related behaviors. PMID:27404655

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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…

  11. OSCAR-collagen signaling in monocytes plays a proinflammatory role and may contribute to the pathogenesis of rheumatoid arthritis.

    PubMed

    Schultz, Heidi S; Guo, Li; Keller, Pernille; Fleetwood, Andrew J; Sun, Mingyi; Guo, Wei; Ma, Chunyan; Hamilton, John A; Bjørkdahl, Olle; Berchtold, Martin W; Panina, Svetlana

    2016-04-01

    Osteoclast-associated receptor (OSCAR) is an activating receptor expressed by human myeloid cells. Collagen type I (ColI) and collagen type II (ColII) serve as ligands for OSCAR. OSCAR-collagen interaction stimulates RANK-dependent osteoclastogenesis. We have recently reported that OSCAR promotes functional maturation of monocyte-derived dendritic cells. OSCAR is upregulated on monocytes from rheumatoid arthritis (RA) patients with active disease, and these monocytes show an increased proosteoclastogenic potential. In the current study, we have addressed a functional role for an OSCAR-collagen interaction on monocytes. We show that OSCAR-ColII signaling promoted the survival of monocytes. Moreover, ColII stimulated the release of proinflammatory cytokines by monocytes from healthy donors, which could be completely blocked by an anti-OSCAR monoclonal antibody. Mononuclear cells from the synovial fluid of RA patients plated on ColII secreted TNF-α and IL-8 in an OSCAR-dependent manner. Global RNA profiling showed that components of multiple signaling pathways relevant to RA pathogenesis are regulated at the transcriptional level by OSCAR in monocytes. Thus, OSCAR can play a proinflammatory role in monocyte-derived cells and may contribute crucially on multiple levels to RA pathogenesis.

  12. 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…

  13. 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

  14. Role-play simulations for climate change adaptation education and engagement

    NASA Astrophysics Data System (ADS)

    Rumore, Danya; Schenk, Todd; Susskind, Lawrence

    2016-08-01

    In order to effectively adapt to climate change, public officials and other stakeholders need to rapidly enhance their understanding of local risks and their ability to collaboratively and adaptively respond to them. We argue that science-based role-play simulation exercises -- a type of 'serious game' involving face-to-face mock decision-making -- have considerable potential as education and engagement tools for enhancing readiness to adapt. Prior research suggests role-play simulations and other serious games can foster public learning and encourage collective action in public policy-making contexts. However, the effectiveness of such exercises in the context of climate change adaptation education and engagement has heretofore been underexplored. We share results from two research projects that demonstrate the effectiveness of role-play simulations in cultivating climate change adaptation literacy, enhancing collaborative capacity and facilitating social learning. Based on our findings, we suggest such exercises should be more widely embraced as part of adaptation professionals' education and engagement toolkits.

  15. 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.

  16. 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.

  17. 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.

  18. 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…

  19. 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.

  20. SLA-PGN-primed dendritic cell-based vaccination induces Th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of PKCβ.

    PubMed

    Jawed, Junaid Jibran; Majumder, Saikat; Bandyopadhyay, Syamdas; Biswas, Satabdi; Parveen, Shabina; Majumdar, Subrata

    2016-07-01

    Emergence of drug resistance during visceral leishmaniasis (VL) is a major obstacle imposed during successful therapy. An effective vaccine strategy against this disease is therefore necessary. Our present study exploited the SLA (soluble leishmanial antigen) and PGN (peptidoglycan) stimulated bone marrow-derived dendritic cells (DCs) as a suitable vaccine candidate during experimental VL. SLA-PGN-stimulated DCs showed a significant decrease in hepatic and splenic parasite burden, which were associated with increased production of nitric oxide and pro-inflammatory cytokines such as IL-12, IFN-γ and IL-17. Elevated level of IL-17 was accompanied with the generation of more Th17 cells. Further studies on DC provided the evidence that these SLA-PGN-stimulated DCs played an important role in providing necessary cytokines such as IL-6, IL-23 and TGF-β for the generation of Th17 cells. Interestingly, inhibition of protein kinase C-β (PKCβ) in DCs led to decreased production of Th17 polarizing cytokines, causing reduction of the Th17 population size. Altogether, our finding highlighted the important role of DC-based PKCβ in regulation of the function and generation of Th17 cells.

  1. Activity-dependent regulation of release probability at excitatory hippocampal synapses: a crucial role of fragile X mental retardation protein in neurotransmission.

    PubMed

    Wang, Xiao-Sheng; Peng, Chun-Zi; Cai, Wei-Jun; Xia, Jian; Jin, Daozhong; Dai, Yuqiao; Luo, Xue-Gang; Klyachko, Vitaly A; Deng, Pan-Yue

    2014-05-01

    Transcriptional silencing of the Fmr1 gene encoding fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), the most common form of inherited intellectual disability and the leading genetic cause of autism. FMRP has been suggested to play important roles in regulating neurotransmission and short-term synaptic plasticity at excitatory hippocampal and cortical synapses. However, the origins and mechanisms of these FMRP actions remain incompletely understood, and the role of FMRP in regulating synaptic release probability and presynaptic function remains debated. Here we used variance-mean analysis and peak-scaled nonstationary variance analysis to examine changes in both presynaptic and postsynaptic parameters during repetitive activity at excitatory CA3-CA1 hippocampal synapses in a mouse model of FXS. Our analyses revealed that loss of FMRP did not affect the basal release probability or basal synaptic transmission, but caused an abnormally elevated release probability specifically during repetitive activity. These abnormalities were not accompanied by changes in excitatory postsynaptic current kinetics, quantal size or postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor conductance. Our results thus indicate that FMRP regulates neurotransmission at excitatory hippocampal synapses specifically during repetitive activity via modulation of release probability in a presynaptic manner. Our study suggests that FMRP function in regulating neurotransmitter release is an activity-dependent phenomenon that may contribute to the pathophysiology of FXS.

  2. Cloning of wrinkle-free, a previously uncharacterized mouse mutation, reveals crucial roles for fatty acid transport protein 4 in skin and hair development.

    PubMed

    Moulson, Casey L; Martin, Daniel R; Lugus, Jesse J; Schaffer, Jean E; Lind, Anne C; Miner, Jeffrey H

    2003-04-29

    Wrinkle-free (wrfr) is a previously uncharacterized, spontaneous, autosomal recessive mouse mutation resulting in very tight, thick skin. wrfr mutant mice exhibit severe breathing difficulties secondary to their tight skin and die shortly after birth. This phenotype is strikingly similar to a very rare human genetic disorder, restrictive dermopathy. wrfr mutant mice display a defective skin barrier, which is normally imparted by the cornified envelope, a composite of protein and lipid that prevents loss of water from within and entry of potentially harmful substances from without. In addition, hair growth from grafted wrfr skin is impaired. Positional cloning of the wrfr mutation revealed a retrotransposon insertion into a coding exon of Slc27a4, the gene encoding fatty acid transport protein (FATP)4. FATP4 is the primary intestinal FATP and is thought to play a major role in dietary fatty acid uptake; it therefore is viewed as a target to prevent or reverse obesity. However, its function in vivo had not been determined. Our results demonstrate an unexpected yet critical role for FATP4 in skin and hair development and suggest Slc27a4 to be a candidate gene for restrictive dermopathy.

  3. Spatial Factors Play a Major Role as Determinants of Endemic Ground Beetle Beta Diversity of Madeira Island Laurisilva

    PubMed Central

    Boieiro, Mário; Carvalho, José C.; Cardoso, Pedro; Aguiar, Carlos A. S.; Rego, Carla; de Faria e Silva, Israel; Amorim, Isabel R.; Pereira, Fernando; Azevedo, Eduardo B.; Borges, Paulo A. V.; Serrano, Artur R. M.

    2013-01-01

    The development in recent years of new beta diversity analytical approaches highlighted valuable information on the different processes structuring ecological communities. A crucial development for the understanding of beta diversity patterns was also its differentiation in two components: species turnover and richness differences. In this study, we evaluate beta diversity patterns of ground beetles from 26 sites in Madeira Island distributed throughout Laurisilva – a relict forest restricted to the Macaronesian archipelagos. We assess how the two components of ground beetle beta diversity (βrepl – species turnover and βrich - species richness differences) relate with differences in climate, geography, landscape composition matrix, woody plant species richness and soil characteristics and the relative importance of the effects of these variables at different spatial scales. We sampled 1025 specimens from 31 species, most of which are endemic to Madeira Island. A spatially explicit analysis was used to evaluate the contribution of pure environmental, pure spatial and environmental spatially structured effects on variation in ground beetle species richness and composition. Variation partitioning showed that 31.9% of species turnover (βrepl) and 40.7% of species richness variation (βrich) could be explained by the environmental and spatial variables. However, different environmental variables controlled the two types of beta diversity: βrepl was influenced by climate, disturbance and soil organic matter content whilst βrich was controlled by altitude and slope. Furthermore, spatial variables, represented through Moran’s eigenvector maps, played a significant role in explaining both βrepl and βrich, suggesting that both dispersal ability and Madeira Island complex orography are crucial for the understanding of beta diversity patterns in this group of beetles. PMID:23724065

  4. 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.

  5. 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

  6. 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.

  7. Recruitment of Gβγ controls the basal activity of G-protein coupled inwardly rectifying potassium (GIRK) channels: crucial role of distal C terminus of GIRK1

    PubMed Central

    Kahanovitch, Uri; Tsemakhovich, Vladimir; Berlin, Shai; Rubinstein, Moran; Styr, Boaz; Castel, Ruth; Peleg, Sagit; Tabak, Galit; Dessauer, Carmen W; Ivanina, Tatiana; Dascal, Nathan

    2014-01-01

    The G-protein coupled inwardly rectifying potassium (GIRK, or Kir3) channels are important mediators of inhibitory neurotransmission via activation of G-protein coupled receptors (GPCRs). GIRK channels are tetramers comprising combinations of subunits (GIRK1–4), activated by direct binding of the Gβγ subunit of Gi/o proteins. Heterologously expressed GIRK1/2 exhibit high, Gβγ-dependent basal currents (Ibasal) and a modest activation by GPCR or coexpressed Gβγ. Inversely, the GIRK2 homotetramers exhibit low Ibasal and strong activation by Gβγ. The high Ibasal of GIRK1 seems to be associated with its unique distal C terminus (G1-dCT), which is not present in the other subunits. We investigated the role of G1-dCT using electrophysiological and fluorescence assays in Xenopus laevis oocytes and protein interaction assays. We show that expression of GIRK1/2 increases the plasma membrane level of coexpressed Gβγ (a phenomenon we term ‘Gβγ recruitment’) but not of coexpressed Gαi3. All GIRK1-containing channels, but not GIRK2 homomers, recruited Gβγ to the plasma membrane. In biochemical assays, truncation of G1-dCT reduces the binding between the cytosolic parts of GIRK1 and Gβγ, but not Gαi3. Nevertheless, the truncation of G1-dCT does not impair activation by Gβγ. In fluorescently labelled homotetrameric GIRK1 channels and in the heterotetrameric GIRK1/2 channel, the truncation of G1-dCT abolishes Gβγ recruitment and decreases Ibasal. Thus, we conclude that G1-dCT carries an essential role in Gβγ recruitment by GIRK1 and, consequently, in determining its high basal activity. Our results indicate that G1-dCT is a crucial part of a Gβγ anchoring site of GIRK1-containing channels, spatially and functionally distinct from the site of channel activation by Gβγ. PMID:25384780

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Arabidopsis RAP2.2 plays an important role in plant resistance to Botrytis cinerea and ethylene responses.

    PubMed

    Zhao, Yang; Wei, Tong; Yin, Kang-Quan; Chen, Zhangliang; Gu, Hongya; Qu, Li-Jia; Qin, Genji

    2012-07-01

    • Ethylene plays a crucial role in plant resistance to necrotrophic pathogens, in which ETHYLENE RESPONSE FACTORs (ERFs) are often involved. • Here, we evaluated the role of an ERF transcription factor, RELATED TO AP2 2 (RAP2.2), in Botrytis resistance and ethylene responses in Arabidopsis. We analyzed the resistance of transgenic plants overexpressing RAP2.2 and the T-DNA insertion mutant to Botrytis cinerea. We assessed its role in the ethylene signaling pathway by molecular and genetic approaches. • RAP2.2-overexpressing transgenic plants showed increased resistance to B. cinerea, whereas its T-DNA insertion mutant rap2.2-3 showed decreased resistance. Overexpression of RAP2.2 in ethylene insensitive 2 (ein2) and ein3 ein3-like 1 (eil1) mutants restored their resistance to B. cinerea. Both ethylene and Botrytis infection induced the expression of RAP2.2 and the induction was disrupted in ein2 and ein3 eil1 mutants. We identified rap2.12-1 as a T-DNA insertion mutant of RAP2.12, the closest homolog of RAP2.2. The hypocotyls of rap2.2-3 rap2.12-1 double mutants showed ethylene insensitivity. The constitutive triple response in constitutive triple response1 (ctr1) was partially released in the rap2.2-3 rap2.12-1 ctr1 triple mutants. • Our findings demonstrate that RAP2.2 functions as an important regulator in Botrytis resistance and ethylene responses.