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Sample records for interleukin-32 positively regulates

  1. Genetic signature of strong recent positive selection at interleukin-32 gene in goat

    Directory of Open Access Journals (Sweden)

    Akhtar Rasool Asif

    2017-07-01

    Full Text Available Objective Identification of the candidate genes that play key roles in phenotypic variations can provide new information about evolution and positive selection. Interleukin (IL-32 is involved in many biological processes, however, its role for the immune response against various diseases in mammals is poorly understood. Therefore, the current investigation was performed for the better understanding of the molecular evolution and the positive selection of single nucleotide polymorphisms in IL-32 gene. Methods By using fixation index (FST based method, IL-32 (9375 gene was found to be outlier and under significant positive selection with the provisional combined allocation of mean heterozygosity and FST. Using nucleotide sequences of 11 mammalian species from National Center for Biotechnology Information database, the evolutionary selection of IL-32 gene was determined using Maximum likelihood model method, through four models (M1a, M2a, M7, and M8 in Codeml program of phylogenetic analysis by maximum liklihood. Results IL-32 is detected under positive selection using the FST simulations method. The phylogenetic tree revealed that goat IL-32 was in close resemblance with sheep IL-32. The coding nucleotide sequences were compared among 11 species and it was found that the goat IL-32 gene shared identity with sheep (96.54%, bison (91.97%, camel (58.39%, cat (56.59%, buffalo (56.50%, human (56.13%, dog (50.97%, horse (54.04%, and rabbit (53.41% respectively. Conclusion This study provides evidence for IL-32 gene as under significant positive selection in goat.

  2. Genetic signature of strong recent positive selection at interleukin-32 gene in goat.

    Science.gov (United States)

    Asif, Akhtar Rasool; Qadri, Sumayyah; Ijaz, Nabeel; Javed, Ruheena; Ansari, Abdur Rahman; Awais, Muhammd; Younus, Muhammad; Riaz, Hasan; Du, Xiaoyong

    2017-07-01

    Identification of the candidate genes that play key roles in phenotypic variations can provide new information about evolution and positive selection. Interleukin (IL)-32 is involved in many biological processes, however, its role for the immune response against various diseases in mammals is poorly understood. Therefore, the current investigation was performed for the better understanding of the molecular evolution and the positive selection of single nucleotide polymorphisms in IL-32 gene. By using fixation index ( F ST ) based method, IL-32 (9375) gene was found to be outlier and under significant positive selection with the provisional combined allocation of mean heterozygosity and F ST . Using nucleotide sequences of 11 mammalian species from National Center for Biotechnology Information database, the evolutionary selection of IL-32 gene was determined using Maximum likelihood model method, through four models (M1a, M2a, M7, and M8) in Codeml program of phylogenetic analysis by maximum liklihood. IL-32 is detected under positive selection using the F ST simulations method. The phylogenetic tree revealed that goat IL-32 was in close resemblance with sheep IL-32. The coding nucleotide sequences were compared among 11 species and it was found that the goat IL-32 gene shared identity with sheep (96.54%), bison (91.97%), camel (58.39%), cat (56.59%), buffalo (56.50%), human (56.13%), dog (50.97%), horse (54.04%), and rabbit (53.41%) respectively. This study provides evidence for IL-32 gene as under significant positive selection in goat.

  3. Phosphatidylethanolamine positively regulates autophagy and longevity.

    Science.gov (United States)

    Rockenfeller, P; Koska, M; Pietrocola, F; Minois, N; Knittelfelder, O; Sica, V; Franz, J; Carmona-Gutierrez, D; Kroemer, G; Madeo, F

    2015-03-01

    Autophagy is a cellular recycling program that retards ageing by efficiently eliminating damaged and potentially harmful organelles and intracellular protein aggregates. Here, we show that the abundance of phosphatidylethanolamine (PE) positively regulates autophagy. Reduction of intracellular PE levels by knocking out either of the two yeast phosphatidylserine decarboxylases (PSD) accelerated chronological ageing-associated production of reactive oxygen species and death. Conversely, the artificial increase of intracellular PE levels, by provision of its precursor ethanolamine or by overexpression of the PE-generating enzyme Psd1, significantly increased autophagic flux, both in yeast and in mammalian cell culture. Importantly administration of ethanolamine was sufficient to extend the lifespan of yeast (Saccharomyces cerevisiae), mammalian cells (U2OS, H4) and flies (Drosophila melanogaster). We thus postulate that the availability of PE may constitute a bottleneck for functional autophagy and that organismal life or healthspan could be positively influenced by the consumption of ethanolamine-rich food.

  4. Regulating positive and negative emotions in daily life.

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    Nezlek, John B; Kuppens, Peter

    2008-06-01

    The present study examined how people regulate their emotions in daily life and how such regulation is related to their daily affective experience and psychological adjustment. Each day for an average of 3 weeks, participants described how they had regulated their emotions in terms of the reappraisal and suppression (inhibiting the expression) of positive and negative emotions, and they described their emotional experience, self-esteem, and psychological adjustment in terms of Beck's triadic model of depression. Reappraisal was used more often than suppression, and suppressing positive emotions was used less than the other three strategies. In general, regulation through reappraisal was found to be beneficial, whereas regulation by suppression was not. Reappraisal of positive emotions was associated with increases in positive affect, self-esteem, and psychological adjustment, whereas suppressing positive emotions was associated with decreased positive emotion, self-esteem, and psychological adjustment, and increased negative emotions. Moreover, relationships between reappraisal and psychological adjustment and self-esteem were mediated by experienced positive affect, whereas relationships between suppression of positive emotions and self-esteem adjustment were mediated by negative affect.

  5. Spo0A positively regulates epr expression by negating the ...

    Indian Academy of Sciences (India)

    2013-03-07

    Mar 7, 2013 ... is involved in the swarming motility of B. subtilis. Deletion studies of the upstream region of epr promoter revealed that epr is co-repressed by transition state regulators, SinR and ScoC. Our study shows that Spo0A positively regulates epr expression by nullifying the repressive effect of co-repressors, SinR ...

  6. An integrative theory-driven positive emotion regulation intervention.

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    Weytens, Fanny; Luminet, Olivier; Verhofstadt, Lesley L; Mikolajczak, Moïra

    2014-01-01

    Over the past fifteen years, positive psychology research has validated a set of happiness enhancing techniques. These techniques are relatively simple exercises that allow happiness seekers to mimic thoughts and behavior of naturally happy people, in order to increase their level of well-being. Because research has shown that the joint use of these exercises increases their effects, practitioners who want to help happiness seekers need validated interventions that combine several of these techniques. To meet this need, we have developed and tested an integrative intervention (Positive Emotion Regulation program - PER program) incorporating a number of validated techniques structured around a theoretical model: the Process Model of Positive Emotion Regulation. To test the effectiveness of this program and to identify its added value relative to existing interventions, 113 undergraduate students were randomly assigned to a 6-week positive emotion regulation pilot program, a loving-kindness meditation training program, or a wait-list control group. Results indicate that fewer participants dropped out from the PER program than from the Loving-Kindness Meditation training. Furthermore, subjects in the PER group showed a significant increase in subjective well-being and life satisfaction and a significant decrease in depression and physical symptoms when compared to controls. Our results suggest that the Process Model of Positive Emotion Regulation can be an effective option to organize and deliver positive integrative interventions.

  7. Compassion-based emotion regulation up-regulates experienced positive affect and associated neural networks

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    Singer, Tania

    2015-01-01

    Emotion regulation research has primarily focused on techniques that attenuate or modulate the impact of emotional stimuli. Recent evidence suggests that this mode regulation can be problematic in the context of regulation of emotion elicited by the suffering of others, resulting in reduced emotional connectedness. Here, we investigated the effects of an alternative emotion regulation technique based on the up-regulation of positive affect via Compassion-meditation on experiential and neural affective responses to depictions of individuals in distress, and compared these with the established emotion regulation strategy of Reappraisal. Using fMRI, we scanned 15 expert practitioners of Compassion-meditation either passively viewing, or using Compassion-meditation or Reappraisal to modulate their emotional reactions to film clips depicting people in distress. Both strategies effectively, but differentially regulated experienced affect, with Compassion primarily increasing positive and Reappraisal primarily decreasing negative affect. Imaging results showed that Compassion, relative to both passive-viewing and Reappraisal increased activation in regions involved in affiliation, positive affect and reward processing including ventral striatum and medial orbitfrontal cortex. This network was shown to be active prior to stimulus presentation, suggesting that the regulatory mechanism of Compassion is the stimulus-independent endogenous generation of positive affect. PMID:25698699

  8. Arabidopsis SUMO protease ASP1 positively regulates flowering time partially through regulating FLC stability 

    KAUST Repository

    Kong, Xiangxiong

    2016-12-07

    The initiation of flowering is tightly regulated by the endogenous and environment signals, which is crucial for the reproductive success of flowering plants. It is well known that autonomous and vernalization pathways repress transcription of FLOWERING LOCUS C (FLC), a focal floral repressor, but how its protein stability is regulated remains largely unknown. Here, we found that mutations in a novel Arabidopsis SUMO protease 1 (ASP1) resulted in a strong late-flowering phenotype under long-days, but to a lesser extent under short-days. ASP1 localizes in the nucleus and exhibited a SUMO protease activity in vitro and in vivo. The conserved Cys-577 in ASP1 is critical for its enzymatic activity, as well as its physiological function in the regulation of flowering time. Genetic and gene expression analyses demonstrated that ASP1 promotes transcription of positive regulators of flowering, such as FT, SOC1 and FD, and may function in both CO-dependent photoperiod pathway and FLC-dependent pathways. Although the transcription level of FLC was not affected in the loss-of-function asp1 mutant, the protein stability of FLC was increased in the asp1 mutant. Taken together, this study identified a novel bona fide SUMO protease, ASP1, which positively regulates transition to flowering at least partly by repressing FLC protein stability.

  9. A socio-cultural instrumental approach to emotion regulation: Culture and the regulation of positive emotions.

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    Ma, Xiaoming; Tamir, Maya; Miyamoto, Yuri

    2018-02-01

    We propose a sociocultural instrumental approach to emotion regulation. According to this approach, cultural differences in the tendency to savor rather than dampen positive emotions should be more pronounced when people are actively pursuing goals (i.e., contexts requiring higher cognitive effort) than when they are not (i.e., contexts requiring lower cognitive efforts), because cultural beliefs about the utility of positive emotions should become most relevant when people are engaging in active goal pursuit. Four studies provided support for our theory. First, European Americans perceived more utility and less harm of positive emotions than Japanese did (Study 1). Second, European Americans reported a stronger relative preference for positive emotions than Asians, but this cultural difference was larger in high cognitive effort contexts than in moderate or low cognitive effort contexts (Study 2). Third, European Americans reported trying to savor rather than dampen positive emotions more than Asians did when preparing to take an exam, a typical high cognitive effort context (Studies 3-4), but these cultural differences were attenuated when an exam was not expected (Study 3) and disappeared when participants expected to interact with a stranger (Study 4). These findings suggest that cultural backgrounds and situational demands interact to shape how people regulate positive emotions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  10. Phosphoenolpyruvate phosphotransferase system components positively regulate Klebsiella biofilm formation

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    Yu-Tze Horng

    2018-04-01

    Full Text Available Background/Purpose: Klebsiella pneumoniae is one of the leading causes of device-related infections (DRIs, which are associated with attachment of bacteria to these devices to form a biofilm. The latter is composed of not only bacteria but also extracellular polymeric substances (EPSes consisting of extracellular DNAs, polysaccharides, and other macromolecules. The phosphoenolpyruvate (PEP:carbohydrate phosphotransferase system (PTS regulates diverse processes of bacterial physiology. In the genome of K. pneumoniae MGH 78578, we found an uncharacterized enzyme II complex homolog of PTS: KPN00353 (EIIA homolog, KPN00352 (EIIB homolog, and KPN00351 (EIIC homolog. The aim of this study was to characterize the potential physiological role of KPN00353, KPN00352, and KPN00351 in biofilm formation by K. pneumoniae. Methods/Results: We constructed the PTS mutants and recombinant strains carrying the gene(s of PTS. The recombinant K. pneumoniae strain overexpressing KPN00353–KPN00352–KPN00351 produced more extracellular matrix than did the vector control according to transmission and scanning electron microscopy. Judging by quantification of biofilm formation, of extracellular DNA (eDNA, and of capsular polysaccharide, the recombinant strain overexpressing KPN00353-KPN00352-KPN00351 produced more biofilm and capsular polysaccharide after overnight culture and more eDNA in the log phase as compared to the vector control. Conclusion: The genes, KPN00353–KPN00352–KPN00351, encode a putative enzyme II complex in PTS and positively regulate biofilm formation by enhancing production of eDNA and capsular polysaccharide in K. pneumoniae. Five proteins related to chaperones, to the citric acid cycle, and to quorum sensing are upregulated by the KPN00353–KPN00352–KPN00351 system. Keywords: Klebsiella, PTS, Biofilm, eDNA, Polysaccharide

  11. LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive endosomes.

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    Takano, Tetsuya; Urushibara, Tomoki; Yoshioka, Nozomu; Saito, Taro; Fukuda, Mitsunori; Tomomura, Mineko; Hisanaga, Shin-Ichi

    2014-06-01

    Neurons extend two types of neurites-axons and dendrites-that differ in structure and function. Although it is well understood that the cytoskeleton plays a pivotal role in neurite differentiation and extension, the mechanisms by which membrane components are supplied to growing axons or dendrites is largely unknown. We previously reported that the membrane supply to axons is regulated by lemur kinase 1 (LMTK1) through Rab11A-positive endosomes. Here we investigate the role of LMTK1 in dendrite formation. Down-regulation of LMTK1 increases dendrite growth and branching of cerebral cortical neurons in vitro and in vivo. LMTK1 knockout significantly enhances the prevalence, velocity, and run length of anterograde movement of Rab11A-positive endosomes to levels similar to those expressing constitutively active Rab11A-Q70L. Rab11A-positive endosome dynamics also increases in the cell body and growth cone of LMTK1-deficient neurons. Moreover, a nonphosphorylatable LMTK1 mutant (Ser34Ala, a Cdk5 phosphorylation site) dramatically promotes dendrite growth. Thus LMTK1 negatively controls dendritic formation by regulating Rab11A-positive endosomal trafficking in a Cdk5-dependent manner, indicating the Cdk5-LMTK1-Rab11A pathway as a regulatory mechanism of dendrite development as well as axon outgrowth. © 2014 Takano et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  12. Phosphatidylserine directly and positively regulates fusion of myoblasts into myotubes

    International Nuclear Information System (INIS)

    Jeong, Jaemin; Conboy, Irina M.

    2011-01-01

    Highlights: → PS broadly and persistently trans-locates to the outer leaflet of plasma membrane during myoblast fusion into myotubes. → Robust myotubes are formed when PS liposomes are added exogenously. → PS increases the width of de novo myotubes and the numbers of myonuclei, but not the myotube length. → Annexin V or PS antibody inhibits myotube formation by masking exposed PS. -- Abstract: Cell membrane consists of various lipids such as phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Among them, PS is a molecular marker of apoptosis, because it is located to the inner leaflet of plasma membrane generally but it is moved to the outer leaflet during programmed cell death. The process of apoptosis has been implicated in the fusion of muscle progenitor cells, myoblasts, into myotubes. However, it remained unclear whether PS regulates muscle cell differentiation directly. In this paper, localization of PS to the outer leaflet of plasma membrane in proliferating primary myoblasts and during fusion of these myoblasts into myotubes is validated using Annexin V. Moreover, we show the presence of PS clusters at the cell-cell contact points, suggesting the importance of membrane ruffling and PS exposure for the myogenic cell fusion. Confirming this conclusion, experimentally constructed PS, but not PC liposomes dramatically enhance the formation of myotubes from myoblasts, thus demonstrating a direct positive effect of PS on the muscle cell fusion. In contrast, myoblasts exposed to PC liposomes produce long myotubes with low numbers of myonuclei. Moreover, pharmacological masking of PS on the myoblast surface inhibits fusion of these cells into myotubes in a dose-dependent manner.

  13. A Lexical Framework for Semantic Annotation of Positive and Negative Regulation Relations in Biomedical Pathways

    DEFF Research Database (Denmark)

    Zambach, Sine; Lassen, Tine

    presented here, we analyze 6 frequently used verbs denoting the regulation relations regulates, positively regulates and negatively regulates through corpus analysis, and propose a formal representation of the acquired knowledge as domain speci¯c semantic frames. The acquired knowledge patterns can thus...

  14. NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling

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    Beiying Qiu

    2014-06-01

    Full Text Available Although much is known about the molecular players in insulin signaling, there is scant information about transcriptional regulation of its key components. We now find that NUCKS is a transcriptional regulator of the insulin signaling components, including the insulin receptor (IR. Knockdown of NUCKS leads to impaired insulin signaling in endocrine cells. NUCKS knockout mice exhibit decreased insulin signaling and increased body weight/fat mass along with impaired glucose tolerance and reduced insulin sensitivity, all of which are further exacerbated by a high-fat diet (HFD. Genome-wide ChIP-seq identifies metabolism and insulin signaling as NUCKS targets. Importantly, NUCKS is downregulated in individuals with a high body mass index and in HFD-fed mice, and conversely, its levels increase upon starvation. Altogether, NUCKS is a physiological regulator of energy homeostasis and glucose metabolism that works by regulating chromatin accessibility and RNA polymerase II recruitment to the promoters of IR and other insulin pathway modulators.

  15. Certification and Regulation of Advanced Practice Nurses. Position Statement.

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    Journal of Professional Nursing, 1996

    1996-01-01

    This position statement of the American Association of Colleges of Nursing asserts that the nursing profession must develop a standardized national advanced practice nursing certification process by 2000. Professional certification validates and standardizes the qualifications and practice competencies of the advanced practice nurse. (Author/JOW)

  16. Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture

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    Marta Esteves da Silva

    2015-11-01

    Full Text Available Lateral diffusion in the membrane and endosomal trafficking both contribute to the addition and removal of AMPA receptors (AMPARs at postsynaptic sites. However, the spatial coordination between these mechanisms has remained unclear, because little is known about the dynamics of AMPAR-containing endosomes. In addition, how the positioning of AMPAR-containing endosomes affects synapse organization and functioning has never been directly explored. Here, we used live-cell imaging in hippocampal neuron cultures to show that intracellular AMPARs are transported in Rab11-positive recycling endosomes, which frequently enter dendritic spines and depend on the microtubule and actin cytoskeleton. By using chemically induced dimerization systems to recruit kinesin (KIF1C or myosin (MyosinV/VI motors to Rab11-positive recycling endosomes, we controlled their trafficking and found that induced removal of recycling endosomes from spines decreases surface AMPAR expression and PSD-95 clusters at synapses. Our data suggest a mechanistic link between endosome positioning and postsynaptic structure and composition.

  17. YY1 positively regulates human UBIAD1 expression

    International Nuclear Information System (INIS)

    Funahashi, Nobuaki; Hirota, Yoshihisa; Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato; Suhara, Yoshitomo; Okano, Toshio

    2015-01-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K 1 ) and a series of bacterial menaquionones (MK-n; vitamin K 2 ). Menadione (vitamin K 3 ) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1 promoter

  18. YY1 positively regulates human UBIAD1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Funahashi, Nobuaki, E-mail: nfunahashi@ri.ncgm.go.jp [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Hirota, Yoshihisa [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka (Japan); Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Suhara, Yoshitomo [Department of Bioscience and Engineering, Shibaura Institute of Technology, Saitama (Japan); Okano, Toshio [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan)

    2015-05-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K{sub 1}) and a series of bacterial menaquionones (MK-n; vitamin K{sub 2}). Menadione (vitamin K{sub 3}) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1

  19. Long Noncoding RNA PANDA Positively Regulates Proliferation of Osteosarcoma Cells.

    Science.gov (United States)

    Kotake, Yojiro; Goto, Taiki; Naemura, Madoka; Inoue, Yasutoshi; Okamoto, Haruna; Tahara, Keiichiro

    2017-01-01

    A long noncoding RNA, p21-associated ncRNA DNA damage-activated (PANDA), associates with nuclear transcription factor Y subunit alpha (NF-YA) and inhibits its binding to promoters of apoptosis-related genes, thereby repressing apoptosis in normal human fibroblasts. Here, we show that PANDA is involved in regulating proliferation in the U2OS human osteosarcoma cell line. U2OS cells were transfected with siRNAs against PANDA 72 h later and they were subjected to reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR and cell-cycle analysis. PANDA was highly expressed in U2OS cells, and its expression was induced by DNA damage. Silencing PANDA caused arrest at the G 1 phase of the cell cycle, leading to inhibition of cell proliferation. Quantitative RT-PCR showed that silencing PANDA increased mRNA levels of the cyclin-dependent kinase inhibitor p18, which caused G 1 phase arrest. These results suggest that PANDA promotes G 1 -S transition by repressing p18 transcription, and thus promotes U2OS cell proliferation. Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. Pectin methylesterase31 positively regulates salt stress tolerance in Arabidopsis.

    Science.gov (United States)

    Yan, Jingwei; He, Huan; Fang, Lin; Zhang, Aying

    2018-02-05

    The alteration of cell wall component and structure is an important adaption to saline environment. Pectins, a major cell wall component, are often present in a highly methylesterified form. The level of methyl esterification determined by pectin methylesterases (PMEs) influences many important wall properties that are believed to relate to the adaption to saline stress. However, little is known about the function of PMEs in response to salt stress. Here, we established a link between pectin methylesterase31 (PME31) and salt stress tolerance. Salt stress significantly increases PME31 expression. PME31 is located in the plasma membrane and the expression level of PME31 was high in dry seeds. Knock-down mutants in PME31 conferred hypersensitive phenotypes to salt stress in seed germination and post-germination growth. Real-time PCR analysis revealed that the transcript levels of several stress genes (DREB2A, RD29A and RD29B) are lower in pme31-2 mutant than that in the wild type in response to salt stress. These results suggested that PME31 could positively modulate salt stress tolerance. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Developmental regulation of a local positive autocontrol of supraoptic neurons.

    Science.gov (United States)

    Chevaleyre, V; Dayanithi, G; Moos, F C; Desarmenien, M G

    2000-08-01

    Mature oxytocin (OT) and vasopressin (AVP) magnocellular neurons of the hypothalamic supraoptic nuclei (SON) autocontrol their electrical activity via somatodendritic release of their respective peptides. Because OT and AVP are synthesized early in development and could play an important role in the maturation of these neurons, we checked whether the peptides are released within the SON and act on their secreting neurons during 3 weeks of postnatal development. We used patch-clamp recordings from SON neurons in rat hypothalamic horizontal slices to show that the spontaneous electrical activity of immature SON neurons is blocked by OT or AVP receptor antagonists, demonstrating a basal somatodendritic release of the peptides. Application of OT or AVP depolarizes SON neurons and stimulates activity typical of the corresponding mature neurons. This effect is directly on SON neurons because it is recorded in dissociated neurons. Radioimmunoassays from isolated SON were used to show that each peptide facilitates its own release at a somatodendritic level, exhibiting a self-sustaining positive feedback loop. This autocontrol is not uniform during development because the proportion of neurons depolarized by the peptides, the amplitude of the depolarization, and the propensity of the peptides to facilitate their own release are maximal during the second postnatal week and decrease thereafter. These data are consistent with a role of autocontrol in the maturation of SON neurons because it is maximal during the delimited period of postnatal development that corresponds to the period of major synapse formation.

  2. Cardiovascular regulation during body unweighting by lower body positive pressure.

    Science.gov (United States)

    Evans, Joyce M; Mohney, Lindsay; Wang, Siqi; Moore, Rachel K; Elayi, Samy-Claude; Stenger, Michael B; Moore, Fritz B; Knapp, Charles F

    2013-11-01

    We hypothesized that human cardiovascular responses to standing in reduced gravity environments, as on the Moon or Mars, could be modeled using a lower body positive pressure (LBPP) chamber. Heart rate, blood pressure, body segment fluid shifts, ECG, indexes of sympathetic, parasympathetic balance, and baroreflex control of the heart and periphery plus echocardiographic measures of cardiac function were recorded from seven men and seven women supine and standing at 100% (Earth), 40% (-Mars), and 20% (-Moon) bodyweights (BW). The fluid shifted from the chest was greater when standing at 100% BW than at 20% and 40% BW, while fluid pooled in the abdomen was similar at all BWs. Compared to moving from supine to standing at 100% BW, moving to 20% and 40% BW resulted in smaller decreases in stroke volume and pulse pressure, smaller increases in heart rate and smaller decreases in parasympathetic control of heart rate, baroreflex slope, numbers of blood pressure ramps, and much reduced indexes of sympathetic drive to the heart and periphery. However, peripheral vascular resistance, systolic pressure, and baroreflex effectiveness were elevated during 20% and 40% BW, compared to supine and standing at 100% BW. Standing at reduced bodyweight suppressed indexes of sympathetic control of heart rate and peripheral vasomotion. Regulatory responses indicated a combination of arterial and cardiopulmonary baroreflex control: mean heart rate, vasomotion, and baroreflex sensitivity appeared to be more under cardiopulmonary control while baroreflex effectiveness appeared to be driven more by the arterial baroreflex.

  3. Dampening or savoring positive emotions: a dialectical cultural script guides emotion regulation.

    Science.gov (United States)

    Miyamoto, Yuri; Ma, Xiaoming

    2011-12-01

    Four studies examined the hypothesis that, although people may generally want to savor, rather than to dampen, their positive emotions (i.e., hedonic emotion regulation), such a hedonic emotion regulation tendency should be less pronounced for Easterners than for Westerners. Using retrospective memory procedures, Study 1 found that Easterners recalled engaging in hedonic emotion regulation less than Westerners did, even after controlling for their initial emotional reactions. Studies 2-3 showed that cultural differences in emotion regulation were mediated by dialectical beliefs about positive emotions. Study 4 replicated the findings by examining online reports of emotion regulation strategies on the day students received a good grade. Furthermore, there were cultural differences in actual emotion change over time, which was partly explained by dialectical beliefs about positive emotions. These findings highlight the active role cultural scripts play in shaping emotion regulation and emotional experiences. (c) 2011 APA, all rights reserved.

  4. Positive academic emotions moderate the relationship between self-regulation and academic achievement.

    Science.gov (United States)

    Villavicencio, Felicidad T; Bernardo, Allan B I

    2013-06-01

    Research has shown how academic emotions are related to achievement and to cognitive/motivational variables that promote achievement. Mediated models have been proposed to account for the relationships among academic emotions, cognitive/motivational variables, and achievement, and research has supported such mediated models, particularly with negative emotions. The study tested the hypotheses: (1) self-regulation and the positive academic emotions of enjoyment and pride are positive predictors of achievement; and (2) enjoyment and pride both moderate the relationship between self-regulation and achievement. Participants were 1,345 students enrolled in various trigonometry classes in one university. Participants answered the Academic Emotions Questionnaire-Math (Pekrun, Goetz, & Frenzel, 2005) and a self-regulation scale (Pintrich, Smith, Garcia, & McKeachie, 1991) halfway through their trigonometry class. The students' final grades in the course were regressed to self-regulation, positive emotions, and the interaction terms to test the moderation effects. Enjoyment and pride were both positive predictors of grades; more importantly, both moderated the relationship between self-regulation and grades. For students who report higher levels of both positive emotions, self-regulation was positively associated with grades. However, for those who report lower levels of pride, self-regulation was not related to grades; and, for those who reported lower levels of enjoyment, self-regulation was negatively related to grades. The results are discussed in terms of how positive emotions indicate positive appraisals of task/outcome value, and thus enhance the positive links between cognitive/motivational variables and learning. ©2012 The British Psychological Society.

  5. 78 FR 70191 - Post-Employment Conflict of Interest Regulations; Exempted Senior Employee Positions; Withdrawal...

    Science.gov (United States)

    2013-11-25

    ...: The Office of Government Ethics is withdrawing the final rule ``Post-Employment Conflict of Interest... / Monday, November 25, 2013 / Rules and Regulations#0;#0; ] OFFICE OF GOVERNMENT ETHICS 5 CFR Part 2641 RIN 3209-AA14 Post-Employment Conflict of Interest Regulations; Exempted Senior Employee Positions...

  6. Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling

    Science.gov (United States)

    Stephen, Terri-Leigh; Higgs, Nathalie F.; Sheehan, David F.; Al Awabdh, Sana; López-Doménech, Guillermo; Arancibia-Carcamo, I. Lorena

    2015-01-01

    It is fast emerging that maintaining mitochondrial function is important for regulating astrocyte function, although the specific mechanisms that govern astrocyte mitochondrial trafficking and positioning remain poorly understood. The mitochondrial Rho-GTPase 1 protein (Miro1) regulates mitochondrial trafficking and detachment from the microtubule transport network to control activity-dependent mitochondrial positioning in neurons. However, whether Miro proteins are important for regulating signaling-dependent mitochondrial dynamics in astrocytic processes remains unclear. Using live-cell confocal microscopy of rat organotypic hippocampal slices, we find that enhancing neuronal activity induces transient mitochondrial remodeling in astrocytes, with a concomitant, transient reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca2+. Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca2+-sensing EF-hand domains of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for activity-driven mitochondrial confinement near synapses. Additionally, activity-dependent mitochondrial positioning by Miro1 reciprocally regulates the levels of intracellular Ca2+ in astrocytic processes. Thus, the regulation of intracellular Ca2+ signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca2+ wave propagation, gliotransmission, and ultimately neuronal function. SIGNIFICANCE STATEMENT Mitochondria are key cellular organelles that play important roles in providing cellular energy and buffering intracellular calcium ions. The mechanisms that control mitochondrial distribution within the processes of glial cells called astrocytes and the impact this may have on calcium signaling remains unclear. We show that activation of glutamate receptors or increased neuronal

  7. Wnt signaling positively regulates endothelial cell fate specification in the Fli1a-positive progenitor population via Lef1.

    Science.gov (United States)

    Hübner, Kathleen; Grassme, Kathrin S; Rao, Jyoti; Wenke, Nina K; Zimmer, Cordula L; Korte, Laura; Mu Ller, Katja; Sumanas, Saulius; Greber, Boris; Herzog, Wiebke

    2017-10-01

    During vertebrate embryogenesis, vascular endothelial cells (ECs) and primitive erythrocytes become specified within close proximity in the posterior lateral plate mesoderm (LPM) from a common progenitor. However, the signaling cascades regulating the specification into either lineage remain largely elusive. Here, we analyze the contribution of β-catenin dependent Wnt signaling to EC and erythrocyte specification during zebrafish embryogenesis. We generated novel β-catenin dependent Wnt signaling reporters which, by using destabilized fluorophores (Venus-Pest, dGFP), specifically allow us to detect Wnt signaling responses in narrow time windows as well as in spatially restricted domains, defined by Cre recombinase expression (Tg(axin2 BAC :Venus-Pest) mu288 ; Tg(14TCF:loxP-STOP-loxP-dGFP) mu202 ). We therefore can detect β-catenin dependent Wnt signaling activity in a subset of the Fli1a-positive progenitor population. Additionally, we show that mesodermal Wnt3a-mediated signaling via the transcription factor Lef1 positively regulates EC specification (defined by kdrl expression) at the expense of primitive erythrocyte specification (defined by gata1 expression) in zebrafish embryos. Using mesoderm derived from human embryonic stem cells, we identified the same principle of Wnt signaling dependent EC specification in conjunction with auto-upregulation of LEF1. Our data indicate a novel role of β-catenin dependent Wnt signaling in regulating EC specification during vasculogenesis. Copyright © 2017. Published by Elsevier Inc.

  8. Modeling the Structure of the Relationship Between Emotion Regulation Difficulties, Positive and Negative affect Sleep Quality

    Directory of Open Access Journals (Sweden)

    S Amiri

    2017-05-01

    Full Text Available Abstract   Background & aim: Poor quality sleep is very common in modern societies and has a significant negative impact on psychological and physiological Dimensions. The purpose of the present study was to investigate correlational relationships and draw up a positive and negative affect mediation model between the difficulty in regulation of emotion and quality of sleep.   Methods: In this descriptive-correlational study, the participants of the study were selected through multi-stage cluster sampling. Then, the difficulty questionnaire was distributed in emotion regulation, affective and negative and sleep quality among the participants . Collected data was analyzed for descriptive, correlation, structural equation modeling to investigate the research objectives.   Results: The results showed that there was a significant positive correlation between the difficulty components of emotion regulation and negative emotion with poor sleep quality and positive correlation between positive affection and high sleep quality (p <0.01. Also, the pattern of structural equation modeling indicates the role of mediating positive and negative affects in the relationship between the difficulty in regulation of emotion and sleep quality . Conclusions: The results supported the hypothesis that the difficulty in regulation of emotion interferes with the quality of sleep, and positive affection can have a moderating role in this regard.    

  9. Metacognitive beliefs and emotion regulation strategies: obese women with negative and positive body images

    Directory of Open Access Journals (Sweden)

    Somayeh Nejati

    2017-07-01

    Full Text Available Women have higher vulnerability regarding to increase prevalence of obesity and its effect on people’s body image and women’s health on the society and future generations’ health is unquestionable role , negative body image influence on women’s eating habits and mental health, so aim of present research is to compare metacognitive beliefs and emotional regulation strategies in obese women with positive and negative body image. This study was a causal-comparative. The statistical population of this study consisted of 100 obese women with a BMI>30 who had referred to five nutritional clinics in Tehran. The clinics and the participants were selected by using the convenience sampling method. The data collection tools were the Structured Clinical Interview for DSM (SCID-I/II, Body Mass Index (BMI, the Metacognitions Questionnaire (MCQ-30, the cognitive emotion regulation questionnaire, and fisher’s body image scale. The multivariate hoteling t-test was used to compare the difference between the two groups. Results indicated that obese women with negative body image had higher mean scores in inefficient emotion regulation strategies including self-blame or focus on thought, catastrophizing and other-blame compared with obese women with positive body image. Moreover, the mean scores of obese women with positive body images was higher in efficient emotional regulation strategies include acceptance, positive refocusing, refocusing on planning, perspective taking and positive reappraisal. Metacognitive beliefs and emotion regulation strategies are significant variables in obese woman with positive and negative body images.

  10. Rethinking emotion: cognitive reappraisal is an effective positive and negative emotion regulation strategy in bipolar disorder.

    Science.gov (United States)

    Gruber, June; Hay, Aleena C; Gross, James J

    2014-04-01

    Bipolar disorder involves difficulties with emotion regulation, yet the precise nature of these emotion regulatory difficulties is unclear. The current study examined whether individuals with remitted bipolar I disorder (n = 23) and healthy controls (n = 23) differ in their ability to use one effective and common form of emotion regulation, cognitive reappraisal. Positive, negative, and neutral films were used to elicit emotion, and participants were cued to watch the film carefully (i.e., uninstructed condition) or reappraise while measures of affect, behavior, and psychophysiology were obtained. Results showed that reappraisal was associated with reductions in emotion reactivity across subjective (i.e., positive and negative affect), behavioral (i.e., positive facial displays), and physiological (i.e., skin conductance) response domains across all participants. Results suggest that reappraisal may be an effective regulation strategy for both negative and positive emotion across both healthy adults and individuals with bipolar disorder. Discussion focuses on clinical and treatment implications for bipolar disorder.

  11. Pathways to positivity from perceived stress in adolescents: multiple mediation of emotion regulation and coping strategies

    Directory of Open Access Journals (Sweden)

    Mehmet Ali Yildiz

    2017-05-01

    Full Text Available Background The current study aimed to examine the multiple mediation of emotion regulation and coping strategies in the relationship between perceived stress and positivity in adolescents. Participants and procedure Participants included 312 adolescents attending high schools. 162 of the participants were female and 150 were male, with an average age of 16.26, SD = 1.21. Data collection was conducted with the Perceived Stress Scale, the Emotion Regulation Scale for Adolescents, the Coping Scale for Children and Youth, and the Positivity Scale. Descriptive statistics, Pearson’s correlation coefficient, regression based on ordinary least squares, and the bootstrap method were used to analyze the research data. Results The research findings indicated that internal dysfunctional emotion regulation, assistance seeking, problem solving, and behavioral avoidance mediated the relationship between perceived stress and positivity. Conclusion In conclusion, internal dysfunctional emotion regulation, seeking assistance, problem solving, and behavioral avoidance were found to mediate the relationship between adolescents’ perceived stress and positivity. Thus, preparing individual and group psychological counseling as well as emotion regulation and coping-oriented psycho-educational programs for adolescents to regulate negative emotions and to cope with stress may be important. The research findings were discussed and interpreted based on the relevant literature, and suggestions for relevant experts were included.

  12. ER-α36-Mediated Rapid Estrogen Signaling Positively Regulates ER-Positive Breast Cancer Stem/Progenitor Cells

    Science.gov (United States)

    Deng, Hao; Zhang, Xin-Tian; Wang, Mo-Lin; Zheng, Hong-Yan; Liu, Li-Jiang; Wang, Zhao-Yi

    2014-01-01

    The breast cancer stem cells (BCSC) play important roles in breast cancer occurrence, recurrence and metastasis. However, the role of estrogen signaling, a signaling pathway important in development and progression of breast cancer, in regulation of BCSC has not been well established. Previously, we identified and cloned a variant of estrogen receptor α, ER-α36, with a molecular weight of 36 kDa. ER-α36 lacks both transactivation domains AF-1 and AF-2 of the 66 kDa full-length ER-α (ER-α66) and mediates rapid estrogen signaling to promote proliferation of breast cancer cells. In this study, we aim to investigate the function and the underlying mechanism of ER-α36-mediated rapid estrogen signaling in growth regulation of the ER-positive breast cancer stem/progenitor cells. ER-positive breast cancer cells MCF7 and T47D as well as the variants with different levels of ER-α36 expression were used. The effects of estrogen on BCSC's abilities of growth, self-renewal, differentiation and tumor-seeding were examined using tumorsphere formation, flow cytometry, indirect immunofluorence staining and in vivo xenograft assays. The underlying mechanisms were also studied with Western-blot analysis. We found that 17-β-estradiol (E2β) treatment increased the population of ER-positive breast cancer stem/progenitor cells while failed to do so in the cells with knocked-down levels of ER-α36 expression. Cells with forced expression of recombinant ER-α36, however, responded strongly to E2β treatment by increasing growth in vitro and tumor-seeding efficiency in vivo. The rapid estrogen signaling via the AKT/GSK3β pathway is involved in estrogen-stimulated growth of ER-positive breast cancer stem/progenitor cells. We concluded that ER-α36-mediated rapid estrogen signaling plays an important role in regulation and maintenance of ER-positive breast cancer stem/progenitor cells. PMID:24558373

  13. Positive regulation of botulinum neurotoxin gene expression by CodY in Clostridium botulinum ATCC 3502.

    Science.gov (United States)

    Zhang, Zhen; Dahlsten, Elias; Korkeala, Hannu; Lindström, Miia

    2014-12-01

    Botulinum neurotoxin, produced mainly by the spore-forming bacterium Clostridium botulinum, is the most poisonous biological substance known. Here, we show that CodY, a global regulator conserved in low-G+C Gram-positive bacteria, positively regulates the botulinum neurotoxin gene expression. Inactivation of codY resulted in decreased expression of botA, encoding the neurotoxin, as well as in reduced neurotoxin synthesis. Complementation of the codY mutation in trans rescued neurotoxin synthesis, and overexpression of codY in trans caused elevated neurotoxin production. Recombinant CodY was found to bind to a 30-bp region containing the botA transcription start site, suggesting regulation of the neurotoxin gene transcription through direct interaction. GTP enhanced the binding affinity of CodY to the botA promoter, suggesting that CodY-dependent neurotoxin regulation is associated with nutritional status. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  14. Response and binding elements for ligand-dependent positive transcription factors integrate positive and negative regulation of gene expression

    International Nuclear Information System (INIS)

    Rosenfeld, M.G.; Glass, C.K.; Adler, S.; Crenshaw, E.B. III; He, X.; Lira, S.A.; Elsholtz, H.P.; Mangalam, H.J.; Holloway, J.M.; Nelson, C.; Albert, V.R.; Ingraham, H.A.

    1988-01-01

    Accurate, regulated initiation of mRNA transcription by RNA polymerase II is dependent on the actions of a variety of positive and negative trans-acting factors that bind cis-acting promoter and enhancer elements. These transcription factors may exert their actions in a tissue-specific manner or function under control of plasma membrane or intracellular ligand-dependent receptors. A major goal in the authors' laboratory has been to identify the molecular mechanisms responsible for the serial activation of hormone-encoding genes in the pituitary during development and the positive and negative regulation of their transcription. The anterior pituitary gland contains phenotypically distinct cell types, each of which expresses unique trophic hormones: adrenocorticotropic hormone, thyroid-stimulating hormone, prolactin, growth hormone, and follicle-stimulating hormone/luteinizing hormone. The structurally related prolactin and growth hormone genes are expressed in lactotrophs and somatotrophs, respectively, with their expression virtually limited to the pituitary gland. The reported transient coexpression of these two structurally related neuroendocrine genes raises the possibility that the prolactin and growth hormone genes are developmentally controlled by a common factor(s)

  15. The neural correlates of regulating positive and negative emotions in medication-free major depression.

    Science.gov (United States)

    Greening, Steven G; Osuch, Elizabeth A; Williamson, Peter C; Mitchell, Derek G V

    2014-05-01

    Depressive cognitive schemas play an important role in the emergence and persistence of major depressive disorder (MDD). The current study adapted emotion regulation techniques to reflect elements of cognitive behavioural therapy (CBT) and related psychotherapies to delineate neurocognitive abnormalities associated with modulating the negative cognitive style in MDD. Nineteen non-medicated patients with MDD and 19 matched controls reduced negative or enhanced positive feelings elicited by emotional scenes while undergoing functional magnetic resonance imaging. Although both groups showed significant emotion regulation success as measured by subjective ratings of affect, the controls were significantly better at modulating both negative and positive emotion. Both groups recruited regions of dorsolateral prefrontal cortex and ventrolateral prefrontal cortex (VLPFC) when regulating negative emotions. Only in controls was this accompanied by reduced activity in sensory cortices and amygdala. Similarly, both groups showed enhanced activity in VLPFC and ventral striatum when enhancing positive affect; however, only in controls was ventral striatum activity correlated with regulation efficacy. The results suggest that depression is associated with both a reduced capacity to achieve relief from negative affect despite recruitment of ventral and dorsal prefrontal cortical regions implicated in emotion regulation, coupled with a disconnect between activity in reward-related regions and subjective positive affect.

  16. The neural correlates of regulating positive and negative emotions in medication-free major depression

    Science.gov (United States)

    Greening, Steven G.; Osuch, Elizabeth A.; Williamson, Peter C.

    2014-01-01

    Depressive cognitive schemas play an important role in the emergence and persistence of major depressive disorder (MDD). The current study adapted emotion regulation techniques to reflect elements of cognitive behavioural therapy (CBT) and related psychotherapies to delineate neurocognitive abnormalities associated with modulating the negative cognitive style in MDD. Nineteen non-medicated patients with MDD and 19 matched controls reduced negative or enhanced positive feelings elicited by emotional scenes while undergoing functional magnetic resonance imaging. Although both groups showed significant emotion regulation success as measured by subjective ratings of affect, the controls were significantly better at modulating both negative and positive emotion. Both groups recruited regions of dorsolateral prefrontal cortex and ventrolateral prefrontal cortex (VLPFC) when regulating negative emotions. Only in controls was this accompanied by reduced activity in sensory cortices and amygdala. Similarly, both groups showed enhanced activity in VLPFC and ventral striatum when enhancing positive affect; however, only in controls was ventral striatum activity correlated with regulation efficacy. The results suggest that depression is associated with both a reduced capacity to achieve relief from negative affect despite recruitment of ventral and dorsal prefrontal cortical regions implicated in emotion regulation, coupled with a disconnect between activity in reward-related regions and subjective positive affect. PMID:23482626

  17. BOC, an Ig superfamily member, associates with CDO to positively regulate myogenic differentiation

    OpenAIRE

    Kang, Jong-Sun; Mulieri, Philip J.; Hu, Yulan; Taliana, Lavinia; Krauss, Robert S.

    2002-01-01

    CDO is a cell surface receptor-like protein that positively regulates myogenic differentiation. Reported here is the identification of BOC, which, with CDO, defines a newly recognized subfamily within the immunoglobulin superfamily. cdo and boc are co-expressed in muscle precursors in the developing mouse embryo. Like CDO, BOC accelerates differentiation of cultured myoblast cell lines and participates in a positive feedback loop with the myogenic transcription factor, MyoD. CDO and BOC form ...

  18. Emotion regulation strategies mediate the associations of positive and negative affect to upper extremity physical function.

    Science.gov (United States)

    Talaei-Khoei, Mojtaba; Nemati-Rezvani, Hora; Fischerauer, Stefan F; Ring, David; Chen, Neal; Vranceanu, Ana-Maria

    2017-05-01

    The Gross process model of emotion regulation holds that emotion-eliciting situations (e.g. musculoskeletal illness) can be strategically regulated to determine the final emotional and behavioral response. Also, there is some evidence that innate emotional traits may predispose an individual to a particular regulating coping style. We enrolled 107 patients with upper extremity musculoskeletal illness in this cross-sectional study. They completed self-report measures of positive and negative affect, emotion regulation strategies (cognitive reappraisal and expressive suppression), upper extremity physical function, pain intensity, and demographics. We used Preacher and Hayes' bootstrapping approach to process analysis to infer the direct effect of positive and negative affect on physical function as well as their indirect effects through activation of emotion regulation strategies. Negative affect was associated with decreased physical function. The association was partly mediated by expressive suppression (b (SE)=-.10 (.05), 95% BCa CI [-.21, -.02]). Positive affect was associated with increased physical function. Cognitive reappraisal partially mediated this association (b (SE)=.11 (.05), 95% BCa CI [.03, .24]). After controlling for pain intensity, the ratio of the mediated effect to total effect grew even larger in controlled model comparing to uncontrolled model (33% vs. 26% for expressive suppression and 32% vs. 30% for cognitive reappraisal). The relationships between affect, emotion regulation strategies and physical function appear to be more dependent on the emotional response to an orthopedic condition rather than the intensity of the nociceptive stimulation of the pain. Findings support integration of emotion regulation training in skill-based psychotherapy in this population to mitigate the effect of negative affect and enhance the influence of positive affect on physical function. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Factor Structure and Initial Validation of a Multidimensional Measure of Difficulties in the Regulation of Positive Emotions: The DERS-Positive.

    Science.gov (United States)

    Weiss, Nicole H; Gratz, Kim L; Lavender, Jason M

    2015-05-01

    Emotion regulation difficulties are a transdiagnostic construct relevant to numerous clinical difficulties. Although the Difficulties in Emotion Regulation Scale (DERS) is a multidimensional measure of maladaptive ways of responding to emotions, it focuses on difficulties with the regulation of negative emotions and does not assess emotion dysregulation in the form of problematic responding to positive emotions. The aim of this study was to develop and validate a measure of clinically relevant difficulties in the regulation of positive emotions (DERS-Positive). Findings revealed a three-factor structure and supported the internal consistency and construct validity of the total and subscale scores. © The Author(s) 2015.

  20. LnqR, a TetR-family transcriptional regulator, positively regulates lacticin Q production in Lactococcus lactis QU 5.

    Science.gov (United States)

    Iwatani, Shun; Ishibashi, Naoki; Flores, Floirendo P; Zendo, Takeshi; Nakayama, Jiro; Sonomoto, Kenji

    2016-09-01

    Lacticin Q is an unmodified leaderless bacteriocin produced by Lactococcus lactis QU 5. It has been revealed that the production and self-immunity of lacticin Q are facilitated by a gene cluster lnqQBCDEF The gene for a putative TetR-family transcriptional regulator, termed lnqR, was found nearby the lnqQBCDEF cluster, but its involvement in lacticin Q biosynthesis remained unknown. In this study, we created an LnqR-overexpressing QU 5 recombinant by using lactococcal constitutive promoter P32 The recombinant QU 5 showed enhanced production of and self-immunity to lacticin Q. RT-PCR analysis has revealed that an overexpression of LnqR increases the amounts of lnqQBCDEF transcripts, and these six genes are transcribed as an operon in a single transcriptional unit. Interestingly, LnqR expression and thus lacticin Q production by L. lactis QU 5 was found temperature dependent, while LnzR, an LnqR-homologue, in L. lactis QU 14 was expressed in a similar but not identical manner to LnqR, resulting in dissimilar bacteriocin productivities by these strains. This report demonstrates LnqR as the first TetR-family transcriptional regulator involved in LAB bacteriocin biosynthesis and that, as an exceptional case of TetR-family regulators, LnqR positively regulates the transcription of these biosynthetic genes. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. The Mechanisms of Virulence Regulation by Small Noncoding RNAs in Low GC Gram-Positive Pathogens

    Directory of Open Access Journals (Sweden)

    Stephanie Pitman

    2015-12-01

    Full Text Available The discovery of small noncoding regulatory RNAs (sRNAs in bacteria has grown tremendously recently, giving new insights into gene regulation. The implementation of computational analysis and RNA sequencing has provided new tools to discover and analyze potential sRNAs. Small regulatory RNAs that act by base-pairing to target mRNAs have been found to be ubiquitous and are the most abundant class of post-transcriptional regulators in bacteria. The majority of sRNA studies has been limited to E. coli and other gram-negative bacteria. However, examples of sRNAs in gram-positive bacteria are still plentiful although the detailed gene regulation mechanisms behind them are not as well understood. Strict virulence control is critical for a pathogen’s survival and many sRNAs have been found to be involved in that process. This review outlines the targets and currently known mechanisms of trans-acting sRNAs involved in virulence regulation in various gram-positive pathogens. In addition, their shared characteristics such as CU interaction motifs, the role of Hfq, and involvement in two-component regulators, riboswitches, quorum sensing, or toxin/antitoxin systems are described.

  2. The interaction of positive and negative sensory feedback loops in dynamic regulation of a motor pattern.

    Science.gov (United States)

    Ausborn, Jessica; Wolf, Harald; Stein, Wolfgang

    2009-10-01

    In many rhythmic behaviors, phasic sensory feedback modifies the motor pattern. This modification is assumed to depend on feedback sign (positive vs. negative). While on a phenomenological level feedback sign is well defined, many sensory pathways also process antagonistic, and possibly contradictory, sensory information. We here model the locust flight pattern generator and proprioceptive feedback provided by the tegula wing receptor to test the functional significance of sensory pathways processing antagonistic information. We demonstrate that the tegula provides delayed positive feedback via interneuron 301, while all other pathways provide negative feedback. Contradictory to previous assumptions, the increase of wing beat frequency when the tegula is activated during flight is due to the positive feedback. By use of an abstract model we reveal that the regulation of motor pattern frequency by sensory feedback critically depends on the interaction of positive and negative feedback, and thus on the weighting of antagonistic pathways.

  3. Unions and NGOs positions on the risks and regulation of nanotechnology

    Directory of Open Access Journals (Sweden)

    Noela Invernizzi

    2013-11-01

    Full Text Available This article discusses the perspectives of a number of Non-Governmental Organizations (NGOs and trade unions on the risks and regulation of nanotechnology. In the context of large public and private investments in nanotechnology, and its rapid incorporation into processes and products, these groups have sought to advance their interests through diverse strategies. Their positions are centered in the application of the precautionary principle and include demands for moratoria, more investigation on environmental, health and occupational risks, specific and mandatory regulation, transparent information and broad public participation in the governance of nanotechnology. We show that these civil society organizations are constructing collaborations and alliances and have had some degree of success in placing the issues of risks and regulation into the government´s agendas.

  4. HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Won Hee Jung

    2010-11-01

    Full Text Available The fungal pathogen Cryptococcus neoformans is a major cause of illness in immunocompromised individuals such as AIDS patients. The ability of the fungus to acquire nutrients during proliferation in host tissue and the ability to elaborate a polysaccharide capsule are critical determinants of disease outcome. We previously showed that the GATA factor, Cir1, is a major regulator both of the iron uptake functions needed for growth in host tissue and the key virulence factors such as capsule, melanin and growth at 37°C. We are interested in further defining the mechanisms of iron acquisition from inorganic and host-derived iron sources with the goal of understanding the nutritional adaptation of C. neoformans to the host environment. In this study, we investigated the roles of the HAP3 and HAPX genes in iron utilization and virulence. As in other fungi, the C. neoformans Hap proteins negatively influence the expression of genes encoding respiratory and TCA cycle functions under low-iron conditions. However, we also found that HapX plays both positive and negative roles in the regulation of gene expression, including a positive regulatory role in siderophore transporter expression. In addition, HapX also positively regulated the expression of the CIR1 transcript. This situation is in contrast to the negative regulation by HapX of genes encoding GATA iron regulatory factors in Aspergillus nidulans and Schizosaccharomyces pombe. Although both hapX and hap3 mutants were defective in heme utilization in culture, only HapX made a contribution to virulence, and loss of HapX in a strain lacking the high-affinity iron uptake system did not cause further attenuation of disease. Therefore, HapX appears to have a minimal role during infection of mammalian hosts and instead may be an important regulator of environmental iron uptake functions. Overall, these results indicated that C. neoformans employs multiple strategies for iron acquisition during infection.

  5. The neural correlates of regulating positive and negative emotions in medication-free major depression

    OpenAIRE

    Greening, Steven G.; Osuch, Elizabeth A.; Williamson, Peter C.; Mitchell, Derek G. V.

    2013-01-01

    Depressive cognitive schemas play an important role in the emergence and persistence of major depressive disorder (MDD). The current study adapted emotion regulation techniques to reflect elements of cognitive behavioural therapy (CBT) and related psychotherapies to delineate neurocognitive abnormalities associated with modulating the negative cognitive style in MDD. Nineteen non-medicated patients with MDD and 19 matched controls reduced negative or enhanced positive feelings elicited by emo...

  6. Effects of body position on autonomic regulation of cardiovascular function in young, healthy adults

    OpenAIRE

    Polus Barbara I; Reece John; Watanabe Nobuhiro

    2007-01-01

    Abstract Background Analysis of rhythmic patterns embedded within beat-to-beat variations in heart rate (heart rate variability) is a tool used to assess the balance of cardiac autonomic nervous activity and may be predictive for prognosis of some medical conditions, such as myocardial infarction. It has also been used to evaluate the impact of manipulative therapeutics and body position on autonomic regulation of the cardiovascular system. However, few have compared cardiac autonomic activit...

  7. CK2-dependent phosphorylation positively regulates stress-induced activation of Msn2 in Saccharomyces cerevisiae.

    Science.gov (United States)

    Cho, Bo-Ram; Hahn, Ji-Sook

    2017-06-01

    CK2 is a highly conserved Ser/Thr protein kinase involved in a large number of cellular processes. Here, we demonstrate that CK2-dependent phosphorylation positively regulates Msn2/4, the general stress response transcriptional activators in Saccharomyces cerevisiae, in response to various types of environmental stress conditions. CK2 overexpression elicits hyperactivation of Msn2/4, whereas deletion of one of the CK2 catalytic subunits, especially CKA2, leads to reduced transcriptional activity of Msn2/4 in response to glucose starvation, H 2 O 2, and lactic acid. The CKA2 deletion mutant also shows increased stress sensitivity. CK2 phosphorylates Ser194 and Ser638 in Msn2 and replacement of Ser638 with alanine leads to reduced Msn2 activity upon stress and reduced tolerance to H 2 O 2 and lactic acid. CKA2 deletion mutant shows shorter nuclear retention time of Msn2 upon lactic acid stress, suggesting that CK2 might regulate nuclear localization of Msn2. However, Msn2 S194A, S638A mutant shows normal nuclear import and export patterns upon stress, suggesting that CK2 might positively regulate the general stress response not only by direct phosphorylation of Msn2/4, but also by regulating cellular translocation machinery. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The histone deacetylase HDAC1 positively regulates Notch signaling during Drosophila wing development

    Directory of Open Access Journals (Sweden)

    Zehua Wang

    2018-02-01

    Full Text Available The Notch signaling pathway is highly conserved across different animal species and plays crucial roles in development and physiology. Regulation of Notch signaling occurs at multiple levels in different tissues and cell types. Here, we show that the histone deacetylase HDAC1 acts as a positive regulator of Notch signaling during Drosophila wing development. Depletion of HDAC1 causes wing notches on the margin of adult wing. Consistently, the expression of Notch target genes is reduced in the absence of HDAC1 during wing margin formation. We further provide evidence that HDAC1 acts upstream of Notch activation. Mechanistically, we show that HDAC1 regulates Notch protein levels by promoting Notch transcription. Consistent with this, the HDAC1-associated transcriptional co-repressor Atrophin (Atro is also required for transcriptional activation of Notch in the wing disc. In summary, our results demonstrate that HDAC1 positively regulates Notch signaling and reveal a previously unidentified function of HDAC1 in Notch signaling.

  9. A balance of positive and negative regulators determines the pace of the segmentation clock

    Science.gov (United States)

    Wiedermann, Guy; Bone, Robert Alexander; Silva, Joana Clara; Bjorklund, Mia

    2015-01-01

    Somitogenesis is regulated by a molecular oscillator that drives dynamic gene expression within the pre-somitic mesoderm. Previous mathematical models of the somitogenesis clock that invoke the mechanism of delayed negative feedback predict that its oscillation period depends on the sum of delays inherent to negative-feedback loops and inhibitor half-lives. We develop a mathematical model that explores the possibility that positive feedback also plays a role in determining the period of clock oscillations. The model predicts that increasing the half-life of the positive regulator, Notch intracellular domain (NICD), can lead to elevated NICD levels and an increase in the oscillation period. To test this hypothesis, we investigate a phenotype induced by various small molecule inhibitors in which the clock is slowed. We observe elevated levels and a prolonged half-life of NICD. Reducing NICD production rescues these effects. These data provide the first indication that tight control of the turnover of positive as well as negative regulators of the clock determines its periodicity. DOI: http://dx.doi.org/10.7554/eLife.05842.001 PMID:26357015

  10. Identification of E2F1 as a positive transcriptional regulator for δ-catenin

    International Nuclear Information System (INIS)

    Kim, Kwonseop; Oh, Minsoo; Ki, Hyunkyoung; Wang Tao; Bareiss, Sonja; Fini, M. Elizabeth.; Li Dawei; Lu Qun

    2008-01-01

    δ-Catenin is upregulated in human carcinomas. However, little is known about the potential transcriptional factors that regulate δ-catenin expression in cancer. Using a human δ-catenin reporter system, we have screened several nuclear signaling modulators to test whether they can affect δ-catenin transcription. Among β-catenin/LEF-1, Notch1, and E2F1, E2F1 dramatically increased δ-catenin-luciferase activities while β-catenin/LEF-1 induced only a marginal increase. Rb suppressed the upregulation of δ-catenin-luciferase activities induced by E2F1 but did not interact with δ-catenin. RT-PCR and Western blot analyses in 4 different prostate cancer cell lines revealed that regulation of δ-catenin expression is controlled mainly at the transcriptional level. Interestingly, the effects of E2F1 on δ-catenin expression were observed only in human cancer cells expressing abundant endogenous δ-catenin. These studies identify E2F1 as a positive transcriptional regulator for δ-catenin, but further suggest the presence of strong negative regulator(s) for δ-catenin in prostate cancer cells with minimal endogenous δ-catenin expression

  11. Expression of POEM, a positive regulator of osteoblast differentiation, is suppressed by TNF-α

    International Nuclear Information System (INIS)

    Tsukasaki, Masayuki; Yamada, Atsushi; Suzuki, Dai; Aizawa, Ryo; Miyazono, Agasa; Miyamoto, Yoichi; Suzawa, Tetsuo; Takami, Masamichi; Yoshimura, Kentaro; Morimura, Naoko; Yamamoto, Matsuo; Kamijo, Ryutaro

    2011-01-01

    Highlights: → TNF-α inhibits POEM gene expression. → Inhibition of POEM gene expression is caused by NF-κB activation by TNF-α. → Over-expression of POEM recovers inhibition of osteoblast differentiation by TNF-α. -- Abstract: POEM, also known as nephronectin, is an extracellular matrix protein considered to be a positive regulator of osteoblast differentiation. In the present study, we found that tumor necrosis factor-α (TNF-α), a key regulator of bone matrix properties and composition that also inhibits terminal osteoblast differentiation, strongly inhibited POEM expression in the mouse osteoblastic cell line MC3T3-E1. TNF-α-induced down-regulation of POEM gene expression occurred in both time- and dose-dependent manners through the nuclear factor kappa B (NF-κB) pathway. In addition, expressions of marker genes in differentiated osteoblasts were down-regulated by TNF-α in a manner consistent with our findings for POEM, while over-expression of POEM recovered TNF-α-induced inhibition of osteoblast differentiation. These results suggest that TNF-α inhibits POEM expression through the NF-κB signaling pathway and down-regulation of POEM influences the inhibition of osteoblast differentiation by TNF-α.

  12. A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells

    International Nuclear Information System (INIS)

    Zhang, Qiao; Yang, Zhe; Wang, Weiping; Guo, Ting; Jia, Zhuqing; Ma, Kangtao; Zhou, Chunyan

    2014-01-01

    Highlights: • ISL-1 is highly expressed in human pancreatic β-cells and DLBCL. • ISL-1 accelerates the tumorigenesis of DLBCL in vivo. • c-Myc positively regulates ISL-1 expression in DLBCL but not in pancreatic β-cells. • ISL-1 and c-Myc forms an ISL-1/c-Myc transcriptional complex only in DLBCL. • Positive feedback regulation of ISL-1 does not exist in normal pancreatic β-cell. - Abstract: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes

  13. A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qiao, E-mail: zhangqiao200824@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Yang, Zhe, E-mail: zheyang@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Wang, Weiping, E-mail: wwp@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Guo, Ting, E-mail: luckyguoting@bjmu.edu.cn [Department of Gastrointestinal Translation Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, 52 Fucheng Road, 100142 Beijing (China); Jia, Zhuqing, E-mail: zhuqingjia@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Ma, Kangtao, E-mail: makangtao11@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Zhou, Chunyan, E-mail: chunyanzhou@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China)

    2014-07-04

    Highlights: • ISL-1 is highly expressed in human pancreatic β-cells and DLBCL. • ISL-1 accelerates the tumorigenesis of DLBCL in vivo. • c-Myc positively regulates ISL-1 expression in DLBCL but not in pancreatic β-cells. • ISL-1 and c-Myc forms an ISL-1/c-Myc transcriptional complex only in DLBCL. • Positive feedback regulation of ISL-1 does not exist in normal pancreatic β-cell. - Abstract: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes.

  14. Salt Stress Represses Soybean Seed Germination by Negatively Regulating GA Biosynthesis While Positively Mediating ABA Biosynthesis

    Directory of Open Access Journals (Sweden)

    Kai Shu

    2017-08-01

    Full Text Available Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA while positively mediating abscisic acid (ABA biogenesis, which leads to a decrease in the GA/ABA ratio. This study suggests that fluridone (FLUN, an ABA biogenesis inhibitor, might be a potential plant growth regulator that can promote soybean seed germination under saline stress. Different soybean cultivars, which possessed distinct genetic backgrounds, showed a similar repressed phenotype during seed germination under exogenous NaCl application. Biochemical analysis revealed that NaCl treatment led to high MDA (malondialdehyde level during germination and the post-germinative growth stages. Furthermore, catalase, superoxide dismutase, and peroxidase activities also changed after NaCl treatment. Subsequent quantitative Real-Time Polymerase Chain Reaction analysis showed that the transcription levels of ABA and GA biogenesis and signaling genes were altered after NaCl treatment. In line with this, phytohormone measurement also revealed that NaCl considerably down-regulated active GA1, GA3, and GA4 levels, whereas the ABA content was up-regulated; and therefore ratios, such as GA1/ABA, GA3/ABA, and GA4/ABA, are decreased. Consistent with the hormonal quantification, FLUN partially rescued the delayed-germination phenotype caused by NaCl-treatment. Altogether, these results demonstrate that NaCl stress inhibits soybean seed germination by decreasing the GA/ABA ratio, and that FLUN might be a potential plant growth regulator that could promote soybean seed germination under salinity stress.

  15. [Regulation of Positive and Negative Emotions as Mediator between Maternal Emotion Socialization and Child Problem Behavior].

    Science.gov (United States)

    Fäsche, Anika; Gunzenhauser, Catherine; Friedlmeier, Wolfgang; von Suchodoletz, Antje

    2015-01-01

    The present study investigated five to six year old children's ability to regulate negative and positive emotions in relation to psychosocial problem behavior (N=53). It was explored, whether mothers' supportive and nonsupportive strategies of emotion socialization influence children's problem behavior by shaping their emotion regulation ability. Mothers reported on children's emotion regulation and internalizing and externalizing problem behavior via questionnaire, and were interviewed about their preferences for socialization strategies in response to children's expression of negative affect. Results showed that children with more adaptive expression of adequate positive emotions had less internalizing behavior problems. When children showed more control of inadequate negative emotions, children were less internalizing as well as externalizing in their behavior. Furthermore, results indicated indirect relations of mothers' socialization strategies with children's problem behavior. Control of inadequate negative emotions mediated the link between non-supportive strategies on externalizing problem behavior. Results suggest that emotion regulatory processes should be part of interventions to reduce the development of problematic behavior in young children. Parents should be trained in dealing with children's emotions in a constructive way.

  16. msaABCR operon positively regulates biofilm development by repressing proteases and autolysis in Staphylococcus aureus.

    Science.gov (United States)

    Sahukhal, Gyan S; Batte, Justin L; Elasri, Mohamed O

    2015-02-01

    Staphylococcus aureus is an important human pathogen that causes nosocomial and community-acquired infections. One of the most important aspects of staphylococcal infections is biofilm development within the host, which renders the bacterium resistant to the host's immune response and antimicrobial agents. Biofilm development is very complex and involves several regulators that ensure cell survival on surfaces within the extracellular polymeric matrix. Previously, we identified the msaABCR operon as an additional positive regulator of biofilm formation. In this study, we define the regulatory pathway by which msaABCR controls biofilm formation. We demonstrate that the msaABCR operon is a negative regulator of proteases. The control of protease production mediates the processing of the major autolysin, Atl, and thus regulates the rate of autolysis. In the absence of the msaABCR operon, Atl is processed by proteases at a high rate, leading to increased cell death and a defect in biofilm maturation. We conclude that the msaABCR operon plays a key role in maintaining the balance between autolysis and growth within the staphylococcal biofilm. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Individual differences in positive and negative emotion regulation: Which strategies explain variability in loneliness?

    Science.gov (United States)

    Kearns, Sinead M; Creaven, Ann-Marie

    2017-02-01

    Loneliness is the distressing feeling accompanying the perception that one's social needs are not being met by one's social relationships. Conceptual models point to a role for cognitive factors in this experience. Because research on determinants of loneliness is sparse, this study investigates associations between individual differences in emotion regulation (ER) and loneliness. Participants (N = 116) completed measures of loneliness, and a vignette-based measure of adaptive and maladaptive ER in response to positive and negative scenarios. Regression analyses indicated that the regulation of positive and negative emotions explained comparable variance in loneliness, and associations were only partially reduced by the inclusion of social support. The specific strategies positive reappraisal, being present and negative mental time travel explained the most variance in loneliness. The findings are consistent with both the cognitive and the social needs models of loneliness and suggest that variability in ER strategies should be considered relevant to loneliness. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Opportunities and Challenges for the Emerging Field of Positive Emotion Regulation: A Commentary on the Special Edition on Positive Emotions and Cognitions in Clinical Psychology.

    Science.gov (United States)

    Dunn, Barnaby D

    2017-01-01

    The importance of developing a better understanding of positive emotion regulation in both healthy and clinical populations is now recognised. This special edition brings together leading figures in the positive emotion regulation field and has contributions characterizing positive phenomena, differentiating them from negative phenomena, and evaluating underlying psychological mechanisms that drive these phenomena. This commentary reviews these articles to highlight challenges and opportunities for this emerging field, including the need to better characterize positive phenomena, to be more explicit about how the links between negative and positive phenomena are conceptualised, to evaluate more robustly underlying mechanisms, to standardize measurement of positive constructs, and to ensure that these scientific findings lead to meaningful changes in real-world policy and practice.

  19. SIRT1 is a positive regulator of the master osteoblast transcription factor, RUNX2.

    Directory of Open Access Journals (Sweden)

    Kayvan Zainabadi

    Full Text Available Activation of SIRT1 has previously been shown to protect mice against osteoporosis through yet ill-defined mechanisms. In this study, we outline a role for SIRT1 as a positive regulator of the master osteoblast transcription factor, RUNX2. We find that ex vivo deletion of sirt1 leads to decreased expression of runx2 downstream targets, but not runx2 itself, along with reduced osteoblast differentiation. Reciprocally, treatment with a SIRT1 agonist promotes osteoblast differentiation, as well as the expression of runx2 downstream targets, in a SIRT1-dependent manner. Biochemical and luciferase reporter assays demonstrate that SIRT1 interacts with and promotes the transactivation potential of RUNX2. Intriguingly, mice treated with the SIRT1 agonist, resveratrol, show similar increases in the expression of RUNX2 targets in their calvaria (bone tissue, validating SIRT1 as a physiologically relevant regulator of RUNX2.

  20. Regulating and facilitating: the role of emotional intelligence in maintaining and using positive affect for creativity.

    Science.gov (United States)

    Parke, Michael R; Seo, Myeong-Gu; Sherf, Elad N

    2015-05-01

    Although past research has identified the effects of emotional intelligence on numerous employee outcomes, the relationship between emotional intelligence and creativity has not been well established. We draw upon affective information processing theory to explain how two facets of emotional intelligence-emotion regulation and emotion facilitation-shape employee creativity. Specifically, we propose that emotion regulation ability enables employees to maintain higher positive affect (PA) when faced with unique knowledge processing requirements, while emotion facilitation ability enables employees to use their PA to enhance their creativity. We find support for our hypotheses using a multimethod (ability test, experience sampling, survey) and multisource (archival, self-reported, supervisor-reported) research design of early career managers across a wide range of jobs. (c) 2015 APA, all rights reserved.

  1. Wingless is a positive regulator of eyespot color patterns in Bicyclus anynana butterflies.

    Science.gov (United States)

    Özsu, Nesibe; Chan, Qian Yi; Chen, Bin; Gupta, Mainak Das; Monteiro, Antónia

    2017-09-01

    Eyespot patterns of nymphalid butterflies are an example of a novel trait yet, the developmental origin of eyespots is still not well understood. Several genes have been associated with eyespot development but few have been tested for function. One of these genes is the signaling ligand, wingless, which is expressed in the eyespot centers during early pupation and may function in eyespot signaling and color ring differentiation. Here we tested the function of wingless in wing and eyespot development by down-regulating it in transgenic Bicyclus anynana butterflies via RNAi driven by an inducible heat-shock promoter. Heat-shocks applied during larval and early pupal development led to significant decreases in wingless mRNA levels and to decreases in eyespot size and wing size in adult butterflies. We conclude that wingless is a positive regulator of eyespot and wing development in B. anynana butterflies. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Position paper on the impact of including methane number in natural gas regulation

    International Nuclear Information System (INIS)

    2014-01-01

    GIIGNL has developed a position paper to describe methane number and the possible impact on the LNG market of a future regulation/specification for this parameter which is linked to natural gas quality. Currently, there are several standards describing calculation methods of natural gas methane number, but there are doubts about their reliability and the results differ from each other. No official regulation which states a minimum value for methane number of natural gas has been identified. A methane number of 80, as recommended by some organisations in Europe, would endanger the LNG supply to the market, limiting acceptable LNG sources, or would require expensive gas treatment. In the long term, if there is a market for high methane number natural gas, this may be an opportunity for LNG terminals able to adjust or manage supplies to the desired methane number

  3. Maternal depression and anxiety, social synchrony, and infant regulation of negative and positive emotions.

    Science.gov (United States)

    Granat, Adi; Gadassi, Reuma; Gilboa-Schechtman, Eva; Feldman, Ruth

    2017-02-01

    Maternal postpartum depression (PPD) exerts long-term negative effects on infants; yet the mechanisms by which PPD disrupts emotional development are not fully clear. Utilizing an extreme-case design, 971 women reported symptoms of depression and anxiety following childbirth and 215 high and low on depressive symptomatology reported again at 6 months. Of these, mothers diagnosed with major depressive disorder (n = 22), anxiety disorders (n = 19), and controls (n = 59) were visited at 9 months. Mother-infant interaction was microcoded for maternal and infant's social behavior and synchrony. Infant negative and positive emotional expression and self-regulation were tested in 4 emotion-eliciting paradigms: anger with mother, anger with stranger, joy with mother, and joy with stranger. Infants of depressed mothers displayed less social gaze and more gaze aversion. Gaze and touch synchrony were lowest for depressed mothers, highest for anxious mothers, and midlevel among controls. Infants of control and anxious mothers expressed less negative affect with mother compared with stranger; however, maternal presence failed to buffer negative affect in the depressed group. Maternal depression chronicity predicted increased self-regulatory behavior during joy episodes, and touch synchrony moderated the effects of PPD on infant self-regulation. Findings describe subtle microlevel processes by which maternal depression across the postpartum year disrupts the development of infant emotion regulation and suggest that diminished social synchrony, low differentiation of attachment and nonattachment contexts, and increased self-regulation during positive moments may chart pathways for the cross-generational transfer of emotional maladjustment from depressed mothers to their infants. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  4. Mindfulness Broadens Awareness and Builds Eudaimonic Meaning: A Process Model of Mindful Positive Emotion Regulation

    Science.gov (United States)

    Garland, Eric L.; Farb, Norman A.; Goldin, Philippe; Fredrickson, Barbara L.

    2015-01-01

    Contemporary scholarship on mindfulness casts it as a form of purely non-evaluative engagement with experience. Yet, traditionally mindfulness was not intended to operate in a vacuum of dispassionate observation, but was seen as facilitative of eudaimonic mental states. In spite of this historical context, modern psychological research has neglected to ask the question of how the practice of mindfulness affects downstream emotion regulatory processes to impact the sense of meaning in life. To fill this lacuna, here we describe the Mindfulness-to-Meaning Theory, from which we derive a novel process model of mindful positive emotion regulation informed by affective science, in which mindfulness is proposed to introduce flexibility in the generation of cognitive appraisals by enhancing interoceptive attention, thereby expanding the scope of cognition to facilitate reappraisal of adversity and savoring of positive experience. This process is proposed to culminate in a deepened capacity for meaning-making and greater engagement with life. PMID:27087765

  5. DMPD: When signaling pathways collide: positive and negative regulation of toll-likereceptor signal transduction. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18631453 When signaling pathways collide: positive and negative regulation of toll-...uction. PubmedID 18631453 Title When signaling pathways collide: positive and neg...l) Show When signaling pathways collide: positive and negative regulation of toll-likereceptor signal transd...likereceptor signal transduction. O'Neill LA. Immunity. 2008 Jul 18;29(1):12-20. (.png) (.svg) (.html) (.csm

  6. Reciprocal positive regulation between TRPV6 and NUMB in PTEN-deficient prostate cancer cells

    International Nuclear Information System (INIS)

    Kim, Sung-Young; Hong, Chansik; Wie, Jinhong; Kim, Euiyong; Kim, Byung Joo; Ha, Kotdaji; Cho, Nam-Hyuk; Kim, In-Gyu; Jeon, Ju-Hong; So, Insuk

    2014-01-01

    Highlights: • TRPV6 interacts with tumor suppressor proteins. • Numb has a selective effect on TRPV6, depending on the prostate cancer cell line. • PTEN is a novel regulator of TRPV6–Numb complex. - Abstract: Calcium acts as a second messenger and plays a crucial role in signaling pathways involved in cell proliferation. Recently, calcium channels related to calcium influx into the cytosol of epithelial cells have attracted attention as a cancer therapy target. Of these calcium channels, TRPV6 is overexpressed in prostate cancer and is considered an important molecule in the process of metastasis. However, its exact role and mechanism is unclear. NUMB, well-known tumor suppressor gene, is a novel interacting partner of TRPV6. We show that NUMB and TRPV6 have a reciprocal positive regulatory relationship in PC-3 cells. We repeated this experiment in two other prostate cancer cell lines, DU145 and LNCaP. Interestingly, there were no significant changes in TRPV6 expression following NUMB knockdown in DU145. We revealed that the presence or absence of PTEN was the cause of NUMB–TRPV6 function. Loss of PTEN caused a positive correlation of TRPV6–NUMB expression. Collectively, we determined that PTEN is a novel interacting partner of TRPV6 and NUMB. These results demonstrated a novel relationship of NUMB–TRPV6 in prostate cancer cells, and show that PTEN is a novel regulator of this complex

  7. Reciprocal positive regulation between TRPV6 and NUMB in PTEN-deficient prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung-Young; Hong, Chansik; Wie, Jinhong [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Kim, Euiyong [Department of Physiology, College of Medicine, Inje University, Busan 614-735 (Korea, Republic of); Kim, Byung Joo [Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870 (Korea, Republic of); Ha, Kotdaji [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Cho, Nam-Hyuk; Kim, In-Gyu [Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Jeon, Ju-Hong [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); So, Insuk, E-mail: insuk@snu.ac.kr [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

    2014-04-25

    Highlights: • TRPV6 interacts with tumor suppressor proteins. • Numb has a selective effect on TRPV6, depending on the prostate cancer cell line. • PTEN is a novel regulator of TRPV6–Numb complex. - Abstract: Calcium acts as a second messenger and plays a crucial role in signaling pathways involved in cell proliferation. Recently, calcium channels related to calcium influx into the cytosol of epithelial cells have attracted attention as a cancer therapy target. Of these calcium channels, TRPV6 is overexpressed in prostate cancer and is considered an important molecule in the process of metastasis. However, its exact role and mechanism is unclear. NUMB, well-known tumor suppressor gene, is a novel interacting partner of TRPV6. We show that NUMB and TRPV6 have a reciprocal positive regulatory relationship in PC-3 cells. We repeated this experiment in two other prostate cancer cell lines, DU145 and LNCaP. Interestingly, there were no significant changes in TRPV6 expression following NUMB knockdown in DU145. We revealed that the presence or absence of PTEN was the cause of NUMB–TRPV6 function. Loss of PTEN caused a positive correlation of TRPV6–NUMB expression. Collectively, we determined that PTEN is a novel interacting partner of TRPV6 and NUMB. These results demonstrated a novel relationship of NUMB–TRPV6 in prostate cancer cells, and show that PTEN is a novel regulator of this complex.

  8. Position Control of Pneumatic Actuator Using Self-Regulation Nonlinear PID

    Directory of Open Access Journals (Sweden)

    Syed Najib Syed Salim

    2014-01-01

    Full Text Available The enhancement of nonlinear PID (N-PID controller for a pneumatic positioning system is proposed to improve the performance of this controller. This is executed by utilizing the characteristic of rate variation of the nonlinear gain that is readily available in N-PID controller. The proposed equation, namely, self-regulation nonlinear function (SNF, is used to reprocess the error signal with the purpose of generating the value of the rate variation, continuously. With the addition of this function, a new self-regulation nonlinear PID (SN-PID controller is proposed. The proposed controller is then implemented to a variably loaded pneumatic actuator. Simulation and experimental tests are conducted with different inputs, namely, step, multistep, and random waveforms, to evaluate the performance of the proposed technique. The results obtained have been proven as a novel initiative at examining and identifying the characteristic based on a new proposal controller resulting from N-PID controller. The transient response is improved by a factor of 2.2 times greater than previous N-PID technique. Moreover, the performance of pneumatic positioning system is remarkably good under various loads.

  9. MCPIP1 is a positive regulator of type I interferons antiviral activity.

    Science.gov (United States)

    Qian, Liping; Zuo, Yibo; Deng, Wenjun; Miao, Ying; Liu, Jin; Yuan, Yukang; Guo, Tingting; Zhang, Liting; Jin, Jun; Wang, Jun; Zheng, Hui

    2018-04-15

    Type-I interferons (IFN-I) are widely used for antiviral immunotherapy in clinic. Therefore, identification of the regulators of IFN-I antiviral activity is important for developing novel targets for IFN-based antiviral therapy. Monocyte chemoattractant protein 1-induced protein 1 (MCPIP1) is critical for cellular inflammatory responses. However, the roles of MCPIP1 in interferons (IFNs)-mediated antiviral immunity are unexplored. In this study, we demonstrate for the first time that MCPIP1 is an important positive regulator of IFNs antiviral activity. We found that MCPIP1 can promote innate antiviral immunity independently of both its RNase and deubiquitinase activity. Furthermore, we reveal that MCPIP1 is an IFN-induced positive feedback signal molecule which promotes IFN-I-mediated antiviral efficacy. Mechanistically, MCPIP1 does not affect the activation of JAK/STAT upstream of IFN-I signaling, but significantly promotes IFN-I signaling by enhancing ISRE promoter activity and expression of interferon-stimulated genes (ISGs). And MCPIP1-mediated activation of IFN-I signaling is independently of its RNase and deubiquitinase activity. These findings uncover a novel innate antiviral mechanism mediated by the IFN-MCPIP1 axis, and may provide potential targets for enhancing IFNs antiviral therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. The Transcription Factors EBF1 and EBF2 Are Positive Regulators of Myelination in Schwann Cells.

    Science.gov (United States)

    Moruzzo, Diego; Nobbio, Lucilla; Sterlini, Bruno; Consalez, G Giacomo; Benfenati, Fabio; Schenone, Angelo; Corradi, Anna

    2017-12-01

    Myelin formation by Schwann cells is tightly controlled by multiple pathways and regulatory molecules. The Ebf2 gene, belonging to the Ebf family of transcription factors regulating cell development and differentiation, is expressed in Schwann cells, and Ebf2 knockout mice show peripheral nerve defects. We also found that Ebf1 is expressed in Schwann cells. To investigate Ebf function in myelination, we silenced Ebf genes in myelinating dorsal root ganglia cultures. Combined downregulation of Ebf genes leads to a severe impairment of myelin formation that is completely rescued by their specific overexpression, suggesting that the expression level of Ebf genes strongly influences axon myelination. In addition, by profiling Ebf target genes, we found several transcripts belonging to pathways actively involved in peripheral myelination, including Gliomedin, a gene with a role in the formation of the nodes of Ranvier and recently implicated in the pathogenesis of the nodo-paranodopathies. Our results suggest that Ebf genes act as positive regulators of myelination and directly regulate the promoter of Gliomedin.

  11. Thy1 is a positive regulator of osteoblast differentiation and modulates bone homeostasis in obese mice.

    Science.gov (United States)

    Paine, Ananta; Woeller, Collynn F; Zhang, Hengwei; de la Luz Garcia-Hernandez, Maria; Huertas, Nelson; Xing, Lianping; Phipps, Richard P; Ritchlin, Christopher T

    2018-01-17

    Thy1 (CD90), a glycosylated, glycophosphatidylinositol-anchored membrane protein highly expressed by subsets of mesenchymal stem cells and fibroblasts, inhibits adipogenesis. The role of Thy1 on bone structure and function has been poorly studied and represents a major knowledge gap. Therefore, we analyzed the long bones of wild-type (WT) and Thy1 knockout (KO) mice with micro-computed tomography (CT) and histomorphometry to compare changes in bone architecture and overall bone structure. micro-CT analysis of long bones revealed Thy1 KO and WT mice fed a high-fat diet demonstrated bone structural parameters at 4 mo that differed significantly between WT and KO mice. A significant reduction in trabecular bone volume was noted in Thy1 KO mice. The most prominent differences were observed in trabecular bone volume ratio and trabecular bone connectivity density. Consistent with micro-CT measurements, histomorphometric analysis also showed decreased bone volume in the obese Thy1 KO mice compared to obese WT mice. In vitro assays revealed that osteogenic conditions increased Thy1 expression during OB differentiation and absence of Thy1 attenuated osteoblastogenesis. Together, these findings support the concept that Thy1 serves as a major mechanistic link to regulate bone formation and negatively regulate adipogenesis.-Paine, A., Woeller, C. F., Zhang, H., Garcia-Hernandez, M. L., Huertas, N., Xing, L., Phipps, R. P., Ritchlin, C. T. Thy1 is a positive regulator of osteoblast differentiation and modulates bone homeostasis in obese mice.

  12. DNA demethylases target promoter transposable elements to positively regulate stress responsive genes in Arabidopsis.

    Science.gov (United States)

    Le, Tuan-Ngoc; Schumann, Ulrike; Smith, Neil A; Tiwari, Sameer; Au, Phil Chi Khang; Zhu, Qian-Hao; Taylor, Jennifer M; Kazan, Kemal; Llewellyn, Danny J; Zhang, Ren; Dennis, Elizabeth S; Wang, Ming-Bo

    2014-09-17

    DNA demethylases regulate DNA methylation levels in eukaryotes. Arabidopsis encodes four DNA demethylases, DEMETER (DME), REPRESSOR OF SILENCING 1 (ROS1), DEMETER-LIKE 2 (DML2), and DML3. While DME is involved in maternal specific gene expression during seed development, the biological function of the remaining DNA demethylases remains unclear. We show that ROS1, DML2, and DML3 play a role in fungal disease resistance in Arabidopsis. A triple DNA demethylase mutant, rdd (ros1 dml2 dml3), shows increased susceptibility to the fungal pathogen Fusarium oxysporum. We identify 348 genes differentially expressed in rdd relative to wild type, and a significant proportion of these genes are downregulated in rdd and have functions in stress response, suggesting that DNA demethylases maintain or positively regulate the expression of stress response genes required for F. oxysporum resistance. The rdd-downregulated stress response genes are enriched for short transposable element sequences in their promoters. Many of these transposable elements and their surrounding sequences show localized DNA methylation changes in rdd, and a general reduction in CHH methylation, suggesting that RNA-directed DNA methylation (RdDM), responsible for CHH methylation, may participate in DNA demethylase-mediated regulation of stress response genes. Many of the rdd-downregulated stress response genes are downregulated in the RdDM mutants nrpd1 and nrpe1, and the RdDM mutants nrpe1 and ago4 show enhanced susceptibility to F. oxysporum infection. Our results suggest that a primary function of DNA demethylases in plants is to regulate the expression of stress response genes by targeting promoter transposable element sequences.

  13. Rasputin functions as a positive regulator of orb in Drosophila oogenesis.

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    Alexandre Costa

    Full Text Available The determination of cell fate and the establishment of polarity axes during Drosophila oogenesis depend upon pathways that localize mRNAs within the egg chamber and control their on-site translation. One factor that plays a central role in regulating on-site translation of mRNAs is Orb. Orb is a founding member of the conserved CPEB family of RNA-binding proteins. These proteins bind to target sequences in 3' UTRs and regulate mRNA translation by modulating poly(A tail length. In addition to controlling the translation of axis-determining mRNAs like grk, fs(1K10, and osk, Orb protein autoregulates its own synthesis by binding to orb mRNA and activating its translation. We have previously shown that Rasputin (Rin, the Drosophila homologue of Ras-GAP SH3 Binding Protein (G3BP, associates with Orb in a messenger ribonucleoprotein (mRNP complex. Rin is an evolutionarily conserved RNA-binding protein believed to function as a link between Ras signaling and RNA metabolism. Here we show that Orb and Rin form a complex in the female germline. Characterization of a new rin allele shows that rin is essential for oogenesis. Co-localization studies suggest that Orb and Rin form a complex in the oocyte at different stages of oogenesis. This is supported by genetic and biochemical analyses showing that rin functions as a positive regulator in the orb autoregulatory pathway by increasing Orb protein expression. Tandem Mass Spectrometry analysis shows that several canonical stress granule proteins are associated with the Orb-Rin complex suggesting that a conserved mRNP complex regulates localized translation during oogenesis in Drosophila.

  14. Rasputin functions as a positive regulator of orb in Drosophila oogenesis.

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    Costa, Alexandre; Pazman, Cecilia; Sinsimer, Kristina S; Wong, Li Chin; McLeod, Ian; Yates, John; Haynes, Susan; Schedl, Paul

    2013-01-01

    The determination of cell fate and the establishment of polarity axes during Drosophila oogenesis depend upon pathways that localize mRNAs within the egg chamber and control their on-site translation. One factor that plays a central role in regulating on-site translation of mRNAs is Orb. Orb is a founding member of the conserved CPEB family of RNA-binding proteins. These proteins bind to target sequences in 3' UTRs and regulate mRNA translation by modulating poly(A) tail length. In addition to controlling the translation of axis-determining mRNAs like grk, fs(1)K10, and osk, Orb protein autoregulates its own synthesis by binding to orb mRNA and activating its translation. We have previously shown that Rasputin (Rin), the Drosophila homologue of Ras-GAP SH3 Binding Protein (G3BP), associates with Orb in a messenger ribonucleoprotein (mRNP) complex. Rin is an evolutionarily conserved RNA-binding protein believed to function as a link between Ras signaling and RNA metabolism. Here we show that Orb and Rin form a complex in the female germline. Characterization of a new rin allele shows that rin is essential for oogenesis. Co-localization studies suggest that Orb and Rin form a complex in the oocyte at different stages of oogenesis. This is supported by genetic and biochemical analyses showing that rin functions as a positive regulator in the orb autoregulatory pathway by increasing Orb protein expression. Tandem Mass Spectrometry analysis shows that several canonical stress granule proteins are associated with the Orb-Rin complex suggesting that a conserved mRNP complex regulates localized translation during oogenesis in Drosophila.

  15. Effects of body position on autonomic regulation of cardiovascular function in young, healthy adults

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    Polus Barbara I

    2007-11-01

    Full Text Available Abstract Background Analysis of rhythmic patterns embedded within beat-to-beat variations in heart rate (heart rate variability is a tool used to assess the balance of cardiac autonomic nervous activity and may be predictive for prognosis of some medical conditions, such as myocardial infarction. It has also been used to evaluate the impact of manipulative therapeutics and body position on autonomic regulation of the cardiovascular system. However, few have compared cardiac autonomic activity in supine and prone positions, postures commonly assumed by patients in manual therapy. We intend to redress this deficiency. Methods Heart rate, heart rate variability, and beat-to-beat blood pressure were measured in young, healthy non-smokers, during prone, supine, and sitting postures and with breathing paced at 0.25 Hz. Data were recorded for 5 minutes in each posture: Day 1 – prone and supine; Day 2 – prone and sitting. Paired t-tests or Wilcoxon signed-rank tests were used to evaluate posture-related differences in blood pressure, heart rate, and heart rate variability. Results Prone versus supine: blood pressure and heart rate were significantly higher in the prone posture (p p Conclusion Cardiac autonomic activity was not measurably different in prone and supine postures, but heart rate and blood pressure were. Although heart rate variability parameters indicated sympathetic dominance during sitting (supporting work of others, blood pressure was higher in the prone posture. These differences should be considered when autonomic regulation of cardiovascular function is studied in different postures.

  16. The F-box protein MAX2 functions as a positive regulator of photomorphogenesis in Arabidopsis.

    Science.gov (United States)

    Shen, Hui; Luong, Phi; Huq, Enamul

    2007-12-01

    Light is vital for plant growth and development. To respond to ambient light signals, plants are equipped with an array of photoreceptors, including phytochromes that sense red (R)/far-R (FR) regions and cryptochromes and phototropins that respond to the ultraviolet-A/blue (B) region of the light spectrum, respectively. Several positively and negatively acting components in light-signaling pathways have been identified using genetic approaches; however, the pathways are not saturated. Here, we characterize a new mutant named pleiotropic photosignaling (pps), isolated from a genetic screen under continuous R light. pps has longer hypocotyls and slightly smaller cotyledons under continuous R, FR, and B light compared to that of the wild type. pps is also hyposensitive to both R and FR light-induced seed germination. Although photosynthetic marker genes are constitutively expressed in pps in the dark at high levels, the expression of early light-regulated genes is reduced in the pps seedlings compared to wild-type seedlings under R light. PPS encodes MAX2/ORE9 (for MORE AXILLARY BRANCHES2/ORESARA9), an F-box protein involved in inflorescence architecture and senescence. MAX2 is expressed ubiquitously in the seedling stage. However, its expression is restricted to vascular tissues and meristems at adult stages. MAX2 is also localized to the nucleus. As an F-box protein, MAX2 is predicted to be a component of the SCF (for SKP, Cullin, and F-box protein) complex involved in regulated proteolysis. These results suggest that SCF(MAX2) plays critical roles in R, FR, and B light-signaling pathways. In addition, MAX2 might regulate multiple targets at different developmental stages to optimize plant growth and development.

  17. The E3 ligase AtCHIP positively regulates Clp proteolytic subunit homeostasis.

    Science.gov (United States)

    Wei, Jia; Qiu, Xiaoyun; Chen, Lin; Hu, Wenjun; Hu, Rongbin; Chen, Jian; Sun, Li; Li, Li; Zhang, Hong; Lv, Zhiqiang; Shen, Guoxin

    2015-09-01

    The caseinolytic peptidase (Clp) core proteins are essential for plant growth and development, especially for chloroplast function. Antisense or overexpression of ClpP4, which is one of the Clp core subunits, causes chlorotic phenotypes in Arabidopsis. An E3 ligase gene, AtCHIP, has previously been found to ubiquitylate ClpP4 in vitro. ClpP4 antisense and overexpressing plants that also overexpressed AtCHIP were constructed to explore the effect of AtCHIP on ClpP4. Overexpression of AtCHIP was found to rescue the chlorotic phenotypes of both ClpP4 antisense and overexpressing plants. The unbalanced levels of Clp core proteins in ClpP4 antisense and overexpressing plants with overexpression of AtCHIP were similar to wild-type levels, suggesting that AtCHIP regulates Clp core proteins. The results also show that AtCHIP can interact with ClpP3 and ClpP5 in yeast and ubiquitylate ClpP3 and ClpP5 in vitro. This suggests that AtCHIP is directly related to ClpP3 and ClpP5. Given these results, the inference is that through selective degradation of Clp subunits, AtCHIP could positively regulate homeostasis of Clp proteolytic subunits and maximize the production of functional chloroplasts. Similar results were obtained from transgenic tobacco plants, suggesting that regulation of the Clp protease by AtCHIP is conserved. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

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    Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui; Ha, Hyunil, E-mail: hyunil74@hotmail.com; Lee, Zang Hee, E-mail: zang1959@snu.ac.kr

    2010-07-23

    Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.

  19. Regulation of the Hippocampal Network by VGLUT3-Positive CCK- GABAergic Basket Cells

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    Caroline Fasano

    2017-05-01

    Full Text Available Hippocampal interneurons release the inhibitory transmitter GABA to regulate excitation, rhythm generation and synaptic plasticity. A subpopulation of GABAergic basket cells co-expresses the GABA/glycine vesicular transporters (VIAAT and the atypical type III vesicular glutamate transporter (VGLUT3; therefore, these cells have the ability to signal with both GABA and glutamate. GABAergic transmission by basket cells has been extensively characterized but nothing is known about the functional implications of VGLUT3-dependent glutamate released by these cells. Here, using VGLUT3-null mice we observed that the loss of VGLUT3 results in a metaplastic shift in synaptic plasticity at Shaeffer’s collaterals – CA1 synapses and an altered theta oscillation. These changes were paralleled by the loss of a VGLUT3-dependent inhibition of GABAergic current in CA1 pyramidal layer. Therefore presynaptic type III metabotropic could be activated by glutamate released from VGLUT3-positive interneurons. This putative presynaptic heterologous feedback mechanism inhibits local GABAergic tone and regulates the hippocampal neuronal network.

  20. Transcription factor interactions: Selectors of positive or negative regulation from a single DNA element

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    Diamond, M.I.; Miner, J.N.; Yoshinaga, S.K.; Yamamoto, K.R. (Univ. of California, San Francisco (USA))

    1990-09-14

    The mechanism by which a single factor evokes opposite regulatory effects from a specific DNA sequence is not well understood. In this study, a 25-base pair element that resides upstream of the mouse proliferin gene was examined; it conferred on linked promoters either positive or negative glucocorticoid regulation, depending upon physiological context. This sequence, denoted a composite glucocorticoid response element (GRE), was bound selective in vitro both by the glucocorticoid receptor and by c-Jun and c-Fos, components of the phorbol ester-activated AP-1 transcription factor. Indeed, c-Jun and c-Fos served as selectors of hormone responsiveness: the composite GRE was inactive in the absence of c-Jun, whereas it conferred a positive glucocorticoid effect in the presence of c-Jun, and a negative glucocorticoid effect in the presence of c-Jun and relatively high levels of c-Fos. The receptor also interacted selectively with c-Jun in vitro. A general model for composite GRE action is proposed that invokes both DNA binding and protein-protein interactions by receptor and nonreceptor factors.

  1. BOC, an Ig superfamily member, associates with CDO to positively regulate myogenic differentiation

    Science.gov (United States)

    Kang, Jong-Sun; Mulieri, Philip J.; Hu, Yulan; Taliana, Lavinia; Krauss, Robert S.

    2002-01-01

    CDO is a cell surface receptor-like protein that positively regulates myogenic differentiation. Reported here is the identification of BOC, which, with CDO, defines a newly recognized subfamily within the immunoglobulin superfamily. cdo and boc are co-expressed in muscle precursors in the developing mouse embryo. Like CDO, BOC accelerates differentiation of cultured myoblast cell lines and participates in a positive feedback loop with the myogenic transcription factor, MyoD. CDO and BOC form complexes in a cis fashion via association of both their ectodomains and their intracellular domains. A soluble fusion protein that contains the entire BOC ectodomain functions similarly to full-length BOC to promote myogenic differentiation, indicating that the intracellular region is dispensable for its activity in this system. Furthermore, a dominant-negative form of CDO inhibits the pro-myogenic effects of soluble BOC, suggesting that BOC is dependent on CDO for its activity. CDO and BOC are proposed to be components of a receptor complex that mediates some of the cell–cell interactions between muscle precursors that are required for myogenesis. PMID:11782431

  2. Chondroitin sulfate proteoglycans negatively regulate the positioning of mitochondria and endoplasmic reticulum to distal axons.

    Science.gov (United States)

    Sainath, Rajiv; Armijo-Weingart, Lorena; Ketscheck, Andrea; Xu, Zhuxuan; Li, Shuxin; Gallo, Gianluca

    2017-12-01

    Chondroitin sulfate proteoglycans (CSPGs) are components of the extracellular matrix that inhibit the extension and regeneration of axons. However, the underlying mechanism of action remains poorly understood. Mitochondria and endoplasmic reticulum (ER) are functionally inter-linked organelles important to axon development and maintenance. We report that CSPGs impair the targeting of mitochondria and ER to the growth cones of chicken embryonic sensory axons. The effect of CSPGs on the targeting of mitochondria is blocked by inhibition of the LAR receptor for CSPGs. The regulation of the targeting of mitochondria and ER to the growth cone by CSPGs is due to attenuation of PI3K signaling, which is known to be downstream of LAR receptor activation. Dynactin is a required component of the dynein motor complex that drives the normally occurring retrograde evacuation of mitochondria from growth cones. CSPGs elevate the levels of p150 Glu dynactin found in distal axons, and inhibition of the interaction of dynactin with dynein increased axon lengths on CSPGs. CSPGs decreased the membrane potential of mitochondria, and pharmacological inhibition of mitochondria respiration at the growth cone independent of manipulation of mitochondria positioning impaired axon extension. Combined inhibition of dynactin and potentiation of mitochondria respiration further increased axon lengths on CSPGs relative to inhibition of dynactin alone. These data reveal that the regulation of the localization of mitochondria and ER to growth cones is a previously unappreciated aspect of the effects of CSPGs on embryonic axons. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1351-1370, 2017. © 2017 Wiley Periodicals, Inc.

  3. AaERF1 positively regulates the resistance to Botrytis cinerea in Artemisia annua.

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    Xu Lu

    Full Text Available Plants are sessile organisms, and they can not move away under abiotic or biotic stresses. Thus plants have evolved a set of genes that response to adverse environment to modulate gene expression. In this study, we characterized and functionally studied an ERF transcription factor from Artemisia annua, AaERF1, which plays an important role in biotic stress responses. The AaERF1 promoter had been cloned and GUS staining results of AaERF1 promoter-GUS transgenic A. annua showed that AaERF1 is expressed ubiquitiously in all organs. Several putative cis-acting elements such as W-box, TGA-box and Py-rich element, which are involved in defense responsiveness, are present in the promoter. The expression of AaERF1 can be induced vigorously by methyl jasmonate as well as by ethephon and wounding, implying that AaERF1 may activate some of the defense genes via the jasmonic acid and ethylene signaling pathways of A. annua. The results of electrophoretic mobility shift assay (EMSA and yeast one-hybrid experiments showed that AaERF1 was able to bind to the GCC box cis-acting element in vitro and in yeast. Ectopic expression of AaERF1 could enhance the expression levels of the defense marker genes PLANT DEFENSIN1.2 (PDF1.2 and BASIC CHITINASE (ChiB, and increase the resistance to Botrytis cinerea in the 35S::AaERF1 transgenic Arabidopsis. The down-regulated expression level of AaERF1 evidently reduced the resistance to B. cinerea in A. annua. The overall results showed that AaERF1 positively regulated the resistance to B. cinerea in A. annua.

  4. BMP-2 Induced Expression of Alx3 That Is a Positive Regulator of Osteoblast Differentiation.

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    Takashi Matsumoto

    Full Text Available Bone morphogenetic proteins (BMPs regulate many aspects of skeletal development, including osteoblast and chondrocyte differentiation, cartilage and bone formation, and cranial and limb development. Among them, BMP-2, one of the most potent osteogenic signaling molecules, stimulates osteoblast differentiation, while it inhibits myogenic differentiation in C2C12 cells. To evaluate genes involved in BMP-2-induced osteoblast differentiation, we performed cDNA microarray analyses to compare BMP-2-treated and -untreated C2C12 cells. We focused on Alx3 (aristaless-like homeobox 3 which was clearly induced during osteoblast differentiation. Alx3, a homeobox gene related to the Drosophilaaristaless gene, has been linked to developmental functions in craniofacial structures and limb development. However, little is known about its direct relationship with bone formation. In the present study, we focused on the mechanisms of Alx3 gene expression and function during osteoblast differentiation induced by BMP-2. In C2C12 cells, BMP-2 induced increase of Alx3 gene expression in both time- and dose-dependent manners through the BMP receptors-mediated SMAD signaling pathway. In addition, silencing of Alx3 by siRNA inhibited osteoblast differentiation induced by BMP-2, as showed by the expressions of alkaline phosphatase (Alp, Osteocalcin, and Osterix, while over-expression of Alx3 enhanced osteoblast differentiation induced by BMP-2. These results indicate that Alx3 expression is enhanced by BMP-2 via the BMP receptors mediated-Smad signaling and that Alx3 is a positive regulator of osteoblast differentiation induced by BMP-2.

  5. Crystal Structure of Human Cyclin K, A Positive Regulator of Cyclin-Dependent Kinase 9

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    Baek,K.; Brown, R.; Birrane, G.; Ladias, J.

    2007-01-01

    K and the closely related cyclins T1, T2a, and T2b interact with cyclin-dependent kinase 9 (CDK9) forming multiple nuclear complexes, referred to collectively as positive transcription elongation factor b (P-TEFb). Through phosphorylation of the C-terminal domain of the RNA polymerase II largest subunit, distinct P-TEFb species regulate the transcriptional elongation of specific genes that play central roles in human physiology and disease development, including cardiac hypertrophy and human immunodeficiency virus-1 pathogenesis. We have determined the crystal structure of human cyclin K (residues 11-267) at 1.5 {angstrom} resolution, which represents the first atomic structure of a P-TEFb subunit. The cyclin K fold comprises two typical cyclin boxes with two short helices preceding the N-terminal box. A prominent feature of cyclin K is an additional helix (H4a) in the first cyclin box that obstructs the binding pocket for the cell-cycle inhibitor p27{sup Kip1}. Modeling of CDK9 bound to cyclin K provides insights into the structural determinants underlying the formation and regulation of this complex. A homology model of human cyclin T1 generated using the cyclin K structure as a template reveals that the two proteins have similar structures, as expected from their high level of sequence identity. Nevertheless, their CDK9-interacting surfaces display significant structural differences, which could potentially be exploited for the design of cyclin-targeted inhibitors of the CDK9-cyclin K and CDK9-cyclin T1 complexes.

  6. The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

    Science.gov (United States)

    Chen, Justin L.; Qian, Hongwei; Liu, Yingying; Bernardo, Bianca C.; Beyer, Claudia; Watt, Kevin I.; Thomson, Rachel E.; Connor, Timothy; Turner, Bradley J.; McMullen, Julie R.; Larsson, Lars; McGee, Sean L.; Harrison, Craig A.

    2013-01-01

    Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders. PMID:24145169

  7. RSL class I genes positively regulate root hair development in Oryza sativa.

    Science.gov (United States)

    Kim, Chul Min; Han, Chang-Deok; Dolan, Liam

    2017-01-01

    Root hairs are filamentous protuberances from superficial cells of plant roots that are critical for nutrient uptake. Genes encoding ROOT HAIR DEFECTIVE-SIX LIKE (RSL) class I basic helix-loop-helix proteins are expressed in future root hair cells (trichoblasts) of the Arabidopsis thaliana root where they positively regulate root hair cell development. We characterized the function of class I genes in Oryza sativa root development. We show that there are three RSL class I genes in O. sativa and that each is expressed in developing root hair cells. Reduction of RSL class I function results in the development of shorter root hairs than in wild-type. Ectopic overexpression results in the development of ectopic root hair cells. These data suggest that expression of individual RSL class I proteins is sufficient for root hair development in the cereal O. sativa (rice). Therefore RSL class I genes have been conserved since O. sativa and A. thaliana last shared a common ancestor. However, given that RSL class I genes are not sufficient for root hair development in A. thaliana, it suggests that there are differences in the mechanisms repressing RSL class I gene activity between members of the Poaceae and Brassicaceae. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  8. Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making

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    Anne M. Farrell

    2018-02-01

    Full Text Available Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI study, we evaluated how fixed wage (FW incentives and performance-based (PB financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events.

  9. Mothering, fathering, and the regulation of negative and positive emotions in high-functioning preschoolers with autism spectrum disorder.

    Science.gov (United States)

    Hirschler-Guttenberg, Yael; Golan, Ofer; Ostfeld-Etzion, Sharon; Feldman, Ruth

    2015-05-01

    Children with autism spectrum disorder (ASD) exhibit difficulties in regulating emotions and authors have called to study the specific processes underpinning emotion regulation (ER) in ASD. Yet, little observational research examined the strategies preschoolers with ASD use to regulate negative and positive emotions in the presence of their mothers and fathers. Forty preschoolers with ASD and 40 matched typically developing children and their mothers and fathers participated. Families were visited twice for identical battery of paradigms with mother or father. Parent-child interactions were coded for parent and child behaviors and children engaged in ER paradigms eliciting negative (fear) and positive (joy) emotions with each parent. ER paradigms were microcoded for negative and positive emotionality, ER strategies, and parent regulation facilitation. During free play, mothers' and fathers' sensitivity and warm discipline were comparable across groups; however, children with ASD displayed lower positive engagement and higher withdrawal. During ER paradigms, children with ASD expressed less positive emotionality overall and more negative emotionality during fear with father. Children with ASD used more simple self-regulatory strategies, particularly during fear, but expressed comparable levels of assistance seeking behavior toward mother and father in negative and positive contexts. Parents of children with ASD used less complex regulation facilitation strategies, including cognitive reappraisal and emotional reframing, and employed simple tactics, such as physical comforting to manage fear and social gaze to maintain joy. Findings describe general and parent- and emotion-specific processes of child ER and parent regulation facilitation in preschoolers with ASD. Results underscore the ability of such children to seek parental assistance during moments of high arousal and the parents' sensitive adaptation to their children's needs. Reduced positive emotionality

  10. The silent information regulator 1 (Sirt1) is a positive regulator of the Notch pathway in Drosophila

    Czech Academy of Sciences Publication Activity Database

    Horváth, Matěj; Mihajlović, Zorana; Slaninová, Věra; Perez-Gomez, Raquel; Moshkin, Y.; Krejčí, Alena

    2016-01-01

    Roč. 473, č. 22 (2016), s. 4129-4143 ISSN 0264-6021 R&D Projects: GA ČR(CZ) GA14-08583S Institutional support: RVO:60077344 Keywords : Drosophila * silent information regulator 1 * Notch pathway Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.797, year: 2016

  11. FK506 biosynthesis is regulated by two positive regulatory elements in Streptomyces tsukubaensis

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    Goranovič Dušan

    2012-10-01

    Full Text Available Abstract Background FK506 (Tacrolimus is an important immunosuppressant, produced by industrial biosynthetic processes using various Streptomyces species. Considering the complex structure of FK506, it is reasonable to expect complex regulatory networks controlling its biosynthesis. Regulatory elements, present in gene clusters can have a profound influence on the final yield of target product and can play an important role in development of industrial bioprocesses. Results Three putative regulatory elements, namely fkbR, belonging to the LysR-type family, fkbN, a large ATP-binding regulator of the LuxR family (LAL-type and allN, a homologue of AsnC family regulatory proteins, were identified in the FK506 gene cluster from Streptomyces tsukubaensis NRRL 18488, a progenitor of industrial strains used for production of FK506. Inactivation of fkbN caused a complete disruption of FK506 biosynthesis, while inactivation of fkbR resulted in about 80% reduction of FK506 yield. No functional role in the regulation of the FK506 gene cluster has been observed for the allN gene. Using RT-PCR and a reporter system based on a chalcone synthase rppA, we demonstrated, that in the wild type as well as in fkbN- and fkbR-inactivated strains, fkbR is transcribed in all stages of cultivation, even before the onset of FK506 production, whereas fkbN expression is initiated approximately with the initiation of FK506 production. Surprisingly, inactivation of fkbN (or fkbR does not abolish the transcription of the genes in the FK506 gene cluster in general, but may reduce expression of some of the tested biosynthetic genes. Finally, introduction of a second copy of the fkbR or fkbN genes under the control of the strong ermE* promoter into the wild type strain resulted in 30% and 55% of yield improvement, respectively. Conclusions Our results clearly demonstrate the positive regulatory role of fkbR and fkbN genes in FK506 biosynthesis in S. tsukubaensis NRRL 18488. We

  12. CCN4/WISP-1 positively regulates chondrogenesis by controlling TGF-β3 function.

    Science.gov (United States)

    Yoshioka, Yuya; Ono, Mitsuaki; Maeda, Azusa; Kilts, Tina M; Hara, Emilio Satoshi; Khattab, Hany; Ueda, Junji; Aoyama, Eriko; Oohashi, Toshitaka; Takigawa, Masaharu; Young, Marian F; Kuboki, Takuo

    2016-02-01

    The CCN family of proteins plays important roles in development and homeostasis of bone and cartilage. To understand the role of CCN4 in chondrogenesis, human bone marrow stromal cells (hBMSCs) were transduced with CCN4 adenovirus (adCCN4) or siRNA to CCN4 (siCCN4) in the presence or absence of transforming growth factor-β3 (TGF-β3). Overexpression of CCN4 enhanced TGF-β3-induced SMAD2/3 phosphorylation and chondrogenesis of hBMSCs in an in vitro assay using a micromass culture model. On the other hand, knockdown of CCN4 inhibited the TGF-β3-induced SMAD2/3 phosphorylation and synthesis of cartilage matrix in micromass cultures of hBMSCs. Immunoprecipitation-western blot analysis revealed that CCN4 bound to TGF-β3 and regulated the ability of TGF-β3 to bind to hBMSCs. In vivo analysis confirmed there was a significant decrease in the gene expression levels of chondrocyte markers in cartilage samples from Ccn4-knock out (KO) mice, compared to those from wild type (WT) control. In order to investigate the regenerative properties of the articular cartilage in Ccn4-KO mice, articular cartilage defects were surgically performed in the knee joints of young mice, and the results showed that the cartilage was partially repaired in WT mice, but not in Ccn4-KO mice. In conclusion, these results show, for the first time, that CCN4 has a positive influence on chondrogenic differentiation by modulating the effects of TGF-β3. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Genes Regulated by Vitamin D in Bone Cells Are Positively Selected in East Asians.

    Directory of Open Access Journals (Sweden)

    Elena Arciero

    Full Text Available Vitamin D and folate are activated and degraded by sunlight, respectively, and the physiological processes they control are likely to have been targets of selection as humans expanded from Africa into Eurasia. We investigated signals of positive selection in gene sets involved in the metabolism, regulation and action of these two vitamins in worldwide populations sequenced by Phase I of the 1000 Genomes Project. Comparing allele frequency-spectrum-based summary statistics between these gene sets and matched control genes, we observed a selection signal specific to East Asians for a gene set associated with vitamin D action in bones. The selection signal was mainly driven by three genes CXXC finger protein 1 (CXXC1, low density lipoprotein receptor-related protein 5 (LRP5 and runt-related transcription factor 2 (RUNX2. Examination of population differentiation and haplotypes allowed us to identify several candidate causal regulatory variants in each gene. Four of these candidate variants (one each in CXXC1 and RUNX2 and two in LRP5 had a >70% derived allele frequency in East Asians, but were present at lower (20-60% frequency in Europeans as well, suggesting that the adaptation might have been part of a common response to climatic and dietary changes as humans expanded out of Africa, with implications for their role in vitamin D-dependent bone mineralization and osteoporosis insurgence. We also observed haplotype sharing between East Asians, Finns and an extinct archaic human (Denisovan sample at the CXXC1 locus, which is best explained by incomplete lineage sorting.

  14. Improving Affect Regulation in Eating Disorders: The Case for Positive Emotions

    OpenAIRE

    Rogowski, Augustina

    2011-01-01

    Evidence from multiple studies suggests that regulation of emotions and intensity of affect may be relevant to understanding disordered eating. Emotion regulation concerns the ways in which emotions are managed in daily life, whereas Affect Intensity (Larsen et al., 1986) refers to individuals‟ typical emotional reactivity. The thesis examines emotion regulation and affect in females with eating pathology (subclinical as well as clinical), and looks at ways dysfunctional regulatory strategies...

  15. PrhN, a putative marR family transcriptional regulator, is involved in positive regulation of type III secretion system and full virulence of Ralstonia solanacearum

    Directory of Open Access Journals (Sweden)

    Zhang eYong

    2015-04-01

    Full Text Available The MarR-family of transcriptional regulators are involved in various cellular processes, including resistance to multiple antibiotics and other toxic chemicals, adaptation to different environments and pathogenesis in many plant and animal pathogens. Here, we reported a new MarR regulator PrhN, which was involved in the pathogenesis of Ralstonia solanacearum. prhN mutant exhibited significantly reduced virulence and stem colonization compared to that of wild type in tomato plants. prhN mutant caused identical hypersensitive response (HR on resistant plants to the wild type. Deletion of prhN gene substantially reduced the expression of type III secretion system (T3SS in vitro and in planta (mainly in tomato plants, which is essential for pathogenicity of R. solanacearum, and the complemented PrhN could restore its virulence and T3SS expression to that of wild type. T3SS is directly controlled by AraC-type transcriptional regulator HrpB, and the transcription of hrpB is activated by HrpG and PrhG. HrpG and PrhG are homologues but are regulated by the PhcA positively and negatively respectively. Deletion of prhN gene also abolished the expression of hrpB and prhG, but didn't change the expression of hrpG and phcA. Together, these results indicated that PrhN positively regulates T3SS expression through PrhG and HrpB. PrhN and PhcA should regulate prhG expression in a parallel way. This is the first report on the pathogenesis of MarR regulator in R. solanacearum, and this new finding will improve our understanding on the various biological functions of MarR regulator and the complex regulatory network on hrp regulon in R. solanacearum.

  16. Cystic Fibrosis Transmembrane Conductance Regulator-Related Metabolic Syndrome and Cystic Fibrosis Screen Positive, Inconclusive Diagnosis.

    Science.gov (United States)

    Ren, Clement L; Borowitz, Drucy S; Gonska, Tanja; Howenstine, Michelle S; Levy, Hara; Massie, John; Milla, Carlos; Munck, Anne; Southern, Kevin W

    2017-02-01

    An unintended consequence of cystic fibrosis (CF) newborn screening (NBS) is the identification of infants with a positive NBS test but inconclusive diagnostic testing. These infants are classified as CF transmembrane conductance regulator-related metabolic syndrome (CRMS) in the US and CF screen positive, inconclusive diagnosis (CFSPID) in other countries. Diagnostic and management decisions of these infants are challenges for CF healthcare professionals and stressful situations for families. As CF NBS has become more widespread across the world, increased information about the epidemiology and outcomes of these infants is becoming available. These data were reviewed at the 2015 CF Foundation Diagnosis Consensus Conference, and a harmonized definition of CRMS and CFSPID was developed. At the consensus conference, participants reviewed published and unpublished studies of CRMS/CFSPID and used a modified Delphi methodology to develop a harmonized approach to the definition of CRMS/CFSPID. Several studies of CRMS/CFSPID from populations around the world have been published in the past year. Although the studies vary in the number of infants studied, study design, and outcome measures, there have been some consistent findings. CRMS/CFSPID occurs relatively frequently, with CF:CRMS that ranges from 3 to 5 cases of CF for every 1 case of CRMS/CFSPID in regions where gene sequencing is not used. The incidence varies by NBS protocol used, and in some regions more cases of CRMS/CFSPID are detected than cases of CF. The majority of individuals with CRMS/CFSPID do not develop CF disease or progress to a diagnosis of CF. However, between 10% and 20% of asymptomatic infants can develop clinical features concerning for CF, such as a respiratory culture positive for Pseudomonas aeruginosa. Most studies have only reported short-term outcomes in the first 1-3 years of life; the long-term outcomes of CRMS/CFSPID remain unknown. The European CF Society definition of CFSPID and the

  17. Self-regulating positive emotion networks by feedback of multiple emotional brain states using real-time fMRI.

    Science.gov (United States)

    Li, Zhonglin; Tong, Li; Wang, Linyuan; Li, Yongli; He, Wenjie; Guan, Min; Yan, Bin

    2016-12-01

    Disordered emotion regulation may affect work efficiency, induce social disharmony, and even cause psychiatric diseases. Despite recent neurocomputing advances, whether positive and negative emotion networks can be voluntarily modulated is still unknown. In the present study, we addressed this question through multivariate voxel pattern analysis and real-time functional MRI neurofeedback (rtfMRI-nf). During a sustained emotion regulation task, participants' emotional states (positive or negative) were given to them as feedback. Participants were able to increase the percentage of positive emotional states, enhancing emotion regulation network activities. Participants showed an improvement on the positive subscale of positive and negative affect scale that came close to significance. Furthermore, the activation of several emotion-related brain regions, including insula, amygdala, anterior cingulate cortex, and dorsomedial prefrontal cortex, was also increased during rtfMRI-nf training. These findings suggest that humans are able to voluntarily modulate positive emotion networks, leading to exciting applications in the treatment of various neurological and psychiatric disorders.

  18. Health care workers' compliance with hand hygiene regulations: Positive effects of a poster

    NARCIS (Netherlands)

    Karreman, Joyce; Berendsen, Femke; Pol, Bert; Dorman, Hilde

    2015-01-01

    Health care workers in nursing homes do not always comply with hand hygiene regulations, such as not wearing jewelry. Non-compliance with these regulations is a threat to patients' safety. We did two studies to investigate if compliance could be improved by a poster that reminds health care workers

  19. Positive muscle protein net balance and differential regulation of atrogene expression after resistance exercise and milk protein supplementation

    DEFF Research Database (Denmark)

    Reitelseder, Søren; Agergaard, Jakob; Doessing, Simon

    2014-01-01

    Purpose Resistance exercise and amino acid availability are positive regulators of muscle protein net balance (NB). However, anabolic responses to resistance exercise and protein supplementation deserve further elucidation. The purpose was to compare intakes of whey, caseinate (both: 0.30 g/kg lean...

  20. The Two-Component Signal Transduction System VxrAB Positively Regulates Vibrio cholerae Biofilm Formation.

    Science.gov (United States)

    Teschler, Jennifer K; Cheng, Andrew T; Yildiz, Fitnat H

    2017-09-15

    Two-component signal transduction systems (TCSs), typically composed of a sensor histidine kinase (HK) and a response regulator (RR), are the primary mechanism by which pathogenic bacteria sense and respond to extracellular signals. The pathogenic bacterium Vibrio cholerae is no exception and harbors 52 RR genes. Using in-frame deletion mutants of each RR gene, we performed a systematic analysis of their role in V. cholerae biofilm formation. We determined that 7 RRs impacted the expression of an essential biofilm gene and found that the recently characterized RR, VxrB, regulates the expression of key structural and regulatory biofilm genes in V. cholerae vxrB is part of a 5-gene operon, which contains the cognate HK vxrA and three genes of unknown function. Strains carrying Δ vxrA and Δ vxrB mutations are deficient in biofilm formation, while the Δ vxrC mutation enhances biofilm formation. The overexpression of VxrB led to a decrease in motility. We also observed a small but reproducible effect of the absence of VxrB on the levels of cyclic di-GMP (c-di-GMP). Our work reveals a new function for the Vxr TCS as a regulator of biofilm formation and suggests that this regulation may act through key biofilm regulators and the modulation of cellular c-di-GMP levels. IMPORTANCE Biofilms play an important role in the Vibrio cholerae life cycle, providing protection from environmental stresses and contributing to the transmission of V. cholerae to the human host. V. cholerae can utilize two-component systems (TCS), composed of a histidine kinase (HK) and a response regulator (RR), to regulate biofilm formation in response to external cues. We performed a systematic analysis of V. cholerae RRs and identified a new regulator of biofilm formation, VxrB. We demonstrated that the VxrAB TCS is essential for robust biofilm formation and that this system may regulate biofilm formation via its regulation of key biofilm regulators and cyclic di-GMP levels. This research furthers

  1. 78 FR 61153 - Post-Employment Conflict of Interest Regulations; Exempted Senior Employee Positions

    Science.gov (United States)

    2013-10-03

    ...: Christopher J. Swartz, Assistant Counsel, Ethics Law & Policy Branch, Office of Government Ethics; telephone... philosophy and the applicable principles of regulation set forth in section 1 of Executive Order 12866...

  2. Emotion regulation and positive affect in the context of salivary alpha-amylase response to pain in children with cancer.

    Science.gov (United States)

    Jenkins, Brooke N; Granger, Douglas A; Roemer, Ryan J; Martinez, Ariana; Torres, Tara K; Fortier, Michelle A

    2018-01-19

    Children with cancer routinely undergo painful medical procedures invoking strong physiological stress responses. Resilience to this pain may be conferred through resources such as emotion regulation strategies and positive affect. This study measured dispositional positive affect in children with cancer (N = 73) and randomly assigned participants to one of three emotion regulation strategy conditions (distraction, reappraisal, or reassurance). Children applied their assigned strategy during an experimental pain procedure (the cold pressor task [CPT]) and provided saliva samples before, immediately after, and 15 min after the CPT. Saliva samples were later assayed for salivary alpha amylase (sAA)-a surrogate marker for autonomic/sympathetic nervous system activity and regulation. Children in the reassurance group had sAA levels that continued to rise after completion of the CPT compared to children in the distraction (b = -1.68, P = 0.021) and reappraisal conditions (b = -1.24, P = 0.084). Furthermore, dispositional positive affect moderated the effect of condition such that children in the reassurance group with lower levels of positive affect had sAA levels that continued to rise after completion of the CPT (dy/dx = 1.56, P = 0.027), whereas children in the reassurance condition with higher levels of positive affect did not exhibit this rise (P > 0.05). Specific emotion regulation strategies, such as distraction and reappraisal, may attenuate the stress response to pain in pediatric patients with cancer, and positive affect may confer resilience in response to pain even with use of less effective coping strategies such as reassurance. © 2018 Wiley Periodicals, Inc.

  3. Regulative feedback in pattern formation: towards a general relativistic theory of positional information.

    Science.gov (United States)

    Jaeger, Johannes; Irons, David; Monk, Nick

    2008-10-01

    Positional specification by morphogen gradients is traditionally viewed as a two-step process. A gradient is formed and then interpreted, providing a spatial metric independent of the target tissue, similar to the concept of space in classical mechanics. However, the formation and interpretation of gradients are coupled, dynamic processes. We introduce a conceptual framework for positional specification in which cellular activity feeds back on positional information encoded by gradients, analogous to the feedback between mass-energy distribution and the geometry of space-time in Einstein's general theory of relativity. We discuss how such general relativistic positional information (GRPI) can guide systems-level approaches to pattern formation.

  4. 75 FR 4143 - Federal Speculative Position Limits for Referenced Energy Contracts and Associated Regulations

    Science.gov (United States)

    2010-01-26

    ... exemptions from the position limits for bona fide hedging transactions and for certain swap dealer risk... apply to swap dealers seeking a risk management exemption from the position limits, as well as related..., including members of the U.S. House and Senate, swap dealers, money managers, futures market participants...

  5. Effects of Regulating Positive Emotions through Reappraisal and Suppression on Verbal and Non-Verbal Recognition Memory

    Science.gov (United States)

    Ortner, Catherine N. M.; de Koning, Monica

    2013-01-01

    Previous research has suggested that regulating emotions through reappraisal does not incur cognitive costs. However, in those experiments, cognitive costs were often assessed by recognition memory for information that was contextually related to the emotionally evocative stimuli and may have been incorporated into the reappraisal script, facilitating memory. Furthermore, there is little research on the cognitive correlates of regulating positive emotions. In the current experiment, we tested memory for information that was contextually unrelated to the emotional stimuli and could not easily be related to the reappraisal. Participants viewed neutral and mildly positive slides and either reappraised, suppressed their emotions, or viewed the images with no emotion regulation instruction. At the same time, they heard abstract words that were unrelated to the picture stimuli. Subsequent verbal recognition memory was lower after reappraising than viewing, whereas non-verbal recognition memory (of the slides) was higher after reappraising, but only for positive pictures and when participants viewed the positive pictures first. Suppression had no significant effect on either verbal or non-verbal recognition scores, although there was a trend towards poorer recognition of verbal information. The findings support the notion that reappraisal is effortful and draws on limited cognitive resources, causing decrements in performance in a concurrent memory task. PMID:23658647

  6. Effects of regulating positive emotions through reappraisal and suppression on verbal and non-verbal recognition memory.

    Directory of Open Access Journals (Sweden)

    Catherine N M Ortner

    Full Text Available Previous research has suggested that regulating emotions through reappraisal does not incur cognitive costs. However, in those experiments, cognitive costs were often assessed by recognition memory for information that was contextually related to the emotionally evocative stimuli and may have been incorporated into the reappraisal script, facilitating memory. Furthermore, there is little research on the cognitive correlates of regulating positive emotions. In the current experiment, we tested memory for information that was contextually unrelated to the emotional stimuli and could not easily be related to the reappraisal. Participants viewed neutral and mildly positive slides and either reappraised, suppressed their emotions, or viewed the images with no emotion regulation instruction. At the same time, they heard abstract words that were unrelated to the picture stimuli. Subsequent verbal recognition memory was lower after reappraising than viewing, whereas non-verbal recognition memory (of the slides was higher after reappraising, but only for positive pictures and when participants viewed the positive pictures first. Suppression had no significant effect on either verbal or non-verbal recognition scores, although there was a trend towards poorer recognition of verbal information. The findings support the notion that reappraisal is effortful and draws on limited cognitive resources, causing decrements in performance in a concurrent memory task.

  7. Effects of regulating positive emotions through reappraisal and suppression on verbal and non-verbal recognition memory.

    Science.gov (United States)

    Ortner, Catherine N M; de Koning, Monica

    2013-01-01

    Previous research has suggested that regulating emotions through reappraisal does not incur cognitive costs. However, in those experiments, cognitive costs were often assessed by recognition memory for information that was contextually related to the emotionally evocative stimuli and may have been incorporated into the reappraisal script, facilitating memory. Furthermore, there is little research on the cognitive correlates of regulating positive emotions. In the current experiment, we tested memory for information that was contextually unrelated to the emotional stimuli and could not easily be related to the reappraisal. Participants viewed neutral and mildly positive slides and either reappraised, suppressed their emotions, or viewed the images with no emotion regulation instruction. At the same time, they heard abstract words that were unrelated to the picture stimuli. Subsequent verbal recognition memory was lower after reappraising than viewing, whereas non-verbal recognition memory (of the slides) was higher after reappraising, but only for positive pictures and when participants viewed the positive pictures first. Suppression had no significant effect on either verbal or non-verbal recognition scores, although there was a trend towards poorer recognition of verbal information. The findings support the notion that reappraisal is effortful and draws on limited cognitive resources, causing decrements in performance in a concurrent memory task.

  8. Counter-regulating on the Internet: Threat elicits preferential processing of positive information.

    Science.gov (United States)

    Greving, Hannah; Sassenberg, Kai; Fetterman, Adam

    2015-09-01

    The Internet is a central source of information. It is increasingly used for information search in self-relevant domains (e.g., health). Self-relevant topics are also associated with specific emotions and motivational states. For example, individuals may fear serious illness and feel threatened. Thus far, the impact of threat has received little attention in Internet-based research. The current studies investigated how threat influences Internet search. Threat is known to elicit the preferential processing of positive information. The self-directed nature of Internet search should particularly provide opportunities for such processing behavior. We predicted that during Internet search, more positive information would be processed (i.e., allocated more attention to) and more positive knowledge would be acquired under threat than in a control condition. Three experiments supported this prediction: Under threat, attention is directed more to positive web pages (Study 1) and positive links (Study 2), and more positive information is acquired (Studies 1 and 3) than in a control condition. Notably, the effect on knowledge acquisition was mediated by the effect on attention allocation during an actual Internet search (Study 1). Thus, Internet search under threat leads to selective processing of positive information and dampens threatened individuals' negative affect. (c) 2015 APA, all rights reserved).

  9. Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E.

    Science.gov (United States)

    Mascher, Gerald; Mertaoja, Anna; Korkeala, Hannu; Lindström, Miia

    2017-10-01

    Clostridium botulinum produces the most potent natural toxin, the botulinum neurotoxin (BoNT), probably to create anaerobiosis and nutrients by killing the host, and forms endospores that facilitate survival in harsh conditions and transmission. Peak BoNT production coincides with initiation of sporulation in C. botulinum cultures, which suggests common regulation. Here, we show that Spo0A, the master regulator of sporulation, positively regulates BoNT production. Insertional inactivation of spo0A in C. botulinum type E strain Beluga resulted in significantly reduced BoNT production and in abolished or highly reduced sporulation in relation to wild-type controls. Complementation with spo0A restored BoNT production and sporulation. Recombinant DNA-binding domain of Spo0A directly bound to a putative Spo0A-binding box (CTTCGAA) within the BoNT/E operon promoter, demonstrating direct regulation. Spo0A is the first neurotoxin regulator reported in C. botulinum type E. Unlike other C. botulinum strains that are terrestrial and employ the alternative sigma factor BotR in directing BoNT expression, C. botulinum type E strains are adapted to aquatic ecosystems, possess distinct epidemiology and lack BotR. Our results provide fundamental new knowledge on the genetic control of BoNT production and demonstrate common regulation of BoNT production and sporulation, providing a key intervention point for control. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  10. Hope, Self-Esteem, and Self-Regulation: Positive Characteristics among Men and Women in Recovery

    Science.gov (United States)

    Ferrari, Joseph R.; Stevens, Edward B.; Legler, Raymond; Jason, Leonard A.

    2012-01-01

    Hopefulness remains unclear in relation to aspects of self-control and self-esteem among adults in substance abuse recovery. The present study explored the relationship between dispositional hope (agency and pathway) with self-esteem (self-liking, self-competency, and self-confidence) and self-regulation (impulse control and self-discipline),…

  11. USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis

    NARCIS (Netherlands)

    Zhang, Y.; Foreman, O.; Wigle, D.A.; Kosari, F.; Vasmatzis, G.; Salisbury, J.L.; Deursen, J. van; Galardy, P.J.

    2012-01-01

    Most human tumors have abnormal numbers of chromosomes, a condition known as aneuploidy. The mitotic checkpoint is an important mechanism that prevents aneuploidy by restraining the activity of the anaphase-promoting complex (APC). The deubiquitinase USP44 was identified as a key regulator of APC

  12. Positive Regulation of RNA Metabolic Process” Ontology Group Highly Regulated in Porcine Oocytes Matured In Vitro: A Microarray Approach

    Directory of Open Access Journals (Sweden)

    Piotr Celichowski

    2018-01-01

    Full Text Available The cumulus-oocyte complexes (COCs growth and development during folliculogenesis and oogenesis are accompanied by changes involving synthesis and accumulation of large amount of RNA and proteins. In this study, the transcriptomic profile of genes involved in “oocytes RNA synthesis” in relation to in vitro maturation in pigs was investigated for the first time. The RNA was isolated from oocytes before and after in vitro maturation (IVM. Interactions between differentially expressed genes/proteins belonging to “positive regulation of RNA metabolic process” ontology group were investigated by STRING10 software. Using microarray assays, we found expression of 12258 porcine transcripts. Genes with fold change higher than 2 and with corrected p value lower than 0.05 were considered as differentially expressed. The ontology group “positive regulation of RNA metabolic process” involved differential expression of AR, INHBA, WWTR1, FOS, MEF2C, VEGFA, IKZF2, IHH, RORA, MAP3K1, NFAT5, SMARCA1, EGR1, EGR2, MITF, SMAD4, APP, and NR5A1 transcripts. Since all of the presented genes were downregulated after IVM, we suggested that they might be significantly involved in regulation of RNA synthesis before reaching oocyte MII stage. Higher expression of “RNA metabolic process” related genes before IVM indicated that they might be recognized as important markers and specific “transcriptomic fingerprint” of RNA template accumulation and storage for further porcine embryos growth and development.

  13. Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

    KAUST Repository

    Aouida, Mustapha

    2013-06-03

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3? nor sam3? single mutant is defective in polyamine transport, while the dur3? sam3? double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2? mutant. Studies of Agp2 localization indicate that in the double mutant dur3? sam3?, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport. © 2013 Aouida et al.

  14. Chitinase expression in Listeria monocytogenes is positively regulated by the Agr system.

    Directory of Open Access Journals (Sweden)

    Dafni Katerina Paspaliari

    Full Text Available The food-borne pathogen Listeria monocytogenes encodes two chitinases, ChiA and ChiB, which allow the bacterium to hydrolyze chitin, the second most abundant polysaccharide in nature. Intriguingly, despite the absence of chitin in human and mammalian hosts, both of the chitinases have been deemed important for infection, through a mechanism that, at least in the case of ChiA, involves modulation of host immune responses. In this study, we show that the expression of the two chitinases is subject to regulation by the listerial agr system, a homologue of the agr quorum-sensing system of Staphylococcus aureus, that has so far been implicated in virulence and biofilm formation. We demonstrate that in addition to these roles, the listerial agr system is required for efficient chitin hydrolysis, as deletion of agrD, encoding the putative precursor of the agr autoinducer, dramatically decreased chitinolytic activity on agar plates. Agr was specifically induced in response to chitin addition in stationary phase and agrD was found to regulate the amount of chiA, but not chiB, transcripts. Although the transcript levels of chiB did not depend on agrD, the extracellular protein levels of both chitinases were reduced in the ΔagrD mutant. The regulatory effect of agr on chiA is potentially mediated through the small RNA LhrA, which we show here to be negatively regulated by agr. LhrA is in turn known to repress chiA translation by binding to the chiA transcript and interfering with ribosome recruitment. Our results highlight a previously unrecognized role of the agr system and suggest that autoinducer-based regulation of chitinolytic systems may be more commonplace than previously thought.

  15. Wnt1 Positively Regulates CD36 Expression via TCF4 and PPAR-γ in Macrophages

    Directory of Open Access Journals (Sweden)

    Shuai Wang

    2015-02-01

    Full Text Available Background: Scavenger receptors including CD36 control the phagocytosis of oxidized low-density lipoprotein and play an important role in macrophage physiology, but the underlying molecular mechanism by which CD36 is regulated in macrophages or during macrophage differentiation from monocytes remains to be determined. Methods: Here, we investigated the relationship between Wnt1 and CD36 during macrophage differentiation. CD36 was suppressed following knockdown of Wnt1 by siRNA, while it was increased by ectopic overexpression of Wnt1 in macrophages. Using a β-catenin inhibitor, peroxisome proliferator-activated receptor gamma (PPAR-γ siRNA, and transcription factor 4 (TCF4 siRNA, we demonstrated that Wnt1 regulates the expression of CD36 through TCF4 and PPAR-γ. Co-immunoprecipitation, chromatin immunoprecipitation, and immunofluorescence experiments showed that β-catenin interacted with PPAR-γ and that PPAR-γ and TCF4 colocalized in the nucleus. Furthermore, Pax3 regulated Wnt1 via binding to the first binding site in the Wnt1 promoter. Results: Our study demonstrated that during macrophage differentiation from monocytes, Wnt1 promotes CD36 expression via activation of PPAR-γ and TCF4. Conclusions: Our findings suggest that Wnt1 plays an important role in macrophage physiology via activation of the canonical Wnt pathway.

  16. NUP37, a positive regulator of YAP/TEAD signaling, promotes the progression of hepatocellular carcinoma.

    Science.gov (United States)

    Luo, Xiaoling; Liu, Yuting; Feng, Weiguang; Lei, Liu; Du, Yemu; Wu, Jinsheng; Wang, Shaochuang

    2017-11-17

    Activation of YAP/TEAD signaling is very common in the progression of HCC (Hepatocellular carcinoma). Nuclear pore complex (NPC) regulates the shuttling of proteins between cytoplasm and nucleus. Nuclear accumulation of YAP protein has been observed in the majority of HCC tissues. However, whether NPC could regulate the YAP/TEAD signaling remains unknown. In this study, it was found NUP37, the component of NPC, significantly up-regulated in HCC clinical samples and mouse model. Over-expression of NUP37 promoted the growth, migration and invasion of HCC cells, while knocking down the expression of NUP37 inhibited the growth, migration, invasion and metastasis of HCC cells and improved the survival of the mouse model. NUP37 interacted with YAP and activated YAP/TEAD signaling by enhancing the interaction between YAP and TEAD. Taken together, these data demonstrated the oncogenic roles of NUP37 in the progression of HCC and suggested that NUP37 might be a promising therapeutic target.

  17. Mental Contrasting of a Negative Future with a Positive Reality Regulates State Anxiety

    Directory of Open Access Journals (Sweden)

    Gunnar Brodersen

    2017-09-01

    Full Text Available Mental contrasting of a desired future with impeding reality is a self-regulatory strategy fostering goal pursuit. However, there is little research on mental contrasting of a negative future with a positive reality. We conducted two experiments, each with four experimental conditions, investigating the effects of mental contrasting a negative future with a positive reality on state anxiety: participants who mentally contrasted a negative future regarding a bacterial epidemic (Study 1, N = 199 or an idiosyncratic negative event (Study 2, N = 206 showed less state anxiety than participants who imagined the negative future only or who reverse contrasted; participants who mentally elaborated on the positive reality also showed less state anxiety. Our findings suggest that mental contrasting of a negative future helps people reduce disproportional anxiety regarding a negative future.

  18. Categorizing Mistaken False Positives in Regulation of Human and Environmental Health

    DEFF Research Database (Denmark)

    Hansen, Steffen Foss; Krayer von Krauss, Martin Paul; Tickner, J.A.

    2007-01-01

    ," including: real risks, "The jury is still out," nonregulated proclaimed risks, "Too narrow a definition of risk," and risk-risk tradeoffs. These categories are defined and examples are presented in order to illustrate their key characteristics. On the basis of our analysis, we were able to identify only...... four cases that could be defined as regulatory false positives in the light of today's knowledge and recognized uncertainty: the Southern Corn Leaf Blight, the Swine Flu, Saccharin, and Food Irradiation in relation to consumer health. We conclude that concerns about false positives do not represent...

  19. TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy.

    Science.gov (United States)

    Vlahakis, Ariadne; Graef, Martin; Nunnari, Jodi; Powers, Ted

    2014-07-22

    The highly conserved Target of Rapamycin (TOR) kinase is a central regulator of cell growth and metabolism in response to nutrient availability. TOR functions in two structurally and functionally distinct complexes, TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2). Through TORC1, TOR negatively regulates autophagy, a conserved process that functions in quality control and cellular homeostasis and, in this capacity, is part of an adaptive nutrient deprivation response. Here we demonstrate that during amino acid starvation TOR also operates independently as a positive regulator of autophagy through the conserved TORC2 and its downstream target protein kinase, Ypk1. Under these conditions, TORC2-Ypk1 signaling negatively regulates the Ca(2+)/calmodulin-dependent phosphatase, calcineurin, to enable the activation of the amino acid-sensing eIF2α kinase, Gcn2, and to promote autophagy. Our work reveals that the TORC2 pathway regulates autophagy in an opposing manner to TORC1 to provide a tunable response to cellular metabolic status.

  20. Noise propagation in gene regulation networks involving interlinked positive and negative feedback loops.

    Directory of Open Access Journals (Sweden)

    Hui Zhang

    Full Text Available It is well known that noise is inevitable in gene regulatory networks due to the low-copy numbers of molecules and local environmental fluctuations. The prediction of noise effects is a key issue in ensuring reliable transmission of information. Interlinked positive and negative feedback loops are essential signal transduction motifs in biological networks. Positive feedback loops are generally believed to induce a switch-like behavior, whereas negative feedback loops are thought to suppress noise effects. Here, by using the signal sensitivity (susceptibility and noise amplification to quantify noise propagation, we analyze an abstract model of the Myc/E2F/MiR-17-92 network that is composed of a coupling between the E2F/Myc positive feedback loop and the E2F/Myc/miR-17-92 negative feedback loop. The role of the feedback loop on noise effects is found to depend on the dynamic properties of the system. When the system is in monostability or bistability with high protein concentrations, noise is consistently suppressed. However, the negative feedback loop reduces this suppression ability (or improves the noise propagation and enhances signal sensitivity. In the case of excitability, bistability, or monostability, noise is enhanced at low protein concentrations. The negative feedback loop reduces this noise enhancement as well as the signal sensitivity. In all cases, the positive feedback loop acts contrary to the negative feedback loop. We also found that increasing the time scale of the protein module or decreasing the noise autocorrelation time can enhance noise suppression; however, the systems sensitivity remains unchanged. Taken together, our results suggest that the negative/positive feedback mechanisms in coupled feedback loop dynamically buffer noise effects rather than only suppressing or amplifying the noise.

  1. Cyclin G Functions as a Positive Regulator of Growth and Metabolism in Drosophila.

    Directory of Open Access Journals (Sweden)

    Patrick Fischer

    2015-08-01

    Full Text Available In multicellular organisms, growth and proliferation is adjusted to nutritional conditions by a complex signaling network. The Insulin receptor/target of rapamycin (InR/TOR signaling cascade plays a pivotal role in nutrient dependent growth regulation in Drosophila and mammals alike. Here we identify Cyclin G (CycG as a regulator of growth and metabolism in Drosophila. CycG mutants have a reduced body size and weight and show signs of starvation accompanied by a disturbed fat metabolism. InR/TOR signaling activity is impaired in cycG mutants, combined with a reduced phosphorylation status of the kinase Akt1 and the downstream factors S6-kinase and eukaryotic translation initiation factor 4E binding protein (4E-BP. Moreover, the expression and accumulation of Drosophila insulin like peptides (dILPs is disturbed in cycG mutant brains. Using a reporter assay, we show that the activity of one of the first effectors of InR signaling, Phosphoinositide 3-kinase (PI3K92E, is unaffected in cycG mutants. However, the metabolic defects and weight loss in cycG mutants were rescued by overexpression of Akt1 specifically in the fat body and by mutants in widerborst (wdb, the B'-subunit of the phosphatase PP2A, known to downregulate Akt1 by dephosphorylation. Together, our data suggest that CycG acts at the level of Akt1 to regulate growth and metabolism via PP2A in Drosophila.

  2. HOPE, SELF-ESTEEM, AND SELF-REGULATION: POSITIVE CHARACTERISTICS AMONG MEN AND WOMEN IN RECOVERY.

    Science.gov (United States)

    Ferrari, Joseph R; Stevens, Edward B; Legler, Raymond; Jason, Leonard A

    2012-04-01

    Hopefulness remains unclear in relation to aspects of self-control and self-esteem among adults in substance abuse recovery. The present study explored the relationship between dispositional hope (agency and pathway) with self-esteem (self-liking, self-competency, and self-confidence) and self-regulation (impulse control and self-discipline), using a latent variable measurement model and structural equation modeling among adults (n = 601) residing in a communal living setting for persons in substance abuse recovery. Results showed that multiple dimensions of these constructs were significant as individual predictors. With persons in recovery, self-regulation included impulsivity control and self-discipline, while self-esteem reflected self-liking, competence, and a sense of self-confidence. Furthermore, both hope-pathways and hope-agency significantly related to self-control/impulse control but not self-control/discipline, and self-esteem/competency was associated with hope-pathways but not hope-agency.

  3. Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in response to cocaine.

    Science.gov (United States)

    Sun, HaoSheng; Damez-Werno, Diane M; Scobie, Kimberly N; Shao, Ning-Yi; Dias, Caroline; Rabkin, Jacqui; Wright, Katherine N; Mouzon, Ezekiell; Kabbaj, Mohamed; Neve, Rachael; Turecki, Gustavo; Shen, Li; Nestler, Eric J

    2017-06-14

    Chromatin regulation, in particular ATP-dependent chromatin remodelers, have previously been shown to be important in the regulation of reward-related behaviors in animal models of mental illnesses. Here we demonstrate that BAZ1A, an accessory subunit of the ISWI family of chromatin remodeling complexes, is downregulated in the nucleus accumbens (NAc) of mice exposed repeatedly to cocaine and of cocaine-addicted humans. Viral-mediated overexpression of BAZ1A in mouse NAc reduces cocaine reward as assessed by conditioned place preference (CPP), but increases cocaine-induced locomotor activation. Furthermore, we investigate nucleosome repositioning genome-wide by conducting chromatin immunoprecipitation (ChIP)-sequencing for total H3 in NAc of control mice and after repeated cocaine administration, and find extensive nucleosome occupancy and shift changes across the genome in response to cocaine exposure. These findings implicate BAZ1A in molecular and behavioral plasticity to cocaine and offer new insight into the pathophysiology of cocaine addiction. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. FIN5 positively regulates far-red light responses in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Cho, D.S.; Hong, S.H.; Nam, H.G.; Soh, M.S.

    2003-01-01

    We report the characterization of a semi-dominant mutation fin5-1 (far-red insensitive 5-1) of Arabidopsis, which was isolated from genetic screening of phytochrome A (phyA) signaling components. Plants with the fin5-1 mutation exhibited a long hypocotyl phenotype when grown under far-red (FR) light, but not under red light. Physiological analyses implied that FIN5 might be differentially involved in diverse responses that are regulated by phyA under continuous FR light. Anthocyanin accumulation, gravitropic response of hypocotyl growth, and FR light-preconditioned blocking of greening were also impaired in the fin5-1 mutant, whereas photoperiodic floral induction was not, if at all, significantly affected. Moreover, light-regulated expression of the CHS, PORA and PsbS genes was attenuated in fin5-1 mutant plants, while the light-induced expression of CAB was normal. The mutation exhibited semi-dominance regarding control of hypocotyl growth in FR light. We suggest that FIN5 defines a novel branch in the network of phyA signaling in Arabidopsis. (author)

  5. Two-Component Signal Transduction System SaeRS Positively Regulates Staphylococcus epidermidis Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Qiang Lou

    2014-01-01

    Full Text Available Staphylococcus epidermidis, which is a causative pathogen of nosocomial infection, expresses its virulent traits such as biofilm and autolysis regulated by two-component signal transduction system SaeRS. In this study, we performed a proteomic analysis of differences in expression between the S. epidermidis 1457 wild-type and saeRS mutant to identify candidates regulated by saeRS using two-dimensional gel electrophoresis (2-DE combined with matrix-assisted laser desorption/lonization mass spectrometry (MALDI-TOF-MS. Of 55 identified proteins that significantly differed in expression between the two strains, 15 were upregulated and 40 were downregulated. The downregulated proteins included enzymes related to glycolysis and TCA cycle, suggesting that glucose is not properly utilized in S. epidermidis when saeRS was deleted. The study will be helpful for treatment of S. epidermidis infection from the viewpoint of metabolic modulation dependent on two-component signal transduction system SaeRS.

  6. Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion.

    Science.gov (United States)

    Li, Tingting; Xu, Jie; Qin, Xinghua; Hou, Zuoxu; Guo, Yongzheng; Liu, Zhenhua; Wu, Jianjiang; Zheng, Hong; Zhang, Xing; Gao, Feng

    2017-11-01

    Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia-reperfusion (I/R) injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. We found that glucose uptake was remarkably diminished in the myocardium following reperfusion in Sprague-Dawley rats as detected by 18 F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by threefold and GLUT4 translocation remained unchanged compared with those of sham-treated rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated I/R injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, whereas its knockdown increased glucose uptake, suggesting that PDK4 has a role in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial I/R. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in the myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial I/R injury. Copyright © 2017 the American Physiological Society.

  7. The transcription factor Pitx2 positions the embryonic axis and regulates twinning

    Science.gov (United States)

    Torlopp, Angela; Khan, Mohsin A F; Oliveira, Nidia M M; Lekk, Ingrid; Soto-Jiménez, Luz Mayela; Sosinsky, Alona; Stern, Claudio D

    2014-01-01

    Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest known factor is cVg1 (homologous to mammalian growth differentiation factor 1, GDF1), a transforming growth factor beta (TGFβ) signal expressed posteriorly before gastrulation. A molecular screen to find upstream regulators of cVg1 in normal embryos and in embryos manipulated to form twins now uncovers the transcription factor Pitx2 as a candidate. We show that Pitx2 is essential for axis formation, and that it acts as a direct regulator of cVg1 expression by binding to enhancers within neighbouring genes. Pitx2, Vg1/GDF1 and Nodal are also key actors in left–right asymmetry, suggesting that the same ancient polarity determination mechanism has been co-opted to different functions during evolution. DOI: http://dx.doi.org/10.7554/eLife.03743.001 PMID:25496870

  8. The Min system and other nucleoid-independent regulators of Z ring positioning

    Directory of Open Access Journals (Sweden)

    William eMargolin

    2015-05-01

    Full Text Available Rod-shaped bacteria such as E. coli have mechanisms to position their cell division plane at the precise center of the cell, to ensure that the daughter cells are equal in size. The two main mechanisms are the Min system and nucleoid occlusion (NO, both of which work by inhibiting assembly of FtsZ, the tubulin-like scaffold that forms the cytokinetic Z ring. Whereas NO prevents Z rings from constricting over unsegregated nucleoids, the Min system is nucleoid-independent and even functions in cells lacking nucleoids and thus NO. The Min proteins of E. coli and B. subtilis form bipolar gradients that inhibit Z ring formation most at the cell poles and least at the nascent division plane. This article will outline the molecular mechanisms behind Min function in E. coli and B. subtilis, and discuss distinct Z ring positioning systems in other bacterial species.

  9. c-di-GMP Regulates Various Phenotypes and Insecticidal Activity of Gram-Positive Bacillus thuringiensis

    Directory of Open Access Journals (Sweden)

    Yang Fu

    2018-02-01

    Full Text Available C-di-GMP has been well investigated to play significant roles in the physiology of many Gram-negative bacteria. However, its effect on Gram-positive bacteria is less known. In order to more understand the c-di-GMP functions in Gram-positive bacteria, we have carried out a detailed study on the c-di-GMP-metabolizing enzymes and their physiological functions in Bacillus thuringiensis, a Gram-positive entomopathogenic bacterium that has been applied as an insecticide successfully. We performed a systematic study on the ten putative c-di-GMP-synthesizing enzyme diguanylate cyclases (DGCs and c-di-GMP-degrading enzyme phosphodiesterases (PDEs in B. thuringiensis BMB171, and artificially elevated the intracellular c-di-GMP level in BMB171 by deleting one or more pde genes. We found increasing level of intracellular c-di-GMP exhibits similar activities as those in Gram-negative bacteria, including altered activities in cell motility, biofilm formation, and cell-cell aggregation. Unexpectedly, we additionally found a novel function exhibited by the increasing level of c-di-GMP to promote the insecticidal activity of this bacterium against Helicoverpa armigera. Through whole-genome transcriptome profile analyses, we found that 4.3% of the B. thuringiensis genes were differentially transcribed when c-di-GMP level was increased, and 77.3% of such gene products are involved in some regulatory pathways not reported in other bacteria to date. In summary, our study represents the first comprehensive report on the c-di-GMP-metabolizing enzymes, their effects on phenotypes, and the transcriptome mediated by c-di-GMP in an important Gram-positive bacterium.

  10. c-di-GMP Regulates Various Phenotypes and Insecticidal Activity of Gram-Positive Bacillus thuringiensis

    Science.gov (United States)

    Fu, Yang; Yu, Zhaoqing; Liu, Shu; Chen, Bo; Zhu, Li; Li, Zhou; Chou, Shan-Ho; He, Jin

    2018-01-01

    C-di-GMP has been well investigated to play significant roles in the physiology of many Gram-negative bacteria. However, its effect on Gram-positive bacteria is less known. In order to more understand the c-di-GMP functions in Gram-positive bacteria, we have carried out a detailed study on the c-di-GMP-metabolizing enzymes and their physiological functions in Bacillus thuringiensis, a Gram-positive entomopathogenic bacterium that has been applied as an insecticide successfully. We performed a systematic study on the ten putative c-di-GMP-synthesizing enzyme diguanylate cyclases (DGCs) and c-di-GMP-degrading enzyme phosphodiesterases (PDEs) in B. thuringiensis BMB171, and artificially elevated the intracellular c-di-GMP level in BMB171 by deleting one or more pde genes. We found increasing level of intracellular c-di-GMP exhibits similar activities as those in Gram-negative bacteria, including altered activities in cell motility, biofilm formation, and cell-cell aggregation. Unexpectedly, we additionally found a novel function exhibited by the increasing level of c-di-GMP to promote the insecticidal activity of this bacterium against Helicoverpa armigera. Through whole-genome transcriptome profile analyses, we found that 4.3% of the B. thuringiensis genes were differentially transcribed when c-di-GMP level was increased, and 77.3% of such gene products are involved in some regulatory pathways not reported in other bacteria to date. In summary, our study represents the first comprehensive report on the c-di-GMP-metabolizing enzymes, their effects on phenotypes, and the transcriptome mediated by c-di-GMP in an important Gram-positive bacterium. PMID:29487570

  11. c-di-GMP Regulates Various Phenotypes and Insecticidal Activity of Gram-PositiveBacillus thuringiensis.

    Science.gov (United States)

    Fu, Yang; Yu, Zhaoqing; Liu, Shu; Chen, Bo; Zhu, Li; Li, Zhou; Chou, Shan-Ho; He, Jin

    2018-01-01

    C-di-GMP has been well investigated to play significant roles in the physiology of many Gram-negative bacteria. However, its effect on Gram-positive bacteria is less known. In order to more understand the c-di-GMP functions in Gram-positive bacteria, we have carried out a detailed study on the c-di-GMP-metabolizing enzymes and their physiological functions in Bacillus thuringiensis , a Gram-positive entomopathogenic bacterium that has been applied as an insecticide successfully. We performed a systematic study on the ten putative c-di-GMP-synthesizing enzyme diguanylate cyclases (DGCs) and c-di-GMP-degrading enzyme phosphodiesterases (PDEs) in B. thuringiensis BMB171, and artificially elevated the intracellular c-di-GMP level in BMB171 by deleting one or more pde genes. We found increasing level of intracellular c-di-GMP exhibits similar activities as those in Gram-negative bacteria, including altered activities in cell motility, biofilm formation, and cell-cell aggregation. Unexpectedly, we additionally found a novel function exhibited by the increasing level of c-di-GMP to promote the insecticidal activity of this bacterium against Helicoverpa armigera . Through whole-genome transcriptome profile analyses, we found that 4.3% of the B. thuringiensis genes were differentially transcribed when c-di-GMP level was increased, and 77.3% of such gene products are involved in some regulatory pathways not reported in other bacteria to date. In summary, our study represents the first comprehensive report on the c-di-GMP-metabolizing enzymes, their effects on phenotypes, and the transcriptome mediated by c-di-GMP in an important Gram-positive bacterium.

  12. Applying High-Speed Vision Sensing to an Industrial Robot for High-Performance Position Regulation under Uncertainties.

    Science.gov (United States)

    Huang, Shouren; Bergström, Niklas; Yamakawa, Yuji; Senoo, Taku; Ishikawa, Masatoshi

    2016-07-29

    It is traditionally difficult to implement fast and accurate position regulation on an industrial robot in the presence of uncertainties. The uncertain factors can be attributed either to the industrial robot itself (e.g., a mismatch of dynamics, mechanical defects such as backlash, etc.) or to the external environment (e.g., calibration errors, misalignment or perturbations of a workpiece, etc.). This paper proposes a systematic approach to implement high-performance position regulation under uncertainties on a general industrial robot (referred to as the main robot) with minimal or no manual teaching. The method is based on a coarse-to-fine strategy that involves configuring an add-on module for the main robot's end effector. The add-on module consists of a 1000 Hz vision sensor and a high-speed actuator to compensate for accumulated uncertainties. The main robot only focuses on fast and coarse motion, with its trajectories automatically planned by image information from a static low-cost camera. Fast and accurate peg-and-hole alignment in one dimension was implemented as an application scenario by using a commercial parallel-link robot and an add-on compensation module with one degree of freedom (DoF). Experimental results yielded an almost 100% success rate for fast peg-in-hole manipulation (with regulation accuracy at about 0.1 mm) when the workpiece was randomly placed.

  13. Foxa1 and Foxa2 positively and negatively regulate Shh signalling to specify ventral midbrain progenitor identity.

    Science.gov (United States)

    Mavromatakis, Yannis E; Lin, Wei; Metzakopian, Emmanouil; Ferri, Anna L M; Yan, Carol H; Sasaki, Hiroshi; Whisett, Jeff; Ang, Siew-Lan

    2011-01-01

    Foxa2, a member of the Foxa family of forkhead/winged helix family of transcription factors, has previously been shown to be an upstream positive regulator of Shh expression in many different tissues. Recent studies also strongly suggest that Foxa2 specify cell fate by inhibiting the expression of cell fate determinants such as Helt1 and Nkx2.2. In this paper, phenotypic analyses of Wnt1cre; Foxa2flox/flox embryos in the midbrain have demonstrated a novel role for Foxa2 and its related family member, Foxa1, to attenuate Shh signalling by inhibiting the expression of its intracellular transducer, Gli2, at the transcriptional level. Chromatin immunoprecipitation experiments indicate that Foxa2 binds to genomic regions of Gli2 and likely regulates its expression in a direct manner. Our studies, involving loss and gain of function studies in mice, also provided further insights into the gene regulatory interactions among Foxa1, Foxa2 and Shh in ventral midbrain progenitors that contribute to midbrain patterning. Altogether, these data indicate that Foxa1 and Foxa2 contribute to the specification of ventral midbrain progenitor identity by regulating Shh signalling in a positive and negative manner. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  14. Small Antisense RNA RblR Positively Regulates RuBisCo inSynechocystissp. PCC 6803.

    Science.gov (United States)

    Hu, Jinlu; Li, Tianpei; Xu, Wen; Zhan, Jiao; Chen, Hui; He, Chenliu; Wang, Qiang

    2017-01-01

    Small regulatory RNAs (sRNAs) function as transcriptional and post-transcriptional regulators of gene expression in organisms from all domains of life. Cyanobacteria are thought to have developed a complex RNA-based regulatory mechanism. In the current study, by genome-wide analysis of differentially expressed small RNAs in Synechocystis sp. PCC 6803 under high light conditions, we discovered an asRNA (RblR) that is 113nt in length and completely complementary to its target gene rbcL , which encodes the large chain of RuBisCO, the enzyme that catalyzes carbon fixation. Further analysis of the RblR(+)/(-) mutants revealed that RblR acts as a positive regulator of rbcL under various stress conditions; Suppressing RblR adversely affects carbon assimilation and thus the yield, and those phenotypes of both the wild type and the overexpressor could be downgraded to the suppressor level by carbonate depletion, indicated a regulatory role of RblR in CO 2 assimilation. In addition, a real-time expression platform in Escherichia coli was setup and which confirmed that RblR promoted the translation of the rbcL mRNA into the RbcL protein. The present study is the first report of a regulatory RNA that targets RbcL in Synechocystis sp. PCC 6803, and provides strong evidence that RblR regulates photosynthesis by positively modulating rbcL expression in Synechocystis .

  15. Negative Regulators of an RNAi-Heterochromatin Positive Feedback Loop Safeguard Somatic Genome Integrity in Tetrahymena.

    Science.gov (United States)

    Suhren, Jan H; Noto, Tomoko; Kataoka, Kensuke; Gao, Shan; Liu, Yifan; Mochizuki, Kazufumi

    2017-03-07

    RNAi-mediated positive feedback loops are pivotal for the maintenance of heterochromatin, but how they are downregulated at heterochromatin-euchromatin borders is not well understood. In the ciliated protozoan Tetrahymena, heterochromatin is formed exclusively on the sequences that are removed from the somatic genome by programmed DNA elimination, and an RNAi-mediated feedback loop is important for assembling heterochromatin on the eliminated sequences. In this study, we show that the heterochromatin protein 1 (HP1)-like protein Coi6p, its interaction partners Coi7p and Lia5p, and the histone demethylase Jmj1p are crucial for confining the production of small RNAs and the formation of heterochromatin to the eliminated sequences. The loss of Coi6p, Coi7p, or Jmj1p causes ectopic DNA elimination. The results provide direct evidence for the existence of a dedicated mechanism that counteracts a positive feedback loop between RNAi and heterochromatin at heterochromatin-euchromatin borders to maintain the integrity of the somatic genome. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. c-Fos downregulation positively regulates EphA5 expression in a congenital hypothyroidism rat model.

    Science.gov (United States)

    Song, Honghua; Zheng, Yuqin; Cai, Fuying; Ma, Yanyan; Yang, Jingyue; Wu, Youjia

    2018-04-01

    The EphA5 receptor is well established as an axon guidance molecule during neural system development and plays an important role in dendritic spine formation and synaptogenesis. Our previous study has showed that EphA5 is decreased in the developing brain of congenital hypothyroidism (CH) and the EphA5 promoter methylation modification participates in its decrease. c-Fos, a well-kown transcription factor, has been considered in association with brain development. Bioinformatics analysis showed that the EphA5 promoter region contained five putative c-fos binding sites. The chromatin immunoprecipitation (ChIP) assays were used to assess the direct binding of c-fos to the EphA5 promoter. Furthermore, dual-luciferase assays showed that these three c-fos protein binding sites were positive regulatory elements for EphA5 expression in PC12 cells. Moreover, We verified c-fos positively regulation for EphA5 expression in CH model. Q-PCR and Western blot showed that c-fos overexpression could upregulate EphA5 expression in hippocampal neurons of rats with CH. Our results suggest that c-fos positively regulates EphA5 expression in CH rat model.

  17. Don't worry, be happy: The role of positive emotionality and adaptive emotion regulation strategies for youth depressive symptoms.

    Science.gov (United States)

    Van Beveren, Marie-Lotte; Harding, Kaitlin; Beyers, Wim; Braet, Caroline

    2018-03-01

    Low positive emotionality (PE) represents a temperamental vulnerability to depression in youth. Until now, little research has examined the mechanisms linking PE to depressive symptoms. Starting from integrated cognitive-affective models of depression, we aimed to study adaptive emotion regulation (ER) as a key underlying mechanism in the temperament-depression relationship. This study investigated whether adaptive ER strategies mediate the association between PE and depressive symptoms in a large community-based sample of youth, using a cross-sectional design. Participants were 1,655 youth (54% girls; 7-16 years, M = 11.41, SD = 1.88) who filled out a set of questionnaires assessing temperament, adaptive ER strategies, and depressive symptoms. Results revealed that low PE was significantly related to higher depressive symptoms among youth and that a lack of total adaptive ER abilities mediated this relationship. More specifically, the infrequent use of problem-solving appeared to be of significant importance. Problems in positive refocusing and a deficient use of forgetting mediated the relationships between low PE and high negative emotionality (NE) in predicting depressive symptoms. Reappraisal and distraction were not significant mediators. Results highlight the need to account for temperamental PE and adaptive ER strategies when studying youth depression. The findings contribute to a more nuanced understanding on the differential role of temperamental risk factors for developing depressive symptoms at an early stage and advocate for greater attention to adaptive ER strategies. Clinical interventions for youth depression may be improved by incorporating adaptive emotion regulation (ER) strategies and enhancing positive emotions. Youth low in positive emotionality (PE) may especially benefit from learning adaptive ER skills. Clinical practitioners should focus on alleviating negative emotions and enhancing positive emotions, especially among youth low in PE

  18. PINK1 positively regulates IL-1β-mediated signaling through Tollip and IRAK1 modulation

    Directory of Open Access Journals (Sweden)

    Lee Hyun Jung

    2012-12-01

    Full Text Available Abstract Background Parkinson disease (PD is characterized by a slow, progressive degeneration of dopaminergic neurons in the substantianigra. The cause of neuronal loss in PD is not well understood, but several genetic loci, including PTEN-induced putative kinase 1 (PINK1, have been linked to early-onset autosomal recessive forms of familial PD. Neuroinflammation greatly contributes to PD neuronal degeneration and pathogenesis. IL-1 is one of the principal cytokines that regulates various immune and inflammatory responses via the activation of the transcription factors NF-κB and activating protein-1. Despite the close relationship between PD and neuroinflammation, the functional roles of PD-linked genes during inflammatory processes remain poorly understood. Methods To explore the functional roles of PINK1 in response to IL-1β stimulation, HEK293 cells, mouse embryonic fibroblasts derived from PINK1-null (PINK1−/− and control (PINK1+/+ mice, and 293 IL-1RI cells stably expressing type 1 IL-1 receptor were used. Immunoprecipitation and western blot analysis were performed to detect protein–protein interaction and protein ubiquitination. To confirm the effect of PINK1 on NF-κB activation, NF-κB-dependent firefly luciferase reporter assay was conducted. Results PINK1 specifically binds two components of the IL-1-mediated signaling cascade, Toll-interacting protein (Tollip and IL-1 receptor-associated kinase 1 (IRAK1. The association of PINK1 with Tollip, a negative regulator of IL-1β signaling, increases upon IL-1β stimulation, which then facilitates the dissociation of Tollip from IRAK1 as well as the assembly of the IRAK1–TNF receptor-associated factor 6 (TRAF6 complex. PINK1 also enhances Lys63-linked polyubiquitination of IRAK1, an essential modification of recruitment of NF-κB essential modulator and subsequent IκB kinase activation, and increases formation of the intermediate signalosome including IRAK1, TRAF6, and

  19. miR-25-3p, Positively Regulated by Transcription Factor AP-2α, Regulates the Metabolism of C2C12 Cells by Targeting Akt1

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2018-03-01

    Full Text Available miR-25, a member of the miR-106b-25 cluster, has been reported as playing an important role in many biological processes by numerous studies, while the role of miR-25 in metabolism and its transcriptional regulation mechanism remain unclear. In this study, gain-of-function and loss-of-function assays demonstrated that miR-25-3p positively regulated the metabolism of C2C12 cells by attenuating phosphoinositide 3-kinase (PI3K gene expression and triglyceride (TG content, and enhancing the content of adenosine triphosphate (ATP and reactive oxygen species (ROS. Furthermore, the results from bioinformatics analysis, dual luciferase assay, site-directed mutagenesis, qRT-PCR, and Western blotting demonstrated that miR-25-3p directly targeted the AKT serine/threonine kinase 1 (Akt1 3′ untranslated region (3′UTR. The core promoter of miR-25-3p was identified, and the transcription factor activator protein-2α (AP-2α significantly increased the expression of mature miR-25-3p by binding to its core promoter in vivo, as indicated by the chromatin immunoprecipitation (ChIP assay, and AP-2α binding also downregulated the expression of Akt1. Taken together, our findings suggest that miR-25-3p, positively regulated by the transcription factor AP-2α, enhances C2C12 cell metabolism by targeting the Akt1 gene.

  20. Lopinavir up-regulates expression of the antiviral protein ribonuclease L in human papillomavirus-positive cervical carcinoma cells.

    Science.gov (United States)

    Batman, Gavin; Oliver, Anthony W; Zehbe, Ingeborg; Richard, Christina; Hampson, Lynne; Hampson, Ian N

    2011-01-01

    We have previously shown that the HIV protease inhibitor lopinavir has selective toxicity against human papillomavirus (HPV)-positive cervical carcinoma cells via an unknown mechanism. SiHa cervical carcinoma cells were stably transfected with the proteasome sensor vector pZsProSensor-1 to confirm lopinavir inhibits the proteasome in these cells. The Panorama Xpress profiler 725 antibody array was then used to analyse specific changes in protein expression in lopinavir-treated versus control untreated SiHa cells followed by PCR and western blotting. Colorimetric growth assays of lopinavir-treated E6/E7 immortalised versus control human keratinocytes were performed. Targeted small interfering RNA gene silencing followed by growth assay comparison of lopinavir-treated/untreated SiHa cells was also used. Lopinavir induced an increase in the fluorescence of pZsProSensor-1 transfected SiHa cells, indicative of proteasomal inhibition. Ribonuclease L (RNASEL) protein was shown to be up-regulated in lopinavir-treated SiHa cells, which was confirmed by PCR and western blot. Targeted silencing of RNASEL reduced the sensitivity of SiHa cells to lopinavir. Selective toxicity against E6/E7 immortalised keratinocytes versus control cells was also seen with lopinavir and was associated with up-regulated RNASEL expression. These data are consistent with the toxicity of lopinavir against HPV-positive cervical carcinoma cells being related to its ability to block viral proteasome activation and induce an up-regulation of the antiviral protein RNASEL. This is supported by the drug's selective toxicity and up-regulation of RNASEL in E6/E7 immortalised keratinocytes combined with the increased resistance to lopinavir observed in SiHa cells following silencing of RNASEL gene expression.

  1. XAP5 CIRCADIAN TIMEKEEPER Positively Regulates RESISTANCE TO POWDERY MILDEW8.1–Mediated Immunity in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Yong-Ju Xu

    2017-11-01

    Full Text Available Ectopic expression of the Arabidopsis RESISTANCE TO POWDERY MILDEW8.1 (RPW8.1 boosts pattern-triggered immunity leading to enhanced resistance to different pathogens in Arabidopsis and rice. However, the underlying regulatory mechanism remains largely elusive. Here, we report that XAP5 CIRCADIAN TIMEKEEPER (XCT, At2g21150 positively regulates RPW8.1-mediated cell death and disease resistance. Forward genetic screen identified the b3-17 mutant that exhibited less cell death and susceptibility to powdery mildew and bacterial pathogens. Map-based cloning identified a G-to-A point mutation at the 3′ splice site of the 8th intron, which resulted in splice shift to 8-bp down-stream of the original splice site of XCT in b3-17, and introduced into a stop codon after two codons leading to a truncated XCT. XCT has previously been identified as a circadian clock gene required for small RNA biogenesis and acting down-stream of ETHYLENE-INSENSITIVE3 (EIN3 in the ethylene-signaling pathway. Here we further showed that mutation or down-regulation of XCT by artificial microRNA reduced RPW8.1-mediated immunity in R1Y4, a transgenic line expressing RPW8.1-YFP from the RPW8.1 native promoter. On the contrary, overexpression of XCT in R1Y4 background enhanced RPW8.1-mediated cell death, H2O2 production and resistance against powdery mildew. Consistently, the expression of RPW8.1 was down- and up-regulated in xct mutant and XCT overexpression lines, respectively. Taken together, these results indicate that XCT positively regulates RPW8.1-mediated cell death and disease resistance, and provide new insight into the regulatory mechanism of RPW8.1-mediated immunity.

  2. Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice

    DEFF Research Database (Denmark)

    Gustavsson, N; Wang, Y; Kang, Y

    2011-01-01

    using synaptotagmin-7 knockout (KO) mice and GLUTag cells with lentiviral-mediated synaptotagmin-7 silencing. RESULTS: We found that synaptotagmin-7 was co-localised with GLP-1 in intestinal L-cells. GLP-1 secretion was impaired in synaptotagmin-7 KO mice when they were challenged by glucose ingestion...... that synaptotagmin-7 functions as a positive regulator of GLP-1 secretion in intestinal L-cells and GLUTag cells, consistent with its proposed role as a calcium sensor in GLP-1 secretion....

  3. Positive and negative regulation of Gli activity by Kif7 in the zebrafish embryo.

    Directory of Open Access Journals (Sweden)

    Ashish Kumar Maurya

    Full Text Available Loss of function mutations of Kif7, the vertebrate orthologue of the Drosophila Hh pathway component Costal2, cause defects in the limbs and neural tubes of mice, attributable to ectopic expression of Hh target genes. While this implies a functional conservation of Cos2 and Kif7 between flies and vertebrates, the association of Kif7 with the primary cilium, an organelle absent from most Drosophila cells, suggests their mechanisms of action may have diverged. Here, using mutant alleles induced by Zinc Finger Nuclease-mediated targeted mutagenesis, we show that in zebrafish, Kif7 acts principally to suppress the activity of the Gli1 transcription factor. Notably, we find that endogenous Kif7 protein accumulates not only in the primary cilium, as previously observed in mammalian cells, but also in cytoplasmic puncta that disperse in response to Hh pathway activation. Moreover, we show that Drosophila Costal2 can substitute for Kif7, suggesting a conserved mode of action of the two proteins. We show that Kif7 interacts with both Gli1 and Gli2a and suggest that it functions to sequester Gli proteins in the cytoplasm, in a manner analogous to the regulation of Ci by Cos2 in Drosophila. We also show that zebrafish Kif7 potentiates Gli2a activity by promoting its dissociation from the Suppressor of Fused (Sufu protein and present evidence that it mediates a Smo dependent modification of the full length form of Gli2a. Surprisingly, the function of Kif7 in the zebrafish embryo appears restricted principally to mesodermal derivatives, its inactivation having little effect on neural tube patterning, even when Sufu protein levels are depleted. Remarkably, zebrafish lacking all Kif7 function are viable, in contrast to the peri-natal lethality of mouse kif7 mutants but similar to some Acrocallosal or Joubert syndrome patients who are homozygous for loss of function KIF7 alleles.

  4. CaCDPK15 positively regulates pepper responses to Ralstonia solanacearum inoculation and forms a positive-feedback loop with CaWRKY40 to amplify defense signaling

    Science.gov (United States)

    Shen, Lei; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Cheng, Wei; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Mou, Shaoliang; Liu, Zhiqin; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-01-01

    CaWRKY40 is a positive regulator of pepper (Capsicum annum) response to Ralstonia solanacearum inoculation (RSI), but the underlying mechanism remains largely unknown. Here, we functionally characterize CaCDPK15 in the defense signaling mediated by CaWRKY40. Pathogen-responsive TGA, W, and ERE boxes were identified in the CaCDPK15 promoter (pCaCDPK15), and pCaCDPK15-driven GUS expression was significantly enhanced in response to RSI and exogenously applied salicylic acid, methyl jasmonate, abscisic acid, and ethephon. Virus-induced gene silencing (VIGS) of CaCDPK15 significantly increased the susceptibility of pepper to RSI and downregulated the immunity-associated markers CaNPR1, CaPR1, and CaDEF1. By contrast, transient CaCDPK15 overexpression significantly activated hypersensitive response associated cell death, upregulated the immunity-associated marker genes, upregulated CaWRKY40 expression, and enriched CaWRKY40 at the promoters of its targets genes. Although CaCDPK15 failed to interact with CaWRKY40, the direct binding of CaWRKY40 to pCaCDPK15 was detected by chromatin immunoprecipitation, which was significantly potentiated by RSI in pepper plants. These combined results suggest that RSI in pepper induces CaCDPK15 and indirectly activates downstream CaWRKY40, which in turn potentiates CaCDPK15 expression. This positive-feedback loop would amplify defense signaling against RSI and efficiently activate strong plant immunity. PMID:26928570

  5. ATR controls cellular adaptation to hypoxia through positive regulation of hypoxia-inducible factor 1 (HIF-1) expression.

    Science.gov (United States)

    Fallone, F; Britton, S; Nieto, L; Salles, B; Muller, C

    2013-09-12

    Tumor cells adaptation to severe oxygen deprivation (hypoxia) plays a major role in tumor progression. The transcription factor HIF-1 (hypoxia-inducible factor 1), whose α-subunit is stabilized under hypoxic conditions is a key component of this process. Recent studies showed that two members of the phosphoinositide 3-kinase-related kinases (PIKKs) family, ATM (ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase), regulate the hypoxic-dependent accumulation of HIF-1. These proteins initiate cellular stress responses when DNA damage occurs. In addition, it has been demonstrated that extreme hypoxia induces a replicative stress resulting in regions of single-stranded DNA at stalled replication forks and the activation of ATR (ataxia telangiectasia and Rad3 related protein), another member of the PIKKs family. Here, we show that even less severe hypoxia (0.1% O2) also induces activation of ATR through replicative stress. Importantly, in using either transiently silenced ATR cells, cells expressing an inactive form of ATR or cells exposed to an ATR inhibitor (CGK733), we demonstrate that hypoxic ATR activation positively regulates the key transcription factor HIF-1 independently of the checkpoint kinase Chk1. We show that ATR kinase activity regulates HIF-1α at the translational level and we find that the elements necessary for the regulation of HIF-1α translation are located within the coding region of HIF-1α mRNA. Finally, by using three independent cellular models, we clearly show that the loss of ATR expression and/or kinase activity results in the decrease of HIF-1 DNA binding under hypoxia and consequently affects protein expression levels of two HIF-1 target genes, GLUT-1 and CAIX. Taken together, our data show a new function for ATR in cellular adaptation to hypoxia through regulation of HIF-1α translation. Our work offers new prospect for cancer therapy using ATR inhibitors with the potential to decrease cellular adaptation in hypoxic

  6. WEREWOLF, a MYB-related protein in Arabidopsis, is a position-dependent regulator of epidermal cell patterning.

    Science.gov (United States)

    Lee, M M; Schiefelbein, J

    1999-11-24

    The formation of the root epidermis of Arabidopsis provides a simple and elegant model for the analysis of cell patterning. A novel gene, WEREWOLF (WER), is described here that is required for position-dependent patterning of the epidermal cell types. The WER gene encodes a MYB-type protein and is preferentially expressed within cells destined to adopt the non-hair fate. Furthermore, WER is shown to regulate the position-dependent expression of the GLABRA2 homeobox gene, to interact with a bHLH protein, and to act in opposition to the CAPRICE MYB. These results suggest a simple model to explain the specification of the two root epidermal cell types, and they provide insight into the molecular mechanisms used to control cell patterning.

  7. Temporal response of positive and negative regulators in response to acute and chronic exercise training in mice.

    Science.gov (United States)

    Olenich, Sara A; Gutierrez-Reed, Navarre; Audet, Gerald N; Olfert, I Mark

    2013-10-15

    Angiogenesis is controlled by a balance between positive and negative angiogenic factors, but temporal protein expression of many key angiogenic regulators in response to exercise are still poorly defined. In C57BL/6 mice, we evaluated the temporal protein expression of several pro-angiogenic and anti-angiogenic factors in response to (1) a single acute bout of exercise and (2) chronic exercise training resulting from 3, 5, 7, 14 and 28 days of voluntary wheel running. Following acute exercise, protein levels of vascular endothelial growth factor-A (VEGF), endostatin and nucleolin were increased at 2-4 h (P responsiveness of VEGF to exercise in untrained mice (i.e. 161% increase, P angiogenesis is controlled by a balance between positive and negative mitogens, and reveals a complex, highly-coordinated, temporal scheme whereby these factors can differentially influence capillary growth in response to acute versus chronic exercise.

  8. CSR-1 RNAi pathway positively regulates histone expression in C. elegans.

    Science.gov (United States)

    Avgousti, Daphne C; Palani, Santhosh; Sherman, Yekaterina; Grishok, Alla

    2012-10-03

    Endogenous small interfering RNAs (endo-siRNAs) have been discovered in many organisms, including mammals. In C. elegans, depletion of germline-enriched endo-siRNAs found in complex with the CSR-1 Argonaute protein causes sterility and defects in chromosome segregation in early embryos. We discovered that knockdown of either csr-1, the RNA-dependent RNA polymerase (RdRP) ego-1, or the dicer-related helicase drh-3, leads to defects in histone mRNA processing, resulting in severe depletion of core histone proteins. The maturation of replication-dependent histone mRNAs, unlike that of other mRNAs, requires processing of their 3'UTRs through an endonucleolytic cleavage guided by the U7 snRNA, which is lacking in C. elegans. We found that CSR-1-bound antisense endo-siRNAs match histone mRNAs and mRNA precursors. Consistently, we demonstrate that CSR-1 directly binds to histone mRNA in an ego-1-dependent manner using biotinylated 2'-O-methyl RNA oligonucleotides. Moreover, we demonstrate that increasing the dosage of histone genes rescues the lethality associated with depletion of CSR-1 and EGO-1. These results support a positive and direct effect of RNAi on histone gene expression.

  9. Autocrine regulation of cell proliferation by estrogen receptor-alpha in estrogen receptor-alpha-positive breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Pan Zhongzong

    2009-01-01

    Full Text Available Abstract Background Estrogen receptor-α (ERα is essential for mammary gland development and is a major oncogene in breast cancer. Since ERα is not colocalized with the cell proliferation marker Ki-67 in the normal mammary glands and the majority of primary breast tumors, it is generally believed that paracrine regulation is involved in ERα mediated cell proliferation. In the paracrine model, ERα-positive cells don't proliferate but will release some paracrine growth factors to stimulate the neighboring cells to proliferate. In a subpopulation of cancer cells in some primary breast tumors, however, ERα does colocalize with the cell proliferation marker Ki-67, suggesting an autocrine regulation by ERα in some primary breast tumors. Methods Colocalization of ERα with Ki-67 in ERα-positive breast cancer cell lines (MCF-7, T47D, and ZR75-1 was evaluated by immunofluorescent staining. Cell cycle phase dependent expression of ERα was determined by co-immunofluorescent staining of ERα and the major cyclins (D, E, A, B, and by flow cytometry analysis of ERαhigh cells. To further confirm the autocrine action of ERα, MCF-7 cells were growth arrested by ICI182780 treatment, followed by treatment with EGFR inhibitor, before estrogen stimulation and analyses for colocalization of Ki-67 and ERα and cell cycle progression. Results Colocalization of ERα with Ki-67 was present in all three ERα-positive breast cancer cell lines. Unlike that in the normal mammary glands and the majority of primary breast tumors, ERα is highly expressed throughout the cell cycle in MCF-7 cells. Without E2 stimulation, MCF-7 cells released from ICI182780 treatment remain at G1 phase. E2 stimulation of ICI182780 treated cells, however, promotes the expression and colocalization of ERα and Ki-67 as well as the cell cycle progressing through the S and G2/M phases. Inhibition of EGFR signaling does not inhibit the autocrine action of ERα. Conclusion Our data indicate

  10. Counterbalancing Regulation in Response Memory of a Positively Autoregulated Two-Component System.

    Science.gov (United States)

    Gao, Rong; Godfrey, Katherine A; Sufian, Mahir A; Stock, Ann M

    2017-09-15

    Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus conditions. The ability to memorize the past event and use the "memory" to make adjustments to current behaviors can lead to a more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carryover of the response proteins to facilitate the recurrent response, but the additional accumulation of response proteins can lead to a deviation from response homeostasis. We used the Escherichia coli PhoB/PhoR two-component system (TCS) as a model system to study how cells cope with the recurrence of environmental phosphate (Pi) starvation conditions. We discovered that "memory" of prior Pi starvation can exert distinct effects through two regulatory pathways, the TCS signaling pathway and the stress response pathway. Although carryover of TCS proteins can lead to higher initial levels of transcription factor PhoB and a faster initial response in prestarved cells than in cells not starved, the response enhancement can be overcome by an earlier and greater repression of promoter activity in prestarved cells due to the memory of the stress response. The repression counterbalances the carryover of the response proteins, leading to a homeostatic response whether or not cells are prestimulated. A computational model based on sigma factor competition was developed to understand the memory of stress response and to predict the homeostasis of other PhoB-regulated response proteins. Our insight into the history-dependent PhoBR response may provide a general understanding of how TCSs respond to recurring stimuli and adapt to fluctuating environmental conditions. IMPORTANCE Bacterial cells in their natural environments experience scenarios that are far more complex than are typically replicated in laboratory experiments. The architectures of signaling systems and the integration of multiple adaptive pathways have evolved to deal with such complexity

  11. CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth.

    Science.gov (United States)

    Zhou, Linli; Yang, Kun; Carpenter, April; Lang, Richard A; Andl, Thomas; Zhang, Yuhang

    2016-10-01

    Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  12. Licensing of safety critical software for nuclear reactors. Common position of seven European nuclear regulators and authorised technical support organisations

    International Nuclear Information System (INIS)

    2010-01-01

    It is widely accepted that the assessment of software cannot be limited to verification and testing of the end product, i.e. the computer code. Other factors such as the quality of the processes and methods for specifying, designing and coding have an important impact on the implementation. Existing standards provide limited guidance on the regulatory and safety assessment of these factors. An undesirable consequence of this situation is that the licensing approaches taken by nuclear safety authorities and by technical support organisations are determined independently with only limited informal technical co-ordination and information exchange. It is notable that several software implementations of nuclear safety systems have been marred by costly delays caused by difficulties in co-ordinating the development and qualification process. It was thus felt necessary to compare the respective licensing approaches, to identify where a consensus already exists, and to see how greater consistency and more mutual acceptance could be introduced into current practices. This report is the result of the work of a group of regulator and safety authorities' experts. The 2007 version was completed at the invitation of the Western European Nuclear Regulators' Association (WENRA). The major result of the work is the identification of consensus and common technical positions on a set of important licensing issues raised by the design and operation of computer based systems used in nuclear power plants for the implementation of safety functions. The purpose is to introduce greater consistency and more mutual acceptance into current practices. To achieve these common positions, detailed consideration was paid to the licensing approaches followed in the different countries represented by the experts of the task force. The report is intended to be useful: - to coordinate regulators' and safety experts' technical viewpoints in the design of regulators' national policies and in revisions

  13. A super-family of transcriptional activators regulates bacteriophage packaging and lysis in Gram-positive bacteria

    Science.gov (United States)

    Quiles-Puchalt, Nuria; Tormo-Más, María Ángeles; Campoy, Susana; Toledo-Arana, Alejandro; Monedero, Vicente; Lasa, Íñigo; Novick, Richard P.; Christie, Gail E.; Penadés, José R.

    2013-01-01

    The propagation of bacteriophages and other mobile genetic elements requires exploitation of the phage mechanisms involved in virion assembly and DNA packaging. Here, we identified and characterized four different families of phage-encoded proteins that function as activators required for transcription of the late operons (morphogenetic and lysis genes) in a large group of phages infecting Gram-positive bacteria. These regulators constitute a super-family of proteins, here named late transcriptional regulators (Ltr), which share common structural, biochemical and functional characteristics and are unique to this group of phages. They are all small basic proteins, encoded by genes present at the end of the early gene cluster in their respective phage genomes and expressed under cI repressor control. To control expression of the late operon, the Ltr proteins bind to a DNA repeat region situated upstream of the terS gene, activating its transcription. This involves the C-terminal part of the Ltr proteins, which control specificity for the DNA repeat region. Finally, we show that the Ltr proteins are the only phage-encoded proteins required for the activation of the packaging and lysis modules. In summary, we provide evidence that phage packaging and lysis is a conserved mechanism in Siphoviridae infecting a wide variety of Gram-positive bacteria. PMID:23771138

  14. CytR Is a Global Positive Regulator of Competence, Type VI Secretion, and Chitinases in Vibrio cholerae

    Science.gov (United States)

    Hammer, Brian K.

    2015-01-01

    The facultative pathogen Vibrio cholerae transitions between its human host and aquatic reservoirs where it colonizes chitinous surfaces. Growth on chitin induces expression of chitin utilization genes, genes involved in DNA uptake by natural transformation, and a type VI secretion system that allows contact-dependent killing of neighboring bacteria. We have previously shown that the transcription factor CytR, thought to primarily regulate the pyrimidine nucleoside scavenging response, is required for natural competence in V. cholerae. Through high-throughput RNA sequencing (RNA-seq), we show that CytR positively regulates the majority of competence genes, the three type VI secretion operons, and the four known or predicted chitinases. We used transcriptional reporters and phenotypic analysis to determine the individual contributions of quorum sensing, which is controlled by the transcription factors HapR and QstR; chitin utilization that is mediated by TfoX; and pyrimidine starvation that is orchestrated by CytR, toward each of these processes. We find that in V. cholerae, CytR is a global regulator of multiple behaviors affecting fitness and adaptability in the environment. PMID:26401962

  15. Type I NKT-cell-mediated TNF-α is a positive regulator of NLRP3 inflammasome priming.

    Science.gov (United States)

    Chow, Melvyn T; Duret, Helene; Andrews, Daniel M; Faveeuw, Christelle; Möller, Andreas; Smyth, Mark J; Paget, Christophe

    2014-07-01

    The NLRP3 inflammasome plays a crucial role in the innate immune response to pathogens and exogenous or endogenous danger signals. Its activity must be precisely and tightly regulated to generate tailored immune responses. However, the immune cell subsets and cytokines controlling NLRP3 inflammasome activity are still poorly understood. Here, we have shown a link between NKT-cell-mediated TNF-α and NLRP3 inflammasome activity. The NLRP3 inflammasome in APCs was critical to potentiate NKT-cell-mediated immune responses, since C57BL/6 NLRP3 inflammasome-deficient mice exhibited reduced responsiveness to α-galactosylceramide. Importantly, NKT cells were found to act as regulators of NLRP3 inflammasome signaling, as NKT-cell-derived TNF-α was required for optimal IL-1β and IL-18 production by myeloid cells in response to α-galactosylceramide, by acting on the NLRP3 inflammasome priming step. Thus, NKT cells play a role in the positive regulation of NLRP3 inflammasome priming by mediating the production of TNF-α, thus demonstrating another means by which NKT cells control early inflammation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Regulatory RNAs in Bacillus subtilis: a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression

    Science.gov (United States)

    Mars, Ruben A. T.; Nicolas, Pierre; Denham, Emma L.

    2016-01-01

    SUMMARY Bacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules include trans-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5′ untranslated region. Thus far, most regulatory RNA research has focused on Gram-negative bacteria, such as Escherichia coli and Salmonella. Hence, there is uncertainty about whether the resulting insights can be extrapolated directly to other bacteria, such as the Gram-positive soil bacterium Bacillus subtilis. A recent study identified 1,583 putative regulatory RNAs in B. subtilis, whose expression was assessed across 104 conditions. Here, we review the current understanding of RNA-based regulation in B. subtilis, and we categorize the newly identified putative regulatory RNAs on the basis of their conservation in other bacilli and the stability of their predicted secondary structures. Our present evaluation of the publicly available data indicates that RNA-mediated gene regulation in B. subtilis mostly involves elements at the 5′ ends of mRNA molecules. These can include 5′ secondary structure elements and metabolite-, tRNA-, or protein-binding sites. Importantly, sense-independent segments are identified as the most conserved and structured potential regulatory RNAs in B. subtilis. Altogether, the present survey provides many leads for the identification of new regulatory RNA functions in B. subtilis. PMID:27784798

  17. The late positive potential predicts emotion regulation strategy use in school-aged children concurrently and two years later.

    Science.gov (United States)

    Babkirk, Sarah; Rios, Victor; Dennis, Tracy A

    2015-09-01

    The ability to use cognitive emotion regulation strategies such as reappraisal may be a core component of emotional competence across development, but due to methodological challenges in measuring such strategies, they are rarely studied in young children. One neurophysiological measure, the late positive potential (LPP), has been examined in response to reappraisal as a potential neurosignature for emotion regulatory capacity in adults. The association between the LPP and emotion regulatory capacity in children is unknown. The present study examined whether the LPP during reappraisal could predict greater observed adaptive emotion regulation strategy use in school-aged children over a two-year period. Thirty-two 5- to 7-year-olds participated in two identical lab visits spaced two years apart. EEG was continuously recorded during a computerized reappraisal task in which children viewed unpleasant images paired with either reappraisal or negative stories. Next they completed a disappointing and a frustrating task during which emotion regulation strategies were observed. As predicted, children who showed reappraisal-induced reductions in the LPP at the first assessment used significantly more adaptive ER strategies concurrently and two years later. These findings provide observation-based evidence that the LPP may be a viable neurosignature for emotion regulatory capacity in children. © 2014 John Wiley & Sons Ltd.

  18. Tomato NAC transcription factor SlSRN1 positively regulates defense response against biotic stress but negatively regulates abiotic stress response.

    Directory of Open Access Journals (Sweden)

    Bo Liu

    Full Text Available Biotic and abiotic stresses are major unfavorable factors that affect crop productivity worldwide. NAC proteins comprise a large family of transcription factors that play important roles in plant growth and development as well as in responses to biotic and abiotic stresses. In a virus-induced gene silencing-based screening to identify genes that are involved in defense response against Botrytis cinerea, we identified a tomato NAC gene SlSRN1 (Solanum lycopersicum Stress-related NAC1. SlSRN1 is a plasma membrane-localized protein with transactivation activity in yeast. Expression of SlSRN1 was significantly induced by infection with B. cinerea or Pseudomonas syringae pv. tomato (Pst DC3000, leading to 6-8 folds higher than that in the mock-inoculated plants. Expression of SlSRN1 was also induced by salicylic acid, jasmonic acid and 1-amino cyclopropane-1-carboxylic acid and by drought stress. Silencing of SlSRN1 resulted in increased severity of diseases caused by B. cinerea and Pst DC3000. However, silencing of SlSRN1 resulted in increased tolerance against oxidative and drought stresses. Furthermore, silencing of SlSRN1 accelerated accumulation of reactive oxygen species but attenuated expression of defense genes after infection by B. cinerea. Our results demonstrate that SlSRN1 is a positive regulator of defense response against B. cinerea and Pst DC3000 but is a negative regulator for oxidative and drought stress response in tomato.

  19. Tomato NAC transcription factor SlSRN1 positively regulates defense response against biotic stress but negatively regulates abiotic stress response.

    Science.gov (United States)

    Liu, Bo; Ouyang, Zhigang; Zhang, Yafen; Li, Xiaohui; Hong, Yongbo; Huang, Lei; Liu, Shixia; Zhang, Huijuan; Li, Dayong; Song, Fengming

    2014-01-01

    Biotic and abiotic stresses are major unfavorable factors that affect crop productivity worldwide. NAC proteins comprise a large family of transcription factors that play important roles in plant growth and development as well as in responses to biotic and abiotic stresses. In a virus-induced gene silencing-based screening to identify genes that are involved in defense response against Botrytis cinerea, we identified a tomato NAC gene SlSRN1 (Solanum lycopersicum Stress-related NAC1). SlSRN1 is a plasma membrane-localized protein with transactivation activity in yeast. Expression of SlSRN1 was significantly induced by infection with B. cinerea or Pseudomonas syringae pv. tomato (Pst) DC3000, leading to 6-8 folds higher than that in the mock-inoculated plants. Expression of SlSRN1 was also induced by salicylic acid, jasmonic acid and 1-amino cyclopropane-1-carboxylic acid and by drought stress. Silencing of SlSRN1 resulted in increased severity of diseases caused by B. cinerea and Pst DC3000. However, silencing of SlSRN1 resulted in increased tolerance against oxidative and drought stresses. Furthermore, silencing of SlSRN1 accelerated accumulation of reactive oxygen species but attenuated expression of defense genes after infection by B. cinerea. Our results demonstrate that SlSRN1 is a positive regulator of defense response against B. cinerea and Pst DC3000 but is a negative regulator for oxidative and drought stress response in tomato.

  20. Positive regulation of DNA double strand break repair activity during differentiation of long life span cells: the example of adipogenesis.

    Directory of Open Access Journals (Sweden)

    Aline Meulle

    Full Text Available Little information is available on the ability of terminally differentiated cells to efficiently repair DNA double strand breaks (DSBs, and one might reasonably speculate that efficient DNA repair of these threatening DNA lesions, is needed in cells of long life span with no or limited regeneration from precursor. Few tissues are available besides neurons that allow the study of DNA DSBs repair activity in very long-lived cells. Adipocytes represent a suitable model since it is generally admitted that there is a very slow turnover of adipocytes in adult. Using both Pulse Field Gel Electrophoresis (PFGE and the disappearance of the phosphorylated form of the histone variant H2AX, we demonstrated that the ability to repair DSBs is increased during adipocyte differentiation using the murine pre-adipocyte cell line, 3T3F442A. In mammalian cells, DSBs are mainly repaired by the non-homologous end-joining pathway (NHEJ that relies on the DNA dependent protein kinase (DNA-PK activity. During the first 24 h following the commitment into adipogenesis, we show an increase in the expression and activity of the catalytic sub-unit of the DNA-PK complex, DNA-PKcs. The increased in DNA DSBs repair activity observed in adipocytes was due to the increase in DNA-PK activity as shown by the use of DNA-PK inhibitor or sub-clones of 3T3F442A deficient in DNA-PKcs using long term RNA interference. Interestingly, the up-regulation of DNA-PK does not regulate the differentiation program itself. Finally, similar positive regulation of DNA-PKcs expression and activity was observed during differentiation of primary culture of pre-adipocytes isolated from human sub-cutaneous adipose tissue. Our results show that DNA DSBs repair activity is up regulated during the early commitment into adipogenesis due to an up-regulation of DNA-PK expression and activity. In opposition to the general view that DNA DSBs repair is decreased during differentiation, our results demonstrate

  1. Testing the mindfulness-to-meaning theory: Evidence for mindful positive emotion regulation from a reanalysis of longitudinal data.

    Directory of Open Access Journals (Sweden)

    Eric L Garland

    Full Text Available The Mindfulness to Meaning Theory (MMT provides a detailed process model of mindful positive emotion regulation.We conducted a post-hoc reanalysis of longitudinal data (N = 107 derived from a RCT of mindfulness-based stress reduction (MBSR versus cognitive-behavioral therapy (CBT for social anxiety disorder to model the core constructs of the MMT (attentional control, decentering, broadened awareness, reappraisal, and positive affect in a multivariate path analysis.Findings indicated that increases in attentional control from baseline to post-training predicted increases in decentering by 3 months post-treatment (p<.01 that in turn predicted increases in broadened awareness of interoceptive and exteroceptive data by 6 months post-treatment (p<.001. In turn, broadened awareness predicted increases in the use of reappraisal by 9 months post-treatment (p<.01, which culminated in greater positive affect at 12 months post-treatment (p<.001. MBSR led to significantly greater increases in decentering (p<.05 and broadened awareness than CBT (p<.05. Significant indirect effects indicated that increases in decentering mediated the effect of mindfulness training on broadening awareness, which in turn mediated enhanced reappraisal efficacy.Results suggest that the mechanisms of change identified by the MMT form an iterative chain that promotes long-term increases in positive affectivity. Though these mechanisms may reflect common therapeutic factors that cut across mindfulness-based and cognitive-behavioral interventions, MBSR specifically boosts the MMT cycle by producing significantly greater increases in decentering and broadened awareness than CBT, providing support for the foundational assumption in the MMT that mindfulness training may be a key means of stimulating downstream positive psychological processes.

  2. Licensing of safety critical software for nuclear reactors. Common position of seven European nuclear regulators and authorised technical support organisations

    International Nuclear Information System (INIS)

    2007-01-01

    The major result of the work is the identification of consensus and common technical positions on a set of important licensing issues raised by the design and operation of computer-based systems used in Nuclear Power Plants for safety functions. The purpose is to introduce greater consistency and more mutual acceptance into current practices. To achieve these common positions, detailed consideration was paid to the licensing approaches followed in the different countries represented by the experts of the task force. The report is intended to be useful: - to coordinate regulators' and safety experts' technical viewpoints in the design of regulators' national policies and in revisions of guidelines; - as a reference in safety cases and demonstrations of safety of software based systems; - as guidance for system design specifications by manufacturers and major I and C suppliers on the international market. The task force decided at an early stage to focus attention on computer based systems used in Nuclear Power Plants for the implementation of safety functions; namely, those systems classified by the IAEA as 'Safety Systems'. Therefore, recommendations of this report - except those of chapter 1.11 - primarily address 'safety systems' and not 'safety related systems'. It was felt that the most difficult aspects of the licensing of digital programmable systems are rooted in the specific properties of the technology. The objective was therefore to delineate practical and technical licensing guidance, rather than discussing or proposing basic principles or requirements. The design requirements and the basic principles of nuclear safety in force in each member state are assumed to remain applicable. This report represents the consensus view achieved by the experts who contributed to the task force. It is the result of what was at the time of its initiation a first attempt at the international level to achieve consensus among nuclear regulators on practical methods for

  3. Ionized calcium-binding adaptor molecule 1 positive macrophages and HO-1 up-regulation in intestinal muscularis resident macrophages

    DEFF Research Database (Denmark)

    Mikkelsen, Hanne B; Huizinga, Jan D; Larsen, Jytte O

    2017-01-01

    Small intestinal muscularis externa macrophages have been associated with interstitial cells of Cajal (ICC). They have been proposed to play various roles in motility disorders and to take part in a microbiota-driven regulation of gastrointestinal motility. Our objective was to understand...... the reaction of resident macrophages of the musculature to a pro-inflammatory stimulator, lipopolysaccharide (LPS). Mice were injected with LPS or saline and sacrificed after 6 hours. Whole mounts were stained with antibodies toward CD169, ionized calcium-binding adaptor molecule 1 (iba1) (microglial/macrophage...... marker) and heme oxygenase-1 (HO-1). Cell densities were measured using unbiased stereology. RESULTS: iba1(pos) cells showed an overall higher density than CD169(pos) and HO-1(pos) cells. Most HO-1(pos) and iba1(pos) cells were positive for CD 169 in serosa and at Auerbach's plexus (AP). At the deep...

  4. miR-21-3p is a positive regulator of L1CAM in several human carcinomas.

    Science.gov (United States)

    Doberstein, Kai; Bretz, Niko P; Schirmer, Uwe; Fiegl, Heidi; Blaheta, Roman; Breunig, Christian; Müller-Holzner, Elisabeth; Reimer, Dan; Zeimet, Alain G; Altevogt, Peter

    2014-11-28

    Expression of L1 cell adhesion molecule (L1CAM) occurs frequently in human cancers and is associated with poor prognosis in cancers such as ovarian, endometrial, breast, renal cell carcinoma and pancreatic ductal adenocarcinoma. L1CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1CAM in cancers is of considerable importance. Transcription factors such as SLUG, β-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1CAM in various types of cancers. There is increasing evidence that micro-RNAs can also have strong effects on gene expression. Here we have identified miR-21-3p as a positive regulator of L1CAM expression. Over-expression of miR-21-3p (miR-21*) but not the complementary sequence miR-21-5p (miR-21) could strongly augment L1CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1CAM and miR-21-3p expressions. Although L1CAM alone was a reliable marker for overall and disease free survival, the combination of L1CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. NF90 Binds the Dengue Virus RNA 3′ Terminus and Is a Positive Regulator of Dengue Virus Replication

    Science.gov (United States)

    Gehrke, Lee

    2011-01-01

    Background Viral RNA translation and replication are regulated by sequence and structural elements in the 5′ and 3′ untranslated regions (UTR) and by host cell and/or viral proteins that bind them. Dengue virus has a single-stranded RNA genome with positive polarity, a 5′ m7GpppG cap, and a conserved 3′-terminal stem loop (SL) that is linked to proposed functions in viral RNA transcription and translation. Mechanisms explaining the contributions of host proteins to viral RNA translation and replication are poorly defined, yet understanding host protein-viral RNA interactions may identify new targets for therapeutic intervention. This study was directed at identifying functionally significant host proteins that bind the conserved dengue virus RNA 3′ terminus. Methodology/Principal Findings Proteins eluted from a dengue 3′ SL RNA affinity column at increasing ionic strength included two with double-strand RNA binding motifs (NF90/DRBP76 and DEAH box polypeptide 9/RNA helicase A (RHA)), in addition to NF45, which forms a heterodimer with NF90. Although detectable NF90 and RHA proteins localized to the nucleus of uninfected cells, immunofluorescence revealed cytoplasmic NF90 in dengue virus-infected cells, leading us to hypothesize that NF90 has a functional role(s) in dengue infections. Cells depleted of NF90 were used to quantify viral RNA transcript levels and production of infectious dengue virus. NF90 depletion was accompanied by a 50%-70% decrease in dengue RNA levels and in production of infectious viral progeny. Conclusions/Significance The results indicate that NF90 interacts with the 3′ SL structure of the dengue RNA and is a positive regulator of dengue virus replication. NF90 depletion diminished the production of infectious dengue virus by more than 50%, which may have important significance for identifying therapeutic targets to limit a virus that threatens more than a billion people worldwide. PMID:21386893

  6. Overexpression of GbWRKY1 positively regulates the Pi starvation response by alteration of auxin sensitivity in Arabidopsis.

    Science.gov (United States)

    Xu, Li; Jin, Li; Long, Lu; Liu, Linlin; He, Xin; Gao, Wei; Zhu, Longfu; Zhang, Xianlong

    2012-12-01

    Overexpression of a cotton defense-related gene GbWRKY1 in Arabidopsis resulted in modification of the root system by enhanced auxin sensitivity to positively regulate the Pi starvation response. GbWRKY1 was a cloned WRKY transcription factor from Gossypium barbadense, which was firstly identified as a defense-related gene and showed moderate similarity with AtWRKY75 from Arabidopsis thaliana. Overexpression of GbWRKY1 in Arabidopsis resulted in attenuated Pi starvation stress symptoms, including reduced accumulation of anthocyanin and impaired density of lateral roots (LR) in low Pi stress. The study also indicated that overexpression of GbWRKY1 caused plants constitutively exhibited Pi starvation response including increased development of LR, relatively high level of total P and Pi, high expression level of some high-affinity Pi transporters and phosphatases as well as enhanced accumulation of acid phosphatases activity during Pi-sufficient. It was speculated that GbWRKY1 may act as a positive regulator in the Pi starvation response as well as AtWRKY75. GbWRKY1 probably involves in the modulation of Pi homeostasis and participates in the Pi allocation and remobilization but do not accumulate more Pi in Pi-deficient condition, which was different from the fact that AtWRKY75 influenced the Pi status of the plant during Pi deprivation by increasing root surface area and accumulation of more Pi. Otherwise, further study suggested that the overexpression plants were more sensitive to auxin than wild-type and GbWRKY1 may partly influence the LPR1-dependent (low phosphate response 1) Pi starvation signaling pathway and was putatively independent of SUMO E3 ligase SIZ1 and PHR1 (phosphate starvation response 1) in response to Pi starvation.

  7. Arabidopsis AtERF15 positively regulates immunity against Pseudomonas syringae pv. tomato DC3000 and Botrytis cinerea

    Directory of Open Access Journals (Sweden)

    Huijuan eZhang

    2015-09-01

    Full Text Available Upon pathogen infection, activation of immune response requires effective transcriptional reprogramming that regulates inducible expression of a large set of defense genes. A number of ethylene-responsive factor transcription factors have been shown to play critical roles in regulating immune responses in plants. In the present study, we explored the functions of Arabidopsis AtERF15 in immune responses against Pseudomonas syringae pv. tomato (Pst DC3000, a (hemibiotrophic bacterial pathogen, and Botrytis cinerea, a necrotrophic fungal pathogen. Expression of AtERF15 was induced by infection of Pst DC3000 and B. cinerea and by treatments with salicylic acid (SA and methyl jasmonate. Biochemical assays demonstrated that AtERF15 is a nucleus-localized transcription activator. The AtERF15-overexpressing (AtERF15-OE plants displayed enhanced resistance while the AtERF15-RNAi plants exhibited decreased resistance against Pst DC3000 and B. cinerea. Meanwhile, Pst DC3000- or B. cinerea-induced expression of defense genes was upregulated in AtERF15-OE plants but downregulated in AtERF15-RNAi plants, as compared to the expression in wild type plants. In response to infection with B. cinerea, the AtERF15-OE plants accumulated less reactive oxygen species (ROS while the AtERF15-RNAi plants accumulated more ROS. The flg22- and chitin-induced oxidative burst was abolished and expression levels of the pattern-triggered immunity-responsive genes AtFRK1 and AtWRKY53 were suppressed in AtER15-RNAi plants upon treatment with flg22 or chitin. Furthermore, SA-induced defense response was also partially impaired in the AtERF15-RNAi plants. These data demonstrate that AtERF15 is a positive regulator of multiple layers of the immune responses in Arabidopsis.

  8. Expression of Death Receptor 4 Is Positively Regulated by MEK/ERK/AP-1 Signaling and Suppressed upon MEK Inhibition*

    Science.gov (United States)

    Yao, Weilong; Oh, You-Take; Deng, Jiusheng; Yue, Ping; Deng, Liang; Huang, Henry; Zhou, Wei; Sun, Shi-Yong

    2016-01-01

    Death receptor 4 (DR4) is a cell surface receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and triggers apoptosis upon ligation with TRAIL or aggregation. MEK/ERK signaling is a well known and the best-studied effector pathway downstream of Ras and Raf. This study focuses on determining the impact of pharmacological MEK inhibition on DR4 expression and elucidating the underlying mechanism. We found that several MEK inhibitors including MEK162, AZD6244, and PD0325901 effectively decreased DR4 protein levels including cell surface DR4 in different cancer cell lines. Accordingly, pre-treatment of TRAIL-sensitive cancer cell lines with a MEK inhibitor desensitized them to TRAIL-induced apoptosis. These results indicate that MEK inhibition negatively regulates DR4 expression and cell response to TRAIL-induced apoptosis. MEK inhibitors did not alter DR4 protein stability, rather decreased its mRNA levels, suggesting a transcriptional regulation. In contrast, enforced activation of MEK/ERK signaling by expressing ectopic B-Raf (V600E) or constitutively activated MEK1 (MEK1-CA) or MEK2 (MEK2-CA) activated ERK and increased DR4 expression; these effects were inhibited when a MEK inhibitor was present. Promoter analysis through deletion and mutation identified the AP-1 binding site as an essential response element for enhancing DR4 transactivation by MEK1-CA. Furthermore, inhibition of AP-1 by c-Jun knockdown abrogated the ability of MEK1-CA to increase DR4 promoter activity and DR4 expression. These results suggest an essential role of AP-1 in mediating MEK/ERK activation-induced DR4 expression. Our findings together highlight a previously undiscovered mechanism that positively regulates DR4 expression through activation of the MEK/ERK/AP-1 signaling pathway. PMID:27576686

  9. Characterisation of SalRAB a salicylic acid inducible positively regulated efflux system of Rhizobium leguminosarum bv viciae 3841.

    Directory of Open Access Journals (Sweden)

    Adrian J Tett

    Full Text Available Salicylic acid is an important signalling molecule in plant-microbe defence and symbiosis. We analysed the transcriptional responses of the nitrogen fixing plant symbiont, Rhizobium leguminosarum bv viciae 3841 to salicylic acid. Two MFS-type multicomponent efflux systems were induced in response to salicylic acid, rmrAB and the hitherto undescribed system salRAB. Based on sequence similarity salA and salB encode a membrane fusion and inner membrane protein respectively. salAB are positively regulated by the LysR regulator SalR. Disruption of salA significantly increased the sensitivity of the mutant to salicylic acid, while disruption of rmrA did not. A salA/rmrA double mutation did not have increased sensitivity relative to the salA mutant. Pea plants nodulated by salA or rmrA strains did not have altered nodule number or nitrogen fixation rates, consistent with weak expression of salA in the rhizosphere and in nodule bacteria. However, BLAST analysis revealed seventeen putative efflux systems in Rlv3841 and several of these were highly differentially expressed during rhizosphere colonisation, host infection and bacteroid differentiation. This suggests they have an integral role in symbiosis with host plants.

  10. β-Catenin Is a Positive Regulator of Estrogen Receptor-α Function in Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Nibedita; Schmitt, Fee; Grebhardt, Sina; Mayer, Doris, E-mail: d.mayer@dkfz.de [Hormones and Signal Transduction Group, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg (Germany)

    2011-07-22

    Estrogen receptor-alpha (ERα) is a key factor in the development of breast cancer in humans. The expression and activity of ERα is regulated by a multitude of intracellular and extracellular signals. Here we show a cross-talk between β-catenin and ERα in human breast cancer cells. Knockdown of β-catenin by RNAi resulted in significant reduction of ERα mRNA and/or protein levels in MCF-7, T-47D, and BT-474 breast cancer cells and in significant reduction of estradiol-induced expression of the ERα target genes pS2 and GREB1. In addition β-catenin silencing resulted in significant decrease of growth of MCF-7 cells both in the absence and presence of estradiol. β-catenin and ERα could not be co-immunoprecipitated by ERα antibodies from lysates of E2-treated or untreated cells suggesting lack of direct physical interaction. It is concluded that β-catenin is a positive regulator of ERα mRNA and protein expression.

  11. The Cotton WRKY Gene GhWRKY41 Positively Regulates Salt and Drought Stress Tolerance in Transgenic Nicotiana benthamiana.

    Directory of Open Access Journals (Sweden)

    Xiaoqian Chu

    Full Text Available WRKY transcription factors constitute a very large family of proteins in plants and participate in modulating plant biological processes, such as growth, development and stress responses. However, the exact roles of WRKY proteins are unclear, particularly in non-model plants. In this study, Gossypium hirsutum WRKY41 (GhWRKY41 was isolated and transformed into Nicotiana benthamiana. Our results showed that overexpression of GhWRKY41 enhanced the drought and salt stress tolerance of transgenic Nicotiana benthamiana. The transgenic plants exhibited lower malondialdehyde content and higher antioxidant enzyme activity, and the expression of antioxidant genes was upregulated in transgenic plants exposed to osmotic stress. A β-glucuronidase (GUS staining assay showed that GhWRKY41 was highly expressed in the stomata when plants were exposed to osmotic stress, and plants overexpressing GhWRKY41 exhibited enhanced stomatal closure when they were exposed to osmotic stress. Taken together, our findings demonstrate that GhWRKY41 may enhance plant tolerance to stress by functioning as a positive regulator of stoma closure and by regulating reactive oxygen species (ROS scavenging and the expression of antioxidant genes.

  12. Expression of the alaE gene is positively regulated by the global regulator Lrp in response to intracellular accumulation of l-alanine in Escherichia coli.

    Science.gov (United States)

    Ihara, Kohei; Sato, Kazuki; Hori, Hatsuhiro; Makino, Yumiko; Shigenobu, Shuji; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2017-04-01

    The alaE gene in Escherichia coli encodes an l-alanine exporter that catalyzes the active export of l-alanine using proton electrochemical potential. In our previous study, alaE expression was shown to increase in the presence of l-alanyl-l-alanine (Ala-Ala). In this study, the global regulator leucine-responsive regulatory protein (Lrp) was identified as an activator of the alaE gene. A promoter less β-galactosidase gene was fused to an alaE upstream region (240 nucleotides). Cells that were lacZ-deficient and harbored this reporter plasmid showed significant induction of β-galactosidase activity (approximately 17-fold) in the presence of 6 mM l-alanine, l-leucine, and Ala-Ala. However, a reporter plasmid possessing a smaller alaE upstream region (180 nucleotides) yielded transformants with strikingly low enzyme activity under the same conditions. In contrast, lrp-deficient cells showed almost no β-galactosidase induction, indicating that Lrp positively regulates alaE expression. We next performed an electrophoretic mobility shift assay (EMSA) and a DNase I footprinting assay using purified hexahistidine-tagged Lrp (Lrp-His). Consequently, we found that Lrp-His binds to the alaE upstream region spanning nucleotide -161 to -83 with a physiologically relevant affinity (apparent K D , 288.7 ± 83.8 nM). Furthermore, the binding affinity of Lrp-His toward its cis-element was increased by l-alanine and l-leucine, but not by Ala-Ala and d-alanine. Based on these results, we concluded that the gene expression of the alaE is regulated by Lrp in response to intracellular levels of l-alanine, which eventually leads to intracellular homeostasis of l-alanine concentrations. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  13. A robot-assisted study of intrinsic muscle regulation on proximal interphalangeal joint stiffness by varying metacarpophalangeal joint position.

    Science.gov (United States)

    Li, Zong-Ming; Davis, Gregg; Gustafson, Norm P; Goitz, Robert J

    2006-03-01

    The tightness of intrinsic hand muscles is a common cause of finger joint stiffness. The purposes of this study were to develop a robot-assisted methodology to obtain torque-angle data of a finger joint, and to investigate the regulation of the intrinsic muscles on finger joint stiffness. Our robot system features the integration of a low payload robot arm, a controller, and a force/torque transducer. The system provided highly reproducible torque-angle curves. Torque-angle data of the proximal interphalangeal joint with the metacarpophalangeal joint at 0 and 60 degrees were obtained from eight asymptomatic hands. The torque-angle curve shifted with the position of the metacarpophalangeal joint. As the metacarpophalangeal joint flexion angle changed from 60 to 0 degrees, the equilibrium of the proximal interphalangeal joint increased more than 20 degrees, and joint stiffness increased more than 50%. The dependence of the stiffness of the proximal interphalangeal joint on metacarpophalangeal joint position supports the regulatory role of the intrinsic muscles on finger joint mechanics. This regulatory mechanics is likely amplified in hands with intrinsic muscle tightness, justifying the commonly used Bunnell Intrinsic Tightness Test. Copyright 2005 Orthopaedic Research Society.

  14. mTORC1 Is a Local, Postsynaptic Voltage Sensor Regulated by Positive and Negative Feedback Pathways

    Directory of Open Access Journals (Sweden)

    Farr Niere

    2017-05-01

    Full Text Available The mammalian/mechanistic target of rapamycin complex 1 (mTORC1 serves as a regulator of mRNA translation. Recent studies suggest that mTORC1 may also serve as a local, voltage sensor in the postsynaptic region of neurons. Considering biochemical, bioinformatics and imaging data, we hypothesize that the activity state of mTORC1 dynamically regulates local membrane potential by promoting and repressing protein synthesis of select mRNAs. Our hypothesis suggests that mTORC1 uses positive and negative feedback pathways, in a branch-specific manner, to maintain neuronal excitability within an optimal range. In some dendritic branches, mTORC1 activity oscillates between the “On” and “Off” states. We define this as negative feedback. In contrast, positive feedback is defined as the pathway that leads to a prolonged depolarized or hyperpolarized resting membrane potential, whereby mTORC1 activity is constitutively on or off, respectively. We propose that inactivation of mTORC1 increases the expression of voltage-gated potassium alpha (Kv1.1 and 1.2 and beta (Kvβ2 subunits, ensuring that the membrane resets to its resting membrane potential after experiencing increased synaptic activity. In turn, reduced mTORC1 activity increases the protein expression of syntaxin-1A and promotes the surface expression of the ionotropic glutamate receptor N-methyl-D-aspartate (NMDA-type subunit 1 (GluN1 that facilitates increased calcium entry to turn mTORC1 back on. Under conditions such as learning and memory, mTORC1 activity is required to be high for longer periods of time. Thus, the arm of the pathway that promotes syntaxin-1A and Kv1 protein synthesis will be repressed. Moreover, dendritic branches that have low mTORC1 activity with increased Kv expression would balance dendrites with constitutively high mTORC1 activity, allowing for the neuron to maintain its overall activity level within an ideal operating range. Finally, such a model suggests that

  15. Intentional Self Regulation in Middle Adolescence: The Emerging Role of Loss-Based Selection in Positive Youth Development

    Science.gov (United States)

    Gestsdottir, Steinunn; Bowers, Edmond; von Eye, Alexander; Napolitano, Christopher M.; Lerner, Richard M.

    2010-01-01

    Intentional self regulation describes how people make choices, plan actions to reach their goals, and regulate the execution of their actions, making processes of intentional self regulation central to healthy human functioning. Prior research has confirmed the presence of three processes of intentional self regulation--elective selection (ES),…

  16. p32, a novel binding partner of Mcl-1, positively regulates mitochondrial Ca{sup 2+} uptake and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Kang [Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (China); Wang, Yinyin; Chang, Zhijie [School of Medicine, Tsinghua University, Beijing (China); Lao, Yuanzhi, E-mail: laurence_ylao@163.com [School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai (China); Chang, Donald C., E-mail: bochang@ust.hk [Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (China)

    2014-08-22

    Highlights: • p32 binds to Mcl-1. • p32 affects apoptosis. • p32 and Mcl-1 regulate mitochondrial Ca{sup 2+}. - Abstract: Mcl-1 is a major anti-apoptotic Bcl-2 family protein. It is well known that Mcl-1 can interact with certain pro-apoptotic Bcl-2 family proteins in normal cells to neutralize their pro-apoptotic functions, thus prevent apoptosis. In addition, it was recently found that Mcl-1 can also inhibit mitochondrial calcium uptake. The detailed mechanism, however, is still not clear. Based on Yeast Two-Hybrid screening and co-immunoprecipitation, we identified a mitochondrial protein p32 (C1qbp) as a novel binding partner of Mcl-1. We found that p32 had a number of interesting properties: (1) p32 can positively regulate UV-induced apoptosis in HeLa cells. (2) Over-expressing p32 could significantly promote mitochondrial calcium uptake, while silencing p32 by siRNA suppressed it. (3) In p32 knockdown cells, Ruthenium Red treatment (an inhibitor of mitochondrial calcium uniporter) showed no further suppressive effect on mitochondrial calcium uptake. In addition, in Ruthenium Red treated cells, Mcl-1 also failed to suppress mitochondrial calcium uptake. Taken together, our findings suggest that p32 is part of the putative mitochondrial uniporter that facilitates mitochondrial calcium uptake. By binding to p32, Mcl-1 can interfere with the uniporter function, thus inhibit the mitochondrial Ca{sup 2+} uploading. This may provide a novel mechanism to explain the anti-apoptotic function of Mcl-1.

  17. Grape Ripening Is Regulated by Deficit Irrigation/Elevated Temperatures According to Cluster Position in the Canopy.

    Science.gov (United States)

    Zarrouk, Olfa; Brunetti, Cecilia; Egipto, Ricardo; Pinheiro, Carla; Genebra, Tânia; Gori, Antonella; Lopes, Carlos M; Tattini, Massimiliano; Chaves, M Manuela

    2016-01-01

    The impact of water deficit on berry quality has been extensively investigated during the last decades. Nonetheless, there is a scarcity of knowledge on the performance of varieties exposed to a combination of high temperatures/water stress during the growing season and under vineyard conditions. The objective of this research was to investigate the effects of two irrigation regimes, sustained deficit irrigation (SDI, 30% ET c ) and regulated deficit irrigation (RDI, 15% ET c ) and of two cluster positions within the canopy (east- and west-exposed sides) on berry ripening in red Aragonez (Tempranillo) grapevines. The study was undertaken for two successive years in a commercial vineyard in South Portugal, monitoring the following parameters: pre-dawn leaf water potential, berry temperature, sugars, polyphenols, abscisic acid (ABA) and related metabolites. Additionally, expression patterns for different transcripts encoding for enzymes responsible for anthocyanin and ABA biosynthesis ( VviUFGT, VvNCED1, Vv β G1, VviHyd1, VviHyd2 ) were analyzed. In both years anthocyanin concentration was lower in RDI at the west side (RDIW- the hottest one) from véraison onwards, suggesting that the most severe water stress conditions exacerbated the negative impact of high temperature on anthocyanin. The down-regulation of VviUFGT expression revealed a repression of the anthocyanin synthesis in berries of RDIW, at early stages of berry ripening. At full-maturation, anthocyanin degradation products were detected, being highest at RDIW. This suggests that the negative impact of water stress and high temperature on anthocyanins results from the repression of biosynthesis at the onset of ripening and from degradation at later stages. On the other hand, berries grown under SDI displayed a higher content in phenolics than those under RDI, pointing out for the attenuation of the negative temperature effects under SDI. Irrigation regime and berry position had small effect on free

  18. Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry Site and Positively Regulates Viral Protein Translation.

    Science.gov (United States)

    Zhang, Hua; Song, Lei; Cong, Haolong; Tien, Po

    2015-10-01

    Enterovirus 71 (EV71) recruits various cellular factors to assist in the replication and translation of its genome. Identification of the host factors involved in the EV71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. In this study, we demonstrated that the cellular factor 68-kDa Src-associated protein in mitosis (Sam68) acts as an internal ribosome entry site (IRES) trans-acting factor (ITAF) that binds specifically to the EV71 5' untranslated region (5'UTR). Interaction sites in both the viral IRES (stem-loops IV and V) and the heterogeneous nuclear ribonucleoprotein K homology (KH) domain of Sam68 protein were further mapped using an electrophoretic mobility shift assay (EMSA) and biotin RNA pulldown assay. More importantly, dual-luciferase (firefly) reporter analysis suggested that overexpression of Sam68 positively regulated IRES-dependent translation of virus proteins. In contrast, both IRES activity and viral protein translation significantly decreased in Sam68 knockdown cells compared with the negative-control cells treated with short hairpin RNA (shRNA). However, downregulation of Sam68 did not have a significant inhibitory effect on the accumulation of the EV71 genome. Moreover, Sam68 was redistributed from the nucleus to the cytoplasm and interacts with cellular factors, such as poly(rC)-binding protein 2 (PCBP2) and poly(A)-binding protein (PABP), during EV71 infection. The cytoplasmic relocalization of Sam68 in EV71-infected cells may be involved in the enhancement of EV71 IRES-mediated translation. Since Sam68 is known to be a RNA-binding protein, these results provide direct evidence that Sam68 is a novel ITAF that interacts with EV71 IRES and positively regulates viral protein translation. The nuclear protein Sam68 is found as an additional new host factor that interacts with the EV71 IRES during infection and could potentially

  19. Grape ripening is regulated by deficit irrigation/elevated temperatures according to cluster position in the canopy

    Directory of Open Access Journals (Sweden)

    Olfa Zarrouk

    2016-11-01

    Full Text Available The impact of water deficit on berry quality has been extensively investigated during the last decades. Nonetheless, there is a scarcity of knowledge on the performance of different varieties exposed to a combination of high temperatures/water stress during the growing season and under vineyard conditions. The objective of this research was to investigate the effects of two irrigation regimes (Sustained deficit irrigation (SDI and regulated deficit irrigation (RDI and of two cluster positions within the canopy (east- and west-exposed sides on berry ripening in red Aragonez (Tempranillo grapevines. The study was undertaken for two successive years in a commercial vineyard in South Portugal, monitoring the following parameters: predawn leaf water potential, berry temperature, sugars, polyphenols, ABA and related metabolites. Additionally, expression patterns for different transcripts encoding for enzymes responsible for anthocyanin and ABA biosynthesis were analysed. In both years anthocyanin concentration was lower in RDI at the west side (RDIW- the hottest one from véraison onwards, suggesting that the most severe water stress conditions exacerbated the negative impact of high temperature on anthocyanin. The down-regulation of VviUFGT expression revealed a repression of the anthocyanin synthesis in berries of RDIW, at early stages of berry ripening. At full-maturation, anthocyanin degradation products were detected, being highest at RDIW. This suggests that the negative impact of water stress and high temperature on anthocyanins results from the repression of biosynthesis at the onset of ripening and from degradation at later stages. Irrigation and berry position had small effect on free-ABA concentration. However, ABA catabolism/conjugation process and ABA biosynthetic pathway were affected by water and heat stresses. This indicates the role of ABA-GE and catabolites in berry ABA homeostasis under abiotic stresses. PCA showed the strongest

  20. Histone demethylase KDM5A is regulated by its reader domain through a positive-feedback mechanism

    Science.gov (United States)

    Torres, Idelisse Ortiz; Kuchenbecker, Kristopher M.; Nnadi, Chimno I.; Fletterick, Robert J.; Kelly, Mark J. S.; Fujimori, Danica Galonić

    2015-02-01

    The retinoblastoma binding protein KDM5A removes methyl marks from lysine 4 of histone H3 (H3K4). Misregulation of KDM5A contributes to the pathogenesis of lung and gastric cancers. In addition to its catalytic jumonji C domain, KDM5A contains three PHD reader domains, commonly recognized as chromatin recruitment modules. It is unknown whether any of these domains in KDM5A have functions beyond recruitment and whether they regulate the catalytic activity of the demethylase. Here using biochemical and nuclear magnetic resonance (NMR)-based structural studies, we show that the PHD1 preferentially recognizes unmethylated H3K4 histone tail, product of KDM5A-mediated demethylation of tri-methylated H3K4 (H3K4me3). Binding of unmodified H3 peptide to the PHD1 stimulates catalytic domain-mediated removal of methyl marks from H3K4me3 peptide and nucleosome substrates. This positive-feedback mechanism—enabled by the functional coupling between a reader and a catalytic domain in KDM5A—suggests a model for the spread of demethylation on chromatin.

  1. A Putative Transcription Factor pcs1 Positively Regulates Both Conidiation and Sexual Reproduction in the Cereal Pathogen Fusarium graminearum

    Directory of Open Access Journals (Sweden)

    Boknam Jung

    2014-09-01

    Full Text Available The plant pathogen Fusarium graminearum causes Fusarium head blight in cereal crops and produces mycotoxins that are harmful to animals and humans. For the initiation and spread of disease, asexual and sexual reproduction is required. Therefore, studies on fungal reproduction contribute to the development of new methods to control and maintain the fungal population. Screening a previously generated transcription factor mutant collection, we identified one putative C₂H₂ zinc-finger transcription factor, pcs1, which is required for both sexual and asexual reproduction. Deleting pcs1 in F. graminearum resulted in a dramatic reduction in conidial production and a complete loss of sexual reproduction. The pathways and gene ontology of pcs1-dependent genes from microarray experiments showed that several G-protein related pathways, oxidase activity, ribosome biogenesis, and RNA binding and processing were highly enriched, suggesting that pcs1 is involved in several different biological processes. Further, overexpression of pcs1 increased conidial production and resulted in earlier maturation of ascospores compared to the wild-type strain. Additionally, the vegetative growth of the overexpression mutants was decreased in nutrient-rich conditions but was not different from the wild-type strain in nutrient-poor conditions. Overall, we discovered that the pcs1 transcription factor positively regulates both conidiation and sexual reproduction and confers nutrient condition-dependent vegetative growth.

  2. A Putative Transcription Factor pcs1 Positively Regulates Both Conidiation and Sexual Reproduction in the Cereal Pathogen Fusarium graminearum.

    Science.gov (United States)

    Jung, Boknam; Park, Jungwook; Son, Hokyoung; Lee, Yin-Won; Seo, Young-Su; Lee, Jungkwan

    2014-09-01

    The plant pathogen Fusarium graminearum causes Fusarium head blight in cereal crops and produces mycotoxins that are harmful to animals and humans. For the initiation and spread of disease, asexual and sexual reproduction is required. Therefore, studies on fungal reproduction contribute to the development of new methods to control and maintain the fungal population. Screening a previously generated transcription factor mutant collection, we identified one putative C2H2 zinc-finger transcription factor, pcs1, which is required for both sexual and asexual reproduction. Deleting pcs1 in F. graminearum resulted in a dramatic reduction in conidial production and a complete loss of sexual reproduction. The pathways and gene ontology of pcs1-dependent genes from microarray experiments showed that several G-protein related pathways, oxidase activity, ribosome biogenesis, and RNA binding and processing were highly enriched, suggesting that pcs1 is involved in several different biological processes. Further, overexpression of pcs1 increased conidial production and resulted in earlier maturation of ascospores compared to the wild-type strain. Additionally, the vegetative growth of the overexpression mutants was decreased in nutrient-rich conditions but was not different from the wild-type strain in nutrient-poor conditions. Overall, we discovered that the pcs1 transcription factor positively regulates both conidiation and sexual reproduction and confers nutrient condition-dependent vegetative growth.

  3. Soybean (Glycine max) WRINKLED1 transcription factor, GmWRI1a, positively regulates seed oil accumulation.

    Science.gov (United States)

    Chen, Liang; Zheng, Yuhong; Dong, Zhimin; Meng, Fanfan; Sun, Xingmiao; Fan, Xuhong; Zhang, Yunfeng; Wang, Mingliang; Wang, Shuming

    2018-04-01

    Soybean is the world's most important leguminous crop producing high-quality protein and oil. Elevating oil accumulation in soybean seed is always many researchers' goal. WRINKLED1 (WRI1) encodes a transcription factor of the APETALA2/ethylene responsive element-binding protein (AP2/EREBP) family that plays important roles during plant seed oil accumulation. In this study, we isolated and characterized three distinct orthologues of WRI1 in soybean (Glycine max) that display different organ-specific expression patterns, among which GmWRI1a was highly expressed in maturing soybean seed. Electrophoretic mobility shift assays and yeast one-hybrid experiments demonstrated that the GmWRI1a protein was capable of binding to AW-box, a conserved sequence in the proximal upstream regions of many genes involved in various steps of oil biosynthesis. Transgenic soybean seeds overexpressing GmWRI1a under the control of the seed-specific napin promoter showed the increased total oil and fatty acid content and the changed fatty acid composition. Furthermore, basing on the activated expressions in transgenic soybean seeds and existence of AW-box element in the promoter regions, direct downstream genes of GmWRI1a were identified, and their products were responsible for fatty acid production, elongation, desaturation and export from plastid. We conclude that GmWRI1a transcription factor can positively regulate oil accumulation in soybean seed by a complex gene expression network related to fatty acid biosynthesis.

  4. On a Pathway Towards Thriving: Evaluating the Effectiveness of Tools to Promote Positive Development and Intentional Self Regulation in Youth

    Directory of Open Access Journals (Sweden)

    Edmond P. Bowers

    2013-12-01

    Full Text Available This article provides initial data about the reliability and validity of tools aimed at promoting youth intentional self regulation (ISR within mentoring programs. Based on the translation of the theory-based research about ISR and youth thriving conducted within the 4-H Study of Positive Youth Development (PYD, the GPS to Success tools use the metaphor of a car’s GPS navigational system to enhance goal-directed behaviors among youth. The core GPS tools are “growth grids,” designed to help mentors appraise ISR skill development and to link these skills to other grids assessing the Five Cs of PYD and Contribution. Data from 152 mentor and youth pairs from 4-H program sites in Oregon and North Carolina indicated that the growth grids were generally reliable. Although validity evidence was mixed, rubrics for “G” and “P” and for a global GPS score were related to a well-validated measure of ISR.

  5. TARGET-DIRECTED RUNNING IN GYMNASTICS: THE ROLE OF THE SPRINGBOARD POSITION AS AN INFORMATIONAL SOURCE TO REGULATE HANDSPRINGS ON VAULT

    OpenAIRE

    T. Heinen; D. Jeraj; M. Thoeren; P.M. Vinken

    2011-01-01

    Empirical evidence highlights the role of visual information to control gymnastics vaulting and thus neglects a stereotyped approach run. However, there is no evidence on which informational source this regulation is based on. The aim of this study was to examine the position of the springboard as an informational source in the regulation of the handspring on vault. The hypothesis tested was that the action of running towards the springboard brings about changes in the approach run kinematics...

  6. THE POSITION AND FUNCTIONS OF LOCAL REGULATIONS (DISTRICT REGULATION DISTRICT/MUNICIPALITY AS AN INSTRUMENT OF REGIONAL AUTONOMY WITHIN A SYSTEM OF LEGISLATION IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Jumadi -

    2016-02-01

    Full Text Available General understanding of the law indicates that the product areas that are made bythe local government, in no way can be separated from the system perundamginvitationnationally. Local regulations made by independent government units(autonomous and Environment Authority an independent anyway. Therefore, doneagainst higher level legislation should not be solely based on pertingkatan, but ratheron the environment authority. in Indonesia is beside as further the elaboration oflegislation on it which produces district regulation delegasian, as well as the specialconditions in passenger areas that generate self-contained district regulation.

  7. Effects of emotion regulation and general self-efficacy on posttraumatic growth in Chinese cancer survivors: assessing the mediating effect of positive affect.

    Science.gov (United States)

    Yu, Yongju; Peng, Li; Tang, Tang; Chen, Long; Li, Min; Wang, Tao

    2014-04-01

    In recent years, there have been increasing concerns about the existence of posttraumatic growth as a result of the struggle with cancer. The present study examined several potential predictors of posttraumatic growth and the mediating role of positive affect among Chinese cancer survivors. Two hundred thirty cancer survivors recruited from two Chinese hospitals completed self-report measures of perceived posttraumatic growth, emotion regulation, positive and negative affect, and general self-efficacy. Correlation analysis, hierarchical linear regression analysis, and Sobel test were used for data analysis. Our findings revealed that perceived level of posttraumatic growth was associated with greater positive affect, more effective emotion regulation, and higher level of general self-efficacy. No significant correlation could be found between negative affect and perceived posttraumatic growth. In addition, positive affect partially mediated the effects of expressive revealing and general self-efficacy on perceived posttraumatic growth while totally mediating the relationship between expressive suppression and perceived posttraumatic growth. Positive affect, expressive revealing, and general self-efficacy are important predictors of perceived posttraumatic growth among cancer survivors. Our findings also suggested that the effects of emotion regulation and general self-efficacy upon perceived posttraumatic growth may be closely related to the level of positive affect. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Indirect Effects of Emotion Regulation on Peer Acceptance and Rejection: The Roles of Positive and Negative Social Behaviors

    Science.gov (United States)

    Blair, Bethany L.; Gangel, Meghan J.; Perry, Nicole B.; O'Brien, Marion; Calkins, Susan D.; Keane, Susan P.; Shanahan, Lilly

    2016-01-01

    A growing body of literature indicates that childhood emotion regulation predicts later success with peers, yet little is known about the processes through which this association occurs. The current study examined mechanisms through which emotion regulation was associated with later peer acceptance and peer rejection, controlling for earlier…

  9. [Relationships between Myers-Briggs Type Indicator (MBTI) psychological type and marital satisfaction, divorce proneness, positive affect, and conflict regulation in clinic couples].

    Science.gov (United States)

    Kong, Seong Sook

    2010-06-01

    The purpose of the study was to investigate the relationships between the Myers-Briggs Type Indicator (MBTI) psychological type and marital satisfaction, divorce proneness, positive affect, and conflict regulation in couple visiting a clinic. Couples (n=62) who visited "M" couple clinic participated in the study. Data were collected from March to June 2009 using the Marital Satisfaction Scale, Marital Status Inventory, Positive Affect Inventory, and Conflict Regulation Inventory. The couples showed no significant differences in marital satisfaction, positive affect, and conflict regulation according to similarities between spouses in MBTI types. However, they showed significant differences in divorce proneness of husband according to a similarity in the Sensing/Intuition indicator. They also showed significant differences in divorce proneness, positive affect, and conflict regulation between the couples for ISTJ (Introversion, Sensing, Thinking, Judging) or ESTJ (Extraversion, Sensing, Thinking, Judging) types compared to other couples. When nurses counsel couples, they should understand that differences in psychological type between spouses affects their marital relationship. In addition, nurses should educate couples on the characteristics of each type according to the couple's types and help them to understand each other, especially for couples where one spouse is the ISTJ/ESTJ type. These interventions will improve marital satisfaction and prevent the divorce in these couples.

  10. The Effects of College Students' Positive Thinking, Learning Motivation and Self-Regulation through a Self-Reflection Intervention in Taiwan

    Science.gov (United States)

    Wang, Hsin-Hui; Chen, Hsiang-Ting; Lin, Huann-Shyang; Hong, Zuway-R

    2017-01-01

    This quasi-experimental study examined the effects of a self-reflection intervention on college (college in this article refers to university-level education) students' positive thinking, learning motivation and self-regulation in Taiwan. One hundred and two college students were selected to participate in an 18-week intervention forming the…

  11. Examining the Effects of Self-Reported Posttraumatic Stress Disorder Symptoms and Positive Relations with Others on Self-Regulated Learning for Student Service Members/Veterans

    Science.gov (United States)

    Ness, Bryan M.; Middleton, Michael J.; Hildebrandt, Michael J.

    2015-01-01

    Objectives: To examine the relationships between self-reported posttraumatic stress disorder (PTSD) symptoms, perceived positive relations with others, self-regulation strategy use, and academic motivation among student service members/veterans (SSM/V) enrolled in postsecondary education. Participants: SSM/V (N = 214), defined as veterans, active…

  12. A Radish Basic Helix-Loop-Helix Transcription Factor, RsTT8 Acts a Positive Regulator for Anthocyanin Biosynthesis

    Directory of Open Access Journals (Sweden)

    Sun-Hyung Lim

    2017-11-01

    Full Text Available The MYB-bHLH-WDR (MBW complex activates anthocyanin biosynthesis through the transcriptional regulation. RsMYB1 has been identified as a key player in anthocyanin biosynthesis in red radish (Raphanus sativus L., but its partner bHLH transcription factor (TF remains to be determined. In this study, we isolated a bHLH TF gene from red radish. Phylogenetic analysis indicated that this gene belongs to the TT8 clade of the IIIF subgroup of bHLH TFs, and we thus designated this gene RsTT8. Subcellular localization analysis showed that RsTT8-sGFP was localized to the nuclei of Arabidopsis thaliana protoplasts harboring the RsTT8-sGFP construct. We evaluated anthocyanin biosynthesis and RsTT8 expression levels in three radish varieties (N, C, and D that display different red phenotypes in the leaves, root flesh, and root skins. The root flesh of the C variety and the leaves and skins of the D variety exhibit intense red pigmentation; in these tissues, RsTT8 expression showed totally positive association with the expression of RsMYB1 TF and of five of eight tested anthocyanin biosynthesis genes (i.e., RsCHS, RsCHI, RsF3H, RsDFR, and RsANS. Heterologous co-expression of both RsTT8 and RsMYB1 in tobacco leaves dramatically increased the expression of endogenous anthocyanin biosynthesis genes and anthocyanin accumulation. Furthermore, a yeast two-hybrid assay showed that RsTT8 interacts with RsMYB1 at the MYB-interacting region (MIR, and a transient transactivation assay indicated that RsTT8 activates the RsCHS and RsDFR promoters when co-expressed with RsMYB1. Complementation of the Arabidopsis tt8-1 mutant, which lacks red pigmentation in the leaves and seeds, with RsTT8 restored red pigmentation, and resulted in high anthocyanin and proanthocyanidin contents in the leaves and seeds, respectively. Together, these results show that RsTT8 functions as a regulatory partner with RsMYB1 during anthocyanin biosynthesis.

  13. PcaO Positively Regulates pcaHG of the β-Ketoadipate Pathway in Corynebacterium glutamicum▿

    OpenAIRE

    Zhao, Ke-Xin; Huang, Yan; Chen, Xi; Wang, Nan-Xi; Liu, Shuang-Jiang

    2010-01-01

    We identified a new regulator, PcaO, which is involved in regulation of the protocatechuate (PCA) branch of the β-ketoadipate pathway in Corynebacterium glutamicum. PcaO is an atypical large ATP-binding LuxR family (LAL)-type regulator and does not have a Walker A motif. A mutant of C. glutamicum in which pcaO was disrupted (RES167ΔpcaO) was unable to grow on PCA, and growth on PCA was restored by complementation with pcaO. Both an enzymatic assay of PCA 3,4-dioxygenase activity (encoded by p...

  14. A complex genetic switch involving overlapping divergent promoters and DNA looping regulates expression of conjugation genes of a gram-positive plasmid.

    Science.gov (United States)

    Ramachandran, Gayetri; Singh, Praveen K; Luque-Ortega, Juan Roman; Yuste, Luis; Alfonso, Carlos; Rojo, Fernando; Wu, Ling J; Meijer, Wilfried J J

    2014-10-01

    Plasmid conjugation plays a significant role in the dissemination of antibiotic resistance and pathogenicity determinants. Understanding how conjugation is regulated is important to gain insights into these features. Little is known about regulation of conjugation systems present on plasmids from Gram-positive bacteria. pLS20 is a native conjugative plasmid from the Gram-positive bacterium Bacillus subtilis. Recently the key players that repress and activate pLS20 conjugation have been identified. Here we studied in detail the molecular mechanism regulating the pLS20 conjugation genes using both in vivo and in vitro approaches. Our results show that conjugation is subject to the control of a complex genetic switch where at least three levels of regulation are integrated. The first of the three layers involves overlapping divergent promoters of different strengths regulating expression of the conjugation genes and the key transcriptional regulator RcoLS20. The second layer involves a triple function of RcoLS20 being a repressor of the main conjugation promoter and an activator and repressor of its own promoter at low and high concentrations, respectively. The third level of regulation concerns formation of a DNA loop mediated by simultaneous binding of tetrameric RcoLS20 to two operators, one of which overlaps with the divergent promoters. The combination of these three layers of regulation in the same switch allows the main conjugation promoter to be tightly repressed during conditions unfavorable to conjugation while maintaining the sensitivity to accurately switch on the conjugation genes when appropriate conditions occur. The implications of the regulatory switch and comparison with other genetic switches involving DNA looping are discussed.

  15. The Position and Functions of Local Regulations (District Regulation) District/municipality as an Instrument of Regional Autonomy Within a System of Legislation in Indonesia

    OpenAIRE

    -, Jumadi

    2016-01-01

    General understanding of the law indicates that the product areas that are made bythe local government, in no way can be separated from the system perundamginvitationnationally. Local regulations made by independent government units(autonomous) and Environment Authority an independent anyway. Therefore, doneagainst higher level legislation should not be solely based on pertingkatan, but ratheron the environment authority. in Indonesia is beside as further the elaboration oflegislation on it w...

  16. TARGET-DIRECTED RUNNING IN GYMNASTICS: THE ROLE OF THE SPRINGBOARD POSITION AS AN INFORMATIONAL SOURCE TO REGULATE HANDSPRINGS ON VAULT

    Directory of Open Access Journals (Sweden)

    T. Heinen

    2011-11-01

    Full Text Available Empirical evidence highlights the role of visual information to control gymnastics vaulting and thus neglects a stereotyped approach run. However, there is no evidence on which informational source this regulation is based on. The aim of this study was to examine the position of the springboard as an informational source in the regulation of the handspring on vault. The hypothesis tested was that the action of running towards the springboard brings about changes in the approach run kinematics and handspring kinematics that relate directly to the position of the springboard. Therefore, kinematics of N = 14 female expert gymnasts’ handsprings on vault and their approach runs were examined while manipulating the position of the springboard. The results revealed that expert gymnasts placed their feet on average in the same position on the springboard and adapted to the springboard position during the last three steps of the approach run. A smaller springboard distance to the front edge of the vaulting table resulted in a different hand placement on the vaulting table, a shorter first flight phase, a take-off angle closer to 90° and a longer second flight phase. Findings suggest that the position of the springboard is a relevant informational source in gymnastics vaulting. We state that knowledge about relationships between informational sources in the environment and the resulting regulatory processes in athletes may help coaches to develop specific training programmes in order to optimize performance in complex skills.

  17. Identification of the sigmaB regulon of Bacillus cereus and conservation of sigmaB-regulated genes in low-GC-content gram-positive bacteria.

    Science.gov (United States)

    van Schaik, Willem; van der Voort, Menno; Molenaar, Douwe; Moezelaar, Roy; de Vos, Willem M; Abee, Tjakko

    2007-06-01

    The alternative sigma factor sigma(B) has an important role in the acquisition of stress resistance in many gram-positive bacteria, including the food-borne pathogen Bacillus cereus. Here, we describe the identification of the set of sigma(B)-regulated genes in B. cereus by DNA microarray analysis of the transcriptome upon a mild heat shock. Twenty-four genes could be identified as being sigma(B) dependent as witnessed by (i) significantly lower expression levels of these genes in mutants with a deletion of sigB and rsbY (which encode the alternative sigma factor sigma(B) and a crucial positive regulator of sigma(B) activity, respectively) than in the parental strain B. cereus ATCC 14579 and (ii) increased expression of these genes upon a heat shock. Newly identified sigma(B)-dependent genes in B. cereus include a histidine kinase and two genes that have predicted functions in spore germination. This study shows that the sigma(B) regulon of B. cereus is considerably smaller than that of other gram-positive bacteria. This appears to be in line with phylogenetic analyses where sigma(B) of the B. cereus group was placed close to the ancestral form of sigma(B) in gram-positive bacteria. The data described in this study and previous studies in which the complete sigma(B) regulon of the gram-positive bacteria Bacillus subtilis, Listeria monocytogenes, and Staphylococcus aureus were determined enabled a comparison of the sets of sigma(B)-regulated genes in the different gram-positive bacteria. This showed that only three genes (rsbV, rsbW, and sigB) are conserved in their sigma(B) dependency in all four bacteria, suggesting that the sigma(B) regulon of the different gram-positive bacteria has evolved to perform niche-specific functions.

  18. Characterization of the SigD regulon of C. difficile and its positive control of toxin production through the regulation of tcdR.

    Directory of Open Access Journals (Sweden)

    Imane El Meouche

    Full Text Available Clostridium difficile intestinal disease is mediated largely by the actions of toxins A (TcdA and B (TcdB, whose production occurs after the initial steps of colonization involving different surface or flagellar proteins. In B. subtilis, the sigma factor SigD controls flagellar synthesis, motility, and vegetative autolysins. A homolog of SigD encoding gene is present in the C.difficile 630 genome. We constructed a sigD mutant in C. difficile 630 ∆erm to analyze the regulon of SigD using a global transcriptomic approach. A total of 103 genes were differentially expressed between the wild-type and the sigD mutant, including genes involved in motility, metabolism and regulation. In addition, the sigD mutant displayed decreased expression of genes involved in flagellar biosynthesis, and also of genes encoding TcdA and TcdB as well as TcdR, the positive regulator of the toxins. Genomic analysis and RACE-PCR experiments allowed us to characterize promoter sequences of direct target genes of SigD including tcdR and to identify the SigD consensus. We then established that SigD positively regulates toxin expression via direct control of tcdR transcription. Interestingly, the overexpression of FlgM, a putative anti-SigD factor, inhibited the positive regulation of motility and toxin synthesis by SigD. Thus, SigD appears to be the first positive regulator of the toxin synthesis in C. difficile.

  19. Developmentally regulated GTP-binding protein 2 is required for stabilization of Rac1-positive membrane tubules.

    Science.gov (United States)

    Mani, Muralidharan; Lee, Unn Hwa; Yoon, Nal Ae; Yoon, Eun Hye; Lee, Byung Ju; Cho, Wha Ja; Park, Jeong Woo

    2017-11-04

    Previously we have reported that developmentally regulated GTP-binding protein 2 (DRG2) localizes on Rab5 endosomes and plays an important role in transferrin (Tfn) recycling. We here identified DRG2 as a key regulator of membrane tubule stability. At 30 min after Tfn treatment, DRG2 localized to membrane tubules which were enriched with phosphatidylinositol 4-monophosphate [PI(4)P] and did not contain Rab5. DRG2 interacted with Rac1 more strongly with GTP-bound Rac1 and tubular localization of DRG2 depended on Rac1 activity. DRG2 depletion led to destabilization of membrane tubules, while ectopic expression of DRG2 rescued the stability of the membrane tubules in DRG2-depleted cells. Our results reveal a novel mechanism for regulation of membrane tubule stability mediated by DRG2. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Chitinase expression in Listeria monocytogenes is positively regulated by the Agr system

    DEFF Research Database (Denmark)

    Paspaliari, Dafni Katerina; Mollerup, Maria Storm; Kallipolitis, Birgitte H.

    2014-01-01

    chitinolytic activity on agar plates. Agr was specifically induced in response to chitin addition in stationary phase and agrD was found to regulate the amount of chiA, but not chiB, transcripts. Although the transcript levels of chiB did not depend on agrD, the extracellular protein levels of both chitinases....... Our results highlight a previously unrecognized role of the agr system and suggest that autoinducer-based regulation of chitinolytic systems may be more commonplace than previously thought....

  1. Pepper CabZIP63 acts as a positive regulator during Ralstonia solanacearum or high temperature–high humidity challenge in a positive feedback loop with CaWRKY40

    Science.gov (United States)

    Shen, Lei; Liu, Zhiqin; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Lin, Wei; Wang, Rongzhang; Yu, Huanxin; Mou, Shaoliang; Hussain, Ansar; Cheng, Wei; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-01-01

    CaWRKY40 is known to act as a positive regulator in the response of pepper (Capsicum annuum) to Ralstonia solanacearum inoculation (RSI) or high temperature–high humidity (HTHH), but the underlying mechanism remains elusive. Herein, we report that CabZIP63, a pepper bZIP family member, participates in this process by regulating the expression of CaWRKY40. CabZIP63 was found to localize in the nuclei, be up-regulated by RSI or HTHH, bind to promoters of both CabZIP63 (pCabZIP63) and CaWRKY40 (pCaWRKY40), and activate pCabZIP63- and pCaWRKY40-driven β-glucuronidase expression in a C- or G-box-dependent manner. Silencing of CabZIP63 by virus-induced gene silencing (VIGS) in pepper plants significantly attenuated their resistance to RSI and tolerance to HTHH, accompanied by down-regulation of immunity- or thermotolerance-associated CaPR1, CaNPR1, CaDEF1, and CaHSP24. Hypersensitive response-mediated cell death and expression of the tested immunity- and thermotolerance-associated marker genes were induced by transient overexpression (TOE) of CabZIP63, but decreased by that of CabZIP63-SRDX. Additionally, binding of CabZIP63 to pCaWRKY40 was up-regulated by RSI or HTHH, and the transcript level of CaWRKY40 and binding of CaWRKY40 to the promoters of CaPR1, CaNPR1, CaDEF1 and CaHSP24 were up-regulated by TOE of CabZIP63. On the other hand, CabZIP63 was also up-regulated transcriptionally by TOE of CaWRKY40. The data suggest collectively that CabZIP63 directly or indirectly regulates the expression of CaWRKY40 at both the transcriptional and post-transcriptional level, forming a positive feedback loop with CaWRKY40 during pepper’s response to RSI or HTHH. Altogether, our data will help to elucidate the underlying mechanism of crosstalk between pepper’s response to RSI and HTHH. PMID:26936828

  2. CRP-dependent positive autoregulation and proteolytic degradation regulate competence activator Sxy of Escherichia coli

    DEFF Research Database (Denmark)

    Jaskólska, Milena; Gerdes, Kenn

    2015-01-01

    Natural competence, the ability of bacteria to take up exogenous DNA and incorporate it into their chromosomes, is in most bacteria a transient phenomenon under complex genetic and environmental control. In the Gram-negative bacteria Haemophilus influenzae and Vibrio cholerae, the master regulator...

  3. Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation

    Science.gov (United States)

    Chang, Jae Won; Jung, Seung-Nam; Kim, Ju-Hee; Shim, Geun-Ae; Park, Hee Sung; Liu, Lihua; Kim, Jin Man; Park, Jongsun; Koo, Bon Seok

    2016-01-01

    The exact regulatory mechanisms of carboxyl-terminal modulator protein (CTMP) and its downstream pathways in cancer have been controversial and are not completely understood. Here, we report a new mechanism of regulation of Akt serine/threonine kinase, one of the most important dysregulated signals in head and neck squamous cell carcinoma (HNSCC) by the CTMP pathway and its clinical implications. We find that HNSCC tumor tissues and cell lines had relatively high levels of CTMP expression. Clinical data indicate that CTMP expression was significantly associated with positive lymph node metastasis (OR = 3.8, P = 0.033) and correlated with poor prognosis in patients with HNSCC. CTMP was also positively correlated with Akt/GSK-3β phosphorylation, Snail up-regulation and E-cadherin down-regulation, which lead to increased proliferation and epithelial-to-mesenchymal transition, suggesting that CTMP expression results in enhanced tumorigenic and metastatic properties of HNSCC cells. Moreover, CTMP suppression restores sensitivity to cisplatin chemotherapy. Intriguingly, all the molecular responses to CTMP regulation are identical regardless of p53 status in HNSCC cells. We conclude that CTMP promotes Akt phosphorylation and functions as an oncogenic driver and prognostic marker in HNSCC irrespective of p53. PMID:27328758

  4. DOF AFFECTING GERMINATION 2 is a positive regulator of light-mediated seed germination and is repressed by DOF AFFECTING GERMINATION 1.

    Science.gov (United States)

    Santopolo, Silvia; Boccaccini, Alessandra; Lorrai, Riccardo; Ruta, Veronica; Capauto, Davide; Minutello, Emanuele; Serino, Giovanna; Costantino, Paolo; Vittorioso, Paola

    2015-03-04

    The transcription factor DOF AFFECTING GERMINATION1 (DAG1) is a repressor of the light-mediated seed germination process. DAG1 acts downstream PHYTOCHROME INTERACTING FACTOR3-LIKE 5 (PIL5), the master repressor, and negatively regulates gibberellin biosynthesis by directly repressing the biosynthetic gene AtGA3ox1. The Dof protein DOF AFFECTING GERMINATION (DAG2) shares a high degree of aminoacidic identity with DAG1. While DAG1 inactivation considerably increases the germination capability of seeds, the dag2 mutant has seeds with a germination potential substantially lower than the wild-type, indicating that these factors may play opposite roles in seed germination. We show here that DAG2 expression is positively regulated by environmental factors triggering germination, whereas its expression is repressed by PIL5 and DAG1; by Chromatin Immuno Precipitation (ChIP) analysis we prove that DAG1 directly regulates DAG2. In addition, we show that Red light significantly reduces germination of dag2 mutant seeds. In agreement with the seed germination phenotype of the dag2 mutant previously published, the present data prove that DAG2 is a positive regulator of the light-mediated seed germination process, and particularly reveal that this protein plays its main role downstream of PIL5 and DAG1 in the phytochrome B (phyB)-mediated pathway.

  5. Seqinspector: position-based navigation through the ChIP-seq data landscape to identify gene expression regulators.

    Science.gov (United States)

    Piechota, Marcin; Korostynski, Michal; Ficek, Joanna; Tomski, Andrzej; Przewlocki, Ryszard

    2016-02-12

    The regulation of gene expression in eukaryotic cells is a complex process that involves epigenetic modifications and the interaction of DNA with multiple transcription factors. This process can be studied with unprecedented sensitivity using a combination of chromatin immunoprecipitation and next-generation DNA sequencing (ChIP-seq). Available ChIP-seq data can be further utilized to interpret new gene expression profiling experiments. Here, we describe seqinspector, a tool that accepts any set of genomic coordinates from ChIP-seq or RNA-seq studies to identify shared transcriptional regulators. The presented web resource includes a large collection of publicly available ChIP-seq and RNA-seq experiments (>1300 tracks) performed on transcription factors, histone modifications, RNA polymerases, enhancers and insulators in humans and mice. Over-representation is calculated based on the coverage computed directly from indexed files storing ChIP-seq data (bigwig). Therefore, seqinspector is not limited to pre-computed sets of gene promoters. The tool can be used to identify common gene expression regulators for sets of co-expressed transcripts (including miRNAs, lncRNAs or any novel unannotated RNAs) or for sets of ChIP-seq peaks to identify putative protein-protein interactions or transcriptional co-factors. The tool is available at http://seqinspector.cremag.org.

  6. Using positive and negative patterns to extract information from journal articles regarding the regulation of a target gene by a transcription factor.

    Science.gov (United States)

    Wang, Hei Chia; Kooi, Tock-Kheng; Kao, Hung-Yu; Lin, Shih Chieh; Tsai, Shaw-Jenq

    2013-12-01

    Gene regulation research concerns the regulatory relationship between transcription factors (TFs) and their target genes (TGenes). Due to the rapid acceleration of biological research, it is impractical for biologists to read all of the relevant literature and manually extract all of the information about the regulatory relationships between a TF and its TGenes. This paper proposes a method utilizing negative and positive textual patterns to extract regulatory information regarding certain TF-TGene pairs, which provides insightful information to biologists and saves them time from excessive literature reading. We hypothesized that the negative patterns could be used for filtering and that the system would mainly rely on the positive patterns to mine the regulatory TF-TGene relationships from the text. We also examined whether WordNet could be utilized to improve the pattern recognition performance. The results show that the negative pattern should be used for initial filtering, and then the positive patterns can extract information related to gene regulation. Moreover, WordNet seems to have little effect on the performance when extracting gene regulations. © 2013 Published by Elsevier Ltd.

  7. Type I and II positive allosteric modulators differentially modulate agonist-induced up-regulation of α7 nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Mikkelsen, Jens D

    2012-01-01

    Long-term treatment with nicotine or selective α7 nicotinic acetylcholine receptor (nAChR) agonists increases the number of α7 nAChRs and this up-regulation may be involved in the mechanism underlying the sustained procognitive effect of these compounds. Here, we investigate the influence of type I...... and II α7 nAChR positive allosteric modulators (PAMs) on agonist-induced α7 nAChR up-regulation. We show that the type II PAMs, PNU-120596 (10 μM) or TQS (1 and 10 μM), inhibit up-regulation, as measured by protein levels, induced by the α7 nAChR agonist A-582941 (10 nM or 10 μM), in SH-EP1 cells stably...... expressing human α7 nAChR, whereas the type I PAMs AVL-3288 or NS1738 do not. Contrarily, neither type I nor II PAMs affect 10 μM nicotine-induced receptor up-regulation, suggesting that nicotine and A-582941 induce up-regulation through different mechanisms. We further show in vivo that 3 mg/kg PNU-120596...

  8. ANALYTICAL CALCULATION OF THE BASIC ELECTROMAGNETIC LOSSES OF THE ENERGY OF THE FREQUENCY-REGULATED ASYNCHRONOUS ENGINE IN POSITIONING

    Directory of Open Access Journals (Sweden)

    V. O. Volkov

    2018-02-01

    Full Text Available Purpose. Obtaining analytical dependencies for the calculation of the main electromagnetic energy losses of a frequency-controlled induction motor in positioning modes with small displacements for various types (linear, parabolic and quasi-optimal of its velocity variation. Methodology. Similarity methods, differential and integral calculus, analytical interpolation, mathematical analysis. Findings. Analytical dependencies for calculation of current electromagnetic power losses and basic electromagnetic energy losses of a frequency-controlled asynchronous motor in the modes of positioning with small displacements for various types (linear, parabolic and quasi-optimal of its velocity are obtained. A universal form of the analytical dependence for calculating the optimal acceleration and deceleration times for a frequency-controlled asynchronous motor for positioning with small displacements, corresponding to minimization of the main electromagnetic energy losses of this engine with the indicated positioning for various species (linear, parabolic and quasi-optimal, is obtained. A comparative quantitative assessment of the change is made: the optimum values of the main electromagnetic energy losses of the frequency-controlled asynchronous engine and the corresponding maximum speed and optimal acceleration and deceleration times, in the function of the set prescribed small displacements for the various engine speed trajectories under consideration. Originality. For the first time, analytical dependencies for the calculation of the main electromagnetic energy losses of a frequency-controlled asynchronous motor are obtained for positioning with small displacements as a function of the set values of the movement of the motor shaft and the set values of its acceleration and deceleration times for the specified specified displacements. For the first time, dependences are obtained for a quantitative estimate of the minimum fundamental electromagnetic

  9. Serum response factor: positive and negative regulation of an epithelial gene expression network in the destrin mutant cornea

    Science.gov (United States)

    Kawakami-Schulz, Sharolyn V.; Verdoni, Angela M.; Sattler, Shannon G.; Jessen, Erik; Kao, Winston W.-Y.; Ikeda, Akihiro

    2014-01-01

    Increased angiogenesis, inflammation, and proliferation are hallmarks of diseased tissues, and in vivo models of these disease phenotypes can provide insight into disease pathology. Dstncorn1 mice, deficient for the actin depolymerizing factor destrin (DSTN), display an increase of serum response factor (SRF) that results in epithelial hyperproliferation, inflammation, and neovascularization in the cornea. Previous work demonstrated that conditional ablation of Srf from the corneal epithelium of Dstncorn1 mice returns the cornea to a wild-type (WT) like state. This result implicated SRF as a major regulator of genes that contributes to abnormal phenotypes in Dstncorn1 cornea. The purpose of this study is to identify gene networks that are affected by increased expression of Srf in the Dstncorn1 cornea. Microarray analysis led to characterization of gene expression changes that occur when conditional knockout of Srf rescues mutant phenotypes in the cornea of Dstncorn1 mice. Comparison of gene expression values from WT, Dstncorn1 mutant, and Dstncorn1 rescued cornea identified >400 differentially expressed genes that are downstream from SRF. Srf ablation had a significant effect on genes associated with epithelial cell-cell junctions and regulation of actin dynamics. The majority of genes affected by SRF are downregulated in the Dstncorn1 mutant cornea, suggesting that increased SRF negatively affects transcription of SRF gene targets. ChIP-seq analysis on Dstncorn1 mutant and WT tissue revealed that, despite being present in higher abundance, SRF binding is significantly decreased in the Dstncorn1 mutant cornea. This study uses a unique model combining genetic and genomic approaches to identify genes that are regulated by SRF. These findings expand current understanding of the role of SRF in both normal and abnormal tissue homeostasis. PMID:24550211

  10. Serum response factor: positive and negative regulation of an epithelial gene expression network in the destrin mutant cornea.

    Science.gov (United States)

    Kawakami-Schulz, Sharolyn V; Verdoni, Angela M; Sattler, Shannon G; Jessen, Erik; Kao, Winston W-Y; Ikeda, Akihiro; Ikeda, Sakae

    2014-04-15

    Increased angiogenesis, inflammation, and proliferation are hallmarks of diseased tissues, and in vivo models of these disease phenotypes can provide insight into disease pathology. Dstn(corn1) mice, deficient for the actin depolymerizing factor destrin (DSTN), display an increase of serum response factor (SRF) that results in epithelial hyperproliferation, inflammation, and neovascularization in the cornea. Previous work demonstrated that conditional ablation of Srf from the corneal epithelium of Dstn(corn1) mice returns the cornea to a wild-type (WT) like state. This result implicated SRF as a major regulator of genes that contributes to abnormal phenotypes in Dstn(corn1) cornea. The purpose of this study is to identify gene networks that are affected by increased expression of Srf in the Dstn(corn1) cornea. Microarray analysis led to characterization of gene expression changes that occur when conditional knockout of Srf rescues mutant phenotypes in the cornea of Dstn(corn1) mice. Comparison of gene expression values from WT, Dstn(corn1) mutant, and Dstn(corn1) rescued cornea identified >400 differentially expressed genes that are downstream from SRF. Srf ablation had a significant effect on genes associated with epithelial cell-cell junctions and regulation of actin dynamics. The majority of genes affected by SRF are downregulated in the Dstn(corn1) mutant cornea, suggesting that increased SRF negatively affects transcription of SRF gene targets. ChIP-seq analysis on Dstn(corn1) mutant and WT tissue revealed that, despite being present in higher abundance, SRF binding is significantly decreased in the Dstn(corn1) mutant cornea. This study uses a unique model combining genetic and genomic approaches to identify genes that are regulated by SRF. These findings expand current understanding of the role of SRF in both normal and abnormal tissue homeostasis.

  11. Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells.

    Science.gov (United States)

    Cheng, Ran; Liu, Ya-Jing; Cui, Jun-Wei; Yang, Man; Liu, Xiao-Ling; Li, Peng; Wang, Zhan; Zhu, Li-Zhang; Lu, Si-Yi; Zou, Li; Wu, Xiao-Qin; Li, Yu-Xia; Zhou, You; Fang, Zheng-Yu; Wei, Wei

    2017-05-02

    Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

  12. Histone demethylase KDM5A is regulated by its reader domain through a positive-feedback mechanism

    OpenAIRE

    Torres, Idelisse Ortiz; Kuchenbecker, Kristopher M.; Nnadi, Chimno I.; Fletterick, Robert J.; Kelly, Mark J.S.; Fujimori, Danica Galonić

    2015-01-01

    The retinoblastoma binding protein KDM5A removes methyl marks from lysine 4 of histone H3 (H3K4). Misregulation of KDM5A contributes to the pathogenesis of lung and gastric cancers. In addition to its catalytic jumonji C domain, KDM5A contains three PHD reader domains, commonly recognized as chromatin recruitment modules. It is unknown whether any of these domains in KDM5A have functions beyond recruitment and whether they regulate the catalytic activity of the demethylase. Here using biochem...

  13. TaMAPK4 Acts as a Positive Regulator in Defense of Wheat Stripe-Rust Infection

    OpenAIRE

    Bing Wang; Na Song; Qiong Zhang; Ning Wang; Zhensheng Kang

    2018-01-01

    Highly conserved mitogen-activated protein kinase (MAPK) cascades regulate numerous plant processes, including hormonal responses, stress, and innate immunity. In this research, TaMAPK4 was predicted to be a target of tae-miR164. We verified the binding and suppression of TaMAPK4 by co-expression in Nicotiana benthamiana. Moreover, we found TaMAPK4 was localized in the cytoplasm and nucleus using transient expression analyses. TaMAPK4 transcripts increased following salicylic acid (SA) treatm...

  14. The heat-inducible essential response regulator WalR positively regulates transcription of sigI, mreBH and lytE in Bacillus subtilis under heat stress.

    Science.gov (United States)

    Huang, Wan-Zhen; Wang, Jyun-Jhih; Chen, Hui-Ju; Chen, Jung-Tze; Shaw, Gwo-Chyuan

    2013-12-01

    The actin homolog MreBH governs cell morphogenesis of Bacillus subtilis through localization of the cell wall hydrolase LytE. The alternative sigma factor SigI of B. subtilis coordinately regulates transcription of mreBH and lytE. Transcription of sigI, mreBH and lytE is heat-inducible. The essential response regulator WalR (YycF) plays a key role in coordinating cell wall metabolism with cell proliferation. We now demonstrate that mreBH is a new member of the WalR regulon. We also found that WalR can positively and directly regulate sigI transcription under heat stress through a binding site located upstream of the σ(I) promoter of sigI. In addition, we found that a WalR binding site located upstream of the SigI binding site in the regulatory region of lytE is important for lytE expression under heat stress. Moreover, we found that walR is a new member of the heat shock stimulon of B. subtilis. WalR appears to coordinately and positively regulate transcription of sigI, mreBH and lytE under heat stress. Finally, our work shows for the first time that WalR can stimulate activities of σ(I) promoters under heat stress. Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  15. Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Joseph L. Regan

    2017-12-01

    Full Text Available Summary: Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs. To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH-positive CSCs. Canonical GLI-dependent Hedgehog signaling is a negative regulator of WNT signaling in normal intestine and intestinal tumors. Here, we show that Hedgehog signaling in colon CSCs is autocrine SHH-dependent, non-canonical PTCH1 dependent, and GLI independent. In addition, using small-molecule inhibitors and RNAi against SHH-palmitoylating Hedgehog acyltransferase (HHAT, we demonstrate that non-canonical Hedgehog signaling is a positive regulator of WNT signaling and required for colon CSC survival. : Colon cancer is a heterogeneous tumor driven by a subpopulation(s of therapy-resistant cancer stem cells (CSCs. Regan et al. use 3D culture models to demonstrate that CSC survival is regulated by non-canonical, SHH-dependent, PTCH1-dependent Hedgehog signaling, which acts as a positive regulator of WNT signaling to block CSC differentiation. Keywords: WNT pathway, non-canonical Hedgehog signaling, cancer stem cell, colon cancer, cancer organoid, PTCH1, HHAT, SHH

  16. An R2R3-MYB gene, LeAN2, positively regulated the thermo-tolerance in transgenic tomato.

    Science.gov (United States)

    Meng, Xia; Wang, Jie-Ru; Wang, Guo-Dong; Liang, Xiao-Qing; Li, Xiao-Dong; Meng, Qing-Wei

    2015-03-01

    LeAN2 is an anthocyanin-associated R2R3-MYB transcription factor, but little is known about its function in imparting thermo-tolerance to higher plants. To examine the function of LeAN2 in the regulation of heat stress in tomato, LeAN2 was isolated and transgenic tomato plants were obtained. Overexpression of LeAN2 under the control of the CaMV35S promoter in tomato induced the up-regulation of several structural genes in the anthocyanin biosynthetic pathway as well as anthocyanin accumulation in transgenic tomato plants. Transgenic tomato plants showed enhanced tolerance to heat stress by maintaining higher fresh weight (FW), net photosynthetic rate (Pn) and maximal photochemical efficiency of photosystem II (PSII) (Fv/Fm) compared with wild-type (WT) plants. Furthermore, transgenic plants showed higher non-enzymatic antioxidant activity, lower levels of reactive oxygen species (ROS), and higher contents of D1 protein than that in WT plants under heat stress. These results indicate that LeAN2 had an important function in heat stress resistance. Copyright © 2014 Elsevier GmbH. All rights reserved.

  17. An oral keratinocyte life cycle model identifies novel host genome regulation by human papillomavirus 16 relevant to HPV positive head and neck cancer.

    Science.gov (United States)

    Evans, Michael R; James, Claire D; Loughran, Oonagh; Nulton, Tara J; Wang, Xu; Bristol, Molly L; Windle, Brad; Morgan, Iain M

    2017-10-10

    Many aspects of the HPV life cycle have been characterized in cervical cell lines (W12, CIN612) and in HPV immortalized primary foreskin keratinocytes. There is now an epidemic of HPV positive oropharyngeal cancers (HPV16 is responsible for 80-90% of these); therefore increased understanding of the HPV16 life cycle in oral keratinocytes is a priority. To date there have been limited reports characterizing the HPV16 life cycle in oral keratinocytes. Using TERT immortalized "normal" oral keratinocytes (NOKs) we generated clonal cell lines maintaining the HPV16 genome as an episome, NOKs+HPV16. Organotypic raft cultures demonstrated appropriate expression of differentiation markers, E1^E4 and E2 expression along with amplification of the viral genome in the upper layers of the epithelium. Using this unique system RNA-seq analysis revealed extensive gene regulation of the host genome by HPV16; many of the changes have not been observed for HPV16 before. The RNA-seq data was validated on a key set of anti-viral innate immune response genes repressed by HPV16 in NOKs+HPV16. We show that the behavior of these NOKs+HPV16 lines is identical to HPV16 immortalized human tonsil keratinocytes with regards innate gene regulation. Finally, using The Cancer Genome Atlas (TCGA) data we examined gene expression patterns from HPV positive and negative head and neck cancers and demonstrate this innate immune gene signature set is also downregulated in HPV positive cancers versus negative. Our system provides a model for understanding HPV16 transcriptional regulation of oral keratinocytes that is directly relevant to HPV positive head and neck cancer.

  18. Regulation of NOX-1 expression in beta cells: a positive feedback loop involving the Src-kinase signaling pathway.

    Science.gov (United States)

    Weaver, J R; Taylor-Fishwick, D A

    2013-04-30

    NADPH oxidase-1 (NOX-1) is upregulated in beta cells in response to pro-inflammatory cytokines. Inhibition of NADPH oxidase activity blocked stimulated NOX-1 expression (pNOX-1 expression in beta cells followed modulation of cellular reactive oxygen species (ROS); pro-oxidants increased NOX-1 (pNOX-1 (pNOX-1 expression (pNOX-1 preserved beta cell function and survival. Collectively, these data indicate that expression of NOX-1 in beta cells is regulated in a feed-forward loop mediated by ROS and Src-kinase. Uncoupling of this feed-forward activation could provide new approaches to preserve and protect beta cells in diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Regulation and gene expression profiling of NKG2D positive human cytomegalovirus-primed CD4+ T-cells

    DEFF Research Database (Denmark)

    Jensen, Helle; Folkersen, Lasse; Skov, Søren

    2012-01-01

    we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D(+) CD4(+) T-cells, generated from HCMV-primed CD4(+) T-cells. We show that the HCMV-primed NKG2D(+) CD4(+) T-cells possess a higher differentiated phenotype...... than the NKG2D(-) CD4(+) T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4(+) T-cells and not by the antigen presenting cells. We observed a correlation...... CD4(+) T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D(+) CD4(+) T-cells, as well as the mechanisms regulating NKG2D cell surface expression....

  20. The EZH1-SUZ12 complex positively regulates the transcription of NF-κB target genes through interaction with UXT.

    Science.gov (United States)

    Su, Shuai-Kun; Li, Chun-Yuan; Lei, Pin-Ji; Wang, Xiang; Zhao, Quan-Yi; Cai, Yang; Wang, Zhen; Li, Lianyun; Wu, Min

    2016-06-15

    Unlike other members of the polycomb group protein family, EZH1 has been shown to positively associate with active transcription on a genome-wide scale. However, the underlying mechanism for this behavior still remains elusive. Here, we report that EZH1 physically interacts with UXT, a small chaperon-like transcription co-activator. UXT specifically interacts with EZH1 and SUZ12, but not EED. Similar to upon knockdown of UXT, knockdown of EZH1 or SUZ12 through RNA interference in the cell impairs the transcriptional activation of nuclear factor (NF)-κB target genes induced by TNFα. EZH1 deficiency also increases TNFα-induced cell death. Interestingly, chromatin immunoprecipitation and the following next-generation sequencing analysis show that H3K27 mono-, di- and tri-methylation on NF-κB target genes are not affected in EZH1- or UXT-deficient cells. EZH1 also does not affect the translocation of the p65 subunit of NF-κB (also known as RELA) from the cytosol to the nucleus. Instead, EZH1 and SUZ12 regulate the recruitment of p65 and RNA Pol II to target genes. Taken together, our study shows that EZH1 and SUZ12 act as positive regulators for NF-κB signaling and demonstrates that EZH1, SUZ12 and UXT work synergistically to regulate pathway activation in the nucleus. © 2016. Published by The Company of Biologists Ltd.

  1. STAT3 inhibition suppresses proliferation of retinoblastoma through down-regulation of positive feedback loop of STAT3/miR-17-92 clusters

    Science.gov (United States)

    Jo, Dong Hyun; Kim, Jin Hyoung; Cho, Chang Sik; Cho, Young-Lai; Jun, Hyoung Oh; Yu, Young Suk; Min, Jeong-Ki; Kim, Jeong Hun

    2014-01-01

    Retinoblastoma, the most common intraocular malignant tumor in children, is characterized by the loss of both functional alleles of RB1 gene, which however alone cannot maintain malignant characteristics of retinoblastoma cells. Nevertheless, the investigation of other molecular aberrations such as matrix metalloproteinases (MMPs) and miRNAs is still lacking. In this study, we demonstrate that STAT3 is activated in retinoblastoma cells, Ki67-positive areas of in vivo orthotopic tumors in BALB/c nude mice, and human retinoblastoma tissues of the advanced stage. Furthermore, target genes of STAT3 including BCL2, BCL2L1, BIRC5, and MMP9 are up-regulated in retinoblastoma cells compared to other retinal constituent cells. Interestingly, STAT3 inhibition by targeted siRNA suppresses the proliferation of retinoblastoma cells and the formation of in vivo orthotopic tumors. In line with these results, STAT3 siRNA effectively induces down-regulation of target genes of STAT3. In addition, miRNA microarray analysis and further real-time PCR experiments with STAT3 siRNA treatment show that STAT3 activation is related to the up-regulation of miR-17-92 clusters in retinoblastoma cells via positive feedback loop between them. In conclusion, we suggest that STAT3 inhibition could be a potential therapeutic approach in retinoblastoma through the suppression of tumor proliferation. PMID:25359779

  2. Expression of alkyl hydroperoxide reductase is regulated negatively by OxyR1 and positively by RpoE2 sigma factor in Azospirillum brasilense Sp7.

    Science.gov (United States)

    Singh, Sudhir; Dwivedi, Susheel Kumar; Singh, Vijay Shankar; Tripathi, Anil Kumar

    2016-10-01

    OxyR proteins are LysR-type transcriptional regulators, which play an important role in responding to oxidative stress in bacteria. Azospirillum brasilense Sp7 harbours two copies of OxyR. The inactivation of the oxyR1, the gene organized divergently to ahpC in A. brasilense Sp7, led to an increased tolerance to alkyl hydroperoxides, which was corroborated by an increase in alkyl hydroperoxide reductase (AhpC) activity, enhanced expression of ahpC :lacZ fusion and increased synthesis of AhpC protein in the oxyR1::km mutant. The upstream region of ahpC promoter harboured a putative OxyR binding site, T-N11-A. Mutation of T, A or both in the T-N11-Amotif caused derepression of ahpC in A. brasilense suggesting that T-N11-A might be the binding site for a negative regulator. Retardation of the electrophoretic mobility of the T-N11-A motif harbouring oxyR1-ahpC intergenic DNA by recombinant OxyR1, under reducing as well as oxidizing conditions, indicated that OxyR1 acts as a negative regulator of ahpC in A. brasilense. Sequence of the promoter of ahpC, predicted on the basis of transcriptional start site, and an enhanced expression of ahpC:lacZ fusion in chrR2::km mutant background suggested that ahpC promoter was RpoE2 dependent. Thus, this study shows that in A. brasilense Sp7, ahpC expression is regulated negatively by OxyR1 but is regulated positively by RpoE2, an oxidative-stress-responsive sigma factor. It also shows that OxyR1 regulates the expression RpoE1, which is known to play an important role during photooxidative stress in A. brasilense.

  3. A role for doctors in assisted dying? An analysis of legal regulations and medical professional positions in six European countries.

    Science.gov (United States)

    Bosshard, G; Broeckaert, B; Clark, D; Materstvedt, L J; Gordijn, B; Müller-Busch, H C

    2008-01-01

    To analyse legislation and medical professional positions concerning the doctor's role in assisted dying in western Europe, and to discuss their implications for doctors. This paper is based on country-specific reports by experts from European countries where assisted dying is legalised (Belgium, The Netherlands), or openly practiced (Switzerland), or where it is illegal (Germany, Norway, UK). Laws on assisted dying in The Netherlands and Belgium are restricted to doctors. In principle, assisted suicide (but not euthanasia) is not illegal in either Germany or Switzerland, but a doctor's participation in Germany would violate the code of professional medical conduct and might contravene of a doctor's legal duty to save life. The Assisted Dying for the Terminally Ill Bill proposed in the UK in 2005 focused on doctors, whereas the Proposal on Assisted Dying of the Norwegian Penal Code Commission minority in 2002 did not. Professional medical organisations in all these countries except The Netherlands maintain the position that medical assistance in dying conflicts with the basic role of doctors. However, in Belgium and Switzerland, and for a time in the UK, these organisations dropped their opposition to new legislation. Today, they regard the issue as primarily a matter for society and politics. This "neutral" stance differs from the official position of the Royal Dutch Medical Association which has played a key role in developing the Dutch practice of euthanasia as a "medical end-of-life decision" since the 1970s. A society moving towards an open approach to assisted dying should carefully identify tasks to assign exclusively to medical doctors, and distinguish those possibly better performed by other professions.

  4. Conditionally positive effect of the TetR-family transcriptional regulator AtrA on streptomycin production by Streptomyces griseus.

    Science.gov (United States)

    Hirano, Setsu; Tanaka, Katsuyuki; Ohnishi, Yasuo; Horinouchi, Sueharu

    2008-03-01

    AtrA, a transcriptional activator for actII-ORF4, encoding the pathway-specific transcriptional activator of the actinorhodin biosynthetic gene cluster in Streptomyces coelicolor A3(2), has been shown to bind the region upstream from the promoter of strR, encoding the pathway-specific transcriptional activator of the streptomycin biosynthetic gene cluster in Streptomyces griseus [Uguru et al. (2005) Mol Microbiol 58, 131-150]. The atrA orthologue (atrA-g) in S. griseus was constitutively transcribed throughout growth from a promoter located about 250 nt upstream of the translational start codon, as determined by S1 nuclease mapping. DNase I footprinting showed that histidine-tagged AtrA-g bound an inverted repeat located upstream of strR at positions -117 to -142 relative to the transcriptional start point of strR as +1. This AtrA-g-binding site was between two AdpA-binding sites at approximately nucleotide positions -270 and -50. AdpA is a central transcriptional activator in the A-factor regulatory cascade and essential for the transcription of strR. AtrA-g and AdpA simultaneously bound the respective binding sites. In contrast to AdpA, AtrA-g was non-essential for strR transcription; an atrA-g-disrupted strain produced streptomycin on routine agar media to the same extent as the wild-type strain. However, the atrA-g-disrupted strain tended to produce a smaller amount of streptomycin than the wild-type strain under some conditions, for example, on Bennett agar containing 1 % maltose and on a minimal medium. Therefore, AtrA-g had a conditionally positive effect on streptomycin production, as a tuner, probably by enhancing the AdpA-dependent transcriptional activation of strR in a still unknown manner.

  5. Temperature regulates positively photoblastic seed germination in four ficus (moraceae) tree species from contrasting habitats in a seasonal tropical rainforest.

    Science.gov (United States)

    Chen, Hui; Cao, Min; Baskin, Jerry M; Baskin, Carol C

    2013-08-01

    Differences in seed germination responses of trees in tropical forests to temperature and light quality may contribute to their coexistence. We investigated the effects of temperature and red:far-red light (R:FR ratio) on seed germination of two gap-demanding species (Ficus hispida and F. racemosa) and two shade-tolerant species (F. altissima and F. auriculata) in a tropical seasonal rainforest in southwest China. A R:FR ratio gradient was created by filtering fluorescent light through polyester filters. Four temperature treatments were used to test the effect of temperature on seed germination of the four Ficus tree species across the R:FR gradient. Seeds of the four Ficus species were positively photoblastic. Seed germination of F. hispida and F. racemosa was not affected across the R:FR ratio gradient (0.25-1.19) at 25/35°C, but it was inhibited under low R:FR at 22/23°C. By contrast, germination percentages of F. altissima and F. auriculata were not inhibited along the entire light gradient in all temperature treatments. Differences in germination responses of Ficus species might contribute to differences in their habitat preferences. The inhibitory effect of understory temperatures in the forest might be a new mechanism that prevents positively photoblastic seeds of the gap-demanding species such as F. hispida and F. racemosa from germinating in the understory and in small canopy gaps.

  6. Impact of Pressure Regulation of Cryogenic Fluids and EPICS EPID Feedback on the Monochromatic Beam Position Stability of the 7ID Beamline at the Advanced Photon Source

    Science.gov (United States)

    Dufresne, Eric M.; Arms, Dohn A.; Landahl, Eric C.; Walko, Donald A.

    2007-01-01

    The first crystal mount of the double-crystal Si (111) cryogenically cooled monochromator of the 7ID beamline at the Advanced Photon Source (APS) is slightly sensitive to pressure variations in the cryogenic lines. Pressure variations during a liquid nitrogen cryocooler fill every 4 hours move the beam by tens of microns. Pressure variations due to the cryocooler closed-loop pressure control with a heater element (around 0.3 psi) move the beam by 5 microns every 15 seconds. We have recently stabilized the coolant pressure with a simple pressure regulator that is in use at many beamlines of the APS. This paper shows the improvements in beam position stability made using this simple yet effective pressure-regulation circuit. We also recently added beam-position feedback to the second-crystal Bragg angle of the monochromator. The Experimental Physics and Industrial Control System (EPICS) Enhanced Proportional-Integral-Differential (EPID) feedback record implementation resulted in an additional improvement of the standard deviation of the beam position to 0.5 μm.

  7. Positive benefits of caring on nurses' motivation and well-being: a diary study about the role of emotional regulation abilities at work.

    Science.gov (United States)

    Donoso, Luis Manuel Blanco; Demerouti, Evangelia; Garrosa Hernández, Eva; Moreno-Jiménez, Bernardo; Carmona Cobo, Isabel

    2015-04-01

    Recent research reveals that not all job demands have negative effects on workers' well-being and suggests that the negative or positive effects of specific job demands depend on the occupational sector. Specifically, emotional job demands form the heart of the work for nurses and for this reason they can be interpreted by nurses as a challenge that promotes motivation and well-being among these professionals, especially if personal and job resources become available. The study had two objectives. First, to examine whether daily emotional demands within a nursing work context have a positive effect on nurses' daily motivation at work (vigour) and well-being at home (vitality and positive affect). Second, to explore whether this positive effect could be enhanced by nurses' emotional regulation abilities. This research used a diary design to explore daily experiences and to analyze how variations in specific job or personal characteristics can affect levels of motivation and well-being across days. Fifty-three nurses working in different Spanish hospitals and primary health care centres completed a general questionnaire and a diary booklet over 5 consecutive working days in two different moments, after work and at night (N=53 participants and N=265 observations). In line with our hypotheses, multi-level analyses revealed that, on the one hand, day-level emotional demands at work had a positive effect on vigour at work and on vitality at home. On the other hand, analyses showed that nurses with higher emotional regulation abilities have more motivation at work and well-being at home when they have to face high emotional demands at work, showing a spill over effect after work. These findings support the idea that emotional demands from the nursing profession can act as challenges which promote motivation and well-being, especially if internal emotional resources become available. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Vibrio cholerae leuO Transcription Is Positively Regulated by ToxR and Contributes to Bile Resistance.

    Science.gov (United States)

    Ante, Vanessa M; Bina, X Renee; Howard, Mondraya F; Sayeed, Sameera; Taylor, Dawn L; Bina, James E

    2015-11-01

    Vibrio cholerae is an aquatic organism and facultative human pathogen that colonizes the small intestine. In the small intestine, V. cholerae is exposed to a variety of antimicrobial compounds, including bile. V. cholerae resistance to bile is multifactorial and includes alterations in the membrane permeability barrier that are mediated by ToxR, a membrane-associated transcription factor. ToxR has also been shown to be required for activation of the LysR family transcription factor leuO in response to cyclic dipeptides. LeuO has been implicated in the regulation of multiple V. cholerae phenotypes, including biofilm production and virulence. In this study, we investigated the effects of bile on leuO expression. We show that leuO transcription increased in response to bile and bile salts but not in response to other detergents. The bile-dependent increase in leuO expression was dependent on ToxR, which was found to bind directly to the leuO promoter. The periplasmic domain of ToxR was required for basal leuO expression and for the bile-dependent induction of both leuO and ompU transcription. V. cholerae mutants that did not express leuO exhibited increased bile susceptibility, suggesting that LeuO contributes to bile resistance. Our collective results demonstrate that ToxR activates leuO expression in response to bile and that LeuO is a component of the ToxR-dependent responses that contribute to bile resistance. The success of Vibrio cholerae as a human pathogen is dependent upon its ability to rapidly adapt to changes in its growth environment. Growth in the human gastrointestinal tract requires the expression of genes that provide resistance to host antimicrobial compounds, including bile. In this work, we show for the first time that the LysR family regulator LeuO mediates responses in V. cholerae that contribute to bile resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Considering an affect regulation framework for examining the association between body dissatisfaction and positive body image in Black older adolescent females: does body mass index matter?

    Science.gov (United States)

    Webb, Jennifer B; Butler-Ajibade, Phoebe; Robinson, Seronda A

    2014-09-01

    The present study provided an initial evaluation of an affect regulation model describing the association between body dissatisfaction and two contemporary measures of positive body image among 247 Black college-bound older adolescent females. We further tested whether possessing a higher body mass index (BMI) would strengthen these associations. Self-reported height and weight were used to calculate BMI. Respondents also completed a culturally-sensitive figure rating scale along with assessments of body appreciation and body image flexibility. Results indicated a robust positive association between the two measures of positive body image; BMI was the strongest predictor of both body appreciation and body image flexibility with body size discrepancy (current minus ideal) contributing incremental variance to both models tested. Implications for improving our understanding of the association between positive and negative body image and bolstering positive body image to promote health-protective behaviors among Black young women at this developmental juncture are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

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    Lu Kun

    2008-12-01

    Full Text Available Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7% stained positive for Her2 (IHC 3+, and 54% (122/223 of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5% were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2

  11. Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte Structure

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    Xueping Fan

    2012-07-01

    Full Text Available Robo2 is the cell surface receptor for the repulsive guidance cue Slit and is involved in axon guidance and neuronal migration. Nephrin is a podocyte slit-diaphragm protein that functions in the kidney glomerular filtration barrier. Here, we report that Robo2 is expressed at the basal surface of mouse podocytes and colocalizes with nephrin. Biochemical studies indicate that Robo2 forms a complex with nephrin in the kidney through adaptor protein Nck. In contrast to the role of nephrin that promotes actin polymerization, Slit2-Robo2 signaling inhibits nephrin-induced actin polymerization. In addition, the amount of F-actin associated with nephrin is increased in Robo2 knockout mice that develop an altered podocyte foot process structure. Genetic interaction study further reveals that loss of Robo2 alleviates the abnormal podocyte structural phenotype in nephrin null mice. These results suggest that Robo2 signaling acts as a negative regulator on nephrin to influence podocyte foot process architecture.

  12. Positive parenting mitigates the effects of poor self-regulation on BMI trajectories from age 4 to 15 years

    Science.gov (United States)

    Connell, Lauren E.; Francis, Lori A.

    2014-01-01

    Objective This study sought to determine whether parenting style moderated the effects of delay of gratification on BMI trajectories from age 4 to 15 years. Methods Longitudinal data were analyzed on 778 children drawn from the Study of Early Child Care and Youth Development. Parenting style (authoritative, authoritarian, permissive, neglectful) was created from measures of mothers’ sensitivity and expectations for self-control when children were age 4 years. Self-regulation was also measured at 4 years using a well-known delay of gratification protocol. BMI was calculated from measured height and weight at each time point. Mixed modeling was used to test the interaction of parenting styles and ability to delay gratification on BMI trajectories from 4 to 15 years. Results There was a significant interaction effect of parenting and ability to delay on BMI growth from 4 to 15 years for boys. Boys who had authoritarian mothers and failed to delay gratification had a significantly steeper rate of growth in BMI from childhood through adolescence than children in any other parenting x delay group. Conclusions Authoritative and permissive parenting styles were protective against more rapid BMI gains for boys who could not delay gratification. Ability to delay gratification was protective against BMI gains for boys who had parents with authoritarian or neglectful parenting styles. PMID:23977874

  13. Epigenetic mechanisms and associated brain circuits in the regulation of positive emotions: A role for transposable elements.

    Science.gov (United States)

    Gaudi, Simona; Guffanti, Guia; Fallon, James; Macciardi, Fabio

    2016-10-15

    Epigenetic programming and reprogramming are at the heart of cellular differentiation and represent developmental and evolutionary mechanisms in both germline and somatic cell lines. Only about 2% of our genome is composed of protein-coding genes, while the remaining 98%, once considered "junk" DNA, codes for regulatory/epigenetic elements that control how genes are expressed in different tissues and across time from conception to death. While we already know that epigenetic mechanisms are at play in cancer development and in regulating metabolism (cellular and whole body), the role of epigenetics in the developing prenatal and postnatal brain, and in maintaining a proper brain activity throughout the various stages of life, in addition to having played a critical role in human evolution, is a relatively new domain of knowledge. Here we present the current state-of-the-art techniques and results of these studies within the domain of emotions, and then speculate on how genomic and epigenetic mechanisms can modify and potentially alter our emotional (limbic) brain and affect our social interactions. J. Comp. Neurol. 524:2944-2954, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. CXCL12-mediated feedback from granule neurons regulates generation and positioning of new neurons in the dentate gyrus.

    Science.gov (United States)

    Abe, Philipp; Wüst, Hannah M; Arnold, Sebastian J; van de Pavert, Serge A; Stumm, Ralf

    2018-03-14

    Adult hippocampal neurogenesis is implicated in learning and memory processing. It is tightly controlled at several levels including progenitor proliferation as well as migration, differentiation and integration of new neurons. Hippocampal progenitors and immature neurons reside in the subgranular zone (SGZ) and are equipped with the CXCL12-receptor CXCR4 which contributes to defining the SGZ as neurogenic niche. The atypical CXCL12-receptor CXCR7 functions primarily by sequestering extracellular CXCL12 but whether CXCR7 is involved in adult neurogenesis has not been assessed. We report that granule neurons (GN) upregulate CXCL12 and CXCR7 during dentate gyrus maturation in the second postnatal week. To test whether GN-derived CXCL12 regulates neurogenesis and if neuronal CXCR7 receptors influence this process, we conditionally deleted Cxcl12 and Cxcr7 from the granule cell layer. Cxcl12 deletion resulted in lower numbers, increased dispersion and abnormal dendritic growth of immature GN and reduced neurogenesis. Cxcr7 ablation caused an increase in progenitor proliferation and progenitor numbers and reduced dispersion of immature GN. Thus, we provide a new mechanism where CXCL12-signals from GN prevent dispersion and support maturation of newborn GN. CXCR7 receptors of GN modulate the CXCL12-mediated feedback from GN to the neurogenic niche. © 2018 Wiley Periodicals, Inc.

  15. AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

    International Nuclear Information System (INIS)

    Liu, Xin; Zhu, Yanming; Zhai, Hong; Cai, Hua; Ji, Wei; Luo, Xiao; Li, Jing; Bai, Xi

    2012-01-01

    Highlights: ► AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. ► AtPP2CG1 up-regulates the expression of marker genes in different pathways. ► AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, and abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2–3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter–GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.

  16. Evidence of circadian rhythm, oxygen regulation capacity, metabolic repeatability and positive correlations between forced and spontaneous maximal metabolic rates in lake sturgeon Acipenser fulvescens.

    Science.gov (United States)

    Svendsen, Jon C; Genz, Janet; Anderson, W Gary; Stol, Jennifer A; Watkinson, Douglas A; Enders, Eva C

    2014-01-01

    Animal metabolic rate is variable and may be affected by endogenous and exogenous factors, but such relationships remain poorly understood in many primitive fishes, including members of the family Acipenseridae (sturgeons). Using juvenile lake sturgeon (Acipenser fulvescens), the objective of this study was to test four hypotheses: 1) A. fulvescens exhibits a circadian rhythm influencing metabolic rate and behaviour; 2) A. fulvescens has the capacity to regulate metabolic rate when exposed to environmental hypoxia; 3) measurements of forced maximum metabolic rate (MMR(F)) are repeatable in individual fish; and 4) MMR(F) correlates positively with spontaneous maximum metabolic rate (MMR(S)). Metabolic rates were measured using intermittent flow respirometry, and a standard chase protocol was employed to elicit MMR(F). Trials lasting 24 h were used to measure standard metabolic rate (SMR) and MMR(S). Repeatability and correlations between MMR(F) and MMR(S) were analyzed using residual body mass corrected values. Results revealed that A. fulvescens exhibit a circadian rhythm in metabolic rate, with metabolism peaking at dawn. SMR was unaffected by hypoxia (30% air saturation (O(2sat))), demonstrating oxygen regulation. In contrast, MMR(F) was affected by hypoxia and decreased across the range from 100% O(2sat) to 70% O(2sat). MMR(F) was repeatable in individual fish, and MMR(F) correlated positively with MMR(S), but the relationships between MMR(F) and MMR(S) were only revealed in fish exposed to hypoxia or 24 h constant light (i.e. environmental stressor). Our study provides evidence that the physiology of A. fulvescens is influenced by a circadian rhythm and suggests that A. fulvescens is an oxygen regulator, like most teleost fish. Finally, metabolic repeatability and positive correlations between MMR(F) and MMR(S) support the conjecture that MMR(F) represents a measure of organism performance that could be a target of natural selection.

  17. Online Coaching of Emotion-Regulation Strategies for Parents: Efficacy of the Online Rational Positive Parenting Program and Attention Bias Modification Procedures.

    Science.gov (United States)

    David, Oana A; Capris, David; Jarda, Alexandra

    2017-01-01

    Parenting programs are currently treatment of choice for behavioral disorders in children and one of their main components is reducing the negativity bias in the child-parent dyad. The Rational Positive Parenting Program (rPPP) is a program with a special focus on parent emotion-regulation functional reappraisal strategies, which has recently received consistent support for reducing child externalizing and internalizing disorders. In the last years, online interventions were proliferated and the Attention Bias Modification (ABM) becoming a promising implicit therapeutic intervention based on attention deployment emotion-regulation strategy, or adjunctive module to usual treatments, with results in multiple domains, varying from pain to self-esteem and emotional disorders (e.g., anxiety). We conducted two studies to investigate (1) the efficacy of the ABM procedures applied to parents and (2) the efficacy of the online version of the rPPP augmented with an ABM module. A total of 42 parents of children aged 2-12 years old participated in the first study, being allocated either to the ABM training or wait-list. Positive results were reported by the parents participating in the ABM group for own distress, satisfaction, positive interactions with the child, and child's strengths. In the second study, 53 parents and their children were allocated either in the rPPP group or in the rPPP + ABM group. Results show that ABM training can boost the effects of the rPPP on the strengths of children reported by the parents after the intervention. Findings are discussed in the light of limited research on using online tools for coaching effective emotion-regulation strategies for parents.

  18. Evidence of circadian rhythm, oxygen regulation capacity, metabolic repeatability and positive correlations between forced and spontaneous maximal metabolic rates in lake sturgeon Acipenser fulvescens.

    Directory of Open Access Journals (Sweden)

    Jon C Svendsen

    Full Text Available Animal metabolic rate is variable and may be affected by endogenous and exogenous factors, but such relationships remain poorly understood in many primitive fishes, including members of the family Acipenseridae (sturgeons. Using juvenile lake sturgeon (Acipenser fulvescens, the objective of this study was to test four hypotheses: 1 A. fulvescens exhibits a circadian rhythm influencing metabolic rate and behaviour; 2 A. fulvescens has the capacity to regulate metabolic rate when exposed to environmental hypoxia; 3 measurements of forced maximum metabolic rate (MMR(F are repeatable in individual fish; and 4 MMR(F correlates positively with spontaneous maximum metabolic rate (MMR(S. Metabolic rates were measured using intermittent flow respirometry, and a standard chase protocol was employed to elicit MMR(F. Trials lasting 24 h were used to measure standard metabolic rate (SMR and MMR(S. Repeatability and correlations between MMR(F and MMR(S were analyzed using residual body mass corrected values. Results revealed that A. fulvescens exhibit a circadian rhythm in metabolic rate, with metabolism peaking at dawn. SMR was unaffected by hypoxia (30% air saturation (O(2sat, demonstrating oxygen regulation. In contrast, MMR(F was affected by hypoxia and decreased across the range from 100% O(2sat to 70% O(2sat. MMR(F was repeatable in individual fish, and MMR(F correlated positively with MMR(S, but the relationships between MMR(F and MMR(S were only revealed in fish exposed to hypoxia or 24 h constant light (i.e. environmental stressor. Our study provides evidence that the physiology of A. fulvescens is influenced by a circadian rhythm and suggests that A. fulvescens is an oxygen regulator, like most teleost fish. Finally, metabolic repeatability and positive correlations between MMR(F and MMR(S support the conjecture that MMR(F represents a measure of organism performance that could be a target of natural selection.

  19. Assessment of effects of differences in trunk posture during Fowler’s position on hemodynamics and cardiovascular regulation in older and younger subjects

    Directory of Open Access Journals (Sweden)

    Kubota S

    2017-03-01

    maintenance of SV and inhibited tachycardic response compared to an upright whole trunk regardless of age, although the autonomic mechanisms underlying tachycardic responses differed between younger and older adults. An upright upper trunk in Fowler’s position might help to reduce orthostatic stress and facilitate routine activities and conversation in frail patients. Keywords: aging, cardiovascular regulation, hemodynamics, Fowler’s position, stroke volume

  20. c-di-AMP: An Essential Molecule in the Signaling Pathways that Regulate the Viability and Virulence of Gram-Positive Bacteria.

    Science.gov (United States)

    Fahmi, Tazin; Port, Gary C; Cho, Kyu Hong

    2017-08-07

    Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis . c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become

  1. Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

    Energy Technology Data Exchange (ETDEWEB)

    Li, Luchuan; Lv, Bin; Chen, Bo [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Guan, Ming [Department of General Surgery, Qihe People' s Hospital, Qihe, Shandong 251100 (China); Sun, Yongfeng [Department of General Surgery, Licheng District People' s Hospital, Jinan, Shandong 250115 (China); Li, Haipeng [Department of General Surgery, Caoxian People' s Hospital, Caoxian, Shandong 274400 (China); Zhang, Binbin; Ding, Changyuan; He, Shan [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Zeng, Qingdong, E-mail: qingdz0201@163.com [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China)

    2015-07-10

    Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.

  2. Interferon Potentiates Toll-Like Receptor-Induced Prostaglandin D2 Production through Positive Feedback Regulation between Signal Transducer and Activators of Transcription 1 and Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Ji-Yun Kim

    2017-12-01

    Full Text Available Prostaglandin D2 (PGD2 is a potent lipid mediator that controls inflammation, and its dysregulation has been implicated in diverse inflammatory disorders. Despite significant progress made in understanding the role of PGD2 as a key regulator of immune responses, the molecular mechanism underlying PGD2 production remains unclear, particularly upon challenge with different and multiple inflammatory stimuli. Interferons (IFNs potentiate macrophage activation and act in concert with exogenous inflammatory mediators such as toll-like receptor (TLR ligands to amplify inflammatory responses. A recent study found that IFN-γ enhanced lipopolysaccharide-induced PGD2 production, indicating a role of IFNs in PGD2 regulation. Here, we demonstrate that TLR-induced PGD2 production by macrophages was significantly potentiated by signaling common to IFN-β and IFN-γ in a signal transducer and activators of transcription (STAT1-dependent mechanism. Such potentiation by IFNs was also observed for PGE2 production, despite the differential regulation of PGD synthase and PGE synthase isoforms mediating PGD2 and PGE2 production under inflammatory conditions. Mechanistic analysis revealed that the generation of intracellular reactive oxygen species (ROS was remarkably potentiated by IFNs and required for PGD2 production, but was nullified by STAT1 deficiency. Conversely, the regulation of STAT1 level and activity by IFNs was largely dependent on ROS levels. Using a model of zymosan-induced peritonitis, the relevance of this finding in vivo was supported by marked inhibition of PGD2 and ROS produced in peritoneal exudate cells by STAT1 deficiency. Collectively, our findings suggest that IFNs, although not activating on their own, are potent amplifiers of TLR-induced PGD2 production via positive-feedback regulation between STAT1 and ROS.

  3. Regulation and gene expression profiling of NKG2D positive human cytomegalovirus-primed CD4+ T-cells.

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    Helle Jensen

    Full Text Available NKG2D is a stimulatory receptor expressed by natural killer (NK cells, CD8(+ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4(+ T-cells, however recently a subset of NKG2D(+ CD4(+ T-cells has been found, which is specific for human cytomegalovirus (HCMV. This particular subset of HCMV-specific NKG2D(+ CD4(+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D(+ CD4(+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4(+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA to investigate the gene expression profile of NKG2D(+ CD4(+ T-cells, generated from HCMV-primed CD4(+ T-cells. We show that the HCMV-primed NKG2D(+ CD4(+ T-cells possess a higher differentiated phenotype than the NKG2D(- CD4(+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4(+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4(+ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4(+ T-cells, whereas it is produced de novo in resting CD4(+ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D(+ CD4(+ T-cells, as well as the mechanisms regulating NKG2D cell surface expression.

  4. Elevated YKL40 is associated with advanced prostate cancer (PCa) and positively regulates invasion and migration of PCa cells.

    Science.gov (United States)

    Jeet, Varinder; Tevz, Gregor; Lehman, Melanie; Hollier, Brett; Nelson, Colleen

    2014-10-01

    Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in tumours from patients with advanced stage cancers, including prostate cancer (PCa). The exact function of YKL40 is poorly understood, but it has been shown to play an important role in promoting tumour angiogenesis and metastasis. The therapeutic value and biological function of YKL40 are unknown in PCa. The objective of this study was to examine the expression and function of YKL40 in PCa. Gene expression analysis demonstrated that YKL40 was highly expressed in metastatic PCa cells when compared with less invasive and normal prostate epithelial cell lines. In addition, the expression was primarily limited to androgen receptor-positive cell lines. Evaluation of YKL40 tissue expression in PCa patients showed a progressive increase in patients with aggressive disease when compared with those with less aggressive cancers and normal controls. Treatment of LNCaP and C4-2B cells with androgens increased YKL40 expression, whereas treatment with an anti-androgen agent decreased the gene expression of YKL40 in androgen-sensitive LNCaP cells. Furthermore, knockdown of YKL40 significantly decreased invasion and migration of PCa cells, whereas overexpression rendered them more invasive and migratory, which was commensurate with an enhancement in the anchorage-independent growth of cells. To our knowledge, this study characterises the role of YKL40 for the first time in PCa. Together, these results suggest that YKL40 plays an important role in PCa progression and thus inhibition of YKL40 may be a potential therapeutic strategy for the treatment of PCa. © 2014 The authors.

  5. Increased a-series gangliosides positively regulate leptin/Ob receptor-mediated signals in hypothalamus of GD3 synthase-deficient mice.

    Science.gov (United States)

    Ji, Shuting; Tokizane, Kyohei; Ohkawa, Yuki; Ohmi, Yuhsuke; Banno, Ryoichi; Okajima, Tetsuya; Kiyama, Hiroshi; Furukawa, Koichi; Furukawa, Keiko

    2016-10-21

    Gangliosides are widely involved in the regulation of cells and organs. However, little is known about their roles in adipose tissues and hypothalamus. In GD3 synthase-knockout (GD3S KO) mice, deletion of b-series gangliosides resulted in the reduction of serum leptin due to disturbed secretion from adipocytes. To examine whether leptin signals altered, leptin/leptin receptor (ObR)-mediated signaling in hypothalamus was analyzed. Hypothalamus of GD3S KO mouse showed increased expression of GM1 and GD1a, and increased activation of ObR-mediated signals such as pSTAT3 and c-Fos. Leptin stimulation of hypothalamus-derived N-41 cells and their transfectants with GD3S cDNA showed that a-series gangliosides positively regulate leptin/ObR-mediated signals. Co-precipitation analysis revealed that ObR interacts with a-series gangliosides with increased association by leptin stimulation. In brown adipose tissues (BAT) of GD3S KO mice, their weights and adipocyte numbers were increased, and BAT markers such as PGC1α and UCP-1 were also up-regulated. These results suggested that leptin/ObRb-mediated signals were enhanced in hypothalamus of GD3S KO mice due to increased a-series gangliosides, leading to the apparently similar features of energy expenditure between the KO and wild type mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

    Directory of Open Access Journals (Sweden)

    Yongsoon Kim

    Full Text Available In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

  7. ASM-3 Acid Sphingomyelinase Functions as a Positive Regulator of the DAF-2/AGE-1 Signaling Pathway and Serves as a Novel Anti-Aging Target

    Science.gov (United States)

    Kim, Yongsoon; Sun, Hong

    2012-01-01

    In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals. PMID:23049887

  8. ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

    Science.gov (United States)

    Kim, Yongsoon; Sun, Hong

    2012-01-01

    In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

  9. Positional mapping and candidate gene analysis of the mouse Ccs3 locus that regulates differential susceptibility to carcinogen-induced colorectal cancer.

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    Charles Meunier

    Full Text Available The Ccs3 locus on mouse chromosome 3 regulates differential susceptibility of A/J (A, susceptible and C57BL/6J (B6, resistant mouse strains to chemically-induced colorectal cancer (CRC. Here, we report the high-resolution positional mapping of the gene underlying the Ccs3 effect. Using phenotype/genotype correlation in a series of 33 AcB/BcA recombinant congenic mouse strains, as well as in groups of backcross populations bearing unique recombinant chromosomes for the interval, and in subcongenic strains, we have delineated the maximum size of the Ccs3 physical interval to a ∼2.15 Mb segment. This interval contains 12 annotated transcripts. Sequencing of positional candidates in A and B6 identified many either low-priority coding changes or non-protein coding variants. We found a unique copy number variant (CNV in intron 15 of the Nfkb1 gene. The CNV consists of two copies of a 54 bp sequence immediately adjacent to the exon 15 splice site, while only one copy is found in CRC-susceptible A. The Nfkb1 protein (p105/p50 expression is much reduced in A tumors compared to normal A colonic epithelium as analyzed by immunohistochemistry. Studies in primary macrophages from A and B6 mice demonstrate a marked differential activation of the NfκB pathway by lipopolysaccharide (kinetics of stimulation and maximum levels of phosphorylated IκBα, with a more robust activation being associated with resistance to CRC. NfκB has been previously implicated in regulating homeostasis and inflammatory response in the intestinal mucosa. The interval contains another positional candidate Slc39a8 that is differentially expressed in A vs B6 colons, and that has recently been associated in CRC tumor aggressiveness in humans.

  10. Triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1

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    Zhou, Heng [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Guo, Wei [Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Long, Cong; Wang, Huan; Wang, Jingchao [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Sun, Xiaoping, E-mail: xsun6@whu.edu.cn [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); State Key Laboratory of Virology, Wuhan University, Wuhan 430072 (China)

    2015-01-16

    Highlights: • Triptolide inhibits proliferation of EBV-positive lymphoma cells in vitro and in vivo. • Triptolide reduces expression of LMP1 by decreasing its transcription level. • Triptolide inhibits ED-L1 promoter activity. - Abstract: Epstein–Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities. In this study, it is determined whether triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes. The CCK-8 assays were performed to examine cell viabilities of EBV-positive B95-8 and P3HR-1 cells treated by triptolide. The mRNA and protein levels of LMP1 were examined by real time-PCR and Western blotting, respectively. The activities of two LMP1 promoters (ED-L1 and TR-L1) were determined by Dual luciferase reportor assay. The results showed that triptolide inhibited the cell viability of EBV-positive B lymphocytes, and the over-expression of LMP1 attenuated this inhibitory effect. Triptolide decreased the LMP1 expression and transcriptional levels in EBV-positive B cells. The activity of LMP1 promoter ED-L1 in type III latent infection was strongly suppressed by triptolide treatment. In addition, triptolide strongly reduced growth of B95-8 induced B lymphoma in BALB/c nude mice. These results suggest that triptolide decreases proliferation of EBV-induced B lymphocytes possibly by a mechanism related to down-regulation of the LMP1 expression.

  11. Local Transformations of Androgens into Estradiol by Aromatase P450 Is Involved in the Regulation of Prolactin and the Proliferation of Pituitary Prolactin-Positive Cells

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    Carretero Hernández, Marta; Iglesias Osma, María Carmen; Carretero, Manuel; Herrero, Julio J.

    2014-01-01

    In previous studies we demonstrated the immunohistochemical expression of aromatase in pituitary cells. In order to determine whether pituitary aromatase is involved in the paracrine regulation of prolactin-producing pituitary cells and the physiological relevance of pituitary aromatase in the control of these cells, an in vivo and in vitro immunocytochemical and morphometric study of prolactin-positive pituitary cells was carried out on the pituitary glands of adult male rats treated with the aromatase antagonist fadrozole. Moreover, we analyzed the expression of mRNA for the enzyme in pituitary cells of male adult rats by in situ hybridization. The aromatase-mRNA was seen to be located in the cytoplasm of 41% of pituitary cells and was well correlated with the immunocytochemical staining. After in vivo treatment with fadrozole, the size (cellular and nuclear areas) of prolactin cells, as well as the percentage of prolactin-positive cells and the percentage of proliferating-prolactin cells, was significantly decreased. Moreover, fadrozole decreased serum prolactin levels. In vitro, treatment with fadrozole plus testosterone induced similar effects on prolactin-positive cells, inhibiting their cellular proliferation. Our results suggest that under physiological conditions aromatase P450 exerts a relevant control over male pituitary prolactin-cells, probably transforming testosterone to estradiol in the pituitary gland. PMID:24978194

  12. AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin, E-mail: fangfei6073@126.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Zhu, Yanming, E-mail: ymzhu2001@neau.edu.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Zhai, Hong, E-mail: Zhai.h@neigaehrb.ac.cn [Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Harbin 150040 (China); Cai, Hua, E-mail: small-big@sohu.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Ji, Wei, E-mail: iwei_j@hotmail.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Luo, Xiao, E-mail: luoxiao2010@yahoo.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Li, Jing, E-mail: lijing@neau.edu.cn [Plant Secondary Metabolism Laboratory, Northeast Agricultural University, Harbin 150030 (China); Bai, Xi, E-mail: baixi@neau.edu.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. Black-Right-Pointing-Pointer AtPP2CG1 up-regulates the expression of marker genes in different pathways. Black-Right-Pointing-Pointer AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, and abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2-3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter-GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.

  13. Up-Regulation of Glioma-Associated Oncogene Homolog 1 Expression by Serum Starvation Promotes Cell Survival in ER-Positive Breast Cancer Cells

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    Juan Xu

    2015-07-01

    Full Text Available Background/Aims: Cancer cells are resistant to ischemia and starvation. Glioma-associated oncogene homolog 1 (Gli1 is a positive transcriptional activator of Hedgehog (Hh pathway and plays an essential role in the development of cancers, including breast cancer. However, how Gli1 promotes cell survival remains elusive. The main purpose of this study is to investigate the pro-survival effect of Gli1 under serum starvation and its molecular mechanism in ER-positive breast cancer cells. Methods: Gene expression was determined by quantitative real-time PCR (QRT-PCR and Western blot. The survival of Gli1 stably transfected ER-positive breast cancer cell lines (Gli1-MCF-7 and Gli1-T47D cells and their untransfected control cells was estimated by WST-8 assay. Microarray analysis was performed to screen downstream Hh/Gli1 target genes in Gli1-overexpressed MCF-7 cells. Transcriptional activities of NF-kappaB were measured by luciferase assays. ChIP analysis was performed to explore whether cIAP2 was a direct target gene of Gli1. Results: Serum starvation significantly up-regulated the expression of Gli1 gene through activating PI3K/AKT pathway. Over-expression of Gli1 markedly promoted cell survival under serum starvation. Microarray analysis revealed that 338 genes were differentially expressed in Gli1-MCF-7 cells compared with those in the control cells. Among these genes, cellular inhibitor of apoptosis 2 (cIAP2, coding an anti-apoptosis and pro-survival protein, was significantly up-regulated not only by Hh/Gli1 pathway, but also by serum starvation. However, ChIP assay revealed no binding of Gli1 to cIAP2 promoter at the region of -1792 to -1568bp. Moreover, over-expression of Gli1 resulted in enhanced trans-activation of transcriptional factor NF-κB. Suppression of NF-κB signaling with NF-κB inhibitor Bay11-7082, significantly reduced the expression of cIAP2 and the cell survival under serum starvation. Conclusion: Serum starvation

  14. TetR is a positive regulator of the tetanus toxin gene in Clostridium tetani and is homologous to botR.

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    Marvaud, J C; Eisel, U; Binz, T; Niemann, H; Popoff, M R

    1998-12-01

    The TetR gene immediately upstream from the tetanus toxin (TeTx) gene was characterized. It encodes a 21,562-Da protein which is related (50 to 65% identity) to the equivalent genes (botR) in Clostridium botulinum. TetR has the feature of a DNA binding protein with a basic pI (9.53). It contains a helix-turn-helix motif and shows 29% identity with other putative regulatory genes in Clostridium, i.e., uviA from C. perfringens and txeR from C. difficile. We report for the first time the transformation of C. tetani by electroporation, which permitted us to investigate the function of tetR. Overexpression of tetR in C. tetani induced an increase in TeTx production and in the level of the corresponding mRNA. This indicates that TetR is a transcriptional activator of the TeTx gene. Overexpression of botR/A (60% identity with TetR at the amino acid level) in C. tetani induced an increase in TeTx production comparable to that for overexpression of tetR. However, botR/C (50% identity with TetR at the amino acid level) was less efficient. This supports that TetR positively regulates the TeTx gene in C. tetani and that a conserved mechanism of regulation of the neurotoxin genes is involved in C. tetani and C. botulinum.

  15. The frequency of double-positive thymocytes expressing an αβ TCR clonotype regulates peripheral CD4 T cell compartment homeostasis

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    Reed, Amy J; Zarrabi, Yasaman; Perate, Alison L; Jeganathan, Arjun; Naji, Ali; Noorchashm, Hooman

    2005-01-01

    The present study aimed to determine whether the frequency of double positive (DP) thymocytes expressing αβ T-cell receptor (TCR) clonotypes at the time of selection regulates peripheral CD4 T-cell compartment size. Scid recipients were inoculated with various ratios of TCR Cα0/0 and wild-type bone marrow (BM) stem cells. Increasing the frequency of TCR Cα0/0 thymocytes at steady-state introduced a graded decrease in the maturation probability of the total DP thymocyte pool. At 12–14 weeks following BM inoculation, the frequency of TCR Cα0/0 DP thymocytes was inversely correlated with that of CD4 single positive (SP) thymocytes. Notwithstanding, a decreased frequency of wild-type DP thymocytes led to a marked increase in their transit efficiency from the DP to SP compartments. The frequency-dependent increase in thymocyte transit efficiency was associated with a CD4 SP cell surface phenotype indicative of increased antigenic experience. Importantly, the frequency of DP thymocytes capable of expressing TCR clonotypes dictated the steady-state size of the peripheral CD4 T cell compartment and its potential for homeostatic proliferation. Collectively, these results indicate that the efficiency of DP to CD4 SP transit is a frequency dependent process, which determines (1) the steady-state size of the peripheral T cell compartment and (2) the threshold for homeostatic expansion of peripheral CD4 T cells. PMID:16236130

  16. The PAM-1 aminopeptidase regulates centrosome positioning to ensure anterior-posterior axis specification in one-cell C. elegans embryos.

    Science.gov (United States)

    Fortin, Samantha M; Marshall, Sara L; Jaeger, Eva C; Greene, Pauline E; Brady, Lauren K; Isaac, R Elwyn; Schrandt, Jennifer C; Brooks, Darren R; Lyczak, Rebecca

    2010-08-15

    In the one-cell Caenorhabditis elegans embryo, the anterior-posterior (A-P) axis is established when the sperm donated centrosome contacts the posterior cortex. While this contact appears to be essential for axis polarization, little is known about the mechanisms governing centrosome positioning during this process. pam-1 encodes a puromycin sensitive aminopeptidase that regulates centrosome positioning in the early embryo. Previously we showed that pam-1 mutants fail to polarize the A-P axis. Here we show that PAM-1 can be found in mature sperm and in cytoplasm throughout early embryogenesis where it concentrates around mitotic centrosomes and chromosomes. We provide further evidence that PAM-1 acts early in the polarization process by showing that PAR-1 and PAR-6 do not localize appropriately in pam-1 mutants. Additionally, we tested the hypothesis that PAM-1's role in polarity establishment is to ensure centrosome contact with the posterior cortex. We inactivated the microtubule motor dynein, DHC-1, in pam-1 mutants, in an attempt to prevent centrosome movement from the cortex and restore anterior-posterior polarity. When this was done, the aberrant centrosome movements of pam-1 mutants were not observed and anterior-posterior polarity was properly established, with proper localization of cortical and cytoplasmic determinants. We conclude that PAM-1's role in axis polarization is to prevent premature movement of the centrosome from the posterior cortex, ensuring proper axis establishment in the embryo. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry.

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    Daniël Splinter

    Full Text Available BICD2 is one of the two mammalian homologues of the Drosophila Bicaudal D, an evolutionarily conserved adaptor between microtubule motors and their cargo that was previously shown to link vesicles and mRNP complexes to the dynein motor. Here, we identified a G2-specific role for BICD2 in the relative positioning of the nucleus and centrosomes in dividing cells. By combining mass spectrometry, biochemical and cell biological approaches, we show that the nuclear pore complex (NPC component RanBP2 directly binds to BICD2 and recruits it to NPCs specifically in G2 phase of the cell cycle. BICD2, in turn, recruits dynein-dynactin to NPCs and as such is needed to keep centrosomes closely tethered to the nucleus prior to mitotic entry. When dynein function is suppressed by RNA interference-mediated depletion or antibody microinjection, centrosomes and nuclei are actively pushed apart in late G2 and we show that this is due to the action of kinesin-1. Surprisingly, depletion of BICD2 inhibits both dynein and kinesin-1-dependent movements of the nucleus and cytoplasmic NPCs, demonstrating that BICD2 is needed not only for the dynein function at the nuclear pores but also for the antagonistic activity of kinesin-1. Our study demonstrates that the nucleus is subject to opposing activities of dynein and kinesin-1 motors and that BICD2 contributes to nuclear and centrosomal positioning prior to mitotic entry through regulation of both dynein and kinesin-1.

  18. Patients with Schizophrenia Fail to Up-Regulate Task-Positive and Down-Regulate Task-Negative Brain Networks: An fMRI Study Using an ICA Analysis Approach.

    Science.gov (United States)

    Nygård, Merethe; Eichele, Tom; Løberg, Else-Marie; Jørgensen, Hugo A; Johnsen, Erik; Kroken, Rune A; Berle, Jan Øystein; Hugdahl, Kenneth

    2012-01-01

    Recent research suggests that the cerebral correlates of cognitive deficits in schizophrenia are nested in the activity of widespread, inter-regional networks rather than being restricted to any specific brain location. One of the networks that have received focus lately is the default mode network. Parts of this network have been reported as hyper-activated in schizophrenia patients (SZ) during rest and during task performance compared to healthy controls (HC), although other parts have been found to be hypo-activated. In contrast to this network, task-positive networks have been reported as hypo-activated compared in SZ during task performance. However, the results are mixed, with, e.g., the dorsolateral prefrontal cortex showing both hyper- and hypo-activation in SZ. In this study we were interested in signal increase and decrease differences between a group of SZ and HC in cortical networks, assuming that the regulatory dynamics of alternating task-positive and task-negative neuronal processes are aberrant in SZ. We compared 31 SZ to age- and gender-matched HC, and used fMRI and independent component analysis (ICA) in order to identify relevant networks. We selected the independent components (ICs) with the largest signal intensity increases (STG, insula, supplementary motor cortex, anterior cingulate cortex, and MTG) and decreases (fusiform gyri, occipital lobe, PFC, cingulate, precuneus, and angular gyrus) in response to a dichotic auditory cognitive task. These ICs were then tested for group differences. Our findings showed deficient up-regulation of the executive network and a corresponding deficit in the down-regulation of the anterior default mode, or effort network during task performance in SZ when compared with HC. These findings may indicate a deficit in the dynamics of alternating task-dependent and task-independent neuronal processes in SZ. The results may cast new light on the mechanisms underlying cognitive deficits in schizophrenia, and may be of

  19. Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

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    Frank Georgy A

    2007-03-01

    Full Text Available Abstract Background High risk type human papilloma viruses (HR-HPV induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16ink4a drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16ink4a overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16ink4a overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas Methods Methylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16ink4a was analyzed by RT-PCR and by immunohistochemical technique. Results The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands. The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16ink4a cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors. Conclusion Hypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical

  20. The Polycistronic miR166k-166h Positively Regulates Rice Immunity via Post-transcriptional Control of EIN2

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    Raquel Salvador-Guirao

    2018-03-01

    Full Text Available MicroRNAs (miRNAs are small RNAs acting as regulators of gene expression at the post-transcriptional level. In plants, most miRNAs are generated from independent transcriptional units, and only a few polycistronic miRNAs have been described. miR166 is a conserved miRNA in plants targeting the HD-ZIP III transcription factor genes. Here, we show that a polycistronic miRNA comprising two miR166 family members, miR166k and miR166h, functions as a positive regulator of rice immunity. Rice plants with activated MIR166k-166h expression showed enhanced resistance to infection by the fungal pathogens Magnaporthe oryzae and Fusarium fujikuroi, the causal agents of the rice blast and bakanae disease, respectively. Disease resistance in rice plants with activated MIR166k-166h expression was associated with a stronger expression of defense responses during pathogen infection. Stronger induction of MIR166k-166h expression occurred in resistant but not susceptible rice cultivars. Notably, the ethylene-insensitive 2 (EIN2 gene was identified as a novel target gene for miR166k. The regulatory role of the miR166h-166k polycistron on the newly identified target gene results from the activity of the miR166k-5p specie generated from the miR166k-166h precursor. Collectively, our findings support a role for miR166k-5p in rice immunity by controlling EIN2 expression. Because rice blast is one of the most destructive diseases of cultivated rice worldwide, unraveling miR166k-166h-mediated mechanisms underlying blast resistance could ultimately help in designing appropriate strategies for rice protection.

  1. A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation

    Science.gov (United States)

    Cheong, Mei-Leng; Wang, Liang-Jie; Chuang, Pei-Yun; Chang, Ching-Wen; Lee, Yun-Shien; Lo, Hsiao-Fan; Tsai, Ming-Song

    2015-01-01

    Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation. PMID:26503785

  2. A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation.

    Science.gov (United States)

    Cheong, Mei-Leng; Wang, Liang-Jie; Chuang, Pei-Yun; Chang, Ching-Wen; Lee, Yun-Shien; Lo, Hsiao-Fan; Tsai, Ming-Song; Chen, Hungwen

    2016-01-01

    Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. A positive feedback loop links opposing functions of P-TEFb/Cdk9 and histone H2B ubiquitylation to regulate transcript elongation in fission yeast.

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    Miriam Sansó

    Full Text Available Transcript elongation by RNA polymerase II (RNAPII is accompanied by conserved patterns of histone modification. Whereas histone modifications have established roles in transcription initiation, their functions during elongation are not understood. Mono-ubiquitylation of histone H2B (H2Bub1 plays a key role in coordinating co-transcriptional histone modification by promoting site-specific methylation of histone H3. H2Bub1 also regulates gene expression through an unidentified, methylation-independent mechanism. Here we reveal bidirectional communication between H2Bub1 and Cdk9, the ortholog of metazoan positive transcription elongation factor b (P-TEFb, in the fission yeast Schizosaccharomyces pombe. Chemical and classical genetic analyses indicate that lowering Cdk9 activity or preventing phosphorylation of its substrate, the transcription processivity factor Spt5, reduces H2Bub1 in vivo. Conversely, mutations in the H2Bub1 pathway impair Cdk9 recruitment to chromatin and decrease Spt5 phosphorylation. Moreover, an Spt5 phosphorylation-site mutation, combined with deletion of the histone H3 Lys4 methyltransferase Set1, phenocopies morphologic and growth defects due to H2Bub1 loss, suggesting independent, partially redundant roles for Cdk9 and Set1 downstream of H2Bub1. Surprisingly, mutation of the histone H2B ubiquitin-acceptor residue relaxes the Cdk9 activity requirement in vivo, and cdk9 mutations suppress cell-morphology defects in H2Bub1-deficient strains. Genome-wide analyses by chromatin immunoprecipitation also demonstrate opposing effects of Cdk9 and H2Bub1 on distribution of transcribing RNAPII. Therefore, whereas mutual dependence of H2Bub1 and Spt5 phosphorylation indicates positive feedback, mutual suppression by cdk9 and H2Bub1-pathway mutations suggests antagonistic functions that must be kept in balance to regulate elongation. Loss of H2Bub1 disrupts that balance and leads to deranged gene expression and aberrant cell

  4. Genome-wide identification of genes involved in the positive and negative regulation of acetic acid-induced programmed cell death in Saccharomyces cerevisiae.

    Science.gov (United States)

    Sousa, Marlene; Duarte, Ana Marta; Fernandes, Tânia R; Chaves, Susana R; Pacheco, Andreia; Leão, Cecília; Côrte-Real, Manuela; Sousa, Maria João

    2013-11-28

    Acetic acid is mostly known as a toxic by-product of alcoholic fermentation carried out by Saccharomyces cerevisiae, which it frequently impairs. The more recent finding that acetic acid triggers apoptotic programmed cell death (PCD) in yeast sparked an interest to develop strategies to modulate this process, to improve several biotechnological applications, but also for biomedical research. Indeed, acetate can trigger apoptosis in cancer cells, suggesting its exploitation as an anticancer compound. Therefore, we aimed to identify genes involved in the positive and negative regulation of acetic acid-induced PCD by optimizing a functional analysis of a yeast Euroscarf knock-out mutant collection. The screen consisted of exposing the mutant strains to acetic acid in YPD medium, pH 3.0, in 96-well plates, and subsequently evaluating the presence of culturable cells at different time points. Several functional categories emerged as greatly relevant for modulation of acetic acid-induced PCD (e.g.: mitochondrial function, transcription of glucose-repressed genes, protein synthesis and modifications, and vesicular traffic for protection, or amino acid transport and biosynthesis, oxidative stress response, cell growth and differentiation, protein phosphorylation and histone deacetylation for its execution). Known pro-apoptotic and anti-apoptotic genes were found, validating the approach developed. Metabolism stood out as a main regulator of this process, since impairment of major carbohydrate metabolic pathways conferred resistance to acetic acid-induced PCD. Among these, lipid catabolism arose as one of the most significant new functions identified. The results also showed that many of the cellular and metabolic features that constitute hallmarks of tumour cells (such as higher glycolytic energetic dependence, lower mitochondrial functionality, increased cell division and metabolite synthesis) confer sensitivity to acetic acid-induced PCD, potentially explaining why

  5. Oxylipin biosynthesis genes positively regulate programmed cell death during compatible infections with the synergistic pair potato virus X-potato virus Y and Tomato spotted wilt virus.

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    García-Marcos, Alberto; Pacheco, Remedios; Manzano, Aranzazu; Aguilar, Emmanuel; Tenllado, Francisco

    2013-05-01

    One of the most severe symptoms caused by compatible plant-virus interactions is systemic necrosis, which shares common attributes with the hypersensitive response to incompatible pathogens. Although several studies have identified viral symptom determinants responsible for systemic necrosis, mechanistic models of how they contribute to necrosis in infected plants remain scarce. Here, we examined the involvement of different branches of the oxylipin biosynthesis pathway in the systemic necrosis response caused either by the synergistic interaction of Potato virus X with Potato virus Y (PVX-PVY) or by Tomato spotted wilt virus (TSWV) in Nicotiana benthamiana. Silencing either 9-lipoxygenase (LOX), 13-LOX, or α-dioxygenase-1 (α-DOX-1) attenuated the programmed cell death (PCD)-associated symptoms caused by infection with either PVX-PVY or TSWV. In contrast, silencing of the jasmonic acid perception gene, COI1 (Coronatine insensitive 1), expedited cell death during infection with compatible viruses. This correlated with an enhanced expression of oxylipin biosynthesis genes and dioxygenase activity in PVX-PVY-infected plants. Moreover, the Arabidopsis thaliana double lox1 α-dox-1 mutant became less susceptible to TSWV infection. We conclude that oxylipin metabolism is a critical component that positively regulates the process of PCD during compatible plant-virus interactions but does not play a role in restraining virus accumulation in planta.

  6. Nrf2 protects the lung against inflammation induced by titanium dioxide nanoparticles: A positive regulator role of Nrf2 on cytokine release.

    Science.gov (United States)

    Delgado-Buenrostro, Norma L; Medina-Reyes, Estefany I; Lastres-Becker, Isabel; Freyre-Fonseca, Verónica; Ji, Zhaoxia; Hernández-Pando, Rogelio; Marquina, Brenda; Pedraza-Chaverri, José; Espada, Sandra; Cuadrado, Antonio; Chirino, Yolanda I

    2015-07-01

    Titanium dioxide nanoparticles (TiO2 NPs) have been classified as possibly carcinogenic to humans and they are an important nanomaterial widely used in pharmaceutical and paint industries. Inhalation is one of the most important routes of exposure in occupational settings. Several experimental models have shown that oxidative stress and inflammation are key mediators of cell damage. In this regard, Nrf2 modulates cytoprotection against oxidative stress and inflammation, however, its role in inflammation induced by TiO2 NPs exposure has been less investigated. The aim of this work was to investigate the role of Nrf2 in the cytokines produced after 4 weeks of TiO2 NPs exposure (5 mg/kg/2 days/week) using wild-type and Nrf2 knockout C57bl6 mice. Results showed that Nrf2 protects against inflammation and oxidative damage induced by TiO2 NPs exposure, however, Nrf2 is a positive mediator in the expression of IFN-γ, TNF-α, and TGF-β in bronchial epithelium and alveolar space after 4 weeks of exposure. These results suggest that Nrf2 has a central role in up-regulation of cytokines released during inflammation induced by TiO2 NPs and those cytokines are needed to cope with histological alterations in lung tissue. © 2014 Wiley Periodicals, Inc.

  7. ETHYLENE RESPONSE FACTOR 96 positively regulates Arabidopsis resistance to necrotrophic pathogens by direct binding to GCC elements of jasmonate - and ethylene-responsive defence genes.

    Science.gov (United States)

    Catinot, Jérémy; Huang, Jing-Bo; Huang, Pin-Yao; Tseng, Min-Yuan; Chen, Ying-Lan; Gu, Shin-Yuan; Lo, Wan-Sheng; Wang, Long-Chi; Chen, Yet-Ran; Zimmerli, Laurent

    2015-12-01

    The ERF (ethylene responsive factor) family is composed of transcription factors (TFs) that are critical for appropriate Arabidopsis thaliana responses to biotic and abiotic stresses. Here we identified and characterized a member of the ERF TF group IX, namely ERF96, that when overexpressed enhances Arabidopsis resistance to necrotrophic pathogens such as the fungus Botrytis cinerea and the bacterium Pectobacterium carotovorum. ERF96 is jasmonate (JA) and ethylene (ET) responsive and ERF96 transcripts accumulation was abolished in JA-insensitive coi1-16 and in ET-insensitive ein2-1 mutants. Protoplast transactivation and electrophoresis mobility shift analyses revealed that ERF96 is an activator of transcription that binds to GCC elements. In addition, ERF96 mainly localized to the nucleus. Microarray analysis coupled to chromatin immunoprecipitation-PCR of Arabidopsis overexpressing ERF96 revealed that ERF96 enhances the expression of the JA/ET defence genes PDF1.2a, PR-3 and PR-4 as well as the TF ORA59 by direct binding to GCC elements present in their promoters. While ERF96-RNAi plants demonstrated wild-type resistance to necrotrophic pathogens, basal PDF1.2 expression levels were reduced in ERF96-silenced plants. This work revealed ERF96 as a key player of the ERF network that positively regulates the Arabidopsis resistance response to necrotrophic pathogens. © 2015 John Wiley & Sons Ltd.

  8. STAP-2 Protein Expression in B16F10 Melanoma Cells Positively Regulates Protein Levels of Tyrosinase, Which Determines Organs to Infiltrate in the Body.

    Science.gov (United States)

    Sekine, Yuichi; Togi, Sumihito; Muromoto, Ryuta; Kon, Shigeyuki; Kitai, Yuichi; Yoshimura, Akihiko; Oritani, Kenji; Matsuda, Tadashi

    2015-07-10

    Melanoma is the most serious type of skin cancer, with a highly metastatic phenotype. In this report, we show that signal transducing adaptor protein 2 (STAP-2) is involved in cell migration, proliferation, and melanogenesis as well as chemokine receptor expression and tumorigenesis in B16F10 melanoma cells. This was evident in mice injected with STAP-2 shRNA (shSTAP-2)-expressing B16F10 cells, which infiltrated organs in a completely different pattern from the original cells, showing massive colonization in the liver, kidney, and neck but not in the lung. The most important finding was that STAP-2 expression determined tyrosinase protein content. STAP-2 colocalized with tyrosinase in lysosomes and protected tyrosinase from protein degradation. It is noteworthy that B16F10 cells with knocked down tyrosinase showed similar cell characteristics as shSTAP-2 cells. These results indicated that tyrosinase contributed to some cellular events beyond melanogenesis. Taken together, one possibility is that STAP-2 positively regulates the protein levels of tyrosinase, which determines tumor invasion via controlling chemokine receptor expression. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. The ER-associated protein ZDHHC1 is a positive regulator of DNA virus-triggered, MITA/STING-dependent innate immune signaling.

    Science.gov (United States)

    Zhou, Qian; Lin, Heng; Wang, Suyun; Wang, Shuai; Ran, Yong; Liu, Ying; Ye, Wen; Xiong, Xiaozhe; Zhong, Bo; Shu, Hong-Bing; Wang, Yan-Yi

    2014-10-08

    Viral DNA sensing within the cytosol of infected cells activates type I interferon (IFN) expression. MITA/STING plays an essential role in this pathway by acting as both a sensor for the second messenger cGAMP and as an adaptor for downstream signaling components. In an expression screen for proteins that can activate the IFNB1 promoter, we identified the ER-associated protein ZDHHC1 as a positive regulator of virus-triggered, MITA/STING-dependent immune signaling. Zdhhc1(-/-) cells failed to effectively produce IFNs and other cytokines in response to infection with DNA but not RNA viruses. Zdhhc1(-/-) mice infected with the neurotropic DNA virus HSV-1 exhibited lower cytokine levels and higher virus titers in the brain, resulting in higher lethality. ZDHHC1 constitutively associated with MITA/STING and mediates dimerization/aggregation of MITA/STING and recruitment of the downstream signaling components TBK1 and IRF3. These findings support a role for ZDHHC1 in mediating MITA/STING-dependent innate immune response against DNA viruses. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Witnessing stressful events induces glutamatergic synapse pathway alterations and gene set enrichment of positive EPSP regulation within the VTA of adult mice: An ontology based approach

    Science.gov (United States)

    Brewer, Jacob S.

    It is well known that exposure to severe stress increases the risk for developing mood disorders. Currently, the neurobiological and genetic mechanisms underlying the functional effects of psychological stress are poorly understood. Presenting a major obstacle to the study of psychological stress is the inability of current animal models of stress to distinguish between physical and psychological stressors. A novel paradigm recently developed by Warren et al., is able to tease apart the effects of physical and psychological stress in adult mice by allowing these mice to "witness," the social defeat of another mouse thus removing confounding variables associated with physical stressors. Using this 'witness' model of stress and RNA-Seq technology, the current study aims to study the genetic effects of psychological stress. After, witnessing the social defeat of another mouse, VTA tissue was extracted, sequenced, and analyzed for differential expression. Since genes often work together in complex networks, a pathway and gene ontology (GO) analysis was performed using data from the differential expression analysis. The pathway and GO analyzes revealed a perturbation of the glutamatergic synapse pathway and an enrichment of positive excitatory post-synaptic potential regulation. This is consistent with the excitatory synapse theory of depression. Together these findings demonstrate a dysregulation of the mesolimbic reward pathway at the gene level as a result of psychological stress potentially contributing to depressive like behaviors.

  11. PacMYBA, a sweet cherry R2R3-MYB transcription factor, is a positive regulator of salt stress tolerance and pathogen resistance.

    Science.gov (United States)

    Shen, Xinjie; Guo, Xinwei; Guo, Xiao; Zhao, Di; Zhao, Wei; Chen, Jingsheng; Li, Tianhong

    2017-03-01

    Plant R2R3-MYB transcription factors play crucial roles in stress responses. We previously isolated a R2R3-MYB homolog from sweet cherry cv. Hong Deng, designated PacMYBA (GenBank accession No. KF974774). To explore the role of PacMYBA in the plant stress response, we heterologously expressed PacMYBA in transgenic Arabidopsis thaliana plants. In a previous study, we demonstrated that PacMYBA is mainly localized to the nucleus and could be induced by abscisic acid (ABA). Analysis of the promoter sequence of PacMYBA revealed that it contains several stress-related cis-elements. QPCR results showed that PacMYBA is induced by salt, salicylic (SA), and jasmonic acid (JA) in sweet cherry leaves. Transgenic Arabidopsis plants heterologously expressing PacMYBA exhibited enhanced salt-tolerance and increased resistance to Pseudomonas syringe pv. tomato (Pst) DC3000 infection. Overexpression of PacMYBA decreased the osmotic potential (OP), increased the free proline content, and increased the peroxidase content in transgenic Arabidopsis plants. Furthermore, overexpression of PacMYBA also affected the expression levels of salt stress- and pathogen defense-related genes in the transgenic plants. These results indicate that PacMYBA is a positive regulator of salt stress tolerance and pathogen resistance. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. OsCCD1, a novel small calcium-binding protein with one EF-hand motif, positively regulates osmotic and salt tolerance in rice.

    Science.gov (United States)

    Jing, Pei; Zou, Juanzi; Kong, Lin; Hu, Shiqi; Wang, Biying; Yang, Jun; Xie, Guosheng

    2016-06-01

    Calcium-binding proteins play key roles in the signal transduction in the growth and stress response in eukaryotes. However, a subfamily of proteins with one EF-hand motif has not been fully studied in higher plants. Here, a novel small calcium-binding protein with a C-terminal centrin-like domain (CCD1) in rice, OsCCD1, was characterized to show high similarity with a TaCCD1 in wheat. As a result, OsCCD1 can bind Ca(2+) in the in vitro EMSA and the fluorescence staining calcium-binding assays. Transient expression of green fluorescent protein (GFP)-tagged OsCCD1 in rice protoplasts showed that OsCCD1 was localized in the nucleus and cytosol of rice cells. OsCCD1 transcript levels were transiently induced by osmotic stress and salt stress through the calcium-mediated ABA signal. The rice seedlings of T-DNA mutant lines showed significantly less tolerance to osmotic and salt stresses than wild type plants (psalt stresses than wild type plants (psalt stresses. In sum, OsCCD1 gene probably affects the DREB2B and its downstream genes to positively regulate osmotic and salt tolerance in rice seedlings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. ERF5 and ERF6 play redundant roles as positive regulators of JA/Et-mediated defense against Botrytis cinerea in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Caroline S Moffat

    Full Text Available The ethylene response factor (ERF family in Arabidopsis thaliana comprises 122 members in 12 groups, yet the biological functions of the majority remain unknown. Of the group IX ERFs, the IXc subgroup has been studied the most, and includes ERF1, ERF14 and ORA59, which play roles in plant innate immunity. Here we investigate the biological functions of two members of the less studied IXb subgroup: ERF5 and ERF6. In order to identify potential targets of these transcription factors, microarray analyses were performed on plants constitutively expressing either ERF5 or ERF6. Expression of defense genes, JA/Et-responsive genes and genes containing the GCC box promoter motif were significantly upregulated in both ERF5 and ERF6 transgenic plants, suggesting that ERF5 and ERF6 may act as positive regulators of JA-mediated defense and potentially overlap in their function. Since defense against necrotrophic pathogens is generally mediated through JA/Et-signalling, resistance against the fungal necrotroph Botrytis cinerea was examined. Constitutive expression of ERF5 or ERF6 resulted in significantly increased resistance. Although no significant difference in susceptibility to B. cinerea was observed in either erf5 or erf6 mutants, the erf5 erf6 double mutant showed a significant increase in susceptibility, which was likely due to compromised JA-mediated gene expression, since JA-induced gene expression was reduced in the double mutant. Taken together these data suggest that ERF5 and ERF6 play positive but redundant roles in defense against B. cinerea. Since mutual antagonism between JA/Et and salicylic acid (SA signalling is well known, the UV-C inducibility of an SA-inducible gene, PR-1, was examined. Reduced inducibilty in both ERF5 and ERF6 constitutive overexepressors was consistent with suppression of SA-mediated signalling, as was an increased susceptibility to avirulent Pseudomonas syringae. These data suggest that ERF5 and ERF6 may also play a

  14. Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California.

    Science.gov (United States)

    Salinas, Danieli B; Sosnay, Patrick R; Azen, Colleen; Young, Suzanne; Raraigh, Karen S; Keens, Thomas G; Kharrazi, Martin

    2016-01-01

    Of the 2007 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutations, 202 have been assigned disease liability. California's racially diverse population, along with CFTR sequencing as part of newborn screening model, provides the opportunity to examine the phenotypes of children with uncategorized mutations to help inform disease liability and penetrance. We conducted a retrospective cohort study based on children screened from 2007 to 2011 and followed for two to six years. Newborns that screened positive were divided into three genotype groups: those with two CF-causing mutations (CF-C); those with one mutation of varying clinic consequence (VCC); and those with one mutation of unknown disease liability (Unknown). Sweat chloride tests, pancreatic sufficiency status, and Pseudomonas aeruginosa colonization were compared. Children with two CF-causing mutations had a classical CF phenotype, while 5% of VCC (4/78) and 11% of Unknown (27/244) met diagnostic criteria of CF. Children carrying Unknown mutations 2215insG with D836Y, and T1036N had early and classical CF phenotype, while others carrying 1525-42G>A, L320V, L967S, R170H, and 296+28A>G had a benign clinical presentation, suggesting that these are non-CF causing. While most infants with VCC and Unknown CFTR mutations do not meet diagnostic criteria for CF, a small proportion do. These findings highlight the range of genotypes and phenotypes in the first few years of life following CF newborn screening when CFTR sequencing is performed.

  15. Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California.

    Directory of Open Access Journals (Sweden)

    Danieli B Salinas

    Full Text Available Of the 2007 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR mutations, 202 have been assigned disease liability. California's racially diverse population, along with CFTR sequencing as part of newborn screening model, provides the opportunity to examine the phenotypes of children with uncategorized mutations to help inform disease liability and penetrance.We conducted a retrospective cohort study based on children screened from 2007 to 2011 and followed for two to six years. Newborns that screened positive were divided into three genotype groups: those with two CF-causing mutations (CF-C; those with one mutation of varying clinic consequence (VCC; and those with one mutation of unknown disease liability (Unknown. Sweat chloride tests, pancreatic sufficiency status, and Pseudomonas aeruginosa colonization were compared.Children with two CF-causing mutations had a classical CF phenotype, while 5% of VCC (4/78 and 11% of Unknown (27/244 met diagnostic criteria of CF. Children carrying Unknown mutations 2215insG with D836Y, and T1036N had early and classical CF phenotype, while others carrying 1525-42G>A, L320V, L967S, R170H, and 296+28A>G had a benign clinical presentation, suggesting that these are non-CF causing.While most infants with VCC and Unknown CFTR mutations do not meet diagnostic criteria for CF, a small proportion do. These findings highlight the range of genotypes and phenotypes in the first few years of life following CF newborn screening when CFTR sequencing is performed.

  16. Keratinocyte-derived IL-24 plays a role in the positive feedback regulation of epidermal inflammation in response to environmental and endogenous toxic stressors.

    Science.gov (United States)

    Jin, Sun Hee; Choi, Dalwoong; Chun, Young-Jin; Noh, Minsoo

    2014-10-15

    Keratinocytes are the major cellular components of human epidermis and play a key role in the modulating cutaneous inflammation and toxic responses. In human chronic skin diseases, the common skin inflammatory phenotypes like skin barrier disruption and epidermal hyperplasia are manifested in epidermal keratinocytes by interactions with T helper (Th) cells. To find a common gene expression signature of human keratinocytes in chronic skin diseases, we performed a whole genome microarray analysis on normal human epidermal keratinocytes (NHKs) treated with IFNγ, IL-4, IL-17A or IL-22, major cytokines from Th1, Th2, Th17 or Th22 cells, respectively. The microarray results showed that the four genes, IL-24, PDZK1IP1, H19 and filaggrin, had common expression profiles in NHKs exposed to Th cell cytokines. In addition, the acute phase pro-inflammatory cytokines, IL-1β, IL-6 and TNFα, also change the gene transcriptional profile of IL-24, PDZK1IP1, H19, and filaggrin in NHKs as those of Th cytokines. Therefore, the signature gene set, consisting of IL-24, PDZK1IP1, H19, and filaggrin, provides essential insights for understanding the process of cutaneous inflammation and toxic responses. We demonstrate that environmental toxic stressors, such as chemical irritants and ultraviolet irradiation stimulate the production of IL-24 in NHKs. IL-24 stimulates the JAK1-STAT3 and MAPK pathways in NHKs, and promotes the secretion of pro-inflammatory mediators IL-8, PGE2, and MMP-1. These results suggest that keratinocyte-derived IL-24 participates in the positive feedback regulation of epidermal inflammation in response to both endogenous and environmental toxic stressors. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Simulated Microgravity Regulates Gene Transcript Profiles of 2T3 Preosteoblasts: Comparison of the Random Positioning Machine and the Rotating Wall Vessel Bioreactor

    Science.gov (United States)

    Patel, Mamta J.; Liu, Wenbin; Sykes, Michelle C.; Ward, Nancy E.; Risin, Semyon A.; Risin, Diana; Hanjoong, Jo

    2007-01-01

    Microgravity of spaceflight induces bone loss due in part to decreased bone formation by osteoblasts. We have previously examined the microgravity-induced changes in gene expression profiles in 2T3 preosteoblasts using the Random Positioning Machine (RPM) to simulate microgravity conditions. Here, we hypothesized that exposure of preosteoblasts to an independent microgravity simulator, the Rotating Wall Vessel (RWV), induces similar changes in differentiation and gene transcript profiles, resulting in a more confined list of gravi-sensitive genes that may play a role in bone formation. In comparison to static 1g controls, exposure of 2T3 cells to RWV for 3 days inhibited alkaline phosphatase activity, a marker of differentiation, and downregulated 61 genes and upregulated 45 genes by more than two-fold as shown by microarray analysis. The microarray results were confirmed with real time PCR for downregulated genes osteomodulin, bone morphogenic protein 4 (BMP4), runx2, and parathyroid hormone receptor 1. Western blot analysis validated the expression of three downregulated genes, BMP4, peroxiredoxin IV, and osteoglycin, and one upregulated gene peroxiredoxin I. Comparison of the microarrays from the RPM and the RWV studies identified 14 gravi-sensitive genes that changed in the same direction in both systems. Further comparison of our results to a published database showing gene transcript profiles of mechanically loaded mouse tibiae revealed 16 genes upregulated by the loading that were shown to be downregulated by RWV and RPM. These mechanosensitive genes identified by the comparative studies may provide novel insights into understanding the mechanisms regulating bone formation and potential targets of countermeasure against decreased bone formation both in astronauts and in general patients with musculoskeletal disorders.

  18. Arabidopsis LIP5, a positive regulator of multivesicular body biogenesis, is a critical target of pathogen-responsive MAPK cascade in plant basal defense.

    Directory of Open Access Journals (Sweden)

    Fei Wang

    2014-07-01

    Full Text Available Multivesicular bodies (MVBs play essential roles in many cellular processes. The MVB pathway requires reversible membrane association of the endosomal sorting complexes required for transports (ESCRTs for sustained protein trafficking. Membrane dissociation of ESCRTs is catalyzed by the AAA ATPase SKD1, which is stimulated by LYST-interacting protein 5 (LIP5. We report here that LIP5 is a target of pathogen-responsive mitogen-activated protein kinases (MPKs and plays a critical role in plant basal resistance. Arabidopsis LIP5 interacts with MPK6 and MPK3 and is phosphorylated in vitro by activated MPK3 and MPK6 and in vivo upon expression of MPK3/6-activating NtMEK2DD and pathogen infection. Disruption of LIP5 has little effects on flg22-, salicylic acid-induced defense responses but compromises basal resistance to Pseudomonas syringae. The critical role of LIP5 in plant basal resistance is dependent on its ability to interact with SKD1. Mutation of MPK phosphorylation sites in LIP5 does not affect interaction with SKD1 but reduces the stability and compromises the ability to complement the lip5 mutant phenotypes. Using the membrane-selective FM1-43 dye and transmission electron microscopy, we demonstrated that pathogen infection increases formation of both intracellular MVBs and exosome-like paramural vesicles situated between the plasma membrane and the cell wall in a largely LIP5-dependent manner. These results indicate that the MVB pathway is positively regulated by pathogen-responsive MPK3/6 through LIP5 phosphorylation and plays a critical role in plant immune system likely through relocalization of defense-related molecules.

  19. HvDep1 Is a Positive Regulator of Culm Elongation and Grain Size in Barley and Impacts Yield in an Environment-Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Toni Wendt

    Full Text Available Heterotrimeric G proteins are intracellular membrane-attached signal transducers involved in various cellular processes in both plants and animals. They consist of three subunits denoted as α, β and γ. The γ-subunits of the so-called AGG3 type, which comprise a transmembrane domain, are exclusively found in plants. In model species, these proteins have been shown to participate in the control of plant height, branching and seed size and could therefore impact the harvestable yield of various crop plants. Whether AGG3-type γ-subunits influence yield in temperate cereals like barley and wheat remains unknown. Using a transgenic complementation approach, we show here that the Scottish malting barley cultivar (cv. Golden Promise carries a loss-of-function mutation in HvDep1, an AGG3-type subunit encoding gene that positively regulates culm elongation and seed size in barley. Somewhat intriguingly, agronomic field data collected over a 12-year period reveals that the HvDep1 loss-of-function mutation in cv. Golden Promise has the potential to confer either a significant increase or decrease in harvestable yield depending on the environment. Our results confirm the role of AGG3-type subunit-encoding genes in shaping plant architecture, but interestingly also indicate that the impact HvDep1 has on yield in barley is both genotypically and environmentally sensitive. This may explain why widespread exploitation of variation in AGG3-type subunit-encoding genes has not occurred in temperate cereals while in rice the DEP1 locus is widely exploited to improve harvestable yield.

  20. Differential regulation of polysaccharide-specific antibody responses to isolated polysaccharides, conjugate vaccines, and intact Gram-positive versus Gram-negative extracellular bacteria.

    Science.gov (United States)

    Snapper, Clifford M

    2016-06-24

    Bacterial capsular polysaccharides are major virulence factors and are key targets in a number of licensed anti-bacterial vaccines. Their major characteristics are their large molecular weight and expression of repeating antigenic epitopes that mediate multivalent B cell receptor cross-linking. In addition, since the majority of these antigens cannot associate with MHC-II they fail to recruit CD4+ T cell help and are referred to as T cell-independent antigens. In this review I will discuss a series of studies from my laboratory that have underscored the importance of understanding polysaccharide-specific antibody responses within the context in which the PS is expressed (i.e. in isolation, as a component of conjugate vaccines, and expressed naturally by intact bacteria). We have shown that multivalent B cell receptor crosslinking, as mediated by polysaccharides, uniquely determines the qualitative response of the B cell to subsequent stimuli, but by itself is insufficient to induce antibody secretion or class switching. For these latter events to occur, second signals must act in concert with primary signals derived from the B cell receptor. The co-expression of polysaccharide and protein within intact bacteria promotes recruitment of CD4+ T cell help for the associated PS-specific IgG response, in contrast to isolated polysaccharides. Further, the particulate nature of extracellular bacteria confers properties to the polysaccharide-specific IgG response that makes it distinct immunologically from soluble conjugate vaccines. Finally, the underlying biochemical and/or structural differences that distinguish Gram-positive and Gram-negative bacteria appear to play critical roles in differentially regulating the associated polysaccharide-specific IgG responses to these groups of pathogens. These studies have a number of implications for the understanding and future design of polysaccharide-based vaccines. Published by Elsevier Ltd.

  1. Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling.

    Science.gov (United States)

    Liu, Jinyan; Hu, Feng; Tang, Jintian; Tang, Shijie; Xia, Kun; Wu, Song; Yin, Chaoqi; Wang, Shaohua; He, Quanyong; Xie, Huiqing; Zhou, Jianda

    2017-04-01

    Vacuum sealing drainage (VSD) is an effective technique used to promote wound healing. However, recent studies have shown that it exerts positive pressure (PP) rather than negative pressure (NP) on skin. In this study, we created a homemade device that could maintain NP on the wound, and compared the therapeutic effects of VSD-induced PP to those of our homemade device which induced NP on wound healing. The NP induced by our device required less time for wound healing and decreased the wound area more efficiently than the PP induced by VSD. NP and PP both promoted the inflammatory response by upregulating neutrophil infiltration and interleukin (IL)‑1β expression, and downregulating IL‑10 expression. Higher levels of epidermal growth factor (EGF), transforming growth factor (TGF)‑β and platelet-derived growth factor (PDGF), and lower levels of basic fibroblast growth factor (bFGF) were observed in the wound tissue treated with NP compared to the wound tissue exposed to PP. Proliferation in the wound tissue exposed to NP on day 10 was significantly higher than that in wound tissue exposed to PP. NP generated more fibroblasts, keratinized stratified epithelium, and less epithelia with stemness than PP. The levels of ccollagen Ⅰ and Ⅲ were both decreased in both the NP and PP groups. NP induced a statistically significant increase in the expression of fibronectin (FN) on days 3 and 10 compared to PP. Furthermore, the level of matrix metalloproteinase (MMP)‑13 increased in the NP group, but decreased in the PP group on day 3. NP also induced a decrease in the levels of tissue inhibitor of metalloproteinase (TIMP)‑1 and TIMP‑2 during the early stages of wound healing, which was significantly different from the increasing effect of PP on TIMP‑1 and TIMP‑2 levels at the corresponding time points. On the whole, our data indicate that our homemade device which induced NP, was more efficient than VSD‑induced PP on wound healing by

  2. Keratinocyte-derived IL-24 plays a role in the positive feedback regulation of epidermal inflammation in response to environmental and endogenous toxic stressors

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Sun Hee [Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of); Choi, Dalwoong [Department of Public Health Science, Korea University, Seoul 136-701 (Korea, Republic of); Chun, Young-Jin [College of Pharmacy, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Noh, Minsoo, E-mail: minsoo@alum.mit.edu [Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2014-10-15

    Keratinocytes are the major cellular components of human epidermis and play a key role in the modulating cutaneous inflammation and toxic responses. In human chronic skin diseases, the common skin inflammatory phenotypes like skin barrier disruption and epidermal hyperplasia are manifested in epidermal keratinocytes by interactions with T helper (Th) cells. To find a common gene expression signature of human keratinocytes in chronic skin diseases, we performed a whole genome microarray analysis on normal human epidermal keratinocytes (NHKs) treated with IFNγ, IL-4, IL-17A or IL-22, major cytokines from Th1, Th2, Th17 or Th22 cells, respectively. The microarray results showed that the four genes, IL-24, PDZK1IP1, H19 and filaggrin, had common expression profiles in NHKs exposed to Th cell cytokines. In addition, the acute phase pro-inflammatory cytokines, IL-1β, IL-6 and TNFα, also change the gene transcriptional profile of IL-24, PDZK1IP1, H19, and filaggrin in NHKs as those of Th cytokines. Therefore, the signature gene set, consisting of IL-24, PDZK1IP1, H19, and filaggrin, provides essential insights for understanding the process of cutaneous inflammation and toxic responses. We demonstrate that environmental toxic stressors, such as chemical irritants and ultraviolet irradiation stimulate the production of IL-24 in NHKs. IL-24 stimulates the JAK1-STAT3 and MAPK pathways in NHKs, and promotes the secretion of pro-inflammatory mediators IL-8, PGE2, and MMP-1. These results suggest that keratinocyte-derived IL-24 participates in the positive feedback regulation of epidermal inflammation in response to both endogenous and environmental toxic stressors. - Highlights: • Cutaneous inflammatory gene signature consists of PDZK1IP1, IL-24, H19 and filaggrin. • Pro-inflammatory cytokines increase IL-24 production in human keratinocytes. • Environmental toxic stressors increase IL-24 production in human keratinocytes. • IL-24 stimulates human keratinocytes to

  3. ErbB-2 signaling plays a critical role in regulating androgen-sensitive and castration-resistant androgen receptor-positive prostate cancer cells.

    Science.gov (United States)

    Muniyan, Sakthivel; Chen, Siu-Ju; Lin, Fen-Fen; Wang, Zhengzhong; Mehta, Parmender P; Batra, Surinder K; Lin, Ming-Fong

    2015-11-01

    While androgen deprivation therapy (ADT) reduces tumor burden, autocrine growth factor loops such as human epidermal growth factor receptor 2 (HER2/ErbB-2/neu) have been proposed to contribute to prostate cancer (PCa) survival and relapse. However, the role of ErbB-2 in regulating androgen-sensitive (AS) and castration-resistant (CR) cell proliferation remains unclear. Here, we determined the role of ErbB-2 in PCa progression and survival under steroid-reduced conditions using two independent PCa cell progression models. In AR-positive androgen-independent (AI) PCa cells that exhibit the CR phenotype, ErbB-2 was constitutively activated, compared to corresponding AS PCa cells. In AS LNCaP C-33 cells, androgen-induced ErbB-2 activation through ERK1/2 mediates PCa cell proliferation. Further, the ErbB-2-specific but not EGFR-specific inhibitor suppresses basal and androgen-stimulated cell proliferation and also blocks ERK1/2 activation. ErbB-2 ectopic expression and cPAcP siRNA transfection of LNCaP C-33 cells each increases ErbB-2 tyrosine phosphorylation, correlating with increased AI PSA secretion and cell proliferation. Conversely, trapping ErbB-2 by transfected endoplasmic reticulum-targeting ScFv5R expression vector abolished DHT-induced LNCaP C-33 cell growth. Moreover, inhibition of ErbB-2 but not EGFR in AI LNCaP C-81 and MDA PCa2b-AI PCa cells significantly abolished AI cell growth. In contrast to androgens via ErbB-2/ERK1/2 signaling in AS PCa cells, the inhibition of ErbB-2 abrogated AI cell proliferation by inhibiting the cell survival protein Akt in those AI cells. These results suggest that ErbB-2 is a prominent player in mediating the ligand-dependent and -independent activation of AR in AS and AI/CR PCa cells respectively for PCa progression and survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. The qTSN positive effect on panicle and flag leaf size of rice is associated with an early down-regulation of tillering

    Directory of Open Access Journals (Sweden)

    Dewi Erika eAdriani

    2016-01-01

    Full Text Available The qTSN4 was identified as rice QTL (Quantitative Traits Locus increasing total spikelet number per panicle and flag leaf area but potentially reducing panicle number depending on the environment. So far, this trade-off was mainly observed at grain maturity and not specifically studied in details, limiting the apprehension of the agronomic interest of qTSN4. This study aimed to understand the effect of qTSN4 and of the environment on panicle sizing, its trade-off with panicle number and finally plant grain production. It compared two high yielding genotypes to their Near Isogenic Lines (NIL carrying either QTL qTSN4 or qTSN12, two distinct QTLs contributing to the enlarged panicle size, thereafter designated as qTSN. Traits describing C sink (organ appearance rate, size, biomass and source (leaf area, photosynthesis, sugar availability were dynamically characterized along plant and/or panicle development within two trials (greenhouse, field, each comparing two treatments contrasting for plant access to light (with or without shading, high or low planting densities. The positive effect of qTSN on panicle size and flag leaf area of the main tiller was confirmed. More precisely, it could be shown that qTSN increased leaf area and internode cross-section, and in some cases of the photosynthetic rate and starch reserves, of the top 3-4 phytomers of the main tiller. This was accompanied by an earlier tillering cessation, that coincided with the initiation of these phytomers, and an enhanced of panicle size on the main tiller. Plant leaf area at flowering was not affected by qTSN but fertile tiller number was reduced to an extent that depended on the environment. Accordingly, plant grain production was enhanced by qTSN only under shading in the greenhouse experiment, where panicle number was not affected and photosynthesis and starch storage in internodes was enhanced. The effect of qTSN on rice phenotype was thus expressed before panicle initiation

  5. Differential expression of interleukin-32 in chronic rhinosinusitis with and without nasal polyps

    NARCIS (Netherlands)

    Keswani, A.; Chustz, R.T.; Suh, L.; Carter, R.; Peters, A.T.; Tan, B.K.; Chandra, R.; Kim, S.H.; Azam, T.; Dinarello, C.A.; Kern, R.C.; Schleimer, R.P.; Kato, A.

    2012-01-01

    BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways and sinuses and is frequently divided into polypoid CRS (CRSwNP) and nonpolypoid CRS (CRSsNP). However, the mechanism of inflammation in CRS has still not been fully

  6. Synthetic double-stranded RNA induces interleukin-32 in bronchial epithelial cells.

    Science.gov (United States)

    Ota, Kyoko; Kawaguchi, Mio; Fujita, Junichi; Kokubu, Fumio; Huang, Shau-Ku; Morishima, Yuko; Matsukura, Satoshi; Kurokawa, Masatsugu; Ishii, Yukio; Satoh, Hiroaki; Sakamoto, Tohru; Hizawa, Nobuyuki

    2015-01-01

    Interleukin (IL)-32 is a novel cytokine and is involved in the pathogenesis of various inflammatory diseases, including asthma and COPD. However, the regulatory mechanisms of IL-32 expression and its precise pathogenic role remain to be defined. Given that viral infections are known to potentially cause and exacerbate airway inflammation, in this study, we investigated the expression of IL-32 induced by synthetic double-stranded (ds) RNA, and its signaling mechanisms involved. Bronchial epithelial cells were stimulated with synthetic dsRNA poly I:C. The levels of IL-32 expression were analyzed using real-time PCR and ELISA. The involvement of transforming growth factor β-activated kinase 1 (TAK1) and a subunit of nuclear factor-κB (NF-κB), p65 was determined by western blot analyses. TAK1 inhibitor, 5Z-7-Oxozeaenol and NF-κB inhibitor, BAY 11-7082 were added to the culture to identify key signaling events leading to the expression of IL-32. Finally, the effect of short interfering RNAs (siRNAs) targeting TAK1 and p65 was investigated. dsRNA significantly induced IL-32 gene and protein expression, concomitant with activation of TAK1 and p65. Pretreatment of 5Z-7-Oxozeaenol diminished dsRNA-induced phosphorylation of NF-κB. Both 5Z-7-Oxozeaenol and BAY 11-7082 significantly abrogated dsRNA-induced IL-32 production. Moreover, transfection of the cells with siRNAs targeting TAK1 and p65 inhibited the expression of IL-32. The expression of IL-32 is induced by dsRNA via the TAK1-NF-κB signaling pathway in bronchial epithelial cells. IL-32 is involved in the pathogenesis of airway inflammation, and may be a novel therapeutic target for airway inflammatory diseases.

  7. Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in CD133-positive glioblastoma stem cells

    Directory of Open Access Journals (Sweden)

    Wen-Shin Song

    2016-10-01

    Conclusion: SOX2 plays a crucial role in regulating tumorigenicity in CD133+ GBM cells. Our results not only revealed the genetic plasticity contributing to drug resistance and stemness but also demonstrated the dominant role of SOX2 in maintenance of GBM CSCs, which may provide a novel therapeutic target to overcome the conundrum of poor survival of brain cancers.

  8. INFLUENZA-INDUCED UP-REGULATION OF TLR3 IN RESPIRATORY EPITHELIAL CELLS MAY OCCUR THROUGH A POSITIVE FEEDBACK LOOP INVOLVING TYPE I INTERFERON

    Science.gov (United States)

    Toll-like receptor 3 (TLR3) plays an important role in the host defense responses against viral infections, including Influenza virus infections. Based on our previous observations showing that Influenza infection of respiratory epithelial cells results in an up-regulation of Tol...

  9. Cutting edge: The adapters EAT-2A and -2B are positive regulators of CD244- and CD84-dependent NK cell functions in the C57BL/6 mouse.

    Science.gov (United States)

    Wang, Ninghai; Calpe, Silvia; Westcott, Jill; Castro, Wilson; Ma, Chunyan; Engel, Pablo; Schatzle, John D; Terhorst, Cox

    2010-11-15

    EWS/FLI1-activated transcript 2 (EAT-2)A and EAT-2B are single SH2-domain proteins, which bind to phosphorylated tyrosines of signaling lymphocyte activation molecule family receptors in murine NK cells. While EAT-2 is a positive regulator in human cells, a negative regulatory role was attributed to the adapter in NK cells derived from EAT-2A-deficient 129Sv mice. To evaluate whether the genetic background or the presence of a selection marker in the mutant mice could influence the regulatory mode of these adapters, we generated EAT-2A-, EAT-2B-, and EAT-2A/B-deficient mice using C57BL/6 embryonic stem cells. We found that NK cells from EAT-2A- and EAT-2A/B-deficient mice were unable to kill tumor cells in a CD244- or CD84-dependent manner. Furthermore, EAT-2A/B positively regulate phosphorylation of Vav-1, which is known to be implicated in NK cell killing. Thus, as in humans, the EAT-2 adapters act as positive regulators of signaling lymphocyte activation molecule family receptor-specific NK cell functions in C57BL/6 mice.

  10. Why does positive mental health buffer against psychopathology? : An exploratory study on self compassion as a resilience mechanism and adaptive emotion regulation strategy

    NARCIS (Netherlands)

    Trompetter, H.R.; De Kleine, E.; Bohlmeijer, E.T.

    2017-01-01

    Growing evidence suggests that positive mental health or wellbeing protects against psychopathology. How and why those who flourish derive these resilient outcomes is, however, unknown. This exploratory study investigated if self-compassion, as it continuously provides a friendly, accepting and

  11. A novel AP2/ERF family transcription factor from Glycine soja, GsERF71, is a DNA binding protein that positively regulates alkaline stress tolerance in Arabidopsis.

    Science.gov (United States)

    Yu, Yang; Duan, Xiangbo; Ding, Xiaodong; Chen, Chao; Zhu, Dan; Yin, Kuide; Cao, Lei; Song, Xuewei; Zhu, Pinghui; Li, Qiang; Nisa, Zaib Un; Yu, Jiyang; Du, Jianying; Song, Yu; Li, Huiqing; Liu, Beidong; Zhu, Yanming

    2017-07-01

    Here we first found that GsERF71, an ERF factor from wild soybean could increase plant alkaline stress tolerance by up-regulating H+-ATPase and by modifing the accumulation of Auxin. Alkaline soils are widely distributed all over the world and greatly limit plant growth and development. In our previous transcriptome analyses, we have identified several ERF (ethylene-responsive factor) genes that responded strongly to bicarbonate stress in the roots of wild soybean G07256 (Glycine soja). In this study, we cloned and functionally characterized one of the genes, GsERF71. When expressed in epidermal cells of onion, GsERF71 localized to the nucleus. It can activate the reporters in yeast cells, and the C-terminus of 170 amino acids is essential for its transactivation activity. Yeast one-hybrid and EMSA assays indicated that GsERF71 specifically binds to the cis-acting elements of the GCC-box, suggesting that GsERF71 may participate in the regulation of transcription of the relevant biotic and abiotic stress-related genes. Furthermore, transgenic Arabidopsis plants overexpressing GsERF71 showed significantly higher tolerance to bicarbonate stress generated by NaHCO 3 or KHCO 3 than the wild type (WT) plants, i.e., the transgenic plants had greener leaves, longer roots, higher total chlorophyll contents and lower MDA contents. qRT-PCR and rhizosphere acidification assays indicated that the expression level and activity of H + -ATPase (AHA2) were enhanced in the transgenic plants under alkaline stress. Further analysis indicated that the expression of auxin biosynthetic genes and IAA contents were altered to a lower extent in the roots of transgenic plants than WT plants under alkaline stress in a short-term. Together, our data suggest that GsERF71 enhances the tolerance to alkaline stress by up-regulating the expression levels of H + -ATPase and by modifying auxin accumulation in transgenic plants.

  12. Positive Regulation of Staphylococcal Enterotoxin H by Rot (Repressor of Toxin) Protein and Its Importance in Clonal Complex 81 Subtype 1 Lineage-Related Food Poisoning.

    Science.gov (United States)

    Sato'o, Yusuke; Hisatsune, Junzo; Nagasako, Yuria; Ono, Hisaya K; Omoe, Katsuhiko; Sugai, Motoyuki

    2015-11-01

    We previously demonstrated the clonal complex 81 (CC81) subtype 1 lineage is the major staphylococcal food poisoning (SFP)-associated lineage in Japan (Y. Sato'o et al., J Clin Microbiol 52:2637-2640, 2014, http://dx.doi.org/10.1128/JCM.00661-14). Strains of this lineage produce staphylococcal enterotoxin H (SEH) in addition to SEA. However, an evaluation of the risk for the recently reported SEH has not been sufficiently conducted. We first searched for staphylococcal enterotoxin (SE) genes and SE proteins in milk samples that caused a large SFP outbreak in Japan. Only SEA and SEH were detected, while there were several SE genes detected in the samples. We next designed an experimental model using a meat product to assess the productivity of SEs and found that only SEA and SEH were detectably produced in situ. Therefore, we investigated the regulation of SEH production using a CC81 subtype 1 isolate. Through mutant analysis of global regulators, we found the repressor of toxin (Rot) functioned oppositely as a stimulator of SEH production. SEA production was not affected by Rot. seh mRNA expression correlated with rot both in media and on the meat product, and the Rot protein was shown to directly bind to the seh promoter. The seh promoter sequence was predicted to form a loop structure and to hide the RNA polymerase binding sequences. We propose Rot binds to the promoter sequence of seh and unfolds the secondary structure that may lead the RNA polymerase to bind the promoter, and then seh mRNA transcription begins. This alternative Rot regulation for SEH may contribute to sufficient toxin production by the CC81 subtype 1 lineage in foods to induce SFP. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder

    Science.gov (United States)

    2014-01-01

    Background HIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals compared to 20% in general population. Cognitive impairment in heavy cigarette smokers has been well reported. However, the synergistic effects of nicotine and HIV infection and the underlying mechanisms in the development of HAND are unknown. Results In this study, we explored the role of nicotine in the progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were infected with HIV-1 in the presence or absence of nicotine for 7 days. We observed significant increase in HIV infectivity in SK-N-MC treated with nicotine compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to significantly dysregulate the expression of synaptic plasticity genes and spine density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted in HIV latency breakdown and recovery of synaptic plasticity genes expression and spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore, increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic translational process, was observed in HIV alone and in co-treatment with nicotine compared to untreated control and nicotine alone treated SK-N-MC cells. Conclusions These results suggest that nicotine and HIV synergize to negatively regulate the synaptic plasticity gene expression and spine density and this may contribute to the increased risk of HAND in HIV infected smokers. Apart from disrupting latency, vorinostat may be a useful therapeutic to inhibit the negative regulatory effects on synaptic plasticity in HIV infected nicotine abusers. PMID:24886748

  14. SIRT6 Is a Positive Regulator of Aldose Reductase Expression in U937 and HeLa cells under Osmotic Stress: In Vitro and In Silico Insights.

    Directory of Open Access Journals (Sweden)

    Ahmet Can Timucin

    Full Text Available SIRT6 is a protein deacetylase, involved in various intracellular processes including suppression of glycolysis and DNA repair. Aldose Reductase (AR, first enzyme of polyol pathway, was proposed to be indirectly associated to these SIRT6 linked processes. Despite these associations, presence of SIRT6 based regulation of AR still remains ambiguous. Thus, regulation of AR expression by SIRT6 was investigated under hyperosmotic stress. A unique model of osmotic stress in U937 cells was used to demonstrate the presence of a potential link between SIRT6 and AR expression. By overexpressing SIRT6 in HeLa cells under hyperosmotic stress, its role on upregulation of AR was revealed. In parallel, increased SIRT6 activity was shown to upregulate AR in U937 cells under hyperosmotic milieu by using pharmacological modulators. Since these modulators also target SIRT1, binding of the inhibitor, Ex-527, specifically to SIRT6 was analyzed in silico. Computational observations indicated that Ex-527 may also target SIRT6 active site residues under high salt concentration, thus, validating in vitro findings. Based on these evidences, a novel regulatory step by SIRT6, modifying AR expression under hyperosmotic stress was presented and its possible interactions with intracellular machinery was discussed.

  15. Feasibility of an Emotion Regulation Intervention to Improve Mental Health and Reduce HIV Transmission Risk Behaviors for HIV-Positive Gay and Bisexual Men with Sexual Compulsivity.

    Science.gov (United States)

    Parsons, Jeffrey T; Rendina, H Jonathon; Moody, Raymond L; Gurung, Sitaji; Starks, Tyrel J; Pachankis, John E

    2017-06-01

    Gay and bisexual men (GBM) report high rates of sexual compulsivity (SC), yet no empirically based treatments exist. An intervention based on the Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders was pilot tested in a sample of 13 HIV-positive GBM with SC. Participants completed a baseline interview, and were offered up to ten intervention sessions. Of those, 11 completed a 3-month follow-up assessment. Despite problems with session attendance (only 4 men completed all 10 sessions), improvements were observed in all psychological outcomes, including SC, depression, and anxiety. Decreases were observed in drug use and HIV risk. The Unified Protocol may be useful in improving the health of HIV-positive GBM, however challenges with session attendance must be addressed. Future work should consider if fewer sessions produce similar results, whether barriers to attending all sessions could be alleviated, and how the intervention would perform compared to treatments.

  16. Insulin-like growth factor-1-mediated regulation of miR-193a expression promotes the migration and proliferation of c-kit-positive mouse cardiac stem cells.

    Science.gov (United States)

    Sun, Yuning; Xu, Rongfeng; Huang, Jia; Yao, Yuyu; Pan, Xiaodong; Chen, Zhongpu; Ma, Genshan

    2018-02-21

    C-kit-positive cardiac stem cells (CSCs) have been shown to be a promising candidate treatment for myocardial infarction and heart failure. Insulin-like growth factor (IGF)-1 is an anabolic growth hormone that regulates cellular proliferation, differentiation, senescence, and death in various tissues. Although IGF-1 promotes the migration and proliferation of c-kit-positive mouse CSCs, the underlying mechanism remains unclear. Cells were isolated from adult mouse hearts, and c-kit-positive CSCs were separated using magnetic beads. The cells were cultured with or without IGF-1, and c-kit expression was measured by Western blotting. IGF-1 induced CSC proliferation and migration, as measured through Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. The miR-193a expression was measured by quantitative real-time PCR (qPCR) assays. IGF-1 enhanced c-kit expression in c-kit-positive CSCs. The activities of the phosphoinositol 3-kinase (PI3K)/AKT signaling pathway and DNA methyltransferases (DNMTs) were enhanced, and their respective inhibitors LY294002 and 5-azacytidine (5-AZA) blunted c-kit expression. Based on the results of quantitative real-time PCR (qPCR) assays, the expression of miR-193a, which is embedded in a CpG island, was down-regulated in the IGF-1-stimulated group and negatively correlated with c-kit expression, whereas c-kit-positive CSCs infected with lentivirus carrying micro-RNA193a displayed reduced c-kit expression, migration and proliferation. IGF-1 upregulated c-kit expression in c-kit-positive CSCs resulting in enhanced CSC proliferation and migration by activating the PI3K/AKT/DNMT signaling pathway to epigenetically silence miR-193a, which negatively modifies the c-kit expression level.

  17. Dual Regulation of Bacillus subtilis kinB Gene Encoding a Sporulation Trigger by SinR through Transcription Repression and Positive Stringent Transcription Control

    Directory of Open Access Journals (Sweden)

    Yasutaro Fujita

    2017-12-01

    Full Text Available It is known that transcription of kinB encoding a trigger for Bacillus subtilis sporulation is under repression by SinR, a master repressor of biofilm formation, and under positive stringent transcription control depending on the adenine species at the transcription initiation nucleotide (nt. Deletion and base substitution analyses of the kinB promoter (PkinB region using lacZ fusions indicated that either a 5-nt deletion (Δ5, nt -61/-57, +1 is the transcription initiation nt or the substitution of G at nt -45 with A (G-45A relieved kinB repression. Thus, we found a pair of SinR-binding consensus sequences (GTTCTYT; Y is T or C in an inverted orientation (SinR-1 between nt -57/-42, which is most likely a SinR-binding site for kinB repression. This relief from SinR repression likely requires SinI, an antagonist of SinR. Surprisingly, we found that SinR is essential for positive stringent transcription control of PkinB. Electrophoretic mobility shift assay (EMSA analysis indicated that SinR bound not only to SinR-1 but also to SinR-2 (nt -29/-8 consisting of another pair of SinR consensus sequences in a tandem repeat arrangement; the two sequences partially overlap the ‘-35’ and ‘-10’ regions of PkinB. Introduction of base substitutions (T-27C C-26T in the upstream consensus sequence of SinR-2 affected positive stringent transcription control of PkinB, suggesting that SinR binding to SinR-2 likely causes this positive control. EMSA also implied that RNA polymerase and SinR are possibly bound together to SinR-2 to form a transcription initiation complex for kinB transcription. Thus, it was suggested in this work that derepression of kinB from SinR repression by SinI induced by Spo0A∼P and occurrence of SinR-dependent positive stringent transcription control of kinB might induce effective sporulation cooperatively, implying an intimate interplay by stringent response, sporulation, and biofilm formation.

  18. Licensing of safety critical software for nuclear reactors - Common position of seven European nuclear regulators and authorised technical support organisations - Revision 2013

    International Nuclear Information System (INIS)

    2013-01-01

    This report is the 5th revision of the report. The task force was formed in 1994 as a group of experts on safety critical software. The members come from regulatory authorities and/or their technical support organization. Bo Liwaang, SSM, has been a member since the work started in 1994. For full information of the historical background, previous revisions of the report and objectives, see the Introduction of the report. The conclusions and viewpoints presented in the report are those of the authors and do not necessarily coincide with those of the SSM. The report, without the SSM cover and this page, will be published by or available at the websites of the other participating organizations. Effect on SSM supervisory and regulatory task: The effect of the report is high as it presents a common view on important issues by experts from seven European regulatory organizations, even though the report is not a regulation or guide

  19. Can we document if regulation and Best Available Techniques (BAT) have any positive impact on the marine environment? A case based on a steel mill in Greece.

    Science.gov (United States)

    Panagiotoulias, I; Botsou, F; Kaberi, H; Karageorgis, A P; Scoullos, M

    2017-10-31

    In order to document the impact of Best Available Techniques (BAT) and implementation of regulation on the improvement of the coastal marine environment state, we examined the case of a representative steel mill located at the Gulf of Elefsis (Greece). The evaluation of metal pollution was based on the analysis of major and trace elements, organic carbon, magnetic properties, and sediment accumulation rates, in sediment cores obtained from the vicinity of the plant. The analytical data are discussed in relation to steel production, changes of production routes, and adoption of BAT introduced in order to fulfill EU and national legislation. The results show that the input of pollutants to sediments and the degree of contamination were reduced by approximately 40-70% in the decade 2003-2015 in comparison to the periods of high discharges (1963-2002), whereas the toxicity risks from "high-to-extremely high" were reduced to "medium-to-high."

  20. Licensing of safety critical software for nuclear reactors - Common position of seven European nuclear regulators and authorised technical support organisations - Revision 2013

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-05-01

    This report is the 5th revision of the report. The task force was formed in 1994 as a group of experts on safety critical software. The members come from regulatory authorities and/or their technical support organization. Bo Liwaang, SSM, has been a member since the work started in 1994. For full information of the historical background, previous revisions of the report and objectives, see the Introduction of the report. The conclusions and viewpoints presented in the report are those of the authors and do not necessarily coincide with those of the SSM. The report, without the SSM cover and this page, will be published by or available at the websites of the other participating organizations. Effect on SSM supervisory and regulatory task: The effect of the report is high as it presents a common view on important issues by experts from seven European regulatory organizations, even though the report is not a regulation or guide.

  1. The utility of siRNA transcripts produced by RNA polymerase i in down regulating viral gene expression and replication of negative- and positive-strand RNA viruses

    International Nuclear Information System (INIS)

    McCown, Matthew; Diamond, Michael S.; Pekosz, Andrew

    2003-01-01

    Short interfering double-stranded RNAs (siRNAs) expressed under the control of an RNA polymerase I promoter system were used to target gene expression of influenza A and West Nile virus. Decreased RNA and protein expression was induced in a sequence-specific manner--reducing sequence complementarity from 21 to 17 nucleotides abrogated the siRNA effect. Reduced M 2 expression resulted in a decrease in total and infectious influenza A virus production. WNV protein expression, genomic RNA, and infectious virus production were all dramatically reduced by siRNAs targeting two distinct viral sequences. The data demonstrate the utility of plasmid-driven siRNAs in regulating the expression of single viral genes, global viral gene expression, as a potential antiviral treatment, and as a genetic tool for viruses whose genomes are difficult to manipulate

  2. Class III PI3K Positively Regulates Platelet Activation and Thrombosis via PI(3)P-Directed Function of NADPH Oxidase.

    Science.gov (United States)

    Liu, Yangyang; Hu, Mengjiao; Luo, Dongjiao; Yue, Ming; Wang, Shuai; Chen, Xiaoyan; Zhou, Yangfan; Wang, Yi; Cai, Yanchun; Hu, Xiaolan; Ke, Yuehai; Yang, Zhongzhou; Hu, Hu

    2017-11-01

    Class III phosphoinositide 3-kinase, also known as VPS34 (vacuolar protein sorting 34), is a highly conserved enzyme regulating important cellular functions such as NADPH oxidase (NOX) assembly, membrane trafficking, and autophagy. Although VPS34 is expressed in platelets, its involvement in platelet activation remains unclear. Herein, we investigated the role of VPS34 in platelet activation and thrombus formation using VPS34 knockout mice. Platelet-specific VPS34-deficient mice were generated and characterized. VPS34 deficiency in platelets did not influence tail bleeding time. In a ferric chloride-induced mesenteric arteriolar thrombosis model, VPS34 -/- mice exhibited a prolonged vessel occlusion time compared with wild-type mice (42.05±4.09 versus 18.30±2.47 minutes). In an in vitro microfluidic whole-blood perfusion assay, thrombus formation on collagen under arterial shear was significantly reduced for VPS34 -/- platelets. VPS34 -/- platelets displayed an impaired aggregation and dense granule secretion in response to low doses of collagen or thrombin. VPS34 deficiency delayed clot retraction but did not influence platelet spreading on fibrinogen. We also demonstrated that VPS34 deficiency altered the basal level of autophagy in resting platelets and hampered NOX assembly and mTOR (mammalian target of rapamycin) signaling during platelet activation. Importantly, we identified the NOX-dependent reactive oxygen species generation as the major downstream effector of VPS34, which in turn can mediate platelet activation. In addition, by using a specific inhibitor 3-methyladenine, VPS34 was found to operate through a similar NOX-dependent mechanism to promote human platelet activation. Platelet VPS34 is critical for thrombosis but dispensable for hemostasis. VPS34 regulates platelet activation by influencing NOX assembly. © 2017 American Heart Association, Inc.

  3. Global regulator IscR positively contributes to antimonite resistance and oxidation in Comamonas testosteroni S44

    DEFF Research Database (Denmark)

    Liu, Hongliang; Zhuang, Weiping; Zhang, Shengzhe

    2015-01-01

    Antimonial compounds can be found as a toxic contaminant in the environment. Knowledge on mechanisms of microbial Sb oxidation and its role in microbial tolerance are limited. Previously, we found that Comamonas testosteroni S44 was resistant to multiple heavy metals and was able to oxidize......(III). Results of electrophoretic mobility shift assay (EMSA) and bacterial one-hybrid (B1H) system demonstrated a positive interaction between IscR and its promoter region. The diverse defective phenotypes and various expression patterns suggest a role for IscR in contributing to multi-metal(loid)s resistance...

  4. Positive Feedback Regulation of Agonist-Stimulated Endothelial Ca2+ Dynamics by KCa3.1 Channels in Mouse Mesenteric Arteries

    DEFF Research Database (Denmark)

    Qian, Xun; Francis, Michael; Köhler, Ralf

    2014-01-01

    Intermediate and small conductance KCa channels IK1 (KCa3.1) and SK3 (KCa2.3) are primary targets of endothelial Ca(2+) signals in the arterial vasculature, and their ablation results in increased arterial tone and hypertension. Activation of IK1 channels by local Ca(2+) transients from internal ...... stores or plasma membrane channels promotes arterial hyperpolarization and vasodilation. Here, we assess arteries from genetically altered IK1 knockout mice (IK1(-/-)) to determine whether IK1 channels exert a positive feedback influence on endothelial Ca(2+) dynamics....

  5. An oral keratinocyte life cycle model identifies novel host genome regulation by human papillomavirus 16 relevant to HPV positive head and neck cancer

    OpenAIRE

    Evans, Michael R.; James, Claire D.; Loughran, Oonagh; Nulton, Tara J.; Wang, Xu; Bristol, Molly L.; Windle, Brad; Morgan, Iain M.

    2017-01-01

    Many aspects of the HPV life cycle have been characterized in cervical cell lines (W12, CIN612) and in HPV immortalized primary foreskin keratinocytes. There is now an epidemic of HPV positive oropharyngeal cancers (HPV16 is responsible for 80-90% of these); therefore increased understanding of the HPV16 life cycle in oral keratinocytes is a priority. To date there have been limited reports characterizing the HPV16 life cycle in oral keratinocytes. Using TERT immortalized “normal” oral kerati...

  6. Positional Concerns and Institutions

    DEFF Research Database (Denmark)

    Landes, Xavier

    2013-01-01

    their implications for economics, positional concerns imply important normative dimensions. There have been presumed to be a symptom of envy, reduce people’s happiness, and create problems of social interaction or economic inefficiencies. Individuals are, for instance, prone to pick states of the world that improve...... that invoking envy or subjective well-being is not fully satisfying for regulating positional concerns. More compelling reasons seem, in complement with efficiency, to be related to considerations for equality. In other words, if institutions could have strong reasons to pay attention to and regulate positional...... concerns, it would be in virtue of their impact on the social product and individuals’ conditions of living....

  7. The legal position of illegitimate children according to the regulations that were in force in the territory of Vojvodina in the Kingdom of Serbs, Croats and Slovenes

    Directory of Open Access Journals (Sweden)

    Drakić Gordana

    2013-01-01

    Full Text Available In the Kingdom of Serbs, Croats and Slovenes existed six different legal territories. Legal particularism that existed in the common state of Serbs, Croats and Slovenes was one of the major problems in state that caused many problems in the everyday life of citizens. One of the main goals of the authorities was to execute equating of laws. Special shortened procedure for equating of laws was established by the St. Vitus' Day Constitution. In the territory of Vojvodina mainly were valid Hungarian laws. Illegitimate children were in a inferior legal position than children born in wedlock according to the laws that were in force in the territory of Vojvodina. Illegitimate child was in kinship only with its mother. Non-marital children could be equated with children born in wedlock in two cases prescribed by law: if parents of illegitimate child enter marriage later on, or pursuant to the Royal Decree. The legal position of non-marital children was one of the outstanding social issues in the state that had to be uniformly resolved.

  8. Progesterone and levonorgestrel regulate expression of 17βHSD-enzymes in progesterone receptor positive breast cancer cell line T47D.

    Science.gov (United States)

    Sivik, Tove; Jansson, Agneta

    2012-05-25

    The use of combined hormone replacement therapy (HRT) with oestrogens and progestins in postmenopausal women has been associated with an increased risk for developing breast cancer. The reasons are not fully understood, but influence of HRT on endogenous conversion of female sex hormones may be involved. The expression of 17β hydroxysteroid dehydrogenases (17βHSD), which are enzymes catalysing the conversion between more or less potent oestrogens, may partly be regulated by progestins. The breast cancer cell lines T47D, MCF7 and ZR75-1 were treated with progesterone, medroxyprogesterone acetate (MPA) or levonorgestrel for 48 and 72 h at 10(-7) and 10(-9)M to investigate influence on 17βHSD1, 17βHSD2 and 17βHSD5 mRNA expression measured by real time PCR. The expression of 17βHSD1 increased in progesterone and levonorgestrel treated T47D cells (48 h 10(-7)M P=0.002; PT47D cells were co-treated with progestins and the progesterone receptor (PgR) inhibitor mifprestone. We show that both reductive (17βHSD1 and 17βHSD5) and oxidative (17βHSD2) members of the 17βHSD-family are under control of progesterone and progestins in breast cancer cell lines. This is most clear in T47D cells which have high PgR expression. 17βHSD-enzymes are important players in the regulation of sex steroids locally in breast tumours and tumoural expression of various 17βHSD-enzymes have prognostic and treatment predictive relevance. We propose a mechanism for increased breast cancer risk after HRT in which hormone replacement affects the expression of 17βHSD-enzymes, favouring the expression of reductive enzymes, which in turn could increase levels of bioactive and mitogenic estrogens in local tissue, e.g. breast tissue. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Positive parenting mitigates the effects of poor self-regulation on body mass index trajectories from ages 4-15 years.

    Science.gov (United States)

    Connell, Lauren E; Francis, Lori A

    2014-08-01

    This study sought to determine whether parenting style moderates the effects of delay of gratification on body mass index (BMI) trajectories from ages 4-15 years. Longitudinal data were analyzed for 778 children drawn from the Study of Early Child Care and Youth Development. Parenting style (i.e., authoritative, authoritarian, permissive, and neglectful) was created from measures of mothers' sensitivity and expectations for self-control when children were age 4 years. Self-regulation was also measured at 4 years using a well-known delay of gratification protocol. BMI was calculated from measured height and weight at each time point. Mixed modeling was used to test the interaction of parenting styles and ability to delay gratification on BMI trajectories from 4-15 years. There was a significant interaction effect of parenting and ability to delay on BMI growth from 4-15 years for boys. Boys who had authoritarian mothers and failed to delay gratification had a significantly steeper rate of growth in BMI from childhood through adolescence than children in any other parenting by delay group. Authoritative and permissive parenting styles were protective against more rapid BMI gains for boys who could not delay gratification. Ability to delay gratification was protective against BMI gains for boys who had parents with authoritarian or neglectful parenting styles.

  10. PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II.

    Science.gov (United States)

    Voz, M L; Agten, N S; Van de Ven, W J; Kas, K

    2000-01-01

    PLAG1, a novel developmentally regulated C2H2 zinc finger gene, is consistently rearranged and overexpressed in pleomorphic adenomas of the salivary glands with 8q12 translocations. In this report, we show that PLAG1 is a nuclear protein that binds DNA in a specific manner. The consensus PLAG1 binding site is a bipartite element containing a core sequence, GRGGC, and a G-cluster, RGGK, separated by seven random nucleotides. DNA binding is mediated mainly via three of the seven zinc fingers, with fingers 6 and 7 interacting with the core and finger 3 with the G-cluster. In transient transactivation assays, PLAG1 specifically activates transcription from its consensus DNA binding site, indicating that PLAG1 is a genuine transcription factor. Potential PLAG1 binding sites were found in the promoter 3 of the human insulin-like growth factor II (IGF-II) gene. We show that PLAG1 binds IGF-II promoter 3 and stimulates its activity. Moreover, IGF-II transcripts derived from the P3 promoter are highly expressed in salivary gland adenomas overexpressing PLAG1. In contrast, they are not detectable in adenomas without abnormal PLAG1 expression nor in normal salivary gland tissue. This indicates a perfect correlation between PLAG1 and IGF-II expression. All of these results strongly suggest that IGF-II is one of the PLAG1 target genes, providing us with the first clue for understanding the role of PLAG1 in salivary gland tumor development.

  11. Tripartite Motif 8 (TRIM8) Positively Regulates Pro-inflammatory Responses in Pseudomonas aeruginosa-Induced Keratitis Through Promoting K63-Linked Polyubiquitination of TAK1 Protein.

    Science.gov (United States)

    Guo, Litao; Dong, Weili; Fu, Xiaoxiao; Lin, Jing; Dong, Zhijun; Tan, Xiaobo; Zhang, Tiemin

    2017-04-01

    Pseudomonas aeruginosa (PA)-induced keratitis is a rapidly progressive ocular infectious disease that often leads to inflammatory epithelial edema, stromal infiltration, tissue destruction, corneal ulceration, and vision loss. In this study, we investigate the role of tripartite motif 8 (TRIM8) in regulating the inflammatory process of PA-induced keratitis. The expression of TRIM8 was increased in mouse corneas and in vitro-cultured macrophages after PA infection. Knockdown of the expression of TRIM8 significantly inhibited the activation of NF-κB signaling and decreased the production of pro-inflammatory cytokines both in vivo and in vitro after infected with PA. Furthermore, we investigated the potential mechanism and we found after PA infection that TRIM8 could promote K63-linked polyubiquitination of transforming growth factor β-activated kinase 1 (TAK1), leading to the activation of TAK1 and enhanced inflammatory responses. Taken together, we demonstrated that TRIM8 has pro-inflammatory effect on PA-induced keratitis and suggest TRIM8 as a potential therapeutic target for keratitis.

  12. The garlic NF-YC gene, AsNF-YC8, positively regulates non-ionic hyperosmotic stress tolerance in tobacco.

    Science.gov (United States)

    Sun, Xiudong; Lian, Haifeng; Liu, Xingchen; Zhou, Shumei; Liu, Shiqi

    2017-05-01

    To investigate the relationship between nuclear factor Y (NF-Y) and stress tolerance in garlic, we cloned a NF-Y family gene AsNF-YC8 from garlic, which was largely upregulated at dehydrate stage. Expression pattern analyses in garlic revealed that AsNF-YC8 is induced through abscisic acid (ABA) and abiotic stresses, such as NaCl and PEG. Compared with wild-type plants, the overexpressing-AsNF-YC8 transgenic tobacco plants showed higher seed germination rates, longer root length and better plant growth under salt and drought stresses. Under drought stress, the transgenic plants maintained higher relative water content (RWC), net photosynthesis, lower levels of malondialdehyde (MDA), and less ion leakage (IL) than wild-type control plants. These results indicate the high tolerance of the transgenic plants to drought stress compared to the WT. The transgenic tobacco lines accumulated less reactive oxygen species (ROS) and exhibited higher antioxidative enzyme activities compared with wild-type (WT) plants under drought stress, which suggested that the overexpression of AsNF-YC8 improves the antioxidant defense system by regulating the activities of these antioxidant enzymes, which in turn protect transgenic lines against drought stress. These results suggest that AsNF-YC8 plays an important role in tolerance to drought and salt stresses.

  13. Promoter of CaZF, a chickpea gene that positively regulates growth and stress tolerance, is activated by an AP2-family transcription factor CAP2.

    Directory of Open Access Journals (Sweden)

    Deepti Jain

    Full Text Available Plants respond to different forms of stresses by inducing transcription of a common and distinct set of genes by concerted actions of a cascade of transcription regulators. We previously reported that a gene, CaZF encoding a C2H2-zinc finger family protein from chickpea (Cicer arietinum imparted high salinity tolerance when expressed in tobacco plants. We report here that in addition to promoting tolerance against dehydration, salinity and high temperature, the CaZF overexpressing plants exhibited similar phenotype of growth and development like the plants overexpressing CAP2, encoding an AP2-family transcription factor from chickpea. To investigate any relationship between these two genes, we performed gene expression analysis in the overexpressing plants, promoter-reporter analysis and chromatin immunoprecipitation. A number of transcripts that exhibited enhanced accumulation upon expression of CAP2 or CaZF in tobacco plants were found common. Transient expression of CAP2 in chickpea leaves resulted in increased accumulation of CaZF transcript. Gel mobility shift and transient promoter-reporter assays suggested that CAP2 activates CaZF promoter by interacting with C-repeat elements (CRTs in CaZF promoter. Chromatin immunoprecipitation (ChIP assay demonstrated an in vivo interaction of CAP2 protein with CaZF promoter.

  14. Receptor of advanced glycation end products (RAGE) positively regulates CD36 expression and reactive oxygen species production in human monocytes in diabetes.

    Science.gov (United States)

    Xanthis, A; Hatzitolios, A; Fidani, S; Befani, C; Giannakoulas, G; Koliakos, G

    Advanced glycation end products (AGEs) engagement of a monocyte surface receptor (RAGE) induces atherosclerosis. AGEs also act as CD36 ligands. We studied reactive oxygen species (ROS) and CD36 expression after siRNA inhibition of RAGE expression in human monocytes. We isolated monocytes from: a) 10 type 2 diabetics, and b) 5 age- and sex-matched healthy individuals. CD36 expression and ROS production were evaluated before and after RAGE knockdown. After incubation of monocytes with AGE + bovine serum albumin (BSA), CD36 expression and intracellular ROS increased significantly in all groups. In RAGE-knockdown monocytes, AGE-induced CD36 expression and ROS generation were also significantly inhibited. Blocking RAGE expression using siRNA in human monocytes led to a significant inhibition of CD36 expression and ROS production, suggesting a positive interaction between RAGE, CD36 expression and ROS generation in monocytes.

  15. Profiling of gene expression regulated by 17β-estradiol and tamoxifen in estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Rangel N

    2017-09-01

    Full Text Available Nelson Rangel,1,2 Victoria E Villegas,2 Milena Rondón-Lagos3 1Department of Medical Sciences, University of Turin, Turin, Italy; 2Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá, Colombia; 3School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, Tunja, Colombia Abstract: One area of great importance in breast cancer (BC research is the study of gene expression regulated by both estrogenic and antiestrogenic agents. Although many studies have been performed in this area, most of them have only addressed the effects of 17β-estradiol (E2 and tamoxifen (TAM on MCF7 cells. This study aimed to determine the effect of low doses of E2 and TAM on the expression levels of 84 key genes, which are commonly involved in breast carcinogenesis, in four BC cell lines differentially expressing estrogen receptor (ER α and HER2 (MCF7, T47D, BT474, and SKBR3. The results allowed us to determine the expression patterns modulated by E2 and TAM in ERα+ and ERα− cell lines, as well as to identify differences in expression patterns. Although the MCF7 cell line is the most frequently used model to determine gene expression profiles in response to E2 and TAM, the changes in gene expression patterns identified in ERα+ and ERα− cell lines could reflect distinctive properties of these cells. Our results could provide important markers to be validated in BC patient samples, and subsequently used for predicting the outcome in ERα+ and ERα− tumors after TAM or hormonal therapy. Considering that BC is a molecularly heterogeneous disease, it is important to understand how well, and which cell lines, best model that diversity. Keywords: breast cancer, cell lines, 17β-estradiol, tamoxifen, ERα+, ERα−, qPCR

  16. SnRK1 phosphorylation of FUSCA3 positively regulates embryogenesis, seed yield, and plant growth at high temperature in Arabidopsis.

    Science.gov (United States)

    Chan, Aaron; Carianopol, Carina; Tsai, Allen Yi-Lun; Varathanajah, Kresanth; Chiu, Rex Shun; Gazzarrini, Sonia

    2017-07-10

    The transcription factor FUSCA3 (FUS3) acts as a major regulator of seed maturation in Arabidopsis. FUS3 is phosphorylated by the SnRK1 catalytic subunit AKIN10/SnRK1α1, which belongs to a conserved eukaryotic kinase complex involved in energy homeostasis. Here we show that AKIN10 and FUS3 share overlapping expression patterns during embryogenesis, and that FUS3 is phosphorylated by AKIN10 in embryo cell extracts. To understand the role of FUS3 phosphorylation, we generated fus3-3 plants carrying FUS3 phosphorylation-null (FUS3S>A) and phosphorylation-mimic (FUS3S>D) variants. While FUS3S>A and FUS3S>D rescued all the fus3-3 seed maturation defects, FUS3S>A showed reduced transcriptional activity and enhanced fus3-3 previously uncharacterized phenotypes. FUS3S>A embryos displayed increased seed abortion due to maternal FUS3S>A and delayed embryo development, which correlated with a strong decrease in seed yield (~50%). Accordingly, the akin10 and akin11 mutants displayed a frequency of seed abortion similar to fus3-3. When plants were grown at elevated temperature, most phenotypes were exaggerated in FUS3S>A plants, and progeny seedlings overall grew poorly, suggesting that phosphorylation of FUS3 plays an important role during early embryogenesis and under heat stress. Collectively, these results suggest that FUS3 phosphorylation and SnRK1 are required for embryogenesis and integration of environmental cues to ensure the survival of the progeny. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  17. Upregulated microRNA-92b regulates the differentiation and proliferation of EpCAM-positive fetal liver cells by targeting C/EBPß.

    Directory of Open Access Journals (Sweden)

    Nian-Song Qian

    Full Text Available microRNAs (miRNAs are short noncoding RNAs that negatively regulate gene expression. Although recent evidences have been indicated that their aberrant expression may play an important role in cancer stem cells, the mechanism of their deregulation in neoplastic transformation of liver cancer stem cells (LCSCs has not been explored. In our study, the HCC model was established in F344 rats by DEN induction. The EpCAM(+ cells were sorted out from unfractionated fetal liver cells and liver cancer cells using the FACS analysis and miRNA expression profiles of two groups were screened through microarray platform. Gain-of-function studies were performed in vitro and in vivo to determine the role of miR-92b on proliferation and differentiation of the hepatic progenitors. In addition, luciferase reporter system and gene function analysis were used to predict miR-92b target. we found that miR-92b was highly downregulated in EpCAM(+ fetal liver cells in expression profiling studies. RT-PCR analysis demonstrated reverse correlation between miR-92b expression and differentiation degree in human HCC samples. Overexpression of miR-92b in EpCAM(+ fetal liver cells significantly increased proliferation and inhibited differentiation as well as in vitro and in vivo studies. Moreover, we verified that C/EBPß is a direct target of miR-92b and contributes to its effects on proliferation and differentiation. We conclude that aberrant expression of miR-92b can result in proliferation increase and differentiation arrest of hepatic progenitors by targeting C/EBPß.

  18. AP2/ERF Transcription Factor, Ii049, Positively Regulates Lignan Biosynthesis in Isatis indigotica through Activating Salicylic Acid Signaling and Lignan/Lignin Pathway Genes

    Directory of Open Access Journals (Sweden)

    Ruifang Ma

    2017-08-01

    Full Text Available Lignans, such as lariciresinol and its derivatives, have been identified as effective antiviral ingredients in Isatis indigotica. Evidence suggests that the APETALA2/ethylene response factor (AP2/ERF family might be related to the biosynthesis of lignans in I. indigotica. However, the special role played by the AP2/ERF family in the metabolism and its underlying putative mechanism still need to be elucidated. One novel AP2/ERF gene, named Ii049, was isolated and characterized from I. indigotica in this study. The quantitative real-time PCR analysis revealed that Ii049 was expressed highest in the root and responded to methyl jasmonate, salicylic acid (SA and abscisic acid treatments to various degrees. Subcellular localization analysis indicated that Ii049 protein was localized in the nucleus. Knocking-down the expression of Ii049 caused a remarkable reduction of lignan/lignin contents and transcript levels of genes involved in the lignan/lignin biosynthetic pathway. Ii049 bound to the coupled element 1, RAV1AAT and CRTAREHVCBF2 motifs of genes IiPAL and IiCCR, the key structural genes in the lignan/lignin pathway. Furthermore, Ii049 was also essential for SA biosynthesis, and SA induced lignan accumulation in I. indigotica. Notably, the transgenic I. indigotica hairy roots overexpressing Ii049 showed high expression levels of lignan/lignin biosynthetic genes and SA content, resulting in significant accumulation of lignan/lignin. The best-engineered line (OVX049-10 produced 425.60 μg·g−1 lariciresinol, an 8.3-fold increase compared with the wild type production. This study revealed the function of Ii049 in regulating lignan/lignin biosynthesis, which had the potential to increase the content of valuable lignan/lignin in economically significant medicinal plants.

  19. Increased Nicotiana tabacum fitness through positive regulation of carotenoid, gibberellin and chlorophyll pathways promoted by Daucus carota lycopene β-cyclase (Dclcyb1) expression.

    Science.gov (United States)

    Moreno, J C; Cerda, A; Simpson, K; Lopez-Diaz, I; Carrera, E; Handford, M; Stange, C

    2016-04-01

    Carotenoids, chlorophylls and gibberellins are derived from the common precursor geranylgeranyl diphosphate (GGPP). One of the enzymes in carotenoid biosynthesis is lycopene β-cyclase (LCYB) that catalyzes the conversion of lycopene into β-carotene. In carrot, Dclcyb1 is essential for carotenoid synthesis in the whole plant. Here we show that when expressed in tobacco, increments in total carotenoids, β-carotene and chlorophyll levels occur. Furthermore, photosynthetic efficiency is enhanced in transgenic lines. Interestingly, and contrary to previous observations where overexpression of a carotenogenic gene resulted in the inhibition of the synthesis of gibberellins, we found raised levels of active GA4 and the concommitant increases in plant height, leaf size and whole plant biomass, as well as an early flowering phenotype. Moreover, a significant increase in the expression of the key carotenogenic genes, Ntpsy1, Ntpsy2 and Ntlcyb, as well as those involved in the synthesis of chlorophyll (Ntchl), gibberellin (Ntga20ox, Ntcps and Ntks) and isoprenoid precursors (Ntdxs2 and Ntggpps) was observed. These results indicate that the expression of Dclcyb1 induces a positive feedback affecting the expression of isoprenoid gene precursors and genes involved in carotenoid, gibberellin and chlorophyll pathways leading to an enhancement in fitness measured as biomass, photosynthetic efficiency and carotenoid/chlorophyll composition. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  20. Automatic affective-motivational regulation processes underlying supportive dyadic coping: the role of increased implicit positive attitudes toward communal goals in response to a stressed relationship partner.

    Science.gov (United States)

    Koranyi, Nicolas; Hilpert, Peter; Job, Veronika; Bodenmann, Guy

    2017-09-01

    We examined the implicit affective mechanisms underlying provision of support in intimate dyads. Specifically, we hypothesized that in individuals with high relationship satisfaction, the perception that one's partner is stressed leads to increased implicit positive attitudes toward communal goals. In turn, this change in implicit attitudes facilitates supportive behavior. In two studies, we induced partner stress by instructing participants to either recall a situation where their partner was highly stressed (Study 1; N = 47 university students) or imagine a specific stressful event (excessive workload; Study 2; N = 85 university students). Subsequently, implicit attitudes toward communal goals were assessed with an Implicit Association Test. In both studies, we found that among participants with high relationship satisfaction partner stress increases preferences for communal goals. In addition, implicit preferences for communal goals predicted stronger inclinations to engage in supportive dyadic coping (Study 2). The current findings provide important insights into the implicit cognitive-affective mechanics of dyadic coping. Moreover, they can explain how people manage to avoid experiencing motivational conflicts between partner-oriented and self-oriented goals in situations characterized by high partner stress.

  1. LY294002 may overcome 5-FU resistance via down-regulation of activated p-AKT in Epstein-Barr virus-positive gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Shin Jung-Young

    2010-08-01

    Full Text Available Abstract Background As EBV-associated gastric cancer has unique features that are different from EBV (- gastric cancer, EBV is considered to have a key role in gastric carcinogenesis. It has been reported that viral latent membrane protein 2A (LMP2A in EBV-transformed tumor cells activates the phosphatidylinositol 3-kinase (PI3K/AKT pathway, which provides a survival signal and chemo-resistance to cytotoxic anti-cancer drugs. This study was to evaluate anti-proliferative effect and cell cycle change when 5-FU and LY294002 (LY, a selective inhibitor of PI3K, were treated separately or combined with different schedules in EBV positive gastric cancer cell line, SNU-719. Methods After single treatment and sequential combination of 5-FU and LY, cytotoxic activity was measured by MTS assay. When 5-FU and LY were treated in single and sequential combinations, the expression of p-AKT, p-NFkB, p-p53 and bcl-2 was observed on different concentrations by Western blot analysis. We also investigated the effect on apoptosis and cell cycle distribution using flow cytometry. The LMP2A siRNA inhibition was done to confirm the reversal of decreased 5-FU activity and p-AKT. Results When 5-FU was sequentially combined with LY, the combination index (CI value indicated synergistic anti-proliferative effect. The expression of p-AKT and p-NFκB was upregulated by 5-FU alone but sequential treatment of 5-FU and LY decreased the expression of both p-AKT and p-NFκB. When 5-FU was combined with LY, G0/G1 and sub G1 cell population (% increased. When 5-FU was added to the cells transfected with LMP2A siRNA, its anti-proliferative effect increased and the expression of p-AKT decreased. In sequential combination of 5-FU and LY, the expression of p-p53 was increased and bcl-2 expression was diminished compared to 5-FU alone. Conclusion These data suggest that sequential combination of 5-FU and LY induce synergistic cytotoxicity and overcome intrinsic and acquired resistance

  2. LY294002 may overcome 5-FU resistance via down-regulation of activated p-AKT in Epstein-Barr virus-positive gastric cancer cells.

    Science.gov (United States)

    Shin, Jung-Young; Kim, Jeong-Oh; Lee, Suk Kyeong; Chae, Hiun-Suk; Kang, Jin-Hyoung

    2010-08-13

    As EBV-associated gastric cancer has unique features that are different from EBV (-) gastric cancer, EBV is considered to have a key role in gastric carcinogenesis. It has been reported that viral latent membrane protein 2A (LMP2A) in EBV-transformed tumor cells activates the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which provides a survival signal and chemo-resistance to cytotoxic anti-cancer drugs. This study was to evaluate anti-proliferative effect and cell cycle change when 5-FU and LY294002 (LY), a selective inhibitor of PI3K, were treated separately or combined with different schedules in EBV positive gastric cancer cell line, SNU-719. After single treatment and sequential combination of 5-FU and LY, cytotoxic activity was measured by MTS assay. When 5-FU and LY were treated in single and sequential combinations, the expression of p-AKT, p-NFkB, p-p53 and bcl-2 was observed on different concentrations by Western blot analysis. We also investigated the effect on apoptosis and cell cycle distribution using flow cytometry. The LMP2A siRNA inhibition was done to confirm the reversal of decreased 5-FU activity and p-AKT. When 5-FU was sequentially combined with LY, the combination index (CI) value indicated synergistic anti-proliferative effect. The expression of p-AKT and p-NF kappaB was upregulated by 5-FU alone but sequential treatment of 5-FU and LY decreased the expression of both p-AKT and p-NF kappaB. When 5-FU was combined with LY, G0/G1 and sub G1 cell population (%) increased. When 5-FU was added to the cells transfected with LMP2A siRNA, its anti-proliferative effect increased and the expression of p-AKT decreased. In sequential combination of 5-FU and LY, the expression of p-p53 was increased and bcl-2 expression was diminished compared to 5-FU alone. These data suggest that sequential combination of 5-FU and LY induce synergistic cytotoxicity and overcome intrinsic and acquired resistance of 5-FU via downregulation of activated p-AKT and

  3. The botrydial biosynthetic gene cluster of Botrytis cinerea displays a bipartite genomic structure and is positively regulated by the putative Zn(II)2Cys6 transcription factor BcBot6.

    Science.gov (United States)

    Porquier, Antoine; Morgant, Guillaume; Moraga, Javier; Dalmais, Bérengère; Luyten, Isabelle; Simon, Adeline; Pradier, Jean-Marc; Amselem, Joëlle; Collado, Isidro González; Viaud, Muriel

    2016-11-01

    Botrydial (BOT) is a non-host specific phytotoxin produced by the polyphagous phytopathogenic fungus Botrytis cinerea. The genomic region of the BOT biosynthetic gene cluster was investigated and revealed two additional genes named Bcbot6 and Bcbot7. Analysis revealed that the G+C/A+T-equilibrated regions that contain the Bcbot genes alternate with A+T-rich regions made of relics of transposable elements that have undergone repeat-induced point mutations (RIP). Furthermore, BcBot6, a Zn(II) 2 Cys 6 putative transcription factor was identified as a nuclear protein and the major positive regulator of BOT biosynthesis. In addition, the phenotype of the ΔBcbot6 mutant indicated that BcBot6 and therefore BOT are dispensable for the development, pathogenicity and response to abiotic stresses in the B. cinerea strain B05.10. Finally, our data revealed that B. pseudocinerea, that is also polyphagous and lives in sympatry with B. cinerea, lacks the ability to produce BOT. Identification of BcBot6 as the major regulator of BOT synthesis is the first step towards a comprehensive understanding of the complete regulation network of BOT synthesis and of its ecological role in the B. cinerea life cycle. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Position Information

    Data.gov (United States)

    Social Security Administration — The Position Information Data Asset provides the ability to search for active SSA position descriptions using various search criteria. An individual may search by PD...

  5. Positioning consumption

    DEFF Research Database (Denmark)

    Halkier, Bente; Keller, Margit

    2014-01-01

    This article analyses the ways in which media discourses become a part of contested consumption activities. We apply a positioning perspective with practice theory to focus on how practitioners relate to media discourse as a symbolic resource in their everyday practices. A typology of performance...... positionings emerges based on empirical examples of research in parent–children consumption. Positionings are flexible discursive fixations of the relationship between the performances of the practitioner, other practitioners, media discourse and consumption activities. The basic positioning types...

  6. Positive Psychology

    Science.gov (United States)

    Peterson, Christopher

    2009-01-01

    Positive psychology is a deliberate correction to the focus of psychology on problems. Positive psychology does not deny the difficulties that people may experience but does suggest that sole attention to disorder leads to an incomplete view of the human condition. Positive psychologists concern themselves with four major topics: (1) positive…

  7. Ubiquitous positioning

    CERN Document Server

    Mannings, Robin

    2008-01-01

    This groundbreaking resource offers a practical, in-depth understanding of Ubiquitous Positioning - positioning systems that identify the location and position of people, vehicles and objects in time and space in the digitized networked economy. The future and growth of ubiquitous positioning will be fueled by the convergence of many other areas of technology, from mobile telematics, Internet technology, and location systems, to sensing systems, geographic information systems, and the semantic web. This first-of-its-kind volume explores ubiquitous positioning from a convergence perspective, of

  8. Positioning consumption

    DEFF Research Database (Denmark)

    Halkier, Bente; Keller, Margit

    2014-01-01

    This article analyses the ways in which media discourses become a part of contested consumption activities. We apply a positioning perspective with practice theory to focus on how practitioners relate to media discourse as a symbolic resource in their everyday practices. A typology of performance...... positionings emerges based on empirical examples of research in parent–children consumption. Positionings are flexible discursive fixations of the relationship between the performances of the practitioner, other practitioners, media discourse and consumption activities. The basic positioning types...... are the practice maintenance and the practice change position, with different sorts of adapting in between. Media discourse can become a resource for a resistant position against social control or for an appropriating position in favour of space for action. Regardless of the current relation to a particular media...

  9. NRC regulations and positions concerning decontamination

    International Nuclear Information System (INIS)

    McCracken, C.

    1982-09-01

    The U.S. Nuclear Regulatory Commission encourages the use of decontamination to reduce man-rem exposure. The Commission feels that there are several processes developed to the point where soft decontamination can be applied to an entire plant in the near future. A utility can do a decontamination under its own licence without coming in for regulatory review if the process does not involve a change in technical specifications for the plant or does not involve unreviewed safety questions. Prior verbal notification is required for some steam generator secondary side cleaning or for decontamination of individual components that have not been removed from the reactor using chemicals not normally added to the reactor coolant. Prior written notification is required for steam generator secondary side crevice cleaning or sludge removal at a dented unit, or for chemical decontamination of reactor coolant systems or safety-related systems using chemicals not normally added to the coolant

  10. HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Wen-Tsung Huang

    2017-12-01

    Full Text Available Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER+ breast cancer patients. Even though dysregulations of histone deacetylases (HDACs are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER+ breast cancer remains unclear. Survivin is a well-known pro-tumor survival molecule and miR-125a-5p is a recently discovered tumor suppressor. In this study, we found that ER+, hormone-independent, tamoxifen-resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and survivin, but show decreased expression of miR-125a-5p, as compared to the parental tamoxifen-sensitive MCF7 breast cancer cells. Molecular down-regulations of HDAC2, HDAC5, and survivin, and ectopic over-expression of miR-125a-5p, increased the sensitivity of MCF7-TamC3 cells to estrogen deprivation and restored the sensitivity to tamoxifen. The same treatments also further increased the sensitivity to estrogen-deprivation in the ER+ hormone-dependent ZR-75-1 breast cancer cells in vitro. Kaplan–Meier analysis and receiver operating characteristic curve analysis of expression cohorts of breast tumor showed that high HDAC2 and survivin, and low miR-125a-5p, expression levels correlate with poor relapse-free survival in endocrine therapy and tamoxifen-treated ER+ breast cancer patients. Further molecular analysis revealed that HDAC2 and HDAC5 positively modulates the expression of survivin, and negatively regulates the expression miR-125a-5p, in ER+ MCF7, MCF7-TamC3, and ZR-75-1 breast cancer cells. These findings indicate that dysregulations of HDAC2 and HDAC5 promote the development of hormone independency and tamoxifen resistance in ERC breast cancer cells in part through expression regulation of survivin and miR-125a-5p.

  11. Nuclear Positioning

    Science.gov (United States)

    Gundersen, Gregg G.; Worman, Howard J.

    2013-01-01

    SUMMARY The nucleus is the largest organelle and is commonly depicted in the center of the cell. Yet during cell division, migration and differentiation, it frequently moves to an asymmetric position aligned with cell function. We consider the toolbox of proteins that move and anchor the nucleus within the cell and how forces generated by the cytoskeleton are coupled to the nucleus to move it. The significance of proper nuclear positioning is underscored by numerous diseases resulting from genetic alterations in the toolbox proteins. Finally, we discuss how nuclear position may influence cellular organization and signaling pathways. PMID:23498944

  12. Radiographic positioning

    International Nuclear Information System (INIS)

    Eisenberg, R.L.; Dennis, C.A.; May, C.

    1989-01-01

    This book concentrates on the routine radiographic examinations commonly performed. It details the wide variety of examinations possible and their place in initial learning and in the radiology department as references for those occasions when an unusual examination is requested. This book provides information ranging from basic terminology to skeletal positioning to special procedures. Positions are discussed and supplemented with a picture of a patient, the resulting radiograph, and a labeled diagram. Immobilization and proper shielding of the patient are also shown

  13. [Positive psychiatry].

    Science.gov (United States)

    Timmerby, Nina; Austin, Stephen; Bech, Per

    2016-02-08

    Positive psychiatry (PP) is a field within psychiatry with a particular focus on promoting well-being in people who already have or are at high risk of developing mental or physical illness. PP should be considered a supplement to trad-tional psychiatry and a call for therapists in psychiatry to focus on the person as a whole rather than just as a patient. PP is in line with current national and international health policy focus on promoting positive mental health.

  14. Position encoder

    International Nuclear Information System (INIS)

    Goursky, Vsevolod

    1975-01-01

    A circuitry for deriving the quotient of signal delivered by position-sensitive detectors is described. Digital output is obtained in the form of 10- to 12-bit words. Impact position may be determined with 0.25% accuracy when the dynamic range of the energy signal is less 1:10, and 0.5% accuracy when the dynamic range is 1:20. The division requires an average time of 5μs for 10-bit words

  15. Position encoder

    International Nuclear Information System (INIS)

    Goursky, V.

    1975-05-01

    This paper describes circuitry for deriving the quotient of signals delivered by position-sensitive detectors. Digital output is obtained in the form of 10 to 12 bit words. Impact position may be determined with 0.25% accuracy when the dynamic range of the energy signal is less than 1:10, and 0.5% accuracy when the dynamic range is 1:20. The division requires an average time of 5μs for 10-bit words [fr

  16. Researcher positioning

    DEFF Research Database (Denmark)

    Mørck, Line Lerche; Khawaja, Iram

    2009-01-01

    abstract  This article focuses on the complex and multi-layered process of researcher positioning, specifically in relation to the politically sensitive study of marginalised and ‘othered' groups such as Muslims living in Denmark. We discuss the impact of different ethnic, religious and racial...... backgrounds, of membership in a minoritised[i] or majoritised group, and the influence of different theoretical and methodological outlooks on our common goal of trying to transcend existing othering and objectifying representations of Muslims in Western societies. This process sometimes entails a direct...... political and personal involvement by the researcher, which challenges traditional perspectives on research and researcher positioning. A key point in this regard is the importance of constant awareness of and reflection on the multiple ways in which one's positioning as a researcher influences the research...

  17. Positional games

    CERN Document Server

    Hefetz, Dan; Stojaković, Miloš; Szabó, Tibor

    2014-01-01

    This text serves as a thorough introduction to the rapidly developing field of positional games. This area constitutes an important branch of combinatorics, whose aim it is to systematically develop an extensive mathematical basis for a variety of two-player perfect information games. These range from such popular games as Tic-Tac-Toe and Hex to purely abstract games played on graphs and hypergraphs. The subject of positional games is strongly related to several other branches of combinatorics such as Ramsey theory, extremal graph and set theory, and the probabilistic method. These notes cover a variety of topics in positional games, including both classical results and recent important developments. They are presented in an accessible way and are accompanied by exercises of varying difficulty, helping the reader to better understand the theory. The text will benefit both researchers and graduate students in combinatorics and adjacent fields.

  18. Tomato SR/CAMTA transcription factors SlSR1 and SlSR3L negatively regulate disease resistance response and SlSR1L positively modulates drought stress tolerance.

    Science.gov (United States)

    Li, Xiaohui; Huang, Lei; Zhang, Yafen; Ouyang, Zhigang; Hong, Yongbo; Zhang, Huijuan; Li, Dayong; Song, Fengming

    2014-10-28

    The SR/CAMTA proteins represent a small family of transcription activators that play important roles in plant responses to biotic and abiotic stresses. Seven SlSR/CAMTA genes were identified in tomato as tomato counterparts of SR/CAMTA; however, the involvement of SlSRs/CAMTAs in biotic and abiotic stress responses is not clear. In this study, we performed functional analysis of the SlSR/CAMTA family for their possible functions in defense response against pathogens and tolerance to drought stress. Expression of SlSRs was induced with distinct patterns by Botrytis cinerea and Pseudomonas syringae pv. tomato (Pst) DC3000. Virus-induced gene silencing (VIGS)-based knockdown of either SlSR1 or SlSR3L in tomato resulted in enhanced resistance to B. cinerea and Pst DC3000 and led to constitutive accumulation of H2O2, elevated expression of defense genes, marker genes for pathogen-associated molecular pattern-triggered immunity, and regulatory genes involved in the salicylic acid- and ethylene-mediated signaling pathways. Furthermore, the expression of SlSR1L and SlSR2L in detached leaves and whole plants was significantly induced by drought stress. Silencing of SlSR1L led to decreased drought stress tolerance, accelerated water loss in leaves, reduced root biomass and attenuated expression of drought stress responsive genes in tomato. The SlSR1 and SlSR3L proteins were localized in the nucleus of plant cells when transiently expressed in Nicotiana benthamiana and had transcriptional activation activity in yeast. VIGS-based functional analyses demonstrate that both SlSR1 and SlSR3L in the tomato SlSR/CAMTA family are negative regulators of defense response against B. cinerea and Pst DC3000 while SlSR1L is a positive regulator of drought stress tolerance in tomato.

  19. Researcher Positioning

    DEFF Research Database (Denmark)

    Khawaja, Iram; Mørck, Line Lerche

    2009-01-01

    involvement by the researcher, which challenges traditional perspectives onresearch and researcher positioning. A key point in this regard is the importance ofconstant awareness of and reflection on the multiple ways in which one's positioningas a researcher influences the research process. Studying the other...

  20. Nucleosome Positioning and Epigenetics

    Science.gov (United States)

    Schwab, David; Bruinsma, Robijn

    2008-03-01

    The role of chromatin structure in gene regulation has recently taken center stage in the field of epigenetics, phenomena that change the phenotype without changing the DNA sequence. Recent work has also shown that nucleosomes, a complex of DNA wrapped around a histone octamer, experience a sequence dependent energy landscape due to the variation in DNA bend stiffness with sequence composition. In this talk, we consider the role nucleosome positioning might play in the formation of heterochromatin, a compact form of DNA generically responsible for gene silencing. In particular, we discuss how different patterns of nucleosome positions, periodic or random, could either facilitate or suppress heterochromatin stability and formation.

  1. Immune responses to novel Escherichia coli and Salmonella typhimurium vectors that express colonization factor antigen I (CFA/I) of enterotoxigenic E. coli in the absence of the CFA/I positive regulator cfaR.

    Science.gov (United States)

    Wu, S; Pascual, D W; VanCott, J L; McGhee, J R; Maneval, D R; Levine, M M; Hone, D M

    1995-12-01

    An asd-stabilized plasmid carrying enterotoxigenic Escherichia coli cfaABCE genes was constructed and called pJGX15C-asd+. Expression of colonization factor antigen I (CFA/I) by this plasmid occurs independently of the cfaABCE positive regulator cfaR in attenuated Salmonella delta aro delta asd strain H683 and nonpathogenic laboratory E. coli asd strain chi 6212. Oral immunization of mice with nonpathogenic E. coli chi 6212 (pJGX15C-asd+) does not elicit significant serum or mucosal responses against CFA/I. In contrast, oral immunization with a single dose of attenuated S. typhimurium H683(pJGX15C-asd+) elicits a 10(5)-fold increase in CFA/I-specific serum immunoglobulin G and significant elevation of CFA/I-specific immunoglobulin A-secreting B cells in the lamina propria, mesenteric lymph nodes, and spleen. Thus, only the Salmonella-CFA/I construct effectively delivered CFA/I to the inductive sites of the gut-associated and systemic lymphoid tissues.

  2. Positioning apparatus

    Science.gov (United States)

    Vogel, Max A.; Alter, Paul

    1986-01-01

    An apparatus for precisely positioning materials test specimens within the optimum neutron flux path emerging from a neutron source located in a housing. The test specimens are retained in a holder mounted on the free end of a support pivotably mounted and suspended from a movable base plate. The support is gravity biased to urge the holder in a direction longitudinally of the flux path against the housing. Means are provided for moving the base plate in two directions to effect movement of the holder in two mutually perpendicular directions normal to the axis of the flux path.

  3. Positive psychology. An introduction.

    Science.gov (United States)

    Seligman, M E; Csikszentmihalyi, M

    2000-01-01

    A science of positive subjective experience, positive individual traits, and positive institutions promises to improve quality of life and prevent the pathologies that arise when life is barren and meaningless. The exclusive focus on pathology that has dominated so much of our discipline results in a model of the human being lacking the positive features that make life worth living. Hope, wisdom, creativity, future mindedness, courage, spirituality, responsibility, and perseverance are ignored or explained as transformations of more authentic negative impulses. The 15 articles in this millennial issue of the American Psychologist discuss such issues as what enables happiness, the effects of autonomy and self-regulation, how optimism and hope affect health, what constitutes wisdom, and how talent and creativity come to fruition. The authors outline a framework for a science of positive psychology, point to gaps in our knowledge, and predict that the next century will see a science and profession that will come to understand and build the factors that allow individuals, communities, and societies to flourish.

  4. GABA and GABA-Alanine from the Red Microalgae Rhodosorus marinus Exhibit a Significant Neuro-Soothing Activity through Inhibition of Neuro-Inflammation Mediators and Positive Regulation of TRPV1-Related Skin Sensitization

    Directory of Open Access Journals (Sweden)

    Amandine Scandolera

    2018-03-01

    marinus extract. Two active molecules, namely, γ-aminobutyric acid (GABA and its structural derivative GABA-alanine, demonstrated a strong capacity to positively regulate skin sensitization mechanisms related to the TRPV1 receptors under PMA-induced inflammatory conditions, therefore providing interesting perspectives for the treatment of sensitive skins, atopia, dermatitis, or psoriasis.

  5. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  6. Benign positional vertigo

    Science.gov (United States)

    Vertigo - positional; Benign paroxysmal positional vertigo; BPPV: dizziness- positional ... Benign positional vertigo is also called benign paroxysmal ... ear has fluid-filled tubes called semicircular canals. When you ...

  7. Studies Of Positive-Position-Feedback Control

    Science.gov (United States)

    Fanson, James L.; Caughey, Thomas K.

    1992-01-01

    Report discusses theoretical and experimental studies of positive-position-feedback control for suppressing vibrations in large flexible structures. Positive-position-feedback control involves placement of actuators and sensors on structure; control voltages applied to actuators in response to outputs of sensors processed via compensator algorithm. Experiments demonstrate feasibility of suppressing vibrations by positive position feedback, and spillover of vibrational energy into uncontrolled modes has stabilizing effect if control gain sufficiently small.

  8. GAS6/Mer axis regulates the homing and survival of the E2A/PBX1 positive B-cell precursor acute lymphoblastic leukemia in the bone marrow niche

    OpenAIRE

    Shiozawa, Yusuke; Pedersen, Elisabeth A.; Taichman, Russell S.

    2009-01-01

    Despite improvements in current combinational chemotherapy regimens, the prognosis of the (1;19)(q23;p13) translocation (E2A/PBX1) positive B-cell precursor acute lymphoblastic leukemia (ALL) is poor in pediatric leukemia patients. In this study, we examined the roles of GAS6/Mer axis in the interactions between E2A/PBX1 positive B-cell precursor ALL cells and the osteoblastic niche in the bone marrow. The data show that primary human osteoblasts secrete GAS6 in response to the Mer-over-expre...

  9. Obg-like ATPase 1 regulates global protein serine/threonine phosphorylation in cancer cells by suppressing the GSK3β-inhibitor 2-PP1 positive feedback loop.

    Science.gov (United States)

    Xu, Dong; Song, Renduo; Wang, Guohui; Jeyabal, Prince V S; Weiskoff, Amanda M; Ding, Kefeng; Shi, Zheng-Zheng

    2016-01-19

    OLA1 is an Obg family P-loop NTPase that possesses both GTP- and ATP-hydrolyzing activities. Here we report that OLA1 is a GSK3β interacting protein, and through its ATPase activity, inhibits the GSK3β-mediated activation of protein serine/threonine phosphatase 1 (PP1). It is hypothesized that GSK3β phosphorylates inhibitor 2 (I-2) of PP1 at Thr-72 and activates the PP1 · I-2 complex, which in turn dephosphorylates and stimulates GSK3β, thus forming a positive feedback loop. We revealed that the positive feedback loop is normally suppressed by OLA1, and becomes over-activated under OLA1 deficiency, resulting in increased cellular PP1 activity and dephosphorylation of multiple Ser/Thr phosphoproteins, and more strikingly, decreased global protein threonine phosphorylation. Furthermore, using xenograft models of colon cancer (H116) and ovarian cancer (SKOV3), we established a correlation among downregulation of OLA1, over-activation of the positive feedback loop as indicated by under-phosphorylation of I-2, and more aggressive tumor growth. This study provides the first evidence for the existence of a GSK3β-I-2-PP1 positive feedback loop in human cancer cells, and identifies OLA1 as an endogenous suppressor of this signaling motif.

  10. Basic residues in the 74-83 and 191-198 segments of protein kinase CK2 catalytic subunit are implicated in negative but not in positive regulation by the beta-subunit

    DEFF Research Database (Denmark)

    Sarno, S; Vaglio, P; Marin, O

    1997-01-01

    by the beta-subunit many fold more than that of alpha wild type, while extrastimulation by beta mutant D55L56E57A, observable with alpha wild type, is abolished with these mutants. These data support the conclusion that down regulation by the acidic residues clustered in the N-terminal moiety of beta......Protein kinase CK2 is a ubiquitous pleiotropic serine/threonine protein kinase whose holoenzyme is comprised of two catalytic (alpha and/or alpha') and two non-catalytic, beta-subunits. The beta-subunit possesses antagonist functions that can be physically dissected by generating synthetic...... fragments encompassing its N-terminal and C-terminal domains. Here we show that by mutating basic residues in the 74-77 and in the 191-198 regions of the alpha-subunit, the negative regulation by the beta-subunit and by its N-terminal synthetic fragment CK2beta-(1-77), which is observable using calmodulin...

  11. Work zone positive protection guidelines for Idaho.

    Science.gov (United States)

    2014-12-01

    The Code of Federal Regulation (CFR) Title 23 Part 630 Subpart K - Temporary Traffic Control (630.1102630.1110) rule states : that positive protection shall be considered where work zone conditions place workers at increased risk from motorized : ...

  12. Position automatic determination technology

    International Nuclear Information System (INIS)

    1985-10-01

    This book tells of method of position determination and characteristic, control method of position determination and point of design, point of sensor choice for position detector, position determination of digital control system, application of clutch break in high frequency position determination, automation technique of position determination, position determination by electromagnetic clutch and break, air cylinder, cam and solenoid, stop position control of automatic guide vehicle, stacker crane and automatic transfer control.

  13. 25-Hydroxyvitamin D3-enhanced PTPN2 positively regulates periodontal inflammation through the JAK/STAT pathway in human oral keratinocytes and a mouse model of type 2 diabetes mellitus.

    Science.gov (United States)

    Zhang, P; Zhang, W; Zhang, D; Wang, M; Aprecio, R; Ji, N; Mohamed, O; Li, Y; Ding, Y; Wang, Q

    2018-03-08

    Periodontitis is an increasingly prevalent complication of diabetes mellitus (known as diabetes mellitus-associated periodontitis), and 25-hydroxyvitamin D 3 (25VD 3 ) was recently found to be a critical regulator of innate immunity in this disease, but the underlying mechanisms remain poorly understood. T-cell protein tyrosine phosphatase non-receptor type 2 (PTPN2) is a potential downstream protein of the 25VD 3 /vitamin D receptor pathway. The aim of this study was to investigate the regulation of PTPN2 in periodontal inflammation in diabetes mellitus-associated periodontitis. Porphyromonas gingivalis-infected db/db mice were treated with 25VD 3 . Their fasting blood glucose and body weight were monitored every other week, and the levels of alveolar bone loss and serum inflammatory cytokines (tumor necrosis factor-α, interferon-γ and interleukin-6) were determined at the time of killing. The effect of PTPN2 on human OKF6-TERT2 oral keratinocytes was examined through the knockout of PTPN2 using the CRISPR/Cas9 knockout plasmid. The expression levels of the PTPN2, vitamin D receptor and JAK1/STAT3 signaling proteins in the gingival epithelium and OKF6-TERT2 cells were determined through western blot and immunohistochemical analyses. After 25VD 3 treatment, db/db mice exhibited alleviated serum inflammatory cytokines and alveolar bone loss, and 25VD 3 -enhanced PTPN2 expression decreased the expression of the JAK1/STAT3 signaling proteins in the gingival epithelium. Analyses of human oral keratinocytes showed that 25VD 3 increased the expression of PTPN2, which dephosphorylates protein substrates in the JAK1/STAT3 signaling pathway. PTPN2 contributed to a decrease in periodontal inflammation in type 2 diabetes mellitus via dephosphorylate protein substrates in the JAK1/STAT3 signaling pathway after 25VD 3 treatment in human oral keratinocytes and a mouse model of type 2 diabetes mellitus. A thorough understanding of PTPN2 and its involvement in inhibiting

  14. 32 CFR Appendix J to Part 154 - ADP Position Categories and Criteria for Designating Positions

    Science.gov (United States)

    2010-07-01

    ... Designating Positions J Appendix J to Part 154 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE PERSONNEL SECURITY PROGRAM REGULATION Pt. 154, App. J Appendix J to Part 154—ADP Position Categories and Criteria for Designating Positions OMB Circular A-71...

  15. Poplar PdC3H17 and PdC3H18 are direct targets of PdMYB3 and PdMYB21, and positively regulate secondary wall formation in Arabidopsis and poplar.

    Science.gov (United States)

    Chai, Guohua; Qi, Guang; Cao, Yingping; Wang, Zengguang; Yu, Li; Tang, Xianfeng; Yu, Yanchong; Wang, Dian; Kong, Yingzhen; Zhou, Gongke

    2014-07-01

    Wood biomass is mainly made of secondary cell walls, whose formation is controlled by a multilevel network. The tandem CCCH zinc finger (TZF) proteins involved in plant secondary wall formation are poorly understood. Two TZF genes, PdC3H17 and PdC3H18, were isolated from Populus deltoides and functionally characterized in Escherichia coli, tobacco, Arabidopsis and poplar. PdC3H17 and PdC3H18 are predominantly expressed in cells of developing wood, and the proteins they encode are targeted to cytoplasmic foci. Transcriptional activation assays showed that PdMYB2/3/20/21 individually activated the PdC3H17 and PdC3H18 promoters, but PdMYB3/21 were most significant. Electrophoretic mobility shift assays revealed that PdMYB3/21 bound directly to the PdC3H17/18 promoters. Overexpression of PdC3H17/18 in poplar increased secondary xylem width and secondary wall thickening in stems, whereas dominant repressors of them had the opposite effects on these traits. Similar alteration in secondary wall thickening was observed in their transgenic Arabidopsis plants. qRT-PCR results showed that PdC3H17/18 regulated the expression of cellulose, xylan and lignin biosynthetic genes, and several wood-associated MYB genes. These results demonstrate that PdC3H17 and PdC3H18 are the targets of PdMYB3 and PdMYB21 and are an additional two components in the regulatory network of secondary xylem formation in poplar. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  16. A novel dual lock method for down-regulation of genes, in which a target mRNA is captured at 2 independent positions by linked locked nucleic acid antisense oligonucleotides.

    Science.gov (United States)

    Takata, Ryohei; Makado, Gouki; Kitamura, Ayaka; Watanabe, Hajime; Wada, Tadashi

    2016-01-01

    Nuclear factor κB (NFκB), which is composed of the RelA and p50 subunits, binds to NFκB response elements (NREs) and stimulates the transcription of inflammation-related genes. Here, locked nucleic acid (LNA) antisense oligonucleotides (ASOs) complementary to the termini of the 3'- and 5'-untranslated regions (UTRs) of the RelA mRNA were generated; these molecules were named 3'-LNA and 5'-LNA, respectively. To evaluate their effects on NFκB activity, HeLa cells were co-transfected with the LNA ASOs and a luciferase reporter gene carrying an NRE. Transfection of the cells with 3'-LNA reduced NFκB activity by 30-40%, without affecting RelA mRNA accumulation. Concomitant transfection of HeLa cells with 5'-LNA and 3'-LNA resulted in a 70% reduction in NFκB activity. Furthermore, partial poly(A) tail shortening occurred in LNA ASO-transfected cells. We also employed triethylene glycol as a spacer to link 5'-LNA and 3'-LNA. Reporter gene assays showed that the spacer-linked LNA ASO reduced NFκB activity similarly to a combination of 5'-LNA and 3'-LNA. In addition, an in vitro translation assay revealed that spacer-linked LNA ASOs inhibited the translation of a target mRNA in a specific manner. In summary, this study describes a novel antisense method capturing the target mRNA at independent positions.

  17. Positive Education: Positive Psychology and Classroom Interventions

    Science.gov (United States)

    Seligman, Martin E. P.; Ernst, Randal M.; Gillham, Jane; Reivich, Karen; Linkins, Mark

    2009-01-01

    Positive education is defined as education for both traditional skills and for happiness. The high prevalence worldwide of depression among young people, the small rise in life satisfaction, and the synergy between learning and positive emotion all argue that the skills for happiness should be taught in school. There is substantial evidence from…

  18. Want Positive Behavior? Use Positive Language

    Science.gov (United States)

    Wood, Chip; Freeman-Loftis, Babs

    2012-01-01

    Positive adult language is the professional use of words and tone of voice to enable students to learn in an engaged, active way. This includes learning social skills. To guide children toward choosing and maintaining positive behaviors, adults need to carefully choose the words and tone of voice used when speaking to them. Learning to use…

  19. Positions, positionings and posture of the enunciator

    Directory of Open Access Journals (Sweden)

    Alain Rabatel

    2013-12-01

    Full Text Available This article draws connections between the notions of enunciator position, positioning and posture, which structure the dialogic, cognitive and interactional co- production of utterances. The notion of enunciative position corresponds to the fact that the (first or second enunciator refers to objects of discourse while positioning himself/herself with regard to them, by indicating from what point of view he/she considers them. In view of the dialogic nature of the discourse, two modal subjects and levels of responsibility can be discerned: the first enunciator has the role of the agent in charge of the discourse and the second enunciator fulfills internal functions of validation, assuming thus a sort of responsibility which does not necessarily commit the first enunciator. The article then analyses the dialogic strategies of positioning by enunciative reduplication and separation which account for auto- dialogic and hetero-dialogic situations. Finally it deals with the enunciative postures of co-enunciation, over-enunciation and under-enunciation, which refine the notions of enunciative reduplication or separation, by specifying the degrees of agreement, according to dialectic between discordant concordance and concordant discordance.

  20. Multi-technology positioning

    CERN Document Server

    Lohan, Elena-Simona; Wymeersch, Henk; Seco-Granados, Gonzalo; Nykänen, Ossi

    2017-01-01

    This book provides an overview of positioning technologies, applications and services in a format accessible to a wide variety of readers. Readers who have always wanted to understand how satellite-based positioning, wireless network positioning, inertial navigation, and their combinations work will find great value in this book. Readers will also learn about the advantages and disadvantages of different positioning methods, their limitations and challenges. Cognitive positioning, adding the brain to determine which technologies to use at device runtime, is introduced as well. Coverage also includes the use of position information for Location Based Services (LBS), as well as context-aware positioning services, designed for better user experience. • Brings understanding of positioning technology to readers from a variety of disciplines • Reviews multiple techniques, providing insight on the pros, cons and challenges related to each • Designed to be a tutorial on basic principles, avoiding unnecessary de...

  1. Navicular bone position determined by positional MRI

    DEFF Research Database (Denmark)

    Hansen, Philip; Johannsen, Finn E; Hangaard, Stine

    2016-01-01

    -scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). RESULTS...

  2. Reflection Positive Doubles

    OpenAIRE

    Jaffe, Arthur; Janssens, Bas

    2016-01-01

    Here we introduce reflection positive doubles, a general framework for reflection positivity, covering a wide variety of systems in statistical physics and quantum field theory. These systems may be bosonic, fermionic, or parafermionic in nature. Within the framework of reflection positive doubles, we give necessary and sufficient conditions for reflection positivity. We use a reflection-invariant cone to implement our construction. Our characterization allows for a direct interpretation in t...

  3. Perception of eye positions

    NARCIS (Netherlands)

    Lorteije, J.A.M.; Wezel, R.J.A. van; Lankheet, M.J.M.

    2002-01-01

    In a two-alternative forced-choice psychophysical test human subjects were tested for their ability to perceive their own viewing direction. A small red flash was presented at different horizontal positions left or right from the subjects' eye position on the screen. Eye positions were recorded with

  4. The Positivity Scale

    Science.gov (United States)

    Caprara, Gian Vittorio; Alessandri, Guido; Eisenberg, Nancy; Kupfer, A.; Steca, Patrizia; Caprara, Maria Giovanna; Yamaguchi, Susumu; Fukuzawa, Ai; Abela, John

    2012-01-01

    Five studies document the validity of a new 8-item scale designed to measure "positivity," defined as the tendency to view life and experiences with a positive outlook. In the first study (N = 372), the psychometric properties of Positivity Scale (P Scale) were examined in accordance with classical test theory using a large number of…

  5. Malignant paroxysmal positional vertigo.

    Science.gov (United States)

    De Stefano, Alessandro; Kulamarva, Gautham; Dispenza, Francesco

    2012-08-01

    An insidious percentage of paroxysmal positional vertigo appears to be intractable with canalith repositioning maneuver and also is not self-limiting. This type of positional vertigo is sustained by the action of intracranial tumors that mimics the clinical aspects of benign paroxysmal positional vertigo.Aim of this study is to clarify the features of these forms of positional vertigo, which we indicate as malignant paroxysmal positional vertigo. We retrospectively reviewed the clinical records of all the patients who presented with vertigo spells and were managed at our tertiary care referral centre over a three years period. Two hundred and eleven patients with diagnosis of positional paroxysmal vertigo were included in the final study. Seven patients were affected by intracranial tumors causing a positional vertigo and were classified as malignant paroxysmal positional vertigo patients after radiological and histological diagnosis. These patients were affected by an internal auditory canal mass alone or with extension in the cerebello pontine angle that mimicked a benign positional vertigo. We can conclude that the clinician should keep in mind the differentiation between benign positional vertigo and malignant positional vertigo. When the patients with positional vertigo presents a strange behaviour of symptoms, nystagmus or response to the canalith repositioning maneuver a radiological investigation must be undertaken in every doubtful case. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Standard types of regulation loops; Chaines de regulation types

    Energy Technology Data Exchange (ETDEWEB)

    Bertrand, M. [ENSAM, Centre d`Enseignement et de Recherche de Lille, 59 - Lille (France)

    1997-12-01

    The aim of this paper is to give help in the analysis of industrial regulation problems using different types of real installations. The increasing complexity of industrial systems requires the use of a decomposition-recomposition procedure using a scheme with different blocs. Examples are given to help the non-specialist users in the mastery of essential choices and in the distinction between operational and material separations. The examples concern: the heating loop of a central heating installation, the sensors and actuators of industrial systems (the temperature regulation of a tubular furnace, the electro-hydraulic positioning systems used in machine tools, forming, aeronautics etc.., the regulation of a mixing system for hot and cold fluids, and the regulation of a fluidizing system. The usual types of regulation loops are presented with the different steps of the resolution of a regulation problem. (J.S.) 7 refs.

  7. Strigolactones positively regulate chilling tolerance in pea and in Arabidopsis.

    Science.gov (United States)

    Cooper, James W; Hu, Yan; Beyyoudh, Leila; Yildiz Dasgan, H; Kunert, Karl; Beveridge, Christine A; Foyer, Christine H

    2018-01-17

    Strigolactones (SL) fulfil important roles in plant development and stress tolerance. Here we characterised the role of SL in the dark chilling tolerance of pea and Arabidopsis by analysis of mutants that are defective in either SL synthesis or signalling. Pea mutants (rms3, rms4, rms5) had significantly greater shoot branching with higher leaf chlorophyll a/b ratios and carotenoid contents than the wild type. Exposure to dark chilling significantly decreased shoot fresh weights but increased leaf numbers in all lines. However, dark chilling treatments decreased biomass (dry weight) accumulation only in rms3 and rms5 shoots. Unlike the wild type plants, chilling-induced inhibition of photosynthetic carbon assimilation was observed in the rms lines and also in max3-9, max4-1, max2-1 mutants that are defective in SL synthesis or signalling. When grown on agar plates the max mutant rosettes accumulated less biomass than the wild type. The synthetic SL, GR24 decreased leaf area in the wild type, max3-9 and max4-1 mutants but not in max2-1 in the absence of stress. Moreover, a chilling-induced decrease in leaf area was observed in all the lines in the presence of GR24. We conclude that SL plays an important role in the control of dark chilling tolerance. This article is protected by copyright. All rights reserved.

  8. Betaine is a positive regulator of mitochondrial respiration

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Icksoo, E-mail: icksoolee@dankook.ac.kr

    2015-01-09

    Highlights: • Betaine enhances cytochrome c oxidase activity and mitochondrial respiration. • Betaine increases mitochondrial membrane potential and cellular energy levels. • Betaine’s anti-tumorigenic effect might be due to a reversal of the Warburg effect. - Abstract: Betaine protects cells from environmental stress and serves as a methyl donor in several biochemical pathways. It reduces cardiovascular disease risk and protects liver cells from alcoholic liver damage and nonalcoholic steatohepatitis. Its pretreatment can rescue cells exposed to toxins such as rotenone, chloroform, and LiCl. Furthermore, it has been suggested that betaine can suppress cancer cell growth in vivo and in vitro. Mitochondrial electron transport chain (ETC) complexes generate the mitochondrial membrane potential, which is essential to produce cellular energy, ATP. Reduced mitochondrial respiration and energy status have been found in many human pathological conditions including aging, cancer, and neurodegenerative disease. In this study we investigated whether betaine directly targets mitochondria. We show that betaine treatment leads to an upregulation of mitochondrial respiration and cytochrome c oxidase activity in H2.35 cells, the proposed rate limiting enzyme of ETC in vivo. Following treatment, the mitochondrial membrane potential was increased and cellular energy levels were elevated. We propose that the anti-proliferative effects of betaine on cancer cells might be due to enhanced mitochondrial function contributing to a reversal of the Warburg effect.

  9. Pretty Easy Pervasive Positioning

    DEFF Research Database (Denmark)

    Hansen, Rene; Wind, Rico; Jensen, Christian Søndergaard

    2009-01-01

    With the increasing availability of positioning based on GPS, Wi-Fi, and cellular technologies and the proliferation of mobile devices with GPS, Wi-Fi and cellular connectivity, ubiquitous positioning is becoming a reality. While offerings by companies such as Google, Skyhook, and Spotigo render...... positioning possible in outdoor settings, including urban environments with limited GPS coverage, they remain unable to offer accurate indoor positioning. We will demonstrate a software infrastructure that makes it easy for anybody to build support for accurate Wi-Fi based positioning in buildings. All...... that is needed is a building with Wi-Fi coverage, access to the building, a floor plan of the building, and a Wi-Fi enabled device. Specifically, we will explain the software infrastructure and the steps that must be completed to obtain support for positioning. And we will demonstrate the positioning obtained...

  10. Positive criminology in practice.

    Science.gov (United States)

    Ronel, Natti; Segev, Dana

    2014-11-01

    The discourse regarding offender rehabilitation has been criticized by various scholars who have claimed that reducing negative causes and managing risk will not automatically prompt positive human development and elements that are associated with desistance. Positive criminology is an innovative concept that challenges the common preoccupation with negative elements, by placing emphasis on human encounters and forces of inclusion that are experienced positively by target individuals and that can promote crime desistance. However, as the concept is relatively new, there are still no guiding principles for the practice of positive criminology that could direct research and the criminal justice system. This article attempts to fill that gap by providing principles that could be practiced by criminal justice personnel and examples of different interventions that reflect positive criminology. The article also provides ideological explanations for adopting the concept of positive criminology in practice. © The Author(s) 2013.

  11. EAACI taskforce position paper

    DEFF Research Database (Denmark)

    Konstantinou, G N; Asero, R; Ferrer, M

    2013-01-01

    between functionality and immunoreactivity. Approximately 25% of CU patients have a positive basophil histamine release assay and show autoreactivity (a positive autologous serum skin test), whereas 50% are negative regarding both. Functionality of CU sera appears to be complement dependent on mast cells...... (positive autoreactivity, functional bioassay and immunoassay) to define preliminary criteria sets for the diagnosis of ACU based on clinical and laboratory features with highest individual sensitivity and specificity....

  12. Positioning and locking apparatus

    Science.gov (United States)

    Hayward, M.L.; Harper, W.H.

    1985-06-19

    A positioning and locking apparatus including a fixture having a rotatable torque ring provided with a plurality of cam segments for automatically guiding a container into a desired location within the fixture. Rotation of the ring turns the container into a final position in pressure sealing relation against a hatch member.

  13. Positioning health professional identity

    DEFF Research Database (Denmark)

    Lund, Ole; Krogh Christensen, Mette; Mørcke, Anne Mette

    2017-01-01

    Drawing on positioning theory, the purpose of this paper is to characterize the activities and positions of students and supervisors at workplaces and on-campus skills training sites across the higher health professional educations of medicine, sports science, and nursing. Furthermore, the study...... explored the impact of work-based learning (WBL) and skills training on students’ personal professional identity development....

  14. Plasma position control method

    International Nuclear Information System (INIS)

    Shirahama, Hidefumi; Sakurai, Yoshimi.

    1988-01-01

    Purpose: To suppress the non-linear relationship between the horizontal position of plasmas and the intensity of the vertical magnetic fields, thereby control the horizontal position of the plasmas stably and at a high speed in a closed loop in a tokamak type thermonuclear device. Method: In a control method for approaching the plasma position to a target position in the tokamak type thermonuclear device, a function circuit having two inputs and one output is disposed in a loop constituting the plasma position control system. The characteristics of the function circuit are so designed as to provide a proportional relationship between the first input and the output, while an inverse proportional relationship between the second input and the output. A detected value for the plasma current is used as a signal for the first input, while the detected value for the plasma position or a operation amount based on the difference with the detected value is used as a signal for the second input. By using the function circuit, it is possible to suppress the non-linear characteristics in the dynamic properties of the plasmas, by which the remarkable change of gains in the plasma position control circuit due to the fluctuations of the plasma current and the position can be prevented. (Ikeda, J.)

  15. Detecting Position Using ARKit

    Science.gov (United States)

    Dilek, Ufuk; Erol, Mustafa

    2018-01-01

    Developed by using ARKit, a novel app which can be used to detect position in physics experiments was introduced. The ARKit relies on a new technique. The result of the experiment presented in this study was satisfactory, suggesting that the new technique can be employed in position detection experiments/demonstrations that are conducted using…

  16. Position display device

    International Nuclear Information System (INIS)

    Nishizawa, Yukio.

    1974-01-01

    Object: To provide a device capable of easily and quickly reading mutual mounting relations of control bodies such as control rods mounted on a nuclear reactor and positions to which the control bodies are driven. Structure: A scanning circuit is provided to scan positions of controllably mounted control bodies such as control rods. Values detected by scanning the positions are converted into character signals according to the values and converted into preranked color signals. The character signals and color signals are stored in a memory circuit by synchronous signals in synchronism with the scanning in the scanning circuit. Outputs of the memory circuit are displayed by a display unit such as a color Braun tube in accordance with the synchronous signals to provide color representations according to positions to which control bodies are driven in the same positional relation as the mounting of the control bodies. (Kamimura, M.)

  17. Precise Point Positioning

    DEFF Research Database (Denmark)

    Zhang, Xiaohong

    performance of point positioning for kinematic applications, the precise point positioning attracted a lot of attention and opened a new alternative door to kinematic positioning. In this report different tests have been done to evaluate the ability and accuracy of the software TriP in the kinematic...... and static case by using internal consistency (residuals, RMS, repeatability etc.), known coordinates, ground truth and double-differenced solutions. The kinematic GPS positioning accuracy using four different software systems has been investigated and tested by comparing the degree of agreement between...... the airborne lidar system misalignment angle by automating the matching of lidar data with ground truth. Kinematic GPS positioning has been widely used, but the available commercial software systems are normally only suitable for the short or medium range kinematic baseline. However, in polar areas, airborne...

  18. POSITIONING STRATEGIES DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Shakhshir Ghassan

    2014-07-01

    Full Text Available The positioning strategy has suffered serious changes in the last few decades, being influenced by the rapid development of competition and the growing focus on specific traits belonging to the market, to the consumer or to the product. The purpose of this paper is to present the developments of theoretical positioning strategies and the orientation from more simple, product oriented strategies, to ones more oriented towards the client and with a briefer period of time. The world is moving in a much faster pace than in the past, thanks to communication development so companies are obliged to adopt more specific strategies in order for them to be effective. This essay represents a literary review presenting a documentary research within the scientific articles and strategy and positioning books. The paper begins with the analysis of company strategies and the marketing strategies in general. The first author to group the product positioning strategies is Porter with his three generic strategies. Following the development of brands and because of the lack of competitiveness in the simple generic positioning strategies, this paper has also presented the newer positioning strategies proposed by Kotler, Treacy & Wiersema, and also more complex ones such as Bowman's Strategy Clock and Blankson and Kalafatis positioning strategy based on the type of the consumer. The fast expansion of local brands in all categories has led to mistakes in positioning strategies, categories also presented in the current essay. The results of this study show that new positioning strategies are more and more based on the consumer and market segments and on the product specification - which have also evolved in the last decades. Adaptability to fast changes in the competitive market will represent the future positioning strategies.

  19. 75 FR 67258 - Position Reports for Physical Commodity Swaps

    Science.gov (United States)

    2010-11-02

    ... recently were largely unregulated financial contracts. The Commission's proposal would require position... COMMODITY FUTURES TRADING COMMISSION 17 CFR Parts 15 and 20 RIN 3038-AD17 Position Reports for... reporting regulations that are reasonably necessary for implementing and enforcing aggregate position limits...

  20. CRANE POSITIONING APPARATUS

    Science.gov (United States)

    Landsiedel, F.W.; Wolff, H.

    1960-06-28

    An apparatus is described for automatically accomplishing the final accurate horizontal positioning of a crane after the latter has been placed to within 1/8 in. of its selected position. For this purpose there is provided a tiltable member on the crane mast for lowering into contact with a stationary probe. Misalignment of the tiltable member, with respect to the probe as the member is lowered, causes tilting of the latter to actuate appropriate switches that energize motors for bringing the mast into proper position. When properly aligned the member is not tilted and a central switch is actuated to indicate the final alignment of the crane.

  1. Mobile ultrasonic transducer positioning

    Directory of Open Access Journals (Sweden)

    Mohammad Omar Khyam

    2017-03-01

    Full Text Available For positioning a moving ultrasonic transmitter, most of the existing ultrasonic positioning systems require the use of a bank of correlators to estimate the Doppler shift associated with its movement which require high computational complexity. In this paper, for positioning a moving transmitter, a computationally efficient a Doppler shift estimation and compensation technique is proposed. As the proposed approach has the ability to measure the Doppler shift directly from the received signal, it does not require to use a bank of correlators to estimate the Doppler shift associated with its movement of the transmitter.

  2. REGULATION OF NATIONAL QUALIFICATIONS SYSTEMS

    Directory of Open Access Journals (Sweden)

    Anna A. Muravyeva

    2014-01-01

    Full Text Available The paper looks into the diverse aspects of qualifications system regulation, designed for balancing the supply and demand in the labor and educational service markets. Both the objects and mechanisms of such regulation are described. Special attention is given to institutions, involved in regulation of qualifications, and their jurisdiction. Another emphasis is on the industry-related regulation of qualifications which proved to be effective both on the national and European level. Such structures were first established on the national levels to regulate the qualifications and ensure their comparability and compatibility, given the economic globalization and growing labor and academic mobility. The author points out the role of the ministries of education and labor in maintaining a steady qualifications system, and outlines the positive experience of Great Britain using the industry councils for continuing development of qualifications system.

  3. Nonlinear dynamic positioning of ships with gain-scheduled wave filtering

    DEFF Research Database (Denmark)

    Torsetnes, Guttorm; Jouffroy, Jerome; Fossen, Thor I.

    This paper presents a globally contracting controller for regulation and dynamic positioning of ships, using only position measurements. For this purpose a globally contracting observer which reconstructs the unmeasured states is constructed. The observer produces accurate estimates of position...

  4. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala...... and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive...... pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor...

  5. Reflection Positivity for Parafermions

    OpenAIRE

    Jaffe, Arthur; Pedrocchi, Fabio L.

    2014-01-01

    We establish reflection positivity for Gibbs trace states for a class of gauge-invariant, reflection-invariant Hamiltonians describing parafermion interactions on a lattice. We relate these results to recent work in the condensed-matter physics literature.

  6. Abnormal Head Position

    Science.gov (United States)

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Abnormal Head Position En Español Read in Chinese What is an abnormal head posture? An abnormal or compensatory head posture occurs ...

  7. Fluorescent optical position sensor

    Science.gov (United States)

    Weiss, Jonathan D.

    2005-11-15

    A fluorescent optical position sensor and method of operation. A small excitation source side-pumps a localized region of fluorescence at an unknown position along a fluorescent waveguide. As the fluorescent light travels down the waveguide, the intensity of fluorescent light decreases due to absorption. By measuring with one (or two) photodetectors the attenuated intensity of fluorescent light emitted from one (or both) ends of the waveguide, the position of the excitation source relative to the waveguide can be determined by comparing the measured light intensity to a calibrated response curve or mathematical model. Alternatively, excitation light can be pumped into an end of the waveguide, which generates an exponentially-decaying continuous source of fluorescent light along the length of the waveguide. The position of a photodetector oriented to view the side of the waveguide can be uniquely determined by measuring the intensity of the fluorescent light emitted radially at that location.

  8. Stress Management: Positive Thinking

    Science.gov (United States)

    Healthy Lifestyle Stress management Positive thinking helps with stress management and can even improve your health. Practice overcoming negative self-talk ... with optimism is a key part of effective stress management. And effective stress management is associated with ...

  9. Detecting position using ARKit

    Science.gov (United States)

    Dilek, Ufuk; Erol, Mustafa

    2018-03-01

    Developed by using ARKit, a novel app which can be used to detect position in physics experiments was introduced. The ARKit relies on a new technique. The result of the experiment presented in this study was satisfactory, suggesting that the new technique can be employed in position detection experiments/demonstrations that are conducted using mobile technology. This technique has several promising advantages over video analysis.

  10. Plasma position control device

    International Nuclear Information System (INIS)

    Takase, Haruhiko.

    1987-01-01

    Purpose: To conduct position control stably to various plasmas and reduce the burden on the control coil power source. Constitution: Among the proportional, integration and differentiation controls, a proportional-differentiation control section and an integration control section are connected in parallel. Then, a signal switching circuit is disposed to the control signal input section for the proportional-differentiation control section such that either a present position of plasmas or deviation between the present plasma position and an aimed value can be selected as a control signal depending on the control procedures or the state of the plasmas. For instance, if a rapid response is required for the control, the deviation between the present plasma position and the aimed value is selected as the input signal to conduct proportional, integration and differentiation controls. While on the other hand, if it is intended to reduce the burden on the control coil power source, it is adapted such that the control signal inputted to the proportional-differentiation control section itself can select the present plasma position. (Yoshihara, H.)

  11. Beyond Positive Psychology?

    Science.gov (United States)

    McNulty, James K.; Fincham, Frank D.

    2014-01-01

    The field of positive psychology rests on the assumption that certain psychological traits and processes are inherently beneficial for well-being. We review evidence that challenges this assumption. First, we review data from 4 independent longitudinal studies of marriage revealing that 4 ostensibly positive processes—forgiveness, optimistic expectations, positive thoughts, and kindness—can either benefit or harm well-being depending on the context in which they operate. Although all 4 processes predicted better relationship well-being among spouses in healthy marriages, they predicted worse relationship well-being in more troubled marriages. Then, we review evidence from other research that reveals that whether ostensibly positive psychological traits and processes benefit or harm well-being depends on the context of various noninterpersonal domains as well. Finally, we conclude by arguing that any movement to promote well-being may be most successful to the extent that it (a) examines the conditions under which the same traits and processes may promote versus threaten well-being, (b) examines both healthy and unhealthy people, (c) examines well-being over substantial periods of time, and (d) avoids labeling psychological traits and processes as positive or negative. PMID:21787036

  12. Massive Galileon positivity bounds

    Science.gov (United States)

    de Rham, Claudia; Melville, Scott; Tolley, Andrew J.; Zhou, Shuang-Yong

    2017-09-01

    The EFT coefficients in any gapped, scalar, Lorentz invariant field theory must satisfy positivity requirements if there is to exist a local, analytic Wilsonian UV completion. We apply these bounds to the tree level scattering amplitudes for a massive Galileon. The addition of a mass term, which does not spoil the non-renormalization theorem of the Galileon and preserves the Galileon symmetry at loop level, is necessary to satisfy the lowest order positivity bound. We further show that a careful choice of successively higher derivative corrections are necessary to satisfy the higher order positivity bounds. There is then no obstruction to a local UV completion from considerations of tree level 2-to-2 scattering alone. To demonstrate this we give an explicit example of such a UV completion.

  13. Positioning devices for patients

    International Nuclear Information System (INIS)

    Heavens, M.

    1981-01-01

    It has been suggested that it is very important to position patients reproducibly at different stages of radiotherapy treatment planning and treatment, or similar procedures. Devices have been described for positioning a patient's upper and lower thorax. This invention provides reproducible positioning for a female patient's breasts, for example in planning treatment of and treating breast tumours. The patient is placed prone, using for example an upper thorax device. A support device is placed central to and beneath her breasts to partially displace them outwards. The device may be triangular in section with one apex contacting the chest wall at the sternum. Restraining straps may be provided to hold the breasts against the support device. Means may be provided to take a healthy breast from the path of radiation through the tumour. (author)

  14. Reflection Positivity and Monotonicity

    OpenAIRE

    Ritter, Gordon; Jaffe, Arthur Michael

    2008-01-01

    We prove general reflection positivity results for both scalar fields and Dirac fields on a Riemannian manifold, and comment on applications to quantum field theory. As another application, we prove the inequality \\(C_D \\leq C_N\\) between Dirichlet and Neumann covariance operators on a manifold with a reflection.

  15. Positionality at the Center

    Directory of Open Access Journals (Sweden)

    Catherine Vanner

    2015-11-01

    Full Text Available As a Western feminist supporting and researching gender equality in education in postcolonial contexts, I often wonder: Am I doing more harm than good? The privilege of my social location means that my efforts to support education in postcolonial contexts risk being patronizing, insulting, threatening, imperialist, and recolonizing. Yet neglecting and ignoring postcolonial contexts similarly reflects and reproduces a privileged position. I provide a tentative framework designed to address positionality, power, and privilege while creating an ethical research process for working in a postcolonial context. Beginning with an identification of positionality, the objectives of research, and guiding theoretical frameworks to situate the research in relation to the participants and context, I proceed to establish a methodology designed to minimize the negative effects of power and maximize participants’ empowerment. I position myself as a bricoleur, layering feminist standpoint theory and postcolonial theory, and propose the collaborative data collection and analysis techniques, with particular attention to ethical and cultural sensitivity, using a social constructivist approach to grounded theory. This article highlights the need for Western researchers to reflect upon the power dynamics of their research in postcolonial contexts and develop a strategy for conducting empowering research that prevents the misrepresentation and exploitation of participants. Observations from my doctoral thesis data collection provide examples of how these concepts were operationalized in practice as well as reflections on the disconnect between theorizing and conducting ethical research in postcolonial contexts.

  16. Attitude and position tracking

    CSIR Research Space (South Africa)

    Candy, LP

    2011-01-01

    Full Text Available Several applications require the tracking of attitude and position of a body based on velocity data. It is tempting to use direction cosine matrices (DCM), for example, to track attitude based on angular velocity data, and to integrate the linear...

  17. Clinical Positioning Space

    DEFF Research Database (Denmark)

    Williams, Lars Peter Hedegaard; Christensen, Mette Krogh; Rytter, Carsten

    2014-01-01

    In this article, we present a case study of residents’ clinical experiences and communication in outpatient oncology consultations. We apply positioning theory, a dynamic alternative to role theory, to investigate how oncology residents and patients situate themselves as persons with rights and d...

  18. Accommodation facilities positioning

    Directory of Open Access Journals (Sweden)

    Dan Pauna

    2014-11-01

    Full Text Available This paper is based on the positioning concept as it was established in 1972 by Al Ries and Jack Trout as being “a tangible good, a service, a company, an organism or even a person. Positioning does not mean what one does with the product but especially what the product represents according to the conception of the one prospecting the market“ ( Ries and Trout 1982. In this case the product accommodation, which is in fact a sum of complex services at the customers’ disposal, makes it impossible to compare on a certain market since the hotels, ˶or commercial accommodation forms˝(Lupu 2010, are classified according to a series of criteria among which the most important being the services offered and the way they are offered, the comfort level or the location in the territory. The aim of this paper is the positioning on a certain market of some accommodation facilities with an agreement on the choice, use and interpretation of common attributes such as: comfort, fares, notoriety, positioning, the complexity of services offered. This undertaking uses the Fishbein-Rosenberg model, as well as the graphic interpretation of the study1 .

  19. Logotherapy and positive psychology

    Directory of Open Access Journals (Sweden)

    Oscar R. Oro

    2015-09-01

    Full Text Available Psychology omitted to approach, during almost a century, the positive aspects from persons, like creativity, humor, optimism, hope, forgiveness, life meaning, and happiness. These themes are approached by Positive Psychology, with Seligman like the principal exponent. Psychology was dedicated to explore the negative aspects from human beings improving human health. Nevertheless, this pathogenic model could not prevent mental disease. Concepts of Positive Psychology have a solid antecedent in Víktor Frankl ́s studies, which is the Logotherapy founder. This allows incorporating another perspective to approach positive aspects, from a philosophical and anthropological focus. Although the ways adopted by Frank and Seligman are different, both considered main aspects of human existence. Nevertheless, they investigated in different countries (from Europe and EE.UU.; in different circumstances (concentration camps, deaths, tortures; vs. academic context; in different historical periods and different social contexts (a country that lost the war and other that gave freedom to Europeans. In this work is used the concept life sense as the focus in professional formation and psychotherapy approach. 

  20. Positive airway pressure treatment

    Science.gov (United States)

    ... and depression and a better mood Normal sleep patterns Lower blood pressure (in people with high blood pressure) Your health care provider will prescribe the type of PAP machine that ... patterns. Bilevel positive airway pressure (BiPAP or BIPAP) has ...

  1. Co-operative approaches to regulation

    National Research Council Canada - National Science Library

    Huigen, Hans; Organisation for Economic Co-operation and Development

    1997-01-01

    ... from traditional command-and-control regulation. The case studies are organized according to a common framework designed to give information about the specific design and use of the alternative, positive and negative results, and more generally...

  2. Benign paroxysmal positional vertigo

    Directory of Open Access Journals (Sweden)

    Guo Xiang-Dong

    2011-01-01

    Full Text Available Benign paroxysmal positional vertigo (BPPV is a common clinical disorder characterized by brief recurrent spells of vertigo often brought about by certain head position changes as may occur with looking up, turning over in bed, or straightening up after bending over. It is important to understand BPPV not only because it may avert expensive and often unnecessary testing, but also because treatment is rapid, easy, and effective in >90% of cases. The diagnosis of BPPV can be made based on the history and examination. Patients usually report episodes of spinning evoked by certain movements, such as lying back or getting out of bed, turning in bed, looking up, or straightening after bending over. At present, the generally accepted recurrence rate of BPPV after successful treatment is 40%-50% at 5 years of average follow-up. There does appear to be a subset of individuals prone to multiple recurrences.

  3. Net positive energy buildings

    International Nuclear Information System (INIS)

    Romero, A.; Barreiro, E.; Sanchez Zabala, V.

    2010-01-01

    Buildings are great consumers of energy, being responsible for almost 36% of CO2 emissions in Europe. Though there are many initiatives towards the reduction of energy consumption and CO2 emissions in buildings, many of the alternatives are diminished due to a lack of a unique and holistic approach to the problem. This paper reports a new innovative concept of Positive Energy Buildings (EB+), as well as an integral methodology that covers the overall design process for achieving them. The methodology evaluates energy efficiency solutions at different scales, from building site to generation systems. An educational building design in Navarra serves as a case study to check the feasibility of the proposed methodology. The study concludes that the key to achieve a Positive Energy Building is a minimized energy demand, complemented by efficient facilities and enhanced by distributed power generation from renewable sources. (Author).

  4. Review of HRP Positions

    Energy Technology Data Exchange (ETDEWEB)

    Center for Reliability Studies

    2007-01-01

    The Department of Energy (DOE) Human Reliability Program (HRP), published as 10 CFR Part 712, is currently being reviewed and revised to address concerns identified during its implementation. Although these ''page changes'' primarily incorporate clarification of terms and language, the following discussion relates to broadening the definition of positions that require HRP certification that is found in {section}712.10.

  5. Are Parton Distributions Positive?

    CERN Document Server

    Forte, Stefano; Ridolfi, Giovanni; Altarelli, Guido; Forte, Stefano; Ridolfi, Giovanni

    1999-01-01

    We show that the naive positivity conditions on polarized parton distributions which follow from their probabilistic interpretation in the naive parton model are reproduced in perturbative QCD at the leading log level if the quark and gluon distribution are defined in terms of physical processes. We show how these conditions are modified at the next-to-leading level, and discuss their phenomenological implications, in particular in view of the determination of the polarized gluon distribution

  6. Are parton distributions positive?

    International Nuclear Information System (INIS)

    Forte, Stefano; Altarelli, Guido; Ridolfi, Giovanni

    1999-01-01

    We show that the naive positivity conditions on polarized parton distributions which follow from their probabilistic interpretation in the naive parton model are reproduced in perturbative QCD at the leading log level if the quark and gluon distribution are defined in terms of physical processes. We show how these conditions are modified at the next-to-leading level, and discuss their phenomenological implications, in particular in view of the determination of the polarized gluon distribution

  7. Global Positioning System Bibliography

    Science.gov (United States)

    1992-03-01

    316. Buisson, J. A., 0. J. Oaks, and H. Warren (1985). "Absolute calibration and precise positioning between major European time observatories and...Fla, 29 November-2 December, pp. 39-46. Krakiwsky, E. J., B. Wanless, B. Buffett , K. P. Schwarz, and M. Nakiboglu (1985). "GPS orbit improvement and...K. P. Schwarz, E. J. Krakiwsky, B. Buffett , and B. Wanless (1984). "A multi-pass, multi-station approach to GPS orbital improvement and precise

  8. Position reconstruction in LUX

    Science.gov (United States)

    Akerib, D. S.; Alsum, S.; Araújo, H. M.; Bai, X.; Bailey, A. J.; Balajthy, J.; Beltrame, P.; Bernard, E. P.; Bernstein, A.; Biesiadzinski, T. P.; Boulton, E. M.; Brás, P.; Byram, D.; Cahn, S. B.; Carmona-Benitez, M. C.; Chan, C.; Currie, A.; Cutter, J. E.; Davison, T. J. R.; Dobi, A.; Druszkiewicz, E.; Edwards, B. N.; Fallon, S. R.; Fan, A.; Fiorucci, S.; Gaitskell, R. J.; Genovesi, J.; Ghag, C.; Gilchriese, M. G. D.; Hall, C. R.; Hanhardt, M.; Haselschwardt, S. J.; Hertel, S. A.; Hogan, D. P.; Horn, M.; Huang, D. Q.; Ignarra, C. M.; Jacobsen, R. G.; Ji, W.; Kamdin, K.; Kazkaz, K.; Khaitan, D.; Knoche, R.; Larsen, N. A.; Lenardo, B. G.; Lesko, K. T.; Lindote, A.; Lopes, M. I.; Manalaysay, A.; Mannino, R. L.; Marzioni, M. F.; McKinsey, D. N.; Mei, D.-M.; Mock, J.; Moongweluwan, M.; Morad, J. A.; Murphy, A. St. J.; Nehrkorn, C.; Nelson, H. N.; Neves, F.; O'Sullivan, K.; Oliver-Mallory, K. C.; Palladino, K. J.; Pease, E. K.; Rhyne, C.; Shaw, S.; Shutt, T. A.; Silva, C.; Solmaz, M.; Solovov, V. N.; Sorensen, P.; Sumner, T. J.; Szydagis, M.; Taylor, D. J.; Taylor, W. C.; Tennyson, B. P.; Terman, P. A.; Tiedt, D. R.; To, W. H.; Tripathi, M.; Tvrznikova, L.; Uvarov, S.; Velan, V.; Verbus, J. R.; Webb, R. C.; White, J. T.; Whitis, T. J.; Witherell, M. S.; Wolfs, F. L. H.; Xu, J.; Yazdani, K.; Young, S. K.; Zhang, C.

    2018-02-01

    The (x, y) position reconstruction method used in the analysis of the complete exposure of the Large Underground Xenon (LUX) experiment is presented. The algorithm is based on a statistical test that makes use of an iterative method to recover the photomultiplier tube (PMT) light response directly from the calibration data. The light response functions make use of a two dimensional functional form to account for the photons reflected on the inner walls of the detector. To increase the resolution for small pulses, a photon counting technique was employed to describe the response of the PMTs. The reconstruction was assessed with calibration data including 83mKr (releasing a total energy of 41.5 keV) and 3H (β- with Q = 18.6 keV) decays, and a deuterium-deuterium (D-D) neutron beam (2.45 MeV) . Within the detector's fiducial volume, the reconstruction has achieved an (x, y) position uncertainty of σ = 0.82 cm and σ = 0.17 cm for events of only 200 and 4,000 detected electroluminescence photons respectively. Such signals are associated with electron recoils of energies ~0.25 keV and ~10 keV, respectively. The reconstructed position of the smallest events with a single electron emitted from the liquid surface (22 detected photons) has a horizontal (x, y) uncertainty of 2.13 cm.

  9. Photon beam position monitor

    Science.gov (United States)

    Kuzay, Tuncer M.; Shu, Deming

    1995-01-01

    A photon beam position monitor for use in the front end of a beamline of a high heat flux and high energy photon source such as a synchrotron radiation storage ring detects and measures the position and, when a pair of such monitors are used in tandem, the slope of a photon beam emanating from an insertion device such as a wiggler or an undulator inserted in the straight sections of the ring. The photon beam position monitor includes a plurality of spaced blades for precisely locating the photon beam, with each blade comprised of chemical vapor deposition (CVD) diamond with an outer metal coating of a photon sensitive metal such as tungsten, molybdenum, etc., which combination emits electrons when a high energy photon beam is incident upon the blade. Two such monitors are contemplated for use in the front end of the beamline, with the two monitors having vertically and horizontally offset detector blades to avoid blade "shadowing". Provision is made for aligning the detector blades with the photon beam and limiting detector blade temperature during operation.

  10. Beam Position Monitor Engineering

    International Nuclear Information System (INIS)

    Smith, Stephen R.

    1996-07-01

    The design of beam position monitors often involves challenging system design choices. Position transducers must be robust, accurate, and generate adequate position signal without unduly disturbing the beam. Electronics must be reliable and affordable, usually while meeting tough requirements on precision. accuracy, and dynamic range. These requirements may be difficult to achieve simultaneously, leading the designer into interesting opportunities for optimization or compromise. Some useful techniques and tools are shown. Both finite element analysis and analytic techniques will be used to investigate quasi-static aspects of electromagnetic fields such as the impedance of and the coupling of beam to striplines or buttons. Finite-element tools will be used to understand dynamic aspects of the electromagnetic fields of beams, such as wake-fields and transmission-line and cavity effects in vacuum-to-air feed through. Mathematical modeling of electrical signals through a processing chain will be demonstrated, in particular to illuminate areas where neither a pure time-domain nor a pure frequency-domain analysis is obviously advantageous. Emphasis will be on calculational techniques, in particular on using both time-domain and frequency domain approaches to the applicable parts of interesting problems

  11. Deep Space Positioning System

    Science.gov (United States)

    Vaughan, Andrew T. (Inventor); Riedel, Joseph E. (Inventor)

    2016-01-01

    A single, compact, lower power deep space positioning system (DPS) configured to determine a location of a spacecraft anywhere in the solar system, and provide state information relative to Earth, Sun, or any remote object. For example, the DPS includes a first camera and, possibly, a second camera configured to capture a plurality of navigation images to determine a state of a spacecraft in a solar system. The second camera is located behind, or adjacent to, a secondary reflector of a first camera in a body of a telescope.

  12. Positive lubrication system

    Science.gov (United States)

    Smith, Dennis W.; Hooper, Fred L.

    1990-01-01

    As part of the development of an autonomous lubrication system for spin bearings, a system was developed to deliver oil to grease-lubricated bearings upon demand. This positive oil delivery system (PLUS) consists of a pressurized reservoir with a built-in solenoid valve that delivers a predictable quantity of oil to the spin bearing through a system of stainless steel tubes. Considerable testing was performed on the PLUS to characterize its performance and verify its effectiveness, along with qualifying it for flight. Additional development is underway that will lead to the fully autonomous active lubrication system.

  13. Dimensions of affect modulated by perceived mood regulation ability.

    Science.gov (United States)

    Hovanitz, Christine A; Hursh, Adrienne N; Hudepohl, Adam D

    2011-06-01

    The ability to regulate mood is a facet of emotional intelligence that may contribute to an individual's physical and mental health. Precisely what is regulated when mood regulation occurs is dependent on what "makes up" mood. The purpose of this study was to evaluate whether perceived mood regulation ability can predict regulation of affect during task engagement and whether affect regulation is specific to valence or arousal. Measures of positive affect, negative affect, and frontal area sEMG (as a measure of arousal) were obtained from a sample of one hundred twenty-four participants categorized by their self report as possessing low or high mood regulation ability. Modulation of positive affect, but not negative affect, was predicted by perceived mood regulation ability. The results of sEMG were mixed. These data provide some support for the hypothesis that mood regulation ability can predict future efforts to regulate affect, at least in the context of task engagement.

  14. Global Positioning System Standard Positioning Service Performance Standard

    Science.gov (United States)

    2008-09-01

    The U.S. Global Positioning System (GPS) Standard Positioning Service (SPS) consists of space-based positioning, navigation, and timing (PNT) signals delivered free of direct user fees for peaceful civil, commercial, and scientific uses worldwide. Th...

  15. Future trends in regulation

    International Nuclear Information System (INIS)

    Remick, F.J.

    1993-01-01

    This report presents a discussion on the future of nuclear regulations and what regulators should strive for. The following 6 trends are described: the regulatory presence around the world will grow; there is a trend towards giving the regulator greater independence; there is a trend toward greater self-regulation by the industry; less prescriptive regulation; regulators may be converging no a quantitative risk goal; increasing recognition of the importance of stability in the regulator

  16. Triangulation positioning system network

    Directory of Open Access Journals (Sweden)

    Sfendourakis Marios

    2017-01-01

    Full Text Available This paper presents ongoing work on localization and positioning through triangulation procedure for a Fixed Sensors Network - FSN.The FSN has to work as a system.As the triangulation problem becomes high complicated in a case with large numbers of sensors and transmitters, an adequate grid topology is needed in order to tackle the detection complexity.For that reason a Network grid topology is presented and areas that are problematic and need further analysis are analyzed.The Network System in order to deal with problems of saturation and False Triangulations - FTRNs will have to find adequate methods in every sub-area of the Area Of Interest - AOI.Also, concepts like Sensor blindness and overall Network blindness, are presented. All these concepts affect the Network detection rate and its performance and ought to be considered in a way that the network overall performance won’t be degraded.Network performance should be monitored contentiously, with right algorithms and methods.It is also shown that as the number of TRNs and FTRNs is increased Detection Complexity - DC is increased.It is hoped that with further research all the characteristics of a triangulation system network for positioning will be gained and the system will be able to perform autonomously with a high detection rate.

  17. What coy smiles say about positive shyness in early infancy

    NARCIS (Netherlands)

    Colonnesi, C.; Bögels, S.M.; de Vente, W.; Majdandžić, M.

    2013-01-01

    Positive shyness is a universal emotion with the specific social function of regulating our interactions by improving trust and liking, and showing politeness. The present study examined early infant production of coy smiles during social interactions as a measure of positive shy behavior. Eighty

  18. Regulation of Meiotic Recombination

    Energy Technology Data Exchange (ETDEWEB)

    Gregory p. Copenhaver

    2011-11-09

    for assaying recombination using tetrad analysis in a higher eukaryotic system (6). This system enabled the measurement of the frequency and distribution of recombination events at a genome wide level in wild type Arabidopsis (7), construction of genetic linkage maps which include positions for each centromere (8), and modeling of the strength and pattern of interference (9). This proposal extends the use of tetrad analysis in Arabidopsis by using it as the basis for assessing the phenotypes of mutants in genes important for recombination and the regulation of crossover interference and performing a novel genetic screen. In addition to broadening our knowledge of a classic genetic problem - the regulation of recombination by crossover interference - this proposal also provides broader impact by: generating pedagogical tools for use in hands-on classroom experience with genetics, building interdisciplinary collegial partnerships, and creating a platform for participation by junior scientists from underrepresented groups. There are three specific aims: (1) Isolate mutants in Arabidopsis MUS81 homologs using T-DNA and TILLING (2) Characterize recombination levels and interference in mus81 mutants (3) Execute a novel genetic screen, based on tetrad analysis, for genes that regulate meiotic recombination

  19. The Animal Welfare Act and the zoo: A positive approach

    Science.gov (United States)

    Olsen, Glenn H.

    1989-01-01

    Interpretations of the Animal Welfare Act and other regulations governing use of research animals in the United States are changing. Recent amendments to the Act have resulted in the inclusion of more species under the umbrella of regulation. The role of the zoo and wildlife veterinarian should be that of leading his or her institution into a positive endorsement of these regulations and their application. Recent additions to the Code of Federal Regulations spell out the roles of the veterinarian and the Animal Care and Use Committee at an institution.

  20. Galileo positioning technology

    CERN Document Server

    Lohan, Elena; Sand, Stephan; Hurskainen, Heikki

    2015-01-01

    This book covers multi-band Galileo receivers (especially E1-E5 bands of Galileo) and addresses all receiver building blocks, from the antenna and front end, through details of the baseband receiver processing blocks, up to the navigation processing, including the Galileo message structure and Position, Velocity, Time (PVT) computation. Moreover, hybridization solutions with communications systems for improved localization are discussed and an open-source GNSS receiver platform (available for download) developed at Tampere University of Technology (TUT) is addressed in detail. • Takes a holistic approach to GALILEO and related systems, such as EGNOS and hybrid solutions on mobile phones; • Provides an invaluable reference to Binary Offset Carrier modulations and related families, which are some of the trademarks of GALILEO; • Includes a detailed survey of GALILEO receiver research in Europe and existing software-defined radio (SDR) GALILEO receiver implementations; • Addresses the multiple challen...

  1. DELTA beam position monitor

    International Nuclear Information System (INIS)

    Brinker, S.; Heisterhagen, R.; Wille, K.

    1991-01-01

    For the electron storage ring DELTA (Dortmund ELectron Test Accelerator) a beam-position-monitor system based on button pickups has been designed. Two different concepts for the monitor electronics have been developed obtaining a long-term stability better than ± 150 μm and a short-term resolution below ± 10 μm. There are no hybrids integrated in the electronic circuits as all four button signals should be amplified and digitized to provide redundancy. First, a concept using four separated electronic branches, one for each button, was tested. Then a concept with a multiplexer in front followed by only one amplifier was designed. This concept, the electronic circuits and the measurements are presented

  2. Algorithms for Global Positioning

    DEFF Research Database (Denmark)

    Borre, Kai; Strang, Gilbert

    and replaces the authors' previous work, Linear Algebra, Geodesy, and GPS (1997). An initial discussion of the basic concepts, characteristics and technical aspects of different satellite systems is followed by the necessary mathematical content which is presented in a detailed and self-contained fashion......The emergence of satellite technology has changed the lives of millions of people. In particular, GPS has brought an unprecedented level of accuracy to the field of geodesy. This text is a guide to the algorithms and mathematical principles that account for the success of GPS technology....... At the heart of the matter are the positioning algorithms on which GPS technology relies, the discussion of which will affirm the mathematical contents of the previous chapters. Numerous ready-to-use MATLAB codes are included for the reader. This comprehensive guide will be invaluable for engineers...

  3. The Global Positioning System

    Science.gov (United States)

    ,

    1999-01-01

    The Global Positioning System (GPS) is a constellation of navigation satellites called Navigation Satellite Timing And Ranging (NAVSTAR), maintained by the U.S. Department of Defense. Many outdoor enthusiasts recognize that a handheld GPS receiver can be an accurate tool for determining their location on the terrain. The GPS receiver helps determine locations on the Earth's surface by collecting signals from three or more satellites through a process called triangulation. Identifying a location on the Earth is more useful if you also know about the surrounding topographic conditions. Using a topographic map with the GPS receiver provides important information about features of the surrounding terrain and can help you plot an effective route from one location to another.

  4. Positive void reactivity

    International Nuclear Information System (INIS)

    Diamond, D.J.

    1992-09-01

    This report is a review of some of the important aspects of the analysis of large loss-of-coolant accidents (LOCAs). One important aspect is the calculation of positive void reactivity. To study this subject the lattice physics codes used for void worth calculations and the coupled neutronic and thermal-hydraulic codes used for the transient analysis are reviewed. Also reviewed are the measurements used to help validate the codes. The application of these codes to large LOCAs is studied with attention focused on the uncertainty factor for the void worth used to bias the results. Another aspect of the subject dealt with in the report is the acceptance criteria that are applied. This includes the criterion for peak fuel enthalpy and the question of whether prompt criticality should also be a criterion. To study the former, fuel behavior measurements and calculations are reviewed. (Author) (49 refs., 2 figs., tab.)

  5. Conference - La discipline positive

    CERN Multimedia

    Staff Association

    2018-01-01

    Eduquer avec fermeté et bienveillance Véronique Genevay Jeudi 31 mai à 19h00 CERN Meyrin, Salle du Conseil 503-1-001 Venez vous familiariser avec la pensée et le positionnement développé dans la discipline positive. Une approche ni permissive, ni punitive, qui vise à enseigner aux enfants des compétences comme la confiance en soi, l’autonomie, le respect de soi-même et le respect mutuel, la responsabilité, la coopération… Inscrivez-vous : https://indico.cern.ch/e/disciplinepositive   Pour plus d’informations : staff.association@cern.ch ou (+41) 022 766 37 38

  6. Position Sensitive Gaseous Photomultipliers

    CERN Document Server

    Martinengo, P; Peskov, V

    2010-01-01

    Advances in the technologies associated with position sensitive gaseous detectors especially featuring CsI as reflective photoconverters will be reviewed. These photodetectors represent the most effective solution for what concerns cost and performance in the case of large area Cherenkov imaging applications in relatively low rate (or low occupancy) high energy physics and astrophysics experiments. Moreover, they are the only choice when the Cherenkov detector is embedded in a magnetic field. Recently proposed single photon MPGDs (Micropattern Gaseous Detectors) will be also discussed in view of the successful efforts so far made to extend their sensitivity to visible light. With some modifications, photosensitive gaseous detectors can also be used in the imaging of X-rays and particles.

  7. The Power of Positive Emotions

    Science.gov (United States)

    ... it going. How Positive Emotions Help Us Positive emotions balance out negative ones, but they have other powerful benefits, too. Instead of narrowing our focus like negative emotions do, positive emotions affect our brains in ways ...

  8. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1991-01-01

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target regulatory'' enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C[sub 15]-C[sub 30]) produced by oil glands.

  9. Position paper on standardization

    International Nuclear Information System (INIS)

    1991-04-01

    The ''NPOC Strategic Plan for Building New Nuclear Plants'' creates a framework within which new standardized nuclear plants may be built. The Strategic Plan is an expression of the nuclear energy industry's serious intent to create the necessary conditions for new plant construction and operation. One of the key elements of the Strategic Plan is a comprehensive industry commitment to standardization: through design certification, combined license, first-of-a-kind engineering, construction, operation and maintenance of nuclear power plants. The NPOC plan proposes four stages of standardization in advanced light water reactors (ALWRs). The first stage is established by the ALWR Utility Requirements Document which specifies owner/operator requirements at a functional level covering all elements of plant design and construction, and many aspects of operations and maintenance. The second stage of standardization is that achieved in the NRC design certification. This certification level includes requirements, design criteria and bases, functional descriptions and performance requirements for systems to assure plant safety. The third stage of standardization, commercial standardization, carries the design to a level of completion beyond that required for design certification to enable the industry to achieve potential increases in efficiency and economy. The final stage of standardization is enhanced standardization beyond design. A standardized approach is being developed in construction practices, operating, maintenance training, and procurement practices. This comprehensive standardization program enables the NRC to proceed with design certification with the confidence that standardization beyond the regulations will be achieved. This confidence should answer the question of design detail required for design certification, and demonstrate that the NRC should require no further regulatory review beyond that required by 10 CFR Part 52

  10. Relationship of condylar position to disc position and morphology

    Energy Technology Data Exchange (ETDEWEB)

    Incesu, L.; Taskaya-Yilmaz, N. E-mail: nergizy@omu.edu.tr; Oeguetcen-Toller, M.; Uzun, E

    2004-09-01

    Introduction/objective: The purpose of this study was to assess whether condylar position, as depicted by magnetic resonance imaging, was an indicator of disc morphology and position. Methods and material: One hundred and twenty two TMJs of 61 patients with temporomandibular joint disorder were examined. Condylar position, disc deformity and degree of anterior disc displacement were evaluated by using magnetic resonance imaging. Results and discussion: Posterior condyle position was found to be the main feature of temporomandibular joints with slight and moderate anterior disc displacement. No statistical significance was found between the condylar position, and reducing and nonreducing disc positions. On the other hand, superior disc position was found to be statistically significant for centric condylar position. Conclusion: It was concluded that posterior condyle position could indicate anterior disc displacement whereas there was no relation between the position of condyle and the disc deformity.

  11. Conflict, Memory, and Positioning

    DEFF Research Database (Denmark)

    Brescó, Ignacio

    2016-01-01

    The aim of this paper was to bring the dialogical and multivoiced dimension of conflict to the fore in the study of how people remember a particular event in the past. Drawing from different case studies, it contains analyses of how subjects identifying with different political actors in the Basq...... with a discussion on the role of history teaching in promoting a more critical, reflexive, and pluralistic way of dealing with memory, and hence with conflict.......The aim of this paper was to bring the dialogical and multivoiced dimension of conflict to the fore in the study of how people remember a particular event in the past. Drawing from different case studies, it contains analyses of how subjects identifying with different political actors in the Basque...... conflict adopted their respective positions, and interpretation of the conflict, and how, in light of same, they reconstruct the failed peace process that took place in 2006 between the terrorist group ETA (Euzkadi ta Azcatasuna, or Basque Country and Freedom in English) and the Spanish government. Results...

  12. Gathering positive experience

    CERN Multimedia

    2009-01-01

    Last Monday, the new CERN Machine Advisory Committee (CMAC) met for the first time, and we had good news to tell its members. Over the weekend, injection tests for both LHC beams were successfully carried out. In other words, we’ve had beam in the LHC for the first time since September 2008. That’s a good feeling, but it’s no reason for complacency. There’s still a long way to go before first physics at the new energy frontier. As the Bulletin has reported over recent weeks, we’re gathering a lot of positive experience with the new quench detection and protection system (QPS), which is already allowing us to monitor the LHC far better than we were able to in the past. So far, the QPS for three of the LHC’s eight sectors has been put through its paces, and we’ve also power tested those sectors to 2000 amperes, the equivalent of around 1.2 TeV per beam. The next step is to slowly increase the current to 4000 amperes, and...

  13. Regulators of Tfh cell differentiation

    Directory of Open Access Journals (Sweden)

    Gajendra Motiram Jogdand

    2016-11-01

    Full Text Available The follicular helper T (Tfh cells help is critical for activation of B cells, antibody class switching and germinal center formation. The Tfh cells are characterized by the expression of CXCR5, ICOS, PD-1, Bcl-6, and IL-21. They are involved in clearing infections and are adversely linked with autoimmune diseases and also have a role in viral replication as well as clearance. Tfh cells are generated from naïve CD4 T cells with sequential steps involving cytokine signaling (IL-21, IL-6, IL-12, activin A, migration and positioning in the germinal center by CXCR5, surface receptors (ICOS/ICOSL, SAP/SLAM as well as transcription factor (Bcl-6, c-Maf, STAT3 signaling and repressor miR155. On the other hand Tfh generation is negatively regulated at specific steps of Tfh generation by specific cytokine (IL-2, IL-7, surface receptor (PD-1, CTLA-4, transcription factors Blimp-1, STAT5, T-bet, KLF-2 signaling and repressor miR 146a. Interestingly, miR 17-92 and FOXO1 acts as a positive as well as a negative regulator of Tfh differentiation depending on the time of expression and disease specificity. Tfh cells are also generated from the conversion of other effector T cells as exemplified by Th1 cells converting into Tfh during viral infection. The mechanistic details of effector T cells conversion into Tfh are yet to be clear. To manipulate Tfh cells for therapeutic implication and or for effective vaccination strategies, it is important to know positive and negative regulators of Tfh generation. Hence, in this review we have highlighted and interlinked molecular signaling from cytokines, surface receptors, transcription factors, ubiquitin Ligase and miRNA as positive and negative regulators for Tfh differentiation.

  14. Thruster allocation for dynamical positioning

    NARCIS (Netherlands)

    Poppe, K.; van den Berg, J.B.; Blank, E.; Archer, C.; Redeker, M.; Kutter, M.; Hemker, P.

    2010-01-01

    Positioning a vessel at a fixed position in deep water is of great importance when working offshore. In recent years a Dynamical Positioning (DP) system was developed at Marin [2]. After the measurement of the current position and external forces (like waves, wind etc.), each thruster of the vessel

  15. Climate change policy position

    International Nuclear Information System (INIS)

    2002-11-01

    The Canadian Association of Petroleum Producers (CAPP) is a firm believer in the need to take action to mitigate the risks associated with climate change, and that clear government policy is called for. The principles of sustainable development must guide this policy development effort. The initiatives required to address greenhouse gas emissions over both the short and long term must be carefully considered, and it is up to industries to ensure their production efficiency and emission intensity. Promoting improved performance of industries in Canada and developing technology that can be deployed internationally for larger global effects represents Canada's best contribution to progress on greenhouse gas emissions. The increase in energy demand along with increases in population and economic growth have contributed to an increase in greenhouse gas emissions despite improved energy efficiency in industry. Significant damage to the economy will result if Canada is to meet its commitment under the Kyoto Protocol, forcing the country to buy large quantities of foreign credits instead of using those funds for increased research and development. CAPP indicated that an effective plan must be: balanced, equitable, responsible, competitive, focused on technology and innovation, and based on agreements on sectoral plans. Each of these principles were discussed, followed by the fundamentals of approach for upstream oil and gas. The framework for climate change policy was described as well as the elements of a sector plan. CAPP wants to work with all levels of government on an appropriate plan for Canada, that considers our unique circumstances. Canada can play a significant role on the international stage by properly implementing the policy position proposed by the CAPP without unnecessary risks to the economy. refs

  16. Positive Technologies for Understanding and Promoting Positive Emotions.

    Science.gov (United States)

    Baños, Rosa María; Carrillo, Alba; Etchemendy, Ernestina; Botella, Cristina

    2017-10-26

    Information and Communication Technologies (ICTs) have become increasingly present in our lives, and their use has spread considerably. This paper presents a review of the way ICTs can help practitioners and researchers to study, promote, and train positive emotions. It is framed within the field of Positive Technologies: the applied scientific approach to the study of the use of technology to improve the quality of personal experience, with the goal of increasing wellbeing. First, the article presents an introduction to the topic of technologies and positive emotions. Then, it describes how ICTs can aid in monitoring, assessing, promoting, modifying, and training positive emotions. Finally, implications and future directions of the role of Positive Technologies in positive emotions are discussed. The authors conclude that, in the near future, Positive Technologies and the field of positive emotions will interact synergistically, producing an exponential growth in the understanding and promotion of positive emotions.

  17. Exposing Position Uncertainty in Middleware

    DEFF Research Database (Denmark)

    Langdal, Jakob; Kjærgaard, Mikkel Baun; Toftkjær, Thomas

    2010-01-01

    Traditionally, the goal for positioning middleware is to provide developers with seamless position transparency, i.e., providing a connection between the application domain and the positioning sensors while hiding the complexity of the positioning technologies in use. A key part of the hidden...... complexity is the uncertainty associated to positions caused by inherent limitations when using sensors to convert physical phenomena to digital representations. We propose to use the notion of seamful design for developers to design a positioning middleware that provides transparent positioning and still...... allows developers some control of the uncertainty aspects of the positioning process. The design presented in this paper shows how uncertainty of positioning can be conceptualized and internalized into a positioning middleware. Furthermore, we argue that a developer who is interacting with uncertainty...

  18. Guideline Implementation: Positioning the Patient.

    Science.gov (United States)

    Burlingame, Byron L

    2017-09-01

    Every surgical procedure requires positioning the patient; however, all surgical positions are associated with the potential for the patient to experience a positioning injury. The locations and types of potential injuries (eg, stretching, compression, pressure injury) depend on the position. Factors that may increase the patient's risk for an injury are the length of the procedure and risk factors inherent to the patient (eg, weight, age, frailty). AORN's updated "Guideline for positioning the patient" provides guidance on injury prevention practices for all surgical positions including supine, Trendelenburg, reverse Trendelenburg, lateral, lithotomy, prone, and sitting positions and modifications of these positions. This article focuses on the key points of the guideline covering the use of prophylactic dressings, neurophysiological monitoring, and safely positioning the patient in the supine and prone positions. Perioperative RNs should review the complete guideline for additional information and for guidance when writing and updating policies and procedures. Copyright © 2017 AORN, Inc. Published by Elsevier Inc. All rights reserved.

  19. Secure positioning in wireless networks

    DEFF Research Database (Denmark)

    Capkun, Srdjan; Hubaux, Jean-Pierre

    2006-01-01

    So far, the problem of positioning in wireless networks has been studied mainly in a non-adversarial settings. In this work, we analyze the resistance of positioning techniques to position and distance spoofing attacks. We propose a mechanism for secure positioning of wireless devices, that we call...... Verifiable Multilateration. We then show how this mechanism can be used to secure positioning in sensor networks. We analyze our system through simulations....

  20. Nucleosome Positioning and NDR Structure at RNA Polymerase III Promoters

    DEFF Research Database (Denmark)

    Helbo, Alexandra Søgaard; Lay, Fides D; Jones, Peter A

    2017-01-01

    Chromatin is structurally involved in the transcriptional regulation of all genes. While the nucleosome positioning at RNA polymerase II (pol II) promoters has been extensively studied, less is known about the chromatin structure at pol III promoters in human cells. We use a high-resolution analy......Chromatin is structurally involved in the transcriptional regulation of all genes. While the nucleosome positioning at RNA polymerase II (pol II) promoters has been extensively studied, less is known about the chromatin structure at pol III promoters in human cells. We use a high....... The +1 nucleosome is located further downstream than at pol II genes and furthermore displays weak positioning. The variable position of the +1 location is seen not only within individual cell populations and between cell types, but also between different pol III promoter subtypes, suggesting that the +1...... the first high-resolution map of nucleosome positioning and occupancy at human pol III promoters at specific loci and genome wide....

  1. Re-Framing Biotechnology Regulation.

    Science.gov (United States)

    Peck, Alison

    Biotechnology is about to spill the banks of federal regulation. New genetic engineering techniques like CRISPR-Cas9 promise revolutionary breakthroughs in medicine, agriculture, and public health—but those techniques would not be regulated under the terms of the Coordinated Framework for Regulation of Biotechnology. This revolutionary moment in biotechnology offers an opportunity to correct the flaws in the framework, which was hastily patched together at the advent of the technology. The framework has never captured all relevant technologies, has never satisfied the public that risk is being effectively managed, and has never been accessible to small companies and publicly-funded labs that increasingly are positioned to make radical, life-saving innovations. This Article offers a proposal for new legislation that would reshape biotechnology regulation to better meet these goals. Key reforms include tying regulation to risk rather than technology category; consolidating agency review; capturing distinct regulatory expertise through inter-agency consultations; creating a clearinghouse to help guide applicants and disseminate information; setting up more comprehensive monitoring of environmental effects; and providing federal leadership to fill key data gaps and address socio-economic impacts.

  2. False Position, Double False Position and Cramer's Rule

    Science.gov (United States)

    Boman, Eugene

    2009-01-01

    We state and prove the methods of False Position (Regula Falsa) and Double False Position (Regula Duorum Falsorum). The history of both is traced from ancient Egypt and China through the work of Fibonacci, ending with a connection between Double False Position and Cramer's Rule.

  3. Videofluoroscopic Investigation of Body Position on Articulatory Positioning

    Science.gov (United States)

    Bae, Youkyung; Perry, Jamie L.; Kuehn, David P.

    2014-01-01

    Purpose: To quantitatively examine the effects of body position on the positioning of the epiglottis, tongue, and velum at rest and during speech. Method: Videofluoroscopic data were obtained from 12 healthy adults in the supine and upright positions at rest and during speech while the participants produced 12 VCV sequences. The effects of body…

  4. Positive Psychology and Positive Education: Old Wine in New Bottles?

    Science.gov (United States)

    Kristjansson, Kristjan

    2012-01-01

    The recently fashionable theories of positive psychology have educational ramifications at virtually every level of engagement, culminating in the model of positive education. In this critical review, I scrutinize positive education as a potential theory in educational psychology. Special attention is given to conceptual controversies and…

  5. An Age-Related Mechanism of Emotion Regulation: Regulating Sadness Promotes Children's Learning by Broadening Information Processing

    Science.gov (United States)

    Davis, Elizabeth L.

    2016-01-01

    Emotion regulation predicts positive academic outcomes like learning, but little is known about "why". Effective emotion regulation likely promotes learning by broadening the scope of what may be attended to after an emotional event. One hundred twenty-six 6- to 13-year-olds' (54% boys) regulation of sadness was examined for changes in…

  6. Contextual positive psychology: Policy recommendations for implementing positive psychology into schools.

    Directory of Open Access Journals (Sweden)

    Joseph Ciarrochi

    2016-10-01

    Full Text Available There has been a rapid growth in positive psychology, a research and intervention approach that focuses on promoting optimal functioning and well-being. Positive psychology interventions are now making their way into classrooms all over the world. However, positive psychology has been criticized for being decontextualized and coercive, and for putting an excessive emphasis on positive states, whilst failing to adequately consider negative experiences. Given this, how should policy be used to regulate and evaluate these interventions? We review evidence that suggests these criticisms may be valid, but only for those interventions that focus almost exclusively on changing the content of people’s inner experience (e.g., make it more positive and personality (improving character strength, and overemphasize the idea that inner experience causes action. We describe a contextualized form of positive psychology that not only deals with the criticisms, but also has clear policy implications for how to best implement and evaluate positive education programs so that they do not do more harm than good.

  7. Contextual Positive Psychology: Policy Recommendations for Implementing Positive Psychology into Schools.

    Science.gov (United States)

    Ciarrochi, Joseph; Atkins, Paul W B; Hayes, Louise L; Sahdra, Baljinder K; Parker, Philip

    2016-01-01

    There has been a rapid growth in positive psychology, a research and intervention approach that focuses on promoting optimal functioning and well-being. Positive psychology interventions are now making their way into classrooms all over the world. However, positive psychology has been criticized for being decontextualized and coercive, and for putting an excessive emphasis on positive states, whilst failing to adequately consider negative experiences. Given this, how should policy be used to regulate and evaluate these interventions? We review evidence that suggests these criticisms may be valid, but only for those interventions that focus almost exclusively on changing the content of people's inner experience (e.g., make it more positive) and personality (improving character strength), and overemphasize the idea that inner experience causes action. We describe a contextualized form of positive psychology that not only deals with the criticisms, but also has clear policy implications for how to best implement and evaluate positive education programs so that they do not do more harm than good.

  8. What Good Are Positive Emotions?

    OpenAIRE

    Fredrickson, Barbara L.

    1998-01-01

    This article opens by noting that positive emotions do not fit existing models of emotions. Consequently, a new model is advanced to describe the form and function of a subset of positive emotions, including joy, interest, contentment, and love. This new model posits that these positive emotions serve to broaden an individual’s momentary thought–action repertoire, which in turn has the effect of building that individual’s physical, intellectual, and social resources. Empirical evidence to sup...

  9. Regulating through leverage: Civil regulation in China

    NARCIS (Netherlands)

    Fürst, K.

    2016-01-01

    The overarching goal of this study is to examine the efforts of Chinese NGOs to prevent and/or control industrial pollution risks and then use the findings of this research to study the nature of civil regulation in, and beyond, China’s authoritarian setting. It first argues that 'regulation through

  10. Introducing Positive Psychology to SLA

    Science.gov (United States)

    MacIntyre, Peter D.; Mercer, Sarah

    2014-01-01

    Positive psychology is a rapidly expanding subfield in psychology that has important implications for the field of second language acquisition (SLA). This paper introduces positive psychology to the study of language by describing its key tenets. The potential contributions of positive psychology are contextualized with reference to prior work,…

  11. Positive Psychology and Outdoor Education

    Science.gov (United States)

    Berman, Dene S.; Davis-Berman, Jennifer

    2005-01-01

    A relatively new movement in psychology, positive psychology, has many implications for the field of outdoor education. Positive psychology has the goal of fostering excellence through the understanding and enhancement of factors that lead to growth. It embraces the view that growth occurs when positive factors are present, as opposed to the…

  12. Positive Stress and Reflective Practice Among Entrepreneurs

    Directory of Open Access Journals (Sweden)

    Kati Tikkamäki

    2016-01-01

    Full Text Available While heavy stress loads seem an unavoidable aspect of entrepreneurship, the positive side of stress (often referred to as ‘eustress’ remains a neglected area of research. This paper contributes to entrepreneurship research by linking the research streams of eustress and reflective practice. As a tool for analysing and developing thoughts and actions, reflective practice plays an important role in the interpretative work essential to positive stress experiences. Following an overview of approaches to stress at work, eustress and reflective practice, the paper explores how entrepreneurs experience the role of positive stress and reflective practice in their work and describes the reflective tools utilized by entrepreneurs in promoting eustress. The research process was designed to support reflective dialogue among the 21 Finnish entrepreneurs from different fields who participated in the study, with results based mainly on qualitative interviews. Nine of the interviewed entrepreneurs also kept a positive stress diary, including a three-day physiological measurement analysing their heartbeat variability. The findings suggest that positive stress and reflective practice are intertwined in the experiences of entrepreneurs and illustrate the role of reflective practice as a crucial toolset for promoting positive stress, comprising six reflective tools: studying oneself, changing one’s point of view, putting things into perspective, harnessing a feeling of trust, regulating resources and engaging in dialogue. Individual reflective capabilities vary, and a theory-driven division of reflective practice into individual, social and contextual dimensions is considered useful in understanding those differences. The research offers a starting point for exploring how eustress and reflective practice affect the well-being of entrepreneurs

  13. Quantifying Position-Dependent Codon Usage Bias

    Science.gov (United States)

    Hockenberry, Adam J.; Sirer, M. Irmak; Amaral, Luís A. Nunes; Jewett, Michael C.

    2014-01-01

    Although the mapping of codon to amino acid is conserved across nearly all species, the frequency at which synonymous codons are used varies both between organisms and between genes from the same organism. This variation affects diverse cellular processes including protein expression, regulation, and folding. Here, we mathematically model an additional layer of complexity and show that individual codon usage biases follow a position-dependent exponential decay model with unique parameter fits for each codon. We use this methodology to perform an in-depth analysis on codon usage bias in the model organism Escherichia coli. Our methodology shows that lowly and highly expressed genes are more similar in their codon usage patterns in the 5′-gene regions, but that these preferences diverge at distal sites resulting in greater positional dependency (pD, which we mathematically define later) for highly expressed genes. We show that position-dependent codon usage bias is partially explained by the structural requirements of mRNAs that results in increased usage of A/T rich codons shortly after the gene start. However, we also show that the pD of 4- and 6-fold degenerate codons is partially related to the gene copy number of cognate-tRNAs supporting existing hypotheses that posit benefits to a region of slow translation in the beginning of coding sequences. Lastly, we demonstrate that viewing codon usage bias through a position-dependent framework has practical utility by improving accuracy of gene expression prediction when incorporating positional dependencies into the Codon Adaptation Index model. PMID:24710515

  14. Navicular bone position determined by positional MRI: a reproducibility study

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Philip; Nybing, Janus D. [Copenhagen University Hospital Frederiksberg and Bispebjerg, Department of Radiology, Frederiksberg (Denmark); Johannsen, Finn E.; Stallknecht, Sandra E. [Copenhagen University Hospital Bispebjerg, Institute of Sports Medicine Copenhagen, Copenhagen, NV (Denmark); Hangaard, Stine; Hansen, Bjarke B. [Copenhagen University Hospital Frederiksberg, Parker Institute, Department of Rheumatology, Frederiksberg (Denmark); Boesen, Mikael [Copenhagen University Hospital Frederiksberg and Bispebjerg, Department of Radiology, Frederiksberg (Denmark); Copenhagen University Hospital Frederiksberg, Parker Institute, Department of Rheumatology, Frederiksberg (Denmark)

    2016-02-15

    To examine intraobserver, interobserver and between-day reproducibility of positional MRI for evaluation of navicular bone height (NVH) and medial navicular position (MNP). Positional MRI (pMRI) of the foot was performed on ten healthy participants (0.25 T G-scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). Intraobserver and interobserver reliability was ''substantial'' in both supine and standing position (ICC 0.86-0.98) and showed good agreement (LOA% 4.9-14.7 %). Between-day reliability of navicular height and medial navicular position in standing position remained substantial (ICC 0.85-0.92) with adequate agreement (LOA% 8.3-19.8 %). In supine position between-day reliability was ''moderate'' for NVH (ICC 0.72) and ''slight'' for MNP (ICC 0.39). Agreement remained adequate between-days for MNP in supine position (LOA% 17.7 %), but it was less than adequate for NVH in supine position (LOA% 24.2 %). Navicular height and medial navicular position can be measured by pMRI in a very reproducible manner within and between observers. Increased measurement variation is observed between-days in supine position, which may be due to small positional differences or other unknown biomechanical factors. (orig.)

  15. Navicular bone position determined by positional MRI: a reproducibility study

    International Nuclear Information System (INIS)

    Hansen, Philip; Nybing, Janus D.; Johannsen, Finn E.; Stallknecht, Sandra E.; Hangaard, Stine; Hansen, Bjarke B.; Boesen, Mikael

    2016-01-01

    To examine intraobserver, interobserver and between-day reproducibility of positional MRI for evaluation of navicular bone height (NVH) and medial navicular position (MNP). Positional MRI (pMRI) of the foot was performed on ten healthy participants (0.25 T G-scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). Intraobserver and interobserver reliability was ''substantial'' in both supine and standing position (ICC 0.86-0.98) and showed good agreement (LOA% 4.9-14.7 %). Between-day reliability of navicular height and medial navicular position in standing position remained substantial (ICC 0.85-0.92) with adequate agreement (LOA% 8.3-19.8 %). In supine position between-day reliability was ''moderate'' for NVH (ICC 0.72) and ''slight'' for MNP (ICC 0.39). Agreement remained adequate between-days for MNP in supine position (LOA% 17.7 %), but it was less than adequate for NVH in supine position (LOA% 24.2 %). Navicular height and medial navicular position can be measured by pMRI in a very reproducible manner within and between observers. Increased measurement variation is observed between-days in supine position, which may be due to small positional differences or other unknown biomechanical factors. (orig.)

  16. Context shapes social judgments of positive emotion suppression and expression.

    Science.gov (United States)

    Kalokerinos, Elise K; Greenaway, Katharine H; Casey, James P

    2017-02-01

    It is generally considered socially undesirable to suppress the expression of positive emotion. However, previous research has not considered the role that social context plays in governing appropriate emotion regulation. We investigated a context in which it may be more appropriate to suppress than express positive emotion, hypothesizing that positive emotion expressions would be considered inappropriate when the valence of the expressed emotion (i.e., positive) did not match the valence of the context (i.e., negative). Six experiments (N = 1,621) supported this hypothesis: when there was a positive emotion-context mismatch, participants rated targets who suppressed positive emotion as more appropriate, and evaluated them more positively than targets who expressed positive emotion. This effect occurred even when participants were explicitly made aware that suppressing targets were experiencing mismatched emotion for the context (e.g., feeling positive in a negative context), suggesting that appropriate emotional expression is key to these effects. These studies are among the first to provide empirical evidence that social costs to suppression are not inevitable, but instead are dependent on context. Expressive suppression can be a socially useful emotion regulation strategy in situations that call for it. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. Polyurethane - positioning aids in radiotherapy

    International Nuclear Information System (INIS)

    Alzen, G.; Boeck, E.G.; Thelen, M.; Kutzner, J.

    1985-01-01

    A simple and cheap method is described for the manufacturing of individual positioning aids made of foamed polyurethane. Some examples are given to demonstrate the applicability of these positioning aids for the irradiation of different body regions. The reproducibility of the radiation field in the head and neck area was investigated with and without positioning aid. It was proved that the field is adjusted more exactly when positioning aids are applied. The dosimetric investigations performed showed a negligible influence of foamed polyurethane on the radiation quality. So the positioning aids could be left within the radiation field when drawing the field borders. (orig.) [de

  18. Emotion complexity and emotion regulation across adulthood

    OpenAIRE

    Hay, Elizabeth L.; Diehl, Manfred

    2011-01-01

    This research used data from a study on daily emotional experience in adulthood to examine the associations between age, emotion complexity, and emotion regulation. Data were drawn from a study of daily stress that included 239 participants ranging in age from 18 to 89 from North Central Florida. Two indicators of emotion complexity were considered: emotion differentiation and the co-occurrence of positive and negative affect. Emotion regulation was assessed in terms of individuals’ likelihoo...

  19. A Sleep Position Trainer for positional sleep apnea

    DEFF Research Database (Denmark)

    Laub, Rasmus R; Tønnesen, Philip; Jennum, Poul J

    2017-01-01

    We tested the effect of the Sleep Position Trainer, a vibrational device, for positional sleep apnea in an open, randomized controlled trial with 101 patients, where 52 patients were allocated to Sleep Position Trainer and 49 patients to a non-treatment control group for 2 months (Part 1). All...... patients were then followed as a cohort for a period of 6 months with use of the Sleep Position Trainer (Part 2). The participants were assessed with polygraphy at entry, and after 2 and 6 months. The mean apnea-hypopnea index supine was 35 per h (SD, 18) in the Sleep Position Trainer group and 38 per h...... (SD, 15) in the control group at entry. In a per protocol analysis, the mean total apnea-hypopnea index at entry and after 2 months in the Sleep Position Trainer group was 18 per h (SD, 10) and 10 per h (SD, 9; P

  20. Are positive emotions just as "positive" across cultures?

    Science.gov (United States)

    Leu, Janxin; Wang, Jennifer; Koo, Kelly

    2011-08-01

    Whereas positive emotions and feeling unequivocally good may be at the heart of well-being among Westerners, positive emotions often carry negative associations within many Asian cultures. Based on a review of East-West cultural differences in dialectical emotions, or co-occurring positive and negative feelings, we predicted culture to influence the association between positive emotions and depression, but not the association between negative emotions and depression. As predicted, in a survey of over 600 European-, immigrant Asian-, and Asian American college students, positive emotions were associated with depression symptoms among European Americans and Asian Americans, but not immigrant Asians. Negative emotions were associated with depression symptoms among all three groups. We also found initial evidence that acculturation (i.e., nativity) may influence the role of positive emotions in depression: Asian Americans fell "in between" the two other groups. These findings suggest the importance of studying the role of culture in positive emotions and in positive psychology. The use of interventions based on promoting positive emotions in clinical psychology among Asian clients is briefly discussed. 2011 APA, all rights reserved

  1. Detecting Positioning Errors and Estimating Correct Positions by Moving Window

    Science.gov (United States)

    Song, Ha Yoon; Lee, Jun Seok

    2015-01-01

    In recent times, improvements in smart mobile devices have led to new functionalities related to their embedded positioning abilities. Many related applications that use positioning data have been introduced and are widely being used. However, the positioning data acquired by such devices are prone to erroneous values caused by environmental factors. In this research, a detection algorithm is implemented to detect erroneous data over a continuous positioning data set with several options. Our algorithm is based on a moving window for speed values derived by consecutive positioning data. Both the moving average of the speed and standard deviation in a moving window compose a moving significant interval at a given time, which is utilized to detect erroneous positioning data along with other parameters by checking the newly obtained speed value. In order to fulfill the designated operation, we need to examine the physical parameters and also determine the parameters for the moving windows. Along with the detection of erroneous speed data, estimations of correct positioning are presented. The proposed algorithm first estimates the speed, and then the correct positions. In addition, it removes the effect of errors on the moving window statistics in order to maintain accuracy. Experimental verifications based on our algorithm are presented in various ways. We hope that our approach can help other researchers with regard to positioning applications and human mobility research. PMID:26624282

  2. Mechanisms Regulating Glioma Invasion

    Science.gov (United States)

    Paw, Ivy; Carpenter, Richard C.; Watabe, Kounosuke; Debinski, Waldemar; Lo, Hui-Wen

    2015-01-01

    Glioblastoma (GBM) is the most aggressive, deadliest, and most common brain malignancy in adults. Despite the advances made in surgical techniques, radiotherapy and chemotherapy, the median survival for GBM patients has remained at a mere 14 months. GBM poses several unique challenges to currently available treatments for the disease. For example, GBM cells have the propensity to aggressively infiltrate/invade into the normal brain tissues and along the vascular tracks, which prevents complete resection of all malignant cells and limits the effect of localized radiotherapy while sparing normal tissue. Although anti-angiogenic treatment exerts anti-edematic effect in GBM, unfortunately, tumors progress with acquired increased invasiveness. Therefore, it is an important task to gain a deeper understanding of the intrinsic and post-treatment invasive phenotypes of GBM in hopes that the gained knowledge would lead to novel GBM treatments that are more effective and less toxic. This review will give an overview of some of the signaling pathways that have been shown to positively and negatively regulate GBM invasion, including, the PI3K/Akt, Wnt, sonic hedgehog-GLI1, and microRNAs. The review will also discuss several approaches to cancer therapies potentially altering GBM invasiveness. PMID:25796440

  3. MDEP Common Position No EPR-01 - Common positions on the EPR instrumentation and controls design

    International Nuclear Information System (INIS)

    2010-01-01

    The purpose of the EPR Working Group (EPRWG) of the Multinational Design Evaluation Program (MDEP) is to identify common positions among the regulators reviewing the EPR Instrumentation and Controls (I and C) Systems in order to: 1. Promote understanding of each country 's regulatory decisions and basis for the decisions, 2. Enhance communication among the members and with external stakeholders, 3. Identify areas where harmonization and convergence of regulations, standards, and guidance can be achieved or improved, and 4. Supports standardization of new reactor designs. Since January 2008, the EPR I and C Technical Expert Subgroup (TESG) members met five times to exchange information regarding their country 's review of the EPR I and C design. The EPR I and C TESG consists of regulators from China, Canada, Finland, France, the United Kingdom, and the United States. The information exchange includes presentation of each country 's review status and technical issues, sharing of guidance documents, and sharing of regulatory decision documents. The TESG focused on the following four core areas of the EPR I and C design: 1. I and C System Independence (particularly for data communications), 2. Level of Defense and Diversity (back-up systems), 3. Qualification/quality of digital platforms, 4. Categorization/classification of systems and functions. As meetings were conducted, some areas were emphasized more depending on the significance of the issues for each country. During the TESG interactions, it became apparent that there were aspects of the EPR design where the countries had common agreement. On November 2, 2009, three of the subgroup countries, France, Finland and the United Kingdom, issued a joint regulatory position on the EPR I and C design as result of the 'Groupe Permanent' meeting in France. This statement of common positions expands upon that joint regulatory position

  4. Regulating fisheries under uncertainty

    DEFF Research Database (Denmark)

    Hansen, Lars Gårn; Jensen, Frank

    2017-01-01

    the effects of these uncertainties into a single welfare measure for comparing tax and quota regulation. It is shown that quotas are always preferred to fees when structural economic uncertainty dominates. Since most regulators are subject to this kind of uncertainty, this result is a potentially important......Regulator uncertainty is decisive for whether price or quantity regulation maximizes welfare in fisheries. In this paper, we develop a model of fisheries regulation that includes ecological uncertainly, variable economic uncertainty as well as structural economic uncertainty. We aggregate...... qualification of the pro-price regulation message dominating the fisheries economics literature. We also believe that the model of a fishery developed in this paper could be applied to the regulation of other renewable resources where regulators are subject to uncertainty either directly or with some...

  5. Ocean Dumping Control Regulations

    International Nuclear Information System (INIS)

    1978-01-01

    These Regulations were made further to the Ocean Dumping Control Act which provides for restrictions in dumping operations. The Regulations contain model applications for permits to dump or load a series of materials. (NEA)

  6. Trout Stream Special Regulations

    Data.gov (United States)

    Minnesota Department of Natural Resources — This layer shows Minnesota trout streams that have a special regulation as described in the 2006 Minnesota Fishing Regulations. Road crossings were determined using...

  7. Positive mood broadens visual attention to positive stimuli.

    Science.gov (United States)

    Wadlinger, Heather A; Isaacowitz, Derek M

    2006-03-01

    In an attempt to investigate the impact of positive emotions on visual attention within the context of Fredrickson's (1998) broaden-and-build model, eye tracking was used in two studies to measure visual attentional preferences of college students (n=58, n=26) to emotional pictures. Half of each sample experienced induced positive mood immediately before viewing slides of three similarly-valenced images, in varying central-peripheral arrays. Attentional breadth was determined by measuring the percentage viewing time to peripheral images as well as by the number of visual saccades participants made per slide. Consistent with Fredrickson's theory, the first study showed that individuals induced into positive mood fixated more on peripheral stimuli than did control participants; however, this only held true for highly-valenced positive stimuli. Participants under induced positive mood also made more frequent saccades for slides of neutral and positive valence. A second study showed that these effects were not simply due to differences in emotional arousal between stimuli. Selective attentional broadening to positive stimuli may act both to facilitate later building of resources as well as to maintain current positive affective states.

  8. COMPANIES WITH MARKET POSITIONING BRANDS

    OpenAIRE

    Ruxandra Radoviciu; Filimon Stremtan

    2009-01-01

    Positioning a company on the market by the usage of brands is defined as the act ofdesigning the supply and its image on the market, so as to occupy a distinct place in the minds of theirtarget audience. The role of positioning in developing marketing strategy to differentiate products andservices involves the selection of attributes that are considered important for consumers. In order togain a strong position on the market the companies must perform a market analysis, an internalanalysis an...

  9. The Role of Positive Emotions in Positive Psychology

    Science.gov (United States)

    Fredrickson, Barbara L.

    2011-01-01

    In this article, the author describes a new theoretical perspective on positive emotions and situates this new perspective within the emerging field of positive psychology. The broaden-and-build theory posits that experiences of positive emotions broaden people's momentary thought-action repertoires, which in turn serves to build their enduring personal resources, ranging from physical and intellectual resources to social and psychological resources. Preliminary empirical evidence supporting the broaden-and-build theory is reviewed, and open empirical questions that remain to be tested are identified. The theory and findings suggest that the capacity to experience positive emotions may be a fundamental human strength central to the study of human flourishing. PMID:11315248

  10. Positivity of the English language.

    Science.gov (United States)

    Kloumann, Isabel M; Danforth, Christopher M; Harris, Kameron Decker; Bliss, Catherine A; Dodds, Peter Sheridan

    2012-01-01

    Over the last million years, human language has emerged and evolved as a fundamental instrument of social communication and semiotic representation. People use language in part to convey emotional information, leading to the central and contingent questions: (1) What is the emotional spectrum of natural language? and (2) Are natural languages neutrally, positively, or negatively biased? Here, we report that the human-perceived positivity of over 10,000 of the most frequently used English words exhibits a clear positive bias. More deeply, we characterize and quantify distributions of word positivity for four large and distinct corpora, demonstrating that their form is broadly invariant with respect to frequency of word use.

  11. Which Positive Integers are Interesting?

    Indian Academy of Sciences (India)

    Keywords. Interesting positive integers; idoneal numbers; Carmichael numbers; Wieferich primes; Mersenne primes; Fermat primes; Bernoulli numbers; Kaprekar constant; Skewes constants; look-and-say sequence; Graham's constant.

  12. CDDIS_VLBI_products_positions

    Data.gov (United States)

    National Aeronautics and Space Administration — Station positions and velocity solutions in Software INdependent EXchange (SINEX) format derived from analysis of Very Long Baseline Interferometry (VLBI) data....

  13. CDDIS_DORIS_products_positions

    Data.gov (United States)

    National Aeronautics and Space Administration — Station position and velocity solutions (weekly and cumulative) in Software INdependent EXchange (SINEX) format derived from analysis of Doppler Orbitography by...

  14. CDDIS_GNSS_products_positions

    Data.gov (United States)

    National Aeronautics and Space Administration — Weekly station positions and velocity solutions in Software INdependent EXchange (SINEX) format derived from analysis of Global Navigation Satellite System (GNSS)...

  15. Radiation Control Regulation 1993

    International Nuclear Information System (INIS)

    1993-01-01

    This Regulation (No. 434-1993) was made in pursuance of the Radiation Control Act 1990 and replaces the Active Substances Regulations 1959 repealed by the Act. It entered into force on 1 September 1993. The Regulation specifies that the technical radiation protection definitions have the same meaning as in the 1990 recommendations. The Regulation provides for the licensing of persons to use radioactive substances and radiation apparatus. It prescribes activities which may only be carried out by an accredited radiation expert and regulates the use of radiation apparatus and radioactive substances as well as the disposal and transport of radiation apparatus and radioactive substances. (NEA)

  16. Load regulating expansion fixture

    International Nuclear Information System (INIS)

    Wagner, L.M.; Strum, M.J.

    1998-01-01

    A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils is disclosed. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located there between. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components. 1 fig

  17. Positive selection drives lactoferrin evolution in mammals.

    Science.gov (United States)

    Liang, Guo Ming; Jiang, Xun Ping

    2010-07-01

    Lactoferrin (LF) is a member of the transferrin family that is abundantly expressed and secreted by glandular epithelial cells. The biological functions of LF involve in iron homeostasis regulation of the body and antibacterial activity. Previous studies demonstrated that it had a high cationic N-terminal domain that could interact with glycosaminoglycans, lipopolysaccharides and the bacterial virulence protein. Two anti-microbial peptides, lactoferricin (LFcin) and lactoferrampin (LFampin), were also isolated and identified in N-terminal of LF. Although the antibacterial mechanism was carefully studied, little was known about the molecular evolution of LF. In this study, we estimated the nonsynonymous-to-synonymous substitution ratios ( ) per site using maximum likelihood method to analyze the LF evolution. The results of omega > 1 and five identified positive selection sites of amino acid suggested that the evolution of LF gene was characterized by positive selection. Further study found that the positive selection sites were either located in the LF-bacteria binding region or the peptides of LFcin and LFampin, indicating that the selection pressure was related to LF-bacteria interaction. The identification of these sites may contribute to the mechanism of bacteria-LF interaction.

  18. Positive technology: using interactive technologies to promote positive functioning.

    Science.gov (United States)

    Riva, Giuseppe; Baños, Rosa M; Botella, Cristina; Wiederhold, Brenda K; Gaggioli, Andrea

    2012-02-01

    It is generally assumed that technology assists individuals in improving the quality of their lives. However, the impact of new technologies and media on well-being and positive functioning is still somewhat controversial. In this paper, we contend that the quality of experience should become the guiding principle in the design and development of new technologies, as well as a primary metric for the evaluation of their applications. The emerging discipline of Positive Psychology provides a useful framework to address this challenge. Positive Psychology is the scientific study of optimal human functioning and flourishing. Instead of drawing on a "disease model" of human behavior, it focuses on factors that enable individuals and communities to thrive and build the best in life. In this paper, we propose the "Positive Technology" approach--the scientific and applied approach to the use of technology for improving the quality of our personal experience through its structuring, augmentation, and/or replacement--as a way of framing a suitable object of study in the field of cyberpsychology and human-computer interaction. Specifically, we suggest that it is possible to use technology to influence three specific features of our experience--affective quality, engagement/actualization, and connectedness--that serve to promote adaptive behaviors and positive functioning. In this framework, positive technologies are classified according to their effects on a specific feature of personal experience. Moreover, for each level, we have identified critical variables that can be manipulated to guide the design and development of positive technologies.

  19. Two Drugs, Different Messages: Media and Marijuana and Alcohol Regulation in Uruguay

    Directory of Open Access Journals (Sweden)

    Mauricio Coitiño

    2017-12-01

    Full Text Available Recently, Uruguay’s cannabis market became regulated while the alcohol market regulation was discussed. Cannabis regulation policy receives more strong opposition than support among Uruguayan public opinion (Boidi, Queirolo y Cruz, 2016a. In contrast, alcohol regulation receives majoritarian approval (Cifra, 2015. Why are these two regulations, both discussed at the same historical time, receiving such a different support from citizens? Is it possible that media coverage on alcohol regulation is positive, while cannabis regulation is mostly negative? This article analyzes Uruguayan main press media coverage on both regulations, and identifies which are the predominant frames and the differences among the treatment received by each regulation.

  20. Yoga as a School-Wide Positive Behavior Support

    Science.gov (United States)

    Accardo, Amy L.

    2017-01-01

    A yoga-based school-wide positive behavior support (SWPBS) may provide a foundation for teaching mindfulness and self-regulation in K-12 schools. Here, the use of yoga as a SWPBS was examined through a review of existing literature and interviews of yoga program facilitators. Yoga was reported to be effective as a pedagogical approach, and found…

  1. Positive Psychology and Career Development

    Science.gov (United States)

    Robertson, Peter J.

    2018-01-01

    Positive psychology has been an influential movement within psychology in the early years of the twenty-first century. It is now timely to assess the value of its contribution to career education and guidance. This paper provides a critique of this perspective. Positive psychology can enrich approaches to career development. It can provide a…

  2. Positive Psychology and Career Development

    Science.gov (United States)

    Aulthouse, Michelle; Kolbert, Jered B.; Bundick, Matthew J.; Crothers, Laura M.

    2017-01-01

    The article details how school counselors can use principles of positive psychology to promote students' career development by facilitating students' pursuit of purpose and meaning. Specifically, the publication identifies how school counselors can actively employ with their students five constructs of positive psychology--namely strengths,…

  3. Indoor Positioning System using Bluetooth

    OpenAIRE

    Sahil Puri

    2015-01-01

    This Paper on Bluetooth Indoor Positioning System is the intersection of Bluetooth Technology and Indoor Positioning Systems. Almost every smartphone today is Bluetooth enabled, making the use of the technology more flexible. We aim at using the RSSI value of Bluetooth signals to track the location of a device.

  4. Signature Strengths in Positive Psychology

    Science.gov (United States)

    Molony, Terry; Henwood, Maureen

    2010-01-01

    Positive psychology can be thought of as the scientific study of what is "right about people" as opposed to the traditional focus on the healing of psychological pain or trauma. The philosophical roots of positive psychology can be traced back to Confucianism, Taoism, Buddhism, Hinduism, Judaism, Christianity, as well as Islamic and Athenian…

  5. Libera Electron Beam Position Processor

    CERN Document Server

    Ursic, Rok

    2005-01-01

    Libera is a product family delivering unprecedented possibilities for either building powerful single station solutions or architecting complex feedback systems in the field of accelerator instrumentation and controls. This paper presents functionality and field performance of its first member, the electron beam position processor. It offers superior performance with multiple measurement channels delivering simultaneously position measurements in digital format with MHz kHz and Hz bandwidths. This all-in-one product, facilitating pulsed and CW measurements, is much more than simply a high performance beam position measuring device delivering micrometer level reproducibility with sub-micrometer resolution. Rich connectivity options and innate processing power make it a powerful feedback building block. By interconnecting multiple Libera electron beam position processors one can build a low-latency high throughput orbit feedback system without adding additional hardware. Libera electron beam position processor ...

  6. Positivity VII (Zaanen Centennial Conference)

    CERN Document Server

    Pagter, Ben; Gaans, Onno; Veraar, Mark

    2016-01-01

    This book presents the proceedings of Positivity VII, held from 22-26 July 2013, in Leiden, the Netherlands. Positivity is the mathematical field concerned with ordered structures and their applications in the broadest sense of the word. A biyearly series of conferences is devoted to presenting the latest developments in this lively and growing discipline. The lectures at the conference covered a broad spectrum of topics, ranging from order-theoretic approaches to stochastic processes, positive solutions of evolution equations and positive operators on vector lattices, to order structures in the context of algebras of operators on Hilbert spaces. The contributions in the book reflect this variety and appeal to university researchers in functional analysis, operator theory, measure and integration theory and operator algebras. Positivity VII was also the Zaanen Centennial Conference to mark the 100th birth year of Adriaan Cornelis Zaanen, who held the chair of Analysis in Leiden for more than 25 years and was ...

  7. Introducing positive psychology to SLA

    Directory of Open Access Journals (Sweden)

    Sarah Mercer

    2014-01-01

    Full Text Available Positive psychology is a rapidly expanding subfield in psychology that has important implications for the field of second language acquisition (SLA. This paper introduces positive psychology to the study of language by describing its key tenets. The potential contributions of positive psychology are contextualized with reference to prior work, including the humanistic movement in language teaching, models of motivation, the concept of an affective filter, studies of the good language learner, and the concepts related to the self. There are reasons for both encouragement and caution as studies inspired by positive psychology are undertaken. Papers in this special issue of SSLLT cover a range of quantitative and qualitative methods with implications for theory, research, and teaching practice. The special issue serves as a springboard for future research in SLA under the umbrella of positive psychology.

  8. Updated thinking on positivity ratios.

    Science.gov (United States)

    Fredrickson, Barbara L

    2013-12-01

    This article presents my response to the article by Brown, Sokal, and Friedman (2013), which critically examined Losada's conceptual and mathematical work (as presented in Losada, 1999; Losada & Heaphy, 2004; and Fredrickson & Losada; 2005) and concluded that mathematical claims for a critical tipping point positivity ratio are unfounded. In the present article, I draw recent empirical evidence together to support the continued value of computing and seeking to elevate positivity ratios. I also underscore the necessity of modeling nonlinear effects of positivity ratios and, more generally, the value of systems science approaches within affective science and positive psychology. Even when scrubbed of Losada's now-questioned mathematical modeling, ample evidence continues to support the conclusion that, within bounds, higher positivity ratios are predictive of flourishing mental health and other beneficial outcomes. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  9. THE LIMITS OF POSITIVE INTERVENTIONS

    Directory of Open Access Journals (Sweden)

    Gonzalo Hervás

    2017-01-01

    Full Text Available Positive interventions have been developed extensively in recent years and they have been tested and applied in very diverse settings. Despite the fact that most of the findings regarding their efficacy can be considered from positive to very positive, the possibility that, in some cases, positive interventions may have unexpected or even iatrogenic effects cannot be discarded. In this article, research from several sources is reviewed in order to inform decisions about what interventions might be inadequate for cases with specific characteristics or vulnerability traits. Finally, the importance of using positive interventions with caution and rigor even when working with individuals who do not have overt problems or psychological disorders is discussed.

  10. [POSITIONING OF IMMOBALE NEUROLOGIC PATIENT].

    Science.gov (United States)

    Maček, Z; Mandić, M

    2016-01-01

    Damage to the central nervous system leads to the loss of motor control, loss of consciousness, sensory, cognitive and perceptive dysfunction. Patients are immobile in the early phase of recovery, therefore therapeutic approach demands appropriate methods of patient positioning in bed. The positioning has to ensure conditions that will stimulate and promote functional rehabilitation and prevent complications of immobility. The positioning has to rely on functional assessment of the patient problem, while it should also be therapeutic and individually adjusted to the patient needs. In the methods of positioning an immobile patient, all medical team members take part, especially nurses, physical therapists and occupational therapists. Results of positioning are better if mobilization and integration of the abilities regained by the patient are included.

  11. CLINICAL EVALUATION OF POSITIONAL VERTIGO

    Directory of Open Access Journals (Sweden)

    Praveen N

    2017-03-01

    Full Text Available BACKGROUND Vertigo is a very common symptom with which patients see a doctor in clinical practice. It is defined as “subjective sense of imbalance”. Vertigo can be broadly classified into Subjective and Objective types. Each can be again divided into episodic lasting for seconds or hours and prolonged lasting for weeks. A common presenting form of vertigo is that which is experienced when the patient turns his head in a particular position i.e. the positional vertigo, in some cases the vertiginous symptoms are also accompanied by a positional nystagmus. Benign Paroxysmal Positional Vertigo (BPPV is one the most common causes of vertigo. In the present study 100 patients were evaluated for Positional Vertigo. The aim of the study is to analyse patients presenting with positional vertigo and to evaluate the Effectiveness of Epley’s manoeuvre in BPPV and Medical management in patients with negative Dix Hallpike’s Positional test. MATERIALS AND METHODS The study included 100 consecutive patients diagnosed with positional vertigo. A detailed history and general examination and ENT examination was done including vestibular function evaluation. X-Ray cervical spine, P T A and caloric test (cold were done. CT scan and MRI performed. Positional test positive patients were treated with Epley’s manoeuvre and results analysed. RESULTS 100 patients with positional vertigo and among them 70 with BPPV were included in the present study. The mean age of the patient’s was 42.34±4.6 years. 30% of the patients belonged to the age group of 51 to 60 years, 25% to the age group of 41 to 50 years, and 20% to the age group of 31 to 40 years. 70/100 patients were treated with Epley’s manoeuvre. The response to Epley’s manoeuvre in the study showed that 65 patients were symptom free after 2 weeks, 67 after 1 month and 69 after 3 to 6 months period. CONCLUSION BPPV is one of the major causes of Positional Vertigo and that it could be very effectively

  12. Study on the Regulating Performance of Sliding Regulation-Valve

    Science.gov (United States)

    Hu, Wei; Peng, Xiaoyong; Zhang, Yuan; Zheng, Yulan; Zhu, Fangyao

    2018-01-01

    Using a proven reliable method of CFD to study the regulating performance of a sliding regulation valve with a conical spool and rugby body. The numerical simulation results indicate that no matter where the spool is located, the flow field always has a vortex at the center of the valve body; When the spool is at the origin, the vortex and resistance coefficient of the valve are the minimum; When the spool moves from the origin to the right (the opening of the valve becomes smaller) to reach a certain position later, vortex currents also begin to appear around the tube wall behind the orifice. In addition, the vortex increases as the throttling port decreases whereas the resistance coefficient of the valve ascends slowly with the increase of the deviation of the spool and the rise in series; This type of regulating valve has S type (slow at both ends, sensitive at the center) flow characteristics at the stroke, and is not affected by the size of Re.

  13. Position-sensitive phoswich detectors

    International Nuclear Information System (INIS)

    Chan, Y.

    1987-01-01

    They have constructed three types of phoswich detectors used frequently in the research programs, (1) a phoswich hodoscope array, (2) modular 1-dimensional position-sensitive phoswich slices (the Plastic Curtain), and also (3) a 2-dimensional position-sensitive 8'' x 8'' phoswich detector. Both the fast and slow components of these detectors are plastic scintillators (NE102, tau∼2.5 ns and NE115 tau∼225 ns). The hodoscope comprises 25 cube-shaped elements. It provides multiplicity information and has good particle identification capability. The Plastic Curtain is made up of 10 25-cm long position-sensitive phoswich modules. The position dependence of the light output, I∞exp(+/-ax+bx 2 ), (where a and b are empirical constants and x is the position measured from the center of the slice) provides the desired position information. The continuous 2-dimensional (X- and Y-) position sensitivity of the large area detector is achieved by measuring light-outputs from all 4-edges of the rectangular-shaped detector via adiabatic light-guide coupling

  14. Positive geometries and canonical forms

    Science.gov (United States)

    Arkani-Hamed, Nima; Bai, Yuntao; Lam, Thomas

    2017-11-01

    Recent years have seen a surprising connection between the physics of scattering amplitudes and a class of mathematical objects — the positive Grassmannian, positive loop Grassmannians, tree and loop Amplituhedra — which have been loosely referred to as "positive geometries". The connection between the geometry and physics is provided by a unique differential form canonically determined by the property of having logarithmic singularities (only) on all the boundaries of the space, with residues on each boundary given by the canonical form on that boundary. The structures seen in the physical setting of the Amplituhedron are both rigid and rich enough to motivate an investigation of the notions of "positive geometries" and their associated "canonical forms" as objects of study in their own right, in a more general mathematical setting. In this paper we take the first steps in this direction. We begin by giving a precise definition of positive geometries and canonical forms, and introduce two general methods for finding forms for more complicated positive geometries from simpler ones — via "triangulation" on the one hand, and "push-forward" maps between geometries on the other. We present numerous examples of positive geometries in projective spaces, Grassmannians, and toric, cluster and flag varieties, both for the simplest "simplex-like" geometries and the richer "polytope-like" ones. We also illustrate a number of strategies for computing canonical forms for large classes of positive geometries, ranging from a direct determination exploiting knowledge of zeros and poles, to the use of the general triangulation and push-forward methods, to the representation of the form as volume integrals over dual geometries and contour integrals over auxiliary spaces. These methods yield interesting representations for the canonical forms of wide classes of positive geometries, ranging from the simplest Amplituhedra to new expressions for the volume of arbitrary convex

  15. The Procyclical Effects of Bank Capital Regulation

    NARCIS (Netherlands)

    Repullo, R.; Suarez, J.

    2010-01-01

    We assess the procyclical effects of bank capital regulation in a dynamic equilibrium model of relationship lending in which banks are unable to access the equity markets every period. Banks anticipate that shocks to their earnings as well as the cyclical position of the economy can impair their

  16. Bank governance, regulation, and risk taking

    NARCIS (Netherlands)

    Laeven, L.; Levine, R.

    2009-01-01

    This paper conducts the first empirical assessment of theories concerning risk taking by banks, their ownership structures, and national bank regulations. We focus on conflicts between bank managers and owners over risk, and we show that bank risk taking varies positively with the comparative power

  17. The Development of Self-Regulation and Executive Function in Young Children

    Science.gov (United States)

    McClelland, Megan M.; Tominey, Shauna L.

    2014-01-01

    Self-regulation lays the foundation for positive social relationships and academic success. In this article, we provide an overview of self-regulation and the key terms related to selfregulation, such as executive function. We discuss research on how self-regulation develops and connections between self-regulation and social and academic outcomes.…

  18. Measuring Individual Differences in Emotion Regulation: The Emotion Regulation Profile-Revised (ERP-R

    Directory of Open Access Journals (Sweden)

    Delphine Nelis

    2011-02-01

    Full Text Available The main purpose of this study was to validate a new instrument aimed to assess emotion regulation: the Emotion Regulation Profile-Revised (ERP-R. Exploratory factor analyses yielded two theoretically meaningful factors: down-regulation of negative emotions and up-regulation of positive emotions. Internal reliability scores of the two factors were good. Findings showed evidence of convergent/discriminant validity, with ERP-R scores being independent of non verbal reasoning and verbal skills while positively related to emotional intelligence and to relevant personality dimensions. There was also preliminary evidence of criterion validity. ERP-R scores also demonstrated incremental validity to predict a number of criteria over and above emotional intelligence and emotional stability. Overall, the results show a clear 2 factors solution for the ERP-R and high correlations with convergent and divergent scales as well as good criterion and incremental validities.

  19. TOWARD MORE EFFECTIVE REGULATION

    Energy Technology Data Exchange (ETDEWEB)

    J. GRAF

    2000-06-01

    This paper proposes a model relationship between the operator engaged in a hazardous activity, the regulator of that activity, and the general public. The roles and responsibilities of each entity are described in a way that allows effective communication flow. The role of the regulator is developed using the steam boiler as an example of a hazard subject to regulation; however, the model applies to any regulated activity. In this model the safety analyst has the extremely important role of communicating sometimes difficult technical information to the regulator in a way that the regulator can provide credible assurance to the general public as to the adequacy of the control of the hazardous activity. The conclusion asserts that acceptance of the model, understanding of the roles and responsibilities and definition of who communicates what information to whom will mitigate frustration on the part of each of the three entities.

  20. The development of regulations

    International Nuclear Information System (INIS)

    Slokan Dusic, D.; Levstek, M.F.; Stritar, A.

    2003-01-01

    In October 2002, The Act on Protection Against Ionising Radiation and Nuclear Safety which regulates all aspects of protection against ionising radiation and nuclear safety entered into force in Slovenia. The Slovenian government and its responsible ministries shall issue several governmental and ministerial regulations to support the above - mentioned act. The Slovenian Nuclear Safety Administration (SNSA) which acts within the Ministry of the Environment, Spatial Planing and Energy takes an active part in drafting the regulations which are defined in the act. Due to a very comprehensive and pretentious task, that is to be completed in a relatively short period of time, taking into consideration the involvement of stakeholders and all competent ministries, the SNSA within the Quality Management System developed a special procedure that insures the systematic approach to the preparation of regulations. The article will briefly represent the process that: defines the preparation, development, harmonisation, review, approval and issue of regulations and uniforms the format of developed regulations. (author)