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  1. Task-dependent activation of distinct fast and slow(er) motor pathways during motor imagery.

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    Keller, Martin; Taube, Wolfgang; Lauber, Benedikt

    2018-02-22

    Motor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions. The aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions. H-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest. In contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions. This study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Crosstalk of ER stress-mediated autophagy and ER-phagy: Involvement of UPR and the core autophagy machinery.

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    Song, Shuling; Tan, Jin; Miao, Yuyang; Zhang, Qiang

    2018-05-01

    Endoplasmic reticulum (ER) stress, a common cellular stress response, is closely related to the activation of autophagy that is an important and evolutionarily conserved mechanism for maintaining cellular homeostasis. Autophagy induced by ER stress mainly includes the ER stress-mediated autophagy and ER-phagy. The ER stress-mediated autophagy is characterized by the generation of autophagosomes that include worn-out proteins, protein aggregates, and damaged organelles. While the autophagosomes of ER-phagy selectively include ER membranes, and the double membranes also derive, at least in part, from the ER. The signaling pathways of IRE1α, PERK, ATF6, and Ca 2+ are necessary for the activation of ER stress-mediated autophagy, while the receptor-mediated selective ER-phagy degrades the ER is Atg40/FAM134B. The ER stress-mediated autophagy and ER-phagy not only have differences, but also have connections. The activation of ER-phagy requires the core autophagy machinery, and the ER-phagy may be a branch of ER stress-mediated autophagy that selectively targets the ER. However, the determined factors that control the changeover switch between ER stress-mediated autophagy and ER-phagy are largely obscure, which may be associated with the type of cells and the extent of stimulation. This review summarized the crosstalk between ER stress-mediated autophagy and ER-phagy and their signaling networks. Additionally, we discussed the possible factors that influence the type of autophagy induced by ER stress. © 2017 Wiley Periodicals, Inc.

  3. Cocaine-mediated induction of microglial activation involves the ER stress-TLR2 axis.

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    Liao, Ke; Guo, Minglei; Niu, Fang; Yang, Lu; Callen, Shannon E; Buch, Shilpa

    2016-02-09

    Neuroinflammation associated with advanced human immunodeficiency virus (HIV)-1 infection is often exacerbated by chronic cocaine abuse. Cocaine exposure has been demonstrated to mediate up-regulation of inflammatory mediators in in vitro cultures of microglia. The molecular mechanisms involved in this process, however, remain poorly understood. In this study, we sought to explore the underlying signaling pathways involved in cocaine-mediated activation of microglial cells. BV2 microglial cells were exposed to cocaine and assessed for toll-like receptor (TLR2) expression by quantitative polymerase chain reaction (qPCR), western blot, flow cytometry, and immunofluorescence staining. The mRNA and protein levels of cytokines (TNFα, IL-6, MCP-1) were detected by qPCR and ELISA, respectively; level of reactive oxygen species (ROS) production was examined by the Image-iT LIVE Green ROS detection kit; activation of endoplasmic reticulum (ER)-stress pathways were detected by western blot. Chromatin immunoprecipitation (ChIP) assay was employed to discern the binding of activating transcription factor 4 (ATF4) with the TLR2 promoter. Immunoprecipitation followed by western blotting with tyrosine antibody was used to determine phosphorylation of TLR2. Cocaine-mediated up-regulation of TLR2 expression and microglial activation was validated in cocaine-injected mice. Exposure of microglial cells to cocaine resulted in increased expression of TLR2 with a concomitant induction of microglial activation. Furthermore, this effect was mediated by NADPH oxidase-mediated rapid accumulation of ROS with downstream activation of the ER-stress pathways as evidenced by the fact that cocaine exposure led to up-regulation of pPERK/peIF2α/ATF4 and TLR2. The novel role of ATF4 in the regulation of TLR2 expression was confirmed using genetic and pharmacological approaches. xThe current study demonstrates that cocaine-mediated activation of microglia involves up-regulation of TLR2 through the

  4. Distinctive amygdala subregions involved in emotion-modulated Stroop interference.

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    Han, Hyun Jung; Lee, Kanghee; Kim, Hyun Taek; Kim, Hackjin

    2014-05-01

    Despite the well-known role of the amygdala in mediating emotional interference during tasks requiring cognitive resources, no definite conclusion has yet been reached regarding the differential roles of functionally and anatomically distinctive subcomponents of the amygdala in such processes. In this study, we examined female participants and attempted to separate the neural processes for the detection of emotional information from those for the regulation of cognitive interference from emotional distractors by adding a temporal gap between emotional stimuli and a subsequent cognitive Stroop task. Reaction time data showed a significantly increased Stroop interference effect following emotionally negative stimuli compared with neutral stimuli, and functional magnetic resonance imaging data revealed that the anterior ventral amygdala (avAMYG) showed greater responses to negative stimuli compared with neutral stimuli. In addition, individuals who scored high in neuroticism showed greater posterior dorsal amygdala (pdAMYG) responses to incongruent compared with congruent Stroop trials following negative stimuli, but not following neutral stimuli. Taken together, the findings of this study demonstrated functionally distinctive contributions of the avAMYG and pdAMYG to the emotion-modulated Stroop interference effect and suggested that the avAMYG encodes associative values of emotional stimuli whereas the pdAMYG resolves cognitive interference from emotional distractors.

  5. Different sets of ER-resident J-proteins regulate distinct polar nuclear-membrane fusion events in Arabidopsis thaliana.

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    Maruyama, Daisuke; Yamamoto, Masaya; Endo, Toshiya; Nishikawa, Shuh-ichi

    2014-11-01

    Angiosperm female gametophytes contain a central cell with two polar nuclei. In many species, including Arabidopsis thaliana, the polar nuclei fuse during female gametogenesis. We previously showed that BiP, an Hsp70 in the endoplasmic reticulum (ER), was essential for membrane fusion during female gametogenesis. Hsp70 function requires partner proteins for full activity. J-domain containing proteins (J-proteins) are the major Hsp70 functional partners. A. thaliana ER contains three soluble J-proteins, AtERdj3A, AtERdj3B, and AtP58(IPK). Here, we analyzed mutants of these proteins and determined that double-mutant ovules lacking AtP58(IPK) and AtERdj3A or AtERdj3B were defective in polar nuclear fusion. Electron microscopy analysis identified that polar nuclei were in close contact, but no membrane fusion occurred in mutant ovules lacking AtP58(IPK) and AtERdj3A. The polar nuclear outer membrane appeared to be connected via the ER remaining at the inner unfused membrane in mutant ovules lacking AtP58(IPK) and AtERdj3B. These results indicate that ER-resident J-proteins, AtP58(IPK)/AtERdj3A and AtP58(IPK)/AtERdj3B, function at distinct steps of polar nuclear-membrane fusion. Similar to the bip1 bip2 double mutant female gametophytes, the aterdj3a atp58(ipk) double mutant female gametophytes defective in fusion of the outer polar nuclear membrane displayed aberrant endosperm proliferation after fertilization with wild-type pollen. However, endosperm proliferated normally after fertilization of the aterdj3b atp58(ipk) double mutant female gametophytes defective in fusion of the inner membrane. Our results indicate that the polar nuclear fusion defect itself does not cause an endosperm proliferation defect. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Involvement of TR3/Nur77 translocation to the endoplasmic reticulum in ER stress-induced apoptosis

    International Nuclear Information System (INIS)

    Liang Bin; Song Xuhong; Liu Gefei; Li Rui; Xie Jianping; Xiao Lifeng; Du Mudan; Zhang Qiaoxia; Xu Xiaoyuan; Gan Xueqiong; Huang Dongyang

    2007-01-01

    Nuclear orphan receptor TR3/Nur77/NGFI-B is a novel apoptotic effector protein that initiates apoptosis largely by translocating from the nucleus to the mitochondria, causing the release of cytochrome c. However, it is possible that TR3 translocates to other organelles. The present study was designed to determine the intracellular localization of TR3 following CD437-induced nucleocytoplasmic translocation and the mechanisms involved in TR3-induced apoptosis. In human neuroblastoma SK-N-SH cells and human esophageal squamous carcinoma EC109 and EC9706 cells, 5 μM CD437 induced translocation of TR3 to the endoplasmic reticulum (ER). This distribution was confirmed by immunofluorescence analysis, subcellular fractionation analysis and coimmunoprecipitation analysis. The translocated TR3 interacted with ER-targeting Bcl-2; initiated an early release of Ca 2+ from ER; resulted in ER stress and induced apoptosis through ER-specific caspase-4 activation, together with induction of mitochondrial stress and subsequent activation of caspase-9. Our results identified a novel distribution of TR3 in the ER and defined two parallel mitochondrial- and ER-based pathways that ultimately result in apoptotic cell death

  7. ER-associated SNAREs and Sey1p mediate nuclear fusion at two distinct steps during yeast mating.

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    Rogers, Jason V; Arlow, Tim; Inkellis, Elizabeth R; Koo, Timothy S; Rose, Mark D

    2013-12-01

    During yeast mating, two haploid nuclei fuse membranes to form a single diploid nucleus. However, the known proteins required for nuclear fusion are unlikely to function as direct fusogens (i.e., they are unlikely to directly catalyze lipid bilayer fusion) based on their predicted structure and localization. Therefore we screened known fusogens from vesicle trafficking (soluble N-ethylmaleimide-sensitive factor attachment protein receptors [SNAREs]) and homotypic endoplasmic reticulum (ER) fusion (Sey1p) for additional roles in nuclear fusion. Here we demonstrate that the ER-localized SNAREs Sec20p, Ufe1p, Use1p, and Bos1p are required for efficient nuclear fusion. In contrast, Sey1p is required indirectly for nuclear fusion; sey1Δ zygotes accumulate ER at the zone of cell fusion, causing a block in nuclear congression. However, double mutants of Sey1p and Sec20p, Ufe1p, or Use1p, but not Bos1p, display extreme ER morphology defects, worse than either single mutant, suggesting that retrograde SNAREs fuse ER in the absence of Sey1p. Together these data demonstrate that SNAREs mediate nuclear fusion, ER fusion after cell fusion is necessary to complete nuclear congression, and there exists a SNARE-mediated, Sey1p-independent ER fusion pathway.

  8. Arabidopsis senescence-associated protein DMP1 is involved in membrane remodeling of the ER and tonoplast

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    Kasaras Alexis

    2012-04-01

    Full Text Available Abstract Background Arabidopsis DMP1 was discovered in a genome-wide screen for senescence-associated membrane proteins. DMP1 is a member of a novel plant-specific membrane protein family of unknown function. In rosette leaves DMP1 expression increases from very low background level several 100fold during senescence progression. Results Expression of AtDMP1 fused to eGFP in Nicotiana benthamiana triggers a complex process of succeeding membrane remodeling events affecting the structure of the endoplasmic reticulum (ER and the vacuole. Induction of spherical structures (“bulbs”, changes in the architecture of the ER from tubular to cisternal elements, expansion of smooth ER, formation of crystalloid ER, and emergence of vacuolar membrane sheets and foamy membrane structures inside the vacuole are proceeding in this order. In some cells it can be observed that the process culminates in cell death after breakdown of the entire ER network and the vacuole. The integrity of the plasma membrane, nucleus and Golgi vesicles are retained until this stage. In Arabidopsis thaliana plants expressing AtDMP1-eGFP by the 35S promoter massive ER and vacuole vesiculation is observed during the latest steps of leaf senescence, whereas earlier in development ER and vacuole morphology are not perturbed. Expression by the native DMP1 promoter visualizes formation of aggregates termed “boluses” in the ER membranes and vesiculation of the entire ER network, which precedes disintegration of the central vacuole during the latest stage of senescence in siliques, rosette and cauline leaves and in darkened rosette leaves. In roots tips, DMP1 is strongly expressed in the cortex undergoing vacuole biogenesis. Conclusions Our data suggest that DMP1 is directly or indirectly involved in membrane fission during breakdown of the ER and the tonoplast during leaf senescence and in membrane fusion during vacuole biogenesis in roots. We propose that these properties of DMP1

  9. Arecoline Induces Neurotoxicity to PC12 Cells: Involvement in ER Stress and Disturbance of Endogenous H2S Generation.

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    Jiang, Jia-Mei; Wang, Li; Gu, Hong-Feng; Wu, Keng; Xiao, Fan; Chen, Ying; Guo, Run-Min; Tang, Xiao-Qing

    2016-08-01

    Arecoline is a major alkaloid of areca nut and has been effect on central nervous system. Although arecoline-induced neurotoxicity has been reported, the possible underlying neurotoxic mechanisms have not yet been elucidated. Increasing evidences have shown that both excessive endoplasmic reticulum (ER) stress and disturbance of hydrogen sulfide (H2S) production are involved in the pathophysiology of numerous neurodegenerative diseases. Here, the purpose of present study was to verify whether ER stress and the disturbance of endogenous H2S generation are also involved in arecoline-caused neurotoxicity. We found that treatment of PC12 cells with arecoline induced the down-regulation of cells viability and up-regulation of apoptosis and the activity of caspase-3, indicating the neurotoxic role of arecoline to PC12 cells. In addition, arecoline also increased the expression of Bax (pro-apoptotic protein) and attenuated the expression of Bcl-2 (anti-apoptotic protein) in PC12 cells. Simultaneously, arecoline caused excessive ER stress in PC12 cells, as evidenced by the up-regulations of Glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), and Cleaved caspase-12 expressions. Notably, the level of H2S in the culture supernatant and the expressions of cystathionine β-synthase and 3-mercaptopyruvate sulfurtransferase (two major enzymes for endogenous H2S generation in PC12 cells) were also reduced by arecoline treatment. These results indicate that arecoline-caused neurotoxicity to PC12 cells is involved in ER stress and disturbance of endogenous H2S generation and suggest that the modulation of ER stress and endogenous H2S generation may be potential therapeutic approach in treatment of arecoline-caused neurotoxicity.

  10. Pathomorphological distinction between Er:YAG and diode lasers on the excisional biopsy of the oral mucosa

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    Georgi T. Tomov

    2013-02-01

    Full Text Available Background – In oral pathology, laser devices can provide important advantages, especially in the treatment of certain lesions. However, there is controversy about the use of some wavelengths in the analysis of suspected dysplastic or neoplastic lesions, raising doubt about the laser's suitability for use in biopsy procedures. The present pilot study evaluates the pathomorphological characteristics and suitability of Er:YAG and diode lasers for performing excisional biopsies in the oral mucosa with special emphasis on the extent of the thermal damage zone created. Material and Methods – 10 patients were randomly assigned to one diode or one Er:YAG laser groups. The Er:YAG laser(2940nm was used in a pulsed wave mode 200mJ/35Hz with a power of 7 W. Power settings for the diode laser(810 nm were 3 W in a pulsed mode. The thermal damage zone of the two lasers and intraoperative and postoperative complications were assessed and compared.All biopsy specimens were evaluated by optical microscopy by threeblinded pathologists. After establishing the pathomorphological diagnosis of the lesion assessed, the pathologists measured the maximal width of the peripheral thermal damage zone in the specimen in μm and classified it using appropriate index. Results – The peripheral thermal damage zone on the borders of the excisional biopsies was significantly smaller with the Er:YAG laser compared to the diode laser regarding values in μm or pathomorphological index scores. No postoperative complications occurred in any of the two groups. Conclusions – The Er:YAG laser seems to be appropriate for excisional biopsies of benign oral mucosal lesions. The Er:YAG laser offers clear advantages in terms of smaller thermal damage zones over the diode laser. Although in some samples thermal damage was minimally visible, in all samples histological evaluation was clearly possible. The study demonstrated that the Er:YAG laser can be safely used in oral biopsy

  11. Docosahexaenoic Acid Ameliorates Fructose-Induced Hepatic Steatosis Involving ER Stress Response in Primary Mouse Hepatocytes

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    Jinying Zheng

    2016-01-01

    Full Text Available The increase in fructose consumption is considered to be a risk factor for developing nonalcoholic fatty liver disease (NAFLD. We investigated the effects of docosahexaenoic acid (DHA on hepatic lipid metabolism in fructose-treated primary mouse hepatocytes, and the changes of Endoplasmic reticulum (ER stress pathways in response to DHA treatment. The hepatocytes were treated with fructose, DHA, fructose plus DHA, tunicamycin (TM or fructose plus 4-phenylbutyric acid (PBA for 24 h. Intracellular triglyceride (TG accumulation was assessed by Oil Red O staining. The mRNA expression levels and protein levels related to lipid metabolism and ER stress response were determined by real-time PCR and Western blot. Fructose treatment led to obvious TG accumulation in primary hepatocytes through increasing expression of fatty acid synthase (FAS and acetyl-CoA carboxylase (ACC, two key enzymes in hepatic de novo lipogenesis. DHA ameliorates fructose-induced TG accumulation by upregulating the expression of carnitine palmitoyltransferase 1A (CPT-1α and acyl-CoA oxidase 1 (ACOX1. DHA treatment or pretreatment with the ER stress inhibitor PBA significantly decreased TG accumulation and reduced the expression of glucose-regulated protein 78 (GRP78, total inositol-requiring kinase 1 (IRE1α and p-IRE1α. The present results suggest that DHA protects against high fructose-induced hepatocellular lipid accumulation. The current findings also suggest that alleviating the ER stress response seems to play a role in the prevention of fructose-induced hepatic steatosis by DHA.

  12. Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis

    International Nuclear Information System (INIS)

    Gao, Wei-Min; Haab, Brian B; Hanash, Samir M; Kuick, Rork; Orchekowski, Randal P; Misek, David E; Qiu, Ji; Greenberg, Alissa K; Rom, William N; Brenner, Dean E; Omenn, Gilbert S

    2005-01-01

    Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profiles may result from the differential expression of relatively abundant serum proteins associated with the host response. Eighty-four antibodies, targeting a wide range of serum proteins, were spotted onto nitrocellulose-coated microscope slides. The abundances of the corresponding proteins were measured in 80 serum samples, from 24 newly diagnosed subjects with lung cancer, 24 healthy controls, and 32 subjects with chronic obstructive pulmonary disease (COPD). Two-color rolling-circle amplification was used to measure protein abundance. Seven of the 84 antibodies gave a significant difference (p < 0.01) for the lung cancer patients as compared to healthy controls, as well as compared to COPD patients. Proteins that exhibited higher abundances in the lung cancer samples relative to the control samples included C-reactive protein (CRP; a 13.3 fold increase), serum amyloid A (SAA; a 2.0 fold increase), mucin 1 and α-1-antitrypsin (1.4 fold increases). The increased expression levels of CRP and SAA were validated by Western blot analysis. Leave-one-out cross-validation was used to construct Diagonal Linear Discriminant Analysis (DLDA) classifiers. At a cutoff where all 56 of the non-tumor samples were correctly classified, 15/24 lung tumor patient sera were correctly classified. Our results suggest that a distinctive serum protein profile involving abundant proteins may be observed in lung cancer patients relative to healthy subjects or patients with chronic disease and may have utility as part of strategies for detecting lung cancer

  13. The nuclear estrogen receptor R-II of the goat uterus: distinct possibility that the R-II is the deglycosylated form of the nonactivated estrogen receptor (naER).

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    Karthikeyan, N; Thampan, R V

    1995-08-20

    Structural and functional characteristics of the goat uterine nuclear estrogen receptor R-II have been subjected to comparison with those of the nonactivated estrogen receptor (naER), purified from the cytosol. The two proteins have the same molecular mass, 66 kDa; they display identical peptide maps and are both recognized by anti-estrogen receptor (R-I) IgG. Both are tyrosine kinases and bind with equal affinity to a column of anti-phosphotyrosine IgG-Sepharose. On the other hand, while naER is a glycoprotein, the R-II does not show any sign of glycosylation. Unlike the naER, the R-II is incapable of dimerization with estrogen receptor activation factor (E-RAF) and, as a consequence, bind to the DNA. R-II has a higher estradiol binding capacity and the resultant reduction in its affinity for the hormone in comparison with the naER. Further, the sedimentation behavior and the Stokes radius of the naER indicate a globular nature in the shape of the protein. The corresponding data for the R-II reveal that the protein has a distinct nonglobular shape. Deglycosylation of the naER using a glycopeptidase resulted in the total conversion of the distinct physical features of the naER to the R-II category. This treatment resulted, without effecting any reduction in its molecular mass, in the loss of the E-RAF dimerization capacity of the naER. The Stokes radius and the sedimentation coefficient of the protein underwent drastic changes and became closely similar to those of the R-II. In addition, the deglycosylation introduced a several-fold enhancement in the capacity of the naER to bind estradiol with a concomitant decrease in its affinity, similar to the corresponding properties of the R-II. The R-II is shown to have a conformational structure different from that of the naER, to interact with the nuclear RNA polymerase II. It is also shown here that the R-II phosphorylates two subunits (molecular mass 91 and 20 kDa) in the RNA polymerase II, in addition to the 40-k

  14. Insights on the involvement of (-)-epigallocatechin gallate in ER stress-mediated apoptosis in age-related macular degeneration.

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    Karthikeyan, Bose; Harini, Lakshminarasimhan; Krishnakumar, Vaithilingam; Kannan, Velu Rajesh; Sundar, Krishnan; Kathiresan, Thandavarayan

    2017-01-01

    Endoplasmic reticulum (ER) stress-mediated apoptosis is a well-known factor in the pathogenesis of age-related macular degeneration (AMD). ER stress leads to accumulation of misfolded proteins, which in turn activates unfolded protein response (UPR) of the cell for its survival. The prolonged UPR of ER stress promotes cell death; however, the transition between adaptation and ER stress-induced apoptosis has not been clearly understood. Hence, the present study investigates the regulatory effect of (-)-epigallocatechin gallate (EGCG) on ER stress-induced by hydrogen peroxide (H 2 O 2 ) and disturbance of calcium homeostasis by thapsigargin (TG) in mouse retinal pigment epithelial (MRPE) cells. The oxidant molecules influenced MRPE cells showed an increased level of intracellular calcium [Ca 2+ ] i in ER and transferred to mitochondria through ER-mitochondrial tether site then increased ROS production. EGCG restores [Ca 2+ ] i homeostasis by decreasing ROS production through inhibition of prohibitin1 which regulate ER-mitochondrial tether site and inhibit apoptosis. Effect of EGCG on ER stress-mediated apoptosis was elucidated by exploring the UPR signalling pathways. EGCG downregulated GRP78, CHOP, PERK, ERO1α, IRE1α, cleaved PARP, cleaved caspase 3, caspase 12 and upregulated expression of calnexinin MRPE cells. In addition to this, inhibition of apoptosis by EGCG was also confirmed with expression of proteins Akt, PTEN and GSK3β. MRPE cells with EGCG upregulates phosphorylation of Akt at ser473 and phospho ser380 of PTEN, but phosphorylation at ser9 of GSK3β was inhibited. Further, constitutively active (myristoylated) CA-Akt transfected in MRPE cells had an increased Akt activity in EGCG influenced cells. These findings strongly suggest that antioxidant molecules inhibit cell death through the proper balancing of [Ca 2+ ] i and ROS production in order to maintain UPR of ER in MRPE cells. Thus, modulation of UPR signalling may provide a potential target for

  15. Differential involvement of E2A-corepressor interactions in distinct leukemogenic pathways.

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    Gow, Chien-Hung; Guo, Chun; Wang, David; Hu, Qiande; Zhang, Jinsong

    2014-01-01

    E2A is a member of the E-protein family of transcription factors. Previous studies have reported context-dependent regulation of E2A-dependent transcription. For example, whereas the E2A portion of the E2A-Pbx1 leukemia fusion protein mediates robust transcriptional activation in t(1;19) acute lymphoblastic leukemia, the transcriptional activity of wild-type E2A is silenced by high levels of corepressors, such as the AML1-ETO fusion protein in t(8;21) acute myeloid leukemia and ETO-2 in hematopoietic cells. Here, we show that, unlike the HEB E-protein, the activation domain 1 (AD1) of E2A has specifically reduced corepressor interaction due to E2A-specific amino acid changes in the p300/CBP and ETO target motif. Replacing E2A-AD1 with HEB-AD1 abolished the ability of E2A-Pbx1 to activate target genes and to induce cell transformation. On the other hand, the weak E2A-AD1-corepressor interaction imposes a critical importance on another ETO-interacting domain, downstream ETO-interacting sequence (DES), for corepressor-mediated repression. Deletion of DES abrogates silencing of E2A activity by AML1-ETO in t(8;21) leukemia cells or by ETO-2 in normal hematopoietic cells. Our results reveal an E2A-specific mechanism important for its context-dependent activation and repression function, and provide the first evidence for the differential involvement of E2A-corepressor interactions in distinct leukemogenic pathways.

  16. Differential white matter involvement associated with distinct visuospatial deficits after right hemisphere stroke.

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    Carter, Alex R; McAvoy, Mark P; Siegel, Joshua S; Hong, Xin; Astafiev, Serguei V; Rengachary, Jennifer; Zinn, Kristi; Metcalf, Nicholas V; Shulman, Gordon L; Corbetta, Maurizio

    2017-03-01

    Visuospatial attention depends on the integration of multiple processes, and people with right hemisphere lesions after a stroke may exhibit severe or no visuospatial deficits. The anatomy of core components of visuospatial attention is an area of intense interest. Here we examine the relationship between the disruption of core components of attention and lesion distribution in a heterogeneous group (N = 70) of patients with right hemisphere strokes regardless of the presence of clinical neglect. Deficits of lateralized spatial orienting, measured as the difference in reaction times for responding to visual targets in the contralesional or ipsilesional visual field, and deficits in re-orienting attention, as measured by the difference in reaction times for invalidly versus validly cued targets, were measured using a computerized spatial orienting task. Both measures were related through logistic regression and a novel ridge regression method to anatomical damage measured with magnetic resonance imaging. While many regions were common to both deficit maps, a deficit in lateralized spatial orienting was more associated with lesions in the white matter underlying the posterior parietal cortex, and middle and inferior frontal gyri. A deficit in re-orienting of attention toward unattended locations was associated with lesions in the white matter of the posterior parietal cortex, insular cortex and less so with white matter involvement of the anterior frontal lobe. An hodological analysis also supports this partial dissociation between the white matter tracts that are damaged in lateralized spatial biases versus impaired re-orienting. Our results underscore that the integrity of fronto-parietal white matter tracts is crucial for visuospatial attention and that different attention components are mediated by partially distinct neuronal substrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Involvement of ER Stress in Dysmyelination of Pelizaeus-Merzbacher Disease with PLP1 Missense Mutations Shown by iPSC-Derived Oligodendrocytes

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    Yuko Numasawa-Kuroiwa

    2014-05-01

    Full Text Available Pelizaeus-Merzbacher disease (PMD is a form of X-linked leukodystrophy caused by mutations in the proteolipid protein 1 (PLP1 gene. Although PLP1 proteins with missense mutations have been shown to accumulate in the rough endoplasmic reticulum (ER in disease model animals and cell lines transfected with mutant PLP1 genes, the exact pathogenetic mechanism of PMD has not previously been clarified. In this study, we established induced pluripotent stem cells (iPSCs from two PMD patients carrying missense mutation and differentiated them into oligodendrocytes in vitro. In the PMD iPSC-derived oligodendrocytes, mislocalization of mutant PLP1 proteins to the ER and an association between increased susceptibility to ER stress and increased numbers of apoptotic oligodendrocytes were observed. Moreover, electron microscopic analysis demonstrated drastically reduced myelin formation accompanied by abnormal ER morphology. Thus, this study demonstrates the involvement of ER stress in pathogenic dysmyelination in the oligodendrocytes of PMD patients with the PLP1 missense mutation.

  18. Transcranial magnetic stimulation reveals two functionally distinct stages of motor cortex involvement during perception of emotional body language

    NARCIS (Netherlands)

    Borgomaneri, Sara; Gazzola, Valeria; Avenanti, Alessio

    Studies indicate that perceiving emotional body language recruits fronto-parietal regions involved in action execution. However, the nature of such motor activation is unclear. Using transcranial magnetic stimulation (TMS) we provide correlational and causative evidence of two distinct stages of

  19. Transcranial magnetic stimulation reveals two functionally distinct stages of motor cortex involvement during perception of emotional body language

    NARCIS (Netherlands)

    Borgomaneri, S.; Gazzola, V.; Avenanti, A.

    2015-01-01

    Studies indicate that perceiving emotional body language recruits fronto-parietal regions involved in action execution. However, the nature of such motor activation is unclear. Using transcranial magnetic stimulation (TMS) we provide correlational and causative evidence of two distinct stages of

  20. Distinct DNA repair pathways involving RecA and nonhomologous end joining in Mycobacterium smegmatis.

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    Korycka-Machala, Malgorzata; Brzostek, Anna; Rozalska, Sylwia; Rumijowska-Galewicz, Anna; Dziedzic, Renata; Bowater, Richard; Dziadek, Jaroslaw

    2006-05-01

    Mycobacterium smegmatis was used to study the relationship between DNA repair processes involving RecA and nonhomologous end joining (NHEJ). The effect of gene deletions in recA and/or in two genes involved in NHEJ (ku and ligD) was tested on the ability of bacteria to join breaks in plasmids transformed into them and in their response to chemicals that damage DNA. The results provide in vivo evidence that only NHEJ is required for the repair of noncompatible DNA ends. By contrast, the response of mycobacteria to mitomycin C preferentially involved a RecA-dependent pathway.

  1. Sodium-potassium ATPase 1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress.

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    Zatyka, Malgorzata; Ricketts, Christopher; da Silva Xavier, Gabriela; Minton, Jayne; Fenton, Sarah; Hofmann-Thiel, Sabine; Rutter, Guy A; Barrett, Timothy G

    2008-01-15

    Wolfram syndrome, an autosomal recessive disorder characterized by diabetes mellitus and optic atrophy, is caused by mutations in the WFS1 gene encoding an endoplasmic reticulum (ER) membrane protein, Wolframin. Although its precise functions are unknown, Wolframin deficiency increases ER stress, impairs cell cycle progression and affects calcium homeostasis. To gain further insight into its function and identify molecular partners, we used the WFS1-C-terminal domain as bait in a yeast two-hybrid screen with a human brain cDNA library. Na+/K+ ATPase beta1 subunit was identified as an interacting clone. We mapped the interaction to the WFS1 C-terminal and transmembrane domains, but not the N-terminal domain. Our mapping data suggest that the interaction most likely occurs in the ER. We confirmed the interaction by co-immunoprecipitation in mammalian cells and with endogenous proteins in JEG3 placental cells, neuroblastoma SKNAS and pancreatic MIN6 beta cells. Na+/K+ ATPase beta1 subunit expression was reduced in plasma membrane fractions of human WFS1 mutant fibroblasts and WFS1 knockdown MIN6 pancreatic beta-cells compared with wild-type cells; Na+/K+ ATPase alpha1 subunit expression was also reduced in WFS-depleted MIN6 beta cells. Induction of ER stress in wild-type cells only partly accounted for the reduced Na+/K+ ATPase beta1 subunit expression observed. We conclude that the interaction may be important for Na+/K+ ATPase beta1 subunit maturation; loss of this interaction may contribute to the pathology seen in Wolfram syndrome via reductions in sodium pump alpha1 and beta1 subunit expression in pancreatic beta-cells.

  2. Distinct DNA repair pathways involving RecA and nonhomologous end joining in Mycobacterium smegmatis.

    OpenAIRE

    Korycka-Machala, M; Brzostek, A; Rozalska, S; Rumijowska-Galewicz, A; Dziedzic, R; Bowater, R; Dziadek, J

    2006-01-01

    Mycobacterium smegmatis was used to study the relationship between DNA repair processes involving RecA and nonhomologous end joining (NHEJ). The effect of gene deletions in recA and/or in two genes involved in NHEJ (ku and ligD) was tested on the ability of bacteria to join breaks in plasmids transformed into them and in their response to chemicals that damage DNA. The results provide in vivo evidence that only NHEJ is required for the repair of noncompatible DNA ends. By contrast, the respon...

  3. Drosophila Ovipositor Extension in Mating Behavior and Egg Deposition Involves Distinct Sets of Brain Interneurons

    Science.gov (United States)

    Kimura, Ken-ichi; Sato, Chiaki; Koganezawa, Masayuki; Yamamoto, Daisuke

    2015-01-01

    Oviposition is a female-specific behavior that directly affects fecundity, and therefore fitness. If a fertilized female encounters another male that she has evaluated to be of better quality than her previous mate, it would be beneficial for her to remate with this male rather than depositing her eggs. Females who decided not to remate exhibited rejection behavior toward a courting male and engaged in oviposition. Although recent studies of Drosophila melanogaster identified sensory neurons and putative second-order ascending interneurons that mediate uterine afferents affecting female reproductive behavior, little is known about the brain circuitry that selectively activates rejection versus oviposition behaviors. We identified the sexually dimorphic pC2l and female-specific pMN2 neurons, two distinct classes of doublesex (dsx)-expressing neurons that can initiate ovipositor extension associated with rejection and oviposition behavior, respectively. pC2l interneurons, which induce ovipositor extrusion for rejection in females, have homologues that control courtship behavior in males. Activation of these two classes of neurons appears to be mutually exclusive and each governs hierarchical control of the motor program in the VNC either for rejection or oviposition, contributing centrally to the switching on or off of the alternative motor programs. PMID:25955600

  4. Are children conservative, liberal, or metacognitive? Preliminary evidence for the involvement of the distinctiveness heuristic in decision making.

    Science.gov (United States)

    Geurten, Marie; Willems, Sylvie; Meulemans, Thierry

    2015-04-01

    The experiment tested whether young children are able to reduce their false recognition rate after distinctive encoding by implementing a strategic metacognitive rule. The participants, 72 children aged 4, 6, and 9 years, studied two lists of unrelated items. One of these lists was visually displayed (picture condition), whereas the other was presented auditorily (word condition). After each study phase, participants completed recognition tests. Finally, they answered questions about their explicit knowledge of the distinctive encoding effect. The results revealed that even the youngest children in our sample showed a smaller proportion of intrusions in the picture condition than in the word condition. Furthermore, the results of the signal detection analyses were consistent with the hypothesis that the lower rate of false recognitions after picture encoding results from the implementation of a conservative response criterion based on metacognitive expectations (distinctiveness heuristic). Moreover, the absence of correlation between children's explicit knowledge of the distinctiveness rule and their effective use of this metacognitive heuristic seems to indicate that its involvement in memory decisions could be mediated by implicit mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Obesity is marked by distinct functional connectivity in brain networks involved in food reward and salience.

    Science.gov (United States)

    Wijngaarden, M A; Veer, I M; Rombouts, S A R B; van Buchem, M A; Willems van Dijk, K; Pijl, H; van der Grond, J

    2015-01-01

    We hypothesized that brain circuits involved in reward and salience respond differently to fasting in obese versus lean individuals. We compared functional connectivity networks related to food reward and saliency after an overnight fast (baseline) and after a prolonged fast of 48 h in lean versus obese subjects. We included 13 obese (2 males, 11 females, BMI 35.4 ± 1.2 kg/m(2), age 31 ± 3 years) and 11 lean subjects (2 males, 9 females, BMI 23.2 ± 0.5 kg/m(2), age 28 ± 3 years). Resting-state functional magnetic resonance imaging scans were made after an overnight fast (baseline) and after a prolonged 48 h fast. Functional connectivity of the amygdala, hypothalamus and posterior cingulate cortex (default-mode) networks was assessed using seed-based correlations. At baseline, we found a stronger connectivity between hypothalamus and left insula in the obese subjects. This effect diminished upon the prolonged fast. After prolonged fasting, connectivity of the hypothalamus with the dorsal anterior cingulate cortex (dACC) increased in lean subjects and decreased in obese subjects. Amygdala connectivity with the ventromedial prefrontal cortex was stronger in lean subjects at baseline, which did not change upon the prolonged fast. No differences in posterior cingulate cortex connectivity were observed. In conclusion, obesity is marked by alterations in functional connectivity networks involved in food reward and salience. Prolonged fasting differentially affected hypothalamic connections with the dACC and the insula between obese and lean subjects. Our data support the idea that food reward and nutrient deprivation are differently perceived and/or processed in obesity. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. RhoA Ambivalently Controls Prominent Myofibroblast Characteritics by Involving Distinct Signaling Routes.

    Directory of Open Access Journals (Sweden)

    Aline Jatho

    Full Text Available RhoA has been shown to be beneficial in cardiac disease models when overexpressed in cardiomyocytes, whereas its role in cardiac fibroblasts (CF is still poorly understood. During cardiac remodeling CF undergo a transition towards a myofibroblast phenotype thereby showing an increased proliferation and migration rate. Both processes involve the remodeling of the cytoskeleton. Since RhoA is known to be a major regulator of the cytoskeleton, we analyzed its role in CF and its effect on myofibroblast characteristics in 2 D and 3D models.Downregulation of RhoA was shown to strongly affect the actin cytoskeleton. It decreased the myofibroblast marker α-sm-actin, but increased certain fibrosis-associated factors like TGF-β and collagens. Also, the detailed analysis of CTGF expression demonstrated that the outcome of RhoA signaling strongly depends on the involved stimulus. Furthermore, we show that proliferation of myofibroblasts rely on RhoA and tubulin acetylation. In assays accessing three different types of migration, we demonstrate that RhoA/ROCK/Dia1 are important for 2D migration and the repression of RhoA and Dia1 signaling accelerates 3D migration. Finally, we show that a downregulation of RhoA in CF impacts the viscoelastic and contractile properties of engineered tissues.RhoA positively and negatively influences myofibroblast characteristics by differential signaling cascades and depending on environmental conditions. These include gene expression, migration and proliferation. Reduction of RhoA leads to an increased viscoelasticity and a decrease in contractile force in engineered cardiac tissue.

  7. The Protein Disulfide Isomerase of Botrytis cinerea: An ER Protein Involved in Protein Folding and Redox Homeostasis Influences NADPH Oxidase Signaling Processes

    Directory of Open Access Journals (Sweden)

    Robert Marschall

    2017-05-01

    Full Text Available Botrytis cinerea is a filamentous plant pathogen, which infects hundreds of plant species; within its lifestyle, the production of reactive oxygen species (ROS and a balanced redox homeostasis are essential parameters. The pathogen is capable of coping with the plant’s oxidative burst and even produces its own ROS to enhance the plant’s oxidative burst. Highly conserved NADPH oxidase (Nox complexes produce the reactive molecules. The membrane-associated complexes regulate a large variety of vegetative and pathogenic processes. Besides their commonly accepted function at the plasma membrane, recent studies reveal that Nox complexes are also active at the membrane of the endoplasmic reticulum. In this study, we identified the essential ER protein BcPdi1 as new interaction partner of the NoxA complex in B. cinerea. Mutants that lack this ER chaperone display overlapping phenotypes to mutants of the NoxA signaling pathway. The protein appears to be involved in all major developmental processes, such as the formation of sclerotia, conidial anastomosis tubes and infection cushions (IC’s and is needed for full virulence. Moreover, expression analyses and reporter gene studies indicate that BcPdi1 affects the redox homeostasis and unfolded protein response (UPR-related genes. Besides the close association between BcPdi1 and BcNoxA, interaction studies provide evidence that the ER protein might likewise be involved in Ca2+ regulated processes. Finally, we were able to show that the potential key functions of the protein BcPdi1 might be affected by its phosphorylation state.

  8. Transcranial magnetic stimulation reveals two functionally distinct stages of motor cortex involvement during perception of emotional body language.

    Science.gov (United States)

    Borgomaneri, Sara; Gazzola, Valeria; Avenanti, Alessio

    2015-09-01

    Studies indicate that perceiving emotional body language recruits fronto-parietal regions involved in action execution. However, the nature of such motor activation is unclear. Using transcranial magnetic stimulation (TMS) we provide correlational and causative evidence of two distinct stages of motor cortex engagement during emotion perception. Participants observed pictures of body expressions and categorized them as happy, fearful or neutral while receiving TMS over the left or right motor cortex at 150 and 300 ms after picture onset. In the early phase (150 ms), we observed a reduction of excitability for happy and fearful emotional bodies that was specific to the right hemisphere and correlated with participants' disposition to feel personal distress. This 'orienting' inhibitory response to emotional bodies was also paralleled by a general drop in categorization accuracy when stimulating the right but not the left motor cortex. Conversely, at 300 ms, greater excitability for negative, positive and neutral movements was found in both hemispheres. This later motor facilitation marginally correlated with participants' tendency to assume the psychological perspectives of others and reflected simulation of the movement implied in the neutral and emotional body expressions. These findings highlight the motor system's involvement during perception of emotional bodies. They suggest that fast orienting reactions to emotional cues--reflecting neural processing necessary for visual perception--occur before motor features of the observed emotional expression are simulated in the motor system and that distinct empathic dispositions influence these two neural motor phenomena. Implications for theories of embodied simulation are discussed.

  9. Proteins Involved in Distinct Phases of Cold Hardening Process in Frost Resistant Winter Barley (Hordeum vulgare L. cv Luxor

    Directory of Open Access Journals (Sweden)

    Radovan Hynek

    2013-04-01

    Full Text Available Winter barley is an economically important cereal crop grown in higher latitudes and altitudes where low temperatures represent an important environmental constraint limiting crop productivity. In this study changes in proteome of leaves and crowns in a frost tolerant winter barley cv. Luxor in relation to short and long term periods of cold followed by a brief frost treatment were studied in order to disclose proteins responsible for the cold hardening process in distinct plant tissues. The mentioned changes have been monitored using two dimensional difference gel electrophoresis (2D-DIGE with subsequent peptide-mapping protein identification. Regarding approximately 600–700 distinct protein spots detected on 2D gels, there has been found at least a two-fold change after exposure to low temperatures in about 10% of proteins in leaves and 13% of proteins in crowns. Protein and nitrogen metabolic processes have been influenced by low temperature to a similar extent in both tissues while catabolism, carbohydrate metabolism and proteins involved in stress response have been more affected in crowns than in leaves. The range of changes in protein abundance was generally higher in leaves and chloroplast proteins were frequently affected which suggests a priority to protect photosynthetic apparatus. Overall, our data proved existence of slightly different response strategies to low temperature stress in crowns and leaves, i.e., tissues with different biological role. Moreover, there have been found several proteins with large increase in accumulation, e.g., 33 kDa oxygen evolving protein of photosystem II in leaves and “enhanced disease susceptibility 1” in crowns; these proteins might have potential to indicate an enhanced level of frost tolerance in barley.

  10. The protein pheromone Er-1 of the ciliate Euplotes raikovi stimulates human T-cell activity: Involvement of interleukin-2 system

    Energy Technology Data Exchange (ETDEWEB)

    Cervia, Davide, E-mail: d.cervia@unitus.it [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Department of Biomedical and Clinical Sciences, “Luigi Sacco” University Hospital, University of Milan, Milano (Italy); Catalani, Elisabetta; Belardinelli, Maria Cristina [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Perrotta, Cristiana [Department of Biomedical and Clinical Sciences, “Luigi Sacco” University Hospital, University of Milan, Milano (Italy); Picchietti, Simona [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Alimenti, Claudio [Department of Environmental and Natural Sciences, University of Camerino, Camerino (Italy); Casini, Giovanni; Fausto, Anna Maria [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Vallesi, Adriana [Department of Environmental and Natural Sciences, University of Camerino, Camerino (Italy)

    2013-02-01

    Water-soluble protein signals (pheromones) of the ciliate Euplotes have been supposed to be functional precursors of growth factors and cytokines that regulate cell–cell interaction in multi-cellular eukaryotes. This work provides evidence that native preparations of the Euplotes raikovi pheromone Er-1 (a helical protein of 40 amino acids) specifically increases viability, DNA synthesis, proliferation, and the production of interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-2, and IL-13 in human Jurkat T-cells. Also, Er-1 significantly decreases the mRNA levels of the β and γ subunits of IL-2 receptor (IL-2R), while the mRNA levels of the α subunit appeared to be not affected. Jurkat T-cell treatments with Er-1 induced the down-regulation of the IL-2Rα subunit by a reversible and time-dependent endocytosis, and increased the levels of phosphorylation of the extracellular signal-regulated kinases (ERK). The cell-type specificity of these effects was supported by the finding that Er-1, although unable to directly influence the growth of human glioma U-373 cells, induced Jurkat cells to synthesize and release factors that, in turn, inhibited the U-373 cell proliferation. Overall, these findings imply that Er-1 coupling to IL-2R and ERK immuno-enhances T-cell activity, and that this effect likely translates to an inhibition of glioma cell growth. -- Highlights: ► Euplotes pheromone Er-1 increases the growth of human Jurkat T-cells. ► Er-1 increases the T-cell production of specific cytokines. ► Er-1 activates interleukin-2 receptor and extracellular signal-regulated kinases. ► The immuno-enhancing effect of Er-1 on Jurkat cells translates to an inhibition of human glioma cell growth.

  11. The PERK-eIF2α signaling pathway is involved in TCDD-induced ER stress in PC12 cells.

    Science.gov (United States)

    Duan, Zhiqing; Zhao, Jianya; Fan, Xikang; Tang, Cuiying; Liang, Lingwei; Nie, Xiaoke; Liu, Jiao; Wu, Qiyun; Xu, Guangfei

    2014-09-01

    Studies have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces apoptotic cell death in neuronal cells. However, whether this is the result of endoplasmic reticulum (ER) stress-mediated apoptosis remains unknown. In this study, we determined whether ER stress plays a role in the TCDD-induced apoptosis of pheochromocytoma (PC12) cells and primary neurons. PC12 cells were exposed to different TCDD concentrations (1, 10, 100, 200, or 500nM) for varying lengths of time (1, 3, 6, 12, or 24h). TCDD concentrations much higher than 10nM (100, 200, or 500nM) markedly increased glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) levels, which are hallmarks of ER stress. We also evaluated the effects of TCDD on ER morphology in PC12 cells and primary neurons that were treated with different TCDD concentrations (1, 10, 50, or 200nM) for 24h. Ultrastructural ER alterations were observed with transmission electron microscopy in PC12 cells and primary neurons treated with high concentrations of TCDD. Furthermore, TCDD-induced ER stress significantly promoted the activation of the PKR-like ER kinase (PERK), a sensor for the unfolded protein response (UPR), and its downstream target eukaryotic translation initiation factor 2 α (eIF2α); in contrast, TCDD did not appear to affect inositol-requiring enzyme 1 (IRE1) and activating transcription factor 6 (ATF6), two other UPR sensors. Importantly, TCDD significantly inhibited eIF2α phosphorylation and triggered apoptosis in PC12 cells after 6-24h of treatment. Salubrinal, which activates the PERK-eIF2α pathway, significantly enhanced eIF2α phosphorylation in PC12 cells and attenuated the TCDD-induced cell death. In contrast, knocking down eIF2α using small interfering RNA markedly enhanced TCDD-induced cell death. Together, these results indicate that the PERK-eIF2α pathway plays an important role in TCDD-induced ER stress and apoptosis in PC12 cells. Copyright © 2014 Elsevier Inc. All rights

  12. Two distinct olfactory bulb sublaminar networks involved in gamma and beta oscillation generation: a CSD study in the anesthetized rat.

    Directory of Open Access Journals (Sweden)

    Nicolas eFourcaud-Trocmé

    2014-07-01

    Full Text Available A prominent feature of olfactory bulb (OB dynamics is the expression of characteristic local field potential (LFP rhythms, including a slow respiration-related rhythm and two fast alternating oscillatory rhythms, beta (15-30 Hz and gamma (40-90 Hz. All of these rhythms are implicated in olfactory coding. Fast oscillatory rhythms are known to involve the mitral-granule cell loops. Although the underlying mechanisms of gamma oscillation have been studied, the origin of beta oscillation remains poorly understood. Whether these two different rhythms share the same underlying mechanism is unknown. This study uses a quantitative and detailed current-source density analysis combined with multi-unit activity recordings to shed light on this question in freely breathing anesthetized rats. In particular, we show that gamma oscillation generation involves mainly upper half of the external plexiform layer (EPL and superficial areas of granule cell layer. In contrast, the generation of beta oscillation involves the lower part of the EPL and deep granule cells. This differential involvement of sublaminar networks is neither dependent on odor quality nor on the precise frequency of the fast oscillation under study. Overall, this study demonstrates a functional sublaminar organization of the rat OB, which is supported by previous anatomical findings.

  13. Transcriptional Control of Dual Transporters Involved in α-Ketoglutarate Utilization Reveals Their Distinct Roles in UropathogenicEscherichia coli.

    Science.gov (United States)

    Cai, Wentong; Cai, Xuwang; Yang, Yongwu; Yan, Shigan; Zhang, Haibin

    2017-01-01

    conditions. Therefore, different transcriptional regulation led to distinct roles played by C5038 and KgtP in KG utilization and fitness in vivo . This study thus potentially expanded our understanding of UPEC pathobiology.

  14. Erv41p and Erv46p: New components of COPII vesicles involved in transport between the ER and Golgi complex

    DEFF Research Database (Denmark)

    Otte, S; Belden, W J; Heidtman, M

    2001-01-01

    , Erv29p, Yif1p, Erv41p, Erv46p, and Emp47p) that had not been localized to ER vesicles. Using antibodies, we demonstrate that these proteins are selectively and efficiently packaged into COPII vesicles. Three of the newly identified vesicle proteins (Erv29p, Erv41p, and Erv46p) represent......Proteins contained on purified COPII vesicles were analyzed by matrix-assisted laser desorption ionization mass spectrometry combined with database searching. We identified four known vesicle proteins (Erv14p, Bet1p, Emp24p, and Erv25p) and an additional nine species (Yip3p, Rer1p, Erp1p, Erp2p...... uncharacterized integral membrane proteins that are conserved across species. Erv41p and Erv46p were further characterized. These proteins colocalized to ER and Golgi membranes and exist in a detergent-soluble complex that was isolated by immunoprecipitation. Yeast strains lacking Erv41p and/or Erv46p are viable...

  15. Single-organ gallbladder vasculitis: characterization and distinction from systemic vasculitis involving the gallbladder. An analysis of 61 patients.

    Science.gov (United States)

    Hernández-Rodríguez, José; Tan, Carmela D; Rodríguez, E René; Hoffman, Gary S

    2014-11-01

    Systemic vasculitis (SV) involving abdominal structures usually has a poor prognosis. Gallbladder vasculitis (GV) has been reported as part of SV (GB-SV) and focal single-organ vasculitis (GB-SOV). We analyzed clinical and histologic characteristics of patients with GV to identify features that differentiate GB-SOV from the systemic forms of GV. To identify affected patients with GV we used pathology databases from our institution and an English-language PubMed search. Clinical manifestations, laboratory and histologic features, treatment administered, and outcomes were recorded. Patients were divided in 2 groups, GB-SOV and GB-SV. As in previous studies of single-organ vasculitis, GB-SOV was only considered to be a sustainable diagnosis if disease beyond the gallbladder was not apparent after a follow-up period of at least 6 months. Sixty-one well-characterized patients with GV were included (6 from our institution). There was no significant sex bias (32 female patients, 29 male). Median age was 52 years (range, 18-94 yr). GB-SOV was found in 20 (33%) and GB-SV in 41 (67%) patients. No differences were observed in age, sex frequency, or duration of gallbladder symptoms between groups. Past episodes of recurrent right-upper quadrant or abdominal pain and lithiasic cholecystitis were more frequent in GB-SOV patients, whereas acalculous cholecystitis occurred more often in GB-SV. In GB-SV, gallbladder-related symptoms occurred more often concomitantly with or after the systemic features, but they sometimes appeared before SV was fully developed (13.5%). Constitutional and musculoskeletal symptoms were reported only in GB-SV patients. Compared to GB-SOV, GB-SV patients presented more often with fever (62.5% vs 20%; p = 0.003) and exhibited higher erythrocyte sedimentation rate levels (80 ± 28 vs 37 ± 25 mm/h, respectively; p = 0.006). All GB-SV patients required glucocorticoids and 50% of them also received cytotoxic agents. Mortality in GB-SV was

  16. ER Stress and Lipid Metabolism in Adipocytes

    Directory of Open Access Journals (Sweden)

    Beth S. Zha

    2012-01-01

    Full Text Available The role of endoplasmic reticulum (ER stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance.

  17. Distinct regions of the large extracellular domain of tetraspanin CD9 are involved in the control of human multinucleated giant cell formation.

    Directory of Open Access Journals (Sweden)

    Rachel S Hulme

    Full Text Available Multinucleated giant cells, formed by the fusion of monocytes/macrophages, are features of chronic granulomatous inflammation associated with infections or the persistent presence of foreign material. The tetraspanins CD9 and CD81 regulate multinucleated giant cell formation: soluble recombinant proteins corresponding to the large extracellular domain (EC2 of human but not mouse CD9 can inhibit multinucleated giant cell formation, whereas human CD81 EC2 can antagonise this effect. Tetraspanin EC2 are all likely to have a conserved three helix sub-domain and a much less well-conserved or hypervariable sub-domain formed by short helices and interconnecting loops stabilised by two or more disulfide bridges. Using CD9/CD81 EC2 chimeras and point mutants we have mapped the specific regions of the CD9 EC2 involved in multinucleated giant cell formation. These were primarily located in two helices, one in each sub-domain. The cysteine residues involved in the formation of the disulfide bridges in CD9 EC2 were all essential for inhibitory activity but a conserved glycine residue in the tetraspanin-defining 'CCG' motif was not. A tyrosine residue in one of the active regions that is not conserved between human and mouse CD9 EC2, predicted to be solvent-exposed, was found to be only peripherally involved in this activity. We have defined two spatially-distinct sites on the CD9 EC2 that are required for inhibitory activity. Agents that target these sites could have therapeutic applications in diseases in which multinucleated giant cells play a pathogenic role.

  18. Interaction of the amyloid precursor protein-like protein 1 (APLP1) E2 domain with heparan sulfate involves two distinct binding modes

    Energy Technology Data Exchange (ETDEWEB)

    Dahms, Sven O., E-mail: sdahms@fli-leibniz.de [Leibniz Institute for Age Research (FLI), Beutenbergstrasse 11, 07745 Jena (Germany); Mayer, Magnus C. [Freie Universität Berlin, Thielallee 63, 14195 Berlin (Germany); Miltenyi Biotec GmbH, Robert-Koch-Strasse 1, 17166 Teterow (Germany); Roeser, Dirk [Leibniz Institute for Age Research (FLI), Beutenbergstrasse 11, 07745 Jena (Germany); Multhaup, Gerd [McGill University Montreal, Montreal, Quebec H3G 1Y6 (Canada); Than, Manuel E., E-mail: sdahms@fli-leibniz.de [Leibniz Institute for Age Research (FLI), Beutenbergstrasse 11, 07745 Jena (Germany)

    2015-03-01

    Two X-ray structures of APLP1 E2 with and without a heparin dodecasaccharide are presented, revealing two distinct binding modes of the protein to heparan sulfate. The data provide a mechanistic explanation of how APP-like proteins bind to heparan sulfates and how they specifically recognize nonreducing structures of heparan sulfates. Beyond the pathology of Alzheimer’s disease, the members of the amyloid precursor protein (APP) family are essential for neuronal development and cell homeostasis in mammals. APP and its paralogues APP-like protein 1 (APLP1) and APP-like protein 2 (APLP2) contain the highly conserved heparan sulfate (HS) binding domain E2, which effects various (patho)physiological functions. Here, two crystal structures of the E2 domain of APLP1 are presented in the apo form and in complex with a heparin dodecasaccharide at 2.5 Å resolution. The apo structure of APLP1 E2 revealed an unfolded and hence flexible N-terminal helix αA. The (APLP1 E2){sub 2}–(heparin){sub 2} complex structure revealed two distinct binding modes, with APLP1 E2 explicitly recognizing the heparin terminus but also interacting with a continuous heparin chain. The latter only requires a certain register of the sugar moieties that fits to a positively charged surface patch and contributes to the general heparin-binding capability of APP-family proteins. Terminal binding of APLP1 E2 to heparin specifically involves a structure of the nonreducing end that is very similar to heparanase-processed HS chains. These data reveal a conserved mechanism for the binding of APP-family proteins to HS and imply a specific regulatory role of HS modifications in the biology of APP and APP-like proteins.

  19. Hvem er vi? Hvem er de?

    DEFF Research Database (Denmark)

    Kryger, Niels

    2016-01-01

    Kommentaren tager afsæt i initiativer i de pædagogiske faglige foreninger i Europa EERA) og i Norden (NERA) og argumenterer for at det er forpligtelse for os som nordiske og europæiske pædagogiske forskere at gå op imod de stadigt mere ekskluderende vi-konstruktioner, som er blevet formuleret i f...

  20. Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

    Science.gov (United States)

    Bravo, Roberto; Gutierrez, Tomás; Paredes, Felipe; Gatica, Damián; Rodriguez, Andrea E.; Pedrozo, Zully; Chiong, Mario; Parra, Valentina; Quest, Andrew F.G.; Rothermel, Beverly A.; Lavandero, Sergio

    2014-01-01

    Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER–mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID:22064245

  1. Ideologi er noget bras

    DEFF Research Database (Denmark)

    Hansen, Brian Benjamin; Jøker Bjerre, Henrik

    medieområdet kan dette skifte betragtes som den endelige sejr for den post-ideologiske konsensus, der går ud fra, at der ikke mere er behov for politisk diskussion, og at vi aldrig mere skal indlade os på farlige politiske eksperimenter. Ideologi er noget bras, sagde jo allerede Poul Schlüter. Med inspiration......, ideologiske ramme for vore liv. Ideologi er noget bras, men bras er også ideologi....

  2. Puf er plat

    DEFF Research Database (Denmark)

    Hansen, Pelle Guldborg; Zeller, Clara

    2015-01-01

    Der er stort set ingen, der har fattet, hvad nudging egentlig er. Et nudge er nemlig hverken ”et lille blidt skub”, eller ”en helt ny videnskabelig metode [der] kan ændre vores adfærd, uden vi opdager det - og uden det koster os noget”, ligesom det heller ikke er ”en måde at friste kunder til at ...

  3. The MyD88 protein 88 pathway is differently involved in immune responses induced by distinct substrains of Leishmania major.

    Science.gov (United States)

    Revaz-Breton, Mélanie; Ronet, Catherine; Ives, Annette; Torre, Yazmin Hauyon-La; Masina, Slavica; Tacchini-Cottier, Fabienne; Launois, Pascal

    2010-06-01

    Host resistance to Leishmania major is highly dependent on the development of a Th1 immune response. The TLR adaptator myeloid differentiation protein 88 (MyD88) has been implicated in the Th1 immune response associated with the resistant phenotype observed in C57BL/6 mice after infection with L. major. To investigate whether the MyD88 pathway is differentially used by distinct substrains of parasites, MyD88(-/-) C57BL/6 mice were infected with two substrains of L. major, namely L. major LV39 and L. major IR75. MyD88(-/-) mice were susceptible to both substrains of L. major, although with different kinetics of infection. The mechanisms involved during the immune response associated with susceptibility of MyD88(-/-) mice to L. major is however, parasite substrain-dependent. Susceptibility of MyD88(-/-) mice infected with L. major IR75 is a consequence of Th2 immune-deviation, whereas susceptibility of MyD88(-/-) mice to infection with L. major LV39 resulted from an impaired Th1 response. Depletion of regulatory T cells (Treg) partially restored IFN-gamma secretion and the Th1 immune response in MyD88(-/-) mice infected with L. major LV39, demonstrating a role of Treg activity in the development of an impaired Th1 response in these mice.

  4. Two Sets of Piwi Proteins Are Involved in Distinct sRNA Pathways Leading to Elimination of Germline-Specific DNA

    Directory of Open Access Journals (Sweden)

    Dominique I. Furrer

    2017-07-01

    Full Text Available Piwi proteins and piRNAs protect eukaryotic germlines against the spread of transposons. During development in the ciliate Paramecium, two Piwi-dependent sRNA classes are involved in the elimination of transposons and transposon-derived DNA: scan RNAs (scnRNAs, associated with Ptiwi01 and Ptiwi09, and iesRNAs, whose binding partners we now identify as Ptiwi10 and Ptiwi11. scnRNAs derive from the maternal genome and initiate DNA elimination during development, whereas iesRNAs continue DNA targeting until the removal process is complete. Here, we show that scnRNAs and iesRNAs are processed by distinct Dicer-like proteins and bind Piwi proteins in a mutually exclusive manner, suggesting separate biogenesis pathways. We also demonstrate that the PTIWI10 gene is transcribed from the developing nucleus and that its transcription depends on prior DNA excision, suggesting a mechanism of gene expression control triggered by the removal of short DNA segments interrupting the gene.

  5. The use of global transcriptional analysis to reveal the biological and cellular events involved in distinct development phases of Trichophyton rubrum conidial germination

    Directory of Open Access Journals (Sweden)

    Ding Guohui

    2007-04-01

    Full Text Available Abstract Background Conidia are considered to be the primary cause of infections by Trichophyton rubrum. Results We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the Saccharomyces Genome Database (SGD. A number of homologues of Saccharomyces cerevisiae genes related to signalling pathways and some important cellular processes were found to be involved in T. rubrum germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions. Conclusion Our results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of T. rubrum.

  6. Cybermagt er spoilermagt

    DEFF Research Database (Denmark)

    Nyemann, Dorthe Bach

    Cybermagt er spoilermagt. Det er overskriften på denne rapport, hvis hovedformål er at indkredse, hvilken rolle magt i cyberspace spiller for forholdet mellem stater. Rapporten undersøger cybermagtens centrale betydning for den øgede destabilisering af internationale relationer, mens den samtidig...... cyberspace via fælles initiativer....

  7. Man er aldrig alene

    DEFF Research Database (Denmark)

    Hoffmeyer, Jesper

    2013-01-01

    Nu ved vi, at der er mange slags DNA i vores krop, og at samarbejdet mellem de organismer, som bærer alt dette DNA, er essentielt for vores overlevelse" … "Kroppen er en slags økosystem, hvor alle slags samarbejde hen ad vejen bliver afprøvet"...

  8. Er alt design?

    DEFF Research Database (Denmark)

    Michelsen, Anders Ib; Engholm, Ida

    2016-01-01

    Design er et ord med mange betydninger. Hvad enten design er det, der kommer ud af en shoppingtur, om det indgår i et dannelsesbegreb, hvor den kultiverede og ”gode stol” har sin plads, er en uddannelse med forskning underneden eller en strategisk indsats for velfærdssamfundets forvandling til et...

  9. Effects of material growth technique and Mg doping on Er3+ photoluminescence in Er-implanted GaN

    International Nuclear Information System (INIS)

    Kim, S.; Henry, R. L.; Wickenden, A. E.; Koleske, D. D.; Rhee, S. J.; White, J. O.; Myoung, J. M.; Kim, K.; Li, X.; Coleman, J. J.

    2001-01-01

    Photoluminescence (PL) and photoluminescence excitation (PLE) spectroscopies have been carried out at 6 K on the ∼1540 nm 4 I 13/2 - 4 I 15/2 emissions of Er 3+ in Er-implanted and annealed GaN. These studies revealed the existence of multiple Er 3+ centers and associated PL spectra in Er-implanted GaN films grown by metalorganic chemical vapor deposition, hydride vapor phase epitaxy, and molecular beam epitaxy. The results demonstrate that the multiple Er 3+ PL centers and below-gap defect-related absorption bands by which they are selectively excited are universal features of Er-implanted GaN grown by different techniques. It is suggested that implantation-induced defects common to all the GaN samples are responsible for the Er site distortions that give rise to the distinctive, selectively excited Er 3+ PL spectra. The investigations of selectively excited Er 3+ PL and PLE spectra have also been extended to Er-implanted samples of Mg-doped GaN grown by various techniques. In each of these samples, the so-called violet-pumped Er 3+ PL band and its associated broad violet PLE band are significantly enhanced relative to the PL and PLE of the other selectively excited Er 3+ PL centers. More importantly, the violet-pumped Er 3+ PL spectrum dominates the above-gap excited Er 3+ PL spectrum of Er-implanted Mg-doped GaN, whereas it was unobservable under above-gap excitation in Er-implanted undoped GaN. These results confirm the hypothesis that appropriate codopants can increase the efficiency of trap-mediated above-gap excitation of Er 3+ emission in Er-implanted GaN. [copyright] 2001 American Institute of Physics

  10. Materials for ER Fluids

    Science.gov (United States)

    Bloodworth, Robert; Wendt, Eckhard

    Recent improvements in the physical understanding of ER fluids have led to the rational design of new ER materials with improved properties. This paper gives an overview of several recent developments in the formulation of ER fluids, concentrating on new particulate phases for ER dispersions. Examples of homogeneous ER fluids are also discussed. The trend leading to designed ER dispersions is demonstrated by a new class of electrorheological fluids based on non-aqueous polyurethane dispersions. The fluids exhibit an attractive combination of properties: low viscosity, high ER effect, and low conductivity. The dispersed phase consists of a specially developed polyurethane elastomer which solvates and stabilizes metal salts. The polymer network density influences the mobility of the dissolved ions, allowing a surprising degree of control over the ER effect. Properties such as the field strength dependence of the ER-effect, switching response, and conductivity of these fluids correlate directly with changes in the polymer structure. Electrorheological measurements in a couette viscometer (shear-mode) and in a model shock absorber (flow-mode) using a commercial polyurethane-based fluid show that the ER effect is also dependent upon the shearing geometry.

  11. Temporal clustering of gene expression links the metabolic transcription factor HNF4α to the ER stress-dependent gene regulatory network

    Directory of Open Access Journals (Sweden)

    Angela M Arensdorf

    2013-09-01

    Full Text Available The unfolded protein response (UPR responds to disruption of endoplasmic reticulum (ER function by initiating signaling cascades that ultimately culminate in extensive transcriptional regulation. Classically, this regulation includes genes encoding ER chaperones, ER-associated degradation factors, and others involved in secretory protein folding and processing, and is carried out by the transcriptional activators that are produced as a consequence of UPR activation. However, up to half of the mRNAs regulated by ER stress are downregulated rather than upregulated, and the mechanisms linking ER stress and UPR activation to mRNA suppression are poorly understood. To begin to address this issue, we used a bottom-up approach to study the metabolic gene regulatory network controlled by the UPR in the liver, because ER in the liver stress leads to lipid accumulation, and fatty liver disease is the most common liver disease in the western world. qRT-PCR profiling of mouse liver mRNAs during ER stress revealed that suppression of the transcriptional regulators C/EBPα, PPARα, and PGC-1α preceded lipid accumulation, and was then followed by suppression of mRNAs encoding key enzymes involved in fatty acid oxidation and lipoprotein biogenesis and transport. Mice lacking the ER stress sensor ATF6α, which experience persistent ER stress and profound lipid accumulation during challenge, were then used as the basis for a functional genomics approach that allowed genes to be grouped into distinct expression profiles. This clustering predicted that ER stress would suppress the activity of the metabolic transcriptional regulator HNF4α--a finding subsequently confirmed by chromatin immunopreciptation at the Cebpa and Pgc1a promoters. Our results establish a framework for hepatic gene regulation during ER stress and suggest that HNF4α occupies the apex of that framework. They also provide a unique resource for the community to further explore the temporal

  12. Different clinical importance of FLT3 internal tandem duplications in AML according to FAB classification: possible existence of distinct leukemogenesis involving monocyte differentiation pathway.

    Science.gov (United States)

    Koh, Youngil; Park, Juwon; Ahn, Kwang-Sung; Kim, Inho; Bang, Soo-Mee; Lee, Jae-Hoon; Yoon, Sung-Soo; Soon Lee, Dong; Yiul Lee, Young; Park, Seonyang; Kim, Byung-Kook

    2009-11-01

    morphologic profile. FLT3-ITD is a predictive and prognostic marker only in monocyte lineage patients. This result suggests an existence of distinct subset of monocyte lineage AML with leukemogenesis involving FLT3 activating pathway.

  13. Vreden er over os

    DEFF Research Database (Denmark)

    Mehlsen, Camilla

    2006-01-01

    Urolige elever, cyklister - der giver fuck-finger, aggressive demonstranter. Samtiden er på vej ind i en æra domineret af vrede, siger rektor Lars-Henrik Schmidt, der er aktuel med bogen 'Om vreden'. Udgivelsesdato: Juni...

  14. Comparative analysis of yellow microbial communities growing on the walls of geographically distinct caves indicates a common core of microorganisms involved in their formation.

    Science.gov (United States)

    Porca, Estefania; Jurado, Valme; Žgur-Bertok, Darja; Saiz-Jimenez, Cesareo; Pašić, Lejla

    2012-07-01

    Morphologically similar microbial communities that often form on the walls of geographically distinct limestone caves have not yet been comparatively studied. Here, we analysed phylotype distribution in yellow microbial community samples obtained from the walls of distinct caves located in Spain, Czech Republic and Slovenia. To infer the level of similarity in microbial community membership, we analysed inserts of 474 16S rRNA gene clones and compared those using statistical tools. The results show that the microbial communities under investigation are composed solely of Bacteria. The obtained phylotypes formed three distinct groups of operational taxonomic units (OTUs). About 60% of obtained sequences formed three core OTUs common to all three sampling sites. These were affiliated with actinobacterial Pseudonocardinae (30-50% of sequences in individual sampling site libraries), but also with gammaproteobacterial Chromatiales (6-25%) and Xanthomonadales (0.5-2.0%). Another 7% of sequences were common to two sampling sites and formed eight OTUs, while the remaining 35% were site specific and corresponded mostly to OTUs containing single sequences. The same pattern was observed when these data were compared with sequence data available from similar studies. This comparison showed that distinct limestone caves support microbial communities composed mostly of phylotypes common to all sampling sites. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  15. MIT HJEM ER HVOR MIT HJERTE ER

    DEFF Research Database (Denmark)

    Høst, Jeppe Engset

    2014-01-01

    Ideen om at arbejde med det man kalder de stedbundne ressourcer på en ny måde, er relevant på Bornholm hvor events som blandt andet festivalen ’Wonderfestiwall’, strandfesten ’Vang Pier Beach Party’, karnevallet ’Svaneke Beach Party, kokkekonkurrencen ’Sol over Gudhjem’ og filmfestivalen ’Bornsho...

  16. Pancreatic insulin content regulation by the estrogen receptor ER alpha.

    Directory of Open Access Journals (Sweden)

    Paloma Alonso-Magdalena

    Full Text Available The function of pancreatic beta-cells is the synthesis and release of insulin, the main hormone involved in blood glucose homeostasis. Estrogen receptors, ER alpha and ER beta, are important molecules involved in glucose metabolism, yet their role in pancreatic beta-cell physiology is still greatly unknown. In this report we show that both ER alpha and ER beta are present in pancreatic beta-cells. Long term exposure to physiological concentrations of 17beta-estradiol (E2 increased beta-cell insulin content, insulin gene expression and insulin release, yet pancreatic beta-cell mass was unaltered. The up-regulation of pancreatic beta-cell insulin content was imitated by environmentally relevant doses of the widespread endocrine disruptor Bisphenol-A (BPA. The use of ER alpha and ER beta agonists as well as ER alphaKO and ER betaKO mice suggests that the estrogen receptor involved is ER alpha. The up-regulation of pancreatic insulin content by ER alpha activation involves ERK1/2. These data may be important to explain the actions of E2 and environmental estrogens in endocrine pancreatic function and blood glucose homeostasis.

  17. er 2000

    DEFF Research Database (Denmark)

    Jensen, J. P.; Søndergaard, M.; Jeppesen, E.

    -kommunale data og rapporter af over-vågningen af de ferske vande. Rapporten Marine områder - Status over miljøtilstanden i 2000 er ba-seret på amtskommunale data og rapporter af overvågningen af kystvande og fjorde samt Dan-marks Miljøundersøgel-sers og vore nabolandes over-vågning af de åbne havområder....... Rapporten Landover-vågningsoplande er baseret på data indbe-rettet af amtskommuner-ne fra 7 overvågnings-oplande og er ud-arbejdet i samarbejde med Danmarks Geologi-ske Un-dersøgel-ser. Endelig er rapporten Atmosfærisk deposition 2000 baseret på Danmarks Miljø-undersø-gelsers overvågning af luftkvaliteten i...

  18. Jeg Er blevet FRANKofil

    DEFF Research Database (Denmark)

    Andersson, Lasse

    2014-01-01

    forhold til Frank, så har jeg holdt mig i skindet og har 5 timer tilbage med iPad og Frank Underwood….og hvilke timer! Hvorfor bruger jeg nu min klumme på Frank og Netflix? For det første så er House of Cards i mine øjne kunst og kultur. For det andet så er det sikkert, at streaming-tjenesterne kommer til...

  19. er 1999

    DEFF Research Database (Denmark)

    Jensen, J. P.; Søndergaard, M.; Jeppesen, E.

    små cladoceer og hjuldyr, og især er maksimumsforekom-sterne af calanoide vandlopper og de små og store cladoceer og daf-nier gået tilbage. Den gennemsnitlige biomasse af dafnier er derimod øget især p.g.a. stigning i de 25 % af søerne med størst forekomster. Dyreplanktons græsning Betragtet under et...

  20. Possible involvement of distinct phylogenetic clusters of HIV-1 variants in the discrepancies between coreceptor tropism predictions based on viral RNA and proviral DNA.

    Science.gov (United States)

    Kotani, Hiroshi; Sudo, Koji; Hasegawa, Naoki; Fujiwara, Hiroshi; Hayakawa, Tomohisa; Iketani, Osamu; Yamaguchi, Masaya; Mochizuki, Mayumi; Iwata, Satoshi; Kato, Shingo

    2016-01-01

    The coreceptor tropism testing should be conducted prior to commencing a regimen containing a CCR5 antagonist for treatment of HIV-1 infection. For aviremic patients on long antiretroviral therapy, proviral DNA is often used instead of viral RNA in genotypic tropism testing. However, the tropism predictions from RNA and DNA are sometimes different. We examined the cause of the discrepancies between HIV-1 tropism predictions based on viral RNA and proviral DNA. The nucleotide sequence of the env C2V3C3 region was determined using pair samples of plasma RNA and peripheral blood mononuclear cell DNA from 50 HIV-1 subtype B-infected individuals using population-based sequencing. The samples with discrepant tropism assessments between RNA and DNA were further analyzed using deep sequencing, followed by phylogenetic analysis. The tropism was assessed using the algorithm geno2pheno with a false-positive rate cutoff of 10 %. In population-based sequencing, five of 50 subjects showed discrepant tropism predictions between their RNA and DNA samples: four exhibited R5 tropism in RNA and X4 tropism in DNA, while one exhibited the opposite pattern. In the deep sequencing and phylogenetic analysis, three subjects had single clusters comprising of RNA- and DNA-derived sequences that were a mixture of R5 and X4 sequences. The other two subjects had two and three distinct phylogenetic clusters of sequences, respectively, each of which was dominated by R5 or X4 sequences; sequences of the R5-dominated cluster were mostly found in RNA, while sequences of the X4-dominated cluster were mostly in DNA. Some of HIV-1 tropism discrepancies between viral RNA and proviral DNA seem to be caused by phylogenetically distinct clusters which resides in plasma and cells in different frequencies. Our findings suggest that the tropism testing using PBMC DNA or deep sequencing may be required when the viral load is not suppressed or rebounds in the course of a CCR5 antagonist-containing regimen.

  1. Distinct effects of estrogen receptor antagonism on object recognition and spatial memory consolidation in ovariectomized mice.

    Science.gov (United States)

    Kim, Jaekyoon; Frick, Karyn M

    2017-11-01

    Exogenous treatment with the potent estrogen 17β-estradiol (E 2 ) or selective estrogen receptor α/β (ERα/β) agonists enhances the consolidation of hippocampal-dependent object recognition (OR) and object placement (OP) memories in ovariectomized rodents. Although such data suggest that individual ERs are sufficient for memory consolidation, the necessity of a given ER for memory consolidation can only be demonstrated by blocking receptor function, for example with an ER antagonist. However, the effects on memory of antagonizing ERα or ERβ function are not well understood. Moreover, ER antagonism in ovariectomized subjects also provides indirect information about the role of individual ERs in the memory-enhancing effects of local hippocampal E 2 synthesis. Therefore, this study used pharmacological inhibition of ERα and ERβ to elucidate the importance of each ER to memory consolidation. Specifically, we examined effects on OR and OP memory consolidation of immediate post-training dorsal hippocampal (DH) infusion of MPP and PHTPP, selective antagonists for ERα and ERβ, respectively. Each drug exhibited a distinct effect on OR and OP. DH infusion of MPP (0.28 or 2.78ng/hemisphere) impaired memory in OP, but not OR. However, DH infusion of PHTPP (0.21 or 2.12ng/hemisphere) impaired memory in both OR and OP. Neither drug affected the elapsed time to accumulate object exploration in either task, suggesting a specific effect on memory. These results indicate that activation of either classical ER within the dorsal hippocampus is important for hippocampal memory consolidation in ovariectomized mice, but suggest that specific ER involvement is memory- or task-specific. The findings also indirectly support a role for ERα and ERβ in mediating the memory-enhancing effects of hippocampally-synthesized E 2 . Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. iTRAQ-based quantitative proteomic analysis reveals the distinct early embryo myofiber type characteristics involved in landrace and miniature pig.

    Science.gov (United States)

    Zhang, Xumeng; Chen, Yaosheng; Pan, Jinchun; Liu, Xiaohong; Chen, Hu; Zhou, Xingyu; Yuan, Zhuning; Wang, Xilong; Mo, Delin

    2016-02-25

    Pig (Sus scrofa) is a major source of dietary proteins for human consumption and is becoming a valuable model in agricultural and biomedical research. The recently developed isobaric tag for relative and absolute quantitation (iTRAQ) method allows sensitive and accurate protein quantification. Here, we performed the first iTRAQ-based quantitative proteomic analyses of Landrace (LR) and Wuzhishan (WZS) pig longissimus dorsi muscle tissues during early embryonic development. The iTRAQ-based early embryonic longissimus dorsi muscle study of LR and WZS ranging from 21 to 42 days post coitus (dpc) identified a total of 4431 proteins from 17,214 peptides, which were matched with 36,4025 spectra at a false discovery rate of 5%. In both WZS and LR, the largest amount of differentially expressed proteins (DEPs) were found between 28 and 35 dpc. 252 breed-DEPs were selected by GO analysis, including 8 myofibrillar proteins. Only MYHCI/IIA mRNA were detected due to early embryonic stages, and significantly higher expression of them were found in WZS during these 4 stages. MYHCI was first found in WZS at 28 dpc and expressed in both breeds at later stages, while MYHCII protein was not detected until 35 dpc in both breeds. Thus, 33 myogenic breed-DEPs selected from last two stages were analyzed by STRING, which showed that some myofibrillar proteins (MYH1, TPM4, MYH10, etc.) and functional proteins (CSRP2, CASQ2, OTC, etc.), together with candidate myogenic proteins (H3F3A, HDGFRP2, etc.), probably participate in the regulatory network of myofiber formation. Our iTRAQ-based early embryonic longissimus dorsi muscle study of LR and WZS provides new data on the in vivo muscle development distinctions during early embryonic development, which contributes to the improved understanding in the regulation mechanism of early myogenesis in agricultural animals.

  3. Ondskaben er fortryllende

    DEFF Research Database (Denmark)

    Schubart, Rikke

    2013-01-01

    Indlæg om tv-serien Once Upon a Time (2011-), der hører til genren fairytale fantasy, der blander eventyr og fantasy. Her bliver alle eventyr brugt i en fortælling om alle beboere i en lille by, der ikke ved, at de i virkeligheden er eventyr-karakterer.......Indlæg om tv-serien Once Upon a Time (2011-), der hører til genren fairytale fantasy, der blander eventyr og fantasy. Her bliver alle eventyr brugt i en fortælling om alle beboere i en lille by, der ikke ved, at de i virkeligheden er eventyr-karakterer....

  4. Transcript profiling of structural genes involved in cyanidin-based anthocyanin biosynthesis between purple and non-purple carrot (Daucus carota L.) cultivars reveals distinct patterns.

    Science.gov (United States)

    Xu, Zhi-Sheng; Huang, Ying; Wang, Feng; Song, Xiong; Wang, Guang-Long; Xiong, Ai-Sheng

    2014-10-01

    Carrots (Daucus carota L.) are among the 10 most economically important vegetable crops grown worldwide. Purple carrot cultivars accumulate rich cyanidin-based anthocyanins in a light-independent manner in their taproots whereas other carrot color types do not. Anthocyanins are important secondary metabolites in plants, protecting them from damage caused by strong light, heavy metals, and pathogens. Furthermore, they are important nutrients for human health. Molecular mechanisms underlying anthocyanin accumulation in purple carrot cultivars and loss of anthocyanin production in non-purple carrot cultivars remain unknown. The taproots of the three purple carrot cultivars were rich in anthocyanin, and levels increased during development. Conversely, the six non-purple carrot cultivars failed to accumulate anthocyanins in the underground part of taproots. Six novel structural genes, CA4H1, CA4H2, 4CL1, 4CL2, CHI1, and F3'H1, were isolated from purple carrots. The expression profiles of these genes, together with other structural genes known to be involved in anthocyanin biosynthesis, were analyzed in three purple and six non-purple carrot cultivars at the 60-day-old stage. PAL3/PAL4, CA4H1, and 4CL1 expression levels were higher in purple than in non-purple carrot cultivars. Expression of CHS1, CHI1, F3H1, F3'H1, DFR1, and LDOX1/LDOX2 was highly correlated with the presence of anthocyanin as these genes were highly expressed in purple carrot taproots but not or scarcely expressed in non-purple carrot taproots. This study isolated six novel structural genes involved in anthocyanin biosynthesis in carrots. Among the 13 analyzed structural genes, PAL3/PAL4, CA4H1, 4CL1, CHS1, CHI1, F3H1, F3'H1, DFR1, and LDOX1/LDOX2 may participate in anthocyanin biosynthesis in the taproots of purple carrot cultivars. CHS1, CHI1, F3H1, F3'H1, DFR1, and LDOX1/LDOX2 may lead to loss of light-independent anthocyanin production in orange and yellow carrots. These results suggest that

  5. Distinct Cell-Specific Expression of Homospermidine Synthase Involved in Pyrrolizidine Alkaloid Biosynthesis in Three Species of the Boraginales1[C][W][OA

    Science.gov (United States)

    Niemüller, Daniel; Reimann, Andreas; Ober, Dietrich

    2012-01-01

    Homospermidine synthase (HSS) is the first specific enzyme in pyrrolizidine alkaloid (PA) biosynthesis, a pathway involved in the plant’s chemical defense. HSS has been shown to be recruited repeatedly by duplication of a gene involved in primary metabolism. Within the lineage of the Boraginales, only one gene duplication event gave rise to HSS. Here, we demonstrate that the tissue-specific expression of HSS in three boraginaceous species, Heliotropium indicum, Symphytum officinale, and Cynoglossum officinale, is unique with respect to plant organ, tissue, and cell type. Within H. indicum, HSS is expressed exclusively in nonspecialized cells of the lower epidermis of young leaves and shoots. In S. officinale, HSS expression has been detected in the cells of the root endodermis and in leaves directly underneath developing inflorescences. In young roots of C. officinale, HSS is detected only in cells of the endodermis, but in a later developmental stage, additionally in the pericycle. The individual expression patterns are compared with those within the Senecioneae lineage (Asteraceae), where HSS expression is reproducibly found in specific cells of the endodermis and the adjacent cortex parenchyma of the roots. The individual expression patterns within the Boraginales species are discussed as being a requirement for the successful recruitment of HSS after gene duplication. The diversity of HSS expression within this lineage adds a further facet to the already diverse patterns of expression that have been observed for HSS in other PA-producing plant lineages, making this PA-specific enzyme one of the most diverse expressed proteins described in the literature. PMID:22566491

  6. Indications for a tumor suppressor gene at 22q11 involved in the pathogenesis of ependymal tumors and distinct from hSNF5/INI1.

    Science.gov (United States)

    Kraus, J A; de Millas, W; Sörensen, N; Herbold, C; Schichor, C; Tonn, J C; Wiestler, O D; von Deimling, A; Pietsch, T

    2001-07-01

    Ependymomas account for approximately 9% of all neuroepithelial tumors and represent the most frequent neuroepithelial tumors of the spinal cord. In adults, allelic loss of chromosome arm 22q occurs in up to 60% of the cases studied. Some of these tumors show an altered neurofibromatosis type 2 (NF2) gene; in others, NF2 appears to be unaffected, indicating the involvement of another tumor suppressor gene. Recently, the tumor suppressor gene hSNF5/INI1, located on 22q11.23, has been shown to contribute to the pathogenesis of renal and extrarenal rhabdoid tumors. In addition, this gene may be responsible for a new hereditary syndrome predisposing to a variety of tumors designated "rhabdoid predisposition syndrome." In the present study, we analyzed a series of 53 ependymal tumors of 48 patients [4 myxopapillary ependymomas (WHO grade I), 3 subependymomas (WHO grade I), 18 ependymomas (WHO grade II), 21 anaplastic ependymomas (WHO grade III) and 2 ependymoblastomas (WHO grade IV)] for mutations and homozygous deletions in the coding region of the hSNF5/INI1 gene and for allelic loss of its flanking chromosomal regions in 39 ependymal tumors of 35 patients. Allelic loss was detected in 11 of 35 informative primary ependymal tumors (31%) with a common region of overlap covered by the markers D22S257 and D22S310 on 22q11 including the marker D22S301. However, a detailed molecular analysis of 53 ependymal tumors for mutations and homozygous deletion of the hSNF5/INI1 gene revealed no alterations. We conclude that the hSNF5/INI1 gene is not involved in the pathogenesis of human ependymal tumors with allelic loss on chromosome arm 22q and an intact NF2 locus. In addition, our study localizes a putative ependymoma tumor suppressor gene(s) to a domain of chromosome arm 22q flanked by the microsatellite markers D22S257 and D22S310.

  7. Acute pyelonephritis in ER

    Directory of Open Access Journals (Sweden)

    Giovanni Volpicelli

    2007-10-01

    Full Text Available Symptoms and signs of acute pyelonephritis sometimes are subtle and emergency physicians attending overcrowded and busy institutions could easily miss the right diagnosis. The presence of a renal damage is decisive in the therapeutic choice. Aims of our study are: 1 to assess prevalence of renal damage in patients presenting to our ED with symptoms and signs of primary urinary tract infection (UTI; 2 to evaluate the reliability of such symptoms and signs in predicting a renal damage; 3 to assess accuracy of the contrast enhanced ultrasound (CEUS in the ED diagnosis of renal damage due to acute uncomplicated pyelonephritis. We studied 54 patients with suspected UTI. Each patient underwent clinical examination, routine blood and urine sampling and conventional renal ultrasound (US. 23 patients had confirmation of acute primary UTI, and performed renal magnetic resonance (MR to rule out renal parenchymal involvement. In 16 patients (69,6% one or more parenchymal lesions were visualized at MR, and diagnosis of acute uncomplicated pyelonephritis was confirmed (group A. The other 7 patients had a diagnosis of UTI without renal involvement (group B. Some of 23 patients presented with few atypical symptoms. Lumbar pain was the most frequent symptom (n = 21, without a statistically significant difference between group A and B (P 0,958; p = 0,328. No other symptom or sign has demonstrated statistically valid in predicting the renal involvement. Renal US was positive in only 3 patients of group A (18,7%. During this first part of our study, CEUS was performed in a limited number of patients (n = 8, and in 7 examinations data were concordant with MR. In conclusion, analysis of our preliminary data confirms that a distinction between patients with different extension of the UTI is not possible through the simple clinical examination and routine tests. CEUS is very promising and its routine employment in the ED could simplify the diagnostic practice in

  8. How the human brain goes virtual: distinct cortical regions of the person-processing network are involved in self-identification with virtual agents.

    Science.gov (United States)

    Ganesh, Shanti; van Schie, Hein T; de Lange, Floris P; Thompson, Evan; Wigboldus, Daniël H J

    2012-07-01

    Millions of people worldwide engage in online role-playing with their avatar, a virtual agent that represents the self. Previous behavioral studies have indicated that many gamers identify more strongly with their avatar than with their biological self. Through their avatar, gamers develop social networks and learn new social-cognitive skills. The cognitive neurosciences have yet to identify the neural processes that underlie self-identification with these virtual agents. We applied functional neuroimaging to 22 long-term online gamers and 21 nongaming controls, while they rated personality traits of self, avatar, and familiar others. Strikingly, neuroimaging data revealed greater avatar-referential cortical activity in the left inferior parietal lobe, a region associated with self-identification from a third-person perspective. The magnitude of this brain activity correlated positively with the propensity to incorporate external body enhancements into one's bodily identity. Avatar-referencing furthermore recruited greater activity in the rostral anterior cingulate gyrus, suggesting relatively greater emotional self-involvement with one's avatar. Post-scanning behavioral data revealed superior recognition memory for avatar relative to others. Interestingly, memory for avatar positively covaried with play duration. These findings significantly advance our knowledge about the brain's plasticity to self-identify with virtual agents and the human cognitive-affective potential to live and learn in virtual worlds.

  9. Er Isak bare paranoid?

    DEFF Research Database (Denmark)

    Raun, Tobias

    2017-01-01

    Med afsæt i hovedpersonen fra tredje sæson, Isak, ser artiklen nærmere på homoseksualitet og maskulinitet. I artiklen introduceres og anvendes centrale queer teoretiske begreber som ’homosocialitet’ og ’heteronormtivitet’. Der vises hvordan fællesskaberne i serien er bygget op omkring stærke homo...

  10. Scenen er blevet din

    DEFF Research Database (Denmark)

    Helms, Niels Henrik

    2008-01-01

    Verden kan betragtes som en skueplads med mange forskellige scener. I bidrgaet vil læseren kunne stifte bekendtskab med forskellige refleksioner over netop denne metaforik som analyseoptik i forhold til begrebet innovation. Afsættet er ønsket om at finde en måde at analysere og begrebsliggøre inn...

  11. Er tang fremtidens superfood?

    DEFF Research Database (Denmark)

    Holdt, Susan Løvstad

    seneste år fået øjnene op for tang indenfor områderne: biokemikalier og bioaktive stoffer, ekstraktion, gastronomi, produktudvikling, foder, bioraffinaderier, dyrkning osv. Men hvad er det tang kan? Dette foredrag vil vise at vi med tangdyrkning kan rykke mere bæredygtig fødevareproduktion ud på havet...

  12. Er praksis prima?

    DEFF Research Database (Denmark)

    Holm, Claus

    2006-01-01

    Tiltroen til praktisk sans er i vækst, mens den teoretiske fornuft møder skepsis. Paradoksalt nok rammer den antiteoretiske bevægelse også universiteterne. To forskere advarer mod, at samfundet forlader sig på praksis....

  13. Riget - alt er tilladt

    DEFF Research Database (Denmark)

    Agger, Gunhild

    2017-01-01

    Riget indtager en nøglestilling, når overgangen mellem faser i Triers produktion skal karakteriseres. Riget danner bro mellem den billedfascination og de radikale stileksperimenter, der præger Triers tidlige produktion, og den genre- og plotbevidsthed, der er typisk for film som Breaking the Waves...

  14. Hvad er tidligt sprog

    DEFF Research Database (Denmark)

    Skriver Jensen, Anders

    2009-01-01

    Forfatteren argumenterer for at "early literacy" kan oversættes til "tidligt sprog"; særligt når der er tale om en helhedsorienteret tilgang med vægt på sprog som et alsidigt medie for kommunikation- og betydningsskabelse. Med inspiration fra Jerome Bruners kulturpsykologi diskuteres mulige...

  15. Er danskerne racister

    DEFF Research Database (Denmark)

    Bech, Henning; Necef, Mehmet Ümit

    Igennem de seneste årtier er det blevet almindeligt at tale om, at der er en udbredt racisme i Danmark. Påstande om danskernes racisme, fremmedhad og diskrimination optræder dagligt i offentligheden og i medierne, og der henvises ofte til, hvad ’forskerne’ og de ’videnskabelige undersøgelser’ siger...... om emnet. Der kan da næppe heller være tvivl om, at der forekommer racistiske holdninger hos nogle danskere. Men er problemet så stort, som det gøres til i den offentlige debat? Bogen ønsker at afklare, hvorvidt der er videnskabelig dokumentation for påstandene om danskernes racisme. Den går i dybden...... med en række forskeres og eksperters udtalelser på området og præsenterer en grundig analyse af deres fremstilling af dansk racisme i forhold til emner som kultur, seksualitet, kriminalitet og arbejdsmarked....

  16. Litteratur er nyttig

    DEFF Research Database (Denmark)

    Kaspersen, Peter

    2012-01-01

    Den anmeldte bog er en forskningsbaseret debatbog om hvilken nytteværdi litteratur har. Bogen placeres i sammenhæng med en række bøger på nordiske sprog og engelsk om litteraturens, litteraturundervisningens og -forskningens legitimitet. Argumentatioen i bogen bygger på Bakhtins litteratursyn, og...

  17. Urban planning of the endoplasmic reticulum (ER): how diverse mechanisms segregate the many functions of the ER.

    Science.gov (United States)

    Lynes, Emily M; Simmen, Thomas

    2011-10-01

    The endoplasmic reticulum (ER) is the biggest organelle in most cell types, but its characterization as an organelle with a continuous membrane belies the fact that the ER is actually an assembly of several, distinct membrane domains that execute diverse functions. Almost 20 years ago, an essay by Sitia and Meldolesi first listed what was known at the time about domain formation within the ER. In the time that has passed since, additional ER domains have been discovered and characterized. These include the mitochondria-associated membrane (MAM), the ER quality control compartment (ERQC), where ER-associated degradation (ERAD) occurs, and the plasma membrane-associated membrane (PAM). Insight has been gained into the separation of nuclear envelope proteins from the remainder of the ER. Research has also shown that the biogenesis of peroxisomes and lipid droplets occurs on specialized membranes of the ER. Several studies have shown the existence of specific marker proteins found on all these domains and how they are targeted there. Moreover, a first set of cytosolic ER-associated sorting proteins, including phosphofurin acidic cluster sorting protein 2 (PACS-2) and Rab32 have been identified. Intra-ER targeting mechanisms appear to be superimposed onto ER retention mechanisms and rely on transmembrane and cytosolic sequences. The crucial roles of ER domain formation for cell physiology are highlighted with the specific targeting of the tumor metastasis regulator gp78 to ERAD-mediating membranes or of the promyelocytic leukemia protein to the MAM. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Down-regulation of 14-3-3β exerts anti-cancer effects through inducing ER stress in human glioma U87 cells: Involvement of CHOP–Wnt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Lei; Lei, Hui; Chang, Ming-Ze; Liu, Zhi-Qin [Department of Neurological Disease, Xi' an Central Hospital, Xi' an Jiaotong University, Xi' an, Shaanxi 710000 (China); Bie, Xiao-Hua, E-mail: biexiaohua_xjtu@126.com [Department of Functional Neurosurgery, Xi' an Red Cross Hospital, Xi' an Jiaotong University, Xi' an, Shaanxi 710054 (China)

    2015-07-10

    We previously identified 14-3-3β as a tumor-specific isoform of 14-3-3 protein in astrocytoma, but its functional role in glioma cells and underlying mechanisms are poorly understood. In the present study, we investigated the effects of 14-3-3β inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA). The results showed that 14-3-3β is highly expressed in U87 cells but not in normal astrocyte SVGp12 cells. Knockdown of 14-3-3β by Si-14-3-3β transfection significantly decreased the cell viability but increased the LDH release in a time-dependent fashion in U87 cells, and these effects were accompanied with G0/G1 cell cycle arrest and apoptosis. In addition, 14-3-3β knockdown induced ER stress in U87 cells, as evidenced by ER calcium release, increased expression of XBP1S mRNA and induction of ER related pro-apoptotic factors. Down-regulation of 14-3-3β significantly decreased the nuclear localization of β-catenin and inhibited Topflash activity, which was shown to be reversely correlated with CHOP. Furthermore, Si-CHOP and sFRP were used to inhibit CHOP and Wnt, respectively. The results showed that the anti-cancer effects of 14-3-3β knockdown in U87 cells were mediated by increased expression of CHOP and followed inhibition of Wnt/β-catenin pathway. In summary, the remarkable efficiency of 14-3-3β knockdown to induce apoptotic cell death in U87 cells may find therapeutic application for the treatment of glioma patients. - Highlights: • Knockdown of 14-3-3β leads to cytotoxicity in human glioma U87 cells. • Knockdown of 14-3-3β induces cell cycle arrest and apoptosis in U87 cells. • Knockdown of 14-3-3β results in ER stress in U87 cells. • Knockdown of 14-3-3β inhibits Wnt/β-catenin pathway via CHOP activation.

  19. Down-regulation of 14-3-3β exerts anti-cancer effects through inducing ER stress in human glioma U87 cells: Involvement of CHOP–Wnt pathway

    International Nuclear Information System (INIS)

    Cao, Lei; Lei, Hui; Chang, Ming-Ze; Liu, Zhi-Qin; Bie, Xiao-Hua

    2015-01-01

    We previously identified 14-3-3β as a tumor-specific isoform of 14-3-3 protein in astrocytoma, but its functional role in glioma cells and underlying mechanisms are poorly understood. In the present study, we investigated the effects of 14-3-3β inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA). The results showed that 14-3-3β is highly expressed in U87 cells but not in normal astrocyte SVGp12 cells. Knockdown of 14-3-3β by Si-14-3-3β transfection significantly decreased the cell viability but increased the LDH release in a time-dependent fashion in U87 cells, and these effects were accompanied with G0/G1 cell cycle arrest and apoptosis. In addition, 14-3-3β knockdown induced ER stress in U87 cells, as evidenced by ER calcium release, increased expression of XBP1S mRNA and induction of ER related pro-apoptotic factors. Down-regulation of 14-3-3β significantly decreased the nuclear localization of β-catenin and inhibited Topflash activity, which was shown to be reversely correlated with CHOP. Furthermore, Si-CHOP and sFRP were used to inhibit CHOP and Wnt, respectively. The results showed that the anti-cancer effects of 14-3-3β knockdown in U87 cells were mediated by increased expression of CHOP and followed inhibition of Wnt/β-catenin pathway. In summary, the remarkable efficiency of 14-3-3β knockdown to induce apoptotic cell death in U87 cells may find therapeutic application for the treatment of glioma patients. - Highlights: • Knockdown of 14-3-3β leads to cytotoxicity in human glioma U87 cells. • Knockdown of 14-3-3β induces cell cycle arrest and apoptosis in U87 cells. • Knockdown of 14-3-3β results in ER stress in U87 cells. • Knockdown of 14-3-3β inhibits Wnt/β-catenin pathway via CHOP activation

  20. Hvid er et usynligt ideal

    DEFF Research Database (Denmark)

    Mehlsen, Camilla

    2010-01-01

    Salget af hudblegecremer er eksploderet. Hvorfor drømmer så mange om at få lys hud? Hvorfor vil børn hellere lege med hvide dukker end brune? Svaret er, at hvid er et globalt ideal. Interview med Dorthe Staunæs og Les Back....

  1. Er HR ude i tovene?

    DEFF Research Database (Denmark)

    Poulfelt, Flemming

    2015-01-01

    HR: Er der behov for nytænkning i HR-land? Artikler i Harvard Business Review - bakket op af en dansk undersøgelse - konkluderer, at HR stadig mangler gennemslagskraft i virksomhederne. Er HR ude i tovene? ... For i undersøgelsen "Ny Dansk Ledelse" (maj 2015), som er baseret på danske lederes...

  2. Facebook er internettet nu

    DEFF Research Database (Denmark)

    Tække, Jesper

    2014-01-01

    Den store vision for world wide web var, at alle kunne få ubegrænset adgang til alverdens information. www var mangfoldigt og anarkistisk. I dag er der rigtig mange, der kun bruger nettet til at være på Facebook. Hvad bruger Facebook det til? Og hvad gør det ved vores udsyn?......Den store vision for world wide web var, at alle kunne få ubegrænset adgang til alverdens information. www var mangfoldigt og anarkistisk. I dag er der rigtig mange, der kun bruger nettet til at være på Facebook. Hvad bruger Facebook det til? Og hvad gør det ved vores udsyn?...

  3. Hvis er lovene?

    DEFF Research Database (Denmark)

    Holm, Isak Winkel

    2015-01-01

    Hvem konstituerer det politiske fællesskab, som laver lovene? Hvad sker der, når folket ikke kender lovene, eller ikke findes værdige til dem? Hvis folket udfordrede adelens love før i tiden, er det måske migranterne, der udfordrer europæernes love og konventioner i dag. Man kan med fordel gå til...... Franz Kafka for at forstå hvordan....

  4. Er havets iltminimumszoner iltfrie?

    DEFF Research Database (Denmark)

    Revsbech, Niels Peter; Larsen, Lars; Gundersen, Jens

    Den centrale del af havets ilt-minimumszoner kan være totalt iltfrie! Ved brug af STOX iltsensoren er det muligt at måle ilt med en detektionsgrænse nær 1 nM (dvs. en faktor 1000 bedre end hidtil muligt) og dermed at opnå en bedre forståelse af omsætningerne i oceanernes ilt-minimumszoner, der bl...

  5. Hvad er en by?

    DEFF Research Database (Denmark)

    Parby, Jakob; Thelle, Mikkel

    2011-01-01

    Nytænkning. Med de moderne megabyer er det slut med at forestille sig byen som noget, man planlægger og giver form. Vi skal lære at se dem som vildtvoksende urbane landskaber. Artikel om megabyer, byudvikling og forestillingen om byen gennem tiderne. Skrevet delvist i anledning af åbningen af uds...... udstillingen Citambulos på Københavns Museum, der handlede om Mexico City....

  6. Hvis er Himmeriget?

    DEFF Research Database (Denmark)

    Holst, Søren

    2007-01-01

    Udtrykket "de fattige i ånden", som kendes fra Bjergprædikenen i Matthæusevangeliet, forekommer også i to af Dødehavsrullerne. Artiklen undersøger disse tekster og argumenterer for, at udtrykket ikke betegner en særligt "åndelig" fattigdom, men derimod de konkret økonomisk fattige, som er "af ånd...

  7. Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance

    DEFF Research Database (Denmark)

    Schneeberger, Marc; Dietrich, Marcelo O; Sebastián, David

    2013-01-01

    Mitofusin 2 (MFN2) plays critical roles in both mitochondrial fusion and the establishment of mitochondria-endoplasmic reticulum (ER) interactions. Hypothalamic ER stress has emerged as a causative factor for the development of leptin resistance, but the underlying mechanisms are largely unknown....... This previously unrecognized role for MFN2 argues for a crucial involvement in mediating ER stress-induced leptin resistance........ Here, we show that mitochondria-ER contacts in anorexigenic pro-opiomelanocortin (POMC) neurons in the hypothalamus are decreased in diet-induced obesity. POMC-specific ablation of Mfn2 resulted in loss of mitochondria-ER contacts, defective POMC processing, ER stress-induced leptin resistance...

  8. Hvad er tekstfiktion?

    DEFF Research Database (Denmark)

    Widell, Peter

    2012-01-01

    artiklen er et bidrag til belysningen af genteori og bygger på ideen om at karakterisere skønlitteratur som et restringeret sæt af universelle tekstparametre. Artiklen fokuserer især på parametren tekstfiktion, hvor jeg forsvarer den position, at en fiktiv tekst hverken kan karakteriseres som en ...... intentioner. Det betyder dog ikke, at sandhed og mening ikke spiller noget rolle ved identifikationen af fiktion, sådan som det hævdes af Walsh og andre....

  9. Features and current status of Pu'er food culture : Challenges toward cultural environment preservation

    OpenAIRE

    Cheng, Xiaomin; Kisihomoto, sayaka; Yu, Ganqian

    2015-01-01

    Pu'er food culture is characterized by distinct uniqueness and diversity on three aspects: culture, material and skill under various influences of regional, ecological and border culture, which is based on tea culture in particular. However, food culture in Pu'er has been facing several problems and risks of gradual assimilation, lack of specific transmission carrier, and the urgent need of building sustainable support system for the preservation of Pu'er food culture. This paper aims to intr...

  10. Binary magnetic structures in HoEr

    DEFF Research Database (Denmark)

    Howard, B.K.; Bohr, J.

    1991-01-01

    The magnetic structure of a single crystal of the rare earth random alloy Ho50% Er50% has been investigated by elastic neutron diffraction measurements in the temperature range 120-10 K. Three distinct magnetic phases are identified below the Neel temperature of 104 K. The high-temperature phase...... observed between 104 K and 47.5 K is a binary magnetic structure where the holmium and erbium moments belong to different modulated c-axis spirals. The intermediate-temperature phase between 47.5 K and 35 K is a simple basal plane spiral. Below 35 K, the measurements suggest a ferrimagnetic structure...

  11. IRE1α-TRAF2-ASK1 pathway is involved in CSTMP-induced apoptosis and ER stress in human non-small cell lung cancer A549 cells.

    Science.gov (United States)

    Zhang, Jiexia; Liang, Ying; Lin, Yongbin; Liu, Yuanbin; YouYou; Yin, Weiqiang

    2016-08-01

    CSTMP, a Tetramethylpyrazine (TMP) analogue, is designed and synthesized based on the pharmacophores of TMP and resveratrol. Recent studies showed that CSTMP had strong protective effects in endothelial cells apoptosis by its anti-oxidant activity. However, the pharmacological function of CSTMP in cancer have not been elucidated to date. The objective of this study was to investigate the anti-cancer effect of CSTMP against human non-small cell lung cancer (NSCLC) A549 cells and the underlying mechanisms. The cell proliferation and apoptosis were detected by MTT assay and flow cytometry. Caspases activity was determined spectrophotometricaly at 405nm using a microtiter plate reader. Western blot and real-time PCR was used to assess the protein and mRNA expression. Immunoprecipitation was used to examine the protein-protein interactions. CSTMP inhibited the proliferation and induced cell cycle arrest and apoptosis of A549 cells. Caspase3, 8, 9 and PARP-1 activation, and Bax/Bcl-2 ratio analyses demonstrated that the anti-cancer effect of CSTMP in A549 cells was mediated by promoting caspase- and mitochondria-dependent apoptosis. Furthermore, CSTMP induced ER stress in A549 cells as evidenced by elevated levels of GRP78, GRP94, CHOP, IRE1α, TRAF2, p-ASK1 and p-JNK, activation of caspase12 and 4, and enhanced formation of an IRE1α-TRAF2-ASK1 complex. Knockdown of IRE1α by siRNA suppressed activation of IRE1α, TRAF2, p-ASK1 and p-JNK in CSTMP treated A549 cells. In addition, the effects of CSTMP on the formation of an IRE1α-TRAF2-ASK1 complex, caspase- and mitochondria-dependent apoptosis were also reversed by IRE1α siRNA in A549 cells. Collectively, we showed that CSTMP induced apoptosis of A549 cells were through IRE1α-TRAF2-ASK1 complex-mediated ER stress, JNK activation, and mitochondrial dysfunction. These insights on this novel compound CSTMP may provide a novel anti-cancer candidate for the treatment of NSCLC. Copyright © 2016 Elsevier Masson SAS. All

  12. Rouw mag er zijn

    Directory of Open Access Journals (Sweden)

    Marlieke Moors

    2015-12-01

    Full Text Available ABSTRACTGrieving is allowedGrief is a human experience. Every form of loss shapes you into the human being you are today. Contrary to what earlier, unproven grief models postulate, grief does not have an end point. That is, bereavement does not have to be completely processed, but it should be integrated into someone’s life. The outdated grief models were often interpreted and used in a normative way, which led to a normative standard model. This portraits the belief that every mourner would experience similar symptoms and would go through a fixed pattern of phases. However, the updated vision emphasizes the individual and unique process of coping with loss: norms concerning grief should be banned. By means of literature research, interviews with professionals and personal experiences, it became clear that finding an equilibrium between restoration-orientated and loss-orientated coping styles is most beneficial. An important aspect in finding this balance is meaningfulness. Furthermore, the ability to bear a loss and to adapt accordingly are important components. Lastly, attaching significance to a loss is a constructive way of integrating the loss into one’s life. The death of a loved one should therefore not be forgotten or tucked away. After all, grief is the price we pay for love. SAMENVATTINGRouw mag er zijnRouw is een menselijke ervaring en elk verlies vormt je als mens. Rouw heeft, in tegenstelling tot wat de verouderde, niet bewezen rouwmodellen beweren, geen eindpunt. Verlies hoeft namelijk niet verwerkt te worden, maar moet juist geïntegreerd worden in iemands leven. De verouderde rouwmodellen zijn vaak normatief opgevat en toegepast, waaruit een normatief standaardmodel is ontstaan. Daarbij werd gedacht dat elke rouwende dezelfde symptomen zou vertonen en het rouwproces volgens vaste fasen zou verlopen. Binnen de vernieuwde visie wordt er juist van uitgegaan dat elk individu een unieke manier van reageren op rouw heeft. Er zou

  13. Alt er ændret. Intet er afklaret

    DEFF Research Database (Denmark)

    Helmersen, Ole

    2017-01-01

    Brexit kan redefinere landets internationale rolle lige så meget som Suezkrisen. Men 15 måneder efter afstemningen er der stadig ingen svar.......Brexit kan redefinere landets internationale rolle lige så meget som Suezkrisen. Men 15 måneder efter afstemningen er der stadig ingen svar....

  14. Er talesprog en medieteknologi?

    DEFF Research Database (Denmark)

    Tække, Jesper

    2013-01-01

    for den menneskelige udfoldelse. Til at løse denne opgave vil jeg trække på den tyske sociolog og systemteoretiker Niklas Luhmann der også udmærker sig som medieteoretiker (Tække 2006a). Luhmann har ikke selv direkte redegjort for sprog som teknologi, men da han både har udviklet et brugbart...... motiver og viden, må give mening til hvad, der meddeles og selektere en forståelse (Luhmann 2000a). Formålet med og berettigelsen for medieteori er ud fra Marshall McLuhans (1967) devise, om at the medium is the message, at sammenligne, hvad det betyder for menneske og samfund, at der kommunikeres i ét...

  15. Fibroblast growth factor 2 induces proliferation and distribution of G2 /M phase of bovine endometrial cells involving activation of PI3K/AKT and MAPK cell signaling and prevention of effects of ER stress.

    Science.gov (United States)

    Lim, Whasun; Bae, Hyocheol; Bazer, Fuller W; Song, Gwonhwa

    2018-04-01

    Fibroblast growth factor 2 (FGF2) is abundantly expressed in conceptuses and endometria during pregnancy in diverse animal models including domestic animals. However, its intracellular mechanism of action has not been reported for bovine endometrial cells. Therefore, the aim of this study was to identify functional roles of FGF2 in bovine endometrial (BEND) cell line which has served as a good model system for investigating regulation of signal transduction following treatment with interferon-tau (IFNT) in vitro. Results of present study demonstrated that administration of FGF2 to BEND cells increased their proliferation and regulated the cell cycle through DNA replication by an increase of PCNA and Cyclin D1. FGF2 also increased phosphorylation of AKT, P70S6K, S6, ERK1/2, JNK, and P38 in BEND cells in a dose-dependent manner, and expression of each of those transcription factors was inhibited by their respective pharmacological inhibitor including Wormannin, U0126, and SP600125. In addition, the increase in proliferation of BEND cells and activation of the protein kinases in response to FGF2 was suppressed by BGJ398, a FGFR inhibitor. Furthermore, proliferation of BEND cells was inhibited by tunicamycin, but treatment of BEND cells with FGF2 restored proliferation of BEND cells. Consistent with this result, the stimulated unfolded protein response (UPR) regulatory proteins induced by tunicamycin were down-regulated by FGF2. Results of this study suggest that FGF2 promotes proliferation of BEND cells and likely enhances uterine capacity and maintenance of pregnancy by activating cell signaling via the PI3K and MAPK pathways and by restoring ER stress through the FGFR. © 2017 Wiley Periodicals, Inc.

  16. De 9 P’er

    DEFF Research Database (Denmark)

    Rennison, Betina Wolfgang

    2017-01-01

    Ledere skal i dag selv skabe deres eget rum til ledelse, men hvad er med til at sætte det, hvilke betingelser og udfordringer er der, og hvordan kan lederne skabe sig selv i et hav af forventninger? Dette katalog inviterer til refleksion herom....

  17. Fremtidens undervisningsmiljøer

    DEFF Research Database (Denmark)

    2013-01-01

    Som oplægget til dette temanummer af LOM også indikerede, så sætter vi fokus på fremtidens undervisningsmiljøer på universiteter og UCer. Fremtidens undervisningsmiljøer har mange facetter, hvilket samlingen af artikler også illustrerer. “Fremtidens Undervisningsmiljø” handler om eksisterende erf...

  18. RNA er jo bare matematik!

    DEFF Research Database (Denmark)

    Blaavand, Jakob Lindblad

    2011-01-01

    Hvordan kan man kurere sygdomme med matematiske geometriske strukturer? Det kan man i princippet, hvis de geometriske figurer er RNA-molekyler, og sygdommen skyldes syge gener.......Hvordan kan man kurere sygdomme med matematiske geometriske strukturer? Det kan man i princippet, hvis de geometriske figurer er RNA-molekyler, og sygdommen skyldes syge gener....

  19. Kollegaerne er den nye chef

    DEFF Research Database (Denmark)

    Fugl, Marie

    2008-01-01

    Den tid, hvor chefen var den, der delte skideballer ud, er slut. Rollen som 'bad cop' er overtaget af kollegateamet, der med hård hånd sørger for, at den enkelte yder sin del. Udgivelsesdato: November...

  20. Den rige personlighed er livsduelig

    DEFF Research Database (Denmark)

    Holm, Claus

    2015-01-01

    For omtrent 160 år siden formulerede Karl Marx forestillingen om en rig individualitet som det kommunistiske samfunds individideal. I dag får forestillingen relevans. Lyder det lidt besynderligt, er det ikke mærkeligt. For de fleste af os går næppe rundt og tror, at vi er lige på trapperne til...

  1. Fraflytning er ikke en naturlov

    DEFF Research Database (Denmark)

    Nørgaard, Helle

    2015-01-01

    DEBAT: Der er brug for en erkendelse af, at det ikke er en naturlov, at folk vil flytte til byerne. Forskning viser, at børnefamilier finder tryghed og ideelle rammer for familielivet på landet. Det skriver Helle Nørgaard, seniorforsker, ph.d., Statens Byggeforskningsinstitut, Aalborg Universitet....

  2. Følelsen er alt

    DEFF Research Database (Denmark)

    Bonde, Lisbeth

    forrige sekelskifte. Det gælder især de ofte mennesketomme landskabsmalerier med ensomme kastanjetræer, som sukker i efterårslyset, og parkerne med de undertiden flygtige menneskeskikkelser, der som partikler kan forsvinde i vinden. Det er alt sammen skildret med vibrerende, næsten ’sfumatiske’ konturer...

  3. Humor er en alvorlig sag

    DEFF Research Database (Denmark)

    Søltoft, Pia

    2016-01-01

    I modsætning til ironi er humor for Kierkegaard fællesskabsgivende – ironikeren hævder sig selv, men humoristen har sympati med den, man ler med. Humor er hos Kierkegaard udtryk for, at humoristen forliger sig med tilværelsen og dens luner, og dermed grænser humoren hos Kierkegaard op til det...

  4. ER stress and cancer: The FOXO forkhead transcription factor link.

    Science.gov (United States)

    Alasiri, Glowi; Fan, Lavender Yuen-Nam; Zona, Stefania; Goldsbrough, Isabella Galeno; Ke, Hui-Ling; Auner, Holger Werner; Lam, Eric Wing-Fai

    2018-02-15

    The endoplasmic reticulum (ER) is a cellular organelle with central roles in maintaining proteostasis due to its involvement in protein synthesis, folding, quality control, distribution and degradation. The accumulation of misfolded proteins in the ER lumen causes 'ER stress' and threatens overall cellular proteostasis. To restore ER homeostasis, cells evoke an evolutionarily conserved adaptive signalling and gene expression network collectively called the 'unfolded protein response (UPR)', a complex biological process which aims to restore proteostasis. When ER stress is overwhelming and beyond rectification, the normally pro-survival UPR can shift to induce cell termination. Emerging evidence from mammalian, fly and nematode worm systems reveals that the FOXO Forkhead proteins integrate upstream ER stress and UPR signals with the transcriptional machinery to decrease translation, promote cell survival/termination and increase the levels of ER-resident chaperones and of ER-associated degradation (ERAD) components to restore ER homeostasis. The high rates of protein synthesis/translation associated with cancer cell proliferation and metabolism, as well as mutations resulting in aberrant proteins, also induce ER stress and the UPR. While the pro-survival side of the UPR underlies its ability to sustain and promote cancers, its apoptotic functions can be exploited for cancer therapies by offering the chance to 'flick the proteostatic switch'. To this end, further studies are required to fully reevaluate the roles and regulation of these UPR signalling molecules, including FOXO proteins and their targets, in cancer initiation and progression as well as the effects on inhibiting their functions in cancer cells. This information will help to establish these UPR signalling molecules as possible therapeutic targets and putative biomarkers in cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. 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

  6. Endoplasmic reticulum involvement in yeast cell death

    International Nuclear Information System (INIS)

    Nicanor Austriaco, O.

    2012-01-01

    Yeast cells undergo programed cell death (PCD) with characteristic markers associated with apoptosis in mammalian cells including chromatin breakage, nuclear fragmentation, reactive oxygen species generation, and metacaspase activation. Though significant research has focused on mitochondrial involvement in this phenomenon, more recent work with both Saccharomyces cerevisiae and Schizosaccharomyces pombe has also implicated the endoplasmic reticulum (ER) in yeast PCD. This minireview provides an overview of ER stress-associated cell death (ER-SAD) in yeast. It begins with a description of ER structure and function in yeast before moving to a discussion of ER-SAD in both mammalian and yeast cells. Three examples of yeast cell death associated with the ER will be highlighted here including inositol starvation, lipid toxicity, and the inhibition of N-glycosylation. It closes by suggesting ways to further examine the involvement of the ER in yeast cell death.

  7. Min mentor er min voksenven

    DEFF Research Database (Denmark)

    Kaiser, Birte

    2009-01-01

    En artikel i bogen: 6 belysninger af vejledning, brydninger, forståelser & praksis. Artiklen er et sammendrag af en diskursanalyse fra 2008 fra projetrapporten: Ind under huden, www.vejledning.net...

  8. Forenklingens fire F'er

    DEFF Research Database (Denmark)

    Bentzen, Tina Øllgaard

    2017-01-01

    At fjerne styring er det, man ofte forbinder med afbureaukratisering, men det er ikke tilstrækkeligt, når man vil gå fra flotte ambitioner til en styring, som reelt opleves enklere. For at forenkle må man også forandre, forankre og fastholde styring, og det må ske i et samspil mellem de aktører...

  9. Er selvmord en synd? Nej

    DEFF Research Database (Denmark)

    Andersen, Svend

    2013-01-01

    Interview med den tese at selvmord ikke kan kaldes 'synd', dels fordi dette begreb er misvisende, dels fordi der findes forskellige former for selvmord: patologisk eller velovervejet. Det sidste må respekteres som udtryk for et myndigt menneskes selvbestemmelse.......Interview med den tese at selvmord ikke kan kaldes 'synd', dels fordi dette begreb er misvisende, dels fordi der findes forskellige former for selvmord: patologisk eller velovervejet. Det sidste må respekteres som udtryk for et myndigt menneskes selvbestemmelse....

  10. Genome-wide association studies identify four ER negative–specific breast cancer risk loci

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

  11. Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-04-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

  12. Proteomic analysis reveals the distinct energy and protein metabolism characteristics involved in myofiber type conversion and resistance of atrophy in the extensor digitorum longus muscle of hibernating Daurian ground squirrels.

    Science.gov (United States)

    Chang, Hui; Jiang, Shanfeng; Ma, Xiufeng; Peng, Xin; Zhang, Jie; Wang, Zhe; Xu, Shenhui; Wang, Huiping; Gao, Yunfang

    2018-02-13

    Previous hibernation studies demonstrated that such a natural model of skeletal muscle disuse causes limited muscle atrophy and a significant fast-to-slow fiber type shift. However, the underlying mechanism as defined in a large-scale analysis remains unclarified. Isobaric tags for relative and absolute quantification (iTRAQ) based quantitative analysis were used to examine proteomic changes in the fast extensor digitorum longus muscles (EDL) of Daurian ground squirrels (Spermophilus dauricus). Although the wet weights and fiber cross-sectional area of the EDL muscle showed no significant decrease, the percentage of slow type fiber was 61% greater (P 1.2-fold and P < 0.05) in the hibernation group, of which 23 proteins were categorized into energy production and conversion and translation and 22 proteins were categorized into ribosomal structure and biogenesis. Along with the validation by western blot, MAPKAP kinase 2, ATP5D, ACADSB, calcineurin, CSTB and EIF2S were up-regulated in the hibernation group, whereas PDK4, COX II and EIF3C were down-regulated in the hibernation group. MAPKAP kinase 2 and PDK4 were associated with glycolysis, COX II and ATP5D were associated with oxidative phosphorylation, ACADSB was associated with fatty acid metabolism, calcineurin and CSTB were associated with catabolism, and EIF2S and EIF3C were associated with anabolism. Moreover, the total proteolysis rate of EDL in the hibernation group was significantly inhibited compared with that in the pre-hibernation group. These distinct energy and protein metabolism characteristics may be involved in myofiber type conversion and resistance to atrophy in the EDL of hibernating Daurian ground squirrels. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells.

    Science.gov (United States)

    Arduino, Daniela M; Esteves, A Raquel; Domingues, A Filipa; Pereira, Claudia M F; Cardoso, Sandra M; Oliveira, Catarina R

    2009-11-30

    Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

  14. Screening af kulturmiljøer

    DEFF Research Database (Denmark)

    2017-01-01

    Arkitektskolen Aarhus sætter fokus på kulturmiljøer i Danmarks yderområder. Screening af Kulturmiljøer (SAK) er et redskab til at vurdere kulturmiljøer ud fra aflæselige parametre, så kulturarvens værdier, egenskaber og udviklingspotentialer bliver synlige. Formålet er at skabe nye muligheder og...

  15. Herp enhances ER-associated protein degradation by recruiting ubiquilins

    International Nuclear Information System (INIS)

    Kim, Tae-Yeon; Kim, Eunmin; Yoon, Sungjoo Kim; Yoon, Jong-Bok

    2008-01-01

    ER-associated protein degradation (ERAD) is a protein quality control system of ER, which eliminates misfolded proteins by proteasome-dependent degradation and ensures export of only properly folded proteins from ER. Herp, an ER membrane protein upregulated by ER stress, is implicated in regulation of ERAD. In the present study, we show that Herp interacts with members of the ubiquilin family, which function as a shuttle factor to deliver ubiquitinated substrates to the proteasome for degradation. Knockdown of ubiquilin expression by small interfering RNA stabilized the ERAD substrate CD3δ, whereas it did not alter or increased degradation of non-ERAD substrates tested. CD3δ was stabilized by overexpressed Herp mutants which were capable of binding to ubiquilins but were impaired in ER membrane targeting by deletion of the transmembrane domain. Our data suggest that Herp binding to ubiquilin proteins plays an important role in the ERAD pathway and that ubiquilins are specifically involved in degradation of only a subset of ubiquitinated targets, including Herp-dependent ERAD substrates

  16. Role of ER-α36 in breast cancer by typical xenoestrogens.

    Science.gov (United States)

    Liu, Jun; Xu, Zhixiang; Ma, Xiaodong; Huang, Bin; Pan, Xuejun

    2015-09-01

    About 10 years have passed since the discovery of the estrogen receptor subtype, estrogen receptor alpha 36 (ER-α36). The relationship between cancerous cells and ER-α36 in mediating xenoestrogens (XEs) is a significant issue in the progression and treatment of breast cancer. XEs can combine with classical estrogen receptors and other receptor subtypes especially ER-α36, resulting in activation of nongenomic pathways as well as genomic pathways. Recently, most laboratories have focused on further study into the rapidly nongenomic mechanisms by overexpressing or knocking down ER-α36 in breast cancer cell lines. These rapid responses can induce the deregulation of cell cycle, and then lead to the abnormal proliferation and differentiation by regulating distinct downstream pathways. It appears that ER-α36 is a key factor in increasing risk of breast cancer. However, in several recent studies, the action mechanisms of ER-α36 by XEs in breast cancer cell lines are not always clear. In this review, we firstly summarize the expression pattern and tumor biology of ER-α36, then discuss these related estrogenic effects of ER-α36, and lastly give the predictive and prognostic value of ER-α36 as diagnostic marker by mediating typical XEs in breast cancer.

  17. Polarized laser selective excitation and electron paramagnetic resonance of Er3+ centers in SrLaAlO4 crystals

    NARCIS (Netherlands)

    Wells, J. P. R.; Yamaga, M.; Mosses, R. W.; Han, T. P. J.; Gallagher, H. G.; Yosida, T.

    2000-01-01

    The crystal growth and optical and magnetic spectroscopies of perovskite phase, strontium lanthanium aluminate (SrLaAlO4) doped with trivalent erbium ape reported. Electron paramagnetic resonance of SrLaAlO4:1% Er3+ identifies two distinct Er3+ ion centers in this material: a tetragonal (C-4v)

  18. Phenotypes of organ involvement in sarcoidosis.

    Science.gov (United States)

    Schupp, Jonas Christian; Freitag-Wolf, Sandra; Bargagli, Elena; Mihailović-Vučinić, Violeta; Rottoli, Paola; Grubanovic, Aleksandar; Müller, Annegret; Jochens, Arne; Tittmann, Lukas; Schnerch, Jasmin; Olivieri, Carmela; Fischer, Annegret; Jovanovic, Dragana; Filipovic, Snežana; Videnovic-Ivanovic, Jelica; Bresser, Paul; Jonkers, René; O'Reilly, Kate; Ho, Ling-Pei; Gaede, Karoline I; Zabel, Peter; Dubaniewicz, Anna; Marshall, Ben; Kieszko, Robert; Milanowski, Janusz; Günther, Andreas; Weihrich, Anette; Petrek, Martin; Kolek, Vitezslav; Keane, Michael P; O'Beirne, Sarah; Donnelly, Seamas; Haraldsdottir, Sigridur Olina; Jorundsdottir, Kristin B; Costabel, Ulrich; Bonella, Francesco; Wallaert, Benoît; Grah, Christian; Peroš-Golubičić, Tatjana; Luisetti, Mauritio; Kadija, Zamir; Pabst, Stefan; Grohé, Christian; Strausz, János; Vašáková, Martina; Sterclova, Martina; Millar, Ann; Homolka, Jiří; Slováková, Alena; Kendrick, Yvonne; Crawshaw, Anjali; Wuyts, Wim; Spencer, Lisa; Pfeifer, Michael; Valeyre, Dominique; Poletti, Venerino; Wirtz, Hubertus; Prasse, Antje; Schreiber, Stefan; Krawczak, Michael; Müller-Quernheim, Joachim

    2018-01-01

    Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies. Copyright ©ERS 2018.

  19. ER-α36, a novel variant of ER-α, mediates estrogen-stimulated proliferation of endometrial carcinoma cells via the PKCδ/ERK pathway.

    Directory of Open Access Journals (Sweden)

    Jing-Shan Tong

    2010-11-01

    Full Text Available Recently, a variant of ER-α, ER-α36 was identified and cloned. ER-α36 lacks intrinsic transcription activity and mainly mediates non-genomic estrogen signaling. The purpose of this study was to investigate the function and the underlying mechanisms of ER-α36 in growth regulation of endometrial Ishikawa cancer cells.The cellular localization of ER-α36 and ER-α66 were determined by immunofluorescence in the Ishikawa cells. Ishikawa endometrial cancer control cells transfected with an empty expression vector, Ishikawa cells with shRNA knockdown of ER-α36 (Ishikawa/RNAiER36 and Ishikawa cells with shRNA knockdown of ER-α66 (Ishikawa/RNAiER66 were treated with E2 and E2-conjugated to bovine serum albumin (E2-BSA, membrane impermeable in the absence and presence of different kinase inhibitors HBDDE, bisindolylmaleimide, rottlerin, H89 and U0126. The phosphorylation levels of signaling molecules and cyclin D1/cdk4 expression were examined with Western blot analysis and cell growth was monitored with the MTT assay.Immunofluorescence staining of Ishikawa cells demonstrated that ER-α36 was expressed mainly on the plasma membrane and in the cytoplasm, while ER-α66 was predominantly localized in the cell nucleus. Both E2 and E2-BSA rapidly activated PKCδ not PKCα in Ishikawa cells, which could be abrogated by ER-α36 shRNA expression. E2-and E2-BSA-induced ERK phosphorylation required ER-α36 and PKCδ. However, only E2 was able to induce Camp-dependent protein kinase A (PKA phosphorylation. Furthermore, E2 enhances cyclin D1/cdk4 expression via ER-α36.E2 activates the PKCδ/ERK pathway and enhances cyclin D1/cdk4 expression via the membrane-initiated signaling pathways mediated by ER-α36, suggesting a possible involvement of ER-α36 in E2-dependent growth-promoting effects in endometrial cancer cells.

  20. Ro på: Solen er stille

    DEFF Research Database (Denmark)

    Pedersen, Jens Olaf Pepke

    2008-01-01

    Efter at Solen har øget sin aktivitet gennem 100 år, er der nu tydelige tegn på, at den er ved at falde til ro. Er den ved at gå i dvale? Og vil det i så fald udløse en global kuldeperiode?......Efter at Solen har øget sin aktivitet gennem 100 år, er der nu tydelige tegn på, at den er ved at falde til ro. Er den ved at gå i dvale? Og vil det i så fald udløse en global kuldeperiode?...

  1. Den sproglige leg er super fly

    DEFF Research Database (Denmark)

    Just, Sine Nørholm

    2013-01-01

    Man kan rappe om alt. I hvert fald hvis man er Marvelous Mosell. I spændingsfeltet mellem fiktion og virkelighed skaber Mosell sin persona i et forjættende 80' er-univers der på en og samme tid er vildt overdrevet og helt autentisk.......Man kan rappe om alt. I hvert fald hvis man er Marvelous Mosell. I spændingsfeltet mellem fiktion og virkelighed skaber Mosell sin persona i et forjættende 80' er-univers der på en og samme tid er vildt overdrevet og helt autentisk....

  2. N-ov-emb-er

    Indian Academy of Sciences (India)

    " to. Andrew Z Fire - Stanford University School of Medicine Stanford, CA, USA. Craig C Mello - University of Massachusetts Medical School Worcester, MA, USA. -96----------------------------~~--------R-ES-O-N-A-N-C-E--1 -N-ov-e-m-b-er--2-oo-6.

  3. ER2OWL: Generating OWL Ontology from ER Diagram

    Science.gov (United States)

    Fahad, Muhammad

    Ontology is the fundamental part of Semantic Web. The goal of W3C is to bring the web into (its full potential) a semantic web with reusing previous systems and artifacts. Most legacy systems have been documented in structural analysis and structured design (SASD), especially in simple or Extended ER Diagram (ERD). Such systems need up-gradation to become the part of semantic web. In this paper, we present ERD to OWL-DL ontology transformation rules at concrete level. These rules facilitate an easy and understandable transformation from ERD to OWL. The set of rules for transformation is tested on a structured analysis and design example. The framework provides OWL ontology for semantic web fundamental. This framework helps software engineers in upgrading the structured analysis and design artifact ERD, to components of semantic web. Moreover our transformation tool, ER2OWL, reduces the cost and time for building OWL ontologies with the reuse of existing entity relationship models.

  4. PODAAC-ERS13-IMWF0

    Data.gov (United States)

    National Aeronautics and Space Administration — The European Remote Sensing Satellite generation 2 (ERS-2) Level 3 Mean Wind Fields dataset is derived from the ERS-2 scatterometer data and is produced and...

  5. Endoplasmic Reticulum (ER Stress and Endocrine Disorders

    Directory of Open Access Journals (Sweden)

    Daisuke Ariyasu

    2017-02-01

    Full Text Available The endoplasmic reticulum (ER is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the “unfolded protein response” (UPR, which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI, Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2 are discussed in this article.

  6. Hvornår er man ung?

    DEFF Research Database (Denmark)

    Gundelach, Peter; Nørregård-Nielsen, Esther C.

    2002-01-01

    Hvornår er man ung, og hvornår er man voksen? Er der forskelle i befolkningens værdier i forhold til arbejde og politik, når det undersøges ud fra henholdsvis et alders- eller generationsperspektiv? Baseret på data fra den danske del af den internationale værdiundersøgelse vises at der er så store...

  7. Gene therapy to target ER stress in brain diseases.

    Science.gov (United States)

    Valenzuela, Vicente; Martínez, Gabriela; Duran-Aniotz, Claudia; Hetz, Claudio

    2016-10-01

    Gene therapy based on the use of Adeno-associated viruses (AAVs) is emerging as a safe and stable strategy to target molecular pathways involved in a variety of brain diseases. Endoplasmic reticulum (ER) stress is proposed as a transversal feature of most animal models and clinical samples from patients affected with neurodegenerative diseases. Manipulation of the unfolded protein response (UPR), a major homeostatic reaction under ER stress conditions, had proved beneficial in diverse models of neurodegeneration. Although increasing number of drugs are available to target ER stress, the use of small molecules to treat chronic brain diseases is challenging because of poor blood brain barrier permeability and undesirable side effects due to the role of the UPR in the physiology of peripheral organs. Gene therapy is currently considered a possible future alternative to circumvent these problems by the delivery of therapeutic agents to selective regions and cell types of the nervous system. Here we discuss current efforts to design gene therapy strategies to alleviate ER stress on a disease context. This article is part of a Special Issue entitled SI:ER stress. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Multiscale Structural Analysis of Plant ER-PM Contact Sites.

    Science.gov (United States)

    McFarlane, Heather E; Lee, Eun Kyoung; van Bezouwen, Laura S; Ross, Bradford; Rosado, Abel; Samuels, A Lacey

    2017-03-01

    Membrane contact sites are recognized across eukaryotic systems as important nanostructures. Endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (EPCS) are involved in excitation-contraction coupling, signaling, and plant responses to stress. In this report, we perform a multiscale structural analysis of Arabidopsis EPCS that combines live cell imaging, quantitative transmission electron microscopy (TEM) and electron tomography over a developmental gradient. To place EPCS in the context of the entire cortical ER, we examined green fluorescent protein (GFP)-HDEL in living cells over a developmental gradient, then Synaptotagmin1 (SYT1)-GFP was used as a specific marker of EPCS. In all tissues examined, young, rapidly elongating cells showed lamellar cortical ER and higher density of SYT1-GFP puncta, while in mature cells the cortical ER network was tubular, highly dynamic and had fewer SYT1-labeled puncta. The higher density of EPCS in young cells was verified by quantitative TEM of cryo-fixed tissues. For all cell types, the size of each EPCS had a consistent range in length along the PM from 50 to 300 nm, with microtubules and ribosomes excluded from the EPCS. The structural characterization of EPCS in different plant tissues, and the correlation of EPCS densities over developmental gradients illustrate how ER-PM communication evolves in response to cellular expansion. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Hvor automatiseret er den danske fremstillingsindustri?

    DEFF Research Database (Denmark)

    Kromann, Lene; Sørensen, Anders

    Denne første rapport i AIM-projektet viser at der er mulighed for yderligere automation i en stor del af de danske fremstillingsvirksomheder. Gennemsnitlig er kun 30% af produktionsprocessen i virksomhederne automatiseret. Det er især inspektion og eksekvering, som mange virksomheder mangler at a...

  10. En sang der er et overlevelsesudstyr

    DEFF Research Database (Denmark)

    Kock, Christian Erik J

    2015-01-01

    Fredmans Epistel N:o 81 er en af de Bellman-sange der oftest er blevet fortolket af sangere og grupper, og som synes at være blandt hans mest virkningsfulde. Hvad er dens virkning, og hvad beror den på? Læsningen her inddrager både ord og musik, lyd og tanke....

  11. Hvorfor er sygeplejersker usynlige i offentlige medier?

    DEFF Research Database (Denmark)

    Joensen, Annemi Lund; Hall, Elisabeth

    2015-01-01

    Når der er sygeplejerelevante emner til debat i de offentlige medier på Færøerne, bærer debatten præg af sygeplejerskers manglende deltagelse. Sygeplejerskerne er usynlige. Et eksempel på dette er en debat om besparelser inden for ældreomsorgen. Til trods for at besparelsen fik omfattende konsekv...

  12. COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport

    International Nuclear Information System (INIS)

    Wang, Ying-Nai; Wang, Hongmei; Yamaguchi, Hirohito; Lee, Hong-Jen; Lee, Heng-Huan; Hung, Mien-Chie

    2010-01-01

    Research highlights: → ARF1 activation is involved in the EGFR transport to the ER and the nucleus. → Assembly of γ-COP coatomer mediates EGFR transport to the ER and the nucleus. → Golgi-to-ER retrograde trafficking regulates nuclear transport of EGFR. -- Abstract: Emerging evidence indicates that cell surface receptors, such as the entire epidermal growth factor receptor (EGFR) family, have been shown to localize in the nucleus. A retrograde route from the Golgi to the endoplasmic reticulum (ER) is postulated to be involved in the EGFR trafficking to the nucleus; however, the molecular mechanism in this proposed model remains unexplored. Here, we demonstrate that membrane-embedded vesicular trafficking is involved in the nuclear transport of EGFR. Confocal immunofluorescence reveals that in response to EGF, a portion of EGFR redistributes to the Golgi and the ER, where its NH 2 -terminus resides within the lumen of Golgi/ER and COOH-terminus is exposed to the cytoplasm. Blockage of the Golgi-to-ER retrograde trafficking by brefeldin A or dominant mutants of the small GTPase ADP-ribosylation factor, which both resulted in the disassembly of the coat protein complex I (COPI) coat to the Golgi, inhibit EGFR transport to the ER and the nucleus. We further find that EGF-dependent nuclear transport of EGFR is regulated by retrograde trafficking from the Golgi to the ER involving an association of EGFR with γ-COP, one of the subunits of the COPI coatomer. Our findings experimentally provide a comprehensive pathway that nuclear transport of EGFR is regulated by COPI-mediated vesicular trafficking from the Golgi to the ER, and may serve as a general mechanism in regulating the nuclear transport of other cell surface receptors.

  13. COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ying-Nai; Wang, Hongmei; Yamaguchi, Hirohito [Department of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030 (United States); Lee, Hong-Jen; Lee, Heng-Huan [Department of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030 (United States); The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030 (United States); Hung, Mien-Chie, E-mail: mhung@mdanderson.org [Department of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030 (United States); The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030 (United States); Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University and Hospital, Taichung 404, Taiwan (China); Asia University, Taichung 413, Taiwan (China)

    2010-09-03

    Research highlights: {yields} ARF1 activation is involved in the EGFR transport to the ER and the nucleus. {yields} Assembly of {gamma}-COP coatomer mediates EGFR transport to the ER and the nucleus. {yields} Golgi-to-ER retrograde trafficking regulates nuclear transport of EGFR. -- Abstract: Emerging evidence indicates that cell surface receptors, such as the entire epidermal growth factor receptor (EGFR) family, have been shown to localize in the nucleus. A retrograde route from the Golgi to the endoplasmic reticulum (ER) is postulated to be involved in the EGFR trafficking to the nucleus; however, the molecular mechanism in this proposed model remains unexplored. Here, we demonstrate that membrane-embedded vesicular trafficking is involved in the nuclear transport of EGFR. Confocal immunofluorescence reveals that in response to EGF, a portion of EGFR redistributes to the Golgi and the ER, where its NH{sub 2}-terminus resides within the lumen of Golgi/ER and COOH-terminus is exposed to the cytoplasm. Blockage of the Golgi-to-ER retrograde trafficking by brefeldin A or dominant mutants of the small GTPase ADP-ribosylation factor, which both resulted in the disassembly of the coat protein complex I (COPI) coat to the Golgi, inhibit EGFR transport to the ER and the nucleus. We further find that EGF-dependent nuclear transport of EGFR is regulated by retrograde trafficking from the Golgi to the ER involving an association of EGFR with {gamma}-COP, one of the subunits of the COPI coatomer. Our findings experimentally provide a comprehensive pathway that nuclear transport of EGFR is regulated by COPI-mediated vesicular trafficking from the Golgi to the ER, and may serve as a general mechanism in regulating the nuclear transport of other cell surface receptors.

  14. Tank 241-ER-311, grab samples, ER311-98-1, ER311-98-2, ER311-98-3 analytical results for the final report

    International Nuclear Information System (INIS)

    FULLER, R.K.

    1999-01-01

    This document is the final report for catch tank 241-ER-311 grab samples. Three grab samples ER311-98-1, ER311-98-2 and ER311-98-3 were taken from East riser of tank 241-ER-311 on August 4, 1998 and received by the 222-S Laboratory on August 4, 1998. Analyses were performed in accordance with the Compatibility Grab Sampling and Analysis Plan (TSAP) (Sasaki, 1998)and the Data Quality Objectives for Tank Farms Waste Compatibility Program (DQO) (Mulkey and Miller, 1997). The analytical results are presented in the data summary report (Table 1). No notification limits were exceeded

  15. Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells.

    Science.gov (United States)

    Fonseca, Sonya G; Ishigaki, Shinsuke; Oslowski, Christine M; Lu, Simin; Lipson, Kathryn L; Ghosh, Rajarshi; Hayashi, Emiko; Ishihara, Hisamitsu; Oka, Yoshitomo; Permutt, M Alan; Urano, Fumihiko

    2010-03-01

    Wolfram syndrome is an autosomal-recessive disorder characterized by insulin-dependent diabetes mellitus, caused by nonautoimmune loss of beta cells, and neurological dysfunctions. We have previously shown that mutations in the Wolfram syndrome 1 (WFS1) gene cause Wolfram syndrome and that WFS1 has a protective function against ER stress. However, it remained to be determined how WFS1 mitigates ER stress. Here we have shown in rodent and human cell lines that WFS1 negatively regulates a key transcription factor involved in ER stress signaling, activating transcription factor 6alpha (ATF6alpha), through the ubiquitin-proteasome pathway. WFS1 suppressed expression of ATF6alpha target genes and repressed ATF6alpha-mediated activation of the ER stress response element (ERSE) promoter. Moreover, WFS1 stabilized the E3 ubiquitin ligase HRD1, brought ATF6alpha to the proteasome, and enhanced its ubiquitination and proteasome-mediated degradation, leading to suppression of ER stress signaling. Consistent with these data, beta cells from WFS1-deficient mice and lymphocytes from patients with Wolfram syndrome exhibited dysregulated ER stress signaling through upregulation of ATF6alpha and downregulation of HRD1. These results reveal a role for WFS1 in the negative regulation of ER stress signaling and in the pathogenesis of diseases involving chronic, unresolvable ER stress, such as pancreatic beta cell death in diabetes.

  16. Fateful music from a talented orchestra with a wicked conductor: Connection between oncogenic BRAF, ER stress, and autophagy in human melanoma.

    Science.gov (United States)

    Giglio, Paola; Fimia, Gian Maria; Lovat, Penny E; Piacentini, Mauro; Corazzari, Marco

    2015-01-01

    Autophagy and endoplasmic reticulum (ER) stress are involved in the development, progression, and chemoresistance of melanoma. We recently reported that oncogenic serine/threonine-protein kinase BRAF induces chronic ER stress, hence increasing baseline autophagy and promoting chemoresistance. The attenuation of ER stress restores basal autophagic activity and resensitizes melanoma cells to apoptosis.

  17. PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy

    Science.gov (United States)

    Tan, S; Wei, X; Song, M; Tao, J; Yang, Y; Khatoon, S; Liu, H; Jiang, J; Wu, B

    2014-01-01

    Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG). p53-upregulated modulator of apoptosis (PUMA) was identified as a BH3-only Bcl-2 family protein that has an essential role in apoptosis induced by a variety of stimuli, including endoplasmic reticulum (ER) stress. However, whether PUMA is involved in mucosal apoptosis in PHG remains unclear, and whether PUMA induces PHG by mediating ER stress remains unknown. The aim of the study is to investigate whether PUMA is involved in PHG by mediating ER stress apoptotic signaling. To identify whether PUMA is involved in PHG by mediating ER stress, gastric mucosal injury and apoptosis were studied in both PHG patients and PHG animal models using PUMA knockout (PUMA-KO) and PUMA wild-type (PUMA-WT) mice. The induction of PUMA expression and ER stress signaling were investigated, and the mechanisms of PUMA-mediated apoptosis were analyzed. GES-1 and SGC7901 cell lines were used to further identify whether PUMA-mediated apoptosis was induced by ER stress in vitro. Epithelial apoptosis and PUMA were markedly induced in the gastric mucosa of PHG patients and mouse PHG models. ER stress had a potent role in the induction of PUMA and apoptosis in PHG models, and the apoptosis was obviously attenuated in PUMA-KO mice. Although the targeted deletion of PUMA did not affect ER stress, mitochondrial apoptotic signaling was downregulated in mice. Meanwhile, PUMA knockdown significantly ameliorated ER stress-induced mitochondria-dependent apoptosis in vitro. These results indicate that PUMA mediates ER stress-induced mucosal epithelial apoptosis through the mitochondrial apoptotic pathway in PHG, and that PUMA is a potentially therapeutic target for PHG. PMID:24625987

  18. QSAR of estrogen receptor modulators: exploring selectivity requirements for ER(alpha) versus ER(beta) binding of tetrahydroisoquinoline derivatives using E-state and physicochemical parameters.

    Science.gov (United States)

    Mukherjee, Subhendu; Saha, Achintya; Roy, Kunal

    2005-02-15

    Considering importance of developing selective estrogen receptor modulators (SERMs), the present paper explores selectivity requirements of tetrahydroisoquinoline derivatives for binding with ER(alpha) versus ER(beta) receptors using E-state index and physicochemical parameters. The best model [n=21, Q(2)=0.512, R(a)(2)=0.613, R=0.819, F=11.6 (df 3,17)] for ER(alpha) binding data obtained from radioligand binding assay showed importance of C(1), C(15) and lipophilicity (logP) while the best model [n=21, Q(2)=0.768, R(a)(2)=0.796, R=0.904, F=40.1 (df 2,18)] for ER(beta) binding data showed importance of C(1) and molar refractivity (MR). While modeling ER(alpha)/ER(beta) selectivity [n=21, Q(2)=0.695, R(a)(2)=0.739, R=0.882, F=19.8 (df 3,17)], C(1), C(15) and molar refractivity were found to be significant contributors. The data obtained from cellular transcription assay were also modeled. In case of ER(alpha), the best equation involving E-state values of C(1) and C(14) and logP explained 62.1% of the variance while the best equation for ER(beta) involving E-state values of C(1) and C(15) and MR explained 64.6% of the variance of the response variable. In case of ER(alpha)/ER(beta) selectivity, the best equation involving E-state values of O(8), C(14) and N(27) showed 48.3% explained variance, which increased to 63.5% on deletion of single outlier. From the analysis it appears that the nitrogen atom of the aminoethoxyphenyl substituent and 6-hydroxy substituent of the tetrahydroisoquinoline nucleus play important roles for ER(alpha)/ER(beta) selectivity in addition to R(1) and R(2) substituents.

  19. Computational visual distinctness metric

    NARCIS (Netherlands)

    Martínez-Baena, J.; Toet, A.; Fdez-Vidal, X.R.; Garrido, A.; Rodríguez-Sánchez, R.

    1998-01-01

    A new computational visual distinctness metric based on principles of the early human visual system is presented. The metric is applied to quantify (1) the visual distinctness of targets in complex natural scenes and (2) the perceptual differences between compressed and uncompressed images. The new

  20. Induction of ER stress in macrophages of tuberculosis granulomas.

    Directory of Open Access Journals (Sweden)

    Tracie A Seimon

    2010-09-01

    Full Text Available The endoplasmic reticulum (ER stress pathway known as the Unfolded Protein Response (UPR is an adaptive survival pathway that protects cells from the buildup of misfolded proteins, but under certain circumstances it can lead to apoptosis. ER stress has been causally associated with macrophage apoptosis in advanced atherosclerosis of mice and humans. Because atherosclerosis shares certain features with tuberculosis (TB with regard to lesional macrophage accumulation, foam cell formation, and apoptosis, we investigated if the ER stress pathway is activated during TB infection.Here we show that ER stress markers such as C/EBP homologous protein (CHOP; also known as GADD153, phosphorylated inositol-requiring enzyme 1 alpha (Ire1α and eukaryotic initiation factor 2 alpha (eIF2α, and activating transcription factor 3 (ATF3 are expressed in macrophage-rich areas of granulomas in lungs of mice infected with virulent Mycobacterium tuberculosis (Mtb. These areas were also positive for numerous apoptotic cells as assayed by TUNEL. Microarray analysis of human caseous TB granulomas isolated by laser capture microdissection reveal that 73% of genes involved in the UPR are upregulated at the mRNA transcript level. The expression of two ER stress markers, ATF3 and CHOP, were also increased in macrophages of human TB granulomas when assayed by immunohistochemistry. CHOP has been causally associated with ER stress-induced macrophage apoptosis. We found that apoptosis was more abundant in granulomas as compared to non-granulomatous tissue isolated from patients with pulmonary TB, and apoptosis correlated with CHOP expression in areas surrounding the centralized areas of caseation.In summary, ER stress is induced in macrophages of TB granulomas in areas where apoptotic cells accumulate in mice and humans. Although macrophage apoptosis is generally thought to be beneficial in initially protecting the host from Mtb infection, death of infected macrophages in

  1. Dual Role of Ancient Ubiquitous Protein 1 (AUP1) in Lipid Droplet Accumulation and Endoplasmic Reticulum (ER) Protein Quality Control

    OpenAIRE

    Klemm, Elizabeth J.; Spooner, Eric; Ploegh, Hidde L.

    2011-01-01

    Quality control of endoplasmic reticulum proteins involves the identification and engagement of misfolded proteins, dislocation of the misfolded protein across the endoplasmic reticulum (ER) membrane, and ubiquitin-mediated targeting to the proteasome for degradation. Ancient ubiquitous protein 1 (AUP1) physically associates with the mammalian HRD1-SEL1L complex, and AUP1 depletion impairs degradation of misfolded ER proteins. One of the functions of AUP1 in ER quality control is to recruit t...

  2. Photoluminescent layered Y/Er silicates

    International Nuclear Information System (INIS)

    Kostova, Mariya H.; Ananias, Duarte; Carlos, Luis D.; Rocha, Joao

    2008-01-01

    The synthesis of new layered rare-earth silicates K 3 [Y 1-a Er a Si 3 O 8 (OH) 2 ] (AV-22 materials) has been reported. The photoluminescence properties of Y/Er-AV-22 and the material resulting from its thermal degradation, K 3 [Y 1-a Er a Si 3 O 9 ] (Y/Er-AV-23), have been studied and compared. Both materials have a similar chemical makeup and structures sharing analogous building blocks, hence providing a unique opportunity for rationalising the evolution of the photoluminescence properties of lanthanide silicates across dimensionality

  3. Er moral bare noget vi leger?

    DEFF Research Database (Denmark)

    Thomsen, Frej Klem

    2014-01-01

    Hvis man er skeptiker, så er moral nemlig altid kun et udtryk for psykologi og kultur, også når det handler om for eksempel misbrug af børn i Tønder-sagen eller terror-angreb i Madrid, London og Mumbai .......Hvis man er skeptiker, så er moral nemlig altid kun et udtryk for psykologi og kultur, også når det handler om for eksempel misbrug af børn i Tønder-sagen eller terror-angreb i Madrid, London og Mumbai ....

  4. Er virksomheder deres sociale ansvar voksent?

    DEFF Research Database (Denmark)

    Øhrgaard, Per

    2018-01-01

    Eftertanken. Virksomheder er i dag ramt af en CSR-bølge. Men hvis definitionen af, hvad et samfundsmæssigt ansvar er, glider over på virksomhedernes hænder, glider det væk fra alle os andre.......Eftertanken. Virksomheder er i dag ramt af en CSR-bølge. Men hvis definitionen af, hvad et samfundsmæssigt ansvar er, glider over på virksomhedernes hænder, glider det væk fra alle os andre....

  5. Der er ingen gode mennesker i Hundestad

    DEFF Research Database (Denmark)

    Nord, Johan Christian

    2015-01-01

    Lars von Trier sig selv, at han er kulturradikal. Men hans film fortæller en anden historie. I dem flænses alle illusioner - også kulturradikalismen. Netop derfor er han stor - meget større end ham de kaldte Store Klaus......Lars von Trier sig selv, at han er kulturradikal. Men hans film fortæller en anden historie. I dem flænses alle illusioner - også kulturradikalismen. Netop derfor er han stor - meget større end ham de kaldte Store Klaus...

  6. Hydrothermal synthesis and characteristic photoluminescence of Er-doped SnO{sub 2} nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Tuan, Pham Van; Hieu, Le Trung; Nga, La Quynh [International Training Institute for Materials Science, Hanoi University of Science and Technology, No.1, Dai Co Viet, Hanoi (Viet Nam); Dung, Nguyen Duc [Advanced Institute of Science and Technology, Hanoi University of Science and Technology, No.1, Dai Co Viet, Hanoi (Viet Nam); Ha, Ngo Ngoc [International Training Institute for Materials Science, Hanoi University of Science and Technology, No.1, Dai Co Viet, Hanoi (Viet Nam); Khiem, Tran Ngoc, E-mail: khiem@itims.edu.vn [International Training Institute for Materials Science, Hanoi University of Science and Technology, No.1, Dai Co Viet, Hanoi (Viet Nam)

    2016-11-15

    We report the characteristic photoluminescence (PL) spectra of erbium ion (Er{sup 3+})-doped tin dioxide (SnO{sub 2})nanoparticles. The materials were prepared via hydrothermal method at 180 °C with in 20 h by using various Er{sup 3+} ion concentrations ranging from 0.0 to 1.0 at%. After the synthesis, the materials were characterized through X-ray diffraction and high-resolution transmission electron microscopy. Crystallite SnO{sub 2} and its average particle diameter of approximately 5 nm did not change with Er{sup 3+} ion dopant concentration. Photoluminescence spectra showed the characteristic light emission from the Er{sup 3+} ions. The PL excitation spectra referred to an efficient energy transfer to Er{sup 3+} ions in the presence of SnO{sub 2}nanoparticles. The most intense Er-related emission of SnO{sub 2}:Er{sup 3+} nanoparticles in near infrared region was found in samples containing an Er{sup 3+} ion concentration of 0.25 at%. Although the absorption bandgaps of the materials were identified at approximately 3.8 eV, we found that efficient excitation comes with low excitation energy band edge. Excitation is possibly involved in shallow defects in SnO{sub 2} nanoparticles.

  7. Hva er det med Irma?

    Directory of Open Access Journals (Sweden)

    Anne Beate Reinertsen

    2016-10-01

    Full Text Available Abstract: This article is about formative quality assessment in a posthuman or newmaterial perspective; embodied knowledges.  Theory and method are written together in immanence to envision complexity.  The aim and scope of the article is to follow the flow of events Irma produces opening up for affirmative poetical critique praxis. Quality is forwarded as an intensity and force in a moment only.  The moment is therefore the only structure of the text, as moving quality. The intention and inner logic of the text is therefore designed to work against fixed definitions and conceptualizations of what quality and quality assessment is.  This way I hope to show what posthuman and newmaterial approaches can contribute with to build cultures of innovation in which quality is assessed and produces again and again. They put differences to work and open up for creating moments of educational justice. Sammendrag: Artikkelen handler om kvalitetsvurdering i et nymaterielt perspektiv: Kroppslig kunnskap og viten. Teori og metode skrives sammen i immanent samtidighet for å gi et bilde på kompleksitet. Både hensikt og mål med artikkelen er å følge den flyten som Irma som hendelse eller event produserer, for å åpne opp potensialitet for en bekreftende eller affirmativ poetiserende kritikkpraksis og en ny forståelse av- og vurdering for kvalitet. Kvalitet skrives fram som en hendelse, intensitet eller kraft i et øyeblikk. Øyeblikket er derfor tekstens eneste og bærende struktur, som kvalitet i bevegelse. Tekstens indre logikk har slik til hensikt å motvirke forsøk på å skape definerte, faste eller bestemte oppfatninger av hva kvalitet er og hvordan kvalitet kan vurderes. På denne måten håper jeg å vise hva nymaterielle perspektiver kan gjøre for å bygge kulturer for innovasjon hvor kvalitet vurderes og produseres igjen og igjen. De setter forskjellighet i bevegelse og åpner opp for å skape rettferdige utdanningsøyeblikk.

  8. The cation diffusion facilitator proteins MamB and MamM of Magnetospirillum gryphiswaldense have distinct and complex functions, and are involved in magnetite biomineralization and magnetosome membrane assembly

    DEFF Research Database (Denmark)

    Uebe, René; Junge, Katja; Henn, Verena

    2011-01-01

    with the magnetosome membrane of Magnetospirillum gryphiswaldense are MamB and MamM, which were implicated in magnetosomal iron transport because of their similarity to the cation diffusion facilitator family. Here we demonstrate that MamB and MamM are multifunctional proteins involved in several steps of magnetosome...... formation. Whereas both proteins were essential for magnetite biomineralization, only deletion of mamB resulted in loss of magnetosome membrane vesicles. MamB stability depended on the presence of MamM by formation of a heterodimer complex. In addition, MamB was found to interact with several other proteins...... including the PDZ1 domain of MamE. Whereas any genetic modification of MamB resulted in loss of function, site‐specific mutagenesis within MamM lead to increased formation of polycrystalline magnetite particles. A single amino acid substitution within MamM resulted in crystals consisting of haematite, which...

  9. The central effects of alpha-melanocyte stimulating hormone (α-MSH) in chicks involve changes in gene expression of neuropeptide Y and other factors in distinct hypothalamic nuclei.

    Science.gov (United States)

    Delp, Meghan S; Cline, Mark A; Gilbert, Elizabeth R

    2017-06-09

    Alpha-melanocyte stimulating hormone (α-MSH) is a satiety-inducing factor in birds and mammals although central mechanisms mediating its effects on appetite in birds are poorly understood. Thus, the objective of the present study was to determine effects of centrally-injected α-MSH on c-Fos and gene expression in chick appetite-associated hypothalamic nuclei. At 4days post-hatch, 3h-fasted chicks were intracerebroventricularly (ICV) injected with 0 (vehicle) or 0.12nmol α-MSH and 1h later, hypothalamus samples were collected for measuring c-Fos immunoreactivity and mRNA abundance of appetite-associated factors in hypothalamic nuclei. There were more c-Fos immunoreactive cells in the arcuate nucleus (ARC), dorsomedial nucleus (DMN), lateral hypothalamus (LH), and paraventricular nucleus (PVN) of α-MSH- than vehicle-injected chicks. Neuropeptide Y (NPY), oxytocin receptor (OXTR), and agouti-related peptide (AgRP) mRNAs were greater in α-MSH- than vehicle-injected chicks in the ARC. In the PVN, NPY receptor sub-type 1 (NPYR1) mRNA was reduced while c-Fos mRNA was increased in response to treatment with α-MSH. NPY, c-Fos, and DOPA decarboxylase (DDC) mRNAs were greater in treated than vehicle-injected chicks in the DMN. Results suggest that during the first hour post-injection, the appetite-inhibiting effects of α-MSH involve activation of the ARC, DMN, PVN, and LH, and corresponding changes in transcriptional regulation of factors involved with NPY, AgRP and mesotocin signaling, and monoamine synthesis. The effects of these changes may include an inhibition of NPY signaling in the PVN to induce satiety and stimulation of NPY/AgRP neurons in the ARC in an attempt to restore homeostatic levels of food intake. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Ungdomslitteratur former(er) sig

    DEFF Research Database (Denmark)

    Henkel, Ayoe Qvist

    2016-01-01

    Igennem en 'mediesensitiv' analyse af romanen "Akavet" af Ronnie Andersen (2014) og perspektivering til andre aktuelle romaner for og med unge undersøger artiklen, hvordan ungdomslitteratur udvikler sig i dialog med digitale og mediebaserede impulser, og hvilke konsekvenser for udsigelserne om...... ungdomsliv og ungdomslitteraturens æstetik og mulige egenart, denne udvikling har. Artiklen baserer sig på en materialitetstilgang særligt inspireret af N. Katherine Hayles, som ikke tidligere har fået opmærksomhed i læsninger af ungdomslitteratur eller i diskussioner af ungdomslitteraturens mulige egenart......, at ungdomslitteratur drejer sig om unges udviklingsproces fra barndom og til voksenhed og dermed skildrer en overgang præget af linearitet, modning og vækst. Artiklen konkluderer, at der er ungdomslitteratur, der realiseres på andre præmisser, og Akavet kan ses som eksponent for en bevægelse fra ungdomslitteratur som...

  11. Vidensamfundet - det er sund fornuft

    DEFF Research Database (Denmark)

    Pedersen, Esther Oluffa

    2008-01-01

      Artiklen analyserer ophavet til det meget ombruste slogan 'fra tanke til faktura' i Danmarks Erhvervsråds rapport Vidensamfundet - en begrebsafklaring fra 2003 og i skyggerapporten udformet af CO-industri og Dansk Industri (DI) i notatet Fra forskning til faktura fra sommeren 2001. Med baggrund i...... disse rapporter og i regeringens efterfølgende udspil til en omstrukturering af de danske universiteter belyses, hvorledes strategiske udspil fra erhvervsinteressenter bliver konkret politik. Nærværende eksempel viser, hvordan CO-industris og DIs agenda på universitetsområdet meget direkte og i løbet af...... meget kort tid har opnået at blive udmøntet som dansk lov. Sigtet med artiklen er (1) at give en kritisk kommentar til den definition af viden, som ligger til grund for sloganet 'fra tanke til faktura'. Rapporterne analyseres for at belyse den ideologiske baggrund, der ligger bag de strategisk...

  12. Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma

    International Nuclear Information System (INIS)

    Ma, Ji; Zhang, Jian; Liu, Wenchao; Guo, Yan; Chen, Suning; Zhong, Cuiping; Xue, Yan; Zhang, Yuan; Lai, Xiaofeng; Wei, Yifang; Yu, Shentong

    2014-01-01

    Tamoxifen, an endocrine therapy drug used to treat breast cancer, is designed to interrupt estrogen signaling by blocking the estrogen receptor (ER). However, many ER-positive patients are low reactive or resistant to tamoxifen. Metformin is a widely used anti-diabetic drug with noteworthy anti-cancer effects. We investigated whether metformin has the additive effects with tamoxifen in ER-positive breast cancer therapy. The efficacy of metformin alone and in combination with tamoxifen against ER-positive breast cancer was analyzed by cell survival, DNA replication activity, plate colony formation, soft-agar, flow cytometry, immunohistochemistry, and nude mice model assays. The involved signaling pathways were detected by western blot assay. When metformin was combined with tamoxifen, the concentration of tamoxifen required for growth inhibition was substantially reduced. Moreover, metformin enhanced tamoxifen-mediated inhibition of proliferation, DNA replication activity, colony formation, soft-agar colony formation, and induction of apoptosis in ER-positive breast cancer cells. In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway. Finally, two-drug combination therapy significantly inhibited tumor growth in vivo. The present work shows that metformin and tamoxifen additively inhibited the growth and augmented the apoptosis of ER-positive breast cancer cells. It provides leads for future research on this drug combination for the treatment of ER-positive breast cancer

  13. "Det man siger er man selv..."

    DEFF Research Database (Denmark)

    Næsby, Torben; Nørgaard, Britta; Uddholm, Mats

    forhold, der er hermeneutisk, strukturelt og relationelt bestemt. Praksisviden kan ikke være objektiv i gængs forstand, men det behøver ikke at diskvalificere denne viden. Forståelse er altid knyttet til den sag og bundet til den situation man står overfor og i som professionel og som menneske....

  14. Er der en underviser til stede?

    DEFF Research Database (Denmark)

    Christiansen, René Boyer; Nortvig, Anne-Mette; Rosenlund, Lea Tilde

    2015-01-01

    I de senere år er MOOC (Massive Open Online Courses) blevet en faktor på uddannelsesområdet. MOOC-forskning er et forholdsvist nyt felt, men har inden for de seneste 2-3 år udviklet sig med hastige skridt (Liyanagunawardena et al. 2013, Bayne & Ross 2014). En stor del af denne forskning har haft...

  15. Coronavirus infection, ER stress and Apoptosis

    Directory of Open Access Journals (Sweden)

    TO SING eFUNG

    2014-06-01

    Full Text Available The replication of coronavirus, a family of important animal and human pathogens, is closely associated with the cellular membrane compartments, especially the endoplasmic reticulum (ER. Coronavirus infection of cultured cells was previously shown to cause ER stress and induce the unfolded protein response (UPR, a process that aims to restore the ER homeostasis by global translation shutdown and increasing the ER folding capacity. However under prolonged ER stress, UPR can also induce apoptotic cell death. Accumulating evidence from recent studies has shown that induction of ER stress and UPR may constitute a major aspect of coronavirus-host interaction. Activation of the three branches of UPR modulates a wide variety of signaling pathways, such as mitogen-activated protein (MAP kinases activation, autophagy, apoptosis and innate immune response. ER stress and UPR activation may therefore contribute significantly to the viral replication and pathogenesis during coronavirus infection. In this review, we summarize current knowledge on coronavirus-induced ER stress and UPR activation, with emphasis on their cross-talking to apoptotic signaling.

  16. Er formen blevet vigtigst i politik?

    DEFF Research Database (Denmark)

    Etemadi, Maziar Haghpaidar

    2005-01-01

    RETORIK: Retorikken er kunsten at tage ordet - skriftligt eller mundtligt - og udtrykke sig smukt og velformuleret. Gorgias (ca. 490-ca. 390 f. Kr.) fra Leontinoi på Sicilien betragtes som ophavsmanden til den første endelige formulering af retorikkens virke og muligheder: "Talen er en mægtig...

  17. Multikulturalisme er en ny slags Apartheid

    DEFF Research Database (Denmark)

    Dyrberg, Torben Bech

    2016-01-01

    I en ny antologi retter forfatterne et kritisk lys mod forsvarerne af multikulturalisme. Og det er der god grund til, mener en af bogens redaktører. For den store gruppe, der hylder multikulturen, glemmer i al dens godhed, at de samtidig er med til at undergrave demokratiet og styrke uheldige mag...

  18. Extended hormone binding site of the human thyroid stimulating hormone receptor: distinctive acidic residues in the hinge region are involved in bovine thyroid stimulating hormone binding and receptor activation.

    Science.gov (United States)

    Mueller, Sandra; Kleinau, Gunnar; Jaeschke, Holger; Paschke, Ralf; Krause, Gerd

    2008-06-27

    The human thyroid stimulating hormone receptor (hTSHR) belongs to the glycoprotein hormone receptors that bind the hormones at their large extracellular domain. The extracellular hinge region of the TSHR connects the N-terminal leucine-rich repeat domain with the membrane-spanning serpentine domain. From previous studies we reasoned that apart from hormone binding at the leucine-rich repeat domain, additional multiple hormone contacts might exist at the hinge region of the TSHR by complementary charge-charge recognition. Here we investigated highly conserved charged residues in the hinge region of the TSHR by site-directed mutagenesis to identify amino acids interacting with bovine TSH (bTSH). Indeed, the residues Glu-297, Glu-303, and Asp-382 in the TSHR hinge region are essential for bTSH binding and partially for signal transduction. Side chain substitutions showed that the negative charge of Glu-297 and Asp-382 is necessary for recognition of bTSH by the hTSHR. Multiple combinations of alanine mutants of the identified positions revealed an increased negative effect on hormone binding. An assembled model suggests that the deciphered acidic residues form negatively charged patches at the hinge region resulting in an extended binding mode for bTSH on the hTSHR. Our data indicate that certain positively charged residues of bTSH might be involved in interaction with the identified negatively charged amino acids of the hTSHR hinge region. We demonstrate that the hinge region represents an extracellular intermediate connector for both hormone binding and signal transduction of the hTSHR.

  19. PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy

    OpenAIRE

    Tan, S; Wei, X; Song, M; Tao, J; Yang, Y; Khatoon, S; Liu, H; Jiang, J; Wu, B

    2014-01-01

    Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG). p53-upregulated modulator of apoptosis (PUMA) was identified as a BH3-only Bcl-2 family protein that has an essential role in apoptosis induced by a variety of stimuli, including endoplasmic reticulum (ER) stress. However, whether PUMA is involved in mucosal apoptosis in PHG remains unclear, and whether PUMA induces PHG by mediating ER stress remains unknown. The aim of th...

  20. Stress sensing in plants by the ER stress sensor/transducer, bZIP28

    Directory of Open Access Journals (Sweden)

    Renu eSrivastava

    2014-02-01

    Full Text Available Two classes of ER stress sensors are known in plants, membrane associated bZIP transcription factors and RNA splicing factors. ER stress occurs under adverse environmental conditions and results from the accumulation of misfolded or unfolded proteins in the ER lumen. One of the membrane-associated transcription factors activated by heat and ER stress agents is bZIP28. In its inactive form, bZIP28 is a type II protein with a single pass transmembrane domain, residing in the ER. bZIP28’s N-terminus, containing a transcriptional activation domain, is oriented towards the cytoplasm and its C-terminal tail is inserted into the ER lumen. In response to stress, bZIP28 exits the ER and moves to the Golgi where it is proteolytically processed, liberating its cytosolic component which relocates to the nucleus to upregulate stress-response genes. bZIP28 is thought to sense stress through its interaction with the major ER chaperone, BIP. BiP binds to bZIP28’s lumenal domain under unstressed conditions and retains it in the ER. BIP binds to the intrinsically disordered regions on bZIP28’s lumen-facing tail. A truncated form of bZIP28, without its C-terminal tail is not retained in the ER but migrates constitutively to the nucleus. Upon stress, BiP releases bZIP28 allowing it to exit the ER. One model to account for the release of bZIP28 by BiP is that BiP is competed away from bZIP28 by the accumulation of misfolded proteins in the ER. However, other forces such as changes in energy charge levels, redox conditions or interaction with DNAJ proteins may also promote release of bZIP28 from BiP. Movement of bZIP28 from the ER to the Golgi is assisted by the interaction of elements of the COPII machinery with the cytoplasmic domain of bZIP28. Thus, the mobilization of bZIP28 in response to stress involves the dissociation of factors that retain it in the ER and the association of factors that mediate its further organelle-to-organelle movement.

  1. Six-Coordinate Ln(III Complexes with Various Coordination Geometries Showing Distinct Magnetic Properties

    Directory of Open Access Journals (Sweden)

    Mei Guo

    2018-01-01

    Full Text Available The syntheses, structural characterization, and magnetic properties of three lanthanide complexes with formulas [Ln(L13] (Ln = Dy (1Dy; Er (1Er; and [Dy(L22] (2Dy were reported. Complexes 1Dy and 1Er are isostructural with the metal ion in distorted trigonal-prismatic coordination geometry, but exhibit distinct magnetic properties due to the different shapes of electron density for DyIII (oblate and ErIII (prolate ions. Complex 1Dy shows obvious SMM behavior under a zero direct current (dc field with an effective energy barrier of 31.4 K, while complex 1Er only features SMM behavior under a 400 Oe external field with an effective energy barrier of 23.96 K. In stark contrast, complex 2Dy with the octahedral geometry only exhibits the frequency dependence of alternating current (ac susceptibility signals without χ″ peaks under a zero dc field.

  2. Mitochondrial pleomorphy in plant cells is driven by contiguous ER dynamics

    Directory of Open Access Journals (Sweden)

    Erica-Ashley eJaipargas

    2015-09-01

    Full Text Available Mitochondria are pleomorphic, double membrane-bound organelles involved in cellular energetics in all eukaryotes. Mitochondria in animal and yeast cells are typically tubular-reticulate structures and several micro-meters long but in green plants they are predominantly observed as 0.2-1.5µm punctae. While fission and fusion, through the coordinated activity of several conserved proteins, shapes mitochondria, the endoplasmic reticulum (ER has recently been identified as an additional player in this process in yeast and mammalian cells. The mitochondria-ER relationship in plant cells remains largely uncharacterized. Here, through live-imaging of the entire range of mitochondria pleomorphy we uncover the underlying basis for the predominantly punctate mitochondrial form in plants. We demonstrate that mitochondrial morphology changes in response to light and cytosolic sugar levels in an ER mediated manner. Whereas large ER polygons and low dynamics under dark conditions favor mitochondrial fusion and elongation, small ER polygons result in increased fission and predominantly small mitochondria. Hypoxia also reduces ER dynamics and increases mitochondrial fusion to produce giant mitochondria. By observing elongated mitochondria in normal plants and fission-impaired Arabidopsis nmt1-2 and drp3a mutants we also establish that thin extensions called matrixules and a beads-on-a-string mitochondrial phenotype are direct consequences of mitochondria-ER interactions.

  3. Mitochondrial pleomorphy in plant cells is driven by contiguous ER dynamics.

    Science.gov (United States)

    Jaipargas, Erica-Ashley; Barton, Kiah A; Mathur, Neeta; Mathur, Jaideep

    2015-01-01

    Mitochondria are pleomorphic, double membrane-bound organelles involved in cellular energetics in all eukaryotes. Mitochondria in animal and yeast cells are typically tubular-reticulate structures and several micro-meters long but in green plants they are predominantly observed as 0.2-1.5 μm punctae. While fission and fusion, through the coordinated activity of several conserved proteins, shapes mitochondria, the endoplasmic reticulum (ER) has recently been identified as an additional player in this process in yeast and mammalian cells. The mitochondria-ER relationship in plant cells remains largely uncharacterized. Here, through live-imaging of the entire range of mitochondria pleomorphy we uncover the underlying basis for the predominantly punctate mitochondrial form in plants. We demonstrate that mitochondrial morphology changes in response to light and cytosolic sugar levels in an ER mediated manner. Whereas, large ER polygons and low dynamics under dark conditions favor mitochondrial fusion and elongation, small ER polygons result in increased fission and predominantly small mitochondria. Hypoxia also reduces ER dynamics and increases mitochondrial fusion to produce giant mitochondria. By observing elongated mitochondria in normal plants and fission-impaired Arabidopsis nmt1-2 and drp3a mutants we also establish that thin extensions called matrixules and a beads-on-a-string mitochondrial phenotype are direct consequences of mitochondria-ER interactions.

  4. Supervision og de tre k´er

    DEFF Research Database (Denmark)

    Schilling, Benedicte; Jacobsen, Claus Haugaard; Nielsen, Jan

    2010-01-01

    Kontrol, kontrakt og kontekst er supervisionens tre k'er. Men hvad er supervision i det hele taget for en størrelse, der spillerså central en rolle for den psykologfaglige profession?......Kontrol, kontrakt og kontekst er supervisionens tre k'er. Men hvad er supervision i det hele taget for en størrelse, der spillerså central en rolle for den psykologfaglige profession?...

  5. Ytringsfriheden er ikke nødvendig

    DEFF Research Database (Denmark)

    Lauritzen, Pia

    2008-01-01

    nemlig godt konstatere, at ytringsfriheden ikke er nødvendig uden dermed at give afkald på frihed og demokrati.Vi kan oven i købet mene, at ytringsfriheden ophører med at være frihed, når vi betragter den som nødvendig. Og det er lige nøjagtig det, jeg efterlyser: at vi bruger filosoffer som Immanuel...... Kant og Luigi Pareyson til at forstå, at friheden er betydelig mere kompleks, end vi gør den til i øjeblikket....

  6. Branding er ikke til at komme udenom

    DEFF Research Database (Denmark)

    Hermansen, Judy

    2008-01-01

    Søren Askegaard definerer branding som "et iscenesat og afkodet symbolunivers". Det vil sige, at vi på den ene side har virksomhedens strategiske profilering, hvor den forsøger at skabe sig en særlig differentieret og positioneret profil, som adskiller den fra andre virksomheder. "Og det er denne...... strategiske kommunikation, der gør at branding er et ledelsesbegreb og ikke kun et markedsføringsbegreb. Det er ikke staffage, men værdier, som skal gennemsyre alle organisationens aktiviteter." Udgivelsesdato: maj...

  7. Protein transport into the human ER and related diseases, Sec61-channelopathies.

    Science.gov (United States)

    Haßdenteufel, Sarah; Klein, Marie-Christine; Melnyk, Armin; Zimmermann, Richard

    2014-12-01

    Protein transport into the human endoplasmic reticulum (ER) is relevant to the biogenesis of most soluble and membrane proteins of organelles, which are involved in endo- or exo-cytsosis. It involves amino-terminal signal peptides in the precursor polypeptides and various transport components in the cytosol plus the ER, and can occur co- or post-translationally. The two mechanisms merge at the level of the ER membrane, specifically at the level of the heterotrimeric Sec61 complex, which forms a dynamic polypeptide-conducting channel in the ER membrane. Since the mammalian ER is also the main intracellular calcium storage organelle, and the Sec61 complex is calcium permeable, the Sec61 complex is tightly regulated in its equilibrium between the closed and open conformations, or "gated", by ligands, such as signal peptides of the transport substrates and the ER lumenal Hsp70-type molecular chaperone BiP. Furthermore, BiP binding to the incoming polypeptide contributes to the efficiency and unidirectionality of transport. Recent insights into the structure and dynamic equilibrium of the Sec61 complex have various mechanistic as well as medical implications.

  8. ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

    Science.gov (United States)

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-09-15

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

  9. ER Consolidated Quarterly Report October 2014

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, John R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-10-01

    This Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) provides the status of ongoing corrective actions and related Long- Term Stewardship (LTS) activities being implemented by Sandia National Laboratories, New Mexico (SNL/NM) ER for the April, May, and June 2014 quarterly reporting period. Section 2.0 provides the status of ER Operations activities including closure activities for the Mixed Waste Landfill (MWL), project management and site closure, and hydrogeologic characterizations. Section 3.0 provides the status of LTS activities that relate to the Chemical Waste Landfill (CWL) and the associated Corrective Action Management Unit (CAMU). Section 4.0 provides the references noted in Section I of this report.

  10. Bæredygtighed hos SMV'er

    DEFF Research Database (Denmark)

    2016-01-01

    Valg af materiale/medie/form: YouTube Valg af arbejdsform: Videoerne kan bruges som caseundervisning Begrundelse for valg af materiale/medie/form/arbejdsform: Caseundervisning er velegnet til at lære om praksis...

  11. Shear mode ER transfer function for robotic applications

    Energy Technology Data Exchange (ETDEWEB)

    Tan, K P; Stanway, R; Bullough, W A [Department of Mechanical Engineering, University of Sheffield, Sheffield (United Kingdom)

    2005-06-07

    Electro-rheological (ER) fluids are becoming popular in modern industrial applications. The advantage of employing ER devices is due to the ease of energizing the ER fluids at fast speeds of response. One innovation in ER applications could be in the positioning control of the robotic arm using an ER clutch. In order to actuate the manipulator, the ER output torque response is required. However, the behaviour of this ER torque response at different input conditions is not clearly understood. Therefore, in this paper, a sample study of the ER output torque is conducted. The ER output torque responses at different input parameters are studied carefully for the establishment of an appropriate ER transfer function in shear mode. This transfer function will serve as an important feature in future ER-actuated robot arm's control process.

  12. Er iPad digital udeskole?

    DEFF Research Database (Denmark)

    Schilhab, Theresa

    2014-01-01

    Hvor ’konkret’ skal en oplevelse være, for at intuitionen om, at det selvoplevede styrker læringen, holder? Er brug af tablets (e.g. iPads) et ligebyrdigt alternativ til den konkrete oplevelse?......Hvor ’konkret’ skal en oplevelse være, for at intuitionen om, at det selvoplevede styrker læringen, holder? Er brug af tablets (e.g. iPads) et ligebyrdigt alternativ til den konkrete oplevelse?...

  13. Snip snap snude - dobbelthagerne er ude

    DEFF Research Database (Denmark)

    Larsen, Malene Charlotte; Kofoed, Jette

    2015-01-01

    Det handler om at være grim. Det står i skarp kontrast til det pæne og polerede på Instagram. Det er flygtigt, useriøst og ligegyldigt. Og så forsvinder det heldigvis igen, så man behøver kun at forholde sig til det i de få sekunder, det foregår. Snapchat vokser i popularitet og er nu det...

  14. Hvad litteraturen kan, er ofte det rigtige ..

    DEFF Research Database (Denmark)

    Bundsgaard, Jeppe; Kühn, Lisbet

    2010-01-01

    Læsning i dansk handler i første omgang om at blive god til at læse, men på mellemtrinnet er det ved at være tiden til også at bruge skønlitteraturen til det, den er god til, nemlig til at få indsigt i menneskelivets kompleksitet. I dette kapitel anbefales det at gøre noget med litteraturen, fx f...

  15. Hvilke Dødehavstekster er "sekteriske"?

    DEFF Research Database (Denmark)

    Holst, Søren

    2003-01-01

    Skønt Dødehavsrullerne antageligt tilhørte en gruppering, der boede i Qumran, tyder alt på, at mange af teksterne er forfattet andre steder. Artiklen undersøger den særlige sprogbrug, som antageligt er typisk for Qumran-samfundet, og som præger forbavsende få af tekserne. En meget stor del af tek...

  16. Arctigenin alleviates ER stress via activating AMPK

    Science.gov (United States)

    Gu, Yuan; Sun, Xiao-xiao; Ye, Ji-ming; He, Li; Yan, Shou-sheng; Zhang, Hao-hao; Hu, Li-hong; Yuan, Jun-ying; Yu, Qiang

    2012-01-01

    Aim: To investigate the protective effects of arctigenin (ATG), a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L (Compositae), against ER stress in vitro and the underlying mechanisms. Methods: A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTT assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKKβ, LKB1, and AMPKα1 genes was achieved by RNA interference (RNAi). An ATP bioluminescent assay kit was employed to measure the intracellular ATP levels. Results: ATG (2.5, 5 and 10 μmol/L) inhibited cell death and unfolded protein response (UPR) in a concentration-dependent manner in cells treated with the ER stress inducer brefeldin A (100 nmol/L). ATG (1, 5 and 10 μmol/L) significantly attenuated protein synthesis in cells through inhibiting mTOR-p70S6K signaling and eEF2 activity, which were partially reversed by silencing AMPKα1 with RNAi. ATG (1-50 μmol/L) reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C (25 μmol/L) rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG (2.5 and 5 μmol/L) efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate (2 mmol/L) in INS-1 β cells. Conclusion: ATG is an effective ER stress alleviator, which protects cells against ER stress through activating AMPK, thus attenuating protein translation and reducing ER load. PMID:22705729

  17. Trump er godt nyt for verdensfreden

    DEFF Research Database (Denmark)

    Jakobsen, Peter Viggo

    2017-01-01

    Trumps uberegnelighed øger ikke risikoen for krig. Den mindsker den ved at få de allierede til at gøre mere og modstanderne til at forhandle. Det er godt for verdensfreden......Trumps uberegnelighed øger ikke risikoen for krig. Den mindsker den ved at få de allierede til at gøre mere og modstanderne til at forhandle. Det er godt for verdensfreden...

  18. Characterization of the ER-Targeted Low Affinity Ca2+ Probe D4ER

    Directory of Open Access Journals (Sweden)

    Elisa Greotti

    2016-09-01

    Full Text Available Calcium ion (Ca2+ is a ubiquitous intracellular messenger and changes in its concentration impact on nearly every aspect of cell life. Endoplasmic reticulum (ER represents the major intracellular Ca2+ store and the free Ca2+ concentration ([Ca2+] within its lumen ([Ca2+]ER can reach levels higher than 1 mM. Several genetically-encoded ER-targeted Ca2+ sensors have been developed over the last years. However, most of them are non-ratiometric and, thus, their signal is difficult to calibrate in live cells and is affected by shifts in the focal plane and artifactual movements of the sample. On the other hand, existing ratiometric Ca2+ probes are plagued by different drawbacks, such as a double dissociation constant (Kd for Ca2+, low dynamic range, and an affinity for the cation that is too high for the levels of [Ca2+] in the ER lumen. Here, we report the characterization of a recently generated ER-targeted, Förster resonance energy transfer (FRET-based, Cameleon probe, named D4ER, characterized by suitable Ca2+ affinity and dynamic range for monitoring [Ca2+] variations within the ER. As an example, resting [Ca2+]ER have been evaluated in a known paradigm of altered ER Ca2+ homeostasis, i.e., in cells expressing a mutated form of the familial Alzheimer’s Disease-linked protein Presenilin 2 (PS2. The lower Ca2+ affinity of the D4ER probe, compared to that of the previously generated D1ER, allowed the detection of a conspicuous, more clear-cut, reduction in ER Ca2+ content in cells expressing mutated PS2, compared to controls.

  19. Nanostructure of Er3+ doped silicates.

    Science.gov (United States)

    Yao, Nan; Hou, Kirk; Haines, Christopher D; Etessami, Nathan; Ranganathan, Varadh; Halpern, Susan B; Kear, Bernard H; Klein, Lisa C; Sigel, George H

    2005-06-01

    We demonstrate nanostructural evolution resulting in highly increased photoluminescence in silicates doped with Er3+ ions. High-resolution transmission electron microscopy (HRTEM) imaging, nano-energy dispersed X-ray (NEDX) spectroscopy, X-ray diffraction (XRD) and photoluminescence analysis confirm the local composition and structure changes of the Er3+ ions upon thermal annealing. We studied two types of amorphous nanopowder: the first is of the composition SiO2/18Al2O3/2Er2O3 (SAE), synthesized by combustion flame-chemical vapor condensation, and the second is with a composition of SiO2/8Y2O3/2Er2O3 (SYE), synthesized by sol-gel synthesis (composition in mol%). Electron diffraction and HRTEM imaging clearly show the formation of nanocrystallites with an average diameter of approximately 8 nm in SAE samples annealed at 1000 degrees C and SYE samples annealed at 1200 degrees C. The volume fraction of the nanocrystalline phase increased with each heat treatment, eventually leading to complete devitrification at 1400 degrees C. Further XRD and NEDX analysis indicates that the nanocrystalline phase has the pyrochlore structure with the formula Er(x)Al(2-x)Si2O7 or Er(x)Y(2-x)Si2O7 and a surrounding silica matrix.

  20. ZmbZIP60 mRNA is spliced in maize in response to ER stress

    Directory of Open Access Journals (Sweden)

    Li Yanjie

    2012-03-01

    Full Text Available Abstract Background Adverse environmental conditions produce ER stress and elicit the unfolded protein response (UPR in plants. Plants are reported to have two "arms" of the ER stress signaling pathway-one arm involving membrane-bound transcription factors and the other involving a membrane-associated RNA splicing factor, IRE1. IRE1 in yeast to mammals recognizes a conserved twin loop structure in the target RNA. Results A segment of the mRNA encoding ZmbZIP60 in maize can be folded into a twin loop structure, and in response to ER stress this mRNA is spliced, excising a 20b intron. Splicing converts the predicted protein from a membrane-associated transcription factor to one that is targeted to the nucleus. Splicing of ZmbZIP60 can be elicited in maize seedlings by ER stress agents such as dithiothreitol (DTT or tunicamycin (TM or by heat treatment. Younger, rather than older seedlings display a more robust splicing response as do younger parts of leaf, along a developmental gradient in a leaf. The molecular signature of an ER stress response in plants includes the upregulation of Binding Protein (BIP genes. Maize has numerous BIP-like genes, and ER stress was found to upregulate one of these, ZmBIPb. Conclusions The splicing of ZmbZIP60 mRNA is an indicator of ER stress in maize seedlings resulting from adverse environmental conditions such as heat stress. ZmbZIP60 mRNA splicing in maize leads predictively to the formation of active bZIP transcription factor targeted to the nucleus to upregulate stress response genes. Among the genes upregulated by ER stress in maize is one of 22 BIP-like genes, ZmBIPb.

  1. Det er nemt at undgå frygtsomme avlsdyr, og der er kun fordele ved det!

    DEFF Research Database (Denmark)

    Møller, Steen Henrik; Hansen, Steffen W

    2009-01-01

    Der er flere fordele ved at undgå frygtsomme mink i avlsarbejdet, og der er effektive og gennemprøvede redskaber til at finde dem - og indsatsen kan tilpasses behovet. Minkens temperament er vigtigt, fordi rolige og nysgerrige mink er bedre tilpassede, lettere at håndtere, skriger mindre, og de...... frygtsomme og aggressive og tilsvarende mere tillidsfulde end tidligere. I dette indlæg beskriver vi en hurtig og effektiv metode til bestemmelse af minks temperament, hvordan man kan bruge dette i valg af avlsdyr, og hvilke effekter man kan forvente. Udgivelsesdato: oktober 2009...

  2. The Signal Sequence Influences Post-Translational ER Translocation at Distinct Stages

    Czech Academy of Sciences Publication Activity Database

    Johnson, Nicholas; Hassdenteufel, S.; Theis, M.; Paton, A. W.; Paton, J. C.; Zimmermann, R.; High, S.

    2013-01-01

    Roč. 8, č. 10 (2013), e75394/1-e75394/11 E-ISSN 1932-6203 Institutional support: RVO:61388963 Keywords : endoplasmic-reticulum membrane * cell-adhesion molecule-1 * prepro-alpha-factor Subject RIV: CE - Biochemistry Impact factor: 3.534, year: 2013 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0075394

  3. Controlling the Er content of porous silicon using the doping current intensity

    KAUST Repository

    Mula, Guido

    2014-07-04

    The results of an investigation on the Er doping of porous silicon are presented. Electrochemical impedance spectroscopy, optical reflectivity, and spatially resolved energy dispersive spectroscopy (EDS) coupled to scanning electron microscopy measurements were used to investigate on the transient during the first stages of constant current Er doping. Depending on the applied current intensity, the voltage transient displays two very different behaviors, signature of two different chemical processes. The measurements show that, for equal transferred charge and identical porous silicon (PSi) layers, the applied current intensity also influences the final Er content. An interpretative model is proposed in order to describe the two distinct chemical processes. The results can be useful for a better control over the doping process.

  4. Robotics for environmental restoration and waste management (ER and WM)

    International Nuclear Information System (INIS)

    Yook, H.

    1991-01-01

    The Department of Energy (DOE) is making a concerted effort to clean up soils, groundwater, and facilities that have been contaminated with radioactive and hazardous substances. Environmental cleanup work and waste management operations at DOE sites involve the storage, monitoring, handling, processing, and disposal of these substances. With current methods this work is often slow and expensive because both personnel and the environment must be protected from the hazards. The ER and WM Robotics Technology Development Program (RTDP) sponsors applied research and development for the application of robotics to ER and WM needs at the DOE sites. Potential benefits are the following: (1) reduced worker exposure and increased safety through remote operation and control of equipment; (2) increased speed and productivity for ER and WM operations through enhanced capabilities and automation; and (3) reduced life-cycle costs through shorter performance times. A needs-based 5-year plan for RTDP was completed in September 1990. The Plan includes technology development in five application areas at DOE sites. These areas are as follows: (1) waste storage tanks - robotic systems to support waste characterization and retrieval and tank decontamination; (2) buried waste retrieval - robotic systems for support characterization, excavation, retrieval, handling, and packaging of buried wastes; (3) waste minimization - automated process and robotics systems for production operations that can reduce generation of wastes; (4) contaminant analysis automation - remote automated sample handling and analysis to reduce worker exposure, increase productivity, and reduce costs; and (5) decontamination and decommissioning - robotic systems for remote operations to remove equipment and decontamination facilities. Four demonstrations of potential robotics applications to ER and WM needs were performed in FY 1990

  5. MappERS-C and MappERS-V. The crowd source for prevention and crisis support

    Science.gov (United States)

    Frigerio, Simone; Schenato, Luca; Bianchizza, Chiara; Del Bianco, Daniele

    2015-04-01

    The responsibilities within natural hazards at local/regional levels involve citizens and volunteers as first actors of civil protection and territorial management. The prevention implicates the capacities of professional operators and technical volunteers, but the priority implies now the involvement and awareness of the citizens over the territory they inhabit. The involvement of population creates context-specific strategies of territorial surveillance and management, skipping the limit to face risks only when they have to bear impacts on their lives. MAppERS (Mobile Application for Emergency Response and Support) is a EU project (funded under programme 2013-2015 Humanitarian Aid and Civil Protection, ECHO A5) which empowers "crowd-sourced mappers" through smart phone applications and sensors, with geo-tagged information, detailed gathered parameters, field-check survey in a contest of geospatial response. The process of development includes feedback from citizens, involving them in training courses on the monitoring as long term objective (raising public awareness and participation). The project deals with the development and testing of the smart phone applications (module MAppERS-V for volunteers, module MAppERS-C for citizens) according to Android SDK environment. A first research described a desk-based investigation on consequences of disasters impacts and costs of prevention strategies in pilot countries. Furthermore a review of state-of-the-art of database management systems (DBMS) in pilot countries and involvement of volunteers/citizens in data collection/monitoring collected basic info on data structure for the development. A desk-based research proposed communication methods/graphic solutions within mobile technologies for disaster management in pilot countries and available smartphone applications linked to centralized web/server database. A technical review is compulsory for a useful design-line for MappERS development, and it is linked with on

  6. Local compositional environment of Er in ZnS:ErF3 thin film electroluminescent phosphors

    Science.gov (United States)

    Davidson, Mark R.; Stoupin, Stanislav; DeVito, David; Collingwood, Joanna F.; Segre, Carlo; Holloway, Paul H.

    2011-03-01

    ZnS:Er thin film electroluminescent phosphors have been shown to exhibit a marked maximum in the near infrared emission (NIR) after a 425 °C post-deposition anneal with a very narrow temperature window of ±25 °C for optimal NIR emission. Extended X-ray absorption fine structure (EXAFS) spectroscopy has been obtained from both the Zn and Er edges in order to examine the local structure of the host and dopant in this NIR phosphor material. Interestingly, the addition of only ˜0.5 mol. % of Er as ErF3 into the host is found to reduce the Zn-S bond length of one of the two nearest Zn-S shells by 0.6 Å relative to high-quality, atomic layer epitaxy (ALE) grown, pure ZnS. The coordination number of this shorter Zn-S bond increases after the optimal 425 °C anneal. Longer range fits indicate a highly disordered structure, overall, consistent with earlier TEM results. Erbium-L3 EXAFS data from the second and third shells show increasing crystallinity with increasing annealing temperature in the vicinity of the Er dopant. Data from the first shell cannot be fit with S atoms, but are fit equally well with either O or F. Comparison with earlier analyses indicates that the Er is most likely surrounded by F in the first shell. Based on these data and previous studies, we develop a model in which the Er dopant is present as an Er:Fx complex with associated S vacancies, which may include one sulfur atom remaining in the Er nearest shell. Upon annealing, there is a reduction in the F present and a rearrangement of the crystal structure in the vicinity of the Er atom. Optimum annealing conditions occur when optimal crystalline environment is achieved prior to the loss of too much F from the Er:Fx complex.

  7. Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial.

    Science.gov (United States)

    Wapnir, Irene L; Price, Karen N; Anderson, Stewart J; Robidoux, André; Martín, Miguel; Nortier, Johan W R; Paterson, Alexander H G; Rimawi, Mothaffar F; Láng, István; Baena-Cañada, José Manuel; Thürlimann, Beat; Mamounas, Eleftherios P; Geyer, Charles E; Gelber, Shari; Coates, Alan S; Gelber, Richard D; Rastogi, Priya; Regan, Meredith M; Wolmark, Norman; Aebi, Stefan

    2018-04-10

    Purpose Isolated locoregional recurrence (ILRR) predicts a high risk of developing breast cancer distant metastases and death. The Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial investigated the effectiveness of chemotherapy (CT) after local therapy for ILRR. A report at 5 years of median follow-up showed significant benefit of CT for estrogen receptor (ER)-negative ILRR, but additional follow-up was required in ER-positive ILRR. Patients and Methods CALOR was an open-label, randomized trial for patients with completely excised ILRR after unilateral breast cancer. Eligible patients were randomly assigned to receive CT or no CT and stratified by prior CT, hormone receptor status, and location of ILRR. Patients with hormone receptor-positive ILRR received adjuvant endocrine therapy. Radiation therapy was mandated for patients with microscopically involved margins, and anti-human epidermal growth factor receptor 2 therapy was optional. End points were disease-free survival (DFS), overall survival, and breast cancer-free interval. Results From August 2003 to January 2010, 162 patients were enrolled: 58 with ER-negative and 104 with ER-positive ILRR. At 9 years of median follow-up, 27 DFS events were observed in the ER-negative group and 40 in the ER-positive group. The hazard ratios (HR) of a DFS event were 0.29 (95% CI, 0.13 to 0.67; 10-year DFS, 70% v 34%, CT v no CT, respectively) in patients with ER-negative ILRR and 1.07 (95% CI, 0.57 to 2.00; 10-year DFS, 50% v 59%, respectively) in patients with ER-positive ILRR ( P interaction = .013). HRs were 0.29 (95% CI, 0.13 to 0.67) and 0.94 (95% CI, 0.47 to 1.85), respectively, for breast cancer-free interval ( P i nteraction = .034) and 0.48 (95% CI, 0.19 to 1.20) and 0.70 (95% CI, 0.32 to 1.55), respectively, for overall survival ( P interaction = .53). Results for the three end points were consistent in multivariable analyses adjusting for location of ILRR, prior CT, and interval from

  8. Determination of energy transfer parameters in Er3+-doped and Er3+, Pr3+-codoped ZBLAN glasses

    NARCIS (Netherlands)

    Marshall, Christopher; Golding, Paul S.; Jackson, Stuart D.; King, Terence A.; Pollnau, Markus

    A detailed characterization of energy level lifetimes and energy-transfer processes in Er3+-doped and Er3+, Pr3+-codoped ZBLAN bulk glasses is presented. Energy transfer upconversion parameters from the Er3+ 4I13/2 and 4I11/2 levels have been measured and are compared to energy transfer from Er3+ to

  9. BP1 Homeoprotein Enhances Metastatic Potential in ER-negative Breast Cancer

    Science.gov (United States)

    Fu, Yebo; Lian, Yi; Kim, Kyung Soon; Zhang, Lei; Hindle, A. Katharine; Brody, Fred; Siegel, Robert S.; McCaffrey, Timothy A.; Fu, Sidney W.

    2010-01-01

    Tumor invasion and metastasis remain a major cause of mortality in breast cancer patients. It was reported that BP1, a homeobox isoform of DLX4, is overexpressed in 80% of breast cancer patients and in 100% of estrogen receptor negative (ER-) tumors. The prevalence of BP1 positive cells and the intensity of BP1 immunoreactivity increased with the extent of ductal proliferation and tumorigenesis. These findings imply that BP1 may play an important role in ER- breast cancer. We sought to determine the effects and mechanisms of BP1 on cell proliferation and metastasis using ER- Hs578T cells as a model. Cells were transfected with either pcDNA3.2 plasmid containing BP1 gene, or pcDNA3.2 vector, then selected and cloned. Overexpression of BP1 increased cell proliferation rate by 2-5 fold (p=2.0. Of those genes, 49 were up-regulated and 22 were down-regulated. Significant pathways were identified involving cell proliferation and metastasis. These data demonstrated that overexpression of BP1 significantly enhanced cell proliferation and metastatic potential in ER- Hs578T cells. Further analysis with more ER- cell lines and patient samples is warranted to establish BP1 as a therapeutic target for ER- breast cancer. PMID:20842225

  10. Sport er hverken sundt eller social

    DEFF Research Database (Denmark)

    Andersen, Tem Frank

    2013-01-01

    Jeg deler ikke Lasch og Kayser Nielsens konklusioner, selvom jeg er meget enig i, at sport er dirty business. Min analyse peger i den retning, at sporten i sin organiserede form ikke er eller kan fungere som leverandør af nogen ”pakkeløsning”. Men sport kan sagtens bidrage med brudstykker til noget...... meningsfuldt, for det enkelte menneske, eller det enkelte lokalsamfund. Sporten kan ikke længere, hvis den skal fremstå som noget ideal, levere en hel pakke, en fuldstændig myte med tilhørende ritualer. Sport kan imidlertid som projekt fortsat godt levere stof til den meningsskabende fortælling om identitet...

  11. DNA as a component of ER materials

    International Nuclear Information System (INIS)

    Minagawa, K; Aoki, Y; Berber, M R; Mori, T; Tanaka, M

    2009-01-01

    Deoxyribonucleic acid (DNA), which is known as a typical biopolymer, has been utilized for a few types of ER materials. Suspensions were prepared with the particles of DNA, DNA/lipid complexes, and LDH (layered double hydroxide)/DNA composites. The purified DNA showed larger ER effect than the others, but this particle tended to absorb water, which caused less stability. Preliminary experiments of preparing composite with LDH indicated that this inorganic material would be useful for hydrophobic modification of DNA particles, although further optimization of composite preparation is needed. In addition, the LDH/DNA suspensions showed interesting behaviours under some conditions, which indicated possibility for controlling ER property in a wide range.

  12. Luminescence of YAB:Er single crystal

    Energy Technology Data Exchange (ETDEWEB)

    Foeldvari, I.; Beregi, E.; Watterich, A. [Research Institute for Solid State Physics and Optics, HAS, Konkoly-Thege u. 29-33, 1121 Budapest (Hungary); Solarz, P.; Dominiak-Dzik, G.; Ryba-Romanowski, W. [Institute of Low Temperature and Structure Research, PAS, Okolna 2, 50422 Wroclaw (Poland)

    2007-03-15

    Luminescence spectra of YAB:Er crystals were studied in the ultraviolet-visible region and in the 10-300 K temperature range. The dominant Er{sup 3+}-emission belonged to the {sup 4}S{sub 3/2} {yields} {sup 4}I{sub 15/2} transition (18000-18500 cm{sup -1}). Its Stark components were assigned and found to be consistent with those derived from the absorption spectra. The lifetime of the luminescence was determined as a function of temperature and Er-concentration, and the decay kinetics was analyzed. (copyright 2007 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  13. Modulation of endothelial cell migration by ER stress and insulin resistance: a role during maternal obesity?

    Directory of Open Access Journals (Sweden)

    Pablo José Sáez

    2014-08-01

    Full Text Available Adverse microenvironmental stimuli can trigger the endoplasmic reticulum (ER stress pathway, which initiates the unfolded protein response (UPR, to restore protein-folding homeostasis. Several studies show induction of ER stress during obesity. Chronic UPR has been linked to different mechanisms of disease in obese and diabetic individuals, including insulin resistance (IR and impaired angiogenesis. Endothelial cell (EC migration is an initial step for angiogenesis, which is associated with remodeling of existing blood vessels. EC migration occurs according to the leader-follower model, involving coordinated processes of chemotaxis, haptotaxis, and mechanotaxis. Thus, a fine-tuning of EC migration is necessary to provide the right timing to form the required vessels during angiogenesis. ER stress modulates EC migration at different levels, usually impairing migration and angiogenesis, although different effects may be observed depending on the tissue and/or microenvironment. In the context of pregnancy, maternal obesity (MO induces IR in the offspring. Interestingly, several proteins associated with obesity-induced IR are also involved in EC migration, providing a potential link with the ER stress-dependent alterations observed in obese individuals. Different signaling cascades that converge on cytoskeleton regulation directly impact EC migration, including the Akt and/or RhoA pathways. In addition, ER is the main intracellular reservoir for Ca2+, which plays a pivotal role during EC migration. Therefore, ER stress-related alterations in Ca2+ signaling or Ca2+ levels might also produce distorted EC migration. However, the above findings have been studied in the context of adult obesity, and no information has been reported regarding the effect of MO on fetal EC migration. Here we summarize the state of knowledge about the possible mechanisms by which ER stress and IR might impact EC migration and angiogenesis in fetal endothelium exposed to MO

  14. ER stress mediates homocysteine-induced endothelial dysfunction: Modulation of IKCa and SKCa channels.

    Science.gov (United States)

    Wang, Xiang-Chong; Sun, Wen-Tao; Yu, Cheuk-Man; Pun, Shun-Hay; Underwood, Malcolm John; He, Guo-Wei; Yang, Qin

    2015-09-01

    It remains incompletely understood how homocysteine impairs endothelial function. Whether mechanisms such as calcium-activated potassium (KCa) channels are involved is uncertain and the significance of endoplasmic reticulum (ER) stress in KCa channel-dependent endothelial function in hyperhomocysteinemia remains unexplored. We investigated the effect of homocysteine on endothelial KCa channels in coronary vasculature with further exploration of the role of ER stress. Vasorelaxation mediated by intermediate- and small-conductance KCa (IKCa and SKCa) channels was studied in porcine coronary arteries in a myograph. IKCa and SKCa channel currents were recorded by whole-cell patch-clamp in coronary endothelial cells. Protein levels of endothelial IKCa and SKCa channels were determined for both whole-cell and surface expressions. Homocysteine impaired bradykinin-induced IKCa and SKCa-dependent EDHF-type relaxation and attenuated the vasorelaxant response to the channel activator. IKCa and SKCa currents were suppressed by homocysteine. Inhibition of ER stress during homocysteine exposure enhanced IKCa and SKCa currents, associated with improved EDHF-type response and channel activator-induced relaxation. Homocysteine did not alter whole-cell protein levels of IKCa and SKCa whereas lowered surface expressions of these channels, which were restored by ER stress inhibition. Homocysteine induces endothelial dysfunction through a mechanism involving ER stress-mediated suppression of IKCa and SKCa channels. Inhibition of cell surface expression of these channels by ER stress is, at least partially, responsible for the suppressive effect of homocysteine on the channel function. This study provides new mechanistic insights into homocysteine-induced endothelial dysfunction and advances our knowledge of the significance of ER stress in vascular disorders. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. Influence of cellular ER alpha/ER beta ratio on the ER alpha-agonist induced proliferation of human T47D breast cancer cells

    NARCIS (Netherlands)

    Sotoca Covaleda, A.M.; Berg, van den H.; Vervoort, J.J.M.; Saag, van der P.; Strom, A.; Gustafsson, J.A.; Rietjens, I.M.C.M.; Murk, A.J.

    2008-01-01

    Breast cancer cells show overexpression of estrogen receptor (ER) relative to ERß compared to normal breast tissues. This observation has lead to the hypothesis that ERß may modulate the proliferative effect of ER. This study investigated how variable cellular expression ratios of the ER and ERß

  16. Er danskerne så lykkelige?

    DEFF Research Database (Denmark)

    Lolle, Henrik; Andersen, Jørgen Goul

    2013-01-01

    Forskning i lykke og livstilfredshed, eller subjective well-being, er i de seneste år nærmest eksploderet, og parallelt hermed har der været en stærkt stigende politisk interesse i begrebet, ikke mindst i nationale sammenligninger af lykke- og tilfredshedsniveau. Men kan vi nu også stole på disse......, herunder ikke mindst at tilfredshed virker som en magnet på danskere, samt at ordet ”lykkelig” er et stort ord, som man varer sig lidt imod at tage i sin mund set i forhold til det engelske ord ”happy”....

  17. New New Nordic Branding er det nye

    DEFF Research Database (Denmark)

    Andersen, Lars Pynt

    2017-01-01

    Konstruktionen af nordisk regionalisme er en stærk tendens som udgangspunkt for Nordic Branding, men har vi egentlig forstået de værdier og spændinger, der driver hele projektet om en ny ’nordiskhed’?......Konstruktionen af nordisk regionalisme er en stærk tendens som udgangspunkt for Nordic Branding, men har vi egentlig forstået de værdier og spændinger, der driver hele projektet om en ny ’nordiskhed’?...

  18. OL er en mirakelkur for verdens storbyer

    DEFF Research Database (Denmark)

    Østergaard, Katrine; Møller Christensen, Søren

    2006-01-01

    Der er kamp om at blive værtsby for de olympiske lege. Legene giver værtsbyen global opmærksomhed, kickstarter byudviklingen og giver efter al sandsynlighed økonomisk overskud. Men ikke alle byer slipper lige godt fra opgaven......Der er kamp om at blive værtsby for de olympiske lege. Legene giver værtsbyen global opmærksomhed, kickstarter byudviklingen og giver efter al sandsynlighed økonomisk overskud. Men ikke alle byer slipper lige godt fra opgaven...

  19. Geometric calibration of ERS satellite SAR images

    DEFF Research Database (Denmark)

    Mohr, Johan Jacob; Madsen, Søren Nørvang

    2001-01-01

    Geometric calibration of the European Remote Sensing (ERS) Satellite synthetic aperture radar (SAR) slant range images is important in relation to mapping areas without ground reference points and also in relation to automated processing. The relevant SAR system parameters are discussed and calib......Geometric calibration of the European Remote Sensing (ERS) Satellite synthetic aperture radar (SAR) slant range images is important in relation to mapping areas without ground reference points and also in relation to automated processing. The relevant SAR system parameters are discussed...

  20. Er computerspil andet end spild af tid?

    DEFF Research Database (Denmark)

    Andersen, Christian Ulrik

    2006-01-01

    Som andre fiktionsmedier gennem tiden kan også computerspillet reflektere og kommentere den virkelighed, og ikke mindst medie-virkelighed, det selv er en del af. Dette belyses gennem verdens første computerspil, Spacewar fra 1962. Udgivelsesdato: Februar...

  1. Creating Smart-er Cities: An Overview

    Science.gov (United States)

    Allwinkle, Sam; Cruickshank, Peter

    2011-01-01

    The following offers an overview of what it means for cities to be "smart." It draws the supporting definitions and critical insights into smart cities from a series of papers presented at the 2009 Trans-national Conference on Creating Smart(er) Cities. What the papers all have in common is their desire to overcome the all too often…

  2. Hvad er PET og fMRI?

    DEFF Research Database (Denmark)

    B. Paulson, Olaf; Balslev, Daniela; Gerlach, Christian

    2007-01-01

    Hvilken rolle spiller følelserne for vores tankeliv, og hvorfor har vi overhovedet følelser? I kraft af avancerede hjerneskanningsteknikker er den moderne hjernevidenskab blevet i stand til at besvare disse spørgsmål. Gennem artiklerne i denne antologi, skrevet af ledende danske forskere, bliver ...

  3. Hvad nu hvis sommerfuglen er ekshibitionist?

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2008-01-01

    Groft sagt vil denne artikel, ved at aflæse hvad hhv. Inger Christensen, Sigmund Freud og Jacques Lacan har at sige om sommerfugle, argumentere for at der er et afgørende skel mellem naturvidenskab og litteraturvidenskab; mellem naturen, dyret, sommerfuglen på den ene side og bevidstheden...

  4. Der er nye elever i klassen

    DEFF Research Database (Denmark)

    Weirsøe, Mathilde

    2010-01-01

    Etniske minoritetsbørn bliver udsat for 'naturlig' forskelsbehandling i de danske skoler, hvor der stadig undervises, som om alle elever hedder Jensen og Petersen. Det er på tide, at pædagogikken anerkender den etniske kompleksitet i vores samfund og indretter undervisningen derefter....

  5. Hvad er kildekritik?

    DEFF Research Database (Denmark)

    Olden-Jørgensen, Sebastian

    2009-01-01

    Hvad er Kildekritik? I stedet for at forstå kildekritik som et stringent system, grundlagt af Leopold von Ranke og i Danmark kanoniseret af Kristian Erslev, kunne man med større historiografisk ret og faglig frugtbarhed opfatte kildekritikken som en faglig tradition med tre lag afsat (sedimentere...

  6. Ledelse af samskabelse er en ny ledelsesdisciplin

    DEFF Research Database (Denmark)

    Ulrich, Jens; Martin Nielsen, Kim; Bartram, Jan

    2018-01-01

    Samskabelse er blevet det nye orienteringspunkt for rigtig mange offentlige organisationer. Det skyldes en udbredt konsensus om, at velfærdsopgaverne ikke kan løses inden for de vante organisatoriske rammer, men må løses i tæt kontakt med de parter, som opgaverne vedrører. Denne nye tilgang til...

  7. Hvad er hjemkundskabslæreren?

    DEFF Research Database (Denmark)

    Benn, Jette

    2009-01-01

        En appetizer: De praktisk-musiske fag på dagsordenen Temaet for denne artikel er hjemkundskabsfaget, -professionen og dens praktisering belyst gennem et interviewstudie fra 2008 af lærerstuderende og deres lærere. Dette studie relateres til forfatterens tidligere studie af fag og profession i...

  8. Finanskrisen - er den markedsorienterede regulering skurken?

    DEFF Research Database (Denmark)

    Grosen, Anders

    2009-01-01

    markedsorienterede opgørelse tilsyneladende skyld i bankernes dårlige resultater. I hvert fald er standardsætteren inden for international regnskabsregulering, IASB, i efteråret 2008 på rekordtid kommet de betrængte virksomheder - herunder bankerne - til undsætning med en regnskabsmæssig hjælpepakke som supplement...

  9. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

    Science.gov (United States)

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-01-01

    ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297

  10. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy.

    Science.gov (United States)

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-08-02

    Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation.

  11. On Hobbes’s distinction of accidents

    Directory of Open Access Journals (Sweden)

    Lupoli Agostino

    2012-06-01

    Full Text Available An interpolation introduced by K. Schuhmann in his critical edition of "De corpore" (chap. VI, § 13 diametrically overturns the meaning of Hobbes’s doctrine of distinction of accidents in comparison with all previous editions. The article focuses on the complexity of this crucial juncture in "De corpore" argument on which depends the interpretation of Hobbes’s whole conception of science. It discusses the reasons pro and contra Schuhmann’s interpolation and concludes against it, because it is not compatible with the rationale underlying the complex architecture of "De corpore", which involves a symmetry between the ‘logical’ distinction of accidents and the ‘metaphysical’ distinction of phantasms.

  12. The membrane-associated transcription factor NAC089 controls ER-stress-induced programmed cell death in plants.

    Science.gov (United States)

    Yang, Zheng-Ting; Wang, Mei-Jing; Sun, Ling; Lu, Sun-Jie; Bi, Dong-Ling; Sun, Le; Song, Ze-Ting; Zhang, Shuang-Shuang; Zhou, Shun-Fan; Liu, Jian-Xiang

    2014-03-01

    The unfolded protein response (UPR) is activated to sustain cell survival by reducing misfolded protein accumulation in the endoplasmic reticulum (ER). The UPR also promotes programmed cell death (PCD) when the ER stress is severe; however, the underlying molecular mechanisms are less understood, especially in plants. Previously, two membrane-associated transcriptions factors (MTFs), bZIP28 and bZIP60, were identified as the key regulators for cell survival in the plant ER stress response. Here, we report the identification of another MTF, NAC089, as an important PCD regulator in Arabidopsis (Arabidopsis thaliana) plants. NAC089 relocates from the ER membrane to the nucleus under ER stress conditions. Inducible expression of a truncated form of NAC089, in which the transmembrane domain is deleted, induces PCD with increased caspase 3/7-like activity and DNA fragmentation. Knock-down NAC089 in Arabidopsis confers ER stress tolerance and impairs ER-stress-induced caspase-like activity. Transcriptional regulation analysis and ChIP-qPCR reveal that NAC089 plays important role in regulating downstream genes involved in PCD, such as NAC094, MC5 and BAG6. Furthermore, NAC089 is up-regulated by ER stress, which is directly controlled by bZIP28 and bZIP60. These results show that nuclear relocation of NAC089 promotes ER-stress-induced PCD, and both pro-survival and pro-death signals are elicited by bZIP28 and bZIP60 during plant ER stress response.

  13. Expression of ER-α and ER-β during peri-implantation period in uterus is essential for implantation and decidualization in golden hamster.

    Science.gov (United States)

    Kumar, Randhir; Yadav, Akhilesh; Pakrasi, P L

    2017-02-01

    The role of estrogen in embryo implantation in golden hamster (Mesocricetus auratus) is still ambiguous. In order to clarify it, we investigated the spatial distribution and expression of estrogen receptors, ER-α and ER-β in the uterus of pregnant hamster during peri-implantation period and identified the effect of estrogen receptor antagonist ICI-182,780 on the embryo implantation. We performed in vivo experiments on early pregnant hamsters involving treatment with ICI-182,780, an estrogen receptor antagonist. Immunohistochemistry, western blot analysis and quantitative PCR were employed to evaluate the spatio-temporal distribution and expression of ER-α and ER-β in the uterus of normal early pregnant and treated hamsters. Results showed that embryo implantation was completely absent in ICI-182,780 treated uterine horn while, normal implantation occurred in control and vehicle treated horns. Both the receptors were differentially expressed in the uterus of hamster from day 1 (D1) to day7 (D7). In contrast, treated horns without any implantation site showed no trace of any receptors. Protein and mRNA expression of both the receptors were high around the day of implantation while, ER-β expression was up-regulated on D7 of embryo implantation. P value˂0.05 is considered significant. Spatio-temporal expression of ERs in the uterus during peri-implantation period have crucial role for endometrium receptivity and implantation in hamster. Recurrent implantation failure is the devastating problem among the desirable couple and is mainly due to defect in endometrium receptivity. This study may provide a new insight to manage the problem of idiopathic infertility. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Bringing distinctive TV drama?

    DEFF Research Database (Denmark)

    Jensen, Pia Majbritt; Raats, Tim

    success in terms of distribution strategy, combining clever marketing and commercial strategies to secure higher budgets and at the same time enlarge the market scope of DR’s drama series. The case comparison builds on a document analysis of enforceable policy regulation with regard to tv drama (in...... charters, management contracts, etc.) and an analysis of existing TV drama series since 2009. By analysing the amount of audiovisual drama productions, the composition of budgets and partnerships involved in production and distribution, we examine the role of Public Service drama as part of a ‘lever...... on an inventory of TV drama series and their respective relative financing compositions from 2009 to 2015. The findings derive from a 2014 analysis of TV drama financing in Flanders and data gathered from the DR and VRT research departments, which are complemented with findings in annual reports and expert...

  15. MGS MARS/MOONS MAG/ER MAPPING ER ANGULAR FLUX V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set consists of calibrated, time-ordered, angle-resolved electron flux data from the Electron Reflectometer (ER) instrument on the Mars Global Surveyor...

  16. Low cytoplasmic pH reduces ER-Golgi trafficking and induces disassembly of the Golgi apparatus.

    Science.gov (United States)

    Soonthornsit, Jeerawat; Yamaguchi, Yoko; Tamura, Daisuke; Ishida, Ryuichi; Nakakoji, Yoko; Osako, Shiho; Yamamoto, Akitsugu; Nakamura, Nobuhiro

    2014-11-01

    The Golgi apparatus was dramatically disassembled when cells were incubated in a low pH medium. The cis-Golgi disassembled quickly, extended tubules and spread to the periphery of cells within 30 min. In contrast, medial- and trans-Golgi were fragmented in significantly larger structures of smaller numbers at a slower rate and remained largely in structures distinct from the cis-Golgi. Electron microscopy revealed the complete disassembly of the Golgi stack in low pH treated cells. The effect of low pH was reversible; the Golgi apparatus reassembled to form a normal ribbon-like structure within 1-2h after the addition of a control medium. The anterograde ER to Golgi transport and retrograde Golgi to ER transport were both reduced under low pH. Phospholipase A2 inhibitors (ONO, BEL) effectively suppressed the Golgi disassembly, suggesting that the phospholipase A2 was involved in the Golgi disassembly. Over-expression of Rab1, 2, 30, 33 and 41 also suppressed the Golgi disassembly under low pH, suggesting that they have protective role against Golgi disassembly. Low pH treatment reduced cytoplasmic pH, but not the luminal pH of the Golgi apparatus, strongly suggesting that reduction of the cytoplasmic pH triggered the Golgi disassembly. Because a lower cytoplasmic pH is induced in physiological or pathological conditions, disassembly of the Golgi apparatus and reduction of vesicular transport through the Golgi apparatus may play important roles in cell physiology and pathology. Furthermore, our findings indicated that low pH treatment can serve as an important tool to analyze the molecular mechanisms that support the structure and function of the Golgi apparatus. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Hvornår er agil projektledelse rigtig?

    DEFF Research Database (Denmark)

    Pries-Heje, Jan

    2011-01-01

    Styrken ved agil projektledelse er hurtigheden og muligheden for at absorbere ændringer hurtigt gennem hele projektets løbetid, men der er naturligvis også nogle svagheder. Nogle af dem nævner jeg i artiklen, men derudover egner agil-formen sig ikke specielt godt til komplicerede projekter, hvor...... liv eller mange penge er på spil. Agil-formen er heller ikke velegnet til umotiverede medarbejdere, fordi de ikke har noget at bidrage med. For en projektleder synes jeg, at det er væsentligt at have et dybdegående kendskab til positive og negative sider ved både agil og plandreven projektledelse....... Verden er kompleks, og vores projekter derfor er tilsvarende komplekse. Som projektleder bør man således kunne analysere sig frem til den rigtige form for projektledelse, uanset om det er agil projektledelse eller ej....

  18. ER Consolidated Qtrly Rpt_April-June 2016_October 2016

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, John R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-10-01

    This Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) provides the status of ongoing corrective action activities being implemented by Sandia National Laboratories, New Mexico (SNL/NM) for the April, May, and June 2016 quarterly reporting period.

  19. TCSP ER-2 MICROWAVE TEMPERATURE PROFILER (MTP) V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The TCSP ER-2 Microwave Temperature Profiler (MTP) dataset was collected by the ER-2 Microwave Temperature Profiler (MTP), which is a passive microwave radiometer...

  20. PODAAC-ERS2X-IMWF0

    Data.gov (United States)

    National Aeronautics and Space Administration — The European Remote Sensing Satellite generation 2 (ERS-2) Level 3 Mean Wind Fields dataset is derived from the ERS-2 scatterometer data and is produced and...

  1. GPM Ground Validation Navigation Data ER-2 OLYMPEX V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The GPM Ground Validation NASA ER-2 Navigation Data OLYMPEX dataset supplies navigation data collected by the NASA ER-2 aircraft for flights that occurred during...

  2. CAMEX-4 ER-2 HIGH ALTITUDE DROPSONDE V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The CAMEX-4 ER-2 High Altitude Dropsonde dataset was collected by the ER-2 High Altitude Dropsonde System (EHAD), which used dropwinsondes fitted with Global...

  3. CAMEX-4 ER-2 LIGHTNING INSTRUMENT PACKAGE (LIP) V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The CAMEX-4 ER-2 Lightning Instrument Package (LIP) dataset was collected by the ER-2 LIP, which allows the vector components of the electric field (i.e, Ex, Ey, Ez...

  4. Senior Sport er læring i virkeligheden

    DEFF Research Database (Denmark)

    Meyer, Erna Rosenlund

    2014-01-01

    Samarbejde mellem fysioterapeutudddannelsen på UCN og Aalborg senior Sport er givende for alle parter, inklusiv studerende.......Samarbejde mellem fysioterapeutudddannelsen på UCN og Aalborg senior Sport er givende for alle parter, inklusiv studerende....

  5. Impact of estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) co-expression on breast cancer disease characteristics: implications for tumor biology and research.

    Science.gov (United States)

    Alqaisi, Abeer; Chen, Li; Romond, Edward; Chambers, Mara; Stevens, Mark; Pasley, Grace; Awasthi, Mukta; Massarweh, Suleiman

    2014-11-01

    ER and HER2 are critical drivers of breast cancer biology and can interact when co-expressed, but less data describe the impact of ER/HER2 co-expression on clinical disease characteristics. We studied the impact of ER and HER2 (co)-expression in a cohort of 1,187 patients with invasive breast cancer and compared disease characteristics among different groups according to ER and HER2 status. Age, tumor size, grade, nodal status, TNM stage, and metastatic sites were compared and significance determined using the appropriate t tests. All p values were two-tailed. Compared to ER-negative/HER2-negative disease as the control group, ER expression was associated with older age, smaller tumors, lower grade, earlier TNM stage, and increased bone involvement in de novo metastasis, while HER2 had no significant impact on these characteristics. ER and HER2 co-expression was associated with lower grade and higher bone involvement in de novo metastasis, reflecting a retained impact for ER. HER2 impact on ER-positive disease was reflected by younger age, higher grade and TNM stage, and increased frequency of visceral involvement in de novo metastasis. Within the ER-positive/HER2-positive group, triple positive breast cancer (ER+/PgR+/HER2+) was associated with younger age compared to ER+/PgR-/HER2+ disease (mean age of 50.8 vs. 56 years, p = 0.0226). PgR was also associated with younger age in ER+/HER2- disease with a mean age of 57.6 years in ER+/PgR+/HER2- disease vs. 63.4 years in ER+/PgR-/HER2- disease (p impact on breast cancer characteristics, including a retained impact when co-expressed with HER2. Similarly, HER2 dramatically modulates ER-positive breast cancer making it more aggressive. PgR association with young age may be related to hormonal levels of the premenopausal state, with HER2 providing an earlier growth advantage in triple positive disease, suggesting a specific dependence for this subset on high estrogen levels.

  6. Er:YAG laser scaling of diseased root surfaces: a histologic study.

    Science.gov (United States)

    Crespi, Roberto; Barone, Antonio; Covani, Ugo

    2006-02-01

    The aim of the present study was to observe the effects of an erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser when used to treat periodontally involved root surfaces. Forty teeth affected by severe periodontal disease and scheduled for extraction were divided into two groups: in group A (control), 20 teeth were treated by hand instrumentation, and in group B (test), 20 teeth were treated by Er:YAG laser. In group A (teeth treated by curets), the root cementum layer was completely removed, but many deep scratches on the dentin layer were also observed. In group B, the laser-treated root surfaces, there was no cracking or carbonization, and the bacterial flora was completely eliminated, leaving a rough and uniform surface. Results of the present study showed that clinical use of an Er:YAG laser in vivo achieves plaque and calculus removal, providing a rough surface morphology.

  7. Optical properties of Er3+-doped strontium barium niobate nanocrystals obtained by thermal treatment in glass

    International Nuclear Information System (INIS)

    Haro-Gonzalez, P.; Lahoz, F.; Gonzalez-Platas, J.; Caceres, J.M.; Gonzalez-Perez, S.; Marrero-Lopez, D.; Capuj, N.; Martin, I.R.

    2008-01-01

    Measurements of the optical properties of Er 3+ ions in strontium barium niobate glass and glass ceramics have been carried out. The glasses have been fabricated using a melt-quenching method, and the glass ceramic samples have been obtained from the glass precursor by a thermal treatment. The ceramic samples formed by a glassy phase, and a crystalline phase contains nanocrystals of Sr 1-x Ba x Nb 2 O 6 (SBN) doped with Er 3+ ions with a mean size of ∼50 nm, as confirmed with XRD. Green up-conversion emission has been obtained under excitation at 800 nm, and the temporal evolution of this emission has been reported with the purpose of determining the involved up-conversion mechanism. These optical measures have confirmed that the Er 3+ ions have been incorporated into the SBN matrix, after a thermal treatment, which produced an increment of the up-conversion efficiency

  8. Hvad skal danske hospitaler med ungecaféer?

    DEFF Research Database (Denmark)

    Kvisgaard Knudsen, Kristina; Bregnballe, Vibeke

    at forbedre unges oplevelse af at være indlagt, er der i Danmark etableret ungecaféer. Formål: At undersøge ungecaféers betydning for indlagte unge. Metode: Fire semistrukturerede interviews er foretaget med kronisk eller alvorligt syge unge i alderen 11-19 år. De unge har besøgt Café Nexus på Aarhus...

  9. Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors

    Directory of Open Access Journals (Sweden)

    Hui eHan

    2013-10-01

    Full Text Available Mortality from liver cancer in humans is increasingly attributable to heavy or long-term alcohol consumption. The mechanisms by which alcohol exerts its carcinogenic effect are not well understood. In this study, the role of alcohol-induced endoplasmic reticulum (ER stress response in liver cancer development was investigated using an animal model with a liver knockout of the chaperone BiP and under constitutive hepatic ER stress. Long-term alcohol and high fat diet (HFD feeding resulted in higher levels of serum alanine aminotransferase (ALT, impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months knockout females than in either middle-aged (6 months knockouts or older (aged 16 months wild type females. In the older knockout females, stronger effects of the alcohol on methylation of CpG islands at promoter regions of genes involved in the ER associated degradation (ERAD were also detected. Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with EGF-like domains 2, Herpud1 (ubiquitin-like domain member, Wfs1 (wolfram syndrome gene, and Yod1 (deubiquinating enzyme 1 was co-present with decreased proteasome activities, increased estrogen receptor alpha variant (ERa36, and enhanced phosphorylations of ERK1/2 (extracellular signal-regulated protein kinases 1 and 2 and STAT3 (the signal transducers and activators of transcription in the older knockout female fed alcohol. Our results suggest that long-term alcohol consumption and ageing may promote liver tumorigenesis in females through interfering with DNA methylation and expression of genes involved in the ER associated degradation.

  10. Distinctive skeletal dysplasia in Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-03-01

    Cockayne syndrome is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvement of the spine.

  11. Tamoxifen-independent recombination in the RIP-CreER mouse.

    Directory of Open Access Journals (Sweden)

    Yanmei Liu

    Full Text Available BACKGROUND: The inducible Cre-lox system is a valuable tool to study gene function in a spatial and time restricted fashion in mouse models. This strategy relies on the limited background activity of the modified Cre recombinase (CreER in the absence of its inducer, the competitive estrogen receptor ligand, tamoxifen. The RIP-CreER mouse (Tg (Ins2-cre/Esr1 1Dam is among the few available β-cell specific CreER mouse lines and thus it has been often used to manipulate gene expression in the insulin-producing cells of the endocrine pancreas. PRINCIPAL FINDINGS: Here, we report the detection of tamoxifen-independent Cre activity as early as 2 months of age in RIP-CreER mice crossed with three distinct reporter strains. SIGNIFICANCE: Evidence of Cre-mediated recombination of floxed alleles even in the absence of tamoxifen administration should warrant cautious use of this mouse for the study of pancreatic β-cells.

  12. NRF1 Is an ER Membrane Sensor that Is Central to Cholesterol Homeostasis.

    Science.gov (United States)

    Widenmaier, Scott B; Snyder, Nicole A; Nguyen, Truc B; Arduini, Alessandro; Lee, Grace Y; Arruda, Ana Paula; Saksi, Jani; Bartelt, Alexander; Hotamisligil, Gökhan S

    2017-11-16

    Cholesterol is a critical nutrient requiring tight constraint in the endoplasmic reticulum (ER) due to its uniquely challenging biophysical properties. While the mechanisms by which the ER defends against cholesterol insufficiency are well described, it remains unclear how the ER senses and effectively defends against cholesterol excess. Here, we identify the ER-bound transcription factor nuclear factor erythroid 2 related factor-1, Nrf1/Nfe2L1, as a critical mediator of this process. We show that Nrf1 directly binds to and specifically senses cholesterol in the ER through a defined domain and that cholesterol regulates Nrf1 turnover, processing, localization, and activity. In Nrf1 deficiency, in vivo cholesterol challenges induce massive hepatic cholesterol accumulation and damage, which is rescued by replacing Nrf1 exogenously. This Nrf1-mediated mechanism involves the suppression of CD36-driven inflammatory signaling and derepression of liver X receptor activity. These findings reveal Nrf1 as a guardian of cholesterol homeostasis and a core component of adaptive responses to excess cellular cholesterol. Copyright © 2017. Published by Elsevier Inc.

  13. Tanshinone-induced ERs suppresses IGFII activation to alleviate Ang II-mediated cardiac hypertrophy.

    Science.gov (United States)

    Chen, Ya-Fang; Lee, Nien-Hung; Pai, Pei-Ying; Chung, Li-Chin; Shen, Chia-Yao; Rajendran, Peramaiyan; Chen, Yu-Feng; Chen, Ray-Jade; Padma Viswanadha, Vijaya; Kuo, Wei-Wen; Huang, Chih-Yang

    2017-10-01

    Cardiomyopathy involves changes in myocardial ultrastructure and cardiac hypertrophy. Angiotensin II (AngII) has previously been shown to stimulate the expression of IGF-2 and IGF-2R in H9c2 cardiomyoblasts and increase of blood pressure, and cardiac hypertrophy. Estrogen receptors (ERs) exert protective effects, such as anti-hypertrophy in cadiomyocytes. Tanshinone IIA (TSN), a main active ingredient from a Chinese medical herb, Salvia miltiorrhiza Bunge (Danshen), was shown to protect cardiomyocytes hypertrophy by different stress signals. We aimed to investigate whether TSN protected H9c2 cardiomyocytes from AngII-induced activation of IGF-2R pathway and hypertrophy by mediating through ERs. AngII resulted in H9c2 cardiomyoblast hypertrophy and increased inflammatory molecular markers. These were down-regulated by TSN via estrogen receptors. AngII resulted in elevation in MAPKs, IGF-2R and hypertrophic protein markers. These, again, were reduced by addition of the phytoestrogen with activation of ERs. Finally, AngII induced phosphorylation of heat shock factor-1 (HSF1) and decreased sirtuin-1 (SIRT1). In addition, AngII also caused an increase in distribution of IGF-2R molecules on cell membrane. In contrast, TSN reduced HSF1 phosphorylation and cell surface IGF-2R while elevating SIRT1 via ERs. TSN was capable of attenuating AngII-induced IGF-2R pathway and hypertrophy through ERs in H9c2 cardiomyoblast cells.

  14. E2F8 confers cisplatin resistance to ER+ breast cancer cells via transcriptionally activating MASTL.

    Science.gov (United States)

    Tian, Jianjun; Lin, Yuting; Yu, Jianhua

    2017-08-01

    MASTL (microtubule-associated serine/threonine kinase-like) is a critical kinase modulating mitotic entry. In this study, we investigated the mechanism of its dysregulation in breast cancer and its involvement in cisplatin resistance in ER+ breast cancer cells. Data mining in Kaplan-Meier Plotter showed that high MASTL expression was associated with worse distant metastasis free survival (DMFS) and relapse free survival (RFS) in ER+ breast cancer patients. In TCGA breast cancer cohort (TCGA-BRCA), MASTL was strongly co-upregulated with E2F8. High E2F8 expression was also strongly associated with unfavorable DMFS and RFS in ER+ breast cancer patients. Promoter scanning in JASPAR Database showed that the MASTL promoter region has a highly possible E2F8 binding site upstream the TSS site. The following western blot, dual luciferase assay and ChIP-qPCR validated this binding site. In MCF-7 cells, E2F8 overexpression alleviated cisplatin induced cell apoptosis by shortening G2/M arrest and promoting mitotic entry, the effect of which was largely canceled by inhibiting MASTL. Therefore, we infer that E2F8 can shorten cisplatin induced G2/M arrest by promoting MASTL mediated mitotic progression in ER+ breast cancer cells. These findings might help to explain why high MASTL or high E2F8 expression is associated with worse RFS in ER+ breast cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Pige klik varsomt, thi scenen er skrå

    DEFF Research Database (Denmark)

    Sandvik, Kjetil

    2007-01-01

    At spille roller er en væsentlig del af mange computerspil. Nogle af disse roller er prædesignede af spildesignerne, andre er mere åbne og spilleren må derfor selv udfylde rollen. I såkaldte 'role-playing-games' (RPGs) har spilleren mulighed for at kreere sin egen rolle ved at anvende spillets...

  16. TCSP ER-2 DOPPLER RADAR (EDOP) V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The TCSP ER-2 DOPPLER RADAR (EDOP) dataset was collected by the ER-2 Doppler radar (EDOP), which is an X-band (9.6 GHz) Doppler radar mounted in the nose of the ER-2...

  17. CAMEX-4 ER-2 DOPPLER RADAR V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The CAMEX-4 ER-2 Doppler Radar dataset was collected by the ER-2 Doppler radar (EDOP), which is an X-band (9.6 GHz) Doppler radar mounted in the nose of ER-2. The...

  18. Gene expression profiling analysis of bisphenol A-induced perturbation in biological processes in ER-negative HEK293 cells.

    Science.gov (United States)

    Yin, Rong; Gu, Liang; Li, Min; Jiang, Cizhong; Cao, Tongcheng; Zhang, Xiaobai

    2014-01-01

    Bisphenol A (BPA) is an environmental endocrine disruptor which has been detected in human bodies. Many studies have implied that BPA exposure is harmful to human health. Previous studies mainly focused on BPA effects on estrogen receptor (ER)-positive cells. Genome-wide impacts of BPA on gene expression in ER-negative cells is unclear. In this study, we performed RNA-seq to characterize BPA-induced cellular and molecular impacts on ER-negative HEK293 cells. The microscopic observation showed that low-dose BPA exposure did not affect cell viability and morphology. Gene expression profiling analysis identified a list of differentially expressed genes in response to BPA exposure in HEK293 cells. These genes were involved in variable important biological processes including ion transport, cysteine metabolic process, apoptosis, DNA damage repair, etc. Notably, BPA up-regulated the expression of ERCC5 encoding a DNA endonuclease for nucleotide-excision repair. Further electrochemical experiment showed that BPA induced significant DNA damage in ER-positive MCF-7 cells but not in ER-negative HEK293 cells. Collectively, our study revealed that ER-negative HEK293 cells employed mechanisms in response to BPA exposure different from ER-positive cells.

  19. DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca2+ Transfer through the MAM

    Directory of Open Access Journals (Sweden)

    Sung Jin Park

    2017-12-01

    Full Text Available Summary: A wide range of Ca2+-mediated functions are enabled by the dynamic properties of Ca2+, all of which are dependent on the endoplasmic reticulum (ER and mitochondria. Disrupted-in-schizophrenia 1 (DISC1 is a scaffold protein that is involved in the function of intracellular organelles and is linked to cognitive and emotional deficits. Here, we demonstrate that DISC1 localizes to the mitochondria-associated ER membrane (MAM. At the MAM, DISC1 interacts with IP3R1 and downregulates its ligand binding, modulating ER-mitochondria Ca2+ transfer through the MAM. The disrupted regulation of Ca2+ transfer caused by DISC1 dysfunction leads to abnormal Ca2+ accumulation in mitochondria following oxidative stress, which impairs mitochondrial functions. DISC1 dysfunction alters corticosterone-induced mitochondrial Ca2+ accumulation in an oxidative stress-dependent manner. Together, these findings link stress-associated neural stimuli with intracellular ER-mitochondria Ca2+ crosstalk via DISC1, providing mechanistic insight into how environmental risk factors can be interpreted by intracellular pathways under the control of genetic components in neurons. : Park et al. show that DISC1 regulates ER-mitochondria Ca2+ transfer through mitochondria-associated ER membrane (MAM. DISC1 dysfunction at MAM increases ER-mitochondria Ca2+ transfer during oxidative stress and excessive amounts of corticosterone, which impairs mitochondrial function. Keywords: DISC1, MAM, mitochondria, Ca2+, IP3R1, oxidative stress

  20. Gene expression profiling analysis of bisphenol A-induced perturbation in biological processes in ER-negative HEK293 cells.

    Directory of Open Access Journals (Sweden)

    Rong Yin

    Full Text Available Bisphenol A (BPA is an environmental endocrine disruptor which has been detected in human bodies. Many studies have implied that BPA exposure is harmful to human health. Previous studies mainly focused on BPA effects on estrogen receptor (ER-positive cells. Genome-wide impacts of BPA on gene expression in ER-negative cells is unclear. In this study, we performed RNA-seq to characterize BPA-induced cellular and molecular impacts on ER-negative HEK293 cells. The microscopic observation showed that low-dose BPA exposure did not affect cell viability and morphology. Gene expression profiling analysis identified a list of differentially expressed genes in response to BPA exposure in HEK293 cells. These genes were involved in variable important biological processes including ion transport, cysteine metabolic process, apoptosis, DNA damage repair, etc. Notably, BPA up-regulated the expression of ERCC5 encoding a DNA endonuclease for nucleotide-excision repair. Further electrochemical experiment showed that BPA induced significant DNA damage in ER-positive MCF-7 cells but not in ER-negative HEK293 cells. Collectively, our study revealed that ER-negative HEK293 cells employed mechanisms in response to BPA exposure different from ER-positive cells.

  1. Ellers er det jo bare en stol

    DEFF Research Database (Denmark)

    Hansen, Per H.

    2013-01-01

    Brands. Kan man sælge Georg Jensen-smykker fra Bahrain? Eller Arne Jacobsens myrestole fra Polen? Der er masser af brands, der har fået halen på komedie ved at overse, hvorfor de selv har opnået så stærk en position i første omgang.......Brands. Kan man sælge Georg Jensen-smykker fra Bahrain? Eller Arne Jacobsens myrestole fra Polen? Der er masser af brands, der har fået halen på komedie ved at overse, hvorfor de selv har opnået så stærk en position i første omgang....

  2. ER-12-1 completion report

    International Nuclear Information System (INIS)

    Russell, C.E.; Gillespie, D.; Cole, J.C.; Drellack, S.L.

    1996-12-01

    The objective of drillhole ER-12-1 was to determine the hydrogeology of paleozoic carbonate rocks and of the Eleana Formation, a regional aquitard, in an area potentially downgradient from underground nuclear testing conducted in nearby Rainier Mesa. This objective was addressed through the drilling of well ER-12-1 at N886,640.26 E640,538.85 Nevada Central Coordinates. Drilling of the 1094 m (3588 ft) well began on July 19, 1991 and was completed on October 17, 1991. Drilling problems included hole deviation and hole instability that prevented the timely completion of this borehole. Drilling methods used include rotary tri-cone and rotary hammer drilling with conventional and reverse circulation using air/water, air/foam (Davis mix), and bentonite mud. Geologic cuttings and geophysical logs were obtained from the well. The rocks penetrated by the ER-12-1 drillhole are a complex assemblage of Silurian, Devonian, and Mississippian sedimentary rocks that are bounded by numerous faults that show substantial stratigraphic offset. The final 7.3 m (24 ft) of this hole penetrated an unusual intrusive rock of Cretaceous age. The geology of this borehole was substantially different from that expected, with the Tongue Wash Fault encountered at a much shallower depth, paleozoic rocks shuffled out of stratigraphic sequence, and the presence of an altered biotite-rich microporphyritic igneous rock at the bottom of the borehole. Conodont CAI analyses and rock pyrolysis analyses indicate that the carbonate rocks in ER-12-1, as well as the intervening sheets of Eleana siltstone, have been thermally overprinted following movement on the faults that separate them. The probable source of heat for this thermal disturbance is the microporphyritic intrusion encountered at the bottom of the hole, and its age establishes that the major fault activity must have occurred prior to 102.3+0.5 Ma (middle Cretaceous)

  3. Developing ER Stress Inhibitors for Treating ALS

    Science.gov (United States)

    2015-11-01

    reflux containing a catalytic amount of p-toluenesulphonic acid produces the nitroketone 3. Reduction of the nitro group in 3 with zinc and ammonium...chloride or hydrochloric acid produces the aminoketone 4. Treatment of the amino ketone 4 with an aldehyde 5 in a solution of acetic acid and...calcium reuptake by the ER. Using calcium mobilization assays we determined that active benzodiazepinone derivatives potentiate store-operated calcium

  4. ER-12-1 completion report

    Energy Technology Data Exchange (ETDEWEB)

    Russell, C.E.; Gillespie, D.; Cole, J.C.; Drellack, S.L. [and others

    1996-12-01

    The objective of drillhole ER-12-1 was to determine the hydrogeology of paleozoic carbonate rocks and of the Eleana Formation, a regional aquitard, in an area potentially downgradient from underground nuclear testing conducted in nearby Rainier Mesa. This objective was addressed through the drilling of well ER-12-1 at N886,640.26 E640,538.85 Nevada Central Coordinates. Drilling of the 1094 m (3588 ft) well began on July 19, 1991 and was completed on October 17, 1991. Drilling problems included hole deviation and hole instability that prevented the timely completion of this borehole. Drilling methods used include rotary tri-cone and rotary hammer drilling with conventional and reverse circulation using air/water, air/foam (Davis mix), and bentonite mud. Geologic cuttings and geophysical logs were obtained from the well. The rocks penetrated by the ER-12-1 drillhole are a complex assemblage of Silurian, Devonian, and Mississippian sedimentary rocks that are bounded by numerous faults that show substantial stratigraphic offset. The final 7.3 m (24 ft) of this hole penetrated an unusual intrusive rock of Cretaceous age. The geology of this borehole was substantially different from that expected, with the Tongue Wash Fault encountered at a much shallower depth, paleozoic rocks shuffled out of stratigraphic sequence, and the presence of an altered biotite-rich microporphyritic igneous rock at the bottom of the borehole. Conodont CAI analyses and rock pyrolysis analyses indicate that the carbonate rocks in ER-12-1, as well as the intervening sheets of Eleana siltstone, have been thermally overprinted following movement on the faults that separate them. The probable source of heat for this thermal disturbance is the microporphyritic intrusion encountered at the bottom of the hole, and its age establishes that the major fault activity must have occurred prior to 102.3+0.5 Ma (middle Cretaceous).

  5. Virtual Reality er dit nye Skype

    DEFF Research Database (Denmark)

    Bødker, Mads

    2016-01-01

    VR er mediet, der kan gøre den flade skærm og det begrænsede blik i for eksempel Skype til et lidt gammeldags digitalt samarbejde. Ved at sætte folk i stand til at kommunikere, dele virtuelle genstande og give dem en øget oplevelse af at være i et rum sammen, kan man mediere nye aspekter af samar...

  6. Hamlet er manden i mit liv

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2009-01-01

    Hamlet er manden i mit liv. Min elskede. Jeg har en drøm om at frelse ham. At redde ham ud af sin mors soveværelse og ind i mit. Væk fra det ødipale Helvede han befinder sig i, fastlåst mellem et svin af en faderskikkelse (Claudius) og en alt for idealiseret far (gamle Hamlet), vågende over sin m...

  7. En hat er vel en hat ... eller?

    DEFF Research Database (Denmark)

    Bøilerehauge, Dorrit

    2007-01-01

    Mens vi kører i høj fart på "the information highway" - i den helt store bus midt på vejen - glemmer vi ofte noget meget vigtigt i vores glæde over, at verden tilsyneladende åbner sig for os, og vi kan kommunikere med hele verden med ét klik. Vi glemmer, at selvom trafikskilte som oftest er ens -...

  8. Her er din motion i 2012

    DEFF Research Database (Denmark)

    Suhr, Lasse Kristian

    2014-01-01

    Motion i naturen, en indendørs fitnessform inspireret af junglens lianer og høj intensitet med crossfit. Det er ifølge en ekspert nogle af de træningstyper, der vil være mest populære i 2012. Året hvor fleksibilitet og frihed vil blive endnu vigtigere, for den måde vi holder os i form på....

  9. Sund livsstil er mere end fysik

    DEFF Research Database (Denmark)

    Nybo, Lars; Thing, Lone Friis; Astrup, Arne

    2015-01-01

    behandling af inaktivitetsrelaterede lidelser bør dog ikke være det vigtigste argument for at oplyse om og opfordre til en sund livsstil. Livskvalitetsaspektet skal være i højsædet, og det er for så vidt en legitim bekymring, at der kommer et overdrevet fokus på samfundsøkonomi og forebyggelse af somatisk...

  10. Protesen er også mig

    DEFF Research Database (Denmark)

    Østergaard, Elisabeth Bomholt

    at gøre med mennesker, der er blevet amputeret. Jeg mødte de primære informanter – flere af dem adskillige gange - forskellige steder. Jeg var hjemme hos tre, med én på café, mødtes med én på vedkommendes arbejdsplads, mødte syv på et fysioterapeutisk GenoptræningsSted (GS) for mennesker med benamputation...

  11. To steder er maden go´

    DEFF Research Database (Denmark)

    Auken, Sune

    2014-01-01

    Gennem en udlægning af et ganske enkelt reklamedigt tydeliggør artiklen en række af de grundlæggende træk der er på spil, når man fortolker en tekst på baggrund af dens genre. Det betyder, at artiklen arbejder med to overordnede spørgsmål 1) hvilke genrer kan teksten tilskrives, og hvad sker der ...

  12. Hvem er befrieren? Idealisme og realisme

    DEFF Research Database (Denmark)

    Rabjerg, Bjørn

    2017-01-01

    Artiklen fokuserer på K.E. Løgstrups (1905-81) begreb om forståelse ved at sætte det i perspektiv til (1) Platons Hulelignelse og (2) Martin Heideggers (1889-1976) udlægning af denne. Anliggendet er at pege på den tidlige og formative indvirkning, som Løgstrups møde med Heidegger, nazisme og...

  13. Friluftsinstallationer i træer

    DEFF Research Database (Denmark)

    Skov, Simon; Thomsen, Iben Margrete

    2015-01-01

    Abebaner, treetop walking, high rope adventure, slackline, træhuse og parkour-baner er alle installationer, som bruger træerne som støtte, enten midlertidigt eller permanent. Den nye sport, turistattraktionen eller team building-redskabet sætter i alle tilfælde træerne på prøve. Der følger positiv...

  14. SYP73 Anchors the ER to the Actin Cytoskeleton for Maintenance of ER Integrity and Streaming in Arabidopsis.

    Science.gov (United States)

    Cao, Pengfei; Renna, Luciana; Stefano, Giovanni; Brandizzi, Federica

    2016-12-05

    The endoplasmic reticulum (ER) is an essential organelle that spreads throughout the cytoplasm as one interconnected network of narrow tubules and dilated cisternae that enclose a single lumen. The ER network undergoes extensive remodeling, which critically depends on membrane-cytoskeleton interactions [1]. In plants, the ER is also highly mobile, and its streaming contributes significantly to the movement of other organelles [2, 3]. The remodeling and motility of the plant ER rely mainly on actin [4] and to a minor extent on microtubules [5]. Although a three-way interaction between the ER, cytosolic myosin-XI, and F-actin mediates the plant ER streaming [6], the mechanisms underlying stable interaction of the ER membrane with actin are unknown. Early electron microscopy studies suggested a direct attachment of the plant ER with actin filaments [7, 8], but it is plausible that yet-unknown proteins facilitate anchoring of the ER membrane with the cytoskeleton. We demonstrate here that SYP73, a member of the plant Syp7 subgroup of SNARE proteins [9] containing actin-binding domains, is a novel ER membrane-associated actin-binding protein. We show that overexpression of SYP73 causes a striking rearrangement of the ER over actin and that, similar to mutations of myosin-XI [4, 10, 11], loss of SYP73 reduces ER streaming and affects overall ER network morphology and plant growth. We propose a model for plant ER remodeling whereby the dynamic rearrangement and streaming of the ER network depend on the propelling action of myosin-XI over actin coupled with a SYP73-mediated bridging, which dynamically anchors the ER membrane with actin filaments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. ER stress, autophagy, and RNA viruses

    Directory of Open Access Journals (Sweden)

    Jia-Rong eJheng

    2014-08-01

    Full Text Available Endoplasmic reticulum (ER stress is a general term for representing the pathway by which various stimuli affect ER functions. ER stress induces the evolutionarily conserved signaling pathways, called the unfolded protein response (UPR, which compromises the stimulus and then determines whether the cell survives or dies. In recent years, ongoing research has suggested that these pathways may be linked to the autophagic response, which plays a key role in the cell’s response to various stressors. Autophagy performs a self-digestion function, and its activation protects cells against certain pathogens. However, the link between the UPR and autophagy may be more complicated. These two systems may act dependently, or the induction of one system may interfere with the other. Experimental studies have found that different viruses modulate these mechanisms to allow them to escape the host immune response or, worse, to exploit the host’s defense to their advantage; thus, this topic is a critical area in antiviral research. In this review, we summarize the current knowledge about how RNA viruses, including influenza virus, poliovirus, coxsackievirus, enterovirus 71, Japanese encephalitis virus, hepatitis C virus, and dengue virus, regulate these processes. We also discuss recent discoveries and how these will produce novel strategies for antiviral treatment.

  16. A distinct endosomal Ca2+/Mn2+ pump affects root growth through the secretory process.

    Science.gov (United States)

    Li, Xiyan; Chanroj, Salil; Wu, Zhongyi; Romanowsky, Shawn M; Harper, Jeffrey F; Sze, Heven

    2008-08-01

    Ca(2+) is required for protein processing, sorting, and secretion in eukaryotic cells, although the particular roles of the transporters involved in the secretory system of plants are obscure. One endomembrane-type Ca-ATPase from Arabidopsis (Arabidopsis thaliana), AtECA3, diverges from AtECA1, AtECA2, and AtECA4 in protein sequence; yet, AtECA3 appears similar in transport activity to the endoplasmic reticulum (ER)-bound AtECA1. Expression of AtECA3 in a yeast (Saccharomyces cerevisiae) mutant defective in its endogenous Ca(2+) pumps conferred the ability to grow on Ca(2+)-depleted medium and tolerance to toxic levels of Mn(2+). A green fluorescent protein-tagged AtECA3 was functionally competent and localized to intracellular membranes of yeast, suggesting that Ca(2+) and Mn(2+) loading into internal compartment(s) enhanced yeast proliferation. In mesophyll protoplasts, AtECA3-green fluorescent protein associated with a subpopulation of endosome/prevacuolar compartments based on partial colocalization with the Ara7 marker. Interestingly, three independent eca3 T-DNA disruption mutants showed severe reduction in root growth normally stimulated by 3 mm Ca(2+), indicating that AtECA3 function cannot be replaced by an ER-associated AtECA1. Furthermore, root growth of mutants is sensitive to 50 microm Mn(2+), indicating that AtECA3 is also important for the detoxification of excess Mn(2+). Curiously, Ateca3 mutant roots produced 65% more apoplastic protein than wild-type roots, as monitored by peroxidase activity, suggesting that the secretory process was altered. Together, these results demonstrate that the role of AtECA3 is distinct from that of the more abundant ER AtECA1. AtECA3 supports Ca(2+)-stimulated root growth and the detoxification of high Mn(2+), possibly through activities mediated by post-Golgi compartments that coordinate membrane traffic and sorting of materials to the vacuole and the cell wall.

  17. Counselor Identity: Conformity or Distinction?

    Science.gov (United States)

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  18. MicroRNAs meet calcium: joint venture in ER proteostasis.

    Science.gov (United States)

    Finger, Fabian; Hoppe, Thorsten

    2014-11-04

    The endoplasmic reticulum (ER) is a cellular compartment that has a key function in protein translation and folding. Maintaining its integrity is of fundamental importance for organism's physiology and viability. The dynamic regulation of intraluminal ER Ca(2+) concentration directly influences the activity of ER-resident chaperones and stress response pathways that balance protein load and folding capacity. We review the emerging evidence that microRNAs play important roles in adjusting these processes to frequently changing intracellular and environmental conditions to modify ER Ca(2+) handling and storage and maintain ER homeostasis. Copyright © 2014, American Association for the Advancement of Science.

  19. SEM investigation of Er:YAG laser apical preparation

    Science.gov (United States)

    Bǎlǎbuc, Cosmin; Todea, Carmen; Locovei, Cosmin; RǎduÅ£ǎ, Aurel

    2016-03-01

    Endodontic surgery involves the incision and flap elevation, the access to the root tip, its resection, the cavity retrograde preparation and filling it with biocompatible material that provides a good seal of the apex[1]. Apicoectomy is compulsory in endodontic surgery. The final stage involves the root retropreparation and the carrying out of the retrograde obturation. In order to perform the retrograde preparation the endodontist can use various tools such as lowspeed conventional handpieces, sonic and ultrasonic equipment. The ideal depth of the preparation should be 3 mm, exceeding this value may affect the long-term success of the obturation [2]. Resection at the depth of 3 mm reduces apical ramifications by 98% and lateral root canals by 93%. The ultrasonic retropreparation has numerous advantages compared to the dental drill. Firstly, the cavity will be in the axis of the tooth which implies a minimum destruction of the root canal morphology. The preparations are precise, and the cutting pattern is perpendicular to the long axis of the root, the advantage being the reduction in the number of dentinal tubules exposed at the resected area [3]. Therefore, the retrograde filling is the procedure when an inert and non-toxic material is compacted in the apically created cavity.[4,5]. The Er:YAG laser is the most common wavelength indicated for dental hard tissue preparation. Its natural selectivity offers a significant advantage compared to the conventional hard tissue preparation [6-9].The purpose of this in vitro study was to investigate the quality of Er:YAG laser apical third preparation using Scanning Electron Microscopy (SEM), in comparison with the conventional ultrasonic method.

  20. ER-localized auxin transporter PIN8 regulates auxin homeostasis and male gametophyte development in Arabidopsis.

    Science.gov (United States)

    Ding, Zhaojun; Wang, Bangjun; Moreno, Ignacio; Dupláková, Nikoleta; Simon, Sibu; Carraro, Nicola; Reemmer, Jesica; Pěnčík, Aleš; Chen, Xu; Tejos, Ricardo; Skůpa, Petr; Pollmann, Stephan; Mravec, Jozef; Petrášek, Jan; Zažímalová, Eva; Honys, David; Rolčík, Jakub; Murphy, Angus; Orellana, Ariel; Geisler, Markus; Friml, Jiří

    2012-07-03

    Auxin is a key coordinative signal required for many aspects of plant development and its levels are controlled by auxin metabolism and intercellular auxin transport. Here we find that a member of PIN auxin transporter family, PIN8 is expressed in male gametophyte of Arabidopsis thaliana and has a crucial role in pollen development and functionality. Ectopic expression in sporophytic tissues establishes a role of PIN8 in regulating auxin homoeostasis and metabolism. PIN8 co-localizes with PIN5 to the endoplasmic reticulum (ER) where it acts as an auxin transporter. Genetic analyses reveal an antagonistic action of PIN5 and PIN8 in the regulation of intracellular auxin homoeostasis and gametophyte as well as sporophyte development. Our results reveal a role of the auxin transport in male gametophyte development in which the distinct actions of ER-localized PIN transporters regulate cellular auxin homoeostasis and maintain the auxin levels optimal for pollen development and pollen tube growth.

  1. Upconversion luminescence properties of Y2O3:Yb3+, Er3+ nanostructures

    International Nuclear Information System (INIS)

    De Gejihu; Qin Weiping; Zhang Jishen; Zhang Jishuang; Wang, Yan; Cao Chunyan; Cui Yang

    2006-01-01

    Cubic Y 2 O 3 nanostructures doped with Yb 3+ and Er 3+ ions were synthesized by a facile hydrothermal method. Three distinct shapes such as nanotubes, nanospheres and nanoflakes formed in the products by adjusting the pH value of reacting solution. Powder X-ray diffraction analyses indicate that all the three nanostructures are pure cubic phase, while electron microscopy measurements confirm the formation of different morphologies. These nanostructures exhibit strong visible upconversion luminescence under the excitation of a 978-nm diode laser. In Yb 3+ - and Er 3+ - codoped Y 2 O 3 nanocrystals, the relative intensity of green emission became stronger as the size and morphology of sample changed from tubes to flakes

  2. Æstetik er tilbage som nøgle til at forstå samtiden

    DEFF Research Database (Denmark)

    Sharma, Devika

    2013-01-01

    Casper Christensen er gakket, Hello Kitty er nuttet og konceptkunsten er interessant. Her er tre nye kategorier at forstå senkapitalismen med. I anledning af Sianne Ngais bog "Our aesthetic categories: zany, cute, interesting" .......Casper Christensen er gakket, Hello Kitty er nuttet og konceptkunsten er interessant. Her er tre nye kategorier at forstå senkapitalismen med. I anledning af Sianne Ngais bog "Our aesthetic categories: zany, cute, interesting" ....

  3. Human cytomegalovirus gH stability and trafficking are regulated by ER-associated degradation and transmembrane architecture.

    Science.gov (United States)

    Gardner, Thomas J; Hernandez, Rosmel E; Noriega, Vanessa M; Tortorella, Domenico

    2016-03-30

    The prototypic betaherpesvirus human cytomegalovirus (CMV) establishes life-long persistence within its human host. While benign in healthy individuals, CMV poses a significant threat to the immune compromised, including transplant recipients and neonates. The CMV glycoprotein complex gH/gL/gO mediates infection of fibroblasts, and together with the gH/gL/UL128/130/131 a pentameric complex permits infection of epithelial, endothethial, and myeloid cells. Given the central role of the gH/gL complex during infection, we were interested in studying cellular trafficking of the gH/gL complex through generation of human cells that stably express gH and gL. When expressed alone, CMV gH and gL were degraded through the ER-associated degradation (ERAD) pathway. However, co-expression of these proteins stabilized the polypeptides and enhanced their cell-surface expression. To further define regulatory factors involved in gH/gL trafficking, a CMV gH chimera in which the gH transmembrane and cytoplasmic tail were replaced with that of human CD4 protein permitted cell surface gH expression in absence of gL. We thus demonstrate the ability of distinct cellular processes to regulate the trafficking of viral glycoproteins. Collectively, the data provide insight into the processing and trafficking requirements of CMV envelope protein complexes and provide an example of the co-opting of cellular processes by CMV.

  4. On the Use of an ER-213 Detonator to Establish a Baseline for the ER-486

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Keith A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Liechty, Gary H. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Jaramillo, Dennis C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Munger, Alan C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); McHugh, Douglas C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Kennedy, James E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-08-19

    This report documents a series of tests using a TSD-115 fireset coupled with an ER-213, a gold exploding bridgewire (EBW) detonator. These tests were designed to fire this EBW with a smaller fireset to obtain current and voltage data as well as timing information at voltage levels below, above, and throughout the threshold firing region. This study could then create a database for comparison to our current ER-486 EBW development, which is designed to be a lower voltage (<500V) device.

  5. GR and ER co-activation alters the expression of differentiation genes and associates with improved ER+ breast cancer outcome

    Science.gov (United States)

    West, Diana C.; Pan, Deng; Tonsing-Carter, Eva Y.; Hernandez, Kyle M.; Pierce, Charles F.; Styke, Sarah C.; Bowie, Kathleen R.; Garcia, Tzintzuni I.; Kocherginsky, Masha; Conzen, Suzanne D.

    2016-01-01

    In estrogen receptor (ER)-negative breast cancer (BC), high tumor glucocorticoid receptor (GR) expression has been associated with a relatively poor outcome. In contrast, using a meta-analysis of several genomic datasets, here we find that tumor GR mRNA expression is associated with improved ER+ relapse-free survival (RFS) (independently of progesterone receptor (PR) expression). To understand the mechanism by which GR expression is associated with a better ER+ BC outcome, the global effect of GR-mediated transcriptional activation in ER+ BC cells was studied. Analysis of GR chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in ER+/GR+ MCF-7 cells revealed that upon co-activation of GR and ER, GR chromatin association became enriched at proximal promoter regions. Furthermore, following ER activation, increased GR chromatin association was observed at ER, FOXO, and AP1 response elements. In addition, ER associated with GR response elements, suggesting that ER and GR interact in a complex. Co-activation of GR and ER resulted in increased expression (relative to ER activation alone) of transcripts that encode proteins promoting cellular differentiation (e.g. KDM4B, VDR) and inhibiting the Wnt-signaling pathway (IGFBP4). Finally, expression of these individual pro-differentiation genes was associated with significantly improved RFS in ER+ BC patients. Together, these data suggest that the co-expression and subsequent activity of tumor cell GR and ER contribute to the less aggressive natural history of early-stage BC by coordinating the altered expression of genes favoring differentiation. Implications The interaction between estrogen and glucocorticoid receptor activity highlights the importance of context-dependent nuclear receptor function in cancer. PMID:27141101

  6. COPII-Dependent ER Export: A Critical Component of Insulin Biogenesis and β-Cell ER Homeostasis.

    Science.gov (United States)

    Fang, Jingye; Liu, Ming; Zhang, Xuebao; Sakamoto, Takeshi; Taatjes, Douglas J; Jena, Bhanu P; Sun, Fei; Woods, James; Bryson, Tim; Kowluru, Anjaneyulu; Zhang, Kezhong; Chen, Xuequn

    2015-08-01

    Pancreatic β-cells possess a highly active protein synthetic and export machinery in the endoplasmic reticulum (ER) to accommodate the massive production of proinsulin. ER homeostasis is vital for β-cell functions and is maintained by the delicate balance between protein synthesis, folding, export, and degradation. Disruption of ER homeostasis by diabetes-causing factors leads to β-cell death. Among the 4 components to maintain ER homeostasis in β-cells, the role of ER export in insulin biogenesis is the least understood. To address this knowledge gap, the present study investigated the molecular mechanism of proinsulin ER export in MIN6 cells and primary islets. Two inhibitory mutants of the secretion-associated RAS-related protein (Sar)1 small GTPase, known to specifically block coat protein complex II (COPII)-dependent ER export, were overexpressed in β-cells using recombinant adenoviruses. Results from this approach, as well as small interfering RNA-mediated Sar1 knockdown, demonstrated that defective Sar1 function blocked proinsulin ER export and abolished its conversion to mature insulin in MIN6 cells, isolated mouse, and human islets. It is further revealed, using an in vitro vesicle formation assay, that proinsulin was packaged into COPII vesicles in a GTP- and Sar1-dependent manner. Blockage of COPII-dependent ER exit by Sar1 mutants strongly induced ER morphology change, ER stress response, and β-cell apoptosis. These responses were mediated by the PKR (double-stranded RNA-dependent kinase)-like ER kinase (PERK)/eukaryotic translation initiation factor 2α (p-eIF2α) and inositol-requiring protein 1 (IRE1)/x-box binding protein 1 (Xbp1) pathways but not via activating transcription factor 6 (ATF6). Collectively, results from the study demonstrate that COPII-dependent ER export plays a vital role in insulin biogenesis, ER homeostasis, and β-cell survival.

  7. Distinction

    OpenAIRE

    2010-01-01

    Pr Serge Haroche La Médaille d’or 2009 du CNRS est décernée au Pr Serge Haroche, titulaire de la chaire de Physique quantique depuis 2001. Serge Haroche est spécialiste de physique atomique et d’optique quantique. Il est l’un des fondateurs de l’électrodynamique quantique en cavité, domaine qui permet, par des expériences conceptuellement simples, d’éclairer les fondements de la théorie quantique et de réaliser des prototypes de systèmes de traitement quantique de l’information. Serge Haroche...

  8. Photoluminescence of Er in SiOx

    International Nuclear Information System (INIS)

    Wan Jun; Sheng Chi; Lu Fang; Gong Dawei; Fan Yongliang; Lin Feng; Wang Xun

    1998-01-01

    Erbium-doped SiO x is prepared by molecular beam epitaxy. The influence of Er on the incorporation of O is studied by using Auger spectroscopy. Photoluminescence (PL) peaks around the wave-length of 1.53 μm have been observed within the temperature range of 18 to 300 K after annealing. The relationship between PL intensity and annealing temperature is discussed. The temperature dependence of the PL intensity shows an exponential decay with an activation energy of 12 meV at low temperatures ( 100 K)

  9. "LICENS ER NOGET VI GIVER TIL HINANDEN"

    OpenAIRE

    Svendsen, Nana Lysbo; Birksholm, Sarah Schlander; Rosendahl, Rasmus; Albrechtsen, Nadja Loran

    2013-01-01

    This study consists of a rhetorical analysis of how the Danish Broadcasting Corporation argues for the compulsory license fee in their campaign video: ’Licens er noget vi giver til hinanden’. On the assumption that a visual product can argue on equal terms with the spoken language, the paper will look at the specific visual tools that are used in the argumentation and the portrayal of the concept of public service and the license fee. In extension to this the paper will examine if the vid...

  10. Synthesis of Er and Er : Yb doped sol–gel derived silica glass and ...

    Indian Academy of Sciences (India)

    Unknown

    doped samples showed enhanced absorption due to 2F7/2 → 2F5/2 transition. The absorption and ... Er3+ emission transition occurs within this wavelength ... reagent) grade. Calculated amount of dopant salts were poured in TEOS under stirring condition at room tem- perature. The molar ratio of TEOS : H2O : HCl was.

  11. Minimising Immunohistochemical False Negative ER Classification Using a Complementary 23 Gene Expression Signature of ER Status

    DEFF Research Database (Denmark)

    Li, Qiyuan; Eklund, Aron Charles; Birkbak, Nicolai Juul

    2010-01-01

    with clinical outcome. METHODOLOGY/PRINCIPAL FINDINGS: Firstly, ER status was discriminated by fitting the bimodal expression of ESR1 to a mixed Gaussian model. The discriminative power of ESR1 suggested bimodal expression as an efficient way to stratify breast cancer; therefore we identified a set of genes...

  12. Synthesis of Er and Er : Yb doped sol–gel derived silica glass and ...

    Indian Academy of Sciences (India)

    Unknown

    indicated in TGA curve). The weight loss at elevated tempe- ratures is probably due to removal of water during con-. Figure 1. Photograph of a gel sample sintered at 900°C. Figure 2. DTA curve for 1⋅0 mol% of Er2O3 doped silica gel. Figure 3.

  13. Dual Role of Ancient Ubiquitous Protein 1 (AUP1) in Lipid Droplet Accumulation and Endoplasmic Reticulum (ER) Protein Quality Control

    Science.gov (United States)

    Klemm, Elizabeth J.; Spooner, Eric; Ploegh, Hidde L.

    2011-01-01

    Quality control of endoplasmic reticulum proteins involves the identification and engagement of misfolded proteins, dislocation of the misfolded protein across the endoplasmic reticulum (ER) membrane, and ubiquitin-mediated targeting to the proteasome for degradation. Ancient ubiquitous protein 1 (AUP1) physically associates with the mammalian HRD1-SEL1L complex, and AUP1 depletion impairs degradation of misfolded ER proteins. One of the functions of AUP1 in ER quality control is to recruit the soluble E2 ubiquitin-conjugating enzyme UBE2G2. We further show that the CUE domain of AUP1 regulates polyubiquitylation and facilitates the interaction of AUP1 with the HRD1 complex and with dislocation substrates. AUP1 localizes both to the ER and to lipid droplets. The AUP1 expression level affects the abundance of cellular lipid droplets and as such represents the first protein with lipid droplet regulatory activity to be linked to ER quality control. These findings indicate a possible connection between ER protein quality control and lipid droplets. PMID:21857022

  14. Comparative study of upper lip frenectomy with the CO2 laser versus the Er, Cr: YSGG laser

    Science.gov (United States)

    Pié-Sánchez, Jordi; España-Tost, Antonio J.; Arnabat-Domínguez, Josep

    2012-01-01

    Objectives: To compare upper lip frenulum reinsertion, bleeding, surgical time and surgical wound healing in frenectomies performed with the CO2 laser versus the Er, Cr:YSGG laser. Study design: A prospective study was carried out on 50 randomized pediatric patients who underwent rhomboidal resection of the upper lip frenulum with either the CO2 laser or the Er,Cr:YSGG laser. Twenty-five patients were assigned to each laser system. All patients were examined at 7, 14, 21 days and 4 months after the operation in order to assess the surgical wound healing. Results: Insertion of the frenulum, which was preoperatively located between the upper central incisors, migrated to the mucogingival junction as a result of using both laser systems in all patients. Only two patients required a single dose of 650 mg of paracetamol, one of either study group. CO2 laser registered improved intraoperative bleeding control results and shorter surgical times. On the other hand, the Er,Cr:YSGG laser achieved faster healing. Conclusions: Upper lip laser frenectomy is a simple technique that results in minimum or no postoperative swelling or pain, and which involves upper lip frenulum reinsertion at the mucogingival junction. The CO2 laser offers a bloodless field and shorter surgical times compared with the Er,Cr:YSGG laser. On the other hand, the Er,Cr:YSGG laser achieved faster wound healing. Key words:Frenectomy, upper lip frenulum, CO2 laser, Er,Cr:YSGG laser, laser. PMID:22143683

  15. QuEChERS extraction of benzodiazepines in biological matrices

    Directory of Open Access Journals (Sweden)

    Jessica L. Westland

    2013-12-01

    Full Text Available Two common analytical chemical problems often encountered when using chromatographic techniques in drug analysis are matrix interferences and ion suppression. Common sample preparation often involves the dilution of the sample prior to injection onto an instrument, especially for liquid chromatography–mass spectrometry (LC–MS analyses. This practice frequently does not minimize or eliminate conditions that may cause ion-suppression and therefore, suffer more from reduced method robustness. In order to achieve higher quality results and minimize possible interferences, various sample preparation techniques may be considered. Through the use of QuEChERS (“catchers”, a novel sample preparation technique used for high aqueous content samples, benzodiazepines can be extracted from biological fluids, such as blood and urine. This approach has shown increased recoveries of target compounds when using quantification by both external and internal standard. This increase in the recoveries has been attributed to a matrix enhancement and was determined through the use of the method of standard addition. While improving the overall analytical method for gas chromatography–mass spectrometry (GC–MS analysis, it is not clear if this approach represents an overall benefit for laboratories that have both GC–MS and high performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS capability. Demonstrating evidence of variable ionization (enhancement, ion source inertness, etc., the method of quantification should be focused on in future studies. Keywords: Forensic science, QuEChERS, Drug analysis, Benzodiazepines, Gas Chromatography–Mass Spectrometry, Biological samples

  16. Functional characterization of the ER stress induced X-box-binding protein-1 (Xbp-1 in the porcine system

    Directory of Open Access Journals (Sweden)

    Jin Dong-Il

    2011-05-01

    Full Text Available Abstract Background The unfolded protein response (UPR is an evolutionary conserved adaptive reaction for increasing cell survival under endoplasmic reticulum (ER stress conditions. X-box-binding protein-1 (Xbp1 is a key transcription factor of UPR that activates genes involved in protein folding, secretion, and degradation to restore ER function. The UPR induced by ER stress was extensively studied in diseases linked to protein misfolding and aggregations. However, in the porcine system, genes in the UPR pathway were not investigated. In this study, we isolated and characterized the porcine Xbp1 (pXbp1 gene in ER stress using porcine embryonic fibroblast (PEF cells and porcine organs. ER stress was induced by the treatment of tunicamycin and cell viability was investigated by the MTT assay. For cloning and analyzing the expression pattern of pXbp1, RT-PCR analysis and Western blot were used. Knock-down of pXbp1 was performed by the siRNA-mediated gene silencing. Results We found that the pXbp1 mRNA was the subject of the IRE1α-mediated unconventional splicing by ER stress. Knock-down of pXbp1 enhanced ER stress-mediated cell death in PEF cells. In adult organs, pXbp1 mRNA and protein were expressed and the spliced forms were detected. Conclusions It was first found that the UPR mechanisms and the function of pXbp1 in the porcine system. These results indicate that pXbp1 plays an important role during the ER stress response like other animal systems and open a new opportunity for examining the UPR pathway in the porcine model system.

  17. Morbillivirus glycoprotein expression induces ER stress, alters Ca2+ homeostasis and results in the release of vasostatin.

    Directory of Open Access Journals (Sweden)

    Jean-Marc Brunner

    Full Text Available Although the pathology of Morbillivirus in the central nervous system (CNS is well described, the molecular basis of neurodegenerative events still remains poorly understood. As a model to explore Morbillivirus-mediated CNS dysfunctions, we used canine distemper virus (CDV that we inoculated into two different cell systems: a monkey cell line (Vero and rat primary hippocampal neurons. Importantly, the recombinant CDV used in these studies not only efficiently infects both cell types but recapitulates the uncommon, non-cytolytic cell-to-cell spread mediated by virulent CDVs in brain of dogs. Here, we demonstrated that both CDV surface glycoproteins (F and H markedly accumulated in the endoplasmic reticulum (ER. This accumulation triggered an ER stress, characterized by increased expression of the ER resident chaperon calnexin and the proapoptotic transcription factor CHOP/GADD 153. The expression of calreticulin (CRT, another ER resident chaperon critically involved in the response to misfolded proteins and in Ca(2+ homeostasis, was also upregulated. Transient expression of recombinant CDV F and H surface glycoproteins in Vero cells and primary hippocampal neurons further confirmed a correlation between their accumulation in the ER, CRT upregulation, ER stress and disruption of ER Ca(2+ homeostasis. Furthermore, CDV infection induced CRT fragmentation with re-localisation of a CRT amino-terminal fragment, also known as vasostatin, on the surface of infected and neighbouring non-infected cells. Altogether, these results suggest that ER stress, CRT fragmentation and re-localization on the cell surface may contribute to cytotoxic effects and ensuing cell dysfunctions triggered by Morbillivirus, a mechanism that might potentially be relevant for other neurotropic viruses.

  18. Employer branding er også intern kommunikation

    DEFF Research Database (Denmark)

    Hansen, Heidi

    2016-01-01

    I videnssamfundet og serviceøkonomien er medarbejderne virksomhedens vigtigste ressource, men milleniumgenerationen er ikke trofaste overfor deres arbejdsplads – de har typisk 15-20 jobs i løbet af deres livstid. Et stærkt employer brand bidrager til at fastholde medarbejdere – og dermed...... kompetencer – i virksomheden, og medarbejderne er dermed en central målgruppe for employer branding....

  19. Approaching the Distinction between Intuition and Insight.

    Science.gov (United States)

    Zhang, Zhonglu; Lei, Yi; Li, Hong

    2016-01-01

    Intuition and insight share similar cognitive and neural basis. Though, there are still some essential differences between the two. Here in this short review, we discriminated between intuition, and insight in two aspects. First, intuition, and insight are toward different aspects of information processing. Whereas intuition involves judgment about "yes or no," insight is related to "what" is the solution. Second, tacit knowledge play different roles in between intuition and insight. On the one hand, tacit knowledge is conducive to intuitive judgment. On the other hand, tacit knowledge may first impede but later facilitate insight occurrence. Furthermore, we share theoretical, and methodological views on how to access the distinction between intuition and insight.

  20. Calcium Homeostasis and ER Stress in Control of Autophagy in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Elżbieta Kania

    2015-01-01

    Full Text Available Autophagy is a basic catabolic process, serving as an internal engine during responses to various cellular stresses. As regards cancer, autophagy may play a tumor suppressive role by preserving cellular integrity during tumor development and by possible contribution to cell death. However, autophagy may also exert oncogenic effects by promoting tumor cell survival and preventing cell death, for example, upon anticancer treatment. The major factors influencing autophagy are Ca2+ homeostasis perturbation and starvation. Several Ca2+ channels like voltage-gated T- and L-type channels, IP3 receptors, or CRAC are involved in autophagy regulation. Glucose transporters, mainly from GLUT family, which are often upregulated in cancer, are also prominent targets for autophagy induction. Signals from both Ca2+ perturbations and glucose transport blockage might be integrated at UPR and ER stress activation. Molecular pathways such as IRE 1-JNK-Bcl-2, PERK-eIF2α-ATF4, or ATF6-XBP 1-ATG are related to autophagy induced through ER stress. Moreover ER molecular chaperones such as GRP78/BiP and transcription factors like CHOP participate in regulation of ER stress-mediated autophagy. Autophagy modulation might be promising in anticancer therapies; however, it is a context-dependent matter whether inhibition or activation of autophagy leads to tumor cell death.

  1. Er Web 2.0 klar til mainstream?

    DEFF Research Database (Denmark)

    Ivang, Reimer

    2009-01-01

    BLOG: Spørgsmålene der relateres til Web 2.0 er mange. Men en af de mest signifikante er om netop din virksomhed skal anvende Web 2.0 teknologier? Hvad kan I få ud af det?......BLOG: Spørgsmålene der relateres til Web 2.0 er mange. Men en af de mest signifikante er om netop din virksomhed skal anvende Web 2.0 teknologier? Hvad kan I få ud af det?...

  2. Danskhed er pizza, kebab og flæskesteg

    DEFF Research Database (Denmark)

    Mehlsen, Camilla

    2010-01-01

    Dannebrog. Kongehuset. Flæskesteg. Folkeskolen. Fodbold og øl. En lang række symboler og fortællinger kendetegner danskhed, men det er en myte, at danskerne er en homogen gruppe, fortæller professor Richard Jenkins.......Dannebrog. Kongehuset. Flæskesteg. Folkeskolen. Fodbold og øl. En lang række symboler og fortællinger kendetegner danskhed, men det er en myte, at danskerne er en homogen gruppe, fortæller professor Richard Jenkins....

  3. Defining poverty as distinctively human

    Directory of Open Access Journals (Sweden)

    H.P.P. Lötter

    2007-05-01

    Full Text Available While it is relatively easy for most people to identify human beings suffering from poverty, it is rather more difficult to come to a proper understanding of poverty. In this article the author wants to deepen our understanding of poverty by interpreting the conventional definitions of poverty in a new light. The article starts with a defence of a claim that poverty is a concept uniquely applicable to humans. It then present a critical discussion of the distinction between absolute and relative poverty and it is then argued that a revision of this distinction can provide general standards applicable to humans everywhere.

  4. The local implementation of clean(er) fuels policies in Europe. A Handbook with guidelines. Final version

    International Nuclear Information System (INIS)

    Mulder, F.; Amara, Sliman Abu; Uustal, M.; Pelkmans, L.; Devriendt, N.; Rogulska, M.; Defranceschi, P.

    2009-05-01

    This handbook aims to guide the local/regional governments all over Europe who are involved in implementing clean(er) fuel policies in transport. The general challenge these governments are facing is how local policies on clean(er) fuels and vehicles can be made operational. Hence, how can the step be made from a vision on the strategic policy level, to a vision on the implementation of these policies. A local/regional policy on clean(er) fuels and vehicles is commonly part of the larger category 'sustainable transport policy', which in itself is part of a broader local environmental policy. The encompassing local/regional sustainable mobility policy will in most cases be based on the three well known main policy aims in this area: CO2 reduction; Improving the local air quality; and Improving the security of supply (locally often less stressed). This handbook will focus on the actual implementation of a clean(er) fuels and vehicles policy. It will describe the main challenges and how these can be overcome. It will describe how the market conditions for clean(er) fuels and vehicles can be created by establishing the vital market elements and which process is required to do so. And it will show how local enterprises can be involved and what the role of the local governments in this process can be. In order to identify the local success factors in overcoming the main challenges for implementation, case studies have been carried out in three European cities, namely Stockholm (Sweden), Graz (Austria) and Lille (France). The choice of these cities was based on their successes in implementing clean(er) fuel policies (although they followed different paths) and the fact that they managed to achieve ambitious clean(er) fuel/ clean(er) vehicle targets. These cities may thus be considered as ?good practice examples?. The case studies are based on existing literature, on multiple stakeholders? interviews in all three cities, and on two small surveys. The objectives of this

  5. Protectin DX suppresses hepatic gluconeogenesis through AMPK-HO-1-mediated inhibition of ER stress.

    Science.gov (United States)

    Jung, Tae Woo; Kim, Hyung-Chun; Abd El-Aty, A M; Jeong, Ji Hoon

    2017-06-01

    Several studies have shown that protectins, which are ω-3 fatty acid-derived proresolution mediators, may improve insulin resistance. Recently, protectin DX (PDX) was documented to attenuate insulin resistance by stimulating IL-6 expression in skeletal muscle, thereby regulating hepatic gluconeogenesis. These findings made us investigate the direct effects of PDX on hepatic glucose metabolism in the context of diabetes. In the current study, we show that PDX regulates hepatic gluconeogenesis in a manner distinct from its indirect glucoregulatory activity via IL-6. We found that PDX stimulated AMP-activated protein kinase (AMPK) phosphorylation, thereby inducing heme oxygenase 1 (HO-1) expression. This induction blocked hepatic gluconeogenesis by suppressing endoplasmic reticulum (ER) stress in hepatocytes under hyperlipidemic conditions. These effects were significantly dampened by silencing AMPK or HO-1 expression with small interfering RNA (siRNA). We also demonstrated that administration of PDX to high fat diet (HFD)-fed mice resulted in increased hepatic AMPK phosphorylation and HO-1 expression, whereas hepatic ER stress was substantially attenuated. Furthermore, PDX treatment suppressed the expression of gluconeogenic genes, thereby decreasing blood glucose levels in HFD-fed mice. In conclusion, our findings suggest that PDX inhibits hepatic gluconeogenesis via AMPK-HO-1-dependent suppression of ER stress. Thus, PDX may be an effective therapeutic target for the treatment of insulin resistance and type 2 diabetes through the regulation of hepatic gluconeogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Distinct Function of Estrogen Receptor α in Smooth Muscle and Fibroblast Cells in Prostate Development

    OpenAIRE

    Vitkus, Spencer; Yeh, Chiuan-Ren; Lin, Hsiu-Hsia; Hsu, Iawen; Yu, Jiangzhou; Chen, Ming; Yeh, Shuyuan

    2012-01-01

    Estrogen signaling, through estrogen receptor (ER)α, has been shown to cause hypertrophy in the prostate. Our recent report has shown that epithelial ERα knockout (KO) will not affect the normal prostate development or homeostasis. However, it remains unclear whether ERα in different types of stromal cells has distinct roles in prostate development. This study proposed to elucidate how KO of ERα in the stromal smooth muscle or fibroblast cells may interrupt cross talk between prostate stromal...

  7. Sirt3-Mediated Autophagy Contributes to Resveratrol-Induced Protection against ER Stress in HT22 Cells

    Directory of Open Access Journals (Sweden)

    Wen-Jun Yan

    2018-02-01

    Full Text Available Endoplasmic reticulum (ER stress occurring in stringent conditions is critically involved in neuronal survival and death. Resveratrol is a non-flavonoid polyphenol that has neuroprotective effects against many neurological disorders. Here, we investigated the potential protective effects of resveratrol in an in vitro ER stress model mimicked by tunicamycin (TM treatment in neuronal HT22 cells. We found that TM dose-dependently decreased cell viability and increased apoptosis, which were both significantly attenuated by resveratrol treatment. Resveratrol markedly reduced the expression or activation of ER stress-associated factors, including GRP78, CHOP, and caspase-12. The results of immunocytochemistry and western blot showed that resveratrol promoted autophagy in TM-treated cells, as evidenced by increased LC3II puncta number, bcelin1 expression and LC3II/LC3I ratio. Pretreatment with the autophagy inhibitor chloroquine could reduce the protective effects of resveratrol. In addition, the expression of Sirt3 protein and its downstream enzyme activities were significantly increased in resveratrol-treated HT22 cells. To confirm the involvement of Sirt3-mediated mechanisms, siRNA transfection was used to knockdown Sirt3 expression in vitro. The results showed that downregulation of Sirt3 could partially prevented the autophagy and protection induced by resveratrol after TM treatment. Our study demonstrates a pivotal role of Sirt3-mediated autophagy in mediating resveratrol-induced protection against ER stress in vitro, and suggests the therapeutic values of resveratrol in ER stress-associated neuronal injury conditions.

  8. Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells.

    Science.gov (United States)

    Zheng, Wanglong; Wang, Bingjie; Si, Mengxue; Zou, Hui; Song, Ruilong; Gu, Jianhong; Yuan, Yan; Liu, Xuezhong; Zhu, Guoqiang; Bai, Jianfa; Bian, Jianchun; Liu, ZongPing

    2018-02-20

    The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress. Our results further showed that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in TM4 cells. In addition, ZEA also induced the ER stress which was involved in the induction of the autophagy through inhibiting the ERK signal pathway to suppress the phosphorylation of mTOR. ER stress was involved in the damage of cytoskeletal structure through induction of autophagy by producing ROS. Taken together, this study revealed that ZEA altered the cytoskeletal structure via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.

  9. ER@CEBAF: Modeling code developments

    Energy Technology Data Exchange (ETDEWEB)

    Meot, F. [Brookhaven National Lab. (BNL), Upton, NY (United States); Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Roblin, Y. [Brookhaven National Lab. (BNL), Upton, NY (United States); Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States)

    2016-04-13

    A proposal for a multiple-pass, high-energy, energy-recovery experiment using CEBAF is under preparation in the frame of a JLab-BNL collaboration. In view of beam dynamics investigations regarding this project, in addition to the existing model in use in Elegant a version of CEBAF is developed in the stepwise ray-tracing code Zgoubi, Beyond the ER experiment, it is also planned to use the latter for the study of polarization transport in the presence of synchrotron radiation, down to Hall D line where a 12 GeV polarized beam can be delivered. This Note briefly reports on the preliminary steps, and preliminary outcomes, based on an Elegant to Zgoubi translation.

  10. Musikkens Hus i Aalborg er demensvenligt

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    2017-01-01

    demensven, er det for at vi som medborgere sætter os lidt mere ind i hvad det vil sige at have en demenssygdom. Det betyder ikke når man sidder i en koncertsal. Har man været vant til at gå til koncerter, vil det vække tryghed og genkendelse at synke ned i sædet når lyset slukkes og musikken begynder...... været vant til at gå til koncerter, vil det vække tryghed og genkendelse at synke ned i sædet når lyset slukkes og musikken begynder. For mennesker med demens kan koncertoplevelsen måske være særlig betydningsfuld. For at give mennesker med demens en håndsrækning besluttede Musikkens Hus i Aalborg...

  11. Final Technical Report for Award # ER64999

    Energy Technology Data Exchange (ETDEWEB)

    Metcalf, William W. [University of Illinois

    2014-10-08

    This report provides a summary of activities for Award # ER64999, a Genomes to Life Project funded by the Office of Science, Basic Energy Research. The project was entitled "Methanogenic archaea and the global carbon cycle: a systems biology approach to the study of Methanosarcina species". The long-term goal of this multi-investigator project was the creation of integrated, multiscale models that accurately and quantitatively predict the role of Methanosarcina species in the global carbon cycle under dynamic environmental conditions. To achieve these goals we pursed four specific aims: (1) genome sequencing of numerous members of the Order Methanosarcinales, (2) identification of genomic sources of phenotypic variation through in silico comparative genomics, (3) elucidation of the transcriptional networks of two Methanosarcina species, and (4) development of comprehensive metabolic network models for characterized strains to address the question of how metabolic models scale with genetic distance.

  12. EC/β+ decay of 161Er

    International Nuclear Information System (INIS)

    Kalinnikov, V.G.; Ibraheem, Y.S.; Stegailov, V.I.

    2004-01-01

    Full text: The study of odd-proton nuclei in rare-earth region has been performed to get more information on the nuclear structure of these nuclei. In the framework of a program at the ISOL complex of YASNAPP-2 at JINR to study the decay of odd-nuclei, 161 Er has been investigated. The experiments have been focused on the 161 Ho level scheme populated in the EC/β + decay of 161 Er for which a few results have been previously reported [1,2]. Spectra of single γ-ray, γ-γ coincidence and internal conversion electrons were measured. There are appreciable disagreements between results of some γ-ray intensities obtained by us and in [2]. The greatest difference was for relative γ-ray intensity of the 11.28 keV, which has reported value I γ ∼ 10 (I γ 211 =1000) in [2], but this leads to an overpopulation of the 211 keV level by 14% of the decay [3]. The relative intensities of transitions with Eγ γ211 =1000). Inaccuracy of Iγ in [2] is probably due to a sudden change in the efficiency curve of their Ge(Li) detector in the low energy region while our HPGe detector feature a much smoother variation in the efficiency curve in this γ-ray energy region. Besides, the levels earlier introduced by us in [4], three new levels in 161 Ho were proposed from γ-γ coincidences at energies 693.2 keV, 859.6 keV, and 957.97 keV. Spins, parities and Nilsson quantum characteristics of some 161 Ho levels were established

  13. ER and PR expression and survival after endometrial cancer.

    Science.gov (United States)

    Smith, Deborah; Stewart, Colin J R; Clarke, Edward M; Lose, Felicity; Davies, Claire; Armes, Jane; Obermair, Andreas; Brennan, Donal; Webb, Penelope M; Nagle, Christina M; Spurdle, Amanda B

    2018-02-01

    To measure association between endometrial carcinoma ER and PR status and endometrial cancer (EC) survival, accounting for inter-observer variation. The intensity and proportion of tumor cell expression of ER and PR in ECs were assessed independently and semi-quantitatively by two pathologists using digital images of duplicate tumor tissue microarrays (TMAs). Cases with inconsistent initial assessment were reviewed and final scoring agreed. The association between overall and EC-specific survival and hormone receptor expression (intensity, proportion and combined) was assessed using Cox regression analysis. The C-index was used to evaluate model discrimination with addition of ER and PR status. Tumor ER and PR analysis was possible in 659 TMAs from 255 patients, and in 459 TMAs from 243 patients, respectively. Initial ER and PR scoring was consistent in 82% and 80% of cases, respectively. In multivariate analyses decreased ER and PR expression was associated with increased tumor-related mortality. Associations reached statistical significance for ER proportion score (P=0.05), ER intensity score (P=0.003), and PR combined score (P=0.04). Decreased expression of combined ER/PR expression was associated with poorer EC-specific survival than decreased expression of either hormone receptor alone (P=0.005). However, hormone receptor status did not significantly improve mortality prediction in individual cases. ER and PR expression combined, using cut-points that capture variation in scoring and across cores, is significantly associated with EC-specific survival in analyses adjusting for known prognostic factors. However, at the individual level, ER and PR expression does not improve mortality prediction. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Educational Psychology: The Distinctive Contribution

    Science.gov (United States)

    Cameron, R. J.

    2006-01-01

    This paper, written in the twenty-first anniversary year of the journal "Educational Psychology in Practice", attempts to uncover those distinctive aspects of the discipline and the practice of applied psychology in general and educational psychology in particular. After considering some of the reasons for attempting this task at this point in…

  15. Ikon. iPod er kongen over mp3. Hvad er hemmeligheden?

    DEFF Research Database (Denmark)

    Dickson, Thomas

    2005-01-01

    iPod er blevet ikonet for det 21. århundrede. Men iPod var hverken den første mp3-afspiller eller den første veldesignede af slagsen. Før iPod så dagens lys var Bang & Olufsen på banen med sin næsten lige så lækre BeoSound2.......iPod er blevet ikonet for det 21. århundrede. Men iPod var hverken den første mp3-afspiller eller den første veldesignede af slagsen. Før iPod så dagens lys var Bang & Olufsen på banen med sin næsten lige så lækre BeoSound2....

  16. Endoplasmic reticulum turnover: ER-phagy and other flavors in selective and non-selective ER clearance [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Ilaria Fregno

    2018-04-01

    Full Text Available The endoplasmic reticulum (ER is a highly dynamic organelle in eukaryotic cells. It is deputed to lipid and protein biosynthesis, calcium storage, and the detoxification of various exogenous and endogenous harmful compounds. ER activity and size must be adapted rapidly to environmental and developmental conditions or biosynthetic demand. This is achieved on induction of thoroughly studied transcriptional/translational programs defined as “unfolded protein responses” that increase the ER volume and the expression of ER-resident proteins regulating the numerous ER functions. Less understood are the lysosomal catabolic processes that maintain ER size at steady state, that prevent excessive ER expansion during ER stresses, or that ensure return to physiologic ER size during recovery from ER stresses. These catabolic processes may also be activated to remove ER subdomains where proteasome-resistant misfolded proteins or damaged lipids have been segregated. Insights into these catabolic mechanisms have only recently emerged with the identification of so-called ER-phagy receptors, which label specific ER subdomains for selective lysosomal delivery for clearance. Here, in eight chapters and one addendum, we comment on recent advances in ER turnover pathways induced by ER stress, nutrient deprivation, misfolded proteins, and live bacteria. We highlight the role of yeast (Atg39 and Atg40 and mammalian (FAM134B, SEC62, RTN3, and CCPG1 ER-phagy receptors and of autophagy genes in selective and non-selective catabolic processes that regulate cellular proteostasis by controlling ER size, turnover, and function.

  17. Discovery of a Novel er1 Allele Conferring Powdery Mildew Resistance in Chinese Pea (Pisum sativum L.) Landraces.

    Science.gov (United States)

    Sun, Suli; Fu, Haining; Wang, Zhongyi; Duan, Canxing; Zong, Xuxiao; Zhu, Zhendong

    2016-01-01

    Pea powdery mildew, caused by Erysiphe pisi D.C., is an important disease worldwide. Deployment of resistant varieties is the main way to control this disease. This study aimed to screen Chinese pea (Pisum sativum L.) landraces resistant to E. pisi, and to characterize the resistance gene(s) at the er1 locus in the resistant landraces, and to develop functional marker(s) specific to the novel er1 allele. The 322 landraces showed different resistance levels. Among them, 12 (3.73%), 4 (1.24%) and 17 (5.28%) landraces showed immunity, high resistance and resistance to E. pisi, respectively. The other landraces appeared susceptible or highly susceptible to E. pisi. Most of the immune and highly resistant landraces were collected from Yunnan province. To characterize the resistance gene at the er1 locus, cDNA sequences of PsMLO1 gene were determined in 12 immune and four highly resistant accessions. The cDNAs of PsMLO1 from the immune landrace G0005576 produced three distinct transcripts, characterized by a 129-bp deletion, and 155-bp and 220-bp insertions, which were consistent with those of er1-2 allele. The PsMLO1 cDNAs in the other 15 resistant landraces produced identical transcripts, which had a new point mutation (T→C) at position 1121 of PsMLO1, indicating a novel er1 allele, designated as er1-6. This mutation caused a leucine to proline change in the amino acid sequence. Subsequently, the resistance allele er1-6 in landrace G0001778 was confirmed by resistance inheritance analysis and genetic mapping on the region of the er1 locus using populations derived from G0001778 × Bawan 6. Finally, a functional marker specific to er1-6, SNP1121, was developed using the high-resolution melting technique, which could be used in pea breeding via marker-assisted selection. The results described here provide valuable genetic information for Chinese pea landraces and a powerful tool for pea breeders.

  18. Discovery of a Novel er1 Allele Conferring Powdery Mildew Resistance in Chinese Pea (Pisum sativum L. Landraces.

    Directory of Open Access Journals (Sweden)

    Suli Sun

    Full Text Available Pea powdery mildew, caused by Erysiphe pisi D.C., is an important disease worldwide. Deployment of resistant varieties is the main way to control this disease. This study aimed to screen Chinese pea (Pisum sativum L. landraces resistant to E. pisi, and to characterize the resistance gene(s at the er1 locus in the resistant landraces, and to develop functional marker(s specific to the novel er1 allele. The 322 landraces showed different resistance levels. Among them, 12 (3.73%, 4 (1.24% and 17 (5.28% landraces showed immunity, high resistance and resistance to E. pisi, respectively. The other landraces appeared susceptible or highly susceptible to E. pisi. Most of the immune and highly resistant landraces were collected from Yunnan province. To characterize the resistance gene at the er1 locus, cDNA sequences of PsMLO1 gene were determined in 12 immune and four highly resistant accessions. The cDNAs of PsMLO1 from the immune landrace G0005576 produced three distinct transcripts, characterized by a 129-bp deletion, and 155-bp and 220-bp insertions, which were consistent with those of er1-2 allele. The PsMLO1 cDNAs in the other 15 resistant landraces produced identical transcripts, which had a new point mutation (T→C at position 1121 of PsMLO1, indicating a novel er1 allele, designated as er1-6. This mutation caused a leucine to proline change in the amino acid sequence. Subsequently, the resistance allele er1-6 in landrace G0001778 was confirmed by resistance inheritance analysis and genetic mapping on the region of the er1 locus using populations derived from G0001778 × Bawan 6. Finally, a functional marker specific to er1-6, SNP1121, was developed using the high-resolution melting technique, which could be used in pea breeding via marker-assisted selection. The results described here provide valuable genetic information for Chinese pea landraces and a powerful tool for pea breeders.

  19. BP1 Homeoprotein Enhances Metastatic Potential in Er-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yebo Fu, Yi Lian, Kyung Soon Kim, Lei Zhang, A. Katharine Hindle, Fred Brody, Robert S. Siegel, Timothy A. McCaffrey, Sidney W. Fu

    2010-01-01

    Full Text Available Tumor invasion and metastasis remain a major cause of mortality in breast cancer patients. It was reported that BP1, a homeobox isoform of DLX4, is overexpressed in 80% of breast cancer patients and in 100% of estrogen receptor negative (ER- tumors. The prevalence of BP1 positive cells and the intensity of BP1 immunoreactivity increased with the extent of ductal proliferation and tumorigenesis. These findings imply that BP1 may play an important role in ER- breast cancer. I sought to determine the effects and mechanisms of BP1 on cell proliferation and metastasis using ER- Hs578T cells as a model. Cells were transfected with either pcDNA3.2 plasmid containing BP1 gene, or pcDNA3.2 vector, then selected and cloned. Overexpression of BP1 increased cell proliferation rate by 2-5 fold (p<0.005, and enhanced the in vitro invasive activity by 25-65 fold (p<0.001. Microarray experiments were performed to identify differentially expressed genes when BP1 is overexpressed. The gene expression profile of the transfected cell lines were compared, resulting in 71 differentially expressed genes with a fold-change of >=2.0. Of those genes, 49 were up-regulated and 22 were down-regulated. Significant pathways were identified involving cell proliferation and metastasis. These data demonstrated that overexpression of BP1 significantly enhanced cell proliferation and metastatic potential in ER- Hs578T cells. Further analysis with more ER- cell lines and patient samples is warranted to establish BP1 as a therapeutic target.

  20. Electrochemical doping of mesoporous silicon with Er: the effect of the current intensity

    Energy Technology Data Exchange (ETDEWEB)

    Mula, Guido, E-mail: guido.mula@unica.it [Dipartimento di Fisica, Università degli Studi di Cagliari, Cittadella Universitaria di Monserrato, S.P. 8 km 0.700, 09042 Cagliari (Italy); Pinna, Elisa [Dipartimento di Fisica, Università degli Studi di Cagliari, Cittadella Universitaria di Monserrato, S.P. 8 km 0.700, 09042 Cagliari (Italy); Falqui, Andrea [Nanochemistry, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, Cittadella Universitaria di Monserrato, S.P. 8 km 0.700, 09042 Cagliari (Italy); Ruffilli, Roberta [Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, Cittadella Universitaria di Monserrato, S.P. 8 km 0.700, 09042 Cagliari (Italy); Palmas, Simonetta; Mascia, Michele [Dipartimento di Ingegneria Meccanica Chimica e dei Materiali, Università degli Studi di Cagliari, Piazza d’Armi, 09126 Cagliari (Italy)

    2014-08-30

    Graphical abstract: - Highlights: • A multidisciplinary approach on porous Si electrochemical Er doping is proposed. • The phenomena taking place at the large developed surface of porous silicon are studied. • Electrochemical, optical and structural characterizations are used. • The early stages of doping are studied by electrochemical impedance spectroscopy. • The dependence of the final amount of Er deposited on the current intensity and not only on the transferred charge is shown. - Abstract: There is an ongoing intense research for cost-effective Er-doped Si-based light-emitting devices at the 1.5 μm wavelength. The efficient electrochemical Er-doping of porous silicon for this purpose requires a good understanding of the phenomena involved, since those taking place at the pores inner surface control the doping process. However, almost no attention has been given, to date, to the relevant effects of the current intensity onto the doping results. In this work, the effect of the current intensity on the doping process is explored by means of electrochemical impedance spectroscopy, optical reflectivity and energy dispersive spectrometry via scanning electron microscopy. The combined analysis of all results strongly suggests that the formation of a gel-like Er ethanolate, unaffected by changes in the sample thickness, occurs from the very first stages of the doping process. Moreover, while for constant current doping processes we show that, under any given doping condition, the doping level is proportional to the transferred charge, we demonstrate that performing the doping process using different current intensities may lead to dramatically different results.

  1. Hvorfor samtalen ikke er demokratiets sjæl ikke er demokratiets sjæl

    Directory of Open Access Journals (Sweden)

    Michael Schudson

    2001-09-01

    Full Text Available Medie- og kommunikationsforskningen har ofte opfattet samtalen, der føres ansigt-til-ansigt, som en hjørnesten i den demokratiske proces. Denne opfattelse stammer bl.a. fra medieforskeren James Carey, der selv har været inspireret af den amerikanske filosof John Dewey. I den- ne artikel præsenterer Michael Schudson en kritik af, hvad han kalder den romantiske forestilling om samtalen. Samtalen ansigt-til-ansigt har været lige så meget i højsædet i aristokratier som i demokratier, og der er faktisk to distinkte og modsatte idealer for samtale: den selskabelige samtale og den problemløsende samtale. Samtalen, der tjener demo- kratiet, er ikke kendetegnet ved egalitarisme, men ved normstyrethed og offentlighed, ikke ved spontanitet men ved høflighed, og ikke ved dens forrang eller overlegenhed i forhold til trykte medier, radio eller tv, men ved dens nødvendige afhængighed af dem. Der argumenteres for, at institutioner og demokratiske normer giver anledning til demokratiske samtaler, snarere end at samtalens iboende demokrati fører til politisk demokratiske normer og institutioner. Artiklen er oversat af Stig Hjarvard.

  2. Hvorfor samtalen ikke er demokratiets sjæl ikke er demokratiets sjæl

    Directory of Open Access Journals (Sweden)

    Michael Schudson

    2001-09-01

    Full Text Available Medie- og kommunikationsforskningen har ofte opfattet samtalen, der føres ansigt-til-ansigt, som en hjørnesten i den demokratiske proces. Denne opfattelse stammer bl.a. fra medieforskeren James Carey, der selv har været inspireret af den amerikanske filosof John Dewey. I den- ne artikel præsenterer Michael Schudson en kritik af, hvad han kalder den romantiske forestilling om samtalen. Samtalen ansigt-til-ansigt har været lige så meget i højsædet i aristokratier som i demokratier, og der er faktisk to distinkte og modsatte idealer for samtale: den selskabelige samtale og den problemløsende samtale. Samtalen, der tjener demo- kratiet, er ikke kendetegnet ved egalitarisme, men ved normstyrethed og offentlighed, ikke ved spontanitet men ved høflighed, og ikke ved dens forrang eller overlegenhed i forhold til trykte medier, radio eller tv, men ved dens nødvendige afhængighed af dem. Der argumenteres for, at institutioner og demokratiske normer giver anledning til demokratiske samtaler, snarere end at samtalens iboende demokrati fører til politisk demokratiske normer og institutioner. Artiklen er oversat af Stig Hjarvard.

  3. Det man hører, er man selv

    DEFF Research Database (Denmark)

    Svømmekjær, Heidi Frank

    2012-01-01

    Katalog til udstillingen "Det man hører, er man selv" på Mediemuseet i Odense 7. september 2012 - 15. januar 2013.......Katalog til udstillingen "Det man hører, er man selv" på Mediemuseet i Odense 7. september 2012 - 15. januar 2013....

  4. Zebrafisken er et vigtigt forsøgsdyr

    DEFF Research Database (Denmark)

    Kjær-Sørensen, Kasper; Alstrup, Aage Kristian Olsen

    2017-01-01

    Det kan ved første øjekast undre, at en almindelig dansk akvariefisk er blevet forskernes favorit. Ikke desto mindre er det tilfældet for den lille zebrafisk (Danio rerio), som i disse år anvendes til at undersøge funktionen af gener, til at lave dyremodeller for menneskets sygdomme og til...

  5. Hvad er fantastisk ved HBO-serien Game of Thrones?

    DEFF Research Database (Denmark)

    Schubart, Rikke

    2013-01-01

    Blogindlæg på videnskab.dk, kaldt "Hvad er fantastisk ved HBO-serien Game of Thrones?" om HBO tv-serien Game of Thrones......Blogindlæg på videnskab.dk, kaldt "Hvad er fantastisk ved HBO-serien Game of Thrones?" om HBO tv-serien Game of Thrones...

  6. Din tandbørste og pejsen er online

    DEFF Research Database (Denmark)

    Damsgaard, Jan

    2016-01-01

    Det er snart definitivt slut med de store mysterier om flys forsvinden og massive eftersøgninger efter overlevende. Danske Naviair er i disse år med til at sende 66 satellitter i kredsløb om Jorden. Så kan alle kommercielle fly følges, uanset hvor på jordkloden de befinder sig....

  7. A decade of ERS satellite orbits and altimetry

    NARCIS (Netherlands)

    Scharroo, R.

    2002-01-01

    The First European Remote Sensing Satellite, ERS-1, was launched in July 1991, fol- lowed by ERS-2 in April 1995. Both satellites carry a radar altimeter to serve oper- ational applications and scientific research in the fields of geodesy, oceanography, glaciology and meteorology. Together, the

  8. CAMEX-4 ER-2 DOPPLER RADAR V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The ER-2 Doppler radar (EDOP) is an X-band (9.6 GHz) Doppler radar mounted in the nose of ER-2. The instrument has two fixed antennas, one pointing at nadir and the...

  9. Optical absorption and fluorescence properties of Er in sodium ...

    Indian Academy of Sciences (India)

    Unknown

    Abstract. Spectroscopic properties of Er3+ ions in sodium borate glass have been studied. The indirect and direct optical band gaps (Eopt) and energy level parameters (Racah (E1, E2 and E3), spin-orbit (ξ4f) and con- figurational interaction (α)) are evaluated. Spectral intensities for various absorption bands of Er3+ doped.

  10. Grænsen mellem tro og videnskab er flydende

    DEFF Research Database (Denmark)

    Kærgård, Niels

    2017-01-01

    I Danmark er man blevet urimelig skeptisk over for religion og ideologi. Danskerne tror fejlagtigt, at de kan klare sig med rationelle og videnskabelige argumenter.......I Danmark er man blevet urimelig skeptisk over for religion og ideologi. Danskerne tror fejlagtigt, at de kan klare sig med rationelle og videnskabelige argumenter....

  11. Er adgang til internettet en grundrettighed i EU?

    DEFF Research Database (Denmark)

    Jakobsen, Søren Sandfeld

    2013-01-01

    Med udgangspunkt i EU-teledirektivpakken behandles spørgsmålet, om adgang til internettet er en grundrettighed efter EU-retten, således at der er væsentlige begrænsninger i medlemsstaternes mulighed for at indføre restriktioner i denne adgang, fx i tilfælde, hvor borgeren misbruger internetadgangen...

  12. Ellipsometric studies of ErMnO3 single crystals

    DEFF Research Database (Denmark)

    Babonas, G.-J.; Grivel, Jean-Claude; Reza, A.

    2007-01-01

    Ellipsometric studies of ErMnO3 single crystals have been carried out in the spectral range of 1-5 eV by means of photometric ellipsometers. Experimental ellipsometric data were analysed in the uniaxial crystal model. For the first time, the components of dielectric function of ErMnO3 were...

  13. Distinct Roles for the Hsp40 and Hsp90 Molecular Chaperones during Cystic Fibrosis Transmembrane Conductance Regulator Degradation in Yeast

    OpenAIRE

    Youker, Robert T.; Walsh, Peter; Beilharz, Traude; Lithgow, Trevor; Brodsky, Jeffrey L.

    2004-01-01

    Aberrant secreted proteins can be destroyed by ER-associated protein degradation (ERAD), and a prominent, medically relevant ERAD substrate is the cystic fibrosis transmembrane conductance regulator (CFTR). To better define the chaperone requirements during CFTR maturation, the protein was expressed in yeast. Because Hsp70 function impacts CFTR biogenesis in yeast and mammals, we first sought ER-associated Hsp40 cochaperones involved in CFTR maturation. Ydj1p and Hlj1p enhanced Hsp70 ATP hydr...

  14. Ambiguous involvement

    DEFF Research Database (Denmark)

    Dannesboe, Karen Ida

    2016-01-01

    This edited collection shows that good parenthood is neither fixed nor stable. The contributors show how parenthood is equally done by men, women and children, in and through practices involving different normative guidelines. The book explores how normative layers of parenthood are constituted...... by notions such as good childhood, family ideals, national public health and educational strategies. The authors illustrate how different versions of parenthood coexist and how complex sets of actions are demanded to fulfil today’s expectations of parenthood in Western societies. This interdisciplinary book...

  15. Differential Expression Patterns of PTEN in Cyclic, Hyperplastic and Malignant Endometrium: Its Relation with ER, PR and Clinico pathological Parameters

    International Nuclear Information System (INIS)

    Abd El-Maqsoud, N.M.R.; El-Gelany, S.

    2009-01-01

    PTEN is a tumor suppressor gene, which is frequently mutated and involved in the control of cell proliferation, differentiation, and apoptosis in a variety of human tumors including endometrium. We hypothesized that PTEN expression in endometrium is variable throughout the menstrual cycle as well as different endometrial lesions, and that steroid hormones regulate PTEN expression because PTEN is critical in many steroid-sensitive tissues such as endometrium. Aim of Work: In this study, we aimed to assess the relationships between PTEN expression and estrogen (ER), progesterone receptors (PR) in normal endometrium, hyperplasia and endometrial carcinoma. We also evaluated the relationship between PTEN expression and clinic pathologic parameters including tumor grade, stage and myomrtial invasion in endometrial carcinoma. Methods: Specimens included 12 cyclical endometrium, 12 cases endometrial hyperplasia without atypia, 8 cases atypical endometrial hyperplasia and 35 endometrial carcinoma specimens. Immunohistochemical staining for PTEN protein, ER and PR was performed with the Streptavidin-biotin method on formalin-fixed and paraffin embedded tissue samples. PTEN, ER and PR expression was represented as the staining score. Results: Immunohistochemistry showed that PTEN, ER and PR were positive for nuclei of cells. The PTEN staining score of normal endometrium was higher in the proliferative phase than in the secretory phase. The PTEN scores in atypical hyperplasia and endometrial carcinoma were significantly lowered than those for cyclic and hyperplasia without atypia. In endometrial carcinoma, PTEN expression was significantly correlated with histological grade while no significant associations with either stage or myometrial invasion were seen. Significant correlations were detected between PTEN and PR in EC cases and between PR and ER in all lesions, while no correlation was seen between ER and PTEN in different lesions. Conclusions: PTEN expression has been

  16. EDEM2 and OS-9 are required for ER-associated degradation of non-glycosylated sonic hedgehog.

    Directory of Open Access Journals (Sweden)

    Hsiang-Yun Tang

    Full Text Available Misfolded proteins of the endoplasmic reticulum (ER are eliminated by the ER-associated degradation (ERAD in eukaryotes. In S. cerevisiae, ER-resident lectins mediate substrate recognition through bipartite signals consisting of an unfolded local structure and the adjacent glycan. Trimming of the glycan is essential for the directional delivery of the substrates. Whether a similar recognition and delivery mechanism exists in mammalian cells is unknown. In this study, we systematically study the function and substrate specificity of known mammalian ER lectins, including EDEM1/2/3, OS-9 and XTP-3B using the recently identified ERAD substrate sonic hedgehog (SHH, a soluble protein carrying a single N-glycan, as well as its nonglycosylated mutant N278A. Efficient ERAD of N278A requires the core processing complex of HRD1, SEL1L and p97, similar to the glycosylated SHH. While EDEM2 was required for ERAD of both glycosylated and non-glycosylated SHHs, EDEM3 was only necessary for glycosylated SHH and EDEM1 was dispensable for both. Degradation of SHH and N278A also required OS-9, but not the related lectin XTP3-B. Robust interaction of both EDEM2 and OS-9 with a non-glycosylated SHH variant indicates that the misfolded polypeptide backbone, rather than a glycan signature, functions as the predominant signal for recognition for ERAD. Notably, SHH-N278A is the first nonglycosylated substrate to require EDEM2 for recognition and targeting for ERAD. EDEM2 also interacts with calnexin and SEL1L, suggesting a potential avenue by which misfolded glycoproteins may be shunted towards SEL1L and ERAD rather than being released into the secretory pathway. Thus, ER lectins participate in the recognition and delivery of misfolded ER substrates differently in mammals, with an underlying mechanism distinct from that of S. cerevisiae.

  17. Unravelling the energy transfer of Er3+-self-sensitized upconversion in Er3+-Yb3+-Er3+clustered core@shell nanoparticles.

    Science.gov (United States)

    Huang, Bolong; Sun, Mingzi; Dougherty, Alan William; Dong, Hao; Xu, Yue-Jiao; Sun, Ling-Dong; Yan, Chun-Hua

    2017-11-30

    Unravelling upconversion (UC) energy transfer mechanisms is significant for designing novel efficient anti-Stokes phosphors. We have studied the correlation of different lanthanide dopants within Er 3+ -self-sensitized core@shell upconversion nanoparticles (UCNPs). Here, our focus will be on high-concentration dopants that are able to sufficiently produce the clustering effect, especially within the interplay between Er 3+ and Yb 3+ . We demonstrate that whatever the amount of the self-sensitizer (e.g., Er 3+ ), abnormal absorption enhancement will occur as long as Yb 3+ clusters are present. This effect originates from the substantial energy transfer between Yb 3+ -Yb 3+ clusters despite the increased energy transfer from Yb 3+ to Er 3+ . Therefore, the energy transfer efficiency is still constrained. However, we conversely used one of the aforementioned quench-paths of UC energy transfer to easily transfer the energy from the in-shell shell layer to the in-core area with the assistance of the energy potential reservoir, which was given by the homogeneous core@shell band offset at the interface region. Indirectly, we actualize the Er 3+ UC luminescence with self-sensitization through an extended energy transfer path. This work provides a solid support and analytic theory for unraveling the energy transfer mechanism from recent works on Er 3+ self-sensitized UC luminescence.

  18. Enhance the Er3+ Upconversion Luminescence by Constructing NaGdF4:Er3+@NaGdF4:Er3+ Active-Core/Active-Shell Nanocrystals.

    Science.gov (United States)

    Du, Xiaoyu; Wang, Xiangfu; Meng, Lan; Bu, Yanyan; Yan, Xiaohong

    2017-12-01

    NaGdF 4 :12%Er 3+ @NaGdF 4 :x%Er 3+ (x = 0, 6, 8, 10, and 12) active-core/active-shell nanoparticles (NPs) were peculiarly synthesized via a delayed nucleation pathway with procedures. The phase, shape, and size of the resulting core-shell NPs are confirmed by transmission electron microscopy and X-ray diffraction. Coated with a NaGdF 4 :10%Er 3+ active shell around the NaGdF 4 :12%Er 3+ core NPs, a maximum luminescent enhancement of about 336 times higher than the NaGdF 4 :12%Er 3+ core-only NPs was observed under the 1540 nm excitation. The intensity ratio of green to red was adjusted through the construction of the core-shell structure and the change of Er 3+ concentration in the shell. By analyzing the lifetimes of emission bands and exploring the energy transition mechanism, the giant luminescence enhancement is mainly attributed to the significant increase in the near-infrared absorption at 1540 nm and efficient energy migration from the shell to core.

  19. Simian Virus 40 depends on ER protein folding and quality control factors for entry into host cells

    DEFF Research Database (Denmark)

    Schelhaas, Mario; Malmström, Johan; Pelkmans, Lucas

    2007-01-01

    Cell entry of Simian Virus 40 (SV40) involves caveolar/lipid raft-mediated endocytosis, vesicular transport to the endoplasmic reticulum (ER), translocation into the cytosol, and import into the nucleus. We analyzed the effects of ER-associated processes and factors on infection and on isolated...... viruses and found that SV40 makes use of the thiol-disulfide oxidoreductases, ERp57 and PDI, as well as the retrotranslocation proteins Derlin-1 and Sel1L. ERp57 isomerizes specific interchain disulfides connecting the major capsid protein, VP1, to a crosslinked network of neighbors, thus uncoupling about...

  20. "Kinesernes drøm er at forbruge som os. Vores mareridt er at arbejde som dem."

    DEFF Research Database (Denmark)

    Mehlsen, Camilla

    2011-01-01

    En tung dyne af frygt har lagt sig over Vesten og sat livet i dvale. Mens Europa er for ambitiøs og pessimistisk, dundrer Asien frem i håb. Konsekvenserne er enorme, og snart betyder brain drain hjerneflugt fra Vesten, hvis ikke vi genvinder håbet. SPdan lyser analysen fra den skarpe franske...

  1. A di-arginine motif contributes to the ER localization of the type I transmembrane ER oxidoreductase TMX4

    DEFF Research Database (Denmark)

    Roth, Doris; Lynes, Emily; Riemer, Jan

    2010-01-01

    -glycosylated type I membrane protein that localizes to the ER. We also demonstrate that TMX4 contains a single ER-luminal thioredoxin-like domain, which, in contrast with similar domains in other PDIs, is mainly oxidized in living cells. The TMX4 transcript displays a wide tissue distribution, and is strongly...

  2. Self-diffusion of Er and Hf inpure and HfO2-doped polycrystalline Er2O3

    International Nuclear Information System (INIS)

    Scheidecker, R.W.

    1979-01-01

    Using a tracer technique, self-diffusion of Er and Hf was measured over the approximate temperature interval of 1600 to 1970 0 C in pure and HfO 2 -doped polycryatalline Er 2 O 3 . Up to about 10 m/o HfO 2 dopant level, the Er self-diffusion coefficients followed a relationship based on cation vacancies. Above 10 m/o HfO 2 , deviation from this relationship occurred, apparently due to clustering of cation vacancies and oxygen interstitials around the dopant hafnia ion. The activation energy for the self-diffusion of Er in pure Er 2 O 3 was 82.2 Kcal/mole and increased with the HfO 2 dopant level present. Self-diffusion of Hf was measured in pure Er 2 O 3 having two impurity levels, and a separation of the grain boundary. The volume diffusion of Hf showed both extrinsic and intrinsic behavior with the transition temperature increasing with the impurity level present in Er 2 O 3 . The activation energy for Hf volume diffusion in the intrinsic region was high, i.e. 235 -+ 9.5 Kcal/mole. The grain boundary diffusion was apparently extrinsic over the entire temperature interval Very low Hf self diffusion rates were found in both pure and HfO 2 doped Er 2 O 3 compositions. Despite a clustering effect, the HfO 2 dopant increased the Hf volume diffusion coefficients

  3. Grima: A Distinct Emotion Concept?

    Science.gov (United States)

    Schweiger Gallo, Inge; Fernández-Dols, José-Miguel; Gollwitzer, Peter M; Keil, Andreas

    2017-01-01

    People experience an unpleasant sensation when hearing a scratch on a board or plate. The present research focuses on this aversive experience known in Spanish as 'grima' with no equivalent term in English and German. We hypothesized that this aversive experience constitutes a distinctive, separate emotional concept. In Study 1, we found that the affective meaning of 'grima' was closer to disgust than to other emotion concepts. Thus, in Study 2 we explored the features of grima and compared them with disgust . As grima was reported to be predominantly elicited by certain auditory stimuli and associated with a distinctive physiological pattern, Study 3 used direct measures of physiological arousal to test the assumption of a distinctive pattern of physiological responses elicited by auditory stimuli of grima and disgust, and found different effects on heart rate but not on skin conductance. In Study 4, we hypothesized that only participants with an implementation intention geared toward down-regulating grima would be able to successfully weaken the grima- but not disgust- experience. Importantly, this effect was specific as it held true for the grima-eliciting sounds only, but did not affect disgust-related sounds. Finally, Study 5 found that English and German speakers lack a single accessible linguistic label for the pattern of aversive reactions termed by Spanish speaking individuals as 'grima', whereas the elicitors of other emotions were accessible and accurately identified by German, English, as well as Spanish speakers.

  4. Anarchy in the UPR: A Ca2+-insensitive PKC inhibits SERCA activity to promote ER stress.

    Science.gov (United States)

    Schmitz-Peiffer, Carsten

    2018-02-08

    Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in Western countries, and is linked to the development of liver cancer and Type 2 diabetes (T2D). It is strongly associated with obesity, but the dysregulation of liver lipid storage is not fully understood. Fatty acid oversupply to hepatocytes can establish a vicious cycle involving diminished protein folding, endoplasmic reticulum (ER) stress, insulin resistance and further lipogenesis. This commentary discusses the recent findings of Lai et al. published in Bioscience Reports, that implicate protein kinase C delta (PKCδ) activation by fatty acids in the inhibition of the SERCA Ca 2+ pump, resulting in reduced ER Ca 2+ loading and protein misfolding. PKCδ therefore represents a target for the treatment of both steatosis and insulin resistance, key to the prevention of NAFLD and T2D. ©2018 The Author(s).

  5. Features of impurity photoconductivity in Si:Er/Si epitaxial diodes

    Energy Technology Data Exchange (ETDEWEB)

    Antonov, A. V.; Kudryavtsev, K. E., E-mail: konstantin@ipmras.ru; Shengurov, D. V.; Shmagin, V. B.; Krasilnik, Z. F. [Russian Academy of Sciences, Institute for Physics of Microstructures (Russian Federation)

    2013-11-15

    The photocurrent spectra of Si:Er/Si epitaxial diode structures are studied. It is shown that the nature of the sub-band-gap photoresponse is determined by the epitaxial growth temperature of the Si:Er layer and is not related to the composition of erbium emission centers. It is found that the absorption of light with photon energies lower than the energy-gap of silicon is determined by impurity-defect complexes that appear during the growth of the epitaxial layer and form a quasi-continuous spectrum of states in the energy gap of silicon. It is assumed that these impurity centers are not related to optically active erbium centers and are not involved in excitation-energy transfer to the rare-earth impurity.

  6. In Vitro Study of Er:YAG and Er, Cr:YSGG Laser Irradiation on Human Gingival Fibroblast Cell Line

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Talebi-Ardakani

    2016-05-01

    Full Text Available The ultimate goal of the periodontal treatments is a regeneration of periodontium. Recently, laser irradiations are commonly used to improve wound repair. Because of many controversies about the effects of laser on soft tissue regeneration, more in vitro studies are still needed. The aim of the present in vitro study was to compare the effects of different doses of Er:YAG (erbium-doped:yttrium, aluminum, garnet and Er, Cr:YSGG (erbium, chromium-doped: yttrium, scandium, gallium, garnet laser treatment on human gingival fibroblasts (HGF proliferation. In this randomized single-blind controlled in vitro trial, HGF cells were irradiated using Er:YAG and Er, Cr:YSGG laser for 10 and 30 seconds or remained unexposed as a control group. After a culture period of 24 and 48 hours, HGF cell proliferation was evaluated by MTT assay. The data were subjected to one-sided analysis of variance and Tukey multiple comparison tests. Our results showed Er:YAG application for 10 and 30 seconds as well as Er, Cr:YSGG irradiation for 10 and 30 seconds induced statistically significant (P<0.05 proliferation of HGF cells as compared with the control at 24 hours up to 18.39%, 26.22%, 21.21%, and 17.06% respectively. In 48 hour incubations, Er:YAG and Er, Cr:YSGG irradiation for 10 and 30 seconds significantly increased cellular proliferation up to 22.9%, 32.24%, 30.52% and 30.02% respectively (P<0.05. This study demonstrates that Er:YAG and Er, Cr:YSGG laser significantly increased HGF cell proliferation compared to the control specimens. This higher proliferation can lead to increased wound repair in clinical conditions.

  7. Tv nyheder: Journalistiske Idealer er under Pres

    DEFF Research Database (Denmark)

    Thomsen, Line Hassall

    2013-01-01

    som tv-journalisterne ville ønske det. Tv-journalister har mange store idealer om god journalistik og public service. Men de vilkår journalisterne arbejder under gør idealerne nærmest umulige at opnå i dagligdagen. I dag er det ikke de journalistiske idealer men markedskræfterne der driver de...... Journalist” inside Public Service TV Newsrooms in the UK and Denmark’. Under ph.d.- studiet har jeg tilbragt halvandet år med deltager-observation på de fire største tv-redaktioner i England og Danmark. Jeg har observeret og deltaget i det daglige arbejde på redaktionerne hos TV Avisen og TV2 Nyhederne og i...... licensfinansieret tv-station. Men der tog jeg fejl. Jeg ledte efter forskelligheder, men fandt ligheder. Efterhånden som feltstudiet tog fat gik det op for mig at journalisterne på de fire forskellige tv-stationer arbejdede og tænkte ens. Derudover gik det op for mig at mange af journalisterne på de forskelligt...

  8. Formal modeling and analysis of ER-α associated Biological Regulatory Network in breast cancer

    Directory of Open Access Journals (Sweden)

    Samra Khalid

    2016-10-01

    Full Text Available Background Breast cancer (BC is one of the leading cause of death among females worldwide. The increasing incidence of BC is due to various genetic and environmental changes which lead to the disruption of cellular signaling network(s. It is a complex disease in which several interlinking signaling cascades play a crucial role in establishing a complex regulatory network. The logical modeling approach of René Thomas has been applied to analyze the behavior of estrogen receptor-alpha (ER-α associated Biological Regulatory Network (BRN for a small part of complex events that leads to BC metastasis. Methods A discrete model was constructed using the kinetic logic formalism and its set of logical parameters were obtained using the model checking technique implemented in the SMBioNet software which is consistent with biological observations. The discrete model was further enriched with continuous dynamics by converting it into an equivalent Petri Net (PN to analyze the logical parameters of the involved entities. Results In-silico based discrete and continuous modeling of ER-α associated signaling network involved in BC provides information about behaviors and gene-gene interaction in detail. The dynamics of discrete model revealed, imperative behaviors represented as cyclic paths and trajectories leading to pathogenic states such as metastasis. Results suggest that the increased expressions of receptors ER-α, IGF-1R and EGFR slow down the activity of tumor suppressor genes (TSGs such as BRCA1, p53 and Mdm2 which can lead to metastasis. Therefore, IGF-1R and EGFR are considered as important inhibitory targets to control the metastasis in BC. Conclusion The in-silico approaches allow us to increase our understanding of the functional properties of living organisms. It opens new avenues of investigations of multiple inhibitory targets (ER-α, IGF-1R and EGFR for wet lab experiments as well as provided valuable insights in the treatment of cancers

  9. Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization.

    LENUS (Irish Health Repository)

    Gupta, Sanjeev

    2010-01-01

    During apoptosis, the process of mitochondrial outer membrane permeabilization (MOMP) represents a point-of-no-return as it commits the cell to death. Here we have assessed the role of caspases, Bcl-2 family members and the mitochondrial permeability transition pore on ER stress-induced MOMP and subsequent cell death. Induction of ER stress leads to upregulation of several genes such as Grp78, Edem1, Erp72, Atf4, Wars, Herp, p58ipk, and ERdj4 and leads to caspase activation, release of mitochondrial intermembrane proteins and dissipation of mitochondrial transmembrane potential (DeltaPsim). Mouse embryonic fibroblasts (MEFs) from caspase-9, -2 and, -3 knock-out mice were resistant to ER stress-induced apoptosis which correlated with decreased processing of pro-caspase-3 and -9. Furthermore, pretreatment of cells with caspase inhibitors (Boc-D.fmk and DEVD.fmk) attenuated ER stress-induced loss of DeltaPsim. However, only deficiency of caspase-9 and -2 could prevent ER stress-mediated loss of DeltaPsim. Bcl-2 overexpression or pretreatment of cells with the cell permeable BH4 domain (BH4-Tat) or the mitochondrial permeability transition pore inhibitors, bongkrekic acid or cyclosporine A, attenuated the ER stress-induced loss of DeltaPsim. These data suggest a role for caspase-9 and -2, Bcl-2 family members and the mitochondrial permeability transition pore in loss of mitochondrial membrane potential during ER stress-induced apoptosis.

  10. Crocin protects human embryonic kidney cells (HEK293) from α- and β-Zearalenol-induced ER stress and apoptosis.

    Science.gov (United States)

    Ben Salem, Intidhar; Boussabbeh, Manel; Prola, Alexandre; Guilbert, Arnaud; Bacha, Hassen; Lemaire, Christophe; Abid-Essefi, Salwa

    2016-08-01

    α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL) are the major metabolites of Zearalenone (ZEN) and are known to induce many toxic effects. In the present study, we investigated the involvement of endoplasmic reticulum (ER) stress in α- and β-ZOL-mediated toxicity in human kidney cells (HEK293) and evaluated the effect of a common dietary compound Crocin (CRO), from saffron. We show that α- and β-ZOL treatment induces ER stress as evidenced by the upregulation of the 78 kDa glucose-regulated protein (GRP78) and the Growth arrest and DNA damage-inducible protein (GADD34). Activation of the ER stress response is associated with activation of the mitochondrial pathway of apoptosis. This apoptotic process is characterized by an increase in ROS generation and lipid peroxidation, a loss of mitochondrial transmembrane potential (ΔΨm) and activation of caspases. We also demonstrate that the antioxidant properties of CRO help to prevent ER stress and reduce α- and β-ZOL-induced apoptosis in HEK293 cells. Our results suggest that saffron consumption might be helpful to prevent α- and β-ZOL-induced ER stress and toxicity.

  11. A Distinct Endosomal Ca2+/Mn2+ Pump Affects Root Growth through the Secretory Process1[C][W][OA

    Science.gov (United States)

    Li, Xiyan; Chanroj, Salil; Wu, Zhongyi; Romanowsky, Shawn M.; Harper, Jeffrey F.; Sze, Heven

    2008-01-01

    Ca2+ is required for protein processing, sorting, and secretion in eukaryotic cells, although the particular roles of the transporters involved in the secretory system of plants are obscure. One endomembrane-type Ca-ATPase from Arabidopsis (Arabidopsis thaliana), AtECA3, diverges from AtECA1, AtECA2, and AtECA4 in protein sequence; yet, AtECA3 appears similar in transport activity to the endoplasmic reticulum (ER)-bound AtECA1. Expression of AtECA3 in a yeast (Saccharomyces cerevisiae) mutant defective in its endogenous Ca2+ pumps conferred the ability to grow on Ca2+-depleted medium and tolerance to toxic levels of Mn2+. A green fluorescent protein-tagged AtECA3 was functionally competent and localized to intracellular membranes of yeast, suggesting that Ca2+ and Mn2+ loading into internal compartment(s) enhanced yeast proliferation. In mesophyll protoplasts, AtECA3-green fluorescent protein associated with a subpopulation of endosome/prevacuolar compartments based on partial colocalization with the Ara7 marker. Interestingly, three independent eca3 T-DNA disruption mutants showed severe reduction in root growth normally stimulated by 3 mm Ca2+, indicating that AtECA3 function cannot be replaced by an ER-associated AtECA1. Furthermore, root growth of mutants is sensitive to 50 μm Mn2+, indicating that AtECA3 is also important for the detoxification of excess Mn2+. Curiously, Ateca3 mutant roots produced 65% more apoplastic protein than wild-type roots, as monitored by peroxidase activity, suggesting that the secretory process was altered. Together, these results demonstrate that the role of AtECA3 is distinct from that of the more abundant ER AtECA1. AtECA3 supports Ca2+-stimulated root growth and the detoxification of high Mn2+, possibly through activities mediated by post-Golgi compartments that coordinate membrane traffic and sorting of materials to the vacuole and the cell wall. PMID:18567829

  12. Curcumin induces ER stress-mediated apoptosis through selective generation of reactive oxygen species in cervical cancer cells.

    Science.gov (United States)

    Kim, Boyun; Kim, Hee Seung; Jung, Eun-Ji; Lee, Jung Yun; K Tsang, Benjamin; Lim, Jeong Mook; Song, Yong Sang

    2016-05-01

    Prolonged accumulation of misfolded or unfolded proteins caused by cellular stress, including oxidative stress, induces endoplasmic reticulum stress, which then activates an unfolded protein response (UPR). ER stress is usually maintained at higher levels in cancer cells as compared to normal cells due to altered metabolism in cancer. Here, we investigated whether curcumin is ER stress-mediated apoptosis in cervical cancer cells, and ROS increased by curcumin are involved in the process as an upstream contributor. Curcumin inhibited proliferation of cervical cancer cells (C33A, CaSki, HeLa, and ME180) and induced apoptotic cell death. Curcumin activated ER-resident UPR sensors, such as PERK, IRE-1α, and ATF6, and their downstream-signaling proteins in cervical cancer cells, but not in normal epithelial cells and peripheral blood mononuclear cells (PBMCs). CHOP, a key factor involved in ER stress-mediated apoptosis, was also activated by curcumin. CHOP decreased the ratio of anti-apoptotic protein Bcl-2 to pro-apoptotic protein Bax expression, and subsequently increased the apoptotic population of cervical cancer cells. Furthermore, curcumin elevated levels of intracellular reactive oxygen species (ROS) in cervical cancer cells, but not in normal epithelial cells. Scavenging ROS resulted in inhibition of ER stress and partially restored cell viability in curcumin-treated cancer cells. Collectively, these observations show that curcumin promotes ER stress-mediated apoptosis in cervical cancer cells through increase of cell type-specific ROS generation. Therefore, modulation of these differential responses to curcumin between normal and cervical cancer cells could be an effective therapeutic strategy without adverse effects on normal cells. © 2015 Wiley Periodicals, Inc.

  13. Internationale medier: Når sproget er den eneste forskel

    DEFF Research Database (Denmark)

    Andersen, Rune Saugmann

    2009-01-01

    forhandlingerne som formålet med dem. Det gør der ikke mere. Efter tusindvis af historier i dusinvis af førende aviser verden over ser det ud til at der kun er én historie tilbage: Det neo-liberale udviklingseventyr. For i perioden 2001-2006 – hvor jeg har analyseret pressedækningen i USA, Spanien, England......, Indien og Argentina – er der sket en bemærkelsesværdig ensretning af presseomtalen af forhandlingerne – i øvrigt sideløbende med at forhandlingerne er blevet stadig mere fastlåste. ...

  14. Lipedema: a clinical entity distinct from lymphedema.

    Science.gov (United States)

    Rudkin, G H; Miller, T A

    1994-11-01

    In a review of 250 cases of lymphedema of the lower extremity, 9 patients were noted to share unique similarities in their history and physical findings. Although these patients had mild swelling in their pretibial areas and were all referred with a diagnosis of lymphedema of the legs, their findings differed significantly from the usual patient with either congenital or acquired lymphedema. Notably, the lower extremity swelling was always bilateral and symmetrical in nature and never involved the feet. Skin changes characteristic of lymphedema were not found, and consistent fat pads were present anterior to the lateral malleoli in each patient. These findings are representative of a clinical entity known as lipedema, which is distinct from lymphedema and for which treatment may be different.

  15. Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival.

    Directory of Open Access Journals (Sweden)

    Tomohisa Mori

    Full Text Available The membrane of the endoplasmic reticulum (ER of a cell forms contacts directly with mitochondria whereby the contact is referred to as the mitochondrion-associated ER membrane or the MAM. Here we found that the MAM regulates cellular survival via an MAM-residing ER chaperone the sigma-1 receptor (Sig-1R in that the Sig-1R chaperones the ER stress sensor IRE1 to facilitate inter-organelle signaling for survival. IRE1 is found in this study to be enriched at the MAM in CHO cells. We found that IRE1 is stabilized at the MAM by Sig-1Rs when cells are under ER stress. Sig-1Rs stabilize IRE1 and thus allow for conformationally correct IRE1 to dimerize into the long-lasting, activated endonuclease. The IRE1 at the MAM also responds to reactive oxygen species derived from mitochondria. Therefore, the ER-mitochondrion interface serves as an important subcellular entity in the regulation of cellular survival by enhancing the stress-responding signaling between mitochondria, ER, and nucleus.

  16. Exciting transition metal doped dilute magnetic thin films: MgO:Er and ZnO:Er

    Science.gov (United States)

    Ćakıcı, T.; Sarıtaş, S.; Muǧlu, G. Merhan; Yıldırım, M.

    2017-02-01

    Erbium doped MgO and doped ZnO thin films have reasonably important properties applications in spintronic devices. These films were synthesized on glass substrates by Chemical Spray Pyrolysis (CSP) method. In the literature there has been almost no report on preparation of MgO:Er dilute magnetic thin films by means of CSP. Because doped thin films show different magnetic behaviors, depending upon the type of magnetic material ions, concentration of them, synthesis route and experimental conditions, synthesized MgO:Er and ZnO:Er films were compared to thin film properties. Optical analyses of the synthesized thin films were examined spectral absorption and transmittance measurements by UV-Vis double beam spectrophotometer technique. Structural analysis of the thin films was examined by using XRD, Raman Analysis, FE-SEM, EDX and AFM techniques. Also, magnetic properties of the MgO:Er and ZnO:Er films were investigated by vibrating sample magnetometer (VSM) which show that diamagnetic behavior of the MgO:Er thin film and ferromagnetic (FM) behavior of the ZnO:Er film were is formed.

  17. Patient participation in ERS guidelines and research projects: the EMBARC experience.

    Science.gov (United States)

    Chalmers, James D; Timothy, Alan; Polverino, Eva; Almagro, Marta; Ruddy, Thomas; Powell, Pippa; Boyd, Jeanette

    2017-09-01

    The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) is a European Respiratory Society (ERS) Clinical Research Collaboration dedicated to improving research and clinical care for people with bronchiectasis. EMBARC has created a European Bronchiectasis Registry, funded by the ERS and by the European Union (EU) Innovative Medicines Initiative Programme. From the outset, EMBARC had the ambition to be a patient-focussed project. In contrast to many respiratory diseases, however, there are no specific patient charities or European patient organisations for patients with bronchiectasis and no existing infrastructure for patient engagement. This article describes the experience of EMBARC and the European Lung Foundation in establishing a patient advisory group and then engaging this group in European guidelines, an international registry and a series of research studies. Patient involvement in research, clinical guidelines and educational activities is increasingly advocated and increasingly important. Genuine patient engagement can achieve a number of goals that are critical to the success of an EU project, including focussing activities on patient priorities, allowing patients to direct the clinical and research agenda, and dissemination of guidelines and research findings to patients and the general public. Here, we review lessons learned and provide guidance for future ERS task forces, EU-funded projects or clinical research collaborations that are considering patient involvement. To understand the different ways in which patients can contribute to clinical guidelines, research projects and educational activities.To understand the barriers and potential solutions to these barriers from a physician's perspective, in order to ensure meaningful patient involvement in clinical projects.To understand the barriers and potential solutions from a patient's perspective, in order to meaningfully involve patients in clinical projects.

  18. Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models

    International Nuclear Information System (INIS)

    Moestue, Siver A; Borgan, Eldrid; Huuse, Else M; Lindholm, Evita M; Sitter, Beathe; Børresen-Dale, Anne-Lise; Engebraaten, Olav; Mælandsmo, Gunhild M; Gribbestad, Ingrid S

    2010-01-01

    Increased concentrations of choline-containing compounds are frequently observed in breast carcinomas, and may serve as biomarkers for both diagnostic and treatment monitoring purposes. However, underlying mechanisms for the abnormal choline metabolism are poorly understood. The concentrations of choline-derived metabolites were determined in xenografted primary human breast carcinomas, representing basal-like and luminal-like subtypes. Quantification of metabolites in fresh frozen tissue was performed using high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). The expression of genes involved in phosphatidylcholine (PtdCho) metabolism was retrieved from whole genome expression microarray analyses. The metabolite profiles from xenografts were compared with profiles from human breast cancer, sampled from patients with estrogen/progesterone receptor positive (ER+/PgR+) or triple negative (ER-/PgR-/HER2-) breast cancer. In basal-like xenografts, glycerophosphocholine (GPC) concentrations were higher than phosphocholine (PCho) concentrations, whereas this pattern was reversed in luminal-like xenografts. These differences may be explained by lower choline kinase (CHKA, CHKB) expression as well as higher PtdCho degradation mediated by higher expression of phospholipase A2 group 4A (PLA2G4A) and phospholipase B1 (PLB1) in the basal-like model. The glycine concentration was higher in the basal-like model. Although glycine could be derived from energy metabolism pathways, the gene expression data suggested a metabolic shift from PtdCho synthesis to glycine formation in basal-like xenografts. In agreement with results from the xenograft models, tissue samples from triple negative breast carcinomas had higher GPC/PCho ratio than samples from ER+/PgR+ carcinomas, suggesting that the choline metabolism in the experimental models is representative for luminal-like and basal-like human breast cancer. The differences in choline metabolite

  19. Fine Mapping of a Gene (ER4.1 that Causes Epidermal Reticulation of Tomato Fruit and Characterization of the Associated Transcriptome

    Directory of Open Access Journals (Sweden)

    Lipeng Cui

    2017-07-01

    Full Text Available The hydrophobic cuticle that covers the surface of tomato (Solanum lycopersicum fruit plays key roles in development and protection against biotic and abiotic stresses, including water loss, mechanical damage, UV radiation, pathogens, and pests. However, many details of the genes and regulatory mechanisms involved in cuticle biosynthesis in fleshy fruits are not well understood. In this study, we describe a novel tomato fruit phenotype, characterized by epidermal reticulation (ER of green fruit and a higher water loss rate than wild type (WT fruit. The ER phenotype is controlled by a single gene, ER4.1, derived from an introgressed chromosomal segment from the wild tomato species S. pennellii (LA0716. We performed fine mapping of the single dominant gene to an ~300 kb region and identified Solyc04g082540, Solyc04g082950, Solyc04g082630, and Solyc04g082910as potential candidate genes for the ER4.1 locus, based on comparative RNA-seq analysis of ER and WT fruit peels. In addition, the transcriptome analysis revealed that the expression levels of genes involved in cutin, wax and flavonoid biosynthesis were altered in the ER fruit compared with WT. This study provides new insights into the regulatory mechanisms and metabolism of the fruit cuticle.

  20. Fine Mapping of a Gene (ER4.1) that Causes Epidermal Reticulation of Tomato Fruit and Characterization of the Associated Transcriptome.

    Science.gov (United States)

    Cui, Lipeng; Qiu, Zhengkun; Wang, Zhirong; Gao, Jianchang; Guo, Yanmei; Huang, Zejun; Du, Yongchen; Wang, Xiaoxuan

    2017-01-01

    The hydrophobic cuticle that covers the surface of tomato ( Solanum lycopersicum ) fruit plays key roles in development and protection against biotic and abiotic stresses, including water loss, mechanical damage, UV radiation, pathogens, and pests. However, many details of the genes and regulatory mechanisms involved in cuticle biosynthesis in fleshy fruits are not well understood. In this study, we describe a novel tomato fruit phenotype, characterized by epidermal reticulation (ER) of green fruit and a higher water loss rate than wild type (WT) fruit. The ER phenotype is controlled by a single gene, ER4.1 , derived from an introgressed chromosomal segment from the wild tomato species S. pennellii (LA0716). We performed fine mapping of the single dominant gene to an ~300 kb region and identified Solyc04g082540, Solyc04g082950, Solyc04g082630 , and Solyc04g082910 as potential candidate genes for the ER4.1 locus, based on comparative RNA-seq analysis of ER and WT fruit peels. In addition, the transcriptome analysis revealed that the expression levels of genes involved in cutin, wax and flavonoid biosynthesis were altered in the ER fruit compared with WT. This study provides new insights into the regulatory mechanisms and metabolism of the fruit cuticle.

  1. ER Stress Induced by Tunicamycin Triggers α-Synuclein Oligomerization, Dopaminergic Neurons Death and Locomotor Impairment: a New Model of Parkinson's Disease.

    Science.gov (United States)

    Cóppola-Segovia, Valentín; Cavarsan, Clarissa; Maia, Flavia G; Ferraz, Anete C; Nakao, Lia S; Lima, Marcelo Ms; Zanata, Silvio M

    2017-10-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons of the substantia nigra pars compacta (SNpc), leading to the major clinical abnormalities that characterize this disease. Although PD's etiology is unknown, α-synuclein aggregation plays a pivotal role in PD pathogenesis, which could be associated to some pathological processes such as oxidative stress, endoplasmic reticulum (ER) stress, impaired protein degradation, and mitochondrial dysfunction. Increasing experimental evidence indicates that ER stress is involved in PD, however most of the described results employed cultured cell lines and genetically modified animal models. In this study, we developed a new ER stress rat model employing the well-known ER stressor tunicamycin (Tm). To evaluate if ER stress was able to induce PD features, we performed an intranigral injection of Tm (0.1 μg/cerebral hemisphere) and animals (male Wistar rats) were analyzed 7 days post injection. The classical 6-OHDA neurotoxin model (1 μg/cerebral hemisphere) was used as an established positive control for PD. We show that Tm injection induced locomotor impairment, dopaminergic neurons death, and activation of astroglia. In addition, we observed an extensive α-synuclein oligomerization in SNpc of Tm-injected animals when compared with DMSO-injected controls. Finally, both Tm and 6-OHDA treated animals presented increased levels of ER stress markers. Taken together, these findings show for the first time that the ER stressor Tm recapitulates some of the phenotypic characteristics observed in rodent models of PD, reinforcing the concept that ER stress could be an important contributor to the pathophysiology of PD. Therefore, we propose the intranigral Tm injection as a new ER stress-based model for the study of PD in vivo.

  2. CAMEX-3 ER-2 NAST-MTS V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The CAMEX-3 ER-2 NPOESS Aircraft Sounder Testbed - Microwave Temperature Sounder (NAST-MTS) dataset contains navigation records and microwave spectral radiance...

  3. Er der forskel på grinder og grise?

    DEFF Research Database (Denmark)

    Heðinsdóttir, Katla; Gjerris, Mickey

    2015-01-01

    Når det gælder grindedrab, burde man måske spørge, om en tradition, som involverer smerte, angst og andre negative følelser for dyr, er værd at holde fast i, og om det ikke er muligt at fastholde en færøsk identitet uden grindefangst.......Når det gælder grindedrab, burde man måske spørge, om en tradition, som involverer smerte, angst og andre negative følelser for dyr, er værd at holde fast i, og om det ikke er muligt at fastholde en færøsk identitet uden grindefangst....

  4. TCSP ER-2 DOPPLER RADAR (EDOP) V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The EDOP provides vertically profiled reflectivity and Doppler velocity at aircraft nadir along the flight track. The ER-2 Doppler radar (EDOP) is an X-band (9.6...

  5. Biocompatible Er:(Na,K)NbO3 nanofibers

    Science.gov (United States)

    Markova, N. P.; Grishin, A. M.

    2017-11-01

    Dense homogeneous fabric composed from continuous bead-free erbium-doped sodium potassium niobate (Er:NKN) 100 μm long and 100-200 nm in diameter nanofibers was sintered by sol-gel calcination assisted electrospinning technique. Er doping with the concentration of 2 at.% provides readily detectable room-temperature broad-band photoluminescence (PL) centered at λPL = 0.55 and 0.98 μm being pumped, respectively, with 532 and 785 nm lasers. Electric field induced resistance switching and strong electric rectification effect were found in nanoporous sandwich Au/Er:NKN/Pt capacitive cell. Memristor-type current-voltage I-V characteristics originate from the electrochemical migration of oxygen vacancies at the n-type Er:NKN oxide/high work function Pt cathode junction interface.

  6. Promoter and Cofactor Requirements for SERM-ER Activity

    National Research Council Canada - National Science Library

    Carroll, Jason S

    2007-01-01

    .... We originally planned to develop a methodology for specifically isolating chromatin to assess associated proteins but due to technical limitations we developed the ChiP-on-chip technique to map ER...

  7. Narrowband Er:YAG nonplanar ring oscillator at 1645 nm.

    Science.gov (United States)

    Chen, Da-Wun; Belden, Paul M; Rose, Todd S; Beck, Steven M

    2011-04-01

    We report 1645 nm narrowband operation of a monolithic Er:YAG nonplanar ring oscillator resonantly pumped at 1532 nm. Unidirectional cw power up to 0.5 W was obtained with a measured linewidth of 21 kHz.

  8. CAMEX-4 ER-2 MICROWAVE TEMPERATURE PROFILER V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The CAMEX-4 ER-2 Microwave Temperature Profiler dataset was collected by the Microwave Temperature Profiler (MTP), which is a passive microwave radiometer which...

  9. Wheel slip control of ABS using ER valve pressure modulator

    Science.gov (United States)

    Choi, Seung-Bok; Cho, Myung-Soo; Kim, Yong-Il; Choi, Young-Tai; Wereley, Norman M.

    2004-07-01

    This paper presents a wheel slip control via sliding mode controller for a new anti-lock brake system (ABS) of a passenger vehicle using electrorheological (ER) valve pressure modulator. The principal design parameters of the ER valves and hydraulic booster are appropriately determined by considering braking pressure variation during ABS operation. An electrically controllable pressure modulator using the ER valves is then constructed and its governing equations are derived. Subsequently, the pressure control performance of the new pressure modulator is experimentally evaluated. The governing equations of motion for a quarter car wheel model are derived and the sliding mode controller is formulated for wheel slip control. Hardware in the loop simulation (HILS) for braking performance evaluation is undertaken in order to demonstrate the effectiveness of the proposed ABS associated with the ER valve pressure modulator.

  10. TCSP ER-2 LIGHTNING INSTRUMENT PACKAGE (LIP) V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The TCSP ER-2 Lightning Instrument Package (LIP) consists of 7 rotating vane type electric field sensors and a two channel conductivity probe along with a central...

  11. TCSP ER-2 MICROWAVE TEMPERATURE PROFILER (MTP) V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The ER2 MTP is a passive microwave radiometer which measures the thermal emission from oxygen molecules in the atmosphere for a selection of elevation angles...

  12. Sygepleje er et selvstændigt fag

    DEFF Research Database (Denmark)

    Scheel, Linda Schumann

    2014-01-01

    DEBAT: Når Kjeld Møller Pedersen er skeptisk over for tanken om, at sygeplejersker skal drive egen praksis, glemmer han ifølge Anne Mette Jørgensen og Linda Schumann Scheel, at sygepleje er et selvstændigt fag. Derfor tager de i denne debat til genmæle over for kritikken.......DEBAT: Når Kjeld Møller Pedersen er skeptisk over for tanken om, at sygeplejersker skal drive egen praksis, glemmer han ifølge Anne Mette Jørgensen og Linda Schumann Scheel, at sygepleje er et selvstændigt fag. Derfor tager de i denne debat til genmæle over for kritikken....

  13. TCSP ER-2 LIGHTNING INSTRUMENT PACKAGE (LIP) V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The ER-2 Lightning Instrument Package (LIP) consists of 7 rotating vane type electric field sensors and a two channel conductivity probe along with a central...

  14. CAMEX-4 ER-2 LIGHTNING INSTRUMENT PACKAGE (LIP) V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The ER-2 Lightning Instrument Package (LIP) allows the vector components of the electric field (i.e, Ex, Ey, Ez )to be readily obtained, and thus, greatly improves...

  15. Nuclear level density of 166Er with static deformation

    International Nuclear Information System (INIS)

    Nasrabadi, M.N.

    2006-01-01

    The level densities of 166 Er is calculated using the microscopic theory of interacting fermions and is compared with experimental. It is concluded that the data can be reproduced with level density formalism for nuclei with static deformation

  16. TCSP ER-2 MODIS AIRBORNE SIMULATOR (MAS) V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The TCSP ER-2 MODIS Airborne Simulator (MAS) dataset was collected by a MODIS Airborne Simulator (MAS), which is a multi-spectral line-scanner system that acquires...

  17. Det man tænker er man selv

    DEFF Research Database (Denmark)

    Rosenbaum, Philip

    2017-01-01

    I en tid, hvor ”det postfaktuelle samfund” er det mest populære udtryk øst for Valby bakke, er det vigtigt for de profaktuelle fanebærere at forstå, at fakta og evidens ikke i sig selv ændrer på folks opfattelse og holdninger. For at evidensbaserede argumenter skal få en vigtig position i samfund...

  18. "Det man hører, er man selv"

    DEFF Research Database (Denmark)

    Bonde, Lars Ole

    2015-01-01

    ”Det man hører, er man selv” er Danmarks Radios P3s yderst velkendte slogan. Det dukkede op i begyndelsen af (20)00erne som opfindsom og populær afspejling af en moderne forståelse af den rolle musik og medieforbrug spiller for den voksne dansker. Denne artikel handler ikke om P3 som musikkanal...

  19. A model for the generation and interconversion of ER morphologies

    OpenAIRE

    Shemesh, Tom; Klemm, Robin W.; Romano, Fabian B.; Wang, Songyu; Vaughan, Joshua; Zhuang, Xiaowei; Tukachinsky, Hanna; Kozlov, Michael M.; Rapoport, Tom A.

    2014-01-01

    The endoplasmic reticulum (ER) is an important membrane-bound organelle in all eukaryotic cells. Depending on cell type and functional state, the ER membrane can adopt different morphologies, including a network of interconnected tubules, and sheets that can contain fenestrations or be stacked on top of each other. How these different morphologies are generated is unclear. Here, we present a comprehensive theoretical model that explains the formation and interconversion of virtually all known...

  20. Structural, dielectric and multiferroic properties of Er and La ...

    Indian Academy of Sciences (India)

    Erbium (Er) and lanthanum (La) substituted BiFeO3 (BFO) ceramics have been prepared through conventional solid solution route. X-ray diffraction data indicated a gradual phase transition from rhombohedral to monoclinic structure in Bi0.9– La0.1Er FeO3 ( = 0.05, 0.07 and 0.1) (BLEFO = 0.05, 0.07,0.1) ceramics.

  1. Paliperidone ER: a review of the clinical trial data

    OpenAIRE

    Janicak, Philip

    2008-01-01

    Philip G Janicak1, Elizabeth A Winans2,31Department of Psychiatry, Rush University Medical Center, Chicago, IL, USA; 2Previously Employed by Scientific Affairs, Ortho-McNeil Janssen, LLC, Chicago, IL, USA; 3Department of Pharmacy Practice, University of Missouri Kansas City, MO, USAAbstract: Paliperidone extended-release tablet (paliperidone ER; INVEGATM) is an oral antipsychotic for the treatment of schizophrenia. The recommended dose range is 3–12 mg per day. Paliperidone ER utili...

  2. Outdoor Adventure er mulighedernes læringslandskab

    DEFF Research Database (Denmark)

    Pedersen, Sune Ib Schou

    2014-01-01

    Global Nutrition and Health er en ny international uddannelse for ernærings- og sundhedsstuderende ved Professionshøjskolen Metropol. De tilbydes Outdoor Adventure, som bryder de vante rammer for undervisning.......Global Nutrition and Health er en ny international uddannelse for ernærings- og sundhedsstuderende ved Professionshøjskolen Metropol. De tilbydes Outdoor Adventure, som bryder de vante rammer for undervisning....

  3. Outdoor Adventure er mulighedernes læringslandskab

    DEFF Research Database (Denmark)

    Pedersen, Sune

    2015-01-01

    Global Nutrition and Health er en ny international uddannelse for ernærings- og sundhedsstuderende ved Professionshøjskolen Metropol. De tilbydes Outdoor Adventure, som bryder de vante rammer for undervisning.......Global Nutrition and Health er en ny international uddannelse for ernærings- og sundhedsstuderende ved Professionshøjskolen Metropol. De tilbydes Outdoor Adventure, som bryder de vante rammer for undervisning....

  4. Er Native Advertising en gråzone?

    DEFF Research Database (Denmark)

    Andersen, Lars Pynt

    2018-01-01

    Native advertising ser ud til at være den perfekte syntese mellem læsernes ønske om interessant indhold og annoncørers ønske om at komme tættere på kunderne. Men native advertising er også anklaget for at være fundamentalt uetisk i sin virkemåde, og måske er de gode oplevelser faktisk netop et...

  5. Misforstået: Er ansvarlighed en borgerpligt?

    DEFF Research Database (Denmark)

    Knudsen, Hanne

    2008-01-01

    Regeringen kører for tiden en kampagne under sloganet ?Mit ansvar? og har i den forbindelse nedsat det midlertidige ?ministerudvalg om det personlige ansvar?. Forældre til skoleelever er blandt de borgere, som ifølge kampagnen skal tage større ansvar. Man kunne spørge, om det er en hjælp til de p...

  6. Søgning er læsning

    DEFF Research Database (Denmark)

    Bundsgaard, Jeppe

    2008-01-01

    Faglig læsning og skrivning er noget, der skal arbejdes med i alle fag. I danskfaget er et af de faglige områder søgning på nettet. Dette kan betragtes som en teknisk færdighed, men det fordrer også flere hidtil ukendte og sjældne læsemåder og læsestrategier. Derfor må der undervises i, at elever...

  7. ER stress response plays an important role in aggregation of α-synuclein

    Directory of Open Access Journals (Sweden)

    Melrose Heather L

    2010-12-01

    Full Text Available Abstract Background Accumulation of filamentous α-synuclein as Lewy bodies is a hallmark of Parkinson's disease. To identify the mechanisms involved in α-synuclein assembly and determine whether the assemblies are cytotoxic, we developed a cell model (3D5 that inducibly expresses wild-type human α-synuclein and forms inclusions that reproduce many morphological and biochemical characteristics of Lewy bodies. In the present study, we evaluated the effects of several histone deacetylase inhibitors on α-synuclein aggregation in 3D5 cells and primary neuronal cultures. These drugs have been demonstrated to protect cells transiently overexpressing α-synuclein from its toxicity. Results Contrary to transient transfectants, the drug treatment did not benefit 3D5 cells and primary cultures. The treated were less viable and contained more α-synuclein oligomers, active caspases 3 and 9, as well as ER stress markers than non-treated counterparts. The drug-treated, induced-3D5 cells, or primary cultures from transgenic mice overexpressing ( Conclusions Our results indicate that an increase of wild-type α-synuclein can elicit ER stress response and sensitize cells to further insults. Most importantly, an increase of ER stress response can promote the aggregation of wild type α-synuclein.

  8. Er:YAG laser: the promising procedure for caries treatment

    Science.gov (United States)

    Ishikawa, Isao; Aoki, Akira; Watanabe, Hisashi; Ando, Yoshinori; Yamada, Toshimoto; Otsuki, Masayuki; Tagami, Junji

    1996-04-01

    The effectiveness of the Er:YAG laser for caries removal was evaluated in vitro and in vivo. As the in vitro study, thirty-two extracted human teeth with cervical root caries were used. An axially divided half of each caries lesion was treated with the Er:YAG laser, and the other was removed with round steel burs mounted on a micromotor or was left untreated as a control. Laser irradiation was performed in contact and non-contact mode at 145 mJ/pulse (51.3 J/cm2/pulse) and 10 pps under water spray. Conventional micromotor treatment was performed at 10,000 rpm using some different size of round steel burs. Measurement of time required for caries removal, histological observation of decalcified serial sections, SEM observation and hardness measurement of the cavity floor dentin were conducted with both laser and conventional treatments. In addition to the above in vitro study, the usefulness of root caries treatment with the Er:YAG laser was assessed in vivo as a clinical trial. The results indicated that removal of carious dentin using the Er:YAG laser was completed effectively to the same extent as the conventional treatment and thermal damage of the lased cavity was minimum. The Er:YAG laser treatment diminished unpleasant sound and vibration, when compared with the conventional rotary technique. We conclude that the Er:YAG laser possesses the promising characteristics for caries removal.

  9. A model for the generation and interconversion of ER morphologies.

    Science.gov (United States)

    Shemesh, Tom; Klemm, Robin W; Romano, Fabian B; Wang, Songyu; Vaughan, Joshua; Zhuang, Xiaowei; Tukachinsky, Hanna; Kozlov, Michael M; Rapoport, Tom A

    2014-12-09

    The peripheral endoplasmic reticulum (ER) forms different morphologies composed of tubules and sheets. Proteins such as the reticulons shape the ER by stabilizing the high membrane curvature in cross-sections of tubules and sheet edges. Here, we show that membrane curvature along the edge lines is also critical for ER shaping. We describe a theoretical model that explains virtually all observed ER morphologies. The model is based on two types of curvature-stabilizing proteins that generate either straight or negatively curved edge lines (R- and S-type proteins). Dependent on the concentrations of R- and S-type proteins, membrane morphologies can be generated that consist of tubules, sheets, sheet fenestrations, and sheet stacks with helicoidal connections. We propose that reticulons 4a/b are representatives of R-type proteins that favor tubules and outer edges of sheets. Lunapark is an example of S-type proteins that promote junctions between tubules and sheets. In a tubular ER network, lunapark stabilizes three-way junctions, i.e., small triangular sheets with concave edges. The model agrees with experimental observations and explains how curvature-stabilizing proteins determine ER morphology.

  10. Vesicular transport of progeny parvovirus particles through ER and Golgi regulates maturation and cytolysis.

    Science.gov (United States)

    Bär, Séverine; Rommelaere, Jean; Nüesch, Jürg P F

    2013-09-01

    Progeny particles of non-enveloped lytic parvoviruses were previously shown to be actively transported to the cell periphery through vesicles in a gelsolin-dependent manner. This process involves rearrangement and destruction of actin filaments, while microtubules become protected throughout the infection. Here the focus is on the intracellular egress pathway, as well as its impact on the properties and release of progeny virions. By colocalization with cellular marker proteins and specific modulation of the pathways through over-expression of variant effector genes transduced by recombinant adeno-associated virus vectors, we show that progeny PV particles become engulfed into COPII-vesicles in the endoplasmic reticulum (ER) and are transported through the Golgi to the plasma membrane. Besides known factors like sar1, sec24, rab1, the ERM family proteins, radixin and moesin play (an) essential role(s) in the formation/loading and targeting of virus-containing COPII-vesicles. These proteins also contribute to the transport through ER and Golgi of the well described analogue of cellular proteins, the secreted Gaussia luciferase in absence of virus infection. It is therefore likely that radixin and moesin also serve for a more general function in cellular exocytosis. Finally, parvovirus egress via ER and Golgi appears to be necessary for virions to gain full infectivity through post-assembly modifications (e.g. phosphorylation). While not being absolutely required for cytolysis and progeny virus release, vesicular transport of parvoviruses through ER and Golgi significantly accelerates these processes pointing to a regulatory role of this transport pathway.

  11. Near ultraviolet to near infrared luminescence spectroscopy of Er3+ doped K2GdF5 crystal

    International Nuclear Information System (INIS)

    Qin, Yanguang; Wei, Xiantao; Li, Xinyue; Chen, Yonghu; Yin, Min

    2014-01-01

    The detailed luminescent properties of K 2 GdF 5 crystal doped with Er 3+ was investigated using excitation spectra, emission spectra and emission decay curve measurements. The excitation bands corresponding to the characteristic Gd 3+ 4f–4f transitions in the excitation spectra of Er 3+ emission indicate an efficient energy transfer from host Gd 3+ to doping Er 3+ ions. Meanwhile, the distinct features observed only in the emission spectra excited with shorter wavelengths (≤312 nm) are assigned to the transitions from 2 P 3/2 levels of Er 3+ . This assignment is further supported by the decay curves measurements and the obtained lifetime of 2 P 3/2 emission (460 μs) is longer than that of 4 S 3/2 emission (248 μs). The luminescence in near infrared (NIR) range from 750 to 1650 nm consists of several well-distinguished bands dominated by the emission around 1540 nm corresponding to the transition of 4 I 13/2 → 4 I 15/2 . NIR quantum cutting processes are observed and discussed with reference to the NIR emission spectra. - Highlights: • Energy transfer from host Gd 3+ to doping Er 3+ ions is efficient. • The transitions from 2 P 3/2 dominate the emissions when excited with shorter wavelengths (≤312 nm). • The lifetime of 2 P 3/2 emissions (460 μs) is longer than that of 4 S 3/2 (248 μs). • The NIR luminescence in the range from 750 to 1650 nm consists of six bands. • NIR quantum cutting processes are observed

  12. AFM observation of OMVPE-grown ErP on InP substrates using a new organometal tris(ethylcyclopentadienyl)erbium (Er(EtCp)3)

    International Nuclear Information System (INIS)

    Akane, T.; Jinno, S.; Yang, Y.; Kuno, T.; Hirata, T.; Isogai, Y.; Watanabe, N.; Fujiwara, Y.; Nakamura, A.; Takeda, Y.

    2003-01-01

    ErP has been grown on InP(0 0 1) substrates by organometallic vapor phase epitaxy (OMVPE) using a new liquid organic Er source: tris(ethylcyclopentadienyl)erbium (Er(EtCp) 3 ). Morphological change of an ErP layer on InP(0 0 1) is investigated together with that of an overgrown capping InP layer. Optimum growth condition of InP causes islanding on over-monolayer-ErP. A relatively low overgrowth temperature of InP is a key factor for attaining complete capping coverage on ErP

  13. GBNV encoded movement protein (NSm) remodels ER network via C-terminal coiled coil domain

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Pratibha; Savithri, H.S., E-mail: bchss@biochem.iisc.ernet.in

    2015-08-15

    Plant viruses exploit the host machinery for targeting the viral genome–movement protein complex to plasmodesmata (PD). The mechanism by which the non-structural protein m (NSm) of Groundnut bud necrosis virus (GBNV) is targeted to PD was investigated using Agrobacterium mediated transient expression of NSm and its fusion proteins in Nicotiana benthamiana. GFP:NSm formed punctuate structures that colocalized with mCherry:plasmodesmata localized protein 1a (PDLP 1a) confirming that GBNV NSm localizes to PD. Unlike in other movement proteins, the C-terminal coiled coil domain of GBNV NSm was shown to be involved in the localization of NSm to PD, as deletion of this domain resulted in the cytoplasmic localization of NSm. Treatment with Brefeldin A demonstrated the role of ER in targeting GFP NSm to PD. Furthermore, mCherry:NSm co-localized with ER–GFP (endoplasmic reticulum targeting peptide (HDEL peptide fused with GFP). Co-expression of NSm with ER–GFP showed that the ER-network was transformed into vesicles indicating that NSm interacts with ER and remodels it. Mutations in the conserved hydrophobic region of NSm (residues 130–138) did not abolish the formation of vesicles. Additionally, the conserved prolines at positions 140 and 142 were found to be essential for targeting the vesicles to the cell membrane. Further, systematic deletion of amino acid residues from N- and C-terminus demonstrated that N-terminal 203 amino acids are dispensable for the vesicle formation. On the other hand, the C-terminal coiled coil domain when expressed alone could also form vesicles. These results suggest that GBNV NSm remodels the ER network by forming vesicles via its interaction through the C-terminal coiled coil domain. Interestingly, NSm interacts with NP in vitro and coexpression of these two proteins in planta resulted in the relocalization of NP to PD and this relocalization was abolished when the N-terminal unfolded region of NSm was deleted. Thus, the NSm

  14. Magnetic Interactions in the Double Perovskites R2NiMnO6 (R = Tb, Ho, Er, Tm) Investigated by Neutron Diffraction.

    Science.gov (United States)

    Retuerto, María; Muñoz, Ángel; Martínez-Lope, María Jesús; Alonso, José Antonio; Mompeán, Federico J; Fernández-Díaz, María Teresa; Sánchez-Benítez, Javier

    2015-11-16

    R2NiMnO6 (R = Tb, Ho, Er, Tm) perovskites have been prepared by soft-chemistry techniques followed by high oxygen-pressure treatments; they have been investigated by X-ray diffraction, neutron powder diffraction (NPD), and magnetic measurements. In all cases the crystal structure is defined in the monoclinic P21/n space group, with an almost complete order between Ni(2+) and Mn(4+) cations in the octahedral perovskite sublattice. The low temperature NPD data and the macroscopic magnetic measurements indicate that all the compounds are ferrimagnetic, with a net magnetic moment different from zero and a distinct alignment of Ni and Mn spins depending on the nature of the rare-earth cation. The magnetic structures are different from the one previously reported for La2NiMnO6, with a ferromagnetic structure involving Mn(4+) and Ni(2+) moments. This spin alignment can be rationalized taking into account the Goodenough-Kanamori rules. The magnetic ordering temperature (TCM) decreases abruptly as the size of the rare earth decreases, since TCM is mainly influenced by the superexchange interaction between Ni(2+) and Mn(4+) (Ni(2+)-O-Mn(4+) angle) and this angle decreases with the rare-earth size. The rare-earth magnetic moments participate in the magnetic structures immediately below TCM.

  15. An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER

    Directory of Open Access Journals (Sweden)

    Daniel F. Markgraf

    2014-01-01

    Full Text Available Eukaryotic cells store neutral lipids such as triacylglycerol (TAG in lipid droplets (LDs. Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER. We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG. During LD breakdown in early exponential phase, an ER membrane protein (Ice2p facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption.

  16. ER signaling is activated to protect human HaCaT keratinocytes from ER stress induced by environmental doses of UVB

    International Nuclear Information System (INIS)

    Mera, Kentaro; Kawahara, Ko-ichi; Tada, Ko-ichi; Kawai, Kazuhiro; Hashiguchi, Teruto; Maruyama, Ikuro; Kanekura, Takuro

    2010-01-01

    Proteins are folded properly in the endoplasmic reticulum (ER). Various stress such as hypoxia, ischemia and starvation interfere with the ER function, causing ER stress, which is defined by the accumulation of unfolded protein (UP) in the ER. ER stress is prevented by the UP response (UPR) and ER-associated degradation (ERAD). These signaling pathways are activated by three major ER molecules, ATF6, IRE-1 and PERK. Using HaCaT cells, we investigated ER signaling in human keratinocytes irradiated by environmental doses of ultraviolet B (UVB). The expression of Ero1-Lα, an upstream signaling molecule of ER stress, decreased at 1-4 h after 10 mJ/cm 2 irradiation, indicating that the environmental dose of UVB-induced ER stress in HaCaT cells, without growth retardation. Furthermore, expression of intact ATF6 was decreased and it was translocated to the nuclei. The expression of XBP-1, a downstream molecule of IRE-1, which is an ER chaperone whose expression is regulated by XBP-1, and UP ubiquitination were induced by 10 mJ/cm 2 UVB at 4 h. PERK, which regulates apoptosis, was not phosphorylated. Our results demonstrate that UVB irradiation generates UP in HaCaT cells and that the UPR and ERAD systems are activated to protect cells from UVB-induced ER stress. This is the first report to show ER signaling in UVB-irradiated keratinocytes.

  17. Eosinophils: multifunctional and distinctive properties.

    Science.gov (United States)

    Kita, Hirohito

    2013-01-01

    The eosinophil is a granulocyte prominent in allergic diseases and inflammatory responses against helminthic parasites. The eosinophil was named by Paul Ehrlich in 1879, and derives from the intense staining of its granules with the acidic dye eosin. It has been the subject of extensive investigation ever since. It is strongly associated with human diseases involving mucosal surfaces, such as allergic asthma, atopic dermatitis and gastrointestinal disorders. Eosinophils are likely involved in tissue homeostasis, modulation of adaptive immune responses, innate immunity to certain microbes and pathological changes in allergic disorders. Thus, the eosinophil is considered a multifunctional leukocyte that contributes to a wide variety of physiological and pathological processes, depending on its location and activation status. Further studies will be necessary to better understand the biology of this extraordinary leukocyte and to reveal the importance of the cell in human health and disease. Copyright © 2013 S. Karger AG, Basel.

  18. Den digitale økonomi er fundamentalt anderledes end den industrielle

    DEFF Research Database (Denmark)

    Andersen, Lene; Rasmussen, Steen

    2015-01-01

    Et teknologidrevet globalt gearskift: På kort tid har en digital revolution fundet sted, og samtidig er biologien begyndt at smelte sammen med teknologierne. Konsekvenserne er uoverskuelige.......Et teknologidrevet globalt gearskift: På kort tid har en digital revolution fundet sted, og samtidig er biologien begyndt at smelte sammen med teknologierne. Konsekvenserne er uoverskuelige....

  19. Genome-wide association studies identify four ER negative-specific breast cancer risk loci

    NARCIS (Netherlands)

    Garcia-Closas, Montserrat; Couch, Fergus J.; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K.; Brook, Mark N.; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S.; Le Marchand, Loic; Buring, Julie E.; Eccles, Diana; Miron, Penelope; Fasching, Peter A.; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K.; Nevanlinna, Heli; Giles, Graham G.; Cox, Angela; Hopper, John L.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J.; Schoof, Nils; Bojesen, Stig E.; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L.; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J.; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S.; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H.; Radice, Paolo; teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C.; Park, Daniel J.; Hammet, Fleur; Stone, Jennifer; Veer, Laura J. Van't; Rutgers, Emiel J.; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G.; Ekici, Arif B.; Beckmann, Matthias W.; dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N.; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O.; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E.; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A.; Feng, Ye; Henderson, Brian E.; Schumacher, Fredrick; Bogdanova, Natalia V.; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A. E. M.; Seynaeve, Caroline M.; Kriege, Mieke; Hooning, Maartje J.; van den Ouweland, Ans M. W.; van Deurzen, Carolien H. M.; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P.; Cross, Simon S.; Reed, Malcolm W. R.; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C.; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B.; Bandera, Elisa V.; John, Esther M.; Chen, Gary K.; Hu, Jennifer J.; Rodriguez-Gil, Jorge L.; Bernstein, Leslie; Press, Michael F.; Ziegler, Regina G.; Millikan, Robert M.; Deming-Halverson, Sandra L.; Nyante, Sarah; Ingles, Sue A.; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K.; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G.; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G.; Montgomery, Grant W.; Slamon, Dennis J.; Rauh, Claudia; Lux, Michael P.; Jud, Sebastian M.; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H.; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N.; Chen, Constance; Beck, Andy; Hankinson, Susan E.; Berg, Christine D.; Hoover, Robert N.; Lissowska, Jolanta; Figueroa, Jonine D.; Chasman, Daniel I.; Gaudet, Mia M.; Diver, W. Ryan; Willett, Walter C.; Hunter, David J.; Simard, Jacques; Benitez, Javier; Dunning, Alison M.; Sherman, Mark E.; Chenevix-Trench, Georgia; Chanock, Stephen J.; Hall, Per; Pharoah, Paul D. P.; Vachon, Celine; Easton, Douglas F.; Haiman, Christopher A.; Kraft, Peter

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including

  20. Patterns of Injuries After Road Traffic Crashes Involving Bodabodas

    African Journals Online (AJOL)

    2010-01-12

    Jan 12, 2010 ... Road traffic crashes generally affect young people and this is most evident in bodaboda crashes because .... ing concussions were classified as head injuries. Injuries involving the thorax including rib fractures ... ers and passengers bear the brunt of the impact (4). About one fourth of the injured had cranial ...

  1. Structural Analysis of the QCM Aboard the ER-2

    Science.gov (United States)

    Jones, Phyllis D.; Bainum, Peter M.; Xing, Guangqian

    1997-01-01

    As a result of recent supersonic transport (SST) studies on the effect they may have on the atmosphere, several experiments have been proposed to capture and evaluate samples of the stratosphere where SST's travel. One means to achieve this is to utilize the quartz crystal microbalance (QCM) installed aboard the ER-2, formerly the U-2 reconnaissance aircraft. The QCM is a cascade impactor designed to perform in-situ, real-time measurements of aerosols and chemical vapors at an altitude of 60,000 - 70,000 feet. The ER-2 is primarily used by NASA for Earth resources to test new sensor systems before they are placed aboard satellites. One of the main reasons the ER-2 is used for this flight experiment is its capability to fly approximately twelve miles above sea level (can reach an altitude of 78,000 feet). Because the ER-2 operates at such a high altitude, it is of special interest to scientists interested in space exploration or supersonic aircraft. Some of the experiments are designed to extract data from the atmosphere around the ER-2. For the current flight experiment, the QCM is housed in a frame that is connected to an outer pod that is attached to the fuselage of the ER-2. Due to the location of the QCM within the housing frame and the location of the pod on the ER-2, the pod and its contents are subject to structural loads. In addition to structural loads, structural vibrations are also of importance because the QCM is a frequency induced instrument. Therefore, a structural analysis of the instrument within the frame is imperative to determine if resonance and/or undesirable deformations occur.

  2. Paliperidone ER: a review of the clinical trial data

    Directory of Open Access Journals (Sweden)

    Philip G Janicak

    2007-01-01

    Full Text Available Philip G Janicak1, Elizabeth A Winans2,31Department of Psychiatry, Rush University Medical Center, Chicago, IL, USA; 2Previously Employed by Scientific Affairs, Ortho-McNeil Janssen, LLC, Chicago, IL, USA; 3Department of Pharmacy Practice, University of Missouri Kansas City, MO, USAAbstract: Paliperidone extended-release tablet (paliperidone ER; INVEGATM is an oral antipsychotic for the treatment of schizophrenia. The recommended dose range is 3–12 mg per day. Paliperidone ER utilizes the OROS® delivery system, which allows for once-daily dosing. Its pharmacokinetic profile results in a more stable serum concentration. Paliperidone is 9-hydroxyrisperidone, the chief active metabolite of risperidone. It undergoes limited hepatic metabolism, thereby minimizing the risks of hepatic drug–drug and drug–disease interactions. Three 6-week trials in patients with acute schizophrenia reported that paliperidone ER was effective, well tolerated, and produced clinically meaningful improvements in personal and social functioning compared with placebo. Post-hoc analysis of these trials in various populations, including recently diagnosed, elderly and more severely ill patients, those with sleep disturbances and those with predominant negative symptoms demonstrated improvement as well. Paliperidone ER was also significantly better than placebo in the prevention of symptom recurrence in a 6-month maintenance study. The most common clinically relevant adverse events associated with paliperidone ER were extrapyramidal symptoms, tachycardia and somnolence. The incidence of Parkinsonism, akathisia and use of anticholinergic medications increased in a dose-related manner. Further, modest QTc interval prolongation was observed but did not produce clinical symptoms. Similar to risperidone, paliperidone ER is associated with increases in serum prolactin levels. Overall, paliperidone ER was effective, well tolerated and provides a new treatment option for

  3. Med sjefen på Facebook: En studie av ledere som er "venner" med sine ansatte

    OpenAIRE

    Jensen, Anita

    2014-01-01

    MR690 Masteroppgave i organisasjon og ledelse - utdanningsledelse Formålet med studien er å belyse hvordan aktiv bruk av sosiale medier, i dette tilfellet Facebook, påvirker relasjoner mellom mennesker. Hva skjer når en tar i bruk en websjanger som i utgangspunktet er umiddelbar og uformell, til jobbrelatert og mer formell kommunikasjon? Er det sjangeren eller relasjonen som endres? Søkelyset rettes mot ledere som er “venner” med sine medarbeidere, og problemstillingen er...

  4. ER-2 #809 awaits pilot entry for the third flight of the SAGE III Ozone Loss and Validation Experime

    Science.gov (United States)

    2000-01-01

    ER-2 #809 awaiting pilot entry for the third flight of the SAGE III Ozone Loss and Validation Experiment (SOLVE). The ER-2, a civilian variant of Lockheed's U-2, and another NASA flying laboratory, Dryden's DC-8, were based north of the Arctic Circle in Kiruna, Sweden during the winter of 2000 to study ozone depletion as part of SOLVE. A large hangar built especially for research, 'Arena Arctica' housed the instrumented aircraft and the scientists. Scientists have observed unusually low levels of ozone over the Arctic during recent winters, raising concerns that ozone depletion there could become more widespread as in the Antarctic ozone hole. The NASA-sponsored international mission took place between November 1999 and March 2000 and was divided into three phases. The DC-8 was involved in all three phases returning to Dryden between each phase. The ER-2 flew sample collection flights between January and March, remaining in Sweden from Jan. 9 through March 16. 'The collaborative campaign will provide an immense new body of information about the Arctic stratosphere,' said program scientist Dr. Michael Kurylo, NASA Headquarters. 'Our understanding of the Earth's ozone will be greatly enhanced by this research.' ER-2s bearing tail numbers 806 and 809 are used as airborne science platforms by NASA's Dryden Flight Research Center. The aircraft are platforms for a variety of high-altitude science missions flown over various parts of the world. They are also used for earth science and atmospheric sensor research and development, satellite calibration and data validation. The ER-2s are capable of carrying a maximum payload of 2,600 pounds of experiments in a nose bay, the main equipment bay behind the cockpit, two wing-mounted superpods and small underbody and trailing edges. Most ER-2 missions last about six hours with ranges of about 2,200 nautical miles. The aircraft typically fly at altitudes above 65,000 feet. On November 19, 1998, an ER-2 set a world record for

  5. Hippocampal ER stress and learning deficits following repeated pyrethroid exposure.

    Science.gov (United States)

    Hossain, Muhammad M; DiCicco-Bloom, Emanuel; Richardson, Jason R

    2015-01-01

    Endoplasmic reticulum (ER) stress is implicated as a significant contributor to neurodegeneration and cognitive dysfunction. Previously, we reported that the widely used pyrethroid pesticide deltamethrin causes ER stress-mediated apoptosis in SK-N-AS neuroblastoma cells. Whether or not this occurs in vivo remains unknown. Here, we demonstrate that repeated deltamethrin exposure (3 mg/kg every 3 days for 60 days) causes hippocampal ER stress and learning deficits in adult mice. Repeated exposure to deltamethrin caused ER stress in the hippocampus as indicated by increased levels of C/EBP-homologous protein (131%) and glucose-regulated protein 78 (96%). This was accompanied by increased levels of caspase-12 (110%) and activated caspase-3 (50%). To determine whether these effects resulted in learning deficits, hippocampal-dependent learning was evaluated using the Morris water maze. Deltamethrin-treated animals exhibited profound deficits in the acquisition of learning. We also found that deltamethrin exposure resulted in decreased BrdU-positive cells (37%) in the dentate gyrus of the hippocampus, suggesting potential impairment of hippocampal neurogenesis. Collectively, these results demonstrate that repeated deltamethrin exposure leads to ER stress, apoptotic cell death in the hippocampus, and deficits in hippocampal precursor proliferation, which is associated with learning deficits. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Aging induced ER stress alters sleep and sleep homeostasis

    Science.gov (United States)

    Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

    2014-01-01

    Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

  7. Overvågning af orkidéer 2000

    DEFF Research Database (Denmark)

    Wind, P.

    Miljø- og Energiministeriets program for overvågning af danske orkidéer har med udgangen af 2000 forløbet i 14 år. I 2000 har 65 overvågere indsendt oplysninger til Danmarks Miljøundersøgelser (DMU) om 297 bestande tilhørende 39 forskellige vildtvoksende orkidéarter fordelt på 216 prøvefelter (se...... truet og sårbar samt de to arter der er omfattet af Habitatdirektivets bilag 2. I 2000 kan det i forhold til 1999 konstateres at der i 15 bestande er optalt et øget antal skud. I 11 bestande er der noteret en nedgang i antallet af skud sammenlignet med optællingerne i 1999. Af disse er der 2 be...... registreret. Dette fald kædes sammen med den tørre og varme forårsperiode fra slut-nin-gen af april til slutningen af maj 2000....

  8. DEBONDING OF CERAMIC BRACKETS BY ER:YAG LASER

    Directory of Open Access Journals (Sweden)

    Fidan ALAKUŞ-SABUNCUOĞLU

    2016-04-01

    Full Text Available Purpose: The objective of the present study is to evaluate the effects of Er:YAG laser debonding of ceramic brackets on the bond strength and the amount of adhesive resin remnant. Materials and Methods: Twenty human mandibular incisors were randomly divided into two groups of 10 and polycrystalline ceramic brackets (Transcend series 6000, 3M Unitek, Monrovia, CA, USA were bonded on enamel surfaces. Group 1 was the control group in which no laser application was performed prior to the shear bond strength (SBS testing. In Group 2, Er:YAG was applied in 3W power for 6 seconds using the scanning method. The brackets were tested for SBS with an Instron universal testing machine and results were expressed in megapascals (MPa. The amount of adhesive remnant was evaluated with Adhesive Remnant Index (ARI. One-way analysis of variance and Tukey’s post-hoc tests were used for statistical analysis. Results: Mean ± standard deviation of SBS values in the control group was 13.42 ±1.23 MPa and 8.47 ±0.71 MPa in the Er:YAG group and this difference was statistically significant (p<0.05. The evaluation of ARI scores demonstrated more adhesive was left on the enamel surface with Er:YAG group. Conclusion: 3W power Er:YAG laser application with the scanning method to polycrystalline ceramic brackets demonstrated lower bond strengths and higher ARI scores during the debonding procedure.

  9. Distinctiveness of Ugandapithecus from Proconsul

    Directory of Open Access Journals (Sweden)

    Gommery, D.

    2009-12-01

    Full Text Available The decision to create the genus Ugandapithecus by Senut et al., 2000 has been criticised, either directly and in detail by MacLatchy & Rossie (2005b who argued that it is a junior synonym of Proconsul, or indirectly without providing reasons, firstly by Harrison (2001 who wrote that he did not retain it as a genus distinct from Proconsul, and then by Suwa et al., (2007 who employed the name “Ugandapithecus” with inverted commas, implying some degree of doubt about its validity as a genus, but without providing details. More recently Harrison & Andrews (2009 have recognised the Meswa sample as a separate species but they argue that it should be maintained within Proconsul, despite the morphological differences that it has from other species of the genus. We here re-examine the question by comparing, on the one hand, the holotype maxilla of Proconsul africanus, the type species of the genus, with the upper dentition of Ugandapithecus major, and, on the other hand, the holotype mandible of Ugandapithecus major with the lower dentition and mandibles previously attributed to Proconsul africanus. We conclude that the differences between the known upper and lower dentitions of P. africanus and U. major are of such a degree that the two taxa warrant generic separation, and that the differences are not related to sexual dimorphism. Where Proconsul africanus differs from Ugandapithecus major, it approaches Proconsul nyanzae and Proconsul heseloni from Rusinga.Furthermore, the range of morphometric variation within the fossil samples previously attributed to Ugandapithecus major is so great that it far surpasses variation in any other hominoid, fossil or extant. Previously this great amount of variation was interpreted to mean that U. major was extremely dimorphic, with huge males and small females, but if this is true, then U. major would be unique among hominoids in having females in which the cheek teeth fall completely outside the range of

  10. User Involvement And Entrepreneurial Action

    Directory of Open Access Journals (Sweden)

    Eva Heiskanen

    2007-01-01

    Full Text Available Involving users in the innovation process is a subject of much research, experimentation, and debate. Less attention has been given to the limits to user involvement that ensue from specific organizational characteristics. This article explores barriers to the utilization of users’ input in two small companies developing interactive digital applications. We contrast our findings to earlier research involving large companies to identify features of entrepreneurial sensemaking and action that influence the utilization of users’ input. We find that the small companies follow a distinct action rationality, leading to rapid implementation of some user inputs, and defensiveness toward others. Both sets of data also reveal common features that are often overlooked in the literature. We reconceptualize user involvement as a form of interaction between users and innovating companies that is facilitated and constrained by micro-sociological processes, on the one hand, and the nature of the competitive environment, on the other.

  11. Identification of remediation needs and technology development focus areas for the Environmental Restoration (ER) Project at Sandia National Laboratories/New Mexico (SNL/NM)

    International Nuclear Information System (INIS)

    Tucker, M.D.

    1995-06-01

    The Environmental Restoration (ER) Project has been tasked with the characterization, assessment, remediation and long-term monitoring of contaminated waste sites at Sandia National Laboratories/New Mexico (SNL/NM). Many of these sites will require remediation which will involve the use of baseline technologies, innovative technologies that are currently under development, and new methods which will be developed in the near future. The Technology Applications Program (TAP) supports the ER Project and is responsible for development of new technologies for use at the contaminated waste sites, including technologies that will be used for remediation and restoration of these sites. The purpose of this report is to define the remediation needs of the ER Project and to identify those remediation needs for which the baseline technologies and the current development efforts are inadequate. The area between the remediation needs and the existing baseline/innovative technology base represents a technology gap which must be filled in order to remediate contaminated waste sites at SNL/NM economically and efficiently. In the first part of this report, the remediation needs of the ER Project are defined by both the ER Project task leaders and by TAP personnel. The next section outlines the baseline technologies, including EPA defined Best Demonstrated Available Technologies (BDATs), that are applicable at SNL/NM ER sites. This is followed by recommendations of innovative technologies that are currently being developed that may also be applicable at SNL/NM ER sites. Finally, the gap between the existing baseline/innovative technology base and the remediation needs is identified. This technology gap will help define the future direction of technology development for the ER Project

  12. Liquidity spillover in international stock markets through distinct time scales.

    Science.gov (United States)

    Righi, Marcelo Brutti; Vieira, Kelmara Mendes

    2014-01-01

    This paper identifies liquidity spillovers through different time scales based on a wavelet multiscaling method. We decompose daily data from U.S., British, Brazilian and Hong Kong stock markets indices in order to calculate the scale correlation between their illiquidities. The sample is divided in order to consider non-crisis, sub-prime crisis and Eurozone crisis. We find that there are changes in correlations of distinct scales and different periods. Association in finest scales is smaller than in coarse scales. There is a rise on associations in periods of crisis. In frequencies, there is predominance for significant distinctions involving the coarsest scale, while for crises periods there is predominance for distinctions on the finest scale.

  13. DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca2+ Transfer through the MAM.

    Science.gov (United States)

    Park, Sung Jin; Lee, Su Been; Suh, Yeongjun; Kim, Su-Jeong; Lee, Namgyu; Hong, Ji-Ho; Park, Cana; Woo, Youngsik; Ishizuka, Koko; Kim, Joung-Hun; Berggren, Per-Olof; Sawa, Akira; Park, Sang Ki

    2017-12-05

    A wide range of Ca 2+ -mediated functions are enabled by the dynamic properties of Ca 2+ , all of which are dependent on the endoplasmic reticulum (ER) and mitochondria. Disrupted-in-schizophrenia 1 (DISC1) is a scaffold protein that is involved in the function of intracellular organelles and is linked to cognitive and emotional deficits. Here, we demonstrate that DISC1 localizes to the mitochondria-associated ER membrane (MAM). At the MAM, DISC1 interacts with IP 3 R1 and downregulates its ligand binding, modulating ER-mitochondria Ca 2+ transfer through the MAM. The disrupted regulation of Ca 2+ transfer caused by DISC1 dysfunction leads to abnormal Ca 2+ accumulation in mitochondria following oxidative stress, which impairs mitochondrial functions. DISC1 dysfunction alters corticosterone-induced mitochondrial Ca 2+ accumulation in an oxidative stress-dependent manner. Together, these findings link stress-associated neural stimuli with intracellular ER-mitochondria Ca 2+ crosstalk via DISC1, providing mechanistic insight into how environmental risk factors can be interpreted by intracellular pathways under the control of genetic components in neurons. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Cooperation of the ER-shaping proteins atlastin, lunapark, and reticulons to generate a tubular membrane network.

    Science.gov (United States)

    Wang, Songyu; Tukachinsky, Hanna; Romano, Fabian B; Rapoport, Tom A

    2016-09-13

    In higher eukaryotes, the endoplasmic reticulum (ER) contains a network of membrane tubules, which transitions into sheets during mitosis. Network formation involves curvature-stabilizing proteins, including the reticulons (Rtns), as well as the membrane-fusing GTPase atlastin (ATL) and the lunapark protein (Lnp). Here, we have analyzed how these proteins cooperate. ATL is needed to not only form, but also maintain, the ER network. Maintenance requires a balance between ATL and Rtn, as too little ATL activity or too high Rtn4a concentrations cause ER fragmentation. Lnp only affects the abundance of three-way junctions and tubules. We suggest a model in which ATL-mediated fusion counteracts the instability of free tubule ends. ATL tethers and fuses tubules stabilized by the Rtns, and transiently sits in newly formed three-way junctions. Lnp subsequently moves into the junctional sheets and forms oligomers. Lnp is inactivated by mitotic phosphorylation, which contributes to the tubule-to-sheet conversion of the ER.

  15. Signaling dynamics of palmitate-induced ER stress responses mediated by ATF4 in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Cho Hyunju

    2013-01-01

    Full Text Available Abstract Background Palmitic acid, the most common saturated free fatty acid, has been implicated in ER (endoplasmic reticulum stress-mediated apoptosis. This lipoapotosis is dependent, in part, on the upregulation of the activating transcription factor-4 (ATF4. To better understand the mechanisms by which palmitate upregulates the expression level of ATF4, we integrated literature information on palmitate-induced ER stress signaling into a discrete dynamic model. The model provides an in silico framework that enables simulations and predictions. The model predictions were confirmed through further experiments in human hepatocellular carcinoma (HepG2 cells and the results were used to update the model and our current understanding of the signaling induced by palmitate. Results The three key things from the in silico simulation and experimental results are: 1 palmitate induces different signaling pathways (PKR (double-stranded RNA-activated protein kinase, PERK (PKR-like ER kinase, PKA (cyclic AMP (cAMP-dependent protein kinase A in a time dependent-manner, 2 both ATF4 and CREB1 (cAMP-responsive element-binding protein 1 interact with the Atf4 promoter to contribute to a prolonged accumulation of ATF4, and 3 CREB1 is involved in ER-stress induced apoptosis upon palmitate treatment, by regulating ATF4 expression and possibly Ca2+ dependent-CaM (calmodulin signaling pathway. Conclusion The in silico model helped to delineate the essential signaling pathways in palmitate-mediated apoptosis.

  16. Bright upconversion luminescence and increased Tc in CaBi2Ta2O9:Er high temperature piezoelectric ceramics

    Science.gov (United States)

    Peng, Dengfeng; Wang, Xusheng; Xu, Chaonan; Yao, Xi; Lin, Jian; Sun, Tiantuo

    2012-05-01

    Er3+ doped CaBi2Ta2O9 (CBT) bismuth layered-structure high temperature piezoelectric ceramics were synthesized by the traditional solid state method. The upconversion (UC) emission properties of Er3+ doped CBT ceramics were investigated as a function of Er3+ concentration and incident pump power. A bright green upconverted emission was obtained under excitation 980 nm at room temperature. The observed strong green and weak red emission bands corresponded to the transitions from 4S3/2 and 4F9/2 to 4I15/2, respectively. The dependence of UC emission intensity on pumping power indicated that a three-photon process was involved in UC emissions. Studies of dielectric with temperature have also been carried out. Introduction of Er increased the Curie temperature of CBT, thus, making this ceramic suitable for sensor applications at higher temperatures. Because of its strong up-converted emission and increased Tc, the multifunctional high temperature piezoelectric ceramic may be useful in high temperature sensor, fluorescence thermometry, and optical-electro integration applications.

  17. Bright upconversion luminescence and increased Tc in CaBi2Ta2O9:Er high temperature piezoelectric ceramics

    International Nuclear Information System (INIS)

    Peng Dengfeng; Wang Xusheng; Yao Xi; Xu Chaonan; Lin Jian; Sun Tiantuo

    2012-01-01

    Er 3+ doped CaBi 2 Ta 2 O 9 (CBT) bismuth layered-structure high temperature piezoelectric ceramics were synthesized by the traditional solid state method. The upconversion (UC) emission properties of Er 3+ doped CBT ceramics were investigated as a function of Er 3+ concentration and incident pump power. A bright green upconverted emission was obtained under excitation 980 nm at room temperature. The observed strong green and weak red emission bands corresponded to the transitions from 4 S 3/2 and 4 F 9/2 to 4 I 15/2 , respectively. The dependence of UC emission intensity on pumping power indicated that a three-photon process was involved in UC emissions. Studies of dielectric with temperature have also been carried out. Introduction of Er increased the Curie temperature of CBT, thus, making this ceramic suitable for sensor applications at higher temperatures. Because of its strong up-converted emission and increased Tc, the multifunctional high temperature piezoelectric ceramic may be useful in high temperature sensor, fluorescence thermometry, and optical-electro integration applications.

  18. The Role of ER Bodies in Brassicaceae Resistance under Clinorotation

    Science.gov (United States)

    Romanchuk, S. M.; Kordyum, E. L.

    2013-02-01

    Results of the electron-microscopic investigation of root apices of Arabidopsis thaliana 3- and 7-day old seedlings grown in the stationary conditions and under clinorotation are presented. It was shown the similarity in the root apex cell ultrastructure in control and under clinorotation. In the same time there were some differences in the ultrustructure of statocytes and the distal elongation zone under clinorotation. For the first time, the sensitivity of ER-bodies, which are derivative of granular endoplasmic reticulum and contain a β-glucosidase enzyme, to the influence of simulated microgravity that was demonstrated by increasing quantity and area of ER-bodies per cell section, as well as by higher variability of their shape under clinorotation. A degree of these changes correlated with the duration of clinorotation. On the basis of obtained data, a protective role of ER-bodies in adaptation of plants to microgravity is discussed.

  19. The ERS role on Tobacco Control Policy in Europe

    Directory of Open Access Journals (Sweden)

    Christina Gratziou

    2016-03-01

    Full Text Available The European Respiratory Society is an international medical organisation that brings together physicians, healthcare professionals, scientists and other experts working in respiratory medicine. Its aim is to alleviate suffering from respiratory diseases and promote lung health globally through science, education and advocacy. ERS has since its founding in 1990 demonstrated strong commitment to tobacco control. Through scientific assemblies, education courses, various alliances and collaboration (Framework Convention Alliance, European Chronic Disease Alliance, World Health Organisation etc. As well as a Tobacco Control Committee (TCC dedicated to advocacy, ERS constantly strives to promote strong and evidence-based policies to reduce the burden of tobacco related diseases. One of the main outcome of the TCC is the creation of Smokehaz, a website aimed at providing policy-makers with scientific information on the Health hazards associated with smoking. Recently, ERS created the Latin-America Working Group which aims at strengthening tobacco control activities in Spain, Portugal and Latin-American countries.

  20. Control Performance of Vehicle Abs Featuring ER Valve Pressure Modulator

    Science.gov (United States)

    Cho, M. S.; Choi, S. B.; Wereley, N. M.

    In this work, an electrically controllable anti-lock brake system (ABS) for passenger vehicle is developed by utilizing electrorheological (ER) fluid. A pressure modulator which consists of a cylindrical ER valve and the hydraulic booster is constructed in order to achieve sufficient brake pressure variation during ABS operation. The principal design parameters of the modulator are determined by considering ER properties as well as required braking pressure. After investigating pressure controllability of the modulator, a vehicle model which is integrated with the proposed pressure modulator is formulated to design yaw rate controller. A sliding mode controller is designed to obtain desired yaw rate, and the friction forces between roads and wheels are estimated via the estimator. Braking performances of the proposed ABS under various roads are evaluated through the hardware-in-the-loop-simulation (HILS) and the steering stability during braking operation is demonstrated by undertaking split-μ test.

  1. Hydrogeology of the Umm Er Radhuma Aquifer (Arabian peninsula)

    Science.gov (United States)

    Dirks, Heiko; Al Ajmi, Hussain; Kienast, Peter; Rausch, Randolf

    2018-03-01

    The aim of this article is to enhance the understanding of the Umm Er Radhuma aquifer's genesis, and its hydraulic and hydrochemical development over time. This is a prerequisite for wise use of the fossil groundwater resources contained within. The Umm Er Radhuma is a karstified limestone aquifer, extending over 1.6 Mio. km2 in the eastern part of the Arabian Peninsula. Both epigene and hypogene karstification contributed to the genesis of what is today the most prolific aquifer in the region. Besides man-made abstractions, even the natural outflows are higher than the small recharge (natural storage depletion). The Umm Er Radhuma shows that large aquifers in arid regions are never in "steady state" (where inflows equal outflows), considering Quaternary climate history. The aquifer's adaption to climate changes (precipitation, sea level) can be traced even after thousands of years, and is slower than the climate changes themselves.

  2. ER=EPR, GHZ, and the consistency of quantum measurements

    Energy Technology Data Exchange (ETDEWEB)

    Susskind, Leonard [Stanford Institute for Theoretical Physics and Department of Physics, Stanford University, Stanford, CA (United States)

    2016-01-15

    This paper illustrates various aspects of the ER=EPR conjecture. It begins with a brief heuristic argument, using the Ryu-Takayanagi correspondence, for why entanglement between black holes implies the existence of Einstein-Rosen bridges. The main part of the paper addresses a fundamental question: Is ER=EPR consistent with the standard postulates of quantum mechanics? Naively it seems to lead to an inconsistency between observations made on entangled systems by different observers. The resolution of the paradox lies in the properties of multiple black holes, entangled in the Greenberger-Horne-Zeilinger pattern. The last part of the paper is about entanglement as a resource for quantum communication. ER=EPR provides a way to visualize protocols like quantum teleportation. In some sense teleportation takes place through the wormhole, but as usual, classical communication is necessary to complete the protocol. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  3. Hip hurra, det er min fødselsdag. Eller?

    DEFF Research Database (Denmark)

    Hansen, Nils Gunder

    2013-01-01

    Den verdensberømte japanske forfatter Haruki Murakami har udvalgt 11 noveller og selv skrevet en 12., der alle kredser om fødselsdage. Det er melankolsk, mørk og frem for alt mesterlig læsning......Den verdensberømte japanske forfatter Haruki Murakami har udvalgt 11 noveller og selv skrevet en 12., der alle kredser om fødselsdage. Det er melankolsk, mørk og frem for alt mesterlig læsning...

  4. Er alle mennesker lige meget værd?

    DEFF Research Database (Denmark)

    Petersen, Thomas Søbirk

    2015-01-01

    Visse personers liv og profession har større indflydelse på omverdenen end andres. Betyder det, at de er mere værd, spørger læser. Thomas Søbirk Petersen, professor i etik og moral og medlem af Etikpanelet, svarer......Visse personers liv og profession har større indflydelse på omverdenen end andres. Betyder det, at de er mere værd, spørger læser. Thomas Søbirk Petersen, professor i etik og moral og medlem af Etikpanelet, svarer...

  5. AFP: Et reklamefossil er genfødt?

    DEFF Research Database (Denmark)

    Andersen, Lars Pynt

    2010-01-01

    Skjult sponsering vinder frem igen, og selv om det har en lang historie, ser det ud til at være mere skjult i de nutidige former end i de klassiske fra radiotiden. http://videnskab.dk/content/dk/blogs/reklamebloggen/afp_et_reklamefossil_er_genfodt   Udgivelsesdato: 7.6.......Skjult sponsering vinder frem igen, og selv om det har en lang historie, ser det ud til at være mere skjult i de nutidige former end i de klassiske fra radiotiden. http://videnskab.dk/content/dk/blogs/reklamebloggen/afp_et_reklamefossil_er_genfodt   Udgivelsesdato: 7.6....

  6. Ln3PO7(Ln-La-Er) oxyphosphates

    International Nuclear Information System (INIS)

    Tselebrovskaya, E.G.; Dzhurinskij, B.F.; Lyamina, O.I.

    1997-01-01

    Ln 3 PO 7 (Ln-La-Er) oxyphosphates are obtained through solid phase synthesis method. La 3 PO 7 monocrystals are grown. Structural changes in the La-Er oxyphosphates series are evaluated through roentgenography and IR-spectroscopy methods; referral of the IR- and RR-spectra to iscillations of interatomic bonds Ln-O, P-O, O-P-O is made; isostructure, sp.gr.Cm. is established and crystal cell parameters for the whole series of compounds is determined. 16 refs.; 3 figs.; 3 tabs

  7. CBS-institutleder: Der er masser af muligheder i blockchain

    DEFF Research Database (Denmark)

    Damsgaard, Jan

    2017-01-01

    Flere virksomheder fokuserer på blockchain, ligesom flere iværksættere og uddannelsesinstitutioner også gør. Derfor er der masser af muligheder i blockchain, der venter på at blive taget i brug......Flere virksomheder fokuserer på blockchain, ligesom flere iværksættere og uddannelsesinstitutioner også gør. Derfor er der masser af muligheder i blockchain, der venter på at blive taget i brug...

  8. Inflation er en af finanskrisens løsninger

    DEFF Research Database (Denmark)

    Boje Rasmussen, Martin Møller

    2013-01-01

    Med en lille anekdote om børnepasning illustrerer den amerikanske stjerneøkonom Paul Krugman, hvorfor økonomiske recessioner opstår, og hvad vi bør stille op over for dem. Inflation er et af svarene.......Med en lille anekdote om børnepasning illustrerer den amerikanske stjerneøkonom Paul Krugman, hvorfor økonomiske recessioner opstår, og hvad vi bør stille op over for dem. Inflation er et af svarene....

  9. Medical student empathy: interpersonal distinctions and correlates.

    Science.gov (United States)

    Jordan, Kevin D; Foster, Penni Smith

    2016-12-01

    Attention to interpersonal behaviors, communication, and relational factors is taking on increasing importance in medical education. Medical student empathy is one aspect of the physician-patient relationship that is often involved in beneficial interactions leading to improved clinical outcomes and patient satisfaction. As an interpersonal quality, empathy is a social behavior well-suited to be examined from an interpersonal perspective. The present study used the interpersonal theory of clinical, personality, and social psychology to examine the construct of empathy and theorize about likely interpersonal correlates. One hundred and sixty-three students from an academic health center in the southeastern United States participated in this study. The medical student version of the Jefferson Scale of Empathy was used to assess empathy and its factors: Perspective taking, compassionate care, and walking in the patient's shoes. Interpersonal assessments included the International Personality Item Pool-Interpersonal Circumplex, the Interpersonal Support Evaluation List, and the UCLA Loneliness Scale. Distinct interpersonal styles and correlates emerged among empathy and its factors. While all factors of empathy were related to interpersonal warmth, perspective taking and compassionate care were also associated with submissiveness. Of note, only walking in the patient's shoes was correlated with both social support and less loneliness. These findings are discussed in light of interpersonal theory with particular attention paid to the implications for medical education and professional development.

  10. Hva er Digital Valuta? Hva slags formuerettslig produkt er digital valuta? Omfattes slike finansielle produkter av gjeldende finansreguleringer og hvordan burde de reguleres?

    OpenAIRE

    Heggen, Vilde Stuvøy

    2014-01-01

    Det er kanskje ingen overraskelse at man i internettalderen har funnet på en valuta som kun eksisterer på nett. Per i dag eksisterer det flere slike nettvalutaer, med varierende grad av oppslutning. Spørsmålet som stilles i oppgaven er hva slags formuerettslig objekt digital valuta er. Jeg regner digital valuta som alle valutaer som hovedsakelig er å finne på nett og som ikke utstedes av eller på vegne av en statsmakt. Definisjonen omfatter både kryptovalutaer som Bitcoin, som nok er mest kje...

  11. An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER

    DEFF Research Database (Denmark)

    Markgraf, Daniel F; Klemm, Robin W; Junker, Mirco

    2014-01-01

    Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary...... phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic...... and explain how cells switch neutral lipid metabolism from storage to consumption....

  12. Optical Transition Probabilities of Er3+ Ions in ErBa3B9O18 Crystal

    Directory of Open Access Journals (Sweden)

    Ming He

    2015-01-01

    Full Text Available The optical absorption and emission intensity of luminescent and birefringent crystal ErBa3B9O18 were examined from optical absorption data based on Judd-Ofelt theory. The three intensity parameters Ωt (t=2,4,6 are 3.10 × 10−20, 0.87 × 10−20, and 1.80 × 10−20 cm2, respectively. From the obtained intensity parameters, the radiative probabilities Ar, radiative lifetime τf, fluorescence branching ratios βc, and integrated emission cross sections ∑ have been calculated. In comparison with other Er-doped luminescent crystals, ErBa3B9O18 may find application in thin disk laser.

  13. Unraveling the role of ER stress inhibitors in the context of metabolic diseases.

    Science.gov (United States)

    Sarvani, Chodisetty; Sireesh, Dornadula; Ramkumar, Kunka Mohanram

    2017-05-01

    ER stress is provoked by the accumulation of unfolded and misfolded proteins in the ER lumen leading to perturbations in ER homeostasis. ER stress activates a signaling cascade called the Unfolded Protein Response (UPR) which triggers a set of transcriptional and translational events that restore ER homeostasis, promoting cell survival and adaptation. If this adaptive response fails, a terminal UPR program commits such cells to apoptosis. Existing preclinical and clinical evidence testify that prolonged ER stress escalates the risk of several metabolic disorders including diabetes, obesity and dyslipidemia. There have been considerable efforts to develop small molecules that are capable of ameliorating ER stress. Few naturally occurring and synthetic molecules have already been demonstrated for their efficacy in abrogating ER stress in both in vitro and in vivo models of metabolic disorders. This review provides a broad overview of the molecular mechanisms of inhibition of ER stress and its association with various metabolic diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Pahute Mesa Well Development and Testing Analyses for Wells ER-20-7, ER-20-8 #2, and ER-EC-11, Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Greg Ruskauff

    2011-12-01

    This report analyzes the following data collected from ER-20-7, ER-20-8 No.2, and ER-EC-11 during WDT operations: (1) Chemical indicators of well development (Section 2.0); (2) Static hydraulic head (Section 3.0); (3) Radiochemistry and geochemistry (Section 4.0); (4) Drawdown observed at locations distal to the pumping well (Section 5.0); and (5) Drilling water production, flow logs, and temperature logs (Section 6.0). The new data are further considered with respect to existing data as to how they enhance or change interpretations of groundwater flow and transport, and an interim small-scale conceptual model is also developed and compared to Phase I concepts. The purpose of well development is to remove drilling fluids and drilling-associated fines from the formation adjacent to a well so samples reflecting ambient groundwater water quality can be collected, and to restore hydraulic properties near the well bore. Drilling fluids can contaminate environmental samples from the well, resulting in nonrepresentative measurements. Both drilling fluids and preexisting fines in the formation adjacent to the well can impede the flow of water from the formation to the well, creating artifacts in hydraulic response data measured in the well.

  15. Acrolein activates cell survival and apoptotic death responses involving the endoplasmic reticulum in A549 lung cells.

    Science.gov (United States)

    Tanel, André; Pallepati, Pragathi; Bettaieb, Ahmed; Morin, Patrick; Averill-Bates, Diana A

    2014-05-01

    Acrolein, a highly reactive α,β-unsaturated aldehyde, is a product of endogenous lipid peroxidation. It is a ubiquitous environmental pollutant that is generated mainly by smoke, overheated cooking oil and vehicle exhaust. Acrolein damages cellular proteins, which could lead to accumulation of aberrantly-folded proteins in the endoplasmic reticulum (ER). This study determines the mechanisms involved in acrolein-induced apoptosis mediated by the ER and possible links with the ER stress response in human A549 lung cells. The exposure of cells to acrolein (15-50μM) for shorter times of 15 to 30min activated several ER stress markers. These included the ER chaperone protein BiP and the three ER sensors: (i) the survival/rescue molecules protein kinase RNA (PKR)-like ER kinase (PERK) and eukaryotic initiation factor 2 alpha (eIF2α) were phosphorylated; (ii) cleavage of activating transcription factor 6 (ATF6) occurred, and (iii) inositol-requiring protein-1 alpha (IRE1α) was phosphorylated. Acrolein (25-50μM) caused apoptotic cell death mediated by the ER after 2h, which was characterised by the induction of CHOP and activation of ER proteases calpain and caspase-4. Calpain and caspase-7 were the initiating factors for caspase-4 activation in acrolein-induced apoptosis. These results increase our knowledge about cellular responses to acrolein in lung cells, which have implications for human health. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Comparative efficacy of Er,Cr:YSGG and Er:YAG lasers for etching of composite for orthodontic bracket bonding.

    Science.gov (United States)

    Mirhashemi, Amir Hossein; Chiniforush, Nasim; Sharifi, Nastaran; Hosseini, Amir Mehdi

    2018-01-11

    Several techniques have been proposed to obtain a durable bond, and the efficacy of these techniques is assessed by measuring parameters such as bond strength. Laser has provided a bond strength as high as that of acid etching in vitro and has simpler use with shorter clinical time compared to acid etching. This study aimed to compare the efficacy of Er:YAG and Er,Cr:YSGG lasers for etching and bonding of composite to orthodontic brackets. No previous study has evaluated the effect of these particular types of laser. A total of 70 composite blocks were randomly divided into five groups (n = 14): group 1, etching with phosphoric acid for 20 s; group 2, Er:YAG laser irradiation with 2 W power for 10 s; group 3, Er:YAG laser with 3 W power for 10 s; group 4, Er,Cr:YSGG laser with 2 W power for 10 s; group 5, Er,Cr:YSGG laser with 3 W power for 10 s. Metal brackets were then bonded to composites, and after 5000 thermal cycles, they were subjected to shear bond strength test in a universal testing machine after 24 h of water storage. One sample of each group was evaluated under a scanning electron microscope (SEM) to assess changes in composite surface after etching. The adhesive remnant index (ARI) was calculated under a stereomicroscope. Data were statistically analyzed. The mean and standard deviation of shear bond strength were 18.65 ± 3.36, 19.68 ± 5.34, 21.31 ± 4.03, 17.38 ± 6.94, and 16.45 ± 4.26 MPa in groups 1-5, respectively. The ARI scores showed that the bond failure mode in all groups was mainly mixed. The groups were not significantly different in terms of shear bond strength. Er:YAG and Er,Cr:YSGG lasers with the mentioned parameters yield optimal shear bond strength and can be used as an alternative to acid etching for bracket bond to composite.

  17. Serious Games pour l’éducation : utiliser, créer, faire créer ?

    OpenAIRE

    Djaouti, Damien

    2016-01-01

    Dans cet article, nous commencerons par revenir sur les définitions du Serious Game, ainsi qu’aux avantages et limites de son utilisation pour l’éducation. Nous passerons ensuite en revue trois approches d’utilisation pédagogique du Serious Game : utiliser des Serious Games existants avec ses étudiants ; créer des Serious Games « sur mesure » pour ses étudiants ; et faire créer des Serious Games directement par les étudiants. Nous analyserons alors la mise en œuvre pratique de ces différentes...

  18. Microtensile bond strength analysis of adhesive systems to Er:YAG and Er,Cr:YSGG laser-treated dentin.

    Science.gov (United States)

    Ramos, Thaysa Monteiro; Ramos-Oliveira, Thayanne Monteiro; Moretto, Simone Gonçalves; de Freitas, Patricia Moreira; Esteves-Oliveira, Marcella; de Paula Eduardo, Carlos

    2014-03-01

    The aim of this in vitro study was to evaluate the effect of different surface treatments (control, diamond bur, erbium-doped yttrium aluminum garnet (Er:YAG) laser, and erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser) on sound dentin surface morphology and on microtensile bond strength (μTBS). Sixteen dentin fragments were randomly divided into four groups (n = 4), and different surface treatments were analyzed by scanning electron microscopy. Ninety-six third molars were randomly divided into eight groups (n = 12) according to type of surface treatment and adhesive system: G1 = Control + Clearfil SE Bond (SE); G2 = Control + Single Bond (SB); G3 = diamond bur (DB) + SE; G4 = DB + SB, G5 = Er:YAG laser (2.94 μm, 60 mJ, 2 Hz, 0.12 W, 19.3 J/cm(2)) + SE; G6 = Er:YAG + SB, G7 = Er,Cr:YSGG laser (2.78 μm, 50 mJ, 30 Hz, 1.5 W, 4.5 J/cm(2)) + SE; and G8 = Er,Cr:YSGG + SB. Composite blocks were bonded to the samples, and after 24-h storage in distilled/deionized water (37 °C), stick-shaped samples were obtained and submitted to μTBS test. Bond strength values (in megapascal) were analyzed by two-way ANOVA and Tukey tests (α = 0.05). G1 (54.69 ± 7.8 MPa) showed the highest mean, which was statistically significantly higher than all the other groups (p systems did not differ statistically from each other. Based on the irradiation parameters considered in this study, it can be concluded that Er:YAG and Er,Cr:YSGG irradiation presented lower values than the control group; however, their association with self-etching adhesive does not have a significantly negative effect on sound dentin (μTBS values of >20 MPa).

  19. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy.

    Science.gov (United States)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-10-15

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Participation and social participation: are they distinct concepts?

    Science.gov (United States)

    Piškur, Barbara; Daniëls, Ramon; Jongmans, Marian J; Ketelaar, Marjolijn; Smeets, Rob J E M; Norton, Meghan; Beurskens, Anna J H M

    2014-03-01

    The concept of participation has been extensively used in health and social care literature since the World Health Organization introduced its description in the International Classification of Functioning, Disability and Health (ICF) in 2001. More recently, the concept of social participation is frequently used in research articles and policy reports. However, in the ICF, no specific definition exists for social participation, and an explanation of differences between the concepts is not available. The central question in this discussion article is whether participation, as defined by the ICF, and social participation are distinct concepts. This article illustrates the concepts of participation and social participation, presents a critical discussion of their definitions, followed by implications for rehabilitation and possible future directions. A clear definition for participation or social participation does not yet exist. Definitions for social participation differ from each other and are not sufficiently distinct from the ICF definition of participation. Although the ICF is regarded an important conceptual framework, it is criticised for not being comprehensive. The relevance of societal involvement of clients is evident for rehabilitation, but the current ICF definition of participation does not sufficiently capture societal involvement. Changing the ICF's definition of participation towards social roles would overcome a number of its shortcomings. Societal involvement would then be understood in the light of social roles. Consequently, there would be no need to make a distinction between social participation and participation.

  1. Final Technical Report, DOE/ER/64323

    Energy Technology Data Exchange (ETDEWEB)

    Valocchi, Albert J. [University of Illinois, Dept of Civil & Environ Engr

    2013-06-05

    The DOE SciDAC program funded a team that developed PFLOTRAN, the next-generation (peta-scale) massively parallel, multiphase, multicomponent reactive flow and transport code. These codes are required to improve understanding and risk management of subsurface contaminant migration and geological sequestration of carbon dioxide. The important fate and transport processes occurring in the subsurface span a wide range of spatial and temporal scales, and involve nonlinear interactions among many different chemical constituents. Due to the complexity of this problem, modeling subsurface processes normally requires simplifying assumptions. However, tools of advanced scientific computing that have been used in other areas such as energy and materials research can also help address challenging problems in the environmental and geoscience fields. The overall project was led by Los Alamos National Laboratory and included Argonne, Oak Ridge and Pacific Northwest National Laboratories, in addition to the University of Illinois. This report summarizes the results of the research done at the University of Illinois, which focused on improvements to the underlying physical and computational modeling of certain transport and mixing processes.

  2. God smag og bordskik er den bedste slankekur

    DEFF Research Database (Denmark)

    Andersen, Boris

    2011-01-01

    Rockwool Fondens Forskningsenhed har for nylig offentliggjort rapporten ’Helbred, trivsel og overvægt blandt danskerne’, der viser, at antallet af svært overvægtige i USA og Storbritannien er over dobbelt så stort som i Danmark. Den franske madsociolog Claude Fischler beskæftiger sig med sammenhæ...

  3. Ersättningsansvar vid kontraktsförhandlingar

    DEFF Research Database (Denmark)

    Edlund, Hans Henrik

    2012-01-01

    I indlægget gøres det synspunkt gældende, at forholdet mellem parter, der forhandler komplekse erhvervskontrakter, kan anskues som en selvstændig aftalerelation, der i enhver henseende skal bedømmes efter de regler der gælder om misligholdelse af kontrakter. Det er i grove træk alene reglerne om ...

  4. Det som er vigtigt ved at eje skov

    DEFF Research Database (Denmark)

    Boon, Tove Enggrob; Meilby, Henrik

    2014-01-01

    I sommeren 2012 blev private skovejere spurgt om betydningen af skovens økonomi samt en række goder. Lignende spørgsmål blev stillet ved en undersøgelse i 2002. Fra 2002 til 2012 er ejernes oplevelse af skovens økonomiske betydning blevet mere positiv. Ejernes oplevelse af forskellige goders vigt...

  5. FANS-3D Users Guide (ESTEP Project ER 201031)

    Science.gov (United States)

    2016-08-01

    TECHNICAL DOCUMENT 3293 August 2016 FANS -3D User’s Guide (ESTEP Project ER-201031) Pei-Fang Wang SSC Pacific Hamn-Ching...1.1 THEORY AND NUMERICAL ALGORITHM OF FANS CODE ............................................. 1 2. FANS -3D SOFTWARE DOCUMENTATION AND EXECUTION...5 3. FANS -3D CODE PARALLELIZATION

  6. [The ethical approach applied to the TV series ER].

    Science.gov (United States)

    Svandra, Philippe

    2013-05-01

    The television series ER presents an opportunity to reflect on ethical dilemmas. This article discusses the example of an episode in which a patient suffering from an incurable disease, unable to express his views clearly, has a tracheotomy performed on him without the consent of the team or his health care proxy.

  7. 1er. Taller internacional sobre oso hormiguero gigante (Myrmecophaga tridactyla)

    OpenAIRE

    M.V. Guillermo Pérez Jimeno

    2008-01-01

    ResumenLos pasados días 2 y 3 de noviembre se llevó a cabo el 1er. Taller internacional sobre oso hormiguero gigante (Myrmecophaga tridactyla), en instalaciones del Zoológico de Florencio Varela. Participaron activamente representantes de Brasil, Colombia, Holanda, Alemania y Argentina.

  8. Ferske vandområder - Søer

    DEFF Research Database (Denmark)

    Jensen, J. P.; Jeppesen, E.; Søndergaard, M.

    Forord: Denne rapport er udarbej-det af Danmarks Mil-jøunder-søgelser som et led i den lands-dæk-ken-de rapportering af Vand-miljøpla-nens Over-vågningspro-gram. Over-vågningsprogram-met blev iværksat efteråret 1988. Hensigten med Vand-miljøplanens over-vågningsprogram er at undersøge effekten af...... de reguleringer og in-vesteringer, som er- gennemført i forbindelse med Vandmil-jøplanen (1987). Sy-stema-tisk ind-samling af data gør det muligt at opgøre udled-nin-ger af kvæl-stof og fosfor til vandmiljøet samt at registrere de økologiske effekter, der følger af ændringer i be-lastningen af vand...... derfor et naturligt led i Danmarks Miljø-undersø-gelsers opgave at forestå den landsdækkende rapportering af overvågningsprogram-met inden for områder-ne: ferske vande, marine om-råder, land-overvågning og atmos-færen. I overvågningsprogram-met er der en klar arbejdsdeling og an-svars-deling mellem...

  9. Aktiv og sund aldring, men hvad er sundhed?

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2014-01-01

    Aldersrelaterede forandringer og helbredsproblemer kræver fokusering på sundhed og opretholdelse af helbredet. Der er behov for et skift fra sygdomsorienteret til sundhedsorienteret biomedicinsk forskning. Forfatteren argumenterer for, at den biologiske tilgang skal ændre sig fra at være fokusere...

  10. PISA er et farligt succesmål

    DEFF Research Database (Denmark)

    Dolin, Jens

    2010-01-01

    PISA-undersøgelsen har for stor indflydelse på den danske uddannelsesverden, mener Jens Dolin fra Institut for Naturfagenes Didaktik, Københavns Universitet. Senest er en 5. plads i PISA blevet regeringens mål for folkeskolen. Jens Dolin siger, at naturfagsundervisningen trænger til et massivt lø...

  11. Merit, dispensationer og anerkendelse af realkompetencer - hvad er hvad?

    DEFF Research Database (Denmark)

    Lindhardtsen, Mette Ramsing; Aagaard, Kirsten

    2009-01-01

    I mange uddannelser er der mulighed for at få merit, dispensation eller anderkendelse af realkompetencer i forhold til de almindelige regler vedrørende adgang til uddannelser. I midlertid bruges begreberne ikke konsistent, og i artiklen forsøger vi at skitsere, hvorledes begreberne kan bruges mest...

  12. Copenhagen vs Everett, Teleportation, and ER=EPR

    OpenAIRE

    Susskind, Leonard

    2016-01-01

    Quantum gravity may have as much to tell us about the foundations and interpretation of quantum mechanics as it does about gravity. The Copenhagen interpretation of quantum mechanics and Everett's Relative State Formulation are complementary descriptions which in a sense are dual to one another. My purpose here is to discuss this duality in the light of the of ER=EPR conjecture.

  13. Magnetic phase diagram of Ho/Er alloys

    DEFF Research Database (Denmark)

    Cowley, R.A.; Simpson, J.A.; Bryn-Jacobsen, C.

    1998-01-01

    The magnetic structures of a series of Ho/Er alloys have been determined by neutron-diffraction techniques. The alloys were prepared as thin films (10000 Angstrom thick) by molecular beam epitaxy, and are single crystals with a mosaic spread of about 0.2 degrees. A variety of magnetic structures...

  14. Er:YAG laser dentistry in special needs patients.

    Science.gov (United States)

    Merigo, Elisabetta; Fornaini, Carlo; Clini, Fabio; Fontana, Matteo; Cella, Luigi; Oppici, Aldo

    2015-10-02

    Between a quarter and a third of adults with intellectual disability is estimated to have dental anxiety. Unpleasant stimuli, such as the injection of local anaesthesia or the noise and vibration of rotary instruments, may provoke anxiety and subsequent low compliance until the opposition to the treatment. The use of Er:YAG laser in conservative dentistry had a great development in these last years thank to new devices and also to their advantages when compared to the conventional instruments. The aim of this clinical study was to show the advantages of the Er:YAG laser in the conservative treatment of Special Care patients. Four cases are here described to show the Er:YAG laser use in our Unit on special needs patients. Based on the experience gained on conservative laser-assisted treatments performed in a time of 5 years at our Dentistry, Special Needs and Maxillo-Facial Surgery Unit we may affirm that Er:YAG laser may be considered as a good way to improve the cooperation, to reduce anxiety related to rotating instruments and to reach better results with equal or shorter operating times.

  15. Danskprøver er alt for skrappe

    DEFF Research Database (Denmark)

    Kristjansdottir, Bergthora

    2015-01-01

    Voksne udlændinges dansksproglige færdigheder testes i Prøve i Dansk 1, 2 eller 3. Testresultaterne misbruges af politikere til at legitimere diskriminerende bestemmelser, der blandt andet kan begrænse aktivt medborgerskab. Danskprøverne er hvad man i teoretisk tænkning om sprogtest kalder for hi...

  16. Når det 'bedste' ikke er godt nok

    DEFF Research Database (Denmark)

    Nielsen, Gritt B.; Sarauw, Laura Louise

    2014-01-01

    Måske inspireret af kommissionens kritik af, at der er for mange uddannelser med lav produktivitet målt på indkomst og beskæftigelsesgrad, bebudede Østergaard derpå, at antallet af universitetsuddannelser skal reduceres. Færre og mere genkendelige uddannelser vil gøre det lettere for studerende...

  17. Completion report for Well Cluster ER-20-6

    International Nuclear Information System (INIS)

    1998-02-01

    The Well Cluster ER-20-6 drilling and completion project was conducted during February, March, and April of 1996 in support of the Nevada Environmental Restoration Project at the Nevada Test Site (NTS), Nye County, Nevada. This project is part of the DOE's Underground Test Area (UGTA) subproject at the NTS. The primary UGTA tasks include collecting geological, geophysical, and hydrological data from new and existing wells to define groundwater quality as well as pathways and rates of groundwater migration at the NTS. A program of drilling wells near the sites of selected underground nuclear tests (near-field drilling) was implemented as part of the UGTA subproject to obtain site-specific data on the nature and extent of migration of radionuclides produced by an underground nuclear explosion. The ER-20-6 near-field drilling project was originally planned to be very similar to that recently conducted at Well Cluster ER-20-5, which was designed to obtain data on the existing hydrologic regime near the site of an underground nuclear explosion (IT, 1995; IT, 1996a). However, after further consideration of the goals of the near-field drilling program and the characteristics of the BULLION site, the TWG recommended that the ER-20-6 project be redesigned to accommodate a forced-gradient experiment. This proposed experiment is expected to yield more realistic estimates of transport parameters than can be deduced from sampling and testing natural groundwater flow systems

  18. Completion report for Well Cluster ER-20-6

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-02-01

    The Well Cluster ER-20-6 drilling and completion project was conducted during February, March, and April of 1996 in support of the Nevada Environmental Restoration Project at the Nevada Test Site (NTS), Nye County, Nevada. This project is part of the DOE`s Underground Test Area (UGTA) subproject at the NTS. The primary UGTA tasks include collecting geological, geophysical, and hydrological data from new and existing wells to define groundwater quality as well as pathways and rates of groundwater migration at the NTS. A program of drilling wells near the sites of selected underground nuclear tests (near-field drilling) was implemented as part of the UGTA subproject to obtain site-specific data on the nature and extent of migration of radionuclides produced by an underground nuclear explosion. The ER-20-6 near-field drilling project was originally planned to be very similar to that recently conducted at Well Cluster ER-20-5, which was designed to obtain data on the existing hydrologic regime near the site of an underground nuclear explosion (IT, 1995; IT, 1996a). However, after further consideration of the goals of the near-field drilling program and the characteristics of the BULLION site, the TWG recommended that the ER-20-6 project be redesigned to accommodate a forced-gradient experiment. This proposed experiment is expected to yield more realistic estimates of transport parameters than can be deduced from sampling and testing natural groundwater flow systems.

  19. The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER.

    Directory of Open Access Journals (Sweden)

    Belinda S Hall

    2014-04-01

    Full Text Available Infection with Mycobacterium ulcerans is characterised by tissue necrosis and immunosuppression due to mycolactone, the necessary and sufficient virulence factor for Buruli ulcer disease pathology. Many of its effects are known to involve down-regulation of specific proteins implicated in important cellular processes, such as immune responses and cell adhesion. We have previously shown mycolactone completely blocks the production of LPS-dependent proinflammatory mediators post-transcriptionally. Using polysome profiling we now demonstrate conclusively that mycolactone does not prevent translation of TNF, IL-6 and Cox-2 mRNAs in macrophages. Instead, it inhibits the production of these, along with nearly all other (induced and constitutive proteins that transit through the ER. This is due to a blockade of protein translocation and subsequent degradation of aberrantly located protein. Several lines of evidence support this transformative explanation of mycolactone function. First, cellular TNF and Cox-2 can be once more detected if the action of the 26S proteasome is inhibited concurrently. Second, restored protein is found in the cytosol, indicating an inability to translocate. Third, in vitro translation assays show mycolactone prevents the translocation of TNF and other proteins into the ER. This is specific as the insertion of tail-anchored proteins into the ER is unaffected showing that the ER remains structurally intact. Fourth, metabolic labelling reveals a near-complete loss of glycosylated and secreted proteins from treated cells, whereas cytosolic proteins are unaffected. Notably, the profound lack of glycosylated and secreted protein production is apparent in a range of different disease-relevant cell types. These studies provide a new mechanism underlying mycolactone's observed pathological activities both in vitro and in vivo. Mycolactone-dependent inhibition of protein translocation into the ER not only explains the deficit of innate

  20. Histo-chemical and biochemical analysis reveals association of er1 mediated powdery mildew resistance and redox balance in pea.

    Science.gov (United States)

    Mohapatra, Chinmayee; Chand, Ramesh; Navathe, Sudhir; Sharma, Sandeep

    2016-09-01

    Powdery mildew caused by Erysiphe pisi is one of the important diseases responsible for heavy yield losses in pea crop worldwide. The most effective method of controlling the disease is the use of resistant varieties. The resistance to powdery mildew in pea is recessive and governed by a single gene er1. The objective of present study is to investigate if er1 mediated powdery mildew resistance is associated with changes in the redox status of the pea plant. 16 pea genotypes were screened for powdery mildew resistance in field condition for two years and, also, analyzed for the presence/absence of er1 gene. Histochemical analysis with DAB and NBT staining indicates accumulation of reactive oxygen species (ROS) in surrounding area of powdery mildew infection which was higher in susceptible genotypes as compared to resistant genotypes. A biochemical study revealed that the activity of superoxide dismutase (SOD) and catalase, enzymes involved in scavenging ROS, was increased in, both, resistant and susceptible genotypes after powdery mildew infection. However, both enzymes level was always higher in resistant than susceptible genotypes throughout time course of infection. Moreover, irrespective of any treatment, the total phenol (TP) and malondialdehyde (MDA) content was significantly high and low in resistant genotypes, respectively. The powdery mildew infection elevated the MDA content but decreased the total phenol in pea genotypes. Statistical analysis showed a strong positive correlation between AUDPC and MDA; however, a negative correlation was observed between AUDPC and SOD, CAT and TP. Heritability of antioxidant was also high. The study identified few novel genotypes resistant to powdery mildew infection that carried the er1 gene and provided further clue that er1 mediated defense response utilizes antioxidant machinery to confer powdery mildew resistance in pea. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Drug involvement in fatal overdoses

    Directory of Open Access Journals (Sweden)

    Christopher J. Ruhm

    2017-12-01

    Full Text Available Death certificate data from the Multiple Cause of Death (MCOD files were analyzed to better understand the drug categories most responsible for the increase in fatal overdoses occurring between 1999 and 2014. Statistical adjustment methods were used to account for the understatement in reported drug involvement occurring because death certificates frequently do not specify which drugs were involved in the deaths. The frequency of combination drug use introduced additional uncertainty and so a distinction was made between any versus exclusive drug involvement. Many results were sensitive to the starting and ending years chosen for examination. Opioid analgesics played a major role in the increased drug deaths for analysis windows starting in 1999 but other drugs, particularly heroin, became more significant for recent time periods. Combination drug use was important for all time periods and needs to be accounted for when designing policies to slow or reverse the increase in overdose deaths.

  2. The expression status of TRX, AR, and cyclin D1 correlates with clinicopathological characteristics and ER status in breast cancer

    Directory of Open Access Journals (Sweden)

    Huang WS

    2016-07-01

    Full Text Available Weisun Huang,1 Weiwei Nie,1 Wenwen Zhang,2 Yanru Wang,1 Aiyu Zhu,1 Xiaoxiang Guan1,2 1Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China Background: The ER signaling pathway plays a critical role in breast cancer. ER signaling pathway-related proteins, such as TRX, AR, and cyclin D1, may have an important function in breast cancer. However, the ways that they influence breast cancer development and progression are still unclear.Patients and methods: A total of 101 Chinese female patients diagnosed with invasive ductal breast adenocarcinoma were retrospectively enrolled in the study. The expression levels of TRX, AR, and cyclin D1 were detected by immunohistochemistry and analyzed via correlation with clinicopathological characteristics and the expression status of ER, PR, and HER2.Results: The expression status of TRX, AR, and cyclin D1 was not associated with the patient’s age, menopausal status, tumor size, or histological differentiation (P>0.05, but was positively correlated with ER and PR (P<0.001, respectively. Most (66/76, 86.8 TRX-positive patients were also HER2-positive (P=0.003. Of AR- or cyclin D1-positive patients, most had relatively earlier I–II tumor stage (P=0.005 and P=0.047, respectively and no metastatic lymph node involvement (P=0.008 and P=0.005, respectively.Conclusion: TRX was found to be positively correlated with ER and PR expression, whereas it was negatively correlated with HER2 expression. In addition, we found that the positive expression of AR and cyclin D1 was correlated with lower TNM stage and fewer metastatic lymph nodes, and it was more common in ER-positive breast cancer than in the basal-like subtype. This may indicate that AR and cyclin D1 are good predictive and prognostic factors and

  3. Development of a new comprehensive and reliable endometrial receptivity map (ER Map/ER Grade) based on RT-qPCR gene expression analysis.

    Science.gov (United States)

    Enciso, M; Carrascosa, J P; Sarasa, J; Martínez-Ortiz, P A; Munné, S; Horcajadas, J A; Aizpurua, J

    2018-02-01

    Is it possible to determine the receptivity status of an endometrium by combined quantitative reverse transcription PCR (RT-qPCR) expression analysis of genes involved in endometrial proliferation and immunity? The new ER Map®/ER Grade® test can predict endometrial receptivity status by RT-qPCR using a new panel of genes involved in endometrial proliferation and the maternal immune response associated to embryonic implantation. The human endometrium reaches a receptive status adequate for embryonic implantation around Days 19-21 of the menstrual cycle. During this period, known as the window of implantation (WOI), the endometrium shows a specific gene expression profile suitable for endometrial function evaluation. The number of molecular diagnostic tools currently available to characterize this process is very limited. In this study, a new system for human endometrial receptivity evaluation was optimized and presented for the first time. ER Map®/ER Grade® validation was achieved on 312 endometrial samples including fertile women and patients undergoing fertility treatment between July 2014 and March 2016. Expression analyses of 184 genes involved in endometrial receptivity and immune response were performed. Samples were additionally tested with an independent endometrial receptivity test. A total of 96 fertile women and 120 assisted reproduction treatment (ART) patients participated in the study. Endometrial biopsy samples were obtained at LH + 2 and LH + 7 days in fertile subjects in a natural cycle and at the window of implantation (WOI) in patients in a hormone-replacement therapy (HRT) cycle. Total RNA was purified, quality-checked and reverse-transcribed. Gene expression was quantified by high-throughput RT-qPCR and statistically analyzed. Informative genes were selected and used to classify samples into four different groups of endometrial receptivity status. Significantly different gene expression levels were found in 85 out of 184 selected genes when

  4. Social conformity despite individual preferences for distinctiveness.

    Science.gov (United States)

    Smaldino, Paul E; Epstein, Joshua M

    2015-03-01

    We demonstrate that individual behaviours directed at the attainment of distinctiveness can in fact produce complete social conformity. We thus offer an unexpected generative mechanism for this central social phenomenon. Specifically, we establish that agents who have fixed needs to be distinct and adapt their positions to achieve distinctiveness goals, can nevertheless self-organize to a limiting state of absolute conformity. This seemingly paradoxical result is deduced formally from a small number of natural assumptions and is then explored at length computationally. Interesting departures from this conformity equilibrium are also possible, including divergence in positions. The effect of extremist minorities on these dynamics is discussed. A simple extension is then introduced, which allows the model to generate and maintain social diversity, including multimodal distinctiveness distributions. The paper contributes formal definitions, analytical deductions and counterintuitive findings to the literature on individual distinctiveness and social conformity.

  5. ER stress-induced protein, VIGG, disturbs plant cation homeostasis, which is correlated with growth retardation and robustness to ER stress

    Energy Technology Data Exchange (ETDEWEB)

    Katoh, Hironori; Fujita, Keiko; Takuhara, Yuki [Laboratory of Fruit Genetic Engineering, The Institute of Enology and Viticulture, University of Yamanashi, Kofu, Yamanashi 400-0005 (Japan); Ogawa, Atsushi [Department of Biological Production, Akita Prefectural University, Shimosinjyou-nakano 241-438, Akita 010-0195 (Japan); Suzuki, Shunji, E-mail: suzukis@yamanashi.ac.jp [Laboratory of Fruit Genetic Engineering, The Institute of Enology and Viticulture, University of Yamanashi, Kofu, Yamanashi 400-0005 (Japan)

    2011-02-18

    Highlights: {yields} VIGG is an ER stress-induced protein in plant. {yields} We examine the characteristics of VIGG-overexpressing Arabidopsis plants. {yields} VIGG-overexpressing plants reveal growth retardation and robustness to ER stress. {yields} VIGG disturbs cation homeostasis in plant. -- Abstract: VIGG is a putative endoplasmic reticulum (ER) resident protein induced by virus infection and ER stress, and is correlated with fruit quality in grapevine. The present study was undertaken to determine the biological function of VIGG in grapevine. Experiments using fluorescent protein-VIGG fusion protein demonstrated that VIGG is localized in ER and the ER targeting sequence is in the N-terminus. The overexpression of VIGG in Arabidopsis plant led to growth retardation. The rosette leaves of VIGG-overexpressing plants were smaller than those of the control plants and rolled at 42 days after seeding. VIGG-overexpressing plants revealed robustness to ER stress as well as the low expression of ER stress marker proteins, such as the luminal binding proteins. These characteristics of VIGG-overexpressing plants were supported by a microarray experiment that demonstrated the disruption of genes related to ER stress response and flowering, as well as cation mobility, in the plants. Finally, cation homeostasis in the plants was disturbed by the overexpression of VIGG. Taken together, these results suggest that VIGG may disturb cation homeostasis in plant, which is correlated with the robustness to ER stress and growth retardation.

  6. ER stress-induced protein, VIGG, disturbs plant cation homeostasis, which is correlated with growth retardation and robustness to ER stress

    International Nuclear Information System (INIS)

    Katoh, Hironori; Fujita, Keiko; Takuhara, Yuki; Ogawa, Atsushi; Suzuki, Shunji

    2011-01-01

    Highlights: → VIGG is an ER stress-induced protein in plant. → We examine the characteristics of VIGG-overexpressing Arabidopsis plants. → VIGG-overexpressing plants reveal growth retardation and robustness to ER stress. → VIGG disturbs cation homeostasis in plant. -- Abstract: VIGG is a putative endoplasmic reticulum (ER) resident protein induced by virus infection and ER stress, and is correlated with fruit quality in grapevine. The present study was undertaken to determine the biological function of VIGG in grapevine. Experiments using fluorescent protein-VIGG fusion protein demonstrated that VIGG is localized in ER and the ER targeting sequence is in the N-terminus. The overexpression of VIGG in Arabidopsis plant led to growth retardation. The rosette leaves of VIGG-overexpressing plants were smaller than those of the control plants and rolled at 42 days after seeding. VIGG-overexpressing plants revealed robustness to ER stress as well as the low expression of ER stress marker proteins, such as the luminal binding proteins. These characteristics of VIGG-overexpressing plants were supported by a microarray experiment that demonstrated the disruption of genes related to ER stress response and flowering, as well as cation mobility, in the plants. Finally, cation homeostasis in the plants was disturbed by the overexpression of VIGG. Taken together, these results suggest that VIGG may disturb cation homeostasis in plant, which is correlated with the robustness to ER stress and growth retardation.

  7. Integrative bioinformatics and proteomics-based discovery of an eEF2K inhibitor (cefatrizine) with ER stress modulation in breast cancer cells.

    Science.gov (United States)

    Yao, Zhiqiang; Li, Juntang; Liu, Zhongyu; Zheng, Lu; Fan, Naijun; Zhang, Ying; Jia, Nan; Lv, Jingjing; Liu, Ningning; Zhu, Xiaoshan; Du, Jiangbo; Lv, Ci; Xie, Feng; Liu, Yigang; Wang, Xingke; Fei, Zhou; Gao, Chunfang

    2016-03-01

    Eukaryotic elongation factor-2 kinase (eEF2K), a unique calcium/calmodulin-dependent protein kinase, is well known to regulate apoptosis, autophagy and ER stress in many types of human cancers. Therefore, eEF2K would be regarded as a promising therapeutic target; however, the eEF2K-regulated mechanism and its targeted inhibitor still remain to be discovered in cancer. Herein, we constructed a protein-protein interaction (PPI) network of eEF2K and achieved an eEF2K-regulated ER stress subnetwork by bioinformatics prediction. Then, we found that the differential protein expressions involved in ER stress in the context of si-eEF2K-treated MCF-7 and MDA-MB-436 cells by iTRAQ-based analyses, respectively. Integrated into these aforementioned results, we constructed a core eEF2K-regulated ER stress subnetwork in breast cancer cells. Subsequently, we screened a series of candidate compounds targeting eEF2K and discovered a novel eEF2K inhibitor (cefatrizine) with an anti-proliferative activity toward breast cancer cells. Moreover, we found that cefatrizine induced ER stress in both MCF-7 and MDA-MB-436 cells. Interestingly, we demonstrated that the mechanism of cefatrizine-induced ER stress was in good agreement with our bioinformatics and proteomics-based results. In conclusion, these results demonstrate that a novel eEF2K inhibitor (cefatrizine) induces ER stress in breast cancer cells by integrating bioinformatics prediction, proteomics analyses and experimental validation, which would provide a clue for exploring more mechanisms of eEF2K and its targeted inhibitors in cancer therapy.

  8. The anti-metastatic effects of the phytoestrogen arctigenin on human breast cancer cell lines regardless of the status of ER expression.

    Science.gov (United States)

    Maxwell, Thressi; Chun, So-Young; Lee, Kyu-Shik; Kim, Soyoung; Nam, Kyung-Soo

    2017-02-01

    Arctigenin is a plant lignan extracted from Arctium lappa that has been shown to have estrogenic properties. In spite of the health benefits of phytoestrogens reducing the risk of osteoporosis, heart disease, and menopausal symptoms, its benefits against the risk of breast cancer have not been fully elucidated. Thus, we investigated the effects of arctigenin on metastasis of breast cancer using both estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cell lines to see if the effects are dependent on the status of ER expression. In ER-positive MCF-7 cells, arctigenin efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration and invasion. The activity of crucial metastatic protease matrix metalloprotease (MMP)-9 in gelatin zymography was also efficiently decreased by arctigenin, as well as its mRNA expression. Notably, arctigenin exhibited similar anti-metastatic effects even in ER-negative MDA-MB-231 cells, suggesting that the anti-metastatic effects of arctigenin were not exerted via the ER. The upstream signaling pathways involved in the regulation of MMP-9 and urokinase plasminogen activator (uPA) were analyzed using western blotting. The activation of Akt, NF-κB and MAPK (ERK 1/2 and JNK 1/2) was found to be inhibited. Taken together, these data suggest that arctigenin confers anti-metastatic effects by inhibiting MMP-9 and uPA via the Akt, NF-κB and MAPK signaling pathways on breast cancer, regardless of ER expression. Therefore, we propose that the intake of arctigenin could be an effective supplement for breast cancer patients.

  9. GPM Ground Validation NASA ER-2 Navigation Data OLYMPEX V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The GPM Ground Validation NASA ER-2 Navigation Data OLYMPEX dataset supplies navigation data collected by the NASA ER-2 aircraft for flights that occurred during...

  10. THe Observing-system Research and predictability experiment ER2 MODIS Airborne Simmulator

    Data.gov (United States)

    National Aeronautics and Space Administration — THORPEX_ER2_MAS data are THe Observing-system Research and Predictability EXperiment (THORPEX) ER_2 MODIS Airborne Simulator (MAS) Data in HDF covering Hawaii and...

  11. 20 CFR 218.44 - When a remarried widow(er) annuity ends.

    Science.gov (United States)

    2010-04-01

    ...(er)— (1) Dies; (2) Becomes entitled to an old age benefit under the Social Security Act that is equal...) remarries unless the marriage is to an individual entitled to a retirement, disability, widow(er)'s, father...

  12. Design Program in Graphic User Interface Environment for Automobile ER Devices

    Science.gov (United States)

    Lim, S. C.; Park, J. S.; Sohn, J. W.; Choi, S. B.

    This work presents a design and analysis program for vehicle devices utilizing an electrorheological (ER) fluid. The program is operated in graphic user interface (GUI) environment and the initial window is consisted of four subprogram modules which are related to ER shock absorber, ER seat damper, ER engine mount, and ER anti-lock brake system (ABS), respectively. In order to execute each module, both material properties and design parameters are to be chosen by the user. Then, the output display window shows the field-dependent performance characteristics to be considered as design criteria. In addition, control performances of the vehicle system equipped with ER devices are displayed in time and frequency domain. In order to demonstrate the effectiveness of the proposed program, ER shock absorber and ER ABS are designed and manufactured and their performance characteristics are evaluated.

  13. Who and What Does Involvement Involve?

    DEFF Research Database (Denmark)

    Hansen, Jeppe Oute; Petersen, A.; Huniche, L.

    2015-01-01

    , and on what grounds, involvement of relatives is perceived in Danish psychiatry. Paradoxically, the current understanding of involvement of relatives fails to take into consideration the perspectives of the relatives per se and families that were being studied. By analyzing involvement from a discourse...... the responsibility toward the mental health of the ill individual as well as toward the psychological milieu of the family....

  14. Programming of Fetal Insulin Resistance in Pregnancies with Maternal Obesity by ER Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Francisco Westermeier

    2014-01-01

    Full Text Available The global epidemics of obesity during pregnancy and excessive gestational weight gain (GWG are major public health problems worldwide. Obesity and excessive GWG are related to several maternal and fetal complications, including diabetes (pregestational and gestational diabetes and intrauterine programming of insulin resistance (IR. Maternal obesity (MO and neonatal IR are associated with long-term development of obesity, diabetes mellitus, and increased global cardiovascular risk in the offspring. Multiple mechanisms of insulin signaling pathway impairment have been described in obese individuals, involving complex interactions of chronically elevated inflammatory mediators, adipokines, and the critical role of the endoplasmic reticulum (ER stress-dependent unfolded protein response (UPR. However, the underlying cellular processes linking MO and IR in the offspring have not been fully elucidated. Here, we summarize the state-of-the-art evidence supporting the possibility that adverse metabolic postnatal outcomes such as IR in the offspring of pregnancies with MO and/or excessive GWG may be related to intrauterine activation of ER stress response.

  15. Yb and Er co-doped Y2Ce2O7 nanoparticles: synthesis and ...

    Indian Academy of Sciences (India)

    Xu et al 2010). In addition, Er3+ ion has abundant energy level structure, so green and red upconversion emissions can be realized in Er3+-doped materials. .... Ce. Count. Engergy (KeV). Ce. O Y. Yb. Ce. Cu. Er. Figure 2. Energy dispersive spectra of Yb3+ and Er3+ co-doped. Y2Ce2O7 nanoparticles prepared for 4 h at ...

  16. Hvordan kan jeg ane det jeg gør er rigtigt?

    DEFF Research Database (Denmark)

    Petersen, Anders

    2014-01-01

    Dømmekraft er i vælten. Men hvad er dømmekraft, og hvordan er det muligt at udvikle sin dømmekraft i en virkelighed, hvor målstyring fylder stadigt mere? Artiklen tager med dømmekraftbegrebet afsæt i den nye pædagoguddannelse. Bekendtgørelsen er præget af en opfordring til at have mere opmærksomh...

  17. Precise orbit analysis and global verification results from ERS-1 altimetry

    Science.gov (United States)

    Shum, C. K.; Tapley, B. D.; Kozel, B. J.; Visser, P.; Ries, J. C.; Seago, J.

    1994-01-01

    A technique which employs dual satellite crossover measurements from ERS-1 and Topology Ocean Experiment (TOPEX)/Poseidon together with laser tracking data and single satellite crossover measurements for ERS-1 precision orbit determination is described. The accuracy assessment of the resulting ERS-1 orbit is provided. Results of global verification of the ERS-1 Ocean Products (OPR02) and the Interim Geophysical Data Records (IGDR) data products in terms of altimeter bias, time lag bias and sea state bias are presented.

  18. Induction of Apoptosis by 11-Dehydrosinulariolide via Mitochondrial Dysregulation and ER Stress Pathways in Human Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Jeff Yi-Fu Chen

    2012-08-01

    Full Text Available In this study the isolated compound 11-dehydrosinulariolide from soft coral Sinularia leptoclados possessed anti-proliferative, anti-migratory and apoptosis-inducing activities against A2058 melanoma cells. Anti-tumor effects of 11-dehydrosinulariolide were determined by MTT assay, cell migration assay and flow cytometry. Growth and migration of melanoma cells were dose-dependently inhibited by 2–8 μg/mL 11-dehydrosinulariolide. Flow cytometric data indicated that 11-dehydrosinulariolide induces both early and late apoptosis in melanoma cells. It was found that the apoptosis induced by 11-dehydrosinulariolide is relevant to mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by loss of mitochondrial membrane potential (∆Ym, release of cytochrome C, activation of caspase-3/-9 and Bax as well as suppression of Bcl-2/Bcl-xL. The cleavage of PARP-1 suggested partial involvement of caspase-independent pathways. Immunoblotting data displayed up-regulations of PERK/eIF2α/ATF4/CHOP and ATF6/CHOP coupling with elevation of ER stress chaperones GRP78, GRP94, calnexin, calreticulin and PDI, implicating the involvement of these factors in ER stress-mediated apoptosis induced by 11-dehydrosinulariolide. The abolishment of apoptotic events after pre-treatment with salubrinal indicated that ER stress-mediated apoptosis is also induced by 11-dehydrosinulariolide against melanoma cells. The data in this study suggest that 11-dehydrosinulariolide potentially induces apoptosis against melanoma cells via mitochondrial dysregulation and ER stress pathways.

  19. Induction of Apoptosis by 11-Dehydrosinulariolide via Mitochondrial Dysregulation and ER Stress Pathways in Human Melanoma Cells

    Science.gov (United States)

    Su, Tzu-Rong; Tsai, Feng-Jen; Lin, Jen-Jie; Huang, Han Hsiang; Chiu, Chien-Chih; Su, Jui-Hsin; Yang, Ya-Ting; Chen, Jeff Yi-Fu; Wong, Bing-Sang; Wu, Yu-Jen

    2012-01-01

    In this study the isolated compound 11-dehydrosinulariolide from soft coral Sinularia leptoclados possessed anti-proliferative, anti-migratory and apoptosis-inducing activities against A2058 melanoma cells. Anti-tumor effects of 11-dehydrosinulariolide were determined by MTT assay, cell migration assay and flow cytometry. Growth and migration of melanoma cells were dose-dependently inhibited by 2–8 μg/mL 11-dehydrosinulariolide. Flow cytometric data indicated that 11-dehydrosinulariolide induces both early and late apoptosis in melanoma cells. It was found that the apoptosis induced by 11-dehydrosinulariolide is relevant to mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by loss of mitochondrial membrane potential (∆Ψm), release of cytochrome C, activation of caspase-3/-9 and Bax as well as suppression of Bcl-2/Bcl-xL. The cleavage of PARP-1 suggested partial involvement of caspase-independent pathways. Immunoblotting data displayed up-regulations of PERK/eIF2α/ATF4/CHOP and ATF6/CHOP coupling with elevation of ER stress chaperones GRP78, GRP94, calnexin, calreticulin and PDI, implicating the involvement of these factors in ER stress-mediated apoptosis induced by 11-dehydrosinulariolide. The abolishment of apoptotic events after pre-treatment with salubrinal indicated that ER stress-mediated apoptosis is also induced by 11-dehydrosinulariolide against melanoma cells. The data in this study suggest that 11-dehydrosinulariolide potentially induces apoptosis against melanoma cells via mitochondrial dysregulation and ER stress pathways. PMID:23015779

  20. Distinct pathways of neural coupling for different basic emotions.

    Science.gov (United States)

    Tettamanti, Marco; Rognoni, Elena; Cafiero, Riccardo; Costa, Tommaso; Galati, Dario; Perani, Daniela

    2012-01-16

    Emotions are complex events recruiting distributed cortical and subcortical cerebral structures, where the functional integration dynamics within the involved neural circuits in relation to the nature of the different emotions are still unknown. Using fMRI, we measured the neural responses elicited by films representing basic emotions (fear, disgust, sadness, happiness). The amygdala and the associative cortex were conjointly activated by all basic emotions. Furthermore, distinct arrays of cortical and subcortical brain regions were additionally activated by each emotion, with the exception of sadness. Such findings informed the definition of three effective connectivity models, testing for the functional integration of visual cortex and amygdala, as regions processing all emotions, with domain-specific regions, namely: i) for fear, the frontoparietal system involved in preparing adaptive motor responses; ii) for disgust, the somatosensory system, reflecting protective responses against contaminating stimuli; iii) for happiness: medial prefrontal and temporoparietal cortices involved in understanding joyful interactions. Consistently with these domain-specific models, the results of the effective connectivity analysis indicate that the amygdala is involved in distinct functional integration effects with cortical networks processing sensorimotor, somatosensory, or cognitive aspects of basic emotions. The resulting effective connectivity networks may serve to regulate motor and cognitive behavior based on the quality of the induced emotional experience. Copyright © 2011. Published by Elsevier Inc.

  1. Distinctiveness and the Attentional Boost Effect.

    Science.gov (United States)

    Smith, S Adam; Mulligan, Neil W

    2018-02-01

    The typical pattern of results in divided attention experiments is that subjects in a full attention (FA) condition perform markedly better on tests of memory than subjects in a divided attention (DA) condition which forces subjects to split their attention between studying to-be-remembered stimuli and completing some peripheral task. Nevertheless, recent research has revealed an exception wherein stimuli presented concurrently with targets in a detection task are better remembered than stimuli which co-occur with distractors. Research on this phenomenon-the Attentional Boost Effect (ABE)-has demonstrated that the ABE is reduced or eliminated for words made distinct by their word frequency or orthographic properties-forms of secondary distinctiveness. However, it is unclear how primary distinctiveness effects may interact with the ABE. The current study observed how perceptual and semantic manipulations of primary distinctiveness via the isolation paradigm interact with the ABE, and revealed these interactions to be fundamentally different than those of secondary distinctiveness. Specifically, whereas the effects of secondary distinctiveness in earlier studies were found to be redundant with the ABE, the current study demonstrated that items characterized by primary distinctiveness enhanced memory performance independently of the ABE. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  2. Regulated Erlin-dependent release of the B12 transmembrane J-protein promotes ER membrane penetration of a non-enveloped virus.

    Directory of Open Access Journals (Sweden)

    Takamasa Inoue

    2017-06-01

    Full Text Available The molecular mechanism by which non-enveloped viruses penetrate biological membranes remains enigmatic. The non-enveloped polyomavirus SV40 penetrates the endoplasmic reticulum (ER membrane to reach the cytosol and cause infection. We previously demonstrated that SV40 creates its own membrane penetration structure by mobilizing select transmembrane proteins to distinct puncta in the ER membrane called foci that likely function as the cytosol entry sites. How these ER membrane proteins reorganize into the foci is unknown. B12 is a transmembrane J-protein that mobilizes into the foci to promote cytosol entry of SV40. Here we identify two closely related ER membrane proteins Erlin1 and Erlin2 (Erlin1/2 as B12-interaction partners. Strikingly, SV40 recruits B12 to the foci by inducing release of this J-protein from Erlin1/2. Our data thus reveal how a non-enveloped virus promotes its own membrane translocation by triggering the release and recruitment of a critical transport factor to the membrane penetration site.

  3. The comER Gene Plays an Important Role in Biofilm Formation and Sporulation in both Bacillus subtilis and Bacillus cereus.

    Science.gov (United States)

    Yan, Fang; Yu, Yiyang; Wang, Luyao; Luo, Yuming; Guo, Jian-Hua; Chai, Yunrong

    2016-01-01

    Bacteria adopt alternative cell fates during development. In Bacillus subtilis, the transition from planktonic growth to biofilm formation and sporulation is controlled by a complex regulatory circuit, in which the most important event is activation of Spo0A, a transcription factor and a master regulator for genes involved in both biofilm formation and sporulation. In B. cereus, the regulatory pathway controlling biofilm formation and cell differentiation is much less clear. In this study, we show that a novel gene, comER, plays a significant role in biofilm formation as well as sporulation in both B. subtilis and B. cereus. Mutations in the comER gene result in defects in biofilm formation and a delay in spore formation in the two Bacillus species. Our evidence supports the idea that comER may be part of the regulatory circuit that controls Spo0A activation. comER likely acts upstream of sda, a gene encoding a small checkpoint protein for both sporulation and biofilm formation, by blocking the phosphor-relay and thereby Spo0A activation. In summary, our studies outlined a conserved, positive role for comER, a gene whose function was previously uncharacterized, in the regulation of biofilm formation and sporulation in the two Bacillus species.

  4. The comER Gene Plays an Important Role in Biofilm Formation and Sporulation in both Bacillus subtilis and Bacillus cereus

    Science.gov (United States)

    Yan, Fang; Yu, Yiyang; Wang, Luyao; Luo, Yuming; Guo, Jian-hua; Chai, Yunrong

    2016-01-01

    Bacteria adopt alternative cell fates during development. In Bacillus subtilis, the transition from planktonic growth to biofilm formation and sporulation is controlled by a complex regulatory circuit, in which the most important event is activation of Spo0A, a transcription factor and a master regulator for genes involved in both biofilm formation and sporulation. In B. cereus, the regulatory pathway controlling biofilm formation and cell differentiation is much less clear. In this study, we show that a novel gene, comER, plays a significant role in biofilm formation as well as sporulation in both B. subtilis and B. cereus. Mutations in the comER gene result in defects in biofilm formation and a delay in spore formation in the two Bacillus species. Our evidence supports the idea that comER may be part of the regulatory circuit that controls Spo0A activation. comER likely acts upstream of sda, a gene encoding a small checkpoint protein for both sporulation and biofilm formation, by blocking the phosphor-relay and thereby Spo0A activation. In summary, our studies outlined a conserved, positive role for comER, a gene whose function was previously uncharacterized, in the regulation of biofilm formation and sporulation in the two Bacillus species. PMID:27446060

  5. Spectral variations and energy transfer processes on both Er 3+ ion concentration and excitation densities in Yb 3+-Er 3+ codoped LaF3 materials

    International Nuclear Information System (INIS)

    Zhang Jisen; Qin Weiping; Zhao Dan; Degejihu; Zhang Jishuang; Wang Yan; Cao Chunyan

    2007-01-01

    In comparison with the up-conversion spectra of Yb 3+ -Er 3+ codopded systems reported previously, the interesting intensity changes of up-conversion luminescence between the violet, the blue, the green and the red on the both Er 3+ ion concentration and excitation density with 978 nm laser diodes as an excitation source were observed in Yb 3+ -Er 3+ codopded LaF 3 powders. In order to clarify the change mechanisms, the up-conversion spectra of LaF 3 : 10 mol% Yb 3+ , 0.5 mol% Er 3+ and LaF 3 : 10 mol% Yb 3+ , 1 mol% Er 3+ were investigated and the results indicated that the cross-relaxation processes between Er 3+ ions and the thermal population of the 2 H 11/2 level play significant roles

  6. Monitoring sea level and sea surface temperature trends from ERS satellites

    DEFF Research Database (Denmark)

    Andersen, Ole Baltazar; Knudsen, Per; Beckley, B.

    2002-01-01

    Data from the two ESA satellites ERS-1 and ERS-2 are used in global and regional analysis of sea level and sea surface temperature trends over the last, 7.8 years. T he ERS satellites and in the future the ENVISAT satellite provide unique opportunity for monitoring both changes in sea level and s...

  7. Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins

    Science.gov (United States)

    Das, Indrajit; Png, Chin Wen; Oancea, Iulia; Hasnain, Sumaira Z.; Lourie, Rohan; Proctor, Martina; Eri, Rajaraman D.; Sheng, Yong; Crane, Denis I.; Florin, Timothy H.

    2013-01-01

    Endoplasmic reticulum (ER) stress in intestinal secretory cells has been linked with colitis in mice and inflammatory bowel disease (IBD). Endogenous intestinal glucocorticoids are important for homeostasis and glucocorticoid drugs are efficacious in IBD. In Winnie mice with intestinal ER stress caused by misfolding of the Muc2 mucin, the glucocorticoid dexamethasone (DEX) suppressed ER stress and activation of the unfolded protein response (UPR), substantially restoring goblet cell Muc2 production. In mice lacking inflammation, a glucocorticoid receptor antagonist increased ER stress, and DEX suppressed ER stress induced by the N-glycosylation inhibitor, tunicamycin (Tm). In cultured human intestinal secretory cells, in a glucocorticoid receptor-dependent manner, DEX suppressed ER stress and UPR activation induced by blocking N-glycosylation, reducing ER Ca2+ or depleting glucose. DEX up-regulated genes encoding chaperones and elements of ER-associated degradation (ERAD), including EDEM1. Silencing EDEM1 partially inhibited DEX’s suppression of misfolding-induced ER stress, showing that DEX enhances ERAD. DEX inhibited Tm-induced MUC2 precursor accumulation, promoted production of mature mucin, and restored ER exit and secretion of Winnie mutant recombinant Muc2 domains, consistent with enhanced protein folding. In IBD, glucocorticoids are likely to ameliorate ER stress by promoting correct folding of secreted proteins and enhancing removal of misfolded proteins from the ER. PMID:23650437

  8. Er vi ved at ødelægge nærværet?

    DEFF Research Database (Denmark)

    Andersen, Tem Frank

    2016-01-01

    Selvom sociologi og psykologi som forskellige videnskabelige felter ikke helt er enige om, hvad der er på spil mellem mennesker, så er medieringsforståelsen eller deres mediebegreb gerne sammenfaldende. De bruger nemlig det, den canadiske medieforsker Joshua Meyrowitz betegner kanalmetaforen...

  9. Mistakes To Avoid In Attacking The Moral/Conventional Distinction

    Directory of Open Access Journals (Sweden)

    Alejandro Rosas

    2012-11-01

    Full Text Available In an experimental critique of the moral/conventional (M/C distinction, Kelly et al. (2007 present new experimental data about responses to transgressions involving harm, where the novelty is that transgressors are grown-ups, rather than children. Their data do not support the moral/conventional distinction. The contrast between grown-up and schoolyard transgressions does not seem, however, to explain their results: they also use two schoolyard transgressions with similar negative results for the M/C distinction.I here attempt to explain away their results by calling attention to two mistakes in their experimental design. One refers to the use of questionnaire-items of the type that Turiel and collaborators have called mixed-domain situations, which extend over both a moral and a conventional domain. Participants respond to these cases differently than to prototypical moral situations, because some allow the authority rule to override the moral rule. The second mistake emerges in the grown-up transgressions labeled as Whipping/temporal, Whipping/Authority, Spanking/Authority, Prisoner abuse/Authority. These are not the typical transgressions unambiguously “involving a victim who has been harmed, whose rights have been violated, or who has been subject to an injustice”. The victims are also transgressors and harm is inflicted on them as punishment. Plausibly, rules about corporal punishment depend on authority in a way that rules about harming the innocent do not.

  10. Sodahvede og glycerol til malkekøer

    DEFF Research Database (Denmark)

    Hvelplund, Torben; Weisbjerg, Martin Riis

    2011-01-01

    Et fodringsforsøg på Kvægbrugets Forsøgscenter har vist, at glycerol kan anvendes som et alternativt fodermiddel til højtydende malkekøer. De anvendte mængder gav dog en lavere EKM ydelse end sodahvede, men øgede samtidigt mælkens proteinindhold.......Et fodringsforsøg på Kvægbrugets Forsøgscenter har vist, at glycerol kan anvendes som et alternativt fodermiddel til højtydende malkekøer. De anvendte mængder gav dog en lavere EKM ydelse end sodahvede, men øgede samtidigt mælkens proteinindhold....

  11. The ER membrane protein complex is a transmembrane domain insertase

    Science.gov (United States)

    Guna, Alina; Volkmar, Norbert; Christianson, John C.; Hegde, Ramanujan S.

    2018-01-01

    Insertion of proteins into membranes is an essential cellular process. The extensive biophysical and topological diversity of membrane proteins necessitates multiple insertion pathways that remain incompletely defined. Here, we found that known membrane insertion pathways fail to effectively engage tail-anchored membrane proteins with moderately hydrophobic transmembrane domains. These proteins are instead shielded in the cytosol by calmodulin. Dynamic release from calmodulin allowed sampling of the endoplasmic reticulum (ER), where the conserved ER membrane protein complex (EMC) was shown to be essential for efficient insertion in vitro and in cells. Purified EMC in synthetic liposomes catalyzed insertion of its substrates in a reconstituted system. Thus, EMC is a transmembrane domain insertase, a function that may explain its widely pleiotropic membrane-associated phenotypes across organisms. PMID:29242231

  12. Atmospheric Ionizing Radiation (AIR) ER-2 Preflight Analysis

    Science.gov (United States)

    Tai, Hsiang; Wilson, John W.; Maiden, D. L.

    1998-01-01

    Atmospheric ionizing radiation (AIR) produces chemically active radicals in biological tissues that alter the cell function or result in cell death. The AIR ER-2 flight measurements will enable scientists to study the radiation risk associated with the high-altitude operation of a commercial supersonic transport. The ER-2 radiation measurement flights will follow predetermined, carefully chosen courses to provide an appropriate database matrix which will enable the evaluation of predictive modeling techniques. Explicit scientific results such as dose rate, dose equivalent rate, magnetic cutoff, neutron flux, and air ionization rate associated with those flights are predicted by using the AIR model. Through these flight experiments, we will further increase our knowledge and understanding of the AIR environment and our ability to assess the risk from the associated hazard.

  13. A unidirectional Er3+-doped fiber ring laser without isolator

    DEFF Research Database (Denmark)

    Shi, Yuan; Sejka, Milan; Poulsen, Ove

    1995-01-01

    An Er3+-doped fiber ring laser with unidirectional operation without optical isolator has been investigated for different cavity conditions. The fiber ring laser cavity is built in such a way that the optical fields propagating in the two directions suffer different losses. As a consequence, the ......, the laser oscillation appears in a quasi-unidirectional form. By incorporating a fiber pigtailed bandpass filter to enhance mode competition, a purely unidirectional tunable fiber ring laser is obtained with high efficiency and broad tunability......An Er3+-doped fiber ring laser with unidirectional operation without optical isolator has been investigated for different cavity conditions. The fiber ring laser cavity is built in such a way that the optical fields propagating in the two directions suffer different losses. As a consequence...

  14. Fredom and Responsibility in the Myth of Er

    Directory of Open Access Journals (Sweden)

    Marina Berzons McCoy

    2012-08-01

    Full Text Available Plato uses the myth of Er in the Republic in order to carve out space for political freedom and responsibility for human freedom in the ordinary polis. While much of the Republic concentrates on the development of an ideal city in speech, that city is fundamentally a mythos presented in order for Socrates and his friends to learn something about political and individual virtue. The city in which Socrates and his friends exist is an imperfect city and myth of Er is intended for those audience members. Its emphasis on the necessity for personal responsibility in the midst of freedom can be understood as a political claim about the place of individual choice in a world that is constrained by both political and cosmic "necessity".

  15. Co- and post-translational protein folding in the ER

    DEFF Research Database (Denmark)

    Ellgaard, Lars; McCaul, Nicholas; Chatsisvili, Anna

    2016-01-01

    The biophysical rules that govern folding of small, single-domain proteins in dilute solutions are now quite well understood. The mechanisms underlying co-translational folding of multidomain and membrane-spanning proteins in complex cellular environments are often less clear. The endoplasmic...... and the variety of ER-specific protein modifications. Here, we review chaperone-assisted co- and post-translational folding and assembly in the ER and underline the influence of protein modifications on these processes. We emphasize how method development has helped advance the field by allowing researchers...... to monitor the progression of folding as it occurs inside living cells, while at the same time probing the intricate relationship between protein modifications during folding....

  16. Photovoltaic Barometer - EurObserv'ER - April 2013

    International Nuclear Information System (INIS)

    2013-04-01

    After the euphoria of 2011, the European Union's photovoltaic market slowed right down in 2012. EurObserv'ER puts newly-connected capacity in 2012 at 16.5 GWp compared to 22 GWp in 2011, which is a 25% slide. At global level the market generally held up, with just over 30 GWp installed, bolstered by the build-up of the America and Asian markets

  17. Beta-delayed proton activities: 147Dy and 149Er

    International Nuclear Information System (INIS)

    Toth, K.S.; Moltz, D.M.; Schloemer, E.C.; Cable, M.D.; Avignone, F.T. III; Ellis-Akovali, Y.A.

    1984-01-01

    The present paper discusses mainly the β-delayed proton spectra of 147 Dy and of the hitherto unknown isotope, 149 Er. However, following the submittal of the abstract for this conference we have now observed delayed protons following the decay of 145 Dy. Additionally, we have identified a 0.5-s delayed-proton emitter and tentatively assign it to the new isotope, 151 Yb

  18. Virtual reality - ja det er virkelig allerede en realitet

    DEFF Research Database (Denmark)

    Andersen, Tem Frank

    2016-01-01

    Allerede tilbage i 1980’erne kunne forskningen i medier og informationsteknologier fremvise de første prototyper på 3D virtual reality. Man kan spekulere længe over, hvad der egentligt motiverede forskningen på det tidspunkt. En motivation kunne være den ingeniørmæssige: Er det muligt at skabe en...

  19. Photovoltaic Barometer - EurObserv'ER - April 2015

    International Nuclear Information System (INIS)

    2015-04-01

    The global photovoltaic market continued to expand between 2013 and 2014, rising from 37.6 GW to almost 40 GW unlike the European Union market that plummeted further. The EurObserv'ER estimate of the European photovoltaic market is about 6.9 GWp in 2014, a 32.3 % drop on 2013, yet three years earlier, in 2011, it hovered around the 22 GWp mark

  20. Er genomisk selektion en revolution af avlsarbejdet med mink?

    DEFF Research Database (Denmark)

    Berg, Peer

    2011-01-01

    Genomisk selektion udnytter, at den enkelte mink kan genotypes for tusindvis af genetiske markører. Et dyrs avlsværdi kan skønnes med ret stor sikkerhed på basis af en blod- eller hårprøve, hvor dyrets sæt af genetiske markører bestemmes. Det er altså ikke nødvendigt at registrere minkens egne eg...

  1. EPR = ER, scattering amplitude and entanglement entropy change

    Energy Technology Data Exchange (ETDEWEB)

    Seki, Shigenori, E-mail: sigenori@hanyang.ac.kr [Research Institute for Natural Science, Hanyang University, Seoul 133-791 (Korea, Republic of); Sin, Sang-Jin, E-mail: sjsin@hanyang.ac.kr [Department of Physics, Hanyang University, Seoul 133-791 (Korea, Republic of)

    2014-07-30

    We study the causal structure of the minimal surface of the four-gluon scattering, and find a world-sheet wormhole parametrized by Mandelstam variables, thereby demonstrate the EPR = ER relation for gluon scattering. We also propose that scattering amplitude is the change of the entanglement entropy by generalizing the holographic entanglement entropy of Ryu–Takayanagi to the case where two regions are divided in space–time.

  2. Klasseværelset er et arnested for demokrati

    DEFF Research Database (Denmark)

    Mehlsen, Camilla

    2003-01-01

    Skolen er et demokratisk lærested, hvor læreren spiller en særdeles vigtig rolle i at klæde eleven på til at indgå i et flerkulturelt, demokratisk samfund. Det mener Irene Christiansen, nyudnævnt adjunkt ved på Institut for pædagogisk psykologi, Danmarks Pædagogiske Universitet. Udgivelsesdato: S...

  3. Heat pumps barometer - EurObserv'ER - September 2015

    International Nuclear Information System (INIS)

    2015-09-01

    Heat pumps have moved up the ranks of renewable energy - producing heating technologies since the mid-2000's. The EU Member States' individual market trends are characterised by the technologies used and their heating and cooling needs. More than 1.7 million systems were sold in the European Union in 2014. According to EurObserv'ER, several market factors were responsible for sales dipping slightly below their 2013 level of just under 2 million

  4. Copenhagen vs Everett, teleportation, and ER=EPR

    Energy Technology Data Exchange (ETDEWEB)

    Susskind, Leonard [Stanford Institute for Theoretical Physics and Department of Physics, Stanford University, Stanford, CA (United States)

    2016-06-15

    Quantum gravity may have as much to tell us about the foundations and interpretation of quantum mechanics as it does about gravity. The Copenhagen interpretation of quantum mechanics and Everett's Relative State Formulation are complementary descriptions which in a sense are dual to one another. My purpose here is to discuss this duality in the light of the of ER=EPR conjecture. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. On the enhancement of Er3+ diffusion in LiNbO3 crystals by Er3+/Ti4+ co-diffusion

    International Nuclear Information System (INIS)

    Almeida, José Manuel Marques Martins de; Sada, Cinzia

    2016-01-01

    Highlights: • Enhancement of the diffusion of erbium ions (Er 3+ ) in lithium niobate crystals. • Incoherence on published results lead to need for systematic revision of literature. • Further insight into the topic of co-diffusion of Er 3+ /Ti 4+ ions into LiNbO 3 . - Abstract: After carrying out a revision of the literature on the enhancement of Er 3+ diffusion in LiNbO 3 crystals by Er 3+ /Ti 4+ co-diffusion and analyzing our own experimental results, we conclude that no reproducible results were reported, meaning that further research on this subject is necessary.

  6. Root canal preparation with Er:YSGG laser

    Science.gov (United States)

    Benthin, Hartmut; Ertl, Thomas P.; Onal, B.; Schruender, Stephan; Mueller, Gerhard J.

    1994-12-01

    The high level of efficiency of hard tissue ablation with Er:YAG and Er:YSGG lasers is well known. Of these lasers it is possible only to transmit Er:YSGG laser radiation with OH reduced quartz fibers. Most of the fibers we use in this study were prepared as hemispherical fiber tips. Fifty single rooted teeth were divided into ten groups (n equals 5). After conventional opening of the pulp chamber, root canal preparation was performed in five groups under water only using the laser. In the other five groups preparation with K-files to size 35 was performed before treatment with laser radiation. All teeth were axially separated with direct access to the root canal and examined in SEM investigations. The groups were compared by measuring the areas with patent dentin tubules. Representative areas were examined by TEM. The temperature at the root surface was measured during laser irradiation with thermocouples positioned at several points. The in-vitro study of the effect of the high delivered energy (50 - 100 mJ per pulse) in the root canal showed a good ablation effect. Most of the dentin tubules were opened. The increase in temperature at the root surface was tolerable.

  7. Isotopic ratios in outbursting comet C/2015 ER61

    Science.gov (United States)

    Yang, Bin; Hutsemékers, Damien; Shinnaka, Yoshiharu; Opitom, Cyrielle; Manfroid, Jean; Jehin, Emmanuël; Meech, Karen J.; Hainaut, Olivier R.; Keane, Jacqueline V.; Gillon, Michaël

    2018-02-01

    Isotopic ratios in comets are critical to understanding the origin of cometary material and the physical and chemical conditions in the early solar nebula. Comet C/2015 ER61 (PANSTARRS) underwent an outburst with a total brightness increase of 2 magnitudes on the night of 2017 April 4. The sharp increase in brightness offered a rare opportunity to measure the isotopic ratios of the light elements in the coma of this comet. We obtained two high-resolution spectra of C/2015 ER61 with UVES/VLT on the nights of 2017 April 13 and 17. At the time of our observations, the comet was fading gradually following the outburst. We measured the nitrogen and carbon isotopic ratios from the CN violet (0, 0) band and found that 12C/13C = 100 ± 15, 14N/15N = 130 ± 15. In addition, we determined the 14N/15N ratio from four pairs of NH2 isotopolog lines and measured 14N/15N = 140 ± 28. The measured isotopic ratios of C/2015 ER61 do not deviate significantly from those of other comets.

  8. Completion Report for Well Cluster ER-6-1

    Energy Technology Data Exchange (ETDEWEB)

    Bechtel Nevada

    2004-10-01

    Well Cluster ER-6-1 was constructed for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office in support of the Nevada Environmental Restoration Division at the Nevada Test Site, Nye County, Nevada. This work was initiated as part of the Groundwater Characterization Project, now known as the Underground Test Area Project. The well cluster is located in southeastern Yucca Flat. Detailed lithologic descriptions with stratigraphic assignments for Well Cluster ER-6-1 are included in this report. These are based on composite drill cuttings collected every 3 meters and conventional core samples taken below 639 meters, supplemented by geophysical log data. Detailed petrographic, chemical, and mineralogical studies of rock samples were conducted on 11 samples to resolve complex interrelationships between several of the Tertiary tuff units. Additionally, paleontological analyses by the U.S. Geological Survey confirmed the stratigraphic assignments below 539 meters within the Paleozoic sedimentary section. All three wells in the Well ER-6-1 cluster were drilled within the Quaternary and Tertiary alluvium section, the Tertiary volcanic section, and into the Paleozoic sedimentary section.

  9. Neuroimaging distinction between neurological and psychiatric disorders.

    Science.gov (United States)

    Crossley, Nicolas A; Scott, Jessica; Ellison-Wright, Ian; Mechelli, Andrea

    2015-11-01

    It is unclear to what extent the traditional distinction between neurological and psychiatric disorders reflects biological differences. To examine neuroimaging evidence for the distinction between neurological and psychiatric disorders. We performed an activation likelihood estimation meta-analysis on voxel-based morphometry studies reporting decreased grey matter in 14 neurological and 10 psychiatric disorders, and compared the regional and network-level alterations for these two classes of disease. In addition, we estimated neuroanatomical heterogeneity within and between the two classes. Basal ganglia, insula, sensorimotor and temporal cortex showed greater impairment in neurological disorders; whereas cingulate, medial frontal, superior frontal and occipital cortex showed greater impairment in psychiatric disorders. The two classes of disorders affected distinct functional networks. Similarity within classes was higher than between classes; furthermore, similarity within class was higher for neurological than psychiatric disorders. From a neuroimaging perspective, neurological and psychiatric disorders represent two distinct classes of disorders. © The Royal College of Psychiatrists 2015.

  10. New approach to equipment quality evaluation method with distinct functions

    Directory of Open Access Journals (Sweden)

    Milisavljević Vladimir M.

    2016-01-01

    Full Text Available The paper presents new approach for improving method for quality evaluation and selection of equipment (devices and machinery by applying distinct functions. Quality evaluation and selection of devices and machinery is a multi-criteria problem which involves the consideration of numerous parameters of various origins. Original selection method with distinct functions is based on technical parameters with arbitrary evaluation of each parameter importance (weighting. Improvement of this method, presented in this paper, addresses the issue of weighting of parameters by using Delphi Method. Finally, two case studies are provided, which included quality evaluation of standard boilers for heating and evaluation of load-haul-dump (LHD machines, to demonstrate applicability of this approach. Analytical Hierarchical Process (AHP is used as a control method.

  11. Identification of distinct molecular subtypes of uterine carcinosarcoma.

    Science.gov (United States)

    An, Yang; Wang, Haojie; Jie, Jingyao; Tang, Yitai; Zhang, Weijuan; Ji, Shaoping; Guo, Xiangqian

    2017-02-28

    Uterine carcinosarcoma (UCS) is a rare but lethal neoplasm with high metastasis and recurrence rate, and to date, no molecular classification of UCS has been defined to achieve targeted therapies. In this study, we identified two distinct molecular subtypes of UCS with distinct gene expression patterns and clinicopathologic characteristics. Subtype I UCS recapitulates low-grade UCS, in contrast subtype II UCS represents high-grade UCS with higher tumor invasion rate and tumor weight. Interestingly, subtype I UCS is characterized by cell adhesion and apoptosis pathways, whereas genes over-expressed in subtype II UCS are more involved in myogenesis/muscle development. We also proposed certain potential subtype specific therapeutic targets, such as SYK (spleen tyrosine kinase) for subtype I and cell-cycle proteins for subtype II. Our findings provide a better recognition of UCS molecular subtypes and subtype specific oncogenesis mechanisms, and can help develop more specific targeted treatment options for these tumors.

  12. TaER Expression Is Associated with Transpiration Efficiency Traits and Yield in Bread Wheat

    Science.gov (United States)

    Zheng, Jiacheng; Yang, Zhiyuan; Madgwick, Pippa J.; Carmo-Silva, Elizabete; Parry, Martin A. J.; Hu, Yin-Gang

    2015-01-01

    ERECTA encodes a receptor-like kinase and is proposed as a candidate for determining transpiration efficiency of plants. Two genes homologous to ERECTA in Arabidopsis were identified on chromosomes 6 (TaER2) and 7 (TaER1) of bread wheat (Triticum aestivum L.), with copies of each gene on the A, B and D genomes of wheat. Similar expression patterns were observed for TaER1 and TaER2 with relatively higher expression of TaER1 in flag leaves of wheat at heading (Z55) and grain-filling (Z73) stages. Significant variations were found in the expression levels of both TaER1 and TaER2 in the flag leaves at both growth stages among 48 diverse bread wheat varieties. Based on the expression of TaER1 and TaER2, the 48 wheat varieties could be classified into three groups having high (5 varieties), medium (27 varieties) and low (16 varieties) levels of TaER expression. Significant differences were also observed between the three groups varying for TaER expression for several transpiration efficiency (TE)- related traits, including stomatal density (SD), transpiration rate, photosynthetic rate (A), instant water use efficiency (WUEi) and carbon isotope discrimination (CID), and yield traits of biomass production plant-1 (BYPP) and grain yield plant-1 (GYPP). Correlation analysis revealed that the expression of TaER1 and TaER2 at the two growth stages was significantly and negatively associated with SD (Pwheat, implying a function for TaER in regulating leaf development of bread wheat and contributing to expression of these traits. Moreover, the results indicate that TaER could be exploitable for manipulating important agronomical traits in wheat improvement. PMID:26047019

  13. Activity-Dependent Dendritic Spine Shrinkage and Growth Involve Downregulation of Cofilin via Distinct Mechanisms

    Science.gov (United States)

    Calabrese, Barbara; Saffin, Jean-Michel; Halpain, Shelley

    2014-01-01

    A current model posits that cofilin-dependent actin severing negatively impacts dendritic spine volume. Studies suggested that increased cofilin activity underlies activity-dependent spine shrinkage, and that reduced cofilin activity induces activity-dependent spine growth. We suggest instead that both types of structural plasticity correlate with decreased cofilin activity. However, the mechanism of inhibition determines the outcome for spine morphology. RNAi in rat hippocampal cultures demonstrates that cofilin is essential for normal spine maintenance. Cofilin-F-actin binding and filament barbed-end production decrease during the early phase of activity-dependent spine shrinkage; cofilin concentration also decreases. Inhibition of the cathepsin B/L family of proteases prevents both cofilin loss and spine shrinkage. Conversely, during activity-dependent spine growth, LIM kinase stimulates cofilin phosphorylation, which activates phospholipase D-1 to promote actin polymerization. These results implicate novel molecular mechanisms and prompt a revision of the current model for how cofilin functions in activity-dependent structural plasticity. PMID:24740405

  14. Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes.

    Science.gov (United States)

    Szpigel, Anaïs; Hainault, Isabelle; Carlier, Aurélie; Venteclef, Nicolas; Batto, Anne-Françoise; Hajduch, Eric; Bernard, Catherine; Ktorza, Alain; Gautier, Jean-François; Ferré, Pascal; Bourron, Olivier; Foufelle, Fabienne

    2018-02-01

    Obesity and type 2 diabetes are concomitant with low-grade inflammation affecting insulin sensitivity and insulin secretion. Recently, the thioredoxin interacting protein (TXNIP) has been implicated in the activation process of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we aim to determine whether the expression of TXNIP is altered in the circulating immune cells of individuals with type 2 vs type 1 diabetes and whether this can be related to specific causes and consequences of inflammation. The expression of TXNIP, inflammatory markers, markers of the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress and enzymes involved in sphingolipid metabolism was quantified by quantitative reverse transcription real-time PCR (qRT-PCR) in peripheral blood mononuclear cells (PBMCs) of 13 non-diabetic individuals, 23 individuals with type 1 diabetes and 81 with type 2 diabetes. A lipidomic analysis on the plasma of 13 non-diabetic individuals, 35 individuals with type 1 diabetes and 94 with type 2 diabetes was performed. The effects of ER stress or of specific lipids on TXNIP and inflammatory marker expression were analysed in human monocyte-derived macrophages (HMDMs) and THP-1 cells. The expression of TXNIP and inflammatory and UPR markers was increased in the PBMCs of individuals with type 2 diabetes when compared with non-diabetic individuals or individuals with type 1 diabetes. TXNIP expression was significantly correlated with plasma fasting glucose, plasma triacylglycerol concentrations and specific UPR markers. Induction of ER stress in THP-1 cells or cultured HMDMs led to increased expression of UPR markers, TXNIP, NLRP3 and IL-1β. Conversely, a chemical chaperone reduced the expression of UPR markers and TXNIP in PBMCs of individuals with type 2 diabetes. The lipidomic plasma analysis revealed an increased concentration of saturated dihydroceramide and sphingomyelin in individuals with type 2

  15. Balanced trafficking between the ER and the Golgi apparatus increases protein secretion in yeast

    DEFF Research Database (Denmark)

    Bao, Jichen; Huang, Mingtao; Petranovic, Dina

    2018-01-01

    of ADP-ribosylation factor GTP activating proteins, Gcs1p and Glo3p, which are involved in the process of COPI-coated vesicle formation. Engineering the retrograde trafficking increased the secretion of alpha-amylase but did not induce production of reactive oxygen species. An expanded ER membrane......The yeast Saccharomyces cerevisiae is widely used as a cell factory to produce recombinant proteins. However, S. cerevisiae naturally secretes only a few proteins, such as invertase and the mating alpha factor, and its secretory capacity is limited. It has been reported that engineering protein...... recombinant proteins, endoglucanase I from Trichoderma reesei and glucan-1,4-alpha-glucosidase from Rhizopus oryzae, indicating overexpression of GLO3 in a SEC16 moderate overexpression strain might be a general strategy for improving production of secreted proteins by yeast....

  16. Communication and Stakeholder Involvement in Environmental Remediation Projects

    International Nuclear Information System (INIS)

    2014-01-01

    The way in which members of the public perceive a contamination situation and an approach to the remediation of contaminated land will influence the decision making process in a variety of ways. Through communication between experts, decision makers and members of stakeholder communities, participatory processes and negotiation between different interest groups can sometimes be used effectively as mechanisms for improving the overall decision making process. The intention is to ensure a technically sound and socially acceptable decision that meets norms of adequacy or satisfactory performance in relation to a whole range of different concerns. Good communication strategies will encourage cooperation and understanding between different interested parties in remediation projects. Involvement of affected or interested persons can prevent fear driven reactions, which potentially damage public response and create undue expectations or unnecessary anxiety. For all environmental remediation (ER) cases, there is a risk that the process will fail if it does not respect social, environmental, political and economic dimensions. This requires open, clear and mutually agreed lines of communication among stakeholders within a well defined legal framework. A general recommendation is to involve them from a very early point in the process. This publication presents ER in plain language in such a way that implementers and regulators can communicate the motives and objectives of remediation projects to a variety of stakeholder communities in order to improve mutual understanding and facilitate dialogue between interested parties. ER is considered from two perspectives: technical and non-technical. A section that gives general ideas on the strategies to deal with stakeholder involvement and which discusses different aspects of the communication approaches in ER is then included. It is recognized that social, cultural and political situations are very diverse in different countries in

  17. Selective modulation of ER-beta by estradiol and xenoestrogens in human breast cancer cell lines.

    Science.gov (United States)

    Cappelletti, V; Saturno, G; Miodini, P; Körner, W; Daidone, M G

    2003-03-01

    In the last decades, substances with estrogenic activity have been dispersed into the environment. Xenoestrogens act by binding to estrogen receptors, ligand-regulated transcription factors, for which two subtypes have been described, ER-alpha and ER-beta, which are often coexpressed at variable amounts in different tissues. We investigated variations in the expression of ER-alpha and ER-beta mRNAs following treatment with four xenoestrogens (bisphenol A, 4-tert octylphenol, 2-hydroxybiphenyl, 4-hydroxybiphenyl) and with 17beta-estradiol in estrogen-sensitive (T47D) and estrogen-insensitive (BT20) breast cancer cell lines. Although to a variable extent, both estradiol and the tested xenoestrogens increased the expression of ER-beta mRNA, whereas a slight effect on ER-alpha was observed only in T47D cells. Upregulation of ER-beta expression by estradiol and xenoestrogens was observed only in the presence of detectable ER-alpha protein levels. These findings indicate a regulatory role for ER-beta in ER-alpha-mediated transcription and a role for ER-beta in mediating xenoestrogen toxicity.

  18. The Rim101 pathway contributes to ER stress adaptation through sensing the state of plasma membrane.

    Science.gov (United States)

    Obara, Keisuke; Kihara, Akio

    2017-01-01

    Yeast cells sense alterations in the plasma membrane (PM) lipid asymmetry and external alkalization by the sensor protein Rim21, which functions in the Rim101 pathway. Rim101 signaling is initiated at the PM by the recruitment of the Rim101 signaling complex. The PM physically associates with the cortical endoplasmic reticulum (ER) to form ER-PM contact sites, where several signaling events, lipid exchange, and ion transport take place. In the present study, we investigated the spatial relationship between ER-PM contact sites and the sites of Rim101 signaling. Rim101 signaling mostly proceeds outside ER-PM contact sites in the PM and did not require intact ER-PM contact for its activation. Rather, the Rim101 pathway was constitutively activated by ER-PM contact site disruption, which is known to cause ER stress. ER stress induced by tunicamycin treatment activated the Rim101 pathway. Furthermore, the sensitivity of cells to tunicamycin without ER-PM contact was considerably elevated by the deletion of RIM21. These results suggest that the Rim101 pathway is important for the adaptation to ER stress by compensating for alterations in PM lipid asymmetry induced by ER stress. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  19. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    International Nuclear Information System (INIS)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-01-01

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  20. ER Stress Signaling Promotes the Survival of Cancer "Persister Cells" Tolerant to EGFR Tyrosine Kinase Inhibitors.

    Science.gov (United States)

    Terai, Hideki; Kitajima, Shunsuke; Potter, Danielle S; Matsui, Yusuke; Quiceno, Laura Gutierrez; Chen, Ting; Kim, Tae-Jung; Rusan, Maria; Thai, Tran C; Piccioni, Federica; Donovan, Katherine A; Kwiatkowski, Nicholas; Hinohara, Kunihiko; Wei, Guo; Gray, Nathanael S; Fischer, Eric S; Wong, Kwok-Kin; Shimamura, Teppei; Letai, Anthony; Hammerman, Peter S; Barbie, David A

    2018-02-15

    An increasingly recognized component of resistance to tyrosine kinase inhibitors (TKI) involves persistence of a drug-tolerant subpopulation of cancer cells that survive despite effective eradication of the majority of the cell population. Multiple groups have demonstrated that these drug-tolerant persister cells undergo transcriptional adaptation via an epigenetic state change that promotes cell survival. Because this mode of TKI drug tolerance appears to involve transcriptional addiction to specific genes and pathways, we hypothesized that systematic functional screening of EGFR TKI/transcriptional inhibitor combination therapy would yield important mechanistic insights and alternative drug escape pathways. We therefore performed a genome-wide CRISPR/Cas9 enhancer/suppressor screen in EGFR-dependent lung cancer PC9 cells treated with erlotinib + THZ1 (CDK7/12 inhibitor) combination therapy, a combination previously shown to suppress drug-tolerant cells in this setting. As expected, suppression of multiple genes associated with transcriptional complexes (EP300, CREBBP, and MED1) enhanced erlotinib/THZ1 synergy. Unexpectedly, we uncovered nearly every component of the recently described ufmylation pathway in the synergy suppressor group. Loss of ufmylation did not affect canonical downstream EGFR signaling. Instead, absence of this pathway triggered a protective unfolded protein response associated with STING upregulation, promoting protumorigenic inflammatory signaling but also unique dependence on Bcl-xL. These data reveal that dysregulation of ufmylation and ER stress comprise a previously unrecognized TKI drug tolerance pathway that engages survival signaling, with potentially important therapeutic implications. Significance: These findings reveal a novel function of the recently described ufmylation pathway, an ER stress survival signaling in drug-tolerant persister cells, which has important biological and therapeutic implications. Cancer Res; 78(4); 1044