The foldase CYPB is a component of the secretory pathway of Aspergillus niger and contains the endoplasmic reticulum retention signal HEEL.

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Derkx, P M; Madrid, S M

2001-12-01

Here we report the isolation and characterization of the cypB gene from Aspergillus niger. The cypB gene encodes a protein with a predicted molecular weight of 20.7 kDa, which shows a high degree of identity to the cyclophilin family of peptidyl prolyl cis-trans isomerases (PPIases) from other eukaryotes. The 5' untranslated region of cypB includes three sequences resembling UPREs (unfolded protein response elements). The expression of cypB is upregulated by tunicamycin and DTT, suggesting that at least one UPRE is functional. The CYPB protein also has a 23-amino acid sequence which serves to target the protein to the endoplasmic reticulum (ER), and the ER retention sequence HEEL. CYPB-(His)(6) was expressed in Escherichia coli; the purified protein is capable of isomerizing a substrate peptide in vitro. This is also the first report to show that C-terminal addition of the sequence HEEL is sufficient to ensure retention of the green fluorescent protein (GFP) within the ER.

Binding to membrane proteins within the endoplasmic reticulum cannot explain the retention of the glucose-regulated protein GRP78 in Xenopus oocytes.

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Ceriotti, A; Colman, A

1988-03-01

We have studied the compartmentation and movement of the rat 78-kd glucose-regulated protein (GRP78) and other secretory and membrane proteins in Xenopus oocytes. Full length GRP78, normally found in the lumen of rat endoplasmic reticulum (ER), is localized to a membraneous compartment in oocytes and is not secreted. A truncated GRP78 lacking the C-terminal (KDEL) ER retention signal is secreted, although at a slow rate. When the synthesis of radioactive GRP78 is confined to a polar (animal or vegetal) region of the oocyte and the subsequent movement across the oocyte monitored, we find that both full-length and truncated GRP78 move at similar rates and only slightly slower than a secretory protein, chick ovalbumin. In contrast, a plasma membrane protein (influenza haemagglutinin) and two ER membrane proteins (rotavirus VP10 and a mutant haemagglutinin) remained confined to their site of synthesis. We conclude that the retention of GRP78 in the ER is not due to its tight binding to a membrane-bound receptor.

HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

LENUS (Irish Health Repository)

Gupta, Sanjeev

2010-01-01

Endoplasmic reticulum (ER) stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR). Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha\\/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

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Sanjeev Gupta

2010-07-01

Full Text Available Endoplasmic reticulum (ER stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR. Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

{sup 3}He retention and structural evolution in erbium tritides: Phase and aging effects

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Zhou, X.S., E-mail: zlxs77@163.com [Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang 621900 (China); Thin Film Centre, Scottish Universities Physics Alliance (SUPA), University of West of Scotland, Paisley PA1 2BE, Scotland (United Kingdom); Zhang, L.; Wang, W.D.; Liu, Q. [Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang 621900 (China); Peng, S.M., E-mail: pengshuming@caep.cn [Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang 621900 (China); Ding, W.; Long, X.G.; Cheng, G.J.; Liang, J.H. [Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang 621900 (China); Fu, Y.Q. [Thin Film Centre, Scottish Universities Physics Alliance (SUPA), University of West of Scotland, Paisley PA1 2BE, Scotland (United Kingdom)

2015-06-15

Highlights: • Effects of phase changes on {sup 3}He retention of Er tritide films were investigated. • The α phase in Er tritide films had no apparent effect on {sup 3}He release/retention. • Tritium content in the β phase showed significant effects on {sup 3}He retention. • Evolution of {sup 3}He in the β phase was apparently influenced by the γ phase. • Effects of phase changes on structure evolution of Er tritides were investigated. - Abstract: Effects of phase changes on {sup 3}He release/retention and crystal lattice evolution during aging of erbium (Er) tritide films were investigated using X-ray diffraction. The contents of α phase and γ phase in the Er tritide films showed significant different effects on {sup 3}He release/retention. The initial tritium stoichiometry or excess tritium atoms accommodated in the octahedral sites and the microstructure (i.e., the texture and Er{sub 2}O{sub 3} oxide inclusions) played an important role for the {sup 3}He release and the evolution of {sup 3}He bubbles in the β phase Er tritide films. In the β + γ region, evolution of {sup 3}He in the β phase was apparently influenced by the γ phase, which could result in a strongly anisotropic lattice dilation and an earlier inflection point of the expansion rate of (1 1 1) lattice parameter. A preferred occupation of {sup 3}He in basal plane of the hexagonal γ phase and the lattice expansion along the hexagonal direction were identified.

Coronavirus infection, ER stress and Apoptosis

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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.

Endoplasmic reticulum protein targeting of phospholamban: a common role for an N-terminal di-arginine motif in ER retention?

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Parveen Sharma

2010-07-01

Full Text Available Phospholamban (PLN is an effective inhibitor of the sarco(endoplasmic reticulum Ca(2+-ATPase, which transports Ca(2+ into the SR lumen, leading to muscle relaxation. A mutation of PLN in which one of the di-arginine residues at positions 13 and 14 was deleted led to a severe, early onset dilated cardiomyopathy. Here we were interested in determining the cellular mechanisms involved in this disease-causing mutation.Mutations deleting codons for either or both Arg13 or Arg14 resulted in the mislocalization of PLN from the ER. Our data show that PLN is recycled via the retrograde Golgi to ER membrane traffic pathway involving COP-I vesicles, since co-immunoprecipitation assays determined that COP I interactions are dependent on an intact di-arginine motif as PLN RDelta14 did not co-precipitate with COP I containing vesicles. Bioinformatic analysis determined that the di-arginine motif is present in the first 25 residues in a large number of all ER/SR Gene Ontology (GO annotated proteins. Mutations in the di-arginine motif of the Sigma 1-type opioid receptor, the beta-subunit of the signal recognition particle receptor, and Sterol-O-acyltransferase, three proteins identified in our bioinformatic screen also caused mislocalization of these known ER-resident proteins.We conclude that PLN is enriched in the ER due to COP I-mediated transport that is dependent on its intact di-arginine motif and that the N-terminal di-arginine motif may act as a general ER retrieval sequence.

ER stress stimulates production of the key antimicrobial peptide, cathelicidin, by forming a previously unidentified intracellular S1P signaling complex.

Science.gov (United States)

Park, Kyungho; Ikushiro, Hiroko; Seo, Ho Seong; Shin, Kyong-Oh; Kim, Young Il; Kim, Jong Youl; Lee, Yong-Moon; Yano, Takato; Holleran, Walter M; Elias, Peter; Uchida, Yoshikazu

2016-03-08

We recently identified a previously unidentified sphingosine-1-phosphate (S1P) signaling mechanism that stimulates production of a key innate immune element, cathelicidin antimicrobial peptide (CAMP), in mammalian cells exposed to external perturbations, such as UVB irradiation and other oxidative stressors that provoke subapoptotic levels of endoplasmic reticulum (ER) stress, independent of the well-known vitamin D receptor-dependent mechanism. ER stress increases cellular ceramide and one of its distal metabolites, S1P, which activates NF-κB followed by C/EBPα activation, leading to CAMP production, but in a S1P receptor-independent fashion. We now show that S1P activates NF-κB through formation of a previously unidentified signaling complex, consisting of S1P, TRAF2, and RIP1 that further associates with three stress-responsive proteins; i.e., heat shock proteins (GRP94 and HSP90α) and IRE1α. S1P specifically interacts with the N-terminal domain of heat shock proteins. Because this ER stress-initiated mechanism is operative in both epithelial cells and macrophages, it appears to be a universal, highly conserved response, broadly protective against diverse external perturbations that lead to increased ER stress. Finally, these studies further illuminate how ER stress and S1P orchestrate critical stress-specific signals that regulate production of one protective response by stimulating production of the key innate immune element, CAMP.

The expression of ER, PR in endometrial cancer and analysis of their correlation with ERK signaling pathway.

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Luo, Lan; Xu, Lina; Tang, Liang

2017-12-12

Endometrial carcinoma (EC) is a common malignant tumor in gynecology. Its incidence and development are closely associated with the levels of estrogenic and progesterone hormone. Extracellular signal-regulated kinase (ERK) signaling pathway abnormity is associated with a variety of tumors. This study detected estrogen receptor (ER), progesterone receptor (PR), ERK1, and ERK2 expression in EC and analyzed their correlations. A total of 40 EC patients in our hospital were selected as test group, while another 40 healthy volunteers were enrolled as control group. ER, PR, ERK1, and ERK2 expression in EC tissue, para-carcinoma tissue, and normal endometrial tissue were detected by immunohistochemistry and Western blot. The positive rate of ER, PR, ERK1, and ERK2 in the test group was 50%, 40%, 60%, and 65%, respectively, which were significantly higher than those in the control (PPR, ERK1, and ERK2 protein expressions in EC cell were significantly higher than those in the control (PPR (PPR, which were correlated with higher levels of ERK1 and ERK2, suggesting they might be involved in the pathogenesis of EC.

Dietary gossypol suppressed postprandial TOR signaling and elevated ER stress pathways in turbot (Scophthalmus maximus L.).

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Bian, Fuyun; Jiang, Haowen; Man, Mingsan; Mai, Kangsen; Zhou, Huihui; Xu, Wei; He, Gen

2017-01-01

Gossypol is known to be a polyphenolic compound toxic to animals. However, its molecular targets are far from fully characterized. To evaluate the physiological and molecular effects of gossypol, we chose turbot (Scophthalmus maximus L.), a carnivorous fish, as our model species. Juvenile turbots (7.83 ± 0.02 g) were fed diets containing gradient levels of gossypol at 0 (G0), 600 (G1), and 1,200 (G2) mg/kg diets for 11 wk. After the feeding trial, fish growth, body protein, and fat contents were significantly reduced in the G2 group compared with those of the G0 group (P TOR) signaling and induced endoplasmic reticulum (ER) stress pathway in both the feeding experiment and cell cultures. Our results demonstrated that gossypol inhibited TOR signaling and elevated ER stress pathways both in vivo and in vitro, thus providing new mechanism of action of gossypol in nutritional physiology. Copyright © 2017 the American Physiological Society.

Ultraviolet (UV and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE Cell Apoptosis

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Jin Yao

2013-05-01

Full Text Available Ultraviolet (UV radiation and reactive oxygen species (ROS impair the physiological functions of retinal pigment epithelium (RPE cells by inducing cell apoptosis, which is the main cause of age-related macular degeneration (AMD. The mechanism by which UV/ROS induces RPE cell death is not fully addressed. Here, we observed the activation of a ceramide-endoplasmic reticulum (ER stress-AMP activated protein kinase (AMPK signaling axis in UV and hydrogen peroxide (H2O2-treated RPE cells. UV and H2O2 induced an early ceramide production, profound ER stress and AMPK activation. Pharmacological inhibitors against ER stress (salubrinal, ceramide production (fumonisin B1 and AMPK activation (compound C suppressed UV- and H2O2-induced RPE cell apoptosis. Conversely, cell permeable short-chain C6 ceramide and AMPK activator AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide mimicked UV and H2O2’s effects and promoted RPE cell apoptosis. Together, these results suggest that UV/H2O2 activates the ceramide-ER stress-AMPK signaling axis to promote RPE cell apoptosis.

Identification of ER Proteins Involved in the Functional Organisation of the Early Secretory Pathway in Drosophila Cells by a Targeted RNAi Screen

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Kondylis, Vangelis; Tang, Yang; Fuchs, Florian; Boutros, Michael; Rabouille, Catherine

2011-01-01

Background In Drosophila, the early secretory apparatus comprises discrete paired Golgi stacks in close proximity to exit sites from the endoplasmic reticulum (tER sites), thus forming tER-Golgi units. Although many components involved in secretion have been identified, the structural components sustaining its organisation are less known. Here we set out to identify novel ER resident proteins involved in the of tER-Golgi unit organisation. Results To do so, we designed a novel screening strategy combining a bioinformatics pre-selection with an RNAi screen. We first selected 156 proteins exhibiting known or related ER retention/retrieval signals from a list of proteins predicted to have a signal sequence. We then performed a microscopy-based primary and confirmation RNAi screen in Drosophila S2 cells directly scoring the organisation of the tER-Golgi units. We identified 49 hits, most of which leading to an increased number of smaller tER-Golgi units (MG for “more and smaller Golgi”) upon depletion. 16 of them were validated and characterised, showing that this phenotype was not due to an inhibition in secretion, a block in G2, or ER stress. Interestingly, the MG phenotype was often accompanied by an increase in the cell volume. Out of 6 proteins, 4 were localised to the ER. Conclusions This work has identified novel proteins involved in the organisation of the Drosophila early secretory pathway. It contributes to the effort of assigning protein functions to gene annotation in the secretory pathway, and analysis of the MG hits revealed an enrichment of ER proteins. These results suggest a link between ER localisation, aspects of cell metabolism and tER-Golgi structural organisation. PMID:21383842

ER-associated degradation is required for vasopressin prohormone processing and systemic water homeostasis

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Somlo, Diane R.M.; Kim, Geun Hyang; Prescianotto-Baschong, Cristina; Sun, Shengyi; Beuret, Nicole; Long, Qiaoming; Rutishauser, Jonas

2017-01-01

Peptide hormones are crucial regulators of many aspects of human physiology. Mutations that alter these signaling peptides are associated with physiological imbalances that underlie diseases. However, the conformational maturation of peptide hormone precursors (prohormones) in the ER remains largely unexplored. Here, we report that conformational maturation of proAVP, the precursor for the antidiuretic hormone arginine-vasopressin, within the ER requires the ER-associated degradation (ERAD) activity of the Sel1L-Hrd1 protein complex. Serum hyperosmolality induces expression of both ERAD components and proAVP in AVP-producing neurons. Mice with global or AVP neuron–specific ablation of Se1L-Hrd1 ERAD progressively developed polyuria and polydipsia, characteristics of diabetes insipidus. Mechanistically, we found that ERAD deficiency causes marked ER retention and aggregation of a large proportion of all proAVP protein. Further, we show that proAVP is an endogenous substrate of Sel1L-Hrd1 ERAD. The inability to clear misfolded proAVP with highly reactive cysteine thiols in the absence of Sel1L-Hrd1 ERAD causes proAVP to accumulate and participate in inappropriate intermolecular disulfide–bonded aggregates, promoted by the enzymatic activity of protein disulfide isomerase (PDI). This study highlights a pathway linking ERAD to prohormone conformational maturation in neuroendocrine cells, expanding the role of ERAD in providing a conducive ER environment for nascent proteins to reach proper conformation. PMID:28920920

Retention and topology of the bovine viral diarrhea virus glycoprotein E2.

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Radtke, Christina; Tews, Birke Andrea

2017-10-01

Pestiviruses are enveloped viruses that bud intracellularly. They have three envelope glycoproteins, E rns , E1, and E2. E2 is the receptor binding protein and the main target for neutralizing antibodies. Both E rns and E2 are retained intracellularly. Here, E2 of the bovine viral diarrhea virus (BVDV) strain CP7 was used to study the membrane topology and intracellular localization of the protein. E2 is localized in the ER and there was no difference between E2 expressed alone or in the context of the viral polyprotein. The mature E2 protein was found to possess a single span transmembrane anchor. For the mapping of a retention signal CD72-E2 fusion proteins, as well as E2 alone were analysed. This confirmed the importance of the transmembrane domain and arginine 355 for intracellular retention, but also revealed a modulating effect on retention through the cytoplasmic tail of the E2 protein, especially through glutamine 370. Mutants with a strong impact on retention were tested in the viral context and we were able to rescue BVDV with certain mutations that in E2 alone impaired intracellular retention and lead to export of E2 to the cells surface.

Baicalin Ameliorates H2O2 Induced Cytotoxicity in HK-2 Cells through the Inhibition of ER Stress and the Activation of Nrf2 Signaling

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Miao Lin

2014-07-01

Full Text Available Renal ischemia-reperfusion injury plays a key role in renal transplantation and greatly affects the outcome of allograft. Our previous study proved that Baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, protects kidney from ischemia-reperfusion injury. This study aimed to study the underlying mechanism in vitro. Human renal proximal tubular epithelial cell line HK-2 cells were stimulated by H2O2 with and without Baicalin pretreatment. The cell viability, apoptosis and oxidative stress level were measured. The expression of endoplasmic reticulum (ER stress hallmarks, such as binding immunoglobulin protein (BiP and C/EBP homologous protein (CHOP, were analyzed by western blot and real-time PCR. NF-E2-related factor 2 (Nrf2 expression was also measured. In the H2O2 group, cell viability decreased and cell apoptosis increased. Reactive Oxygen Species (ROS and Glutathione/Oxidized Glutathione (GSH/GSSG analysis revealed increased oxidative stress. ER stress and Nrf2 signaling also increased. Baicalin pretreatment ameliorated H2O2-induced cytotoxicity, reduced oxidative stress and ER stress and further activated the anti-oxidative Nrf2 signaling pathway. The inducer of ER stress and the inhibitor of Nrf2 abrogated the protective effects, while the inhibitor of ER stress and the inducer of Nrf2 did not improve the outcome. This study revealed that Baicalin pretreatment serves a protective role against H2O2-induced cytotoxicity in HK-2 cells, where the inhibition of ER stress and the activation of downstream Nrf2 signaling are involved.

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

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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.

The effect of extensive reading and paired-associate learning on long-term vocabulary retention: an event-related potential study.

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Chun, Eunjin; Choi, Sungmook; Kim, Junsoo

2012-07-19

We investigated the relative efficacy of extensive reading (ER) and paired-associate learning (PAL) in the ability of second language (L2) learners to retain new vocabulary words. To that end, we combined behavioral measures (i.e., vocabulary tests) and an event-related potential (ERP) investigation with a focus on the N400 ERP component to track short- and long-term vocabulary retention as a consequence of the two different approaches. Behavioral results indicated that both ER and PAL led to substantial short-term retention of the target words. In contrast, on a long-term basis, ER was more effective than PAL to a considerable degree as indicated by a large-size effect (d=1.35). Evidence from the N400 effects (d=1.70) observed in the parietal electrode group (P3, Pz, P4) provided further support for the superior effects of ER over PAL on long-term vocabulary retention. The converging evidence challenges the assumptions of some L2 researchers and makes a significant contribution to the literature of vocabulary acquisition, because it provides the first ERP evidence that ER is more conducive to long-term vocabulary retention than PAL. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Rescue of cAMP response element-binding protein signaling reversed spatial memory retention impairments induced by subanesthetic dose of propofol.

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Zhang, Hao; Zhang, Shao-Bo; Zhang, Qing-Qing; Liu, Meng; He, Xing-Ying; Zou, Zui; Sun, Hai-Jing; You, Zhen-Dong; Shi, Xue-Yin

2013-07-01

The intravenous anesthetic propofol caused episodic memory impairments in human. We hypothesized propofol caused episodic-like spatial memory retention but not acquisition impairments in rats and rescuing cAMP response element-binding protein (CREB) signaling using selective type IV phosphodiesterase (PDEIV) inhibitor rolipram reversed these effects. Male Sprague-Dawley rats were randomized into four groups: control; propofol (25 mg/kg, intraperitoneal); rolipram; and rolipram + propofol (pretreatment of rolipram 25 min before propofol, 0.3 mg/kg, intraperitoneal). Sedation and motor coordination were evaluated 5, 15, and 25 min after propofol injection. Invisible Morris water maze (MWM) acquisition and probe test (memory retention) were performed 5 min and 24 h after propofol injection. Visible MWM training was simultaneously performed to resist nonspatial effects. Hippocampal CREB signaling was detected 5 min, 50 min, and 24 h after propofol administration. Rolipram did not change propofol-induced anesthetic/sedative states or impair motor skills. No difference was found on the latency to the platform during the visible MWM. Propofol impaired spatial memory retention but not acquisition. Rolipram reversed propofol-induced spatial memory impairments and suppression on cAMP levels, CaMKIIα and CREB phosphorylation, brain-derived neurotropic factor (BDNF) and Arc protein expression. Propofol caused spatial memory retention impairments but not acquisition inability possibly by inhibiting CREB signaling. © 2013 John Wiley & Sons Ltd.

16 CFR Figure 8 to Part 1203 - Apparatus for Test of Retention System Strength

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2010-01-01

...—Apparatus for Test of Retention System Strength ER10MR98.008 ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Apparatus for Test of Retention System Strength 8 Figure 8 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT...

Role of Estrogen Receptor Signaling in Breast Cancer Metastasis

International Nuclear Information System (INIS)

Roy, S.S.; Vadlamudi, R.K.

2012-01-01

Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis

IRE1: ER stress sensor and cell fate executor.

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Chen, Yani; Brandizzi, Federica

2013-11-01

Cells operate a signaling network termed the unfolded protein response (UPR) to monitor protein-folding capacity in the endoplasmic reticulum (ER). Inositol-requiring enzyme 1 (IRE1) is an ER transmembrane sensor that activates the UPR to maintain the ER and cellular function. Although mammalian IRE1 promotes cell survival, it can initiate apoptosis via decay of antiapoptotic miRNAs. Convergent and divergent IRE1 characteristics between plants and animals underscore its significance in cellular homeostasis. This review provides an updated scenario of the IRE1 signaling model, discusses emerging IRE1 sensing mechanisms, compares IRE1 features among species, and outlines exciting future directions in UPR research. Copyright © 2013 Elsevier Ltd. All rights reserved.

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. �

Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

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Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng, E-mail: zhouqs@suda.edu.cn

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. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice. �

Deubiquitinase inhibitor b-AP15 activates endoplasmic reticulum (ER) stress and inhibits Wnt/Notch1 signaling pathway leading to the reduction of cell survival in hepatocellular carcinoma cells.

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Ding, Youming; Chen, Xiaoyan; Wang, Bin; Yu, Bin; Ge, Jianhui

2018-04-15

b-AP15, a potent and selective inhibitor of the ubiquitin-specific peptidase 14 (USP14), displays in vitro and in vivo antitumor abilities on some types of cancer cells. However, the mechanism underlying its action is not well elucidated. The purposes of the present study are to observe the potential impacts of b-AP15 on cell survival of hepatocellular carcinoma cells and to investigate whether and how this compound inhibits some survival-promoting signaling pathways. We found that b-AP15 significantly decreased cell viability and increased cell apoptosis in a dose-dependent manner in hepatocellular carcinoma cells, along with the perturbation of cell cycle and the decreased expressions of cell cycle-related proteins. We also demonstrated that the endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) were enhanced by b-AP15 supplementation. The inhibition of ER stress/UPR only partly attenuated the cytotoxicity of b-AP15 on hepatocellular carcinoma cells. In addition, b-AP15 treatment inhibited Wnt/β-catenin and Notch1 signaling pathways, and suppressed phosphorylation of STAT3, Akt, and Erk1/2, which were not restored by the inhibition of ER stress/UPR. Furthermore, the expression levels of signaling molecules in Notch1 were reduced by specific inhibitor of Wnt/β-catenin pathway. Notably, either Wnt or Notch1 signaling inhibitor mitigated phosphorylation of STAT3, Akt, and Erk1/2, and mimicked the cytotoxicity of b-AP15 on hepatocellular carcinoma cells. These results clearly indicate that b-AP15 induced cytotoxic response to hepatocellular carcinoma cells by augmenting ER stress/UPR and inhibiting Wnt/Notch1 signaling pathways. This new finding provides a novel mechanism by which b-AP15 produces its antitumor therapeutic effects. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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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

Mechanism underlying the inner membrane retention of Escherichia coli lipoproteins caused by Lol avoidance signals.

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Hara, Takashi; Matsuyama, Shin-ichi; Tokuda, Hajime

2003-10-10

Escherichia coli lipoproteins are localized to either the inner or outer membrane depending on the residue at position 2. The inner membrane retention signal, Asp at position 2 in combination with certain residues at position 3, functions as a Lol avoidance signal, i.e. the signal inhibits the recognition of lipoproteins by LolCDE that releases lipoproteins from the inner membrane. To understand the role of the residue at position 2, outer membrane-specific lipoproteins with Cys at position 2 were subjected to chemical modification followed by the release reaction in reconstituted proteoliposomes. Sulfhydryl-specific introduction of nonprotein molecules or a negative charge to Cys did not inhibit the LolCDE-dependent release. In contrast, oxidation of Cys to cysteic acid resulted in generation of the Lol avoidance signal, indicating that the Lol avoidance signal requires a critical length of negative charge at the second residue. Furthermore, not only modification of the carboxylic acid of Asp at position 2 but also that of the amine of phosphatidylethanolamine abolished the Lol avoidance function. Based on these results, the Lol avoidance mechanism is discussed.

Pre-emptive Quality Control Protects the ER from Protein Overload via the Proximity of ERAD Components and SRP

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Hisae Kadowaki

2015-11-01

Full Text Available Cells possess ER quality control systems to adapt to ER stress and maintain their function. ER-stress-induced pre-emptive quality control (ER pQC selectively degrades ER proteins via translocational attenuation during ER stress. However, the molecular mechanism underlying this process remains unclear. Here, we find that most newly synthesized endogenous transthyretin proteins are rerouted to the cytosol without cleavage of the signal peptide, resulting in proteasomal degradation in hepatocytes during ER stress. Derlin family proteins (Derlins, which are ER-associated degradation components, reroute specific ER proteins, but not ER chaperones, from the translocon to the proteasome through interactions with the signal recognition particle (SRP. Moreover, the cytosolic chaperone Bag6 and the AAA-ATPase p97 contribute to the degradation of ER pQC substrates. These findings demonstrate that Derlins-mediated substrate-specific rerouting and Bag6- and p97-mediated effective degradation contribute to the maintenance of ER homeostasis without the need for translocation.

Effect of Er:YAG Laser and Sandblasting in Recycling of Ceramic Brackets.

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Yassaei, Soghra; Aghili, Hossein; Hosseinzadeh Firouzabadi, Azadeh; Meshkani, Hamidreza

2017-01-01

Introduction: This study was performed to determine the shear bond strength of rebonded mechanically retentive ceramic brackets after recycling with Erbium-Doped Yttrium Aluminum Garnet (Er:YAG) laser or sandblasting. Methods: Twenty-eight debonded ceramic brackets plus 14 intact new ceramic brackets were used in this study. Debonded brackets were randomly divided into 2 groups of 14. One group was treated by Er:YAG laser and the other with sandblasting. All the specimens were randomly bonded to 42 intact human upper premolars. The shear bond strength of all specimens was determined with a universal testing machine at a crosshead speed of 0.5 mm/min until bond failure occurred. The recycled bracket base surfaces were observed under a scanning electron microscope (SEM). Analysis of variance (ANOVA) and Tukey tests were used to compare the shear bond strength of the 3 groups. Fisher exact test was used to evaluate the differences in adhesive remnant index (ARI) scores. Results: The highest bond strength belonged to brackets recycled by Sandblasting (16.83 MPa). There was no significant difference between the shear bond strength of laser and control groups. SEM photographs showed differences in 2 recycling methods. The laser recycled bracket appeared to have as well-cleaned base as the new bracket. Although the sandblasted bracket photographs showed no remnant adhesives, remarkable micro-roughening of the base of the bracket was apparent. Conclusion: According to the results of this study, both Er:YAG laser and sandblasting were efficient to mechanically recondition retentive ceramic brackets. Also, Er:YAG laser did not change the design of bracket base while removing the remnant adhesives which might encourage its application in clinical practice.

Rab7a modulates ER stress and ER morphology.

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Mateus, Duarte; Marini, Elettra Sara; Progida, Cinzia; Bakke, Oddmund

2018-05-01

The Endoplasmic Reticulum (ER) is a membranous organelle with diverse structural and functional domains. Peripheral ER includes interconnected tubules, and dense tubular arrays called "ER matrices" together with bona fide flat cisternae. Transitions between these states are regulated by membrane-associated proteins and cytosolic factors. Recently, the small GTPases Rab10 and Rab18 were reported to control ER shape by regulating ER dynamics and fusion. Here, we present evidence that another Rab protein, Rab7a, modulates the ER morphology by controlling the ER homeostasis and ER stress. Indeed, inhibition of Rab7a expression by siRNA or expression of the dominant negative mutant Rab7aT22 N, leads to enlargement of sheet-like ER structures and spreading towards the cell periphery. Notably, such alterations are ascribable neither to a direct modulation of the ER shaping proteins Reticulon-4b and CLIMP63, nor to interactions with Protrudin, a Rab7a-binding protein known to affect the ER organization. Conversely, depletion of Rab7a leads to basal ER stress, in turn causing ER membrane expansion. Both ER enlargement and basal ER stress are reverted in rescue experiments by Rab7a re-expression, as well as by the ER chemical chaperone tauroursodeoxycholic acid (TUDCA). Collectively, these findings reveal a new role of Rab7a in ER homeostasis, and indicate that genetic and pharmacological ER stress manipulation may restore ER morphology in Rab7a silenced cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

Energy Technology Data Exchange (ETDEWEB)

Friedrich, Stephan [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Boyd, Stephen [Univ. of New Mexico, Albuquerque, NM (United States); Cantor, Robin [STAR Cryoelectronics, Santa Fe, NM (United States)

2015-11-25

This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

Energy Technology Data Exchange (ETDEWEB)

Friedrich, Stephan [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Boyd, Stephen [Univ. of New Mexico, Albuquerque, NM (United States); Cantor, Robin [STAR Cryoelectronics, Santa Fe, NM (United States)

2016-05-06

This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

International Nuclear Information System (INIS)

Friedrich, Stephan; Boyd, Stephen; Cantor, Robin

2016-01-01

This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

International Nuclear Information System (INIS)

Friedrich, Stephan; Boyd, Stephen; Cantor, Robin

2015-01-01

This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

Noncontact Er:YAG laser ablation: clinical evaluation.

Science.gov (United States)

Dostálová, T; Jelínková, H; Kucerová, H; Krejsa, O; Hamal, K; Kubelka, J; Procházka, S

1998-10-01

The aim of this study is to evaluate the quality of laser ablation in comparison with the classical drilling preparation. For the experiment, the Er:YAG laser drilling machine was used. The system had a laser head, water cooler, and power supply with automatic control. Spot size of 300-350 microns was used for the preparation. Repetition rate of 1-4 Hz, and pulse energies of 100-400 mJ with water spray were chosen. Cavity shape in comparison with classical drill, time of preparation, and influence of cavity shape on filling materials retention in accordance with the U.S. Public Health Service System were used. The evaluation criteria for noncontact Er:YAG ablation were done. The cavity shape is irregular, but spot surface has larger area and microretentive appearance. Caries of enamel and dentin were treated with a noncontact preparation. It was possible to remove the old insufficient fillings, except for amalgam or metal alloys. The average number of pulses was 111.22 (SE 67.57). Vibrations of microexplosions during preparation were felt by patients on 14 cavities; however, nobody felt unpleasant pain. The qualities of filling materials in laser cavities were very stable; however, cavo surface margin discoloration of 82-86% of Alfa rating could be a problem. Changes of the color and anatomic form of the tooth were observed in 4-8%. In comparison with the classical treatment, it could be said that the retention and quality of filling materials is the same or very similar.

Arctigenin alleviates ER stress via activating AMPK

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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

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

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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.

Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer.

Science.gov (United States)

Choi, Hee-Joo; Joo, Hyeong-Seok; Won, Hee-Young; Min, Kyueng-Whan; Kim, Hyung-Yong; Son, Taekwon; Oh, Young-Ha; Lee, Jeong-Yeon; Kong, Gu

2018-04-01

resistance (RBP2-overexpressing cells: % cell viability [SD], tamoxifen = 89.0 [3.8]%, vs tamoxifen with BKM120 = 41.3 [5.6]%, P < .001). RBP2 activates ER-IGF1R-ErbB signaling cascade in multiple ways to induce tamoxifen resistance, suggesting that RBP2 is a potential therapeutic target for ER-driven cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Expression profiling on soybean leaves reveals integration of ER- and osmotic-stress pathways

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Dewey Ralph E

2007-11-01

Full Text Available Abstract Background Despite the potential of the endoplasmic reticulum (ER stress response to accommodate adaptive pathways, its integration with other environmental-induced responses is poorly understood in plants. We have previously demonstrated that the ER-stress sensor binding protein (BiP from soybean exhibits an unusual response to drought. The members of the soybean BiP gene family are differentially regulated by osmotic stress and soybean BiP confers tolerance to drought. While these results may reflect crosstalk between the osmotic and ER-stress signaling pathways, the lack of mutants, transcriptional response profiles to stresses and genome sequence information of this relevant crop has limited our attempts to identify integrated networks between osmotic and ER stress-induced adaptive responses. As a fundamental step towards this goal, we performed global expression profiling on soybean leaves exposed to polyethylene glycol treatment (osmotic stress or to ER stress inducers. Results The up-regulated stress-specific changes unmasked the major branches of the ER-stress response, which include enhancing protein folding and degradation in the ER, as well as specific osmotically regulated changes linked to cellular responses induced by dehydration. However, a small proportion (5.5% of total up-regulated genes represented a shared response that seemed to integrate the two signaling pathways. These co-regulated genes were considered downstream targets based on similar induction kinetics and a synergistic response to the combination of osmotic- and ER-stress-inducing treatments. Genes in this integrated pathway with the strongest synergistic induction encoded proteins with diverse roles, such as plant-specific development and cell death (DCD domain-containing proteins, an ubiquitin-associated (UBA protein homolog and NAC domain-containing proteins. This integrated pathway diverged further from characterized specific branches of ER-stress as

ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells

International Nuclear Information System (INIS)

Sun, Qing; Liang, Ying; Zhang, Tianli; Wang, Kun; Yang, Xingsheng

2017-01-01

Objective: Estrogen receptor alpha 36 (ER-α36), a truncated variant of ER-α, is different from other nuclear receptors of the ER-α family. Previous findings indicate that ER-α36 might be involved in cell growth, proliferation, and differentiation in carcinomas and primarily mediates non-genomic estrogen signaling. However, studies on ER-α36 and cervical cancer are rare. This study aimed to detect the expression of ER-α36 in cervical cancer; the role of ER-α36 in 17-β-estradiol (E2)-induced invasion, migration and proliferation of cervical cancer; and their probable molecular mechanisms. Methods: Immunohistochemistry and immunofluorescence were used to determine the location of ER-α36 in cervical cancer tissues and cervical cell lines. CaSki and HeLa cell lines were transfected with lentiviruses to establish stable cell lines with knockdown and overexpression of ER-α36. Wound healing assay, transwell invasion assay, and EdU incorporation proliferation assay were performed to evaluate the migration, invasion, and proliferation ability. The phosphorylation levels of mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling molecules were examined with western blot analysis. Results: ER-α36 expression was detected in both cervical cell lines and cervical cancer tissues. Downregulation of ER-α36 significantly inhibited cell invasion, migration, and proliferation. Moreover, upregulation of ER-α36 increased the invasion, migration, and proliferation ability of CaSki and HeLa cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation. Conclusion: ER-α36 is localized on the plasma membrane and cytoplasm in both cervical cancer tissues and cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells. - Highlights: • ER-α36 is expressed on both cervical cell lines and cervical cancer tissues. • ER-α36 mediates estrogen

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

Purple perilla extracts allay ER stress in lipid-laden macrophages.

Directory of Open Access Journals (Sweden)

Sin-Hye Park

Full Text Available There is a growing body of evidence that excess lipids, hypoxic stress and other inflammatory signals can stimulate endoplasmic reticulum (ER stress in metabolic diseases. However, the pathophysiological importance and the underlying mechanisms of this phenomenon remain unknown. The current study investigated that 50 ng/ml oxidized LDL promoted unfolded protein response (UPR and ER stress in J774A1 murine macrophages, which was blocked by extracts (PPE of purple Perilla frutescens, a plant of the mint family Lamiaceae. The ER stressor tunicamycin was employed as a positive control. Treating 1-10 µg/ml oxidized LDL for 24 h elicited lipotoxic apoptosis in macrophages with obvious nuclear condensation and DNA fragmentation, which was inhibited by PPE. Tunicamycin and oxidized LDL activated and induced the UPR components of activating transcription factor 6 and ER resident chaperone BiP/Grp78 in temporal manners and such effects were blocked by ≥5 µg/ml PPE. In addition, PPE suppressed the enhanced mRNA transcription and splicing of X-box binding protein 1 (XBP1 by tunicamycin and oxidized LDL. The protein induction and nuclear translocation of XBP1 were deterred in PPE-treated macrophages under ER stress. The induction of ATP-binding cassette transporter A1 (ABCA1, scavenger receptor-B1 (SR-B1 and intracellular adhesion molecule-1 (ICAM-1 was abolished by the ER stressor in activated macrophages. The protein induction of ABCA1 and ICAM1 but not SR-B1 was retrieved by adding 10 µg/ml PPE to cells. These results demonstrate that PPE inhibited lipotoxic apoptosis and demoted the induction and activation of UPR components in macrophages. PPE restored normal proteostasis in activated macrophages oxidized LDL. Therefore, PPE was a potent agent antagonizing macrophage ER stress due to lipotoxic signals associated with atherosclerosis.

Interactome Screening Identifies the ER Luminal Chaperone Hsp47 as a Regulator of the Unfolded Protein Response Transducer IRE1α.

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Sepulveda, Denisse; Rojas-Rivera, Diego; Rodríguez, Diego A; Groenendyk, Jody; Köhler, Andres; Lebeaupin, Cynthia; Ito, Shinya; Urra, Hery; Carreras-Sureda, Amado; Hazari, Younis; Vasseur-Cognet, Mireille; Ali, Maruf M U; Chevet, Eric; Campos, Gisela; Godoy, Patricio; Vaisar, Tomas; Bailly-Maitre, Béatrice; Nagata, Kazuhiro; Michalak, Marek; Sierralta, Jimena; Hetz, Claudio

2018-01-18

Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). IRE1α is a major UPR transducer, determining cell fate under ER stress. We used an interactome screening to unveil several regulators of the UPR, highlighting the ER chaperone Hsp47 as the major hit. Cellular and biochemical analysis indicated that Hsp47 instigates IRE1α signaling through a physical interaction. Hsp47 directly binds to the ER luminal domain of IRE1α with high affinity, displacing the negative regulator BiP from the complex to facilitate IRE1α oligomerization. The regulation of IRE1α signaling by Hsp47 is evolutionarily conserved as validated using fly and mouse models of ER stress. Hsp47 deficiency sensitized cells and animals to experimental ER stress, revealing the significance of Hsp47 to global proteostasis maintenance. We conclude that Hsp47 adjusts IRE1α signaling by fine-tuning the threshold to engage an adaptive UPR. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Mineralocorticoid-induced sodium appetite and renal salt retention: Evidence for common signaling and effector mechanisms

Science.gov (United States)

Fu, Yiling; Vallon, Volker

2014-01-01

An increase in renal sodium chloride (salt) retention and an increase in sodium appetite is the body's response to salt restriction or depletion in order to restore salt balance. Renal salt retention and increased sodium appetite can also be maladaptive and sustain the pathophysiology in conditions like salt-sensitive hypertension and chronic heart failure. Here we review the central role of the mineralocorticoid aldosterone in both the increase in renal salt reabsorption and sodium appetite. We discuss the working hypothesis that aldosterone activates similar signaling and effector mechanisms in the kidney and brain, including the mineralocorticoid receptor, the serum-and-glucocorticoid-induced kinase SGK1, the ubiquitin ligase NEDD4-2, and the epithelial sodium channel ENaC. The latter also mediates the gustatory salt sensing in the tongue, which is required for the manifestation of increased salt intake. Effects of aldosterone on both brain and kidney synergize with the effects of angiotensin II. Thus, mineralocorticoids appear to induce similar molecular pathways in the kidney, brain, and possibly tongue, which could provide opportunities for more effective therapeutic interventions. Inhibition of renal salt reabsorption is compensated by stimulation of salt appetite and vice versa; targeting both mechanisms should be more effective. Inhibiting the arousal to consume salty food may improve a patient's compliance to reducing salt intake. While a better understanding of the molecular mechanisms is needed and will provide new options, current pharmacological interventions that target both salt retention and sodium appetite include mineralocorticoid receptor antagonists and potentially inhibitors of angiotensin II and ENaC. PMID:25376899

Development of microstructured large area magnetic calorimeters with Au:Er- and Ag:Er-sensors for the detection of x-ray quanta and high energetic particles; Entwicklung grossflaechiger mikrostrukturierter magnetischer Kalorimeter mit Au:Er- und Ag:Er-Sensoren fuer den energieaufgeloesten Nachweis von Roentgenquanten und hochenergetischen Teilchen

Energy Technology Data Exchange (ETDEWEB)

Burck, Andreas

2008-11-04

This thesis describes the development of large-area magnetic calorimeters which could for example be used for the investigation of the dissociative recombination or the measurement of the Lamb-shift for hydrogenlike heavy ions. The detectors consist of two meandershaped niobium thin film pickup coils and a paramagnetic sensor. The deposition of energy in the sensor results in a temperature change and therefore in a change of magnetisation of the sensor, which can be measured by a SQUID-magnetometer with high precision. As sensormaterials a dilute alloy of gold-erbium (Au:Er) as well as silver-erbium (Ag:Er) were used. Whereas the Ag:Er-sensor was glued on the pickup coil the Au:Er-sensor was for the first time microstructured by a novel microstructuring process established in this thesis. For the characterisation of the detectors and the sensormaterials a fluorescence source and a {sup 55}Fe source were used. The thermodynamic properties of the Au:Er-sensors thereby show promising results, as the magnetisation shows bulk properties down to 20 mK. The measurements of the signalize and the magnetisation with the detector which was equipped with a Ag:Er-sensor showed that the thermodynamic properties of the Ag:Eralloy could be fully described. Furthermore the shape of the pulses, the noise and the energy resolution of both detectors will be discussed. (orig.)

Potential mechanisms underlying estrogen-induced expression of the molluscan estrogen receptor (ER) gene

Energy Technology Data Exchange (ETDEWEB)

Tran, Thi Kim Anh [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia); Department of Agriculture, Forestry and Fisheries, Vinh University, 182 Le Duan St., Vinh City, Nghe An (Viet Nam); MacFarlane, Geoff R. [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia); Kong, Richard Yuen Chong [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong Special Administrative Region (China); O’Connor, Wayne A. [New South Wales Department of Primary Industries, Port Stephens Fisheries Institute, Taylors Beach, NSW 2316 (Australia); Yu, Richard Man Kit, E-mail: Richard.Yu@newcastle.edu.au [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia)

2016-10-15

Highlights: • This is the first report on the putative promoter sequence of a molluscan ER gene. • The gene promoter contains putative binding sites for direct and indirect interaction with ER. • E2 upregulates ER gene expression in the ovary in vitro and in vivo. • E2-induced gene expression may require a novel ligand-dependent receptor. • The ER proximal promoter is hypomethylated regardless of gene expression levels. - Abstract: In vertebrates, estrogens and estrogen mimicking chemicals modulate gene expression mainly through a genomic pathway mediated by the estrogen receptors (ERs). Although the existence of an ER orthologue in the mollusc genome has been known for some time, its role in estrogen signalling has yet to be deciphered. This is largely due to its constitutive (ligand-independent) activation and a limited mechanistic understanding of its regulation. To fill this knowledge gap, we cloned and characterised an ER cDNA (sgER) and the 5′-flanking region of the gene from the Sydney rock oyster Saccostrea glomerata. The sgER cDNA is predicted to encode a 477-amino acid protein that contains a DNA-binding domain (DBD) and a ligand-binding domain (LBD) typically conserved among both vertebrate and invertebrate ERs. A comparison of the sgER LBD sequence with those of other ligand-dependent ERs revealed that the sgER LBD is variable at several conserved residues known to be critical for ligand binding and receptor activation. Ligand binding assays using fluorescent-labelled E2 and purified sgER protein confirmed that sgER is devoid of estrogen binding. In silico analysis of the sgER 5′-flanking sequence indicated the presence of three putative estrogen responsive element (ERE) half-sites and several putative sites for ER-interacting transcription factors, suggesting that the sgER promoter may be autoregulated by its own gene product. sgER mRNA is ubiquitously expressed in adult oyster tissues, with the highest expression found in the ovary

ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER.

Science.gov (United States)

Costello, Joseph L; Castro, Inês G; Hacker, Christian; Schrader, Tina A; Metz, Jeremy; Zeuschner, Dagmar; Azadi, Afsoon S; Godinho, Luis F; Costina, Victor; Findeisen, Peter; Manner, Andreas; Islinger, Markus; Schrader, Michael

2017-02-01

Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO-ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A-binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5-VAPB interaction regulates PO-ER associations. Moreover, we demonstrate that loss of PO-ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO-ER associations in mammalian cells and report a new function for ACBD5 in PO-ER tethering. © 2017 Costello et al.

Mammary Ductal Environment Is Necessary for Faithful Maintenance of Estrogen Signaling in ER+ Breast Cancer

OpenAIRE

Haricharan, Svasti; Lei, Jonathan; Ellis, Matthew

2016-01-01

In this issue of Cancer Cell, Sflomos et al. (2016) describe a robust preclinical animal model of ER+ breast cancer. The authors identify the critical role of the breast microenvironment in determining hormone response of ER+ breast cancer cells and in driving the luminal phenotype of breast cancer.

Thermodynamic assessments of the Ag-Er and Er-Y systems

International Nuclear Information System (INIS)

Wang, S.L.; Wang, C.P.; Liu, X.J.; Tang, A.T.; Pan, F.S.; Ishida, K.

2010-01-01

The phase diagrams and thermodynamic properties in the Ag-Er and Er-Y binary systems have been assessed by using the CALPHAD (Calculation of Phase Diagrams) method on the basis of the experimental data including the thermodynamic properties and phase equilibria. The Gibbs free energies of the liquid, bcc, fcc, and hcp phases were described by the subregular solution model with the Redlich-Kister equation, and those of intermetallic compounds (Ag 2 Er and AgEr phases) were treated as stoichiometric compounds, and Ag 51 Er 14 phase was modeled by the sublattice model in the Ag-Er binary system. The thermodynamic parameters of the Ag-Er and Er-Y binary systems were obtained, and an agreement between the calculated results and experimental data was obtained for each binary system.

Mammary Ductal Environment Is Necessary for Faithful Maintenance of Estrogen Signaling in ER+ Breast Cancer

Science.gov (United States)

Haricharan, Svasti; Lei, Jonathan; Ellis, Matthew

2016-01-01

In this issue of Cancer Cell, Sflomos et al. (2016) describe a robust preclinical animal model of ER+ breast cancer. The authors identify the critical role of the breast microenvironment in determining hormone response of ER+ breast cancer cells and in driving the luminal phenotype of breast cancer. PMID:26977876

ARTEMIN promotes de novo angiogenesis in ER negative mammary carcinoma through activation of TWIST1-VEGF-A signalling.

Directory of Open Access Journals (Sweden)

Arindam Banerjee

Full Text Available The neurotrophic factor ARTEMIN (ARTN has been reported to possess a role in mammary carcinoma progression and metastasis. Herein, we report that ARTN modulates endothelial cell behaviour and promotes angiogenesis in ER-mammary carcinoma (ER-MC. Human microvascular endothelial cells (HMEC-1 do not express ARTN but respond to exogenously added, and paracrine ARTN secreted by ER-MC cells. ARTN promoted endothelial cell proliferation, migration, invasion and 3D matrigel tube formation. Angiogenic behaviour promoted by ARTN secreted by ER-MC cells was mediated by AKT with resultant increased TWIST1 and subsequently VEGF-A expression. In a patient cohort of ER-MC, ARTN positively correlated with VEGF-A expression as measured by Spearman's rank correlation analysis. In xenograft experiments, ER-MC cells with forced expression of ARTN produced tumors with increased VEGF-A expression and increased microvessel density (CD31 and CD34 compared to tumors formed by control cells. Functional inhibition of ARTN by siRNA decreased the angiogenic effects of ER-MC cells. Bevacizumab (a humanized monoclonal anti-VEGF-A antibody partially inhibited the ARTN mediated angiogenic effects of ER-MC cells and combined inhibition of ARTN and VEGF-A by the same resulted in further significant decrease in the angiogenic effects of ER-MC cells. Thus, ARTN stimulates de novo tumor angiogenesis mediated in part by VEGF-A. ARTN therefore co-ordinately regulates multiple aspects of tumor growth and metastasis.

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.

Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology

Energy Technology Data Exchange (ETDEWEB)

Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît; Maldonado-Báez, Lymarie; Park, Seong Hee; Blackstone, Craig, E-mail: blackstc@ninds.nih.gov

2016-11-15

Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. - Highlights: • NIH-3T3 cells lacking all three atlastin paralogs were generated using CRISPR/Cas9. • Cells lacking all atlastin GTPases exhibit far fewer 3-way ER tubule junctions. • ER morphology defects in atlastin knockout cells are rescued by distant plant and yeast orthologs. • Atlastin knock out cells also

Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology

International Nuclear Information System (INIS)

Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît; Maldonado-Báez, Lymarie; Park, Seong Hee; Blackstone, Craig

2016-01-01

Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. - Highlights: • NIH-3T3 cells lacking all three atlastin paralogs were generated using CRISPR/Cas9. • Cells lacking all atlastin GTPases exhibit far fewer 3-way ER tubule junctions. • ER morphology defects in atlastin knockout cells are rescued by distant plant and yeast orthologs. • Atlastin knock out cells also

Low Estrogen Receptor (ER)-Positive Breast Cancer and Neoadjuvant Systemic Chemotherapy: Is Response Similar to Typical ER-Positive or ER-Negative Disease?

Science.gov (United States)

Landmann, Alessandra; Farrugia, Daniel J; Zhu, Li; Diego, Emilia J; Johnson, Ronald R; Soran, Atilla; Dabbs, David J; Clark, Beth Z; Puhalla, Shannon L; Jankowitz, Rachel C; Brufsky, Adam M; Ahrendt, Gretchen M; McAuliffe, Priscilla F; Bhargava, Rohit

2018-05-08

Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors. Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded. The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases. Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy.

The relationship between estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression of breast cancer and the retention index in dual phase {sup 18}F-FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

Noh, Woo Chul; Kim, Hyun Ah; Kim, Eun Kyu [Dept.of Surgery, Korea Cancer Center HospitalKorea Institute of Radiological and Medical Sciences (KIRAMS), Seoul (Korea, Republic of); and others

2016-09-15

This study investigates the correlation of retention index (RI) using the dual phase FDG PET/CT scan with the breast cancer biomarkers. A total of 55 patients with breast cancer underwent dual phase FDG PET/CT scans (60 and 120 min after FDG injection) before treatment. SUVmax and SUVmean of the primary breast tumors were measured, then the percent change of SUVmax and SUVmean between the two scans were calculated, and denoted as RImax and RImean, respectively. After the surgical resection of the breast tumor, the status of biomarkers (ER, PR, and HER-2) was evaluated in the postsurgical specimen. RImean was significantly higher in ER (−) (median, 16.2; IQR, 10.8–21.0) or HER-2 (+) (median, 16.1; IQR, 10.7–21.6) tumors than in ER (+) tumors (median, 9.9; IQR, 5.5–15.3) or HER-2 (−) tumors (median, 10.5; IQR, 5.5–16.1). However, there were no significant differences of SUVmax or RImax according to the ER or HER-2 status. There were no significant differences of any PET parameters between PR (+) and PR (−) tumors. Based off ROC curve analyses, RImean predicted the ER (+) tumors (AUC, 0.699; p = 0.006), and HER-2 (+) tumors (AUC, 0.674; p = 0.022), but not the PR (+) tumors. However, neither SUVmax nor RImax predicted ER (+), PR (+), or HER-2 (+) tumors. Retention index of SUVmean can reflect the ER and HER-2 status of breast cancers. Higher retention index of SUVmean might associate with lower ER expression and higher HER-2 expression.

Decoherence and absorption of Er3+:KTiOPO4 (KTP) at 1.5 μm

International Nuclear Information System (INIS)

Böttger, Thomas; Thiel, C.W.; Sun, Y.; Macfarlane, R.M.; Cone, R.L.

2016-01-01

We present results of laser absorption spectroscopy and two-pulse photon echo decoherence measurements on the lowest 4 I 15/2 to lowest 4 I 13/2 transition in Er 3+ : KTiOPO 4 (KTP—potassium titanyl phosphate) for the optical transition located at 1537.238 nm. This transition was found to have an inhomogeneous absorption linewidth of 950 MHz and pronounced polarization dependence. Two-pulse photon echo decay measurements as a function of applied magnetic field strength at 1.9 K revealed a narrow homogeneous linewidth of 2.5 kHz at 0.2 T that increased to 5.8 kHz at 1.2 T and then decreased to 1.6 kHz at 4.5 T. This behavior was successfully described by decoherence due to Er 3+ –Er 3+ magnetic dipole interactions. Significant superhyperfine coupling of Er 3+ spins to the nuclear moments of ions in the host lattice was observed, modulating the photon echo decay at low magnetic fields and limiting the effective homogenous linewidth at high fields. Combined with the well-established potential of KTP for fabrication of high-quality optical waveguides and integrated non-linear frequency conversion, our results suggest that Er 3+ :KTP is a promising material system for practical spectral hole burning, signal processing, and quantum information applications. - Highlights: • Bulk Er 3+ :KTP has dominant Er 3+ site at 1537.238 nm with Γ inh of 950 MHz and T 1 of 16.9 ms. • Two-pulse photon echoes revealed magnetic field dependent kHz-wide homogeneous linewidth. • Decoherence modeled using direct-phonon driven Er 3+ –Er 3+ magnetic dipole-dipole interactions. • Evidence of superhyperfine coupling of Er 3+ spins to nuclear moments of host ions. • Er 3+ :KTP is a promising material system for quantum memory and signal processing applications.

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.

Hvis en kartoffel er forkert, hvad er en Mars-bar så?

DEFF Research Database (Denmark)

Lichtenstein, Mia Beck; Thomsen, Freja; Hinze, Cecilie

2016-01-01

Danske unge er de slankeste af 41 europæiske unge, men de føler sig ofte tykke og går på slankekur. Hvad er årsagen, og hvorfor er det et problem?......Danske unge er de slankeste af 41 europæiske unge, men de føler sig ofte tykke og går på slankekur. Hvad er årsagen, og hvorfor er det et problem?...

ER phospholipid composition modulates lipogenesis during feeding and in obesity.

Science.gov (United States)

Rong, Xin; Wang, Bo; Palladino, Elisa Nd; de Aguiar Vallim, Thomas Q; Ford, David A; Tontonoz, Peter

2017-10-02

Sterol regulatory element-binding protein 1c (SREBP-1c) is a central regulator of lipogenesis whose activity is controlled by proteolytic cleavage. The metabolic factors that affect its processing are incompletely understood. Here, we show that dynamic changes in the acyl chain composition of ER phospholipids affect SREBP-1c maturation in physiology and disease. The abundance of polyunsaturated phosphatidylcholine in liver ER is selectively increased in response to feeding and in the setting of obesity-linked insulin resistance. Exogenous delivery of polyunsaturated phosphatidylcholine to ER accelerated SREBP-1c processing through a mechanism that required an intact SREBP cleavage-activating protein (SCAP) pathway. Furthermore, induction of the phospholipid-remodeling enzyme LPCAT3 in response to liver X receptor (LXR) activation promoted SREBP-1c processing by driving the incorporation of polyunsaturated fatty acids into ER. Conversely, LPCAT3 deficiency increased membrane saturation, reduced nuclear SREBP-1c abundance, and blunted the lipogenic response to feeding, LXR agonist treatment, or obesity-linked insulin resistance. Desaturation of the ER membrane may serve as an auxiliary signal of the fed state that promotes lipid synthesis in response to nutrient availability.

Marginal microleakage in vitro study on class V cavities prepared with Er:YAG laser and etched with acid or etched with Er:YAG laser and acid; Estudo in vitro da microinfiltracao marginal em cavidades classe V preparadas com laser de Er:YAG e condicionadas com acido ou com laser de Er:YAG e acido

Energy Technology Data Exchange (ETDEWEB)

Tavares, Henrique Dutra Simoes

2001-07-01

Microleakage at the interface between the teeth and the restorative materials remains a problem with composite resin restorations. Microleakage at the gingival margins of class V cavities restorations still challenge as they are usually placed in dentin and/or cementum. Previous studies have shown that the cavity preparation with Er:YAG laser is possible. It has been reported that Er:YAG laser has ability to create irregular surface providing micromechanical retention for adhesive dental restorative materials and to improve marginal sealing. The purpose of this in vitro study was to evaluate the marginal microleakage on class V cavities prepared with Er:YAG laser and etched with acid or with Er:YAG laser and acid, in compared to those prepared and etched conventionally. Thirty human molars were divided into three groups, namely: group I - prepared with Er:YAG laser (KaVo KEY Laser II - Germany) and etched with 37% phosphoric acid; group II - prepared with Er:YAG laser and etched with Er:YAG laser and 37% phosphoric acid; group III (control group) - prepared with high speed drill and etched with 37% phosphoric acid. All cavities were treated with same adhesive system (Single Bond - 3M) and restored with the composite resin (Z100 - 3M), according to the manufacturer's instructions. The specimens were stored at 37 deg C in water for 24 hours, polished with Sof-Lex discs (3M), thermally stressed, sealed with a nail polish coating except for the area of the restoration and 1 mm around it, and immersed in a 50% aqueous solution of silver nitrate for 24 hours. After that, the specimens were rinsed in water, soaked in a photodeveloping solution and exposed to a fluorescent light for 8 hours. The teeth were embedded in an autopolymerizing resin and sectioned longitudinally using a diamond saw microtome under running water. The sections were photographed. The microleakage at the occlusal cavity and at the gingival margins of each specimen was evaluated with scores (0-3) by

Marginal microleakage in vitro study on class V cavities prepared with Er:YAG laser and etched with acid or etched with Er:YAG laser and acid; Estudo in vitro da microinfiltracao marginal em cavidades classe V preparadas com laser de Er:YAG e condicionadas com acido ou com laser de Er:YAG e acido

Energy Technology Data Exchange (ETDEWEB)

Tavares, Henrique Dutra Simoes

2001-07-01

Microleakage at the interface between the teeth and the restorative materials remains a problem with composite resin restorations. Microleakage at the gingival margins of class V cavities restorations still challenge as they are usually placed in dentin and/or cementum. Previous studies have shown that the cavity preparation with Er:YAG laser is possible. It has been reported that Er:YAG laser has ability to create irregular surface providing micromechanical retention for adhesive dental restorative materials and to improve marginal sealing. The purpose of this in vitro study was to evaluate the marginal microleakage on class V cavities prepared with Er:YAG laser and etched with acid or with Er:YAG laser and acid, in compared to those prepared and etched conventionally. Thirty human molars were divided into three groups, namely: group I - prepared with Er:YAG laser (KaVo KEY Laser II - Germany) and etched with 37% phosphoric acid; group II - prepared with Er:YAG laser and etched with Er:YAG laser and 37% phosphoric acid; group III (control group) - prepared with high speed drill and etched with 37% phosphoric acid. All cavities were treated with same adhesive system (Single Bond - 3M) and restored with the composite resin (Z100 - 3M), according to the manufacturer's instructions. The specimens were stored at 37 deg C in water for 24 hours, polished with Sof-Lex discs (3M), thermally stressed, sealed with a nail polish coating except for the area of the restoration and 1 mm around it, and immersed in a 50% aqueous solution of silver nitrate for 24 hours. After that, the specimens were rinsed in water, soaked in a photodeveloping solution and exposed to a fluorescent light for 8 hours. The teeth were embedded in an autopolymerizing resin and sectioned longitudinally using a diamond saw microtome under running water. The sections were photographed. The microleakage at the occlusal cavity and at the gingival margins of each specimen was evaluated with scores (0

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.

Development of microstructured large area magnetic calorimeters with Au:Er- and Ag:Er-sensors for the detection of x-ray quanta and high energetic particles

International Nuclear Information System (INIS)

Burck, Andreas

2008-01-01

This thesis describes the development of large-area magnetic calorimeters which could for example be used for the investigation of the dissociative recombination or the measurement of the Lamb-shift for hydrogenlike heavy ions. The detectors consist of two meandershaped niobium thin film pickup coils and a paramagnetic sensor. The deposition of energy in the sensor results in a temperature change and therefore in a change of magnetisation of the sensor, which can be measured by a SQUID-magnetometer with high precision. As sensormaterials a dilute alloy of gold-erbium (Au:Er) as well as silver-erbium (Ag:Er) were used. Whereas the Ag:Er-sensor was glued on the pickup coil the Au:Er-sensor was for the first time microstructured by a novel microstructuring process established in this thesis. For the characterisation of the detectors and the sensormaterials a fluorescence source and a 55 Fe source were used. The thermodynamic properties of the Au:Er-sensors thereby show promising results, as the magnetisation shows bulk properties down to 20 mK. The measurements of the signalize and the magnetisation with the detector which was equipped with a Ag:Er-sensor showed that the thermodynamic properties of the Ag:Eralloy could be fully described. Furthermore the shape of the pulses, the noise and the energy resolution of both detectors will be discussed. (orig.)

Arabidopsis ETR1 and ERS1 Differentially Repress the Ethylene Response in Combination with Other Ethylene Receptor Genes1[W

Science.gov (United States)

Liu, Qian; Wen, Chi-Kuang

2012-01-01

The ethylene response is negatively regulated by a family of five ethylene receptor genes in Arabidopsis (Arabidopsis thaliana). The five members of the ethylene receptor family can physically interact and form complexes, which implies that cooperativity for signaling may exist among the receptors. The ethylene receptor gene mutations etr1-1(C65Y)(for ethylene response1-1), ers1-1(I62P) (for ethylene response sensor1-1), and ers1C65Y are dominant, and each confers ethylene insensitivity. In this study, the repression of the ethylene response by these dominant mutant receptor genes was examined in receptor-defective mutants to investigate the functional significance of receptor cooperativity in ethylene signaling. We showed that etr1-1(C65Y), but not ers1-1(I62P), substantially repressed various ethylene responses independent of other receptor genes. In contrast, wild-type receptor genes differentially supported the repression of ethylene responses by ers1-1(I62P); ETR1 and ETHYLENE INSENSITIVE4 (EIN4) supported ers1-1(I62P) functions to a greater extent than did ERS2, ETR2, and ERS1. The lack of both ETR1 and EIN4 almost abolished the repression of ethylene responses by ers1C65Y, which implied that ETR1 and EIN4 have synergistic effects on ers1C65Y functions. Our data indicated that a dominant ethylene-insensitive receptor differentially repressed ethylene responses when coupled with a wild-type ethylene receptor, which supported the hypothesis that the formation of a variety of receptor complexes may facilitate differential receptor signal output, by which ethylene responses can be repressed to different extents. We hypothesize that plants can respond to a broad ethylene concentration range and exhibit tissue-specific ethylene responsiveness with differential cooperation of the multiple ethylene receptors. PMID:22227969

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.

Relationship between vortex pinning properties and microstructure in Ba–Nb–O-doped YBa2Cu3Oy and ErBa2Cu3Oy films

International Nuclear Information System (INIS)

Haruta, Masakazu; Saura, Keisuke; Fujita, Natsuto; Ogura, Yuta; Ichinose, Ataru; Maeda, Toshihiko; Horii, Shigeru

2013-01-01

Highlights: •Y123 and Er123 films with Ba–Nb–O nanorods were prepared by PLD. •Nanorod morphology depended on growth temperature (T s ). •Nanorod morphology was different between the Y123 and Er123 with the same T s . •Distribution of local J c depended on nanorod morphology. -- Abstract: In-field J c s were improved by introducing Ba–Nb–O (BNO)-nanorods in YBa 2 Cu 3 O y (Y123) and ErBa 2 Cu 3 O y (Er123) films. Retention of J c against the magnetic field for the BNO-doped Er123 film was superior to that for the BNO-doped Y123 film. Sharp distribution of local critical current density originating from vortex pinning by nanorods with uniform morphology was demonstrated in the Er123 film. On the other hand, fluctuating microstructures of nanorods formed in the Y123 film prepared by the same deposition conditions. Moreover, different growth temperature dependences of nanorod morphology between the Y123 and Er123 films were clarified

Marginal microleakage in vitro study on class V cavities prepared with Er:YAG laser and etched with acid or etched with Er:YAG laser and acid

International Nuclear Information System (INIS)

Tavares, Henrique Dutra Simoes

2001-01-01

Microleakage at the interface between the teeth and the restorative materials remains a problem with composite resin restorations. Microleakage at the gingival margins of class V cavities restorations still challenge as they are usually placed in dentin and/or cementum. Previous studies have shown that the cavity preparation with Er:YAG laser is possible. It has been reported that Er:YAG laser has ability to create irregular surface providing micromechanical retention for adhesive dental restorative materials and to improve marginal sealing. The purpose of this in vitro study was to evaluate the marginal microleakage on class V cavities prepared with Er:YAG laser and etched with acid or with Er:YAG laser and acid, in compared to those prepared and etched conventionally. Thirty human molars were divided into three groups, namely: group I - prepared with Er:YAG laser (KaVo KEY Laser II - Germany) and etched with 37% phosphoric acid; group II - prepared with Er:YAG laser and etched with Er:YAG laser and 37% phosphoric acid; group III (control group) - prepared with high speed drill and etched with 37% phosphoric acid. All cavities were treated with same adhesive system (Single Bond - 3M) and restored with the composite resin (Z100 - 3M), according to the manufacturer's instructions. The specimens were stored at 37 deg C in water for 24 hours, polished with Sof-Lex discs (3M), thermally stressed, sealed with a nail polish coating except for the area of the restoration and 1 mm around it, and immersed in a 50% aqueous solution of silver nitrate for 24 hours. After that, the specimens were rinsed in water, soaked in a photodeveloping solution and exposed to a fluorescent light for 8 hours. The teeth were embedded in an autopolymerizing resin and sectioned longitudinally using a diamond saw microtome under running water. The sections were photographed. The microleakage at the occlusal cavity and at the gingival margins of each specimen was evaluated with scores (0-3) by

The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs

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Chunman Li

2017-10-01

Full Text Available G-protein-coupled receptors (GPCRs constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of Rab43 function significantly alters the surface presentation and signaling of all GPCRs studied without affecting non-GPCR membrane proteins. Rab43 specifically regulates the transport of nascent GPCRs from the endoplasmic reticulum (ER to the Golgi. More interestingly, Rab43 directly interacts with GPCRs in an activation-dependent fashion. The Rab43-binding domain identified in the receptors effectively converts non-GPCR membrane protein transport into a Rab43-dependent pathway. These data reveal a crucial role for Rab43 in anterograde ER-Golgi transport of nascent GPCRs, as well as the ER sorting of GPCR members by virtue of its ability to interact directly.

FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells

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Lukasz Turczyk

2017-10-01

Full Text Available Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa. Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy.

The CFTR-Associated Ligand Arrests the Trafficking of the Mutant ΔF508 CFTR Channel in the ER Contributing to Cystic Fibrosis

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Emily Bergbower

2018-01-01

Full Text Available Background/Aims: The CFTR-Associated Ligand (CAL, a PDZ domain containing protein with two coiled-coil domains, reduces cell surface WT CFTR through degradation in the lysosome by a well-characterized mechanism. However, CAL’s regulatory effect on ΔF508 CFTR has remained almost entirely uninvestigated. Methods: In this study, we describe a previously unknown pathway for CAL by which it regulates the membrane expression of ΔF508 CFTR through arrest of ΔF508 CFTR trafficking in the endoplasmic reticulum (ER using a combination of cell biology, biochemistry and electrophysiology. Results: We demonstrate that CAL is an ER localized protein that binds to ΔF508 CFTR and is degraded in the 26S proteasome. When CAL is inhibited, ΔF508 CFTR retention in the ER decreases and cell surface expression of mature functional ΔF508 CFTR is observed alongside of enhanced expression of plasma membrane scaffolding protein NHERF1. Chaperone proteins regulate this novel process, and ΔF508 CFTR binding to HSP40, HSP90, HSP70, VCP, and Aha1 changes to improve ΔF508 CFTR cell surface trafficking. Conclusion: Our results reveal a pathway in which CAL regulates the cell surface availability and intracellular retention of ΔF508 CFTR.

Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions

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Devarakonda K

2014-08-01

Full Text Available Krishna Devarakonda,1 Terri Morton,1 Rachel Margulis,2 Michael Giuliani,3 Thomas Barrett4 1Clinical Pharmacology and Pharmacokinetics, 2Clinical Operations, 3Research and Development, 4Clinical Affairs, Mallinckrodt Inc., Hazelwood, MO, USA Background: XARTEMIS™ XR (formerly MNK-795 is a combination oxycodone (OC and acetaminophen (APAP analgesic with both immediate-release and extended-release (ER components (ER OC/APAP. The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets versus fasted conditions on the PK of ER OC/APAP was performed. Methods: This Phase I study used an open-label randomized single-dose three-period six-sequence crossover single-center design. Healthy adult participants (n=48 were randomized to receive two tablets of ER OC/APAP under three conditions: following a high-fat meal; following a low-fat meal; and fasted. Plasma concentration versus time data from predose throughout designated times up to 48 hours postdose was used to estimate the PK parameters of oxycodone and APAP. Results: Thirty-one participants completed all three treatment periods. Both oxycodone and APAP were rapidly absorbed under fasted conditions. Total oxycodone and APAP exposures (area under the plasma drug concentration-time curve [AUC] from ER OC/APAP were not significantly affected by food, and minimal changes to maximum observed plasma concentration for oxycodone and APAP were also noted. However, food marginally delayed the time to maximum observed plasma concentration of oxycodone and APAP. There was no indication that tolerability was affected by food. Conclusion: The findings from this study suggest that ER OC

Excessive signal transduction of gain-of-function variants of the calcium-sensing receptor (CaSR are associated with increased ER to cytosol calcium gradient.

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Marianna Ranieri

Full Text Available In humans, gain-of-function mutations of the calcium-sensing receptor (CASR gene are the cause of autosomal dominant hypocalcemia or type 5 Bartter syndrome characterized by an abnormality of calcium metabolism with low parathyroid hormone levels and excessive renal calcium excretion. Functional characterization of CaSR activating variants has been so far limited at demonstrating an increased sensitivity to external calcium leading to lower Ca-EC50. Here we combine high resolution fluorescence based techniques and provide evidence that for the efficiency of calcium signaling system, cells expressing gain-of-function variants of CaSR monitor cytosolic and ER calcium levels increasing the expression of the Sarco-Endoplasmic Reticulum Calcium-ATPase (SERCA and reducing expression of Plasma Membrane Calcium-ATPase (PMCA. Wild-type CaSR (hCaSR-wt and its gain-of-function (hCaSR-R990G; hCaSR-N124K variants were transiently transfected in HEK-293 cells. Basal intracellular calcium concentration was significantly lower in cells expressing hCaSR-wt and its gain of function variants compared to mock. In line, FRET studies using the D1ER probe, which detects [Ca2+]ER directly, demonstrated significantly higher calcium accumulation in cells expressing the gain of function CaSR variants compared to hCaSR-wt. Consistently, cells expressing activating CaSR variants showed a significant increase in SERCA activity and expression and a reduced PMCA expression. This combined parallel regulation in protein expression increases the ER to cytosol calcium gradient explaining the higher sensitivity of CaSR gain-of-function variants to external calcium. This control principle provides a general explanation of how cells reliably connect (and exacerbate receptor inputs to cell function.

Inhibition of the sarco/endoplasmic reticulum (ER) Ca2+-ATPase by thapsigargin analogs induces cell death via ER Ca2+ depletion and the unfolded protein response

DEFF Research Database (Denmark)

Sehgal, Pankaj; Szalai, Paula; Olesen, Claus

2017-01-01

Calcium (Ca2+) is a fundamental regulator of cell signaling and function. Thapsigargin (Tg) blocks the sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA), disrupts Ca2+ homeostasis, and causes cell death. However, the exact mechanisms whereby SERCA-inhibition induces cell death are incompletely...... extensive drainage of the ER Ca2+ stores. This Ca2+ depletion was followed by markedly reduced cell proliferation rates and morphological changes that developed over 2–4 days and culminated in cell death. Interestingly, these changes were not accompanied by bulk increases in cytosolic Ca2+ levels. Moreover...... and their detrimental effects on cell viability. Furthermore, caspase activation and cell death were associated with a sustained unfolded protein response (UPR). We conclude that ER Ca2+ drainage and sustained UPR activation are key for initiation of apoptosis at low concentrations of Tg and Tg analogs, whereas high...

The incidence of acute urinary retention secondary to BPH is increasing among California men.

Science.gov (United States)

Groves, H K; Chang, D; Palazzi, K; Cohen, S; Parsons, J K

2013-09-01

Current epidemiological patterns of adverse events of clinical BPH remain unclear. We investigated trends in acute urinary retention (AUR) associated with BPH in a large, population-based cohort. We utilized the California Office of Statewide Health Planning and Development Database to examine 3 724 016 emergency room (ER) visits in California among men aged  50 years from 2007 to 2010. Outcomes included AUR for which BPH was the primary diagnosis, AUR for which BPH was a secondary diagnosis and urethral catheterization for AUR. We generated adjusted odds ratios (ORadj) using multivariate logistic regression to determine longitudinal trends. A total of 17 023 men presented with a diagnosis of BPH-associated AUR, the unadjusted incidence of which increased from 4.00 per 1000 ER visits in 2007 to 5.23 per 1000 ER visits in 2010 (PBPH-associated AUR increased substantially in a large and ethnically diverse male population of the United States.

Inflammation and ER Stress Downregulate BDH2 Expression and Dysregulate Intracellular Iron in Macrophages

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Susu M. Zughaier

2014-01-01

Full Text Available Macrophages play a very important role in host defense and in iron homeostasis by engulfing senescent red blood cells and recycling iron. Hepcidin is the master iron regulating hormone that limits dietary iron absorption from the gut and limits iron egress from macrophages. Upon infection macrophages retain iron to limit its bioavailability which limits bacterial growth. Recently, a short chain butyrate dehydrogenase type 2 (BDH2 protein was reported to contain an iron responsive element and to mediate cellular iron trafficking by catalyzing the synthesis of the mammalian siderophore that binds labile iron; therefore, BDH2 plays a crucial role in intracellular iron homeostasis. However, BDH2 expression and regulation in macrophages have not yet been described. Here we show that LPS-induced inflammation combined with ER stress led to massive BDH2 downregulation, increased the expression of ER stress markers, upregulated hepcidin expression, downregulated ferroportin expression, caused iron retention in macrophages, and dysregulated cytokine release from macrophages. We also show that ER stress combined with inflammation synergistically upregulated the expression of the iron carrier protein NGAL and the stress-inducible heme degrading enzyme heme oxygenase-1 (HO-1 leading to iron liberation. This is the first report to show that inflammation and ER stress downregulate the expression of BDH2 in human THP-1 macrophages.

Endoplasmic reticulum (ER Chaperones and Oxidoreductases: Critical Regulators of Tumor Cell Survival and Immunorecognition

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Thomas eSimmen

2014-10-01

Full Text Available Endoplasmic reticulum (ER chaperones and oxidoreductases are abundant enzymes that mediate the production of fully folded secretory and transmembrane proteins. Resisting the Golgi and plasma membrane-directed bulk flow, ER chaperones and oxidoreductases enter retrograde trafficking whenever they are pulled outside of the ER. However, solid tumors are characterized by the increased production of reactive oxygen species (ROS, combined with reduced blood flow that leads to low oxygen supply and ER stress. Under these conditions, hypoxia and the unfolded protein response (UPR upregulate ER chaperones and oxidoreductases. When this occurs, ER oxidoreductases and chaperones become important regulators of tumor growth. However, under these conditions, these proteins not only promote the production of proteins, but also alter the properties of the plasma membrane and hence modulate tumor immune recognition. For instance, high levels of calreticulin serve as an eat-me signal on the surface of tumor cells. Conversely, both intracellular and surface BiP/GRP78 promotes tumor growth. Other ER folding assistants able to modulate the properties of tumor tissue include protein disulfide isomerase (PDI, Ero1α and GRP94. Understanding the roles and mechanisms of ER chaperones in regulating tumor cell functions and immunorecognition will lead to important insight for the development of novel cancer therapies.

The integrative epigenomic-transcriptomic landscape of ER positive breast cancer.

Science.gov (United States)

Gao, Yang; Jones, Allison; Fasching, Peter A; Ruebner, Matthias; Beckmann, Matthias W; Widschwendter, Martin; Teschendorff, Andrew E

2015-01-01

While recent integrative analyses of copy number and gene expression data in breast cancer have revealed a complex molecular landscape with multiple subtypes and many oncogenic/tumour suppressor driver events, much less is known about the role of DNA methylation in shaping breast cancer taxonomy and defining driver events. Here, we applied a powerful integrative network algorithm to matched DNA methylation and RNA-Seq data for 724 estrogen receptor (ER)-positive (ER+) breast cancers and 111 normal adjacent tissue specimens from The Cancer Genome Atlas (TCGA) project, in order to identify putative epigenetic driver events and to explore the resulting molecular taxonomy. This revealed the existence of nine functionally deregulated epigenetic hotspots encompassing a total of 146 genes, which we were able to validate in independent data sets encompassing over 1000 ER+ breast cancers. Integrative clustering of the matched messenger RNA (mRNA) and DNA methylation data over these genes resulted in only two clusters, which correlated very strongly with the luminal-A and luminal B subtypes. Overall, luminal-A and luminal-B breast cancers shared the same epigenetically deregulated hotspots but with luminal-B cancers exhibiting increased aberrant DNA methylation patterns relative to normal tissue. We show that increased levels of DNA methylation and mRNA expression deviation from the normal state define a marker of poor prognosis. Our data further implicates epigenetic silencing of WNT signalling antagonists and bone morphogenetic proteins (BMP) as key events underlying both luminal subtypes but specially of luminal-B breast cancer. Finally, we show that DNA methylation changes within the identified epigenetic interactome hotspots do not exhibit mutually exclusive patterns within the same cancer sample, instead exhibiting coordinated changes within the sample. Our results indicate that the integrative DNA methylation and transcriptomic landscape of ER+ breast cancer is

Decoherence and absorption of Er{sup 3+}:KTiOPO{sub 4} (KTP) at 1.5 μm

Energy Technology Data Exchange (ETDEWEB)

Böttger, Thomas, E-mail: tbottger@usfca.edu [Department of Physics & Astronomy, University of San Francisco, 2130 Fulton St., San Francisco, CA 94117 (United States); Thiel, C.W. [Department of Physics, Montana State University, Bozeman, MT 59717 (United States); Sun, Y. [Deptartment of Physics, University of South Dakota, Vermillion, SD 57069 (United States); Macfarlane, R.M. [Department of Physics, Montana State University, Bozeman, MT 59717 (United States); IBM Almaden Research Center, 650 Harry Road, San Jose, CA 95120 (United States); Cone, R.L. [Department of Physics, Montana State University, Bozeman, MT 59717 (United States)

2016-01-15

We present results of laser absorption spectroscopy and two-pulse photon echo decoherence measurements on the lowest {sup 4}I{sub 15/2} to lowest {sup 4}I{sub 13/2} transition in Er{sup 3+}: KTiOPO{sub 4} (KTP—potassium titanyl phosphate) for the optical transition located at 1537.238 nm. This transition was found to have an inhomogeneous absorption linewidth of 950 MHz and pronounced polarization dependence. Two-pulse photon echo decay measurements as a function of applied magnetic field strength at 1.9 K revealed a narrow homogeneous linewidth of 2.5 kHz at 0.2 T that increased to 5.8 kHz at 1.2 T and then decreased to 1.6 kHz at 4.5 T. This behavior was successfully described by decoherence due to Er{sup 3+}–Er{sup 3+} magnetic dipole interactions. Significant superhyperfine coupling of Er{sup 3+} spins to the nuclear moments of ions in the host lattice was observed, modulating the photon echo decay at low magnetic fields and limiting the effective homogenous linewidth at high fields. Combined with the well-established potential of KTP for fabrication of high-quality optical waveguides and integrated non-linear frequency conversion, our results suggest that Er{sup 3+}:KTP is a promising material system for practical spectral hole burning, signal processing, and quantum information applications. - Highlights: • Bulk Er{sup 3+}:KTP has dominant Er{sup 3+} site at 1537.238 nm with Γ{sub inh} of 950 MHz and T{sub 1} of 16.9 ms. • Two-pulse photon echoes revealed magnetic field dependent kHz-wide homogeneous linewidth. • Decoherence modeled using direct-phonon driven Er{sup 3+}–Er{sup 3+} magnetic dipole-dipole interactions. • Evidence of superhyperfine coupling of Er{sup 3+} spins to nuclear moments of host ions. • Er{sup 3+}:KTP is a promising material system for quantum memory and signal processing applications.

Politik er ikke lykken

DEFF Research Database (Denmark)

Steenbuch, Johannes Aakjær

2011-01-01

Der er ikke længere nogen højere sandhed i livet end den, flertallet bestemmer sig for – og dermed ingen del af livet, der ikke er politisk. Højre- og venstrefløjen er i bund og grund enige - enige om, at det er politikernes opgave at forære os det gode liv. Dermed bliver demokratiet totalitært. ...

Fluorescence methods for analysis of interactions between Ca(2+) signaling, lysosomes, and endoplasmic reticulum.

Science.gov (United States)

Prole, David L; López-Sanjurjo, Cristina I; Tovey, Stephen C; Taylor, Colin W

2015-01-01

The endoplasmic reticulum (ER) is both the major source of intracellular Ca(2+) for cell signaling and the organelle that forms the most extensive contacts with the plasma membrane and other organelles. Lysosomes fulfill important roles in degrading cellular materials and in cholesterol handling, but they also contribute to Ca(2+) signaling by both releasing and sequestering Ca(2+). Interactions between ER and other Ca(2+)-transporting membranes, notably mitochondria and the plasma membrane, often occur at sites where the two membranes are closely apposed, allowing local Ca(2+) signaling between them. These interactions are often facilitated by scaffold proteins. Recent evidence suggests similar local interactions between ER and lysosomes. We describe simple fluorescence-based methods that allow the interplay between Ca(2+) signals, the ER, and lysosomes to be examined. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Memory control with selective retention

NARCIS (Netherlands)

2012-01-01

The present invention relates to a memory circuit and a method of controlling data retention in the memory circuit, wherein a supply signal is selectively switched to a respective one of at least two virtual supply lines (24) each shared by a respective one of a plurality of groups (30-1 to 30-n) of

Memory control with selective retention

NARCIS (Netherlands)

2010-01-01

The present invention relates to a memory circuit and a method of controlling data retention in the memory circuit, wherein a supply signal is selectively switched to a respective one of at least two virtual supply lines (24) each shared by a respective one of a plurality of groups (30-1 to 30-n) of

ApoER2 Function in the Establishment and Maintenance of Retinal Synaptic Connectivity

Science.gov (United States)

Trotter, Justin H.; Klein, Martin; Jinwal, Umesh K.; Abisambra, Jose F.; Dickey, Chad A.; Tharkur, Jeremy; Masiulis, Irene; Ding, Jindong; Locke, Kirstin G.; Rickman, Catherine Bowes; Birch, David G.; Weeber, Edwin J.; Herz, Joachim

2011-01-01

The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoprotein E (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and degeneration, respectively. Here we describe the function of ApoER2 in the developing and adult retina. ApoER2 expression was highest during postnatal inner retinal synaptic development and was considerably lower in the mature retina. Both during development and in the adult ApoER2 was expressed by A-II amacrine cells. ApoER2 knockout (KO) mice had rod bipolar morphogenic defects, altered A-II amacrine dendritic development, and impaired rod-driven retinal responses. The presence of an intact ApoER2 NPxY motif, necessary for binding disabled-1 (Dab1) and transducing the Reelin signal, was also necessary for development of the rod bipolar pathway while the alternatively-spliced exon19 was not. Mice deficient in another Reelin receptor, very low-density lipoprotein receptor (VLDLR), had normal rod bipolar morphology but altered A-II amacrine dendritic development. VLDLR KO mice also had reductions in oscillatory potentials and delayed synaptic response intervals. Interestingly, age-related reductions in rod and cone function were observed in both ApoER2 and VLDLR KOs. These results support a pivotal role for ApoER2 in the establishment and maintenance of normal retinal synaptic connectivity. PMID:21976526

Modeling of Yb3+-sensitized Er3+-doped silica waveguide amplifiers

DEFF Research Database (Denmark)

Lester, Christian; Bjarklev, Anders Overgaard; Rasmussen, Thomas

1995-01-01

A model for Yb3+-sensitized Er3+-doped silica waveguide amplifiers is described and numerically investigated in the small-signal regime. The amplified spontaneous emission in the ytterbium-band and the quenching process between excited erbium ions are included in the model. For pump wavelengths...

Membrane–initiated estradiol signaling regulating sexual receptivity

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Paul E Micevych

2011-09-01

Full Text Available Estradiol has profound actions on the structure and function of the nervous system. In addition to nuclear actions that directly modulate gene expression, the idea that estradiol can rapidly activate cell signaling by binding to membrane estrogen receptors (mERs has emerged. Even the regulation of sexual receptivity, an action previously thought to be completely regulated by nuclear ERs, has been shown to have a membrane-initiated estradiol signaling (MIES component. This highlighted the question of the nature of mERs. Several candidates have been proposed, ERα, ERβ, ER-X, GPR30 (G protein coupled estrogen receptor; GPER, and a receptor activated by a diphenylacrylamide compound, STX. Although each of these receptors has been shown to be active in specific assays, we present evidence for and against their participation in sexual receptivity by acting in the lordosis-regulating circuit. The initial MIES that activates the circuit is in the arcuate nucleus of the hypothalamus (ARH. Using both activation of μ-opioid receptors (MOR in the medial preoptic nucleus and lordosis behavior, we document that both ERα and the STX receptor participate in the required MIES. ERα and the STX receptor activation of cell signaling are dependent on the transactivation of type 1 metabotropic glutamate receptors (mGluR1a that augment progesterone synthesis in astrocytes and protein kinase C (PKC in ARH neurons. While estradiol-induced sexual receptivity does not depend on neuroprogesterone, proceptive behaviors do. Moreover, the ERα and the STX receptor activation of medial preoptic MORs and augmentation of lordosis were sensitive to mGluR1a blockade. These observations suggest a common mechanism through which mERs are coupled to intracellular signaling cascades, not just in regulating reproduction, but in actions throughout the neuraxis including the cortex, hippocampus, striatum and DRGs.

Membrane-Initiated Estradiol Signaling Regulating Sexual Receptivity

Science.gov (United States)

Micevych, Paul E.; Dewing, Phoebe

2011-01-01

Estradiol has profound actions on the structure and function of the nervous system. In addition to nuclear actions that directly modulate gene expression, the idea that estradiol can rapidly activate cell signaling by binding to membrane estrogen receptors (mERs) has emerged. Even the regulation of sexual receptivity, an action previously thought to be completely regulated by nuclear ERs, has been shown to have a membrane-initiated estradiol signaling (MIES) component. This highlighted the question of the nature of mERs. Several candidates have been proposed, ERα, ERβ, ER-X, GPR30 (G protein coupled estrogen receptor), and a receptor activated by a diphenylacrylamide compound, STX. Although each of these receptors has been shown to be active in specific assays, we present evidence for and against their participation in sexual receptivity by acting in the lordosis-regulating circuit. The initial MIES that activates the circuit is in the arcuate nucleus of the hypothalamus (ARH). Using both activation of μ-opioid receptors (MOR) in the medial preoptic nucleus and lordosis behavior, we document that both ERα and the STX-receptor participate in the required MIES. ERα and the STX-receptor activation of cell signaling are dependent on the transactivation of type 1 metabotropic glutamate receptors (mGluR1a) that augment progesterone synthesis in astrocytes and protein kinase C (PKC) in ARH neurons. While estradiol-induced sexual receptivity does not depend on neuroprogesterone, proceptive behaviors do. Moreover, the ERα and the STX-receptor activation of medial preoptic MORs and augmentation of lordosis were sensitive to mGluR1a blockade. These observations suggest a common mechanism through which mERs are coupled to intracellular signaling cascades, not just in regulating reproduction, but in actions throughout the neuraxis including the cortex, hippocampus, striatum, and dorsal root ganglias. PMID:22649369

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......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...

ER stress signaling and neurodegeneration: At the intersection between Alzheimer's disease and Prion-related disorders.

Science.gov (United States)

Torres, Mauricio; Matamala, José Manuel; Duran-Aniotz, Claudia; Cornejo, Victor Hugo; Foley, Andrew; Hetz, Claudio

2015-09-02

Alzheimer's and Prion diseases are two neurodegenerative conditions sharing different pathophysiological characteristics. Disease symptoms are associated with the abnormal accumulation of protein aggregates, which are generated by the misfolding and oligomerization of specific proteins. Recent functional studies uncovered a key role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in the occurrence of synaptic dysfunction and neurodegeneration in Prion-related disorders and Alzheimer's disease. Here we review common pathological features of both diseases, emphasizing the link between amyloid formation, its pathogenesis and alterations in ER proteostasis. The potential benefits of targeting the UPR as a therapeutic strategy is also discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

The expression status of TRX, AR, and cyclin D1 correlates with clinicopathological characteristics and ER status in breast cancer.

Science.gov (United States)

Huang, Weisun; Nie, Weiwei; Zhang, Wenwen; Wang, Yanru; Zhu, Aiyu; Guan, Xiaoxiang

2016-01-01

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. 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. 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 (PTRX-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). 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 closely interact with ER signaling pathway. Further studies will be necessary to investigate the response and clinical outcomes of treatment targeting TRX, AR, and cyclin D1.

WNT4 mediates estrogen receptor signaling and endocrine resistance in invasive lobular carcinoma cell lines.

Science.gov (United States)

Sikora, Matthew J; Jacobsen, Britta M; Levine, Kevin; Chen, Jian; Davidson, Nancy E; Lee, Adrian V; Alexander, Caroline M; Oesterreich, Steffi

2016-09-20

Invasive lobular carcinoma (ILC) of the breast typically presents with clinical biomarkers consistent with a favorable response to endocrine therapies, and over 90 % of ILC cases express the estrogen receptor (ER). However, a subset of ILC cases may be resistant to endocrine therapies, suggesting that ER biology is unique in ILC. Using ILC cell lines, we previously demonstrated that ER regulates a distinct gene expression program in ILC cells, and we hypothesized that these ER-driven pathways modulate the endocrine response in ILC. One potential novel pathway is via the Wnt ligand WNT4, a critical signaling molecule in mammary gland development regulated by the progesterone receptor. The ILC cell lines MDA-MB-134-VI, SUM44PE, and BCK4 were used to assess WNT4 gene expression and regulation, as well as the role of WNT4 in estrogen-regulated proliferation. To assess these mechanisms in the context of endocrine resistance, we developed novel ILC endocrine-resistant long-term estrogen-deprived (ILC-LTED) models. ILC and ILC-LTED cell lines were used to identify upstream regulators and downstream signaling effectors of WNT4 signaling. ILC cells co-opted WNT4 signaling by placing it under direct ER control. We observed that ER regulation of WNT4 correlated with use of an ER binding site at the WNT4 locus, specifically in ILC cells. Further, WNT4 was required for endocrine response in ILC cells, as WNT4 knockdown blocked estrogen-induced proliferation. ILC-LTED cells remained dependent on WNT4 for proliferation, by either maintaining ER function and WNT4 regulation or uncoupling WNT4 from ER and upregulating WNT4 expression. In the latter case, WNT4 expression was driven by activated nuclear factor kappa-B signaling in ILC-LTED cells. In ILC and ILC-LTED cells, WNT4 led to suppression of CDKN1A/p21, which is critical for ILC cell proliferation. CDKN1A knockdown partially reversed the effects of WNT4 knockdown. WNT4 drives a novel signaling pathway in ILC cells, with a

Photoluminescence characterization of porous YAG: Yb{sup 3+}–Er{sup 3+} nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Desirena, H., E-mail: hagdes@cio.mx [Centro de Investigaciones en Óptica, A. P. 1-948, León 37150, Guanajuato (Mexico); Diaz-Torres, L.A. [Centro de Investigaciones en Óptica, A. P. 1-948, León 37150, Guanajuato (Mexico); Rodríguez, R.A. [Centro Universitario de Los Lagos, Universidad de Guadalajara, Lagos de Moreno, Jalisco (Mexico); Meza, O. [Instituto de Física, Benemérita Universidad Autónoma de Puebla, Apartado Postal J-48, Centro Historico 72570, Puebla (Mexico); Salas, P. [Centro de Física Aplicada y Tecnología Avanzada, Universidad Nacional Autónoma de México, Apartado Postal 1-1010, Querétaro 76000, Querétaro México (Mexico); Angeles-Chávez, C. [Instituto Mexicano del Petróleo, Ciudad México, D.F. 07730, México (Mexico); Tobar, E.H.; Castañeda-Contreras, J. [Centro Universitario de Los Lagos, Universidad de Guadalajara, Lagos de Moreno, Jalisco (Mexico); De la Rosa, E., E-mail: elder@cio.mx [Centro de Investigaciones en Óptica, A. P. 1-948, León 37150, Guanajuato (Mexico)

2014-09-15

Yb{sup 3+}/Er{sup 3+} codoped yttrium aluminium garnet (YAG) porous nanocrystals were prepared by glycolate method assisted with poly-vinyl alcohol (PVA) and urea. The typical cubic structure for YAG was confirmed from XRD with crystallite average size of ∼40 nm, calculated from Scherrer formula and corroborated by TEM. Strong green and red upconversion emissions are observed readily with the naked eyes, and the color coordinates were obtained from emission spectra. A theoretical model to calculate CIE coordinate as a function of donor (Yb{sup 3+}) and acceptors (Er{sup 3+}) concentration is proposed. The eye-safe near infrared emitted signal and fluorescence lifetime were also measured and results show lifetime as large as 8.5 ms. The maximum energy transfer efficiency from Yb{sup 3+} to Er{sup 3+} was 72% for 20 mol% of Yb{sub 2}O{sub 3}. The proposed mechanisms for signal emitted are explained in terms of direct and energy back transfer processes, and cross relaxation. - Highlights: • Strong upconversion emission were observed in YAG:Er{sup 3+}–Yb{sup 3+} samples. • Color emission can be tuned from green to red by choosing properly the Yb{sup 3+} concentration. • The experimental colour coordinates match very well with the proposed theoretical model. • Cross relaxation and energy back transfer are mainly responsible for the red emission. • Fluorescence lifetime of {sup 4}I{sub 13/2} level increase with the Yb{sup 3+} concentration.

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

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"...

Upregulation of ER signaling as an adaptive mechanism of cell survival in HER2-positive breast tumors treated with anti-HER2 therapy

Science.gov (United States)

Giuliano, Mario; Hu, Huizhong; Wang, Yen-Chao; Fu, Xiaoyong; Nardone, Agostina; Herrera, Sabrina; Mao, Sufeng; Contreras, Alejandro; Gutierrez, Carolina; Wang, Tao; Hilsenbeck, Susan G.; De Angelis, Carmine; Wang, Nicholas J.; Heiser, Laura M.; Gray, Joe W.; Lopez-Tarruella, Sara; Pavlick, Anne C.; Trivedi, Meghana V.; Chamness, Gary C.; Chang, Jenny C.; Osborne, C. Kent; Rimawi, Mothaffar F.; Schiff, Rachel

2015-01-01

Purpose To investigate the direct effect and therapeutic consequences of epidermal growth factor receptor 2 (HER2)-targeting therapy on expression of estrogen receptor (ER) and Bcl2 in preclinical models and clinical tumor samples. Experimental design Archived xenograft tumors from two preclinical models (UACC812 and MCF7/HER2-18) treated with ER and HER2-targeting therapies, and also HER2+ clinical breast cancer specimens collected in a lapatinib neoadjuvant trial (baseline and week 2 post treatment), were used. Expression levels of ER and Bcl2 were evaluated by immunohistochemistry and western blot. The effects of Bcl2 and ER inhibition, by ABT-737 and fulvestrant respectively, were tested in parental versus lapatinib-resistant UACC812 cells in vitro. Results Expression of ER and Bcl2 was significantly increased in xenograft tumors with acquired resistance to anti-HER2 therapy, compared with untreated tumors, in both preclinical models (UACC812: ER p=0.0014; Bcl2 p<0.001. MCF7/HER2-18: ER p=0.0007; Bcl2 p=0.0306). In the neoadjuvant clinical study, lapatinib treatment for two weeks was associated with parallel upregulation of ER and Bcl2 (Spearman’s coefficient: 0.70; p=0.0002). Importantly, 18% of tumors originally ER-negative (ER−) converted to ER+ upon anti-HER2 therapy. In ER−/HER2+ MCF7/HER2-18 xenografts, ER re-expression was primarily observed in tumors responding to potent combination of anti-HER2 drugs. Estrogen deprivation added to this anti-HER2 regimen significantly delayed tumor progression (p=0.018). In the UACC812 cells, fulvestrant, but not ABT-737, was able to completely inhibit anti-HER2-resistant growth (p<0.0001). Conclusion HER2 inhibition can enhance or restore ER expression with parallel Bcl2 upregulation, representing an ER-dependent survival mechanism potentially leading to anti-HER2 resistance. PMID:26015514

Designed modulation of sex steroid signaling inhibits telomerase activity and proliferation of human prostate cancer cells

International Nuclear Information System (INIS)

Verma, Vikas; Sharma, Vikas; Singh, Vishal; Sharma, Siddharth; Bishnoi, Ajay Kumar; Chandra, Vishal; Maikhuri, J.P.; Dwivedi, Anila; Kumar, Atul; Gupta, Gopal

2014-01-01

The predominant estrogen-receptor (ER)-β signaling in normal prostate is countered by increased ER-α signaling in prostate cancer (CaP), which in association with androgen-receptor (AR) signaling results in pathogenesis of the disease. However CaP treatments mostly target AR signaling which is initially effective but eventually leads to androgen resistance, hence simultaneous targeting of ERs has been proposed. A novel series of molecules were designed with multiple sex-steroid receptor modulating capabilities by coalescing the pharmacophores of known anti-CaP molecules that act via modulation of ER(α/β) and/or AR, viz. 3,3′diindolylmethane (DIM), mifepristone, toremifene, tamoxifen and raloxifene. N,N-diethyl-4-((2-(4-methoxyphenyl)-1H-indol-3-yl)methyl) aniline (DIMA) was identified as the most promising structure of this new series. DIMA increased annexin-V labelling, cell-cycle arrest and caspase-3 activity, and decreased expression of AR and prostate specific antigen in LNCaP cells, in vitro. Concurrently, DIMA increased ER-β, p21 and p27 protein levels in LNCaP cells and exhibited ∼ 5 times more selective binding for ER-β than ER-α, in comparison to raloxifene. DIMA exhibited a dose-dependent ER-β agonism and ER-α antagonism in classical gene reporter assay and decreased hTERT (catalytic subunit of telomerase) transcript levels in LNCaP at 3.0 μM (P < 0.05). DIMA also dose-dependently decreased telomerase enzyme activity in prostate cancer cells. It is thus concluded that DIMA acts as a multi-steroid receptor modulator and effectively inhibits proliferation of prostate cancer cells through ER-β mediated telomerase inhibition, by countering actions of ER-α and AR. Its unique molecular design can serve as a lead structure for generation of potent agents against endocrine malignancies like the CaP

Designed modulation of sex steroid signaling inhibits telomerase activity and proliferation of human prostate cancer cells

Energy Technology Data Exchange (ETDEWEB)

Verma, Vikas; Sharma, Vikas; Singh, Vishal [Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226 031 (India); Sharma, Siddharth; Bishnoi, Ajay Kumar [Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226 031 (India); Chandra, Vishal; Maikhuri, J.P.; Dwivedi, Anila [Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226 031 (India); Kumar, Atul [Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226 031 (India); Gupta, Gopal, E-mail: g_gupta@cdri.res.in [Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226 031 (India)

2014-10-15

The predominant estrogen-receptor (ER)-β signaling in normal prostate is countered by increased ER-α signaling in prostate cancer (CaP), which in association with androgen-receptor (AR) signaling results in pathogenesis of the disease. However CaP treatments mostly target AR signaling which is initially effective but eventually leads to androgen resistance, hence simultaneous targeting of ERs has been proposed. A novel series of molecules were designed with multiple sex-steroid receptor modulating capabilities by coalescing the pharmacophores of known anti-CaP molecules that act via modulation of ER(α/β) and/or AR, viz. 3,3′diindolylmethane (DIM), mifepristone, toremifene, tamoxifen and raloxifene. N,N-diethyl-4-((2-(4-methoxyphenyl)-1H-indol-3-yl)methyl) aniline (DIMA) was identified as the most promising structure of this new series. DIMA increased annexin-V labelling, cell-cycle arrest and caspase-3 activity, and decreased expression of AR and prostate specific antigen in LNCaP cells, in vitro. Concurrently, DIMA increased ER-β, p21 and p27 protein levels in LNCaP cells and exhibited ∼ 5 times more selective binding for ER-β than ER-α, in comparison to raloxifene. DIMA exhibited a dose-dependent ER-β agonism and ER-α antagonism in classical gene reporter assay and decreased hTERT (catalytic subunit of telomerase) transcript levels in LNCaP at 3.0 μM (P < 0.05). DIMA also dose-dependently decreased telomerase enzyme activity in prostate cancer cells. It is thus concluded that DIMA acts as a multi-steroid receptor modulator and effectively inhibits proliferation of prostate cancer cells through ER-β mediated telomerase inhibition, by countering actions of ER-α and AR. Its unique molecular design can serve as a lead structure for generation of potent agents against endocrine malignancies like the CaP.

Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis.

Science.gov (United States)

Song, Yu-Feng; Hogstrand, Christer; Wei, Chuan-Chuan; Wu, Kun; Pan, Ya-Xiong; Luo, Zhi

2017-09-01

The present study was performed to determine the effect of Zn exposure influencing endoplasmic reticulum (ER) stress, explore the underlying molecular mechanism of Zn-induced hepatic lipolysis in a fish species of significance for aquaculture, yellow catfish Pelteobagrus fulvidraco. We found that waterborne Zn exposure evoked ER stress and unfolded protein response (UPR), and activated cAMP/PKA pathway, and up-regulated hepatic lipolysis. The increase in ER stress and lipolysis were associated with activation of cAMP/PKA signaling pathway. Zn also induced an increase in intracellular Ca 2+ level, which could be partially prevented by dantrolene (RyR receptor inhibitor) and 2-APB (IP3 receptor inhibitor), demonstrating that the disturbed Ca 2+ homeostasis in ER contributed to ER stress and dysregulation of lipolysis. Inhibition of ER stress by PBA attenuated UPR, inhibited the activation of cAMP/PKA pathway and resulted in down-regulation of lipolysis. Inhibition of protein kinase RNA-activated-like ER kinase (PERK) by GSK2656157 and inositol-requiring enzyme (IRE) by STF-083010 differentially influenced Zn-induced changes of lipid metabolism, indicating that PERK and IRE pathways played different regulatory roles in Zn-induced lipolysis. Inhibition of PKA by H89 blocked the Zn-induced activation of cAMP/PKA pathway with a concomitant inhibition of ER stress-mediated lipolysis. Taken together, our findings highlight the importance of the ER stress-cAMP/PKA axis in Zn-induced lipolysis, which provides new insights into Zn toxicology in fish and probably in other vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ozone (O{sub 3}) elicits neurotoxicity in spinal cord neurons (SCNs) by inducing ER Ca{sup 2+} release and activating the CaMKII/MAPK signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Li, Yun; Lin, Xiaowen; Zhao, XueJun; Xie, Juntian; JunNan, Wang; Sun, Tao; Fu, Zhijian, E-mail: zhijian_fu@163.com

2014-11-01

Ozone (O{sub 3}) is widely used in the treatment of spinal cord related diseases. Excess or accumulation of this photochemical air can however be neurotoxic. In this study, in vitro cultured Wister rat spinal cord neurons (SCNs) were used to investigate the detrimental effects and underlying mechanisms of O{sub 3}. Ozone in a dose-dependent manner inhibited cell viability at a range of 20 to 500 μg/ml, with the dose at 40 μg/ml resulting in a decrease of cell viability to 75%. The cell death after O{sub 3} exposure was related to endoplasmic reticulum (ER) calcium (Ca{sup 2+}) release. Intracellular Ca{sup 2+} chelator, ER stabilizer (inositol 1,4,5-trisphosphate receptor (IP3R) antagonist and ryanodine receptor (RyR) antagonist) and calcium/calmodulin-dependent protein kinase II (CaMKII) antagonist could effectively block Ca{sup 2+} mobilization and inhibit cell death following 40 μg/ml O{sub 3} exposure. In addition, ER Ca{sup 2+} release due to O{sub 3} exposure enhanced phospho-p38 and phospho-JNK levels and apoptosis of SCNs through activating CaMKII. Based on these results, we confirm that ozone elicits neurotoxicity in SCNs via inducing ER Ca{sup 2+} release and activating CaMKII/MAPK signaling pathway. Therefore, physicians should get attention to the selection of treatment concentrations of oxygen/ozone. And, approaches, such as chelating intracellular Ca{sup 2+} and stabilizing neuronal Ca{sup 2+} homeostasis could effectively ameliorate the neurotoxicity of O{sub 3}. - Highlights: • Exposure to O{sub 3} can reduce the viability of SCNs and cause the cell death. • Exposure to O{sub 3} can trigger RyR and IP3R dependent intracellular Ca{sup 2+} release. • Exposure to O{sub 3} can enhance the phospho-CaMKII, phospho-JNK and phospho-p38 levels.

Membrane-initiated non-genomic signaling by estrogens in the hypothalamus: cross-talk with glucocorticoids with implications for behavior

Directory of Open Access Journals (Sweden)

Jennifer eRainville

2015-02-01

Full Text Available The estrogen receptor (ER and glucocorticoid receptor (GR are members of the nuclear receptor superfamily that can signal using both non-genomic and genomic transcriptional modes. Though genomic modes of signaling have been well characterized and several behaviors attributed to this signaling mechanism, the physiological significance of non-genomic modes of signaling has not been well understood. This has partly been due to the controversy regarding the identity of the membrane ER (mER or membrane GR (mGR that may mediate rapid, non-genomic signaling and the downstream signaling cascades that may result as a consequence of steroid ligands binding the mER or the mGR. Both estrogens and glucocorticoids exert a number of actions on the hypothalamus, including feedback. This review focuses on the various candidates for the mER or mGR in the hypothalamus and the contribution of non-genomic signaling to classical hypothalamically-driven behaviors and changes in neuronal morphology. It also attempts to categorize some of the possible functions of non-genomic signaling at both the cellular level and at the organismal level that are relevant for behavior, including some behaviors that are regulated by both estrogens and glucocorticoids in a potentially synergistic manner. Lastly, it attempts to show that steroid signaling via non-genomic modes may provide the organism with rapid behavioral responses to stimuli.

ERK1/2 signalling protects against apoptosis following endoplasmic reticulum stress but cannot provide long-term protection against BAX/BAK-independent cell death.

Science.gov (United States)

Darling, Nicola J; Balmanno, Kathryn; Cook, Simon J

2017-01-01

Disruption of protein folding in the endoplasmic reticulum (ER) causes ER stress. Activation of the unfolded protein response (UPR) acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is thought to proceed through the cell intrinsic, mitochondrial pathway. Indeed, cells that lack the key executioner proteins BAX and BAK are protected from ER stress-induced apoptosis. Here we show that chronic ER stress causes the progressive inhibition of the extracellular signal-regulated kinase (ERK1/2) signalling pathway. This is causally related to ER stress since reactivation of ERK1/2 can protect cells from ER stress-induced apoptosis whilst ERK1/2 pathway inhibition sensitises cells to ER stress. Furthermore, cancer cell lines harbouring constitutively active BRAFV600E are addicted to ERK1/2 signalling for protection against ER stress-induced cell death. ERK1/2 signalling normally represses the pro-death proteins BIM, BMF and PUMA and it has been proposed that ER stress induces BIM-dependent cell death. We found no evidence that ER stress increased the expression of these proteins; furthermore, BIM was not required for ER stress-induced death. Rather, ER stress caused the PERK-dependent inhibition of cap-dependent mRNA translation and the progressive loss of pro-survival proteins including BCL2, BCLXL and MCL1. Despite these observations, neither ERK1/2 activation nor loss of BAX/BAK could confer long-term clonogenic survival to cells exposed to ER stress. Thus, ER stress induces cell death by at least two biochemically and genetically distinct pathways: a classical BAX/BAK-dependent apoptotic response that can be inhibited by ERK1/2 signalling and an alternative ERK1/2- and BAX/BAK-independent cell death pathway.

ERK1/2 signalling protects against apoptosis following endoplasmic reticulum stress but cannot provide long-term protection against BAX/BAK-independent cell death.

Directory of Open Access Journals (Sweden)

Nicola J Darling

Full Text Available Disruption of protein folding in the endoplasmic reticulum (ER causes ER stress. Activation of the unfolded protein response (UPR acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is thought to proceed through the cell intrinsic, mitochondrial pathway. Indeed, cells that lack the key executioner proteins BAX and BAK are protected from ER stress-induced apoptosis. Here we show that chronic ER stress causes the progressive inhibition of the extracellular signal-regulated kinase (ERK1/2 signalling pathway. This is causally related to ER stress since reactivation of ERK1/2 can protect cells from ER stress-induced apoptosis whilst ERK1/2 pathway inhibition sensitises cells to ER stress. Furthermore, cancer cell lines harbouring constitutively active BRAFV600E are addicted to ERK1/2 signalling for protection against ER stress-induced cell death. ERK1/2 signalling normally represses the pro-death proteins BIM, BMF and PUMA and it has been proposed that ER stress induces BIM-dependent cell death. We found no evidence that ER stress increased the expression of these proteins; furthermore, BIM was not required for ER stress-induced death. Rather, ER stress caused the PERK-dependent inhibition of cap-dependent mRNA translation and the progressive loss of pro-survival proteins including BCL2, BCLXL and MCL1. Despite these observations, neither ERK1/2 activation nor loss of BAX/BAK could confer long-term clonogenic survival to cells exposed to ER stress. Thus, ER stress induces cell death by at least two biochemically and genetically distinct pathways: a classical BAX/BAK-dependent apoptotic response that can be inhibited by ERK1/2 signalling and an alternative ERK1/2- and BAX/BAK-independent cell death pathway.

Er3+ phosphate glass optical waveguide amplifiers at 1.5 μm on silicon

Science.gov (United States)

Yan, Yingchao; Faber, Anne J.; de Waal, Henk

1996-01-01

RF-sputtering techniques were employed to produce Er-doped phosphate glass films on thermally oxidized silicon wafers. Film compositions were characterized by X-ray photoelectron spectroscopy. As-deposited films showed very low Er luminescence lifetimes. By postannealing of deposited films in pure oxygen, Er photoluminescence emission lifetime of the 4I13/2 - 4I15/2 transition could be increased from 1 - 2 ms to 8 - 9 ms. The long Er lifetime of the deposited films is very promising for achieving an optical gain. A dependence of measured lifetimes on pump power was observed which are related to a up-conversion quenching process. After postannealing, the sputtered waveguides showed relatively low attenuation loss at the potential pumping and signaling wavelengths. The loss spectrum from 700 nm to 1600 nm was measured by two-prism coupling. The films were easy to be patterned by lithography and ridge channel waveguides were developed by argon plasma etching.

Aging induced ER stress alters sleep and sleep homeostasis

OpenAIRE

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

2013-01-01

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 ...

ER EXPORT AND SURFACE TARGETING OF THE DOPAMINE TRANSPORTER ARE DEPENDENT ON THE DISTAL C-TERMINUS BUT OCCURS INDEPENDENTLY OF PDZ DOMAIN INTERACTIONS

DEFF Research Database (Denmark)

Bjerggaard(Vægter), Christian; Loland, Claus; Hastrup, Hanne

. Neuron 2001, 30:121-34). As expected, we find that deletion of the PDZ binding sequence (LKV) or substitution with three histidines resulted in retention of hDAT in the ER in both HEK293 and N2A neuroblastoma cells. However, substitution of LKV with the type 2 PDZ binding sequence SLL of the beta2...

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

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....

Interaction between endoplasmic/sarcoplasmic reticulum stress (ER/SR stress), mitochondrial signaling and Ca(2+) regulation in airway smooth muscle (ASM).

Science.gov (United States)

Delmotte, Philippe; Sieck, Gary C

2015-02-01

Airway inflammation is a key aspect of diseases such as asthma. Several inflammatory cytokines (e.g., TNFα and IL-13) increase cytosolic Ca(2+) ([Ca(2+)]cyt) responses to agonist stimulation and Ca(2+) sensitivity of force generation, thereby enhancing airway smooth muscle (ASM) contractility (hyper-reactive state). Inflammation also induces ASM proliferation and remodeling (synthetic state). In normal ASM, the transient elevation of [Ca(2+)]cyt induced by agonists leads to a transient increase in mitochondrial Ca(2+) ([Ca(2+)]mito) that may be important in matching ATP production with ATP consumption. In human ASM (hASM) exposed to TNFα and IL-13, the transient increase in [Ca(2+)]mito is blunted despite enhanced [Ca(2+)]cyt responses. We also found that TNFα and IL-13 induce reactive oxidant species (ROS) formation and endoplasmic/sarcoplasmic reticulum (ER/SR) stress (unfolded protein response) in hASM. ER/SR stress in hASM is associated with disruption of mitochondrial coupling with the ER/SR membrane, which relates to reduced mitofusin 2 (Mfn2) expression. Thus, in hASM it appears that TNFα and IL-13 result in ROS formation leading to ER/SR stress, reduced Mfn2 expression, disruption of mitochondrion-ER/SR coupling, decreased mitochondrial Ca(2+) buffering, mitochondrial fragmentation, and increased cell proliferation.

Progesterone receptors (PR) mediate STAT actions: PR and prolactin receptor signaling crosstalk in breast cancer models.

Science.gov (United States)

Leehy, Katherine A; Truong, Thu H; Mauro, Laura J; Lange, Carol A

2018-02-01

Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy. Indeed, these pathways are fully integrated via activation of shared signaling pathways (i.e. JAKs, MAPKs) as well as by the convergence of PRs and STATs at target genes relevant to both mammary gland biology and breast cancer progression (i.e. proliferation, stem cell outgrowth, tissue cell type heterogeneity). Thus, rather than a single mediator such as ER, transcription factor cascades (ER>PR>STATs) are responsible for rapid proliferative and developmental programming in the normal mammary gland. It is not surprising that these same mediators typify uncontrolled proliferation in a majority of breast cancers, where ER and PR are most often co-expressed and may cooperate to drive malignant tumor progression. This review will primarily focus on the integration of PR and PRL signaling in breast cancer models and the importance of this cross-talk in cancer progression in the context of mammographic density. Components of these PR/PRL signaling pathways could offer alternative drug targets and logical complements to anti-ER or anti-estrogen-based endocrine therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

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....

ER-tethered Transcription Factor CREBH Regulates Hepatic Lipogenesis, Fatty Acid Oxidation, and Lipolysis upon Metabolic Stress

OpenAIRE

Zhang, Chunbin; Wang, Guohui; Zheng, Ze; Maddipati, Krishna Rao; Zhang, Xuebao; Dyson, Gregory; Williams, Paul; Duncan, Stephen A.; Kaufman, Randal J.; Zhang, Kezhong

2012-01-01

CREBH is a liver-specific transcription factor that is localized in the endoplasmic reticulum (ER) membrane. Our previous work demonstrated that CREBH is activated by ER stress or inflammatory stimuli to induce an acute-phase hepatic inflammation. Here we demonstrate that CREBH is a key metabolic regulator of hepatic lipogenesis, fatty acid (FA) oxidation, and lipolysis under metabolic stress. Saturated FA, insulin signals, or an atherogenic high-fat diet can induce CREBH activation in the li...

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.

Activation of PERK signaling through fluoride-mediated endoplasmic reticulum stress in OS732 cells

International Nuclear Information System (INIS)

Xu, Hui; Zhou, Yu-lai; Zhang, Xiu-yun; Lu, Peng; Li, Guang-sheng

2010-01-01

Our proteomical analysis of osteoblasts exposed to fluoride revealed a distinctive upregulation of proteins in osteoblast. These upregulated proteins play key roles in the protein folding. The PRK-like ER kinase (PERK) signaling, one branch of unfolded protein response (UPR) to combat ER stress, is a transcription factor needed for osteoblast proliferation and differentiation. The mechanism of skeletal fluorosis by which fluoride regulates osteoblast is not fully defined. Here we studied the effect of fluoride on PERK signaling genes and x-box binding protein 1 (xbp-1) in OS7232 cells (human osteoblast-like cell line). Meantime, genes associated with bone turnover were examined in this study. We found that early and continuous fluoride exposure increased the binding immunoglobulin protein (BiP) expression and activated the PERK signaling pathway, resulting in activation of transcription factor 4 (ATF4) and nuclear factor erythroid 2-related factor 2 (Nrf2). The altered expression of cbfa1, osteoprotegerin (OPG)/nuclear factor kappa B ligand (RANKL) were viewed in this study. These results showed fluoride impelled a distinctive ER stress response in OS732 cells, primarily by activating PERK and PERK-dependent signaling. Little effects were viewed for activating xbp-1, a common target of the other two canonical sensors of ER stress, ATF6 and IRE1. In this study the altered expression of bone turnover genes were consistent with activation of ER stress and PERK signaling. This study proved that PERK signaling play major roles in action of fluoride on osteoblast, and suggested that bone response in skeletal fluorosis may be due in part to PERK signaling pathway.

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.

Optimizing signal intensity correction during evaluation of hepatic parenchymal enhancement on gadoxetate disodium-enhanced MRI: Comparison of three methods

International Nuclear Information System (INIS)

Onoda, Minori; Hyodo, Tomoko; Murakami, Takamichi; Okada, Masahiro; Uto, Tatsuro; Hori, Masatoshi; Miyati, Tosiaki

2015-01-01

Highlights: •Signal intensity is often used to evaluate hepatic enhancement with Gd-EOB-DTPA in the hepatobiliary phase. •Comparison of uncorrected signal intensity with T 1 value revealed signal intensity instability. •Measurement of uncorrected liver SI or SNR often yields erroneous results on late-phase gadoxetate MRI due to shimming and other optimization techniques. •Signal intensity corrected by scale and rescale slope from DICOM data gave comparable results. -- Abstract: Objective: To compare signal intensity (SI) correction using scale and rescale slopes with SI correction using SIs of spleen and muscle for quantifying multiphase hepatic contrast enhancement with Gd-EOB-DTPA by assessing their correlation with T 1 values generated from Look-Locker turbo-field-echo (LL-TFE) sequence data (ER-T 1 ). Materials and methods: Thirty patients underwent Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in this prospective clinical study. For each patient, breath-hold T 1 -weighted fat-suppressed three-dimensional (3D) gradient echo sequences (e-THRIVE) were acquired before and 2 (first phase), 10 (second phase), and 20 min (third phase) after intravenous Gd-EOB-DTPA. Look-Locker turbo-field-echo (LL-TFE) sequences were acquired before and 1.5 (first phase), 8 (second phase), and 18 min (third phase) postcontrast. The liver parenchyma enhancement ratios (ER) of each phase were calculated using the SI from e-THRIVE sequences (ER-SI) and the T 1 values generated from LL-TFE sequence data (ER-T 1 ) respectively. ER-SIs were calculated in three ways: (1) comparing with splenic SI (ER-SI-s), (2) comparing with muscle SI (ER-SI-m), (3) using scale and rescale slopes obtained from DICOM headers (ER-SI-c), to eliminate the effects of receiver gain and scaling. For each of the first, second and third phases, correlation and agreement were assessed between each ER-SI and ER-T 1 . Results: In the first phase, all ER-SIs correlated weakly with ER-T 1 . In the second

Mate retention tactics in Spain: personality, sex differences, and relationship status.

Science.gov (United States)

de Miguel, Adelia; Buss, David M

2011-06-01

Mate retention is an important problem in romantic relationships because of mate poachers, infidelity, and the risk of outright defection. The current study (N=892) represents the first study of mate retention tactics conducted in Spain. We tested hypotheses about the effects of gender, relationship commitment status, and personality on mate retention tactics. Women and men differed in the use of resource display, appearance enhancement, intrasexual violence, and submission/self-abasement as mate retention tactics. Those in more committed relationships reported higher levels of resource display, appearance enhancement, love, and verbal signals of possession. Those in less committed relationships more often reported intentionally evoking jealousy in their partner as a mate retention tactic. Personality characteristics, particularly Neuroticism and Agreeableness, correlated in coherent ways with mate retention tactics, supporting two evolution-based hypotheses. Discussion focuses on the implications, future research directions, and interdisciplinary syntheses emerging between personality and social psychology and evolutionary psychology. © 2011 The Authors. Journal of Personality © 2011, Wiley Periodicals, Inc.

Site of Er ions in silica layers codoped with Si nanoclusters and Er

International Nuclear Information System (INIS)

Pellegrino, P.; Garrido, B.; Arbiol, J.; Garcia, C.; Lebour, Y.; Morante, J.R.

2006-01-01

Silica layers implanted with Si and Er ions to various doses and annealed at 950 deg. C have been investigated by means of energy-filtered transmission electron microscopy (EFTEM) and high annular angle dark field (HAADF). EFTEM analysis reveals Si nanoclusters (Si-nc) with an average size around 3 nm for high Si content (15 at. %) whereas no clusters can be imaged for the lowest Si excess (5 at. %). Raman scattering supports that amorphous Si precipitates are present in all the samples. Moreover, the filtered images show that Er ions appear preferentially located outside the Si-nc. HAADF analysis confirms that the Er atoms form agglomerations of 5-10 nm size when the Er concentration exceeds 1x10 20 cm -3 . This observation correlates well with the reduction of the Er population excitable by Si nanoclusters, in the best case corresponding to 10% of the total. A suitable tuning of the annealing drastically reduces this deleterious effect

A Comparative Study of Er3+, Er3+-Eu3+, Er3+-Tb3+, and Er3+-Eu3+-Tb3+ Codoped Y2O3 Nanoparticles as Optical Heaters

Directory of Open Access Journals (Sweden)

G. A. Sobral

2015-01-01

Full Text Available Fluorescence intensity ratio (FIR technique, based on the thermal coupling of H11/22 and S3/24 energy levels of erbium ions, was used to study the optical heating behavior of rare earth doped yttrium oxide nanophosphors (Y2O3:Er3+, Y2O3:Er3+-Eu3+, Y2O3:Er3+-Tb3+, and Y2O3:Er3+-Eu3+-Tb3+ synthesized via PVA-assisted sol-gel route. The samples were optically heated by an 800 nm CW diode laser, while the upconverted green emissions were used to measure their temperatures in real time. The experimental results indicate that the studied nanoparticles are promising candidates to applications such as photothermal treatments and hyperthermia.

Fluxus-øer

DEFF Research Database (Denmark)

van der Meijden, Peter Alexander

2008-01-01

"Fluxus-øer" er en introduktion til Fluxus med udgangspunkt i den tyske galleri-ejer René Blocks samling, som udstillingen "Food for Thought" i Sukkerfabrikken i Stege (Møn) præsenterede et udvalg af. Artiklen beskriver Fluxus som et heterotopi som beskrevet af Michel Foucault i "Of Other Spaces"...

Effect of the unfolded protein response on ER protein export: a potential new mechanism to relieve ER stress.

Science.gov (United States)

Shaheen, Alaa

2018-05-05

The unfolded protein response (UPR) is an adaptive cellular response that aims to relieve endoplasmic reticulum (ER) stress via several mechanisms, including inhibition of protein synthesis and enhancement of protein folding and degradation. There is a controversy over the effect of the UPR on ER protein export. While some investigators suggested that ER export is inhibited during ER stress, others suggested the opposite. In this article, their conflicting studies are analyzed and compared in attempt to solve this controversy. The UPR appears indeed to enhance ER export, possibly via multiple mechanisms. However, another factor, which is the integrity of the folding machinery/environment inside ER, determines whether ER export will appear increased or decreased during experimentation. Also, different methods of stress induction appear to have different effects on ER export. Thus, improvement of ER export may represent a new mechanism by which the UPR alleviates ER stress. This may help researchers to understand how the UPR works inside cells and how to manipulate it to alter cell fate during stress, either to promote cell survival or death. This may open up new approaches for the treatment of ER stress-related diseases.

Optical signal inverter of erbium-doped yttrium aluminum garnet with red shift of laser diodes.

Science.gov (United States)

Maeda, Y

1994-08-10

An optical signal inverter was demonstrated in a simple structure that combined a laser diode with Er-doped YAG crystal. The optical signal inversion occurred at a response time of 7 ns and was caused by the decrease of transmission of Er:YAG against the red shift of the wavelength of the laser diode.

CDIP1-BAP31 Complex Transduces Apoptotic Signals from Endoplasmic Reticulum to Mitochondria under Endoplasmic Reticulum Stress

Directory of Open Access Journals (Sweden)

Takushi Namba

2013-10-01

Full Text Available Resolved endoplasmic reticulum (ER stress response is essential for intracellular homeostatic balance, but unsettled ER stress can lead to apoptosis. Here, we show that a proapoptotic p53 target, CDIP1, acts as a key signal transducer of ER-stress-mediated apoptosis. We identify B-cell-receptor-associated protein 31 (BAP31 as an interacting partner of CDIP1. Upon ER stress, CDIP1 is induced and enhances an association with BAP31 at the ER membrane. We also show that CDIP1 binding to BAP31 is required for BAP31 cleavage upon ER stress and for BAP31-Bcl-2 association. The recruitment of Bcl-2 to the BAP31-CDIP1 complex, as well as CDIP1-dependent truncated Bid (tBid and caspase-8 activation, contributes to BAX oligomerization. Genetic knockout of CDIP1 in mice leads to impaired response to ER-stress-mediated apoptosis. Altogether, our data demonstrate that the CDIP1/BAP31-mediated regulation of mitochondrial apoptosis pathway represents a mechanism for establishing an ER-mitochondrial crosstalk for ER-stress-mediated apoptosis signaling.

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?...

Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-κB regulation

Science.gov (United States)

Chhunchha, Bhavana; Fatma, Nigar; Kubo, Eri; Rai, Prerana; Singh, Sanjay P.

2013-01-01

Oxidative stress and endoplasmic reticulum (ER) stress are emerging as crucial events in the etiopathology of many neurodegenerative diseases. While the neuroprotective contributions of the dietary compound curcumin has been recognized, the molecular mechanisms underlying curcumin's neuroprotection under oxidative and ER stresses remains elusive. Herein, we show that curcumin protects HT22 from oxidative and ER stresses evoked by the hypoxia (1% O2 or CoCl2 treatment) by enhancing peroxiredoxin 6 (Prdx6) expression. Cells exposed to CoCl2 displayed reduced expression of Prdx6 with higher reactive oxygen species (ROS) expression and activation of NF-κB with IκB phosphorylation. When NF-κB activity was blocked by using SN50, an inhibitor of NF-κB, or cells treated with curcumin, the repression of Prdx6 expression was restored, suggesting the involvement of NF-κB in modulating Prdx6 expression. These cells were enriched with an accumulation of ER stress proteins, C/EBP homologous protein (CHOP), GRP/78, and calreticulin, and had activated states of caspases 12, 9, and 3. Reinforced expression of Prdx6 in HT22 cells by curcumin reestablished survival signaling by reducing propagation of ROS and blunting ER stress signaling. Intriguingly, knockdown of Prdx6 by antisense revealed that loss of Prdx6 contributed to cell death by sustaining enhanced levels of ER stress-responsive proapoptotic proteins, which was due to elevated ROS production, suggesting that Prdx6 deficiency is a cause of initiation of ROS-mediated ER stress-induced apoptosis. We propose that using curcumin to reinforce the naturally occurring Prdx6 expression and attenuate ROS-based ER stress and NF-κB-mediated aberrant signaling improves cell survival and may provide an avenue to treat and/or postpone diseases associated with ROS or ER stress. PMID:23364261

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.

‘WNT-er is coming’: WNT signalling in chronic lung diseases

Science.gov (United States)

Baarsma, H A

2017-01-01

Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD. While many studies have focused on the canonical WNT/β-catenin signalling pathway, recent reports highlight that non-canonical WNT signalling may also significantly contribute to chronic lung pathologies; these studies will be particularly featured in this review. We further discuss recent advances uncovering the role of WNT signalling early in life, the potential of pharmaceutically modulating WNT signalling pathways and highlight (pre)clinical studies describing promising new therapies for chronic lung diseases. PMID:28416592

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...

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

Optimizing signal intensity correction during evaluation of hepatic parenchymal enhancement on gadoxetate disodium-enhanced MRI: Comparison of three methods

Energy Technology Data Exchange (ETDEWEB)

Onoda, Minori, E-mail: onoda@radt.med.kindai.ac.jp [Department of Radiological Technology, Kinki University Hospital, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942 (Japan); Hyodo, Tomoko, E-mail: neneth@m.ehime-u.ac.jp [Department of Radiology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Murakami, Takamichi, E-mail: murakami@med.kindai.ac.jp [Department of Radiology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Okada, Masahiro, E-mail: okada777@med.u-ryukyu.ac.jp [Department of Radiology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Uto, Tatsuro, E-mail: chuho@med.kindai.ac.jp [Department of Radiological Technology, Kinki University Hospital, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Hori, Masatoshi, E-mail: mhori@radiol.med.osaka-u.ac.jp [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Miyati, Tosiaki, E-mail: ramiyati@mhs.mp.kanazawa-u.ac.jp [Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942 (Japan)

2015-03-15

Highlights: •Signal intensity is often used to evaluate hepatic enhancement with Gd-EOB-DTPA in the hepatobiliary phase. •Comparison of uncorrected signal intensity with T{sub 1} value revealed signal intensity instability. •Measurement of uncorrected liver SI or SNR often yields erroneous results on late-phase gadoxetate MRI due to shimming and other optimization techniques. •Signal intensity corrected by scale and rescale slope from DICOM data gave comparable results. -- Abstract: Objective: To compare signal intensity (SI) correction using scale and rescale slopes with SI correction using SIs of spleen and muscle for quantifying multiphase hepatic contrast enhancement with Gd-EOB-DTPA by assessing their correlation with T{sub 1} values generated from Look-Locker turbo-field-echo (LL-TFE) sequence data (ER-T{sub 1}). Materials and methods: Thirty patients underwent Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in this prospective clinical study. For each patient, breath-hold T{sub 1}-weighted fat-suppressed three-dimensional (3D) gradient echo sequences (e-THRIVE) were acquired before and 2 (first phase), 10 (second phase), and 20 min (third phase) after intravenous Gd-EOB-DTPA. Look-Locker turbo-field-echo (LL-TFE) sequences were acquired before and 1.5 (first phase), 8 (second phase), and 18 min (third phase) postcontrast. The liver parenchyma enhancement ratios (ER) of each phase were calculated using the SI from e-THRIVE sequences (ER-SI) and the T{sub 1} values generated from LL-TFE sequence data (ER-T{sub 1}) respectively. ER-SIs were calculated in three ways: (1) comparing with splenic SI (ER-SI-s), (2) comparing with muscle SI (ER-SI-m), (3) using scale and rescale slopes obtained from DICOM headers (ER-SI-c), to eliminate the effects of receiver gain and scaling. For each of the first, second and third phases, correlation and agreement were assessed between each ER-SI and ER-T{sub 1}. Results: In the first phase, all ER-SIs correlated

Metabolomics er fremtiden

DEFF Research Database (Denmark)

Pedersern, Birger

2010-01-01

Forskningen i fødevarer har fået et potent redskab i hånden. Metabolomics er vejen frem, mener professor Søren Balling Engelsen fra Københavns Universitet......Forskningen i fødevarer har fået et potent redskab i hånden. Metabolomics er vejen frem, mener professor Søren Balling Engelsen fra Københavns Universitet...

Innovation er brugerdreven!

DEFF Research Database (Denmark)

Helms, Niels Henrik

2008-01-01

Brugerdreven innovation er blevet svaret på mange af de udfordringer, som vores moderne samfund står overfor.Det er skrevet ind i såvel regeringsgrundlaget som i de forskellige tiltag, som skal ruste Danmark i forhold til globaliseringen. Vi har ifølge argumentationen her enrække særlige forudsæt....... Udgivelsesdato: marts 2008...

Søer 2000

DEFF Research Database (Denmark)

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

styrke det fagli-ge grundlag for de mil-jøpolitiske prioriteringer og beslut-ninger. En væsentlig del af denne opgave er overvågning af miljø og natur. Det er derfor et naturligt led i Danmarks Miljø-undersø-gelsers opgave at forestå den landsdækkende rapportering af overvågnings-program-met inden...

Jeg Er blevet FRANKofil

DEFF Research Database (Denmark)

Andersson, Lasse

2014-01-01

afhængig af Frank Underwood fra serien House of Cards på den fremadstormende TV-streamingstjenesten Netflix. Jeg har opdaget et nyt internetbaseret datingforhold. Et surrealt, fedt miks af det kyniske og joviale personificeret i karakteren Frank Underwood, som er helt igennem ubehagelig, men fantastisk...... spillet af Kevin Spacey. Og tak til Spacey der for en tid har forladt teateret ’The Old Vic’ i London for at begejstre mig. Der er generelt to årsager til mine FRANKofile tilbøjeligheder. For det første er Netflix’s remake af den tyve år gamle BBC serie House of Cards efter min menig et stykke tv...... anden grund, til at jeg er blevet Frankofil, er, at jeg ikke skal sidde og vente på næste søndag efter søndag efter søndag for at få lov at se næste afsnit. Netflix lagde alle tretten timer af sæson 2 ud på nettet. Jeg afgør selv, hvornår jeg skal have mere Frank! Men på trods af mit narkomanlignende...

Online Mate-Retention Tactics on Facebook Are Associated With Relationship Aggression.

Science.gov (United States)

Brem, Meagan J; Spiller, Laura C; Vandehey, Michael A

2015-10-01

A measure of Facebook-related mate-retention tactics was developed to investigate the relationship between online behaviors and intimate partner aggression. One hundred and seventy-seven young adults (65 men, 112 women) completed questionnaires that included measures of online and offline mate-retention tactics, Facebook jealousy, Facebook surveillance, and intimate partner violence. A factor analysis yielded four subscales for the Facebook Mate-Retention Tactic Inventory (FMRTI): Care and Affection, Jealousy and Surveillance, Possession Signals, and Punishment of Infidelity Threat. The FMRTI total scores were positively correlated with Facebook jealousy, Facebook surveillance, and use of offline mate-retention tactics. The Jealousy and Surveillance subscale uniquely predicted intimate partner psychological and physical aggression over and above existing measures. Facebook mate-retention tactics fully mediated the relation between Facebook jealousy and both intimate partner psychological and physical aggression. The current study provides preliminary evidence for conceptualizing Facebook as an environment for the use of mate-retention tactics that have real-life implications for intimate partner violence. © The Author(s) 2014.

Liver Inflammation and Metabolic Signaling in ApcMin/+ Mice: The Role of Cachexia Progression

Science.gov (United States)

Narsale, Aditi A.; Enos, Reilly T.; Puppa, Melissa J.; Chatterjee, Saurabh; Murphy, E. Angela; Fayad, Raja; Pena, Majorette O’; Durstine, J. Larry; Carson, James A.

2015-01-01

The ApcMin/+ mouse exhibits an intestinal tumor associated loss of muscle and fat that is accompanied by chronic inflammation, insulin resistance and hyperlipidemia. Since the liver governs systemic energy demands through regulation of glucose and lipid metabolism, it is likely that the liver is a pathological target of cachexia progression in the ApcMin/+ mouse. The purpose of this study was to determine if cancer and the progression of cachexia affected liver endoplasmic reticulum (ER)-stress, inflammation, metabolism, and protein synthesis signaling. The effect of cancer (without cachexia) was examined in wild-type and weight-stable ApcMin/+ mice. Cachexia progression was examined in weight-stable, pre-cachectic, and severely-cachectic ApcMin/+ mice. Livers were analyzed for morphology, glycogen content, ER-stress, inflammation, and metabolic changes. Cancer induced hepatic expression of ER-stress markers BiP (binding immunoglobulin protein), IRE-1α (endoplasmic reticulum to nucleus signaling 1), and inflammatory intermediate STAT-3 (signal transducer and activator of transcription 3). While gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was suppressed by cancer, glycogen content or protein synthesis signaling remained unaffected. Cachexia progression depleted liver glycogen content and increased mRNA expression of glycolytic enzyme PFK (phosphofrucktokinase) and gluconeogenic enzyme PEPCK. Cachexia progression further increased pSTAT-3 but suppressed p-65 and JNK (c-Jun NH2-terminal kinase) activation. Interestingly, progression of cachexia suppressed upstream ER-stress markers BiP and IRE-1α, while inducing its downstream target CHOP (DNA-damage inducible transcript 3). Cachectic mice exhibited a dysregulation of protein synthesis signaling, with an induction of p-mTOR (mechanistic target of rapamycin), despite a suppression of Akt (thymoma viral proto-oncogene 1) and S6 (ribosomal protein S6) phosphorylation. Thus, cancer

Liver inflammation and metabolic signaling in ApcMin/+ mice: the role of cachexia progression.

Directory of Open Access Journals (Sweden)

Aditi A Narsale

Full Text Available The ApcMin/+ mouse exhibits an intestinal tumor associated loss of muscle and fat that is accompanied by chronic inflammation, insulin resistance and hyperlipidemia. Since the liver governs systemic energy demands through regulation of glucose and lipid metabolism, it is likely that the liver is a pathological target of cachexia progression in the ApcMin/+ mouse. The purpose of this study was to determine if cancer and the progression of cachexia affected liver endoplasmic reticulum (ER-stress, inflammation, metabolism, and protein synthesis signaling. The effect of cancer (without cachexia was examined in wild-type and weight-stable ApcMin/+ mice. Cachexia progression was examined in weight-stable, pre-cachectic, and severely-cachectic ApcMin/+ mice. Livers were analyzed for morphology, glycogen content, ER-stress, inflammation, and metabolic changes. Cancer induced hepatic expression of ER-stress markers BiP (binding immunoglobulin protein, IRE-1α (endoplasmic reticulum to nucleus signaling 1, and inflammatory intermediate STAT-3 (signal transducer and activator of transcription 3. While gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK mRNA expression was suppressed by cancer, glycogen content or protein synthesis signaling remained unaffected. Cachexia progression depleted liver glycogen content and increased mRNA expression of glycolytic enzyme PFK (phosphofrucktokinase and gluconeogenic enzyme PEPCK. Cachexia progression further increased pSTAT-3 but suppressed p-65 and JNK (c-Jun NH2-terminal kinase activation. Interestingly, progression of cachexia suppressed upstream ER-stress markers BiP and IRE-1α, while inducing its downstream target CHOP (DNA-damage inducible transcript 3. Cachectic mice exhibited a dysregulation of protein synthesis signaling, with an induction of p-mTOR (mechanistic target of rapamycin, despite a suppression of Akt (thymoma viral proto-oncogene 1 and S6 (ribosomal protein S6 phosphorylation. Thus

A stabilized optical frequency comb based on an Er-doped fiber femtosecond laser

Science.gov (United States)

Xia, Chuanqing; Wu, Tengfei; Zhao, Chunbo; Xing, Shuai

2018-03-01

An optical frequency comb based on a 250 MHz home-made Er-doped fiber femtosecond laser is presented in this paper. The Er-doped fiber laser has a ring cavity and operates mode-locked in femtosecond regime with the technique of nonlinear polarization rotation. The pulse duration is 118 fs and the spectral width is 30 nm. A part of the femtosecond laser is amplified in Er-doped fiber amplifier before propagating through a piece of highly nonlinear fiber for expanding the spectrum. The carrier-envelope offset frequency of the comb which has a signal-to-noise ratio more than 35 dB is extracted by means of f-2f beating. It demonstrates that both carrier-envelope offset frequency and repetition frequency keep phase locked to a Rubidium atomic clock simultaneously for 2 hours. The frequency stabilized fiber combs will be increasingly applied in optical metrology, attosecond pulse generation, and absolute distance measurement.

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...

Søer 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...

The role of the AR/ER ratio in ER-positive breast cancer patients.

Science.gov (United States)

Rangel, Nelson; Rondon-Lagos, Milena; Annaratone, Laura; Osella-Abate, Simona; Metovic, Jasna; Mano, Maria Piera; Bertero, Luca; Cassoni, Paola; Sapino, Anna; Castellano, Isabella

2018-03-01

The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours. The aim of the present study was to analyse the prognostic impact of AR/ER ratio, evaluated by immunohistochemistry (IHC), correlating this value with clinical, pathological and molecular characteristics. We retrospectively selected a cohort of 402 ER+BC patients. On each tumour, IHC analyses for AR, ER, PgR, HER2 and Ki67 were performed and AR+ cases were used to calculate the AR/ER value. A cut-off of ≥2 was selected using receiver-operating characteristic (ROC) curve analyses. RNA from 19 cases with AR/ER≥2 was extracted and used for Prosigna-PAM50 assays. Tumours with AR/ER≥2 (6%) showed more frequent metastatic lymph nodes, larger size, higher histological grade and lower PgR levels than cases with AR/ERAR/ER≥2 had worse disease-free interval (DFI) and disease-specific survival (DSS) (hazard ratios (HR) = 4.96 for DFI and HR = 8.69 for DSS, both P  ≤ 0.004). According to the Prosigna-PAM50 assay, 63% (12/19) of these cases resulted in intermediate or high risk of recurrence categories. Additionally, although all samples were positive for ER assessed by IHC, the molecular test assigned 47.4% (9/19) of BCs to intrinsic non-luminal subtypes. In conclusion, the AR/ER ratio ≥2 identifies a subgroup of patients with aggressive biological features and may represent an additional independent marker of worse BC prognosis. Moreover, the Prosigna-PAM50 results indicate that a significant number of cases with AR/ER≥2 could be non-luminal tumours. © 2018 Society for Endocrinology.

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.

Stem development through vascular tissues: EPFL-ERECTA family signaling that bounces in and out of phloem.

Science.gov (United States)

Tameshige, Toshiaki; Ikematsu, Shuka; Torii, Keiko U; Uchida, Naoyuki

2017-01-01

Plant cells communicate with each other using a variety of signaling molecules. Recent studies have revealed that various types of secreted peptides, as well as phytohormones known since long ago, mediate cell-cell communication in diverse contexts of plant life. These peptides affect cellular activities, such as proliferation and cell fate decisions, through their perception by cell surface receptors located on the plasma membrane of target cells. ERECTA (ER), an Arabidopsis thaliana receptor kinase gene, was first identified as a stem growth regulator, and since then an increasing number of studies have shown that ER is involved in a wide range of developmental and physiological processes. In particular, molecular functions of ER have been extensively studied in stomatal patterning. Furthermore, the importance of ER signaling in vascular tissues of inflorescence stems, especially in phloem cells, has recently been highlighted. In this review article, first we briefly summarize the history of ER research including studies on stomatal development, then introduce ER functions in vascular tissues, and discuss its interactions with phytohormones and other receptor kinase signaling pathways. Future questions and challenges will also be addressed. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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.

Endoplasmic Reticulum (ER) Stress and Endocrine Disorders

Science.gov (United States)

Ariyasu, Daisuke; Yoshida, Hiderou; Hasegawa, Yukihiro

2017-01-01

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. PMID:28208663

Enhancing retention of partial dentures using elastomeric retention rings

Directory of Open Access Journals (Sweden)

Kakkirala Revathi

2015-01-01

Full Text Available This report presents an alternative method for the retention of partial dentures that relies on the engagement of tooth undercuts by a lining material. The lab procedures are also presented. A new maxillary and mandibular acrylic partial dentures were fabricated using elastomeric retention technique for a partially dentate patient. A partially dentate man reported difficulty in retaining his upper removable partial denture (RPD. The maxillary RPD was designed utilizing elastomeric retention technique. During follow-up, it was necessary to replace the retention rings due to wear. The replacement of the retention rings, in this case, was done through a chairside reline technique. Elastomeric retention technique provides exceptionally good retention can be indicated to stabilize, cushion, splint periodontally involved teeth, no enough undercut for clasps, eliminate extractions, single or isolated teeth.

The structure of the 168Er nucleus and the 166Er(t,p) 168 Er reaction in terms of the sdg interacting boson model

Science.gov (United States)

Akiyama, Y.; Heyde, K.; Arima, A.; Yoshinaga, N.

1986-05-01

Extending the interacting boson model by incorporating besides s and d, also the g-boson, we can describe the population of positive parity states of 168Er in the 166Er(t,P) 168Er reaction rather well. In particular, the excitation of I,Kπi = 4,3 +1; 2,2 +2; 0,0 +3 and 0,0 +4 states is much improved over the sd-IBM approach.

Synaptotagmin SYTA forms ER-plasma membrane junctions that are recruited to plasmodesmata for plant virus movement.

Science.gov (United States)

Levy, Amit; Zheng, Judy Y; Lazarowitz, Sondra G

2015-08-03

Metazoan synaptotagmins are Ca(2+) sensors that regulate exocytosis and endocytosis in various cell types, notably in nerve and neuroendocrine cells [1, 2]. Recently, the structurally related extended synaptotagmins were shown to tether the cortical ER to the plasma membrane in human and yeast cells to maintain ER morphology and stabilize ER-plasma membrane (ER-PM) contact sites for intracellular lipid and Ca(2+) signaling [3, 4]. The Arabidopsis synaptotagmin SYTA regulates endocytosis and the ability of plant virus movement proteins (MPs) to alter plasmodesmata to promote virus cell-to-cell transport [5, 6]. Yet how MPs modify plasmodesmata, the cellular functions of SYTA and how these aid MP activity, and the proteins essential to form plant cell ER-PM contact sites remain unknown. We addressed these questions using an Arabidopsis SYTA knockdown line syta-1 and a Tobamovirus movement protein MP(TVCV) [5, 7]. We report here that SYTA localized to ER-PM contact sites. These sites were depleted and the ER network collapsed in syta-1, and both reformed upon rescue with SYTA. MP(TVCV) accumulation in plasmodesmata, but not secretory trafficking, was also inhibited in syta-1. During infection, MP(TVCV) recruited SYTA to plasmodesmata, and SYTA and the cortical ER were subsequently remodeled to form viral replication sites adjacent to plasmodesmata in which MP(TVCV) and SYTA directly interacted caged within ER membrane. SYTA also accumulated in plasmodesmata active in MP(TVCV) transport. Our findings show that SYTA is essential to form ER-PM contact sites and suggest that MPs interact with SYTA to recruit these sites to alter plasmodesmata for virus cell-to-cell movement. Copyright © 2015 Elsevier Ltd. All rights reserved.

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....

Effect of Er3+ Concentration on Upconversion in Hexagonal-Phase NaYF4:Er3+ Nanocrystals

International Nuclear Information System (INIS)

Luo, X J; Yuminami, R; Sakurai, T; Akimoto, K

2013-01-01

A facile synthesis method was developed to produce hexagonal-phase of NaYF 4 nanocrystals (NCs) doped with Er 3+ in different concentration, which showed upconversion (UC) emission from infrared to visible spectral region. This proposed method is simple and less toxic compared with generally used method so far. It was found that up-conversion emission spectra of NaYF 4 :Er 3+ NCs, excited at 1550 nm, included four peaks at about 980 nm, 800 nm, 660 nm and 540 nm. The effect of Er 3+ concentration on UC in β-phase NaYF 4 :Er 3+ NCs were discussed based on the excitation power dependence. The optimum Er 3+ concentration for 2-step and 3-step UC was found to be around 10∼30%.

Hvor anvendelig er PKI?

OpenAIRE

Nielsen, Jon Magne

2006-01-01

Denne oppgaven ser på bruken av elektronisk ID i statlige etater i Norge i dag. Det ses spesielt på om bruken av tekologien PKI er en god løsning på etatenes behov på dette området. Som utgangspunkt for analysen er det sett spesielt på to statlige etater. Disse etatenes behov og bruk av elektronisk ID generelt og PKI spesielt blir undersøkt. Det er videre gjort rede for hvilke lover, forskrifter og andre førende dokumenter som danner de formelle rammebetingelsene for etaters bruk av PKI. ...

Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity.

Science.gov (United States)

Chen, Yaqin; Wu, Zhihong; Zhao, Shuiping; Xiang, Rong

2016-06-08

Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese.

Hvad f er meningen?

DEFF Research Database (Denmark)

Rydén, Pernille; Ringberg, Torsten; Wilke, Ricky

En forskningsrapport fra CBS om danske lederes opfattelse af sociale medier i detail- og servicebranchen. Rapporten er udarbejdet i regi af Service Platform.......En forskningsrapport fra CBS om danske lederes opfattelse af sociale medier i detail- og servicebranchen. Rapporten er udarbejdet i regi af Service Platform....

Investigating the evolution of local structure around Er and Yb in ZnO:Er and ZnO:Er, Yb on annealing using X-ray absorption spectroscopy

Science.gov (United States)

Anjana, R.; Jayaraj, M. K.; Yadav, A. K.; Jha, S. N.; Bhattacharyya, D.

2018-04-01

The local structure around Er and Yb centre in ZnO favouring upconversion luminescence was studied using EXAFS (Extended X-ray absorption fine structure spectroscopy). Due to the ionic radii difference between Zn and Er, Yb ions, the dopants cannot replace Zn in the ZnO lattice properly. Er2O3 and Yb2O3 impurity phases are formed at the grain boundaries of ZnO. It is found that the local structure around the Er centre in ZnO is modified on annealing in air. The symmetry around both erbium and ytterbium reduces with increase in annealing temperature. Symmetry reduction will favour the intra-4f transition and the energy transitions causing upconversion luminescence. By fitting the EXAFS data with theoretically simulated data, it is found that the Er centre forms a local structure similar to C4ν symmetry which is a distorted octahedron. On annealing the sample to 1200 °C, all the erbium centres are transformed to C4ν symmetry causing enhanced upconversion emission. Yb centre has also been modified on annealing. The decrease in co-ordination number with annealing temperature will decrease the symmetry and increase the near infrared absorption cross section. The decrease in symmetry around both the erbium and ytterbium centre and formation of C4ν symmetry around Er centre is the reason behind the activation of upconversion luminescence with high temperature annealing in both Er doped and Er, Yb co-doped ZnO samples. The study will be useful for the synthesis of high efficiency upconversion materials.

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.

ER Stress: A Therapeutic Target in Rheumatoid Arthritis?

Science.gov (United States)

Rahmati, Marveh; Moosavi, Mohammad Amin; McDermott, Michael F

2018-04-22

Diverse physiological and pathological conditions that impact on protein folding of the endoplasmic reticulum (ER) cause ER stress. The unfolded protein response (UPR) and the ER-associated degradation (ERAD) pathway are activated to cope with ER stress. In rheumatoid arthritis (RA), inflammation and ER stress work in parallel by driving inflammatory cells to release cytokines that induce chronic ER stress pathways. This chronic ER stress may contribute to the pathogenesis of RA through synoviocyte proliferation and proinflammatory cytokine production. Therefore, ER stress pathways and their constituent elements are attractive targets for RA drug development. In this review, we integrate current knowledge of the contribution of ER stress to the overall pathogenesis of RA, and suggest some therapeutic implications of these discoveries. Copyright © 2018 Elsevier Ltd. All rights reserved.

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...

Suppression of concentration quenching of Er-related luminescence in Er-doped GaN

International Nuclear Information System (INIS)

Chen Shaoqiang; Tomita, Shigeo; Kudo, Hiroshi; Akimoto, Katsuhiro; Dierre, Benjamin; Lee, Woong; Sekiguchi, Takashi

2010-01-01

Erbium-doped GaN with different doping concentrations were grown by ammonia-source molecular beam epitaxy. The intra-4f-shell transitions related green luminescence were observed by both photoluminescence (PL) and cathodoluminescence (CL) measurements. It was found that concentration quenching of Er-related luminescence was observed in PL measurements while not in CL measurements. The different excitation and relaxation processes are suggested as the cause of the concentration quenching characteristics between PL and CL. The strong Er-related CL intensity in highly doped GaN demonstrates that high energy excitation is a promising approach to suppress the concentration quenching in Er-doped GaN.

E2/ER β Enhances Calcineurin Protein Degradation and PI3K/Akt/MDM2 Signal Transduction to Inhibit ISO-Induced Myocardial Cell Apoptosis

Directory of Open Access Journals (Sweden)

Kuan-Ho Lin

2017-04-01

Full Text Available Secretion of multifunctional estrogen and its receptor has been widely considered as the reason for markedly higher frequency of heart disease in men than in women. 17β-Estradiol (E2, for instance, has been reported to prevent development of cardiac apoptosis via activation of estrogen receptors (ERs. In addition, protein phosphatase such as protein phosphatase 1 (PP1 and calcineurin (PP2B are also involved in cardiac hypertrophy and cell apoptosis signaling. However, the mechanism by which E2/ERβ suppresses apoptosis is not fully understood, and the role of protein phosphatase in E2/ERβ action also needs further investigation. In this study, we observed that E2/ERβ inhibited isoproterenol (ISO-induced myocardial cell apoptosis, cytochrome c release and downstream apoptotic markers. Moreover, we found that E2/ERβ blocks ISO-induced apoptosis in H9c2 cells through the enhancement of calcineurin protein degradation through PI3K/Akt/MDM2 signaling pathway. Our results suggest that supplementation with estrogen and/or overexpression of estrogen receptor β gene may prove to be effective means to treat stress-induced myocardial damage.

Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort.

Science.gov (United States)

Sarink, Danja; Schock, Helena; Johnson, Theron; Overvad, Kim; Holm, Marianne; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; His, Mathilde; Kvaskoff, Marina; Boeing, Heiner; Lagiou, Pagona; Papatesta, Eleni-Maria; Trichopoulou, Antonia; Palli, Domenico; Pala, Valeria; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H B As; van Gils, Carla H; Peeters, Petra H; Weiderpass, Elisabete; Agudo, Antonio; Sánchez, Maria-José; Chirlaque, Maria-Dolores; Ardanaz, Eva; Amiano, Pilar; Khaw, Kay Tee; Travis, Ruth; Dossus, Laure; Gunter, Mark; Rinaldi, Sabina; Merritt, Melissa; Riboli, Elio; Kaaks, Rudolf; Fortner, Renée T

2017-09-01

Receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANKL) signaling promotes mammary tumor development in experimental models. Circulating concentrations of soluble RANKL (sRANKL) may influence breast cancer risk via activation of RANK signaling; this may be modulated by osteoprotegerin (OPG), the decoy receptor for RANKL. sRANKL and breast cancer risk by hormone receptor subtype has not previously been investigated. A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. This study included 1,976 incident invasive breast cancer cases [estrogen receptor positive (ER+), n = 1,598], matched 1:1 to controls. Women were pre- or postmenopausal at blood collection. Serum sRANKL was quantified using an ELISA, serum OPG using an electrochemiluminescent assay. Risk ratios (RR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. Associations between sRANKL and breast cancer risk differed by tumor hormone receptor status ( P het = 0.05). Higher concentrations of sRANKL were positively associated with risk of ER+ breast cancer [5th vs. 1st quintile RR 1.28 (95% CI, 1.01-1.63); P trend = 0.20], but not ER- disease. For both ER+ and estrogen and progesterone receptor positive (ER+PR+) breast cancer, results considering the sRANKL/OPG ratio were similar to those for sRANKL; we observed a suggestive inverse association between the ratio and ER-PR- disease [5th vs. 1st quintile RR = 0.60 (0.31-1.14); P trend = 0.03]. This study provides the first large-scale prospective data on circulating sRANKL and breast cancer. We observed limited evidence for an association between sRANKL and breast cancer risk. Cancer Prev Res; 10(9); 525-34. ©2017 AACR . ©2017 American Association for Cancer Research.

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 ....

Serum soluble ST2 is associated with ER-positive breast cancer

International Nuclear Information System (INIS)

Lu, Da-peng; Zhou, Xiang-yu; Yao, Lu-tian; Liu, Cai-gang; Ma, Wei; Jin, Feng; Wu, Yun-fei

2014-01-01

ST2, a member of the interleukin (IL)-1receptor family, regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions. However, the role of ST2 signaling in tumor growth and metastasis of breast cancers has not been investigated. This study investigated the possible role of soluble ST2 (sST2) in breast cancer. The serum levels of IL-33, sST2, and vascular endothelial growth factor (VEGF) in 150 breast cancer patients and 90 healthy women were measured by enzyme-linked immunosorbent assay. Estrogen receptor(ER), progesterone receptor, human epithelial receptor (HER)-2, and cell cycle regulated protein Ki-67 were measured. Clinical stage, tumor size, lymph node metastasis, and histological type were also recorded. The serum levels of sST2, IL-33, and VEGF were significantly higher in breast cancer patients than in the control group (P < 0.05, each). Serum sST2 levels in ER-positive breast cancer patients were significantly associated with age, histological type, clinical stage, tumor size, and Ki-67 status (P < 0.05, each). Moreover, the serum levels of IL-33 and sST2 in breast cancers significantly correlated with VEGF levels (IL-33: r = 0.375, P < 0.0001; sST2: r = 0.164, P = 0.045). Serum levels of sST2, IL-33, and VEGF decreased after modified radical mastectomy in ER-positive breast cancers. Serum levels of IL-33, sST2, and VEGF and clinicopathological factors were not significantly correlated with disease-free survival and overall survival of ER-positive breast cancer women during follow-up. Serum sST2 levels in ER-positive breast cancer patients are significantly associated with factors that indicate poor prognosis

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

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

Cladding-pumped 70-kW-peak-power 2-ns-pulse Er-doped fiber amplifier

Science.gov (United States)

Khudyakov, M. M.; Bubnov, M. M.; Senatorov, A. K.; Lipatov, D. S.; Guryanov, A. N.; Rybaltovsky, A. A.; Butov, O. V.; Kotov, L. V.; Likhachev, M. E.

2018-02-01

An all-fiber pulsed erbium laser with pulse width of 2.4 ns working in a MOPA configuration has been created. Cladding pumped double clad erbium doped large mode area fiber was used in the final stage amplifier. Peculiarity of the current work is utilization of custom-made multimode diode wavelength stabilized at 981+/-0.5 nm - wavelength of maximum absorption by Er ions. It allowed us to shorten Er-doped fiber down to 1.7 m and keep a reasonably high pump-to signal conversion efficiency of 8.4%. The record output peak power for all-fiber amplifiers of 84 kW was achieved within 1555.9+/-0.15 nm spectral range.

ApoER2 Controls Not Only Neuronal Migration in the Intermediate Zone But Also Termination of Migration in the Developing Cerebral Cortex.

Science.gov (United States)

Hirota, Yuki; Kubo, Ken-Ichiro; Fujino, Takahiro; Yamamoto, Tokuo T; Nakajima, Kazunori

2018-01-01

Neuronal migration contributes to the establishment of mammalian brain. The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, the apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor and exerts essential roles in the neuronal migration and formation of the layered neocortex. However, the cellular and molecular functions of Reelin signaling in the cortical development are not yet fully understood. Here, to gain insight into the role of Reelin signaling during cortical development, we examined the migratory behavior of Apoer2-deficient neurons in the developing brain. Stage-specific labeling of newborn neurons revealed that the neurons ectopically invaded the marginal zone (MZ) and that neuronal migration of both early- and late-born neurons was disrupted in the intermediate zone (IZ) in the Apoer2 KO mice. Rescue experiments showed that ApoER2 functions both in cell-autonomous and noncell-autonomous manners, that Rap1, integrin, and Akt are involved in the termination of migration beneath the MZ, and that Akt also controls neuronal migration in the IZ downstream of ApoER2. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing neocortex. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Er jeres ledere 'likeable'?

DEFF Research Database (Denmark)

Nielsen, Rikke Kristine

2013-01-01

Færdigheder: Oftest er lederne langtfra de første til at kaste sig over ny teknologi. It-kundskaberne på chefgangen trænger til en opgradering.......Færdigheder: Oftest er lederne langtfra de første til at kaste sig over ny teknologi. It-kundskaberne på chefgangen trænger til en opgradering....

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

Indian Academy of Sciences (India)

Unknown

Materials Science Centre, †Central Research Facility, Optical Fibre Unit, Indian Institute of Technology,. Kharagpur 721 302, India. MS received 1 March 2004; revised 4 July 2004. Abstract. Er3+ and Er3+ : Yb3+ doped optical quality, crack and bubble free glasses for possible use in mak- ing laser material have been ...

A novel transgenic mouse model of growth plate dysplasia reveals that decreased chondrocyte proliferation due to chronic ER stress is a key factor in reduced bone growth

Directory of Open Access Journals (Sweden)

Benedetta Gualeni

2013-11-01

Disease mechanisms leading to different forms of chondrodysplasia include extracellular matrix (ECM alterations and intracellular stress resulting in abnormal changes to chondrocyte proliferation and survival. Delineating the relative contribution of these two disease mechanisms is a major challenge in understanding disease pathophysiology in genetic skeletal diseases and a prerequisite for developing effective therapies. To determine the influence of intracellular stress and changes in chondrocyte phenotype to the development of chondrodysplasia, we targeted the expression of the G2320R mutant form of thyroglobulin to the endoplasmic reticulum (ER of resting and proliferating chondrocytes. Previous studies on this mutant protein have shown that it induces intracellular aggregates and causes cell stress and death in the thyroid gland. The expression and retention of this exogenous mutant protein in resting and proliferating chondrocytes resulted in a chronic cell stress response, growth plate dysplasia and reduced bone growth, without inducing any alterations to the architecture and organization of the cartilage ECM. More significantly, the decreased bone growth seemed to be the direct result of reduced chondrocyte proliferation in the proliferative zone of growth plates in transgenic mice, without transcriptional activation of a classical unfolded protein response (UPR or apoptosis. Overall, these data show that mutant protein retention in the ER of resting and proliferative zone chondrocytes is sufficient to cause disrupted bone growth. The specific disease pathways triggered by mutant protein retention do not necessarily involve a prototypic UPR, but all pathways impact upon chondrocyte proliferation in the cartilage growth plate.

Variance in exposed perturbations impairs retention of visuomotor adaptation.

Science.gov (United States)

Canaveral, Cesar Augusto; Danion, Frédéric; Berrigan, Félix; Bernier, Pierre-Michel

2017-11-01

Sensorimotor control requires an accurate estimate of the state of the body. The brain optimizes state estimation by combining sensory signals with predictions of the sensory consequences of motor commands using a forward model. Given that both sensory signals and predictions are uncertain (i.e., noisy), the brain optimally weights the relative reliance on each source of information during adaptation. In support, it is known that uncertainty in the sensory predictions influences the rate and generalization of visuomotor adaptation. We investigated whether uncertainty in the sensory predictions affects the retention of a new visuomotor relationship. This was done by exposing three separate groups to a visuomotor rotation whose mean was common at 15° counterclockwise but whose variance around the mean differed (i.e., SD of 0°, 3.2°, or 4.5°). Retention was assessed by measuring the persistence of the adapted behavior in a no-vision phase. Results revealed that mean reach direction late in adaptation was similar across groups, suggesting it depended mainly on the mean of exposed rotations and was robust to differences in variance. However, retention differed across groups, with higher levels of variance being associated with a more rapid reversion toward nonadapted behavior. A control experiment ruled out the possibility that differences in retention were accounted for by differences in success rates. Exposure to variable rotations may have increased the uncertainty in sensory predictions, making the adapted forward model more labile and susceptible to change or decay. NEW & NOTEWORTHY The brain predicts the sensory consequences of motor commands through a forward model. These predictions are subject to uncertainty. We use visuomotor adaptation and modulate uncertainty in the sensory predictions by manipulating the variance in exposed rotations. Results reveal that variance does not influence the final extent of adaptation but selectively impairs the retention of

Vidensledelse er også en social praksis

DEFF Research Database (Denmark)

Lauring, Jakob; Waldstrøm, Christian

2006-01-01

lys er det utroligt vigtigt at personalefunktionen i virksomheden er klar over de processer der udspiller sig, og aktivt tager fat om problemerne der ligger i disse barrierer. Vores egne undersøgelser viser, at på trods af opstillingen af teknologiske systemer til vidensdeling, er der stadig...... væsentlige ledelsesmæssige opgaver i forhold til sociale aspekter ved arbejdet i en organisation, som skal varetages hvis vidensdelingen skal fremmes succesfuldt. Det er væsentligt at forstå, at vidensledelse ikke blot handler om cirkulering af information, men også er forbundet mere generelt til ledelse som...

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, ...

Oleosome-Associated Protein of the Oleaginous Diatom Fistulifera solaris Contains an Endoplasmic Reticulum-Targeting Signal Sequence

Directory of Open Access Journals (Sweden)

Yoshiaki Maeda

2014-06-01

Full Text Available Microalgae tend to accumulate lipids as an energy storage material in the specific organelle, oleosomes. Current studies have demonstrated that lipids derived from microalgal oleosomes are a promising source of biofuels, while the oleosome formation mechanism has not been fully elucidated. Oleosome-associated proteins have been identified from several microalgae to elucidate the fundamental mechanisms of oleosome formation, although understanding their functions is still in infancy. Recently, we discovered a diatom-oleosome-associated-protein 1 (DOAP1 from the oleaginous diatom, Fistulifera solaris JPCC DA0580. The DOAP1 sequence implied that this protein might be transported into the endoplasmic reticulum (ER due to the signal sequence. To ensure this, we fused the signal sequence to green fluorescence protein. The fusion protein distributed around the chloroplast as like a meshwork membrane structure, indicating the ER localization. This result suggests that DOAP1 could firstly localize at the ER, then move to the oleosomes. This study also demonstrated that the DOAP1 signal sequence allowed recombinant proteins to be specifically expressed in the ER of the oleaginous diatom. It would be a useful technique for engineering the lipid synthesis pathways existing in the ER, and finally controlling the biofuel quality.

ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response

Directory of Open Access Journals (Sweden)

Jarom Heijmans

2013-04-01

Full Text Available Stem cells generate rapidly dividing transit-amplifying cells that have lost the capacity for self-renewal but cycle for a number of times until they exit the cell cycle and undergo terminal differentiation. We know very little of the type of signals that trigger the earliest steps of stem cell differentiation and mediate a stem cell to transit-amplifying cell transition. We show that in normal intestinal epithelium, endoplasmic reticulum (ER stress and activity of the unfolded protein response (UPR are induced at the transition from stem cell to transit-amplifying cell. Induction of ER stress causes loss of stemness in a Perk-eIF2α-dependent manner. Inhibition of Perk-eIF2α signaling results in stem cell accumulation in organoid culture of primary intestinal epithelium. Our findings show that the UPR plays an important role in the regulation of intestinal epithelial stem cell differentiation.

New insights on the functional role of URG7 in the cellular response to ER stress.

Science.gov (United States)

Armentano, Maria Francesca; Caterino, Marianna; Miglionico, Rocchina; Ostuni, Angela; Pace, Maria Carmela; Cozzolino, Flora; Monti, Maria; Milella, Luigi; Carmosino, Monica; Pucci, Piero; Bisaccia, Faustino

2018-04-28

Up-regulated Gene clone 7 (URG7) is an ER resident protein, whose expression is up-regulated in the presence of hepatitis B virus X antigen (HBxAg) during HBV infection. In virus-infected hepatocytes, URG7 shows an anti-apoptotic activity due to the PI3K/AKT signalling activation, does not seem to have tumorigenic properties, but it appears to promote the development and progression of fibrosis. However, the molecular mechanisms underlying URG7 activity remain largely unknown. To shed light on URG7 activity, we first analysed its interactome in HepG2 transfected cells: this analysis suggests that URG7 could have a role in affecting protein synthesis, folding and promoting proteins degradation. Moreover, keeping into account its subcellular localisation in the ER and that several viral infections give rise to ER stress, a panel of experiments was performed to evaluate a putative role of URG7 in ER stress. Our main results demonstrate that in ER-stressed cells URG7 is able to modulate the expression of Unfolded Protein Response (UPR) markers towards survival outcomes, up-regulating GRP78 protein and down-regulating the pro-apoptotic protein CHOP. Furthermore, URG7 reduces the ER stress by decreasing the amount of unfolded proteins, by increasing both the total protein ubiquitination and the AKT activation and reducing Caspase 3 activation. All together these data suggest that URG7 plays a pivotal role as a reliever of ER stress-induced apoptosis. This is the first characterisation of URG7 activity under ER stress conditions. The results presented here will help to hypothesise new strategies to counteract the antiapoptotic activity of URG7 in the context of the viral infection. © 2018 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Chaperone-Mediated Sec61 Channel Gating during ER Import of Small Precursor Proteins Overcomes Sec61 Inhibitor-Reinforced Energy Barrier

Directory of Open Access Journals (Sweden)

Sarah Haßdenteufel

2018-05-01

Full Text Available Summary: Protein transport into the mammalian endoplasmic reticulum (ER is mediated by the heterotrimeric Sec61 channel. The signal recognition particle (SRP and TRC systems and Sec62 have all been characterized as membrane-targeting components for small presecretory proteins, whereas Sec63 and the lumenal chaperone BiP act as auxiliary translocation components. Here, we report the transport requirements of two natural, small presecretory proteins and engineered variants using semipermeabilized human cells after the depletion of specific ER components. Our results suggest that hSnd2, Sec62, and SRP and TRC receptor each provide alternative targeting pathways for short secretory proteins and define rules of engagement for the actions of Sec63 and BiP during their membrane translocation. We find that the Sec62/Sec63 complex plus BiP can facilitate Sec61 channel opening, thereby allowing precursors that have weak signal peptides or other inhibitory features to translocate. A Sec61 inhibitor can mimic the effect of BiP depletion on Sec61 gating, suggesting that they both act at the same essential membrane translocation step. : Protein transport into the human endoplasmic reticulum (ER is mediated by the heterotrimeric Sec61 channel. Haßdenteufel et al. map the determinants for requirement of different targeting pathways and different auxiliary components of the Sec61 channel in ER import of short presecretory proteins. Different characteristics of precursor polypeptides dictate the engagement of each component. Keywords: endoplasmic reticulum, protein targeting and translocation, Sec61 channel gating, Sec62, Sec63, BiP, CAM741, signal peptide, mature region, cluster of positive charges

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.

Optimal fodring af goldkøer

DEFF Research Database (Denmark)

Bjerre-Harpøth, Vibeke; Damgaard, Birthe Marie

2013-01-01

Et forsøg har vist, at køer på lavt energiniveau i goldperioden var fysiologisk sundere og havde mindre risiko for at udvikle stofskiftesygdomme end køer på et højt energiniveau. Forsøget viste også, at køer på et normalt energiniveau i senlaktationen gav mere mælk i den efterfølgende laktation e...

Er KU et mobbeuniversitet?

DEFF Research Database (Denmark)

Olden-Jørgensen, Sebastian

2009-01-01

Ansatte på KU mobber hverken mere eller mindre end på andre danske arbejdspladser. Mediernes dækning af APV-undersøgelsens resultater mht. mobning er sensationalistisk og delvis vildledende.......Ansatte på KU mobber hverken mere eller mindre end på andre danske arbejdspladser. Mediernes dækning af APV-undersøgelsens resultater mht. mobning er sensationalistisk og delvis vildledende....

Spectral-converting behaviors of Er{sup 3+} and Er{sup 3+}–Yb{sup 3+} doped YOCl phosphors

Energy Technology Data Exchange (ETDEWEB)

Park, Sangmoon, E-mail: spark@silla.ac.kr [Center for Green Fusion Technology and Department of Engineering in Energy and Applied Chemistry, Silla University, Busan 617-736 (Korea, Republic of); Cho, So-Hye [Center for Materials Architecturing, Institute of Multidisciplinary Convergence of Materials, Korea Institute of Science and Technology, Seoul 130-650 (Korea, Republic of)

2014-01-25

Highlights: • Luminescent materials of YOCl:Er,Yb were prepared using NH{sub 4}Cl flux. • Interesting spectral-converting behaviors were observed in the phosphors. • 980 or 1550 nm diode laser was irradiated for up-converting study. • A multi-photon process in the phosphors was calculated. -- Abstract: Luminescent materials composed of Y{sub 1−m−n}Er{sub m}Yb{sub n}OCl (m = 0.001–0.1, n = 0.005–0.1) were prepared via a solid-state reaction using NH{sub 4}Cl flux. Photoluminescence spectra, the dependence of the luminescent intensity as a function of Er{sup 3+} content, and their CIE coordinates of the Er{sup 3+}-doped layered YOCl compounds were also investigated under near-ultraviolet (NUV) and visible lights. The spectral up-converting properties of Er{sup 3+} and Er{sup 3+}–Yb{sup 3+} in YOCl phosphors were elucidated under 980 and 1550 nm diode laser irradiations. This up-conversion emission spectra and the pump power dependence versus emission intensity observed in the Y{sub 0.9}Er{sub 0.1}OCl up-conversion phosphors gave rise to one- and two-photon processes. The up-conversion mechanism of Er{sup 3+} and Yb{sup 3+} ions in YOCl was described by a schematic energy-level diagram. Through the use of these up-conversion luminescent materials, the desired emitting lights throughout the orange and red regions of the spectra were achieved.

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.

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.

Structure of the /sup 168/Er nucleus and the /sup 166/Er(t,p)/sup 168/Er reaction in terms of the sdg interacting boson model

Energy Technology Data Exchange (ETDEWEB)

Akiyama, Y.; Heyde, K.; Arima, A.; Yoshinaga, N.

1986-05-29

Extending the interacting boson model by incorporating besides s and d, also the g-boson, we can describe the population of positive parity states of /sup 168/Er in the /sup 166/Er(t,P)/sup 168/Er reaction rather well. In particular, the excitation of I,Ksub(i)sup(..pi..) = 4,3/sub 1//sup +/; 2,2/sub 2//sup +/; 0,0/sub 3//sup +/ and 0,0/sub 4//sup +/ states is much improved over the sd-IBM appraoch.

Pæren er faldet langt fra stammen

DEFF Research Database (Denmark)

Haarder, Jon Helt

2013-01-01

Roman: Hassan Preislers vellykkede debutroman udleverer ikke bare multikulti-industrien. Den er også en rablende diagnosticering af det moderne menneskes livsvilkår HASSAN PREISLER BRUN MANDS BYRDE 224 sider, 249,95 Lindhardt og Ringhof Er udkommet 4......Roman: Hassan Preislers vellykkede debutroman udleverer ikke bare multikulti-industrien. Den er også en rablende diagnosticering af det moderne menneskes livsvilkår HASSAN PREISLER BRUN MANDS BYRDE 224 sider, 249,95 Lindhardt og Ringhof Er udkommet 4...

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?...

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...

Multi-temporal RADARSAT-1 and ERS backscattering signatures of coastal wetlands in southeastern Louisiana

Science.gov (United States)

Kwoun, Oh-Ig; Lu, Z.

2009-01-01

Using multi-temporal European Remote-sensing Satellites (ERS-1/-2) and Canadian Radar Satellite (RADARSAT-1) synthetic aperture radar (SAR) data over the Louisiana coastal zone, we characterize seasonal variations of radar backscat-tering according to vegetation type. Our main findings are as follows. First, ERS-1/-2 and RADARSAT-1 require careful radiometric calibration to perform multi-temporal backscattering analysis for wetland mapping. We use SAR backscattering signals from cities for the relative calibration. Second, using seasonally averaged backscattering coefficients from ERS-1/-2 and RADARSAT-1, we can differentiate most forests (bottomland and swamp forests) and marshes (freshwater, intermediate, brackish, and saline marshes) in coastal wetlands. The student t-test results support the usefulness of season-averaged backscatter data for classification. Third, combining SAR backscattering coefficients and an optical-sensor-based normalized difference vegetation index can provide further insight into vegetation type and enhance the separation between forests and marshes. Our study demonstrates that SAR can provide necessary information to characterize coastal wetlands and monitor their changes.

Antecedent wetness conditions based on ERS scatterometer data

Science.gov (United States)

Brocca, L.; Melone, F.; Moramarco, T.; Morbidelli, R.

2009-01-01

SummarySoil moisture is widely recognized as a key parameter in environmental processes mainly for the role of rainfall partitioning into runoff and infiltration. Therefore, for storm rainfall-runoff modeling the estimation of the antecedent wetness conditions ( AWC) is one of the most important aspect. In this context, this study investigates the potential of scatterometer on board of the ERS satellites for the assessment of wetness conditions in three Tiber sub-catchments (Central Italy), of which one includes an experimental area for soil moisture monitoring. The satellite soil moisture data are taken from the ERS/METOP soil moisture archive. First, the scatterometer-derived soil wetness index ( SWI) data are compared with two on-site soil moisture data sets acquired by different methodologies on areas of different extension ranging from 0.01 km 2 to ˜60 km 2. Moreover, the reliability of SWI to estimate the AWC at a catchment scale is investigated considering the relationship between SWI and the soil potential maximum retention parameter, S, of the Soil Conservation Service-Curve Number (SCS-CN) method for abstraction. Several flood events occurred from 1992 to 2005 are selected for this purpose. Specifically, the performance of the SWI for S estimation is compared with two antecedent precipitation indices ( API) and one base flow index ( BFI). The S values obtained through the observed direct runoff volume and rainfall depth are used as benchmark. Results show the great reliability of the SWI for the estimation of wetness conditions both at the plot and catchment scale despite the complex orography of the investigated areas. As far as the comparison with on site soil moisture data set is concerned, the SWI is found quite reliable in representing the soil moisture at layer depth of 15 cm, with a mean correlation coefficient equal to 0.81. The characteristic time length parameter variations, as expected, is depended on soil type, with values in accordance with

An ER protein functionally couples neutral lipid metabolism on lipid droplets to membrane lipid synthesis in the ER.

Science.gov (United States)

Markgraf, Daniel F; Klemm, Robin W; Junker, Mirco; Hannibal-Bach, Hans K; Ejsing, Christer S; Rapoport, Tom A

2014-01-16

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. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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.

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.

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....

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

The Role of Unfolded Protein Response and Mitogen-Activated Protein Kinase Signaling in Neurodegenerative Diseases with Special Focus on Prion Diseases

Directory of Open Access Journals (Sweden)

Lifeng Yang

2017-05-01

Full Text Available Prion diseases are neurodegenerative pathologies characterized by the accumulation of a protease-resistant form of the cellular prion protein named prion protein scrapie (PrPSc in the brain. PrPSc accumulation in the endoplasmic reticulum (ER result in a dysregulated calcium (Ca2+ homeostasis and subsequent initiation of unfolded protein response (UPR leading to neuronal dysfunction and apoptosis. The molecular mechanisms for the transition between adaptation to ER stress and ER stress-induced apoptosis are still unclear. Mitogen-activated protein kinases (MAPKs are serine/threonine protein kinases that rule the signaling of many extracellular stimuli from plasma membrane to the nucleus. However the identification of numerous points of cross talk between the UPR and MAPK signaling pathways may contribute to our understanding of the consequences of ER stress in prion diseases. Indeed the MAPK signaling network is known to regulate cell cycle progression and cell survival or death responses following a variety of stresses including misfolded protein response stress. In this article, we review the UPR signaling in prion diseases and discuss the triad of MAPK signaling pathways. We also describe the role played by MAPK signaling cascades in Alzheimer’s (AD and Parkinson’s disease (PD. We will also overview the mechanisms of cell death and the role of MAPK signaling in prion disease progression and highlight potential avenues for therapeutic intervention.

The novel ER membrane protein PRO41 is essential for sexual development in the filamentous fungus Sordaria macrospora.

Science.gov (United States)

Nowrousian, Minou; Frank, Sandra; Koers, Sandra; Strauch, Peter; Weitner, Thomas; Ringelberg, Carol; Dunlap, Jay C; Loros, Jennifer J; Kück, Ulrich

2007-05-01

The filamentous fungus Sordaria macrospora develops complex fruiting bodies (perithecia) to propagate its sexual spores. Here, we present an analysis of the sterile mutant pro41 that is unable to produce mature fruiting bodies. The mutant carries a deletion of 4 kb and is complemented by the pro41 open reading frame that is contained within the region deleted in the mutant. In silico analyses predict PRO41 to be an endoplasmic reticulum (ER) membrane protein, and a PRO41-EGFP fusion protein colocalizes with ER-targeted DsRED. Furthermore, Western blot analysis shows that the PRO41-EGFP fusion protein is present in the membrane fraction. A fusion of the predicted N-terminal signal sequence of PRO41 with EGFP is secreted out of the cell, indicating that the signal sequence is functional. pro41 transcript levels are upregulated during sexual development. This increase in transcript levels was not observed in the sterile mutant pro1 that lacks a transcription factor gene. Moreover, microarray analysis of gene expression in the mutants pro1, pro41 and the pro1/41 double mutant showed that pro41 is partly epistatic to pro1. Taken together, these data show that PRO41 is a novel ER membrane protein essential for fruiting body formation in filamentous fungi.

Interrelation of androgen receptor and miR-30a and miR-30a function in ER-, PR-, AR+ MDA-MB-453 breast cancer cells.

Science.gov (United States)

Lyu, Shuhua; Liu, Han; Liu, Xia; Liu, Shan; Wang, Yahong; Yu, Qi; Niu, Yun

2017-10-01

The association between androgen-induced androgen receptor (AR) activating signal and microRNA (miR)-30a was investigated, as well as the function of miR-30a in estrogen receptor-negative (ER - ), progesterone receptor-negative (PR - ), and AR-positive (AR + ) MDA-MB-453 breast cancer cells. Androgen-induced AR activating signal upregulated the expression of AR, and downregulated the expression of miR-30a, b and c. Bioinformatics analysis indicated a putative miR-30a, b and c binding site in the 3'-untranslated region of AR mRNA. It was confirmed that the AR gene is a direct target of miR-30a, whereas AR does not target the miR-30a promoter, and AR activating signal may indirectly downregulate miR-30a through other cell signaling pathways. In this positive feedback mechanism AR is then upregulated through miR-30a. Overexpression of miR-30a inhibited cell proliferation, whereas inhibition of miR-30a expression by specific antisense oligonucleotides, increased cell growth. Previously, androgen-induced AR activating signal was demonstrated to inhibit cell proliferation in ER - , PR - and AR + MDA-MB-453 breast cancer cells, but AR activating signal downregulated the expression of miR-30a, relieving the inhibition of MDA-MB-453 cell growth. Therefore, in MDA-MB-453 breast cancer cells, miR-30a has two different functions regarding cell growth: Inhibition of cell proliferation through a positive feedback signaling pathway; and the relative promotion of cell proliferation through downregulation of miR-30a. Thus, the association between AR activating signal and microRNAs is complex, and microRNAs may possess different functions due to different signaling pathways. Although the results of the present study were obtained in one cell line, they contribute to subsequent studies on ER - , PR - and AR + breast cancer.

Transcription factor Brn-3α mRNA in cancers, relationship with AR, ER receptors and AKT/m-TOR pathway components

Science.gov (United States)

Spirina, L. V.; Gorbunov, A. K.; Chigevskaya, S. Y.; Usynin, Y. A.; Kondakova, I. V.; Slonimskaya, E. M.; Usynin, E. A.; Choinzonov, E. L.; Zaitseva, O. S.

2017-09-01

Transcription factors POU4F1 (neurogenic factor Brn-3α) play a pivotal role in cancers development. The aim of the study was to reveal the Brn-3α expression, AR, ER expression in cancers development, association with AKT/mTOR pathway activation. 30 patients with locally advanced prostate cancer, 20 patients with papillary thyroid cancer, T2-3N0-1M0 stages and 40 patients with renal cell cancer T2-3N0M0-1 were involved into the study. The expressions of Brn-3α, AR, ERα, components of AKT/m-TOR signaling pathway genes were performed by real-time PCR. The dependence of Brn-3α expression on mRNA levels of steroid hormone receptors and components of AKT/m-TOR signaling pathway in studied cancers were shown. High levels of mRNA of nuclear factor, steroid hormone receptors were found followed by the activation of this signaling pathway in prostate cancer tissue. The reduction of transcription factor Brn-3α was accompanied with tumor invasive growth with increasing rates of AR, ER and 4E-BP1 mRNA. Thyroid cancer development happened in a case of a Brn-3α and steroid hormone receptors decrease. The activation of AKT/m-TOR signaling pathway was established in the metastatic renal cancers, accompanied with the increase of ER mRNA. But there was no correlation between the steroid receptor and Brn-3α. One-direction changes of Brn-3α were observed in the development of prostate and thyroid cancer due to its effect on the steroid hormone receptors and the activation of AKT/m-TOR signaling pathway components. The influence of this factor on the development of the kidney cancer was mediated through m-TOR activity modifications, the key enzyme of oncogenesis.

A Low Leakage Autonomous Data Retention Flip-Flop with Power Gating Technique

Directory of Open Access Journals (Sweden)

Xiaohui Fan

2014-01-01

Full Text Available With the scaling of technology process, leakage power becomes an increasing portion of total power. Power gating technology is an effective method to suppress the leakage power in VLSI design. When the power gating technique is applied in sequential circuits, such as flip-flops and latches, the data retention is necessary to store the circuit states. A low leakage autonomous data retention flip-flop (ADR-FF is proposed in this paper. Two high-Vth transistors are utilized to reduce the leakage power consumption in the sleep mode. The data retention cell is composed of a pair of always powered cross-coupled inverters in the slave latch. No extra control signals and complex operations are needed for controlling the data retention and restoration. The data retention flip-flops are simulated with NCSU 45 nm technology. The postlayout simulation results show that the leakage power of the ADR-FF reduces 51.39% compared with the Mutoh-FF. The active power of the ADR-FF is almost equal to other data retention flip-flops. The average state mode transition time of ADR-FF decreases 55.98%, 51.35%, and 21.07% as compared with Mutoh-FF, Balloon-FF, and Memory-TG-FF, respectively. Furthermore, the area overhead of ADR-FF is smaller than other data retention flip-flops.

Molecular Pathways for Immune Recognition of Preproinsulin Signal Peptide in Type 1 Diabetes.

Science.gov (United States)

Kronenberg-Versteeg, Deborah; Eichmann, Martin; Russell, Mark A; de Ru, Arnoud; Hehn, Beate; Yusuf, Norkhairin; van Veelen, Peter A; Richardson, Sarah J; Morgan, Noel G; Lemberg, Marius K; Peakman, Mark

2018-04-01

The signal peptide region of preproinsulin (PPI) contains epitopes targeted by HLA-A-restricted (HLA-A0201, A2402) cytotoxic T cells as part of the pathogenesis of β-cell destruction in type 1 diabetes. We extended the discovery of the PPI epitope to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and HLA-B*3801 (protective) alleles, revealing that four of six alleles present epitopes derived from the signal peptide region. During cotranslational translocation of PPI, its signal peptide is cleaved and retained within the endoplasmic reticulum (ER) membrane, implying it is processed for immune recognition outside of the canonical proteasome-directed pathway. Using in vitro translocation assays with specific inhibitors and gene knockout in PPI-expressing target cells, we show that PPI signal peptide antigen processing requires signal peptide peptidase (SPP). The intramembrane protease SPP generates cytoplasm-proximal epitopes, which are transporter associated with antigen processing (TAP), ER-luminal epitopes, which are TAP independent, each presented by different HLA class I molecules and N-terminal trimmed by ER aminopeptidase 1 for optimal presentation. In vivo, TAP expression is significantly upregulated and correlated with HLA class I hyperexpression in insulin-containing islets of patients with type 1 diabetes. Thus, PPI signal peptide epitopes are processed by SPP and loaded for HLA-guided immune recognition via pathways that are enhanced during disease pathogenesis. © 2018 by the American Diabetes Association.

Lysosomes shape Ins(1,4,5)P3-evoked Ca2+ signals by selectively sequestering Ca2+ released from the endoplasmic reticulum

Science.gov (United States)

López-Sanjurjo, Cristina I.; Tovey, Stephen C.; Prole, David L.; Taylor, Colin W.

2013-01-01

Summary Most intracellular Ca2+ signals result from opening of Ca2+ channels in the plasma membrane or endoplasmic reticulum (ER), and they are reversed by active transport across these membranes or by shuttling Ca2+ into mitochondria. Ca2+ channels in lysosomes contribute to endo-lysosomal trafficking and Ca2+ signalling, but the role of lysosomal Ca2+ uptake in Ca2+ signalling is unexplored. Inhibition of lysosomal Ca2+ uptake by dissipating the H+ gradient (using bafilomycin A1), perforating lysosomal membranes (using glycyl-L-phenylalanine 2-naphthylamide) or lysosome fusion (using vacuolin) increased the Ca2+ signals evoked by receptors that stimulate inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] formation. Bafilomycin A1 amplified the Ca2+ signals evoked by photolysis of caged Ins(1,4,5)P3 or by inhibition of ER Ca2+ pumps, and it slowed recovery from them. Ca2+ signals evoked by store-operated Ca2+ entry were unaffected by bafilomycin A1. Video-imaging with total internal reflection fluorescence microscopy revealed that lysosomes were motile and remained intimately associated with the ER. Close association of lysosomes with the ER allows them selectively to accumulate Ca2+ released by Ins(1,4,5)P3 receptors. PMID:23097044

Aberrant accumulation of the diabetes autoantigen GAD65 in Golgi membranes in conditions of ER stress and autoimmunity

DEFF Research Database (Denmark)

Phelps, Edward A; Cianciaruso, Chiara; Michael, Iacovos P

2016-01-01

Pancreatic islet beta cells are particularly susceptible to endoplasmic reticulum (ER) stress, which is implicated in beta cell dysfunction and loss during the pathogenesis of type 1 diabetes (T1D). The peripheral membrane protein GAD65 is an autoantigen in human T1D. GAD65 synthesizes GABA......, an important autocrine and paracrine signaling molecule and a survival factor in islets. We show that ER stress in primary beta cells perturbs the palmitoylation cycle controlling GAD65 endomembrane distribution, resulting in aberrant accumulation of the palmitoylated form in trans-Golgi membranes...... release from stressed and/or damaged beta cells, triggering autoimmunity....

Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity*

OpenAIRE

Marty, Caroline; Chaligné, Ronan; Lacout, Catherine; Constantinescu, Stefan N.; Vainchenker, William; Villeval, Jean-Luc

2009-01-01

The activating W515L mutation in the thrombopoietin receptor (MPL) has been identified in primary myelofibrosis and essential thrombocythemia. MPL belongs to a subset of the cytokine receptor superfamily that requires the JAK2 kinase for signaling. We examined whether the ligand-independent MPLW515L mutant could signal intracellularly. Addition of the endoplasmic reticulum (ER) retention KDEL sequence to the receptor C terminus efficiently locked MPLW515L within its na...

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...

Retention of CXCR4 in the endoplasmic reticulum blocks dissemination of a T cell hybridoma.

Science.gov (United States)

Zeelenberg, I S; Ruuls-Van Stalle, L; Roos, E

2001-07-01

The dissemination of T cell hybridomas to multiple nonhematopoietic tissues is blocked by pertussis toxin, suggesting the involvement of a chemokine. To study whether this chemokine is SDF-1, we employed a strategy proposed previously for gene therapy of AIDS, whereby the SDF-1 receptor CXCR4 (also a coreceptor for HIV) is retained in the endoplasmic reticulum (ER) and fails to reach the cell surface. We transfected SDF-1, carrying an ER retention sequence, into a T cell hybridoma. This altered chemokine is retained in the ER, where it binds CXCR4 and prevents the latter protein from reaching the surface. These cells failed to migrate toward SDF-1 or to invade fibroblast monolayers, although they could still migrate toward thymus and activation-regulated chemokine (TARC) and invade TARC-treated monolayers. Furthermore, the ability of the transfected cells to disseminate to multiple organs upon intravenous injection into mice was abolished. This dissemination reflects the in vivo migration patterns of activated and memory T cells into nonhematopoietic tissues, which is thus likely to depend on CXCR4. Attempts to block CXCR4 function as a therapy for AIDS may affect this migration with consequences for T cell function. Our results also suggest a decisive role for CXCR4 in the dissemination of hematopoietic malignancies expressing this receptor.

Brandulykker er et socialt problem

DEFF Research Database (Denmark)

Leth, Peter Mygind

1999-01-01

Det er de gamle, de syge, de handicappede og alkoholikerne, der brænder inde. Typisk har de tabt en cigaret eller tændstik på tøjet. En del af disse brandulykker opstår på plejehjem og andre institutioner, hvor det ofte er plejepersonalet, der opdager og slukker branden....

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......-miljøet med nærings-salte. Danmarks Miljøundersø-gelser har som sektor-forskningsinstitu-tion i Miljø- og Energiministeriet til opgave at forbedre og styrke det fagli-ge grundlag for de mil-jøpolitiske prioriteringer og beslut-ninger. En væsentlig del af denne opgave er overvågning af miljø og natur. Det er...

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats.

Science.gov (United States)

Hu, Min; Zhang, Yuehui; Feng, Jiaxing; Xu, Xue; Zhang, Jiao; Zhao, Wei; Guo, Xiaozhu; Li, Juan; Vestin, Edvin; Cui, Peng; Li, Xin; Wu, Xiao-Ke; Brännström, Mats; Shao, Linus R; Billig, Håkan

2018-05-01

Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here, we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2 , two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions. © 2018 Society for Endocrinology.

Factors That Influence Enrolment and Retention in Ghana’ National Health Insurance Scheme

Science.gov (United States)

Millicent Kotoh, Agnes; Aryeetey, Genevieve Cecilia; der Geest, Sjaak Van

2018-01-01

Background: The government of Ghana introduced the National Health Insurance Scheme (NHIS) in 2004 with the goal of achieving universal coverage within 5 years. Evidence, however, shows that expanding NHIS coverage and especially retaining members have remained a challenge. A multilevel perspective was employed as a conceptual framework and methodological tool to examine why enrolment and retention in the NHIS remains low. Methods: A household survey was conducted after 20 months educational and promotional activities aimed at improving enrolment and retention rates in 15 communities in the Central and Eastern Regions (ERs) of Ghana. Observation, indepth interviews and informal conversations were used to collect qualitative data. Forty key informants (community members, health providers and district health insurance schemes’ [DHISs] staff) purposely selected from two casestudy communities in the Central Region (CR) were interviewed. Several community members, health providers and DHISs’ staff were also engaged in informal conversations in the other five communities in the region. Also, four staff of the Ministry of Health (MoH), Ghana Health Service (GHS) and National Health Insurance Authority (NHIA) were engaged in in-depth interviews. Descriptive statistics was used to analyse quantitative data. Qualitative data was analysed using thematic content analysis. Results: The results show that factors that influence enrolment and retention in the NHIS are multi-dimensional and cut across all stakeholders. People enrolled and renewed their membership because of NHIS’ benefits and health providers’ positive behaviour. Barriers to enrolment and retention included: poverty, traditional risk-sharing arrangements influence people to enrol or renew their membership only when they need healthcare, dissatisfaction about health providers’ behaviour and service delivery challenges. Conclusion: Given the multi-dimensional nature of barriers to enrolment and retention

Hvad er ledelse af brugerinddragelse?

DEFF Research Database (Denmark)

Holm-Petersen, Christina; Navne, Laura Emdal

2015-01-01

Brugerinddragelse i det danske sundhedsvæsen står højt på den politiske dagsorden, men det er stadig en udfordring at implementere visionen i klinisk praksis. Ledelse af brugerinddragelse bliver aktuelt udpeget som en central nøgle til at føre visionen ud i livet. Samtidig er der kun relativt lidt......, at brugerinddragelse skal implementeres i en verden, hvor der allerede er en række andre mål tilstede. En central ledelsesudfordring er derfor, at nogle af målene med brugerinddragelse forudsætter nye måder at organisere ikke bare arbejdet og kompetencer på, men også relationer til patienter og pårørende. En væsentlig...... that organize relations Patient involvement in the health services in Denmark is high on the political agenda, though continues to be a challenge to implement. It is increasingly said that leadership is crucial to the implementation process. However, research into the role of leaders in patient involvement...

Er3+ infrared fluorescence affected by spatial distribution synchronicity of Ba2+ and Er3+ in Er3+-doped BaO–SiO2 glasses

Directory of Open Access Journals (Sweden)

Atsunobu Masuno

2016-02-01

Full Text Available Glasses with the composition xBaO–(99.9 − xSiO2–0.1ErO3/2 (0 ≤x ≤ 34.9 were fabricated by a levitation technique. The glasses in the immiscibility region were opaque due to chemical inhomogeneity, while the other glasses were colorless and transparent. The scanning electron microscope observations and electron probe microanalysis scan profiles revealed that more Er3+ ions were preferentially distributed in the regions where more Ba2+ ions existed in the chemically inhomogeneous glasses. The synchronicity of the spatial distributions of the two ions initially increased with increasing x and then decreased when the Ba2+ concentration exceeded a certain value. The peak shape and lifetime of the fluorescence at 1.55 μm depended on x as well as the spatial distribution of both ions. These results indicate that although ErOn polyhedra are preferentially coordinated with Ba2+ ions and their local structure is affected by the coordination of Ba2+, there is a maximum in the amount of Ba2+ ions that can coordinate ErOn polyhedra since the available space for Ba2+ ions is limited. These findings provide us with efficient ways to design the chemical composition of glasses with superior Er3+ fluorescence properties for optical communication network systems.

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...

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...

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...

Periodontal disease level-butyric acid amounts locally administered in the rat gingival mucosa induce ER stress in the systemic blood.

Science.gov (United States)

Cueno, Marni E; Saito, Yuko; Ochiai, Kuniyasu

2016-05-01

Periodontal diseases have long been postulated to contribute to systemic diseases and, likewise, it has been proposed that periodontal disease treatment may ameliorate certain systemic diseases. Short-chain fatty acids (SCFA) are major secondary metabolites produced by oral anaerobic bacteria and, among the SCFAs, butyric acid (BA) in high amounts contribute to periodontal disease development. Periodontal disease level-butyric acid (PDL-BA) is found among patients suffering from periodontal disease and has previously shown to induce oxidative stress, whereas, oxidative stress is correlated to endoplasmic reticulum (ER) stress. This would imply that PDL-BA may likewise stimulate ER stress, however, this was never elucidated. A better understanding of the correlation between PDL-BA and systemic ER stress stimulation could shed light on the possible systemic effects of PDL-BA-related periodontal diseases. Here, PDL-BA was injected into the gingival mucosa and the systemic blood obtained from the rat jugular was collected at 0, 15, 60, and 180 min post-injection. Collected blood samples were purified and only the blood cytosol was used throughout this study. Subsequently, we measured blood cytosolic GADD153, Ca(2+), representative apoptotic and inflammatory caspases, and NF-κB amounts. We found that PDL-BA presence increased blood cytosolic GADD153 and Ca(2+) amounts. Moreover, we observed that blood cytosolic caspases and NF-κB were activated only at 60 and 180 min post-injection in the rat gingival mucosa. This suggests that PDL-BA administered through the gingival mucosa may influence the systemic blood via ER stress stimulation and, moreover, prolonged PDL-BA retention in the gingival mucosa may play a significant role in ER stress-related caspase and NF-κB activation. In a periodontal disease scenario, we propose that PDL-BA-related ER stress stimulation leading to the simultaneous activation of apoptosis and inflammation may contribute to periodontal disease

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....

Hvorfor er danske fødevarer dyre?

DEFF Research Database (Denmark)

Hansen, Henning Otte

2015-01-01

De danske fødevarepriser er generelt høje set i forhold til resten af EU og også i forhold til lande uden for EU. Overordnet set er der en række forklaringer på internationale prisforskelle, og der er også flere mulige årsager til de høje danske fødevarepriser. Forskelle i moms, kvalitet...

TMBIM3/GRINA is a novel unfolded protein response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis.

Science.gov (United States)

Rojas-Rivera, D; Armisén, R; Colombo, A; Martínez, G; Eguiguren, A L; Díaz, A; Kiviluoto, S; Rodríguez, D; Patron, M; Rizzuto, R; Bultynck, G; Concha, M L; Sierralta, J; Stutzin, A; Hetz, C

2012-06-01

Transmembrane BAX inhibitor motif-containing (TMBIM)-6, also known as BAX-inhibitor 1 (BI-1), is an anti-apoptotic protein that belongs to a putative family of highly conserved and poorly characterized genes. Here we report the function of TMBIM3/GRINA in the control of cell death by endoplasmic reticulum (ER) stress. Tmbim3 mRNA levels are strongly upregulated in cellular and animal models of ER stress, controlled by the PERK signaling branch of the unfolded protein response. TMBIM3/GRINA synergies with TMBIM6/BI-1 in the modulation of ER calcium homeostasis and apoptosis, associated with physical interactions with inositol trisphosphate receptors. Loss-of-function studies in D. melanogaster demonstrated that TMBIM3/GRINA and TMBIM6/BI-1 have synergistic activities against ER stress in vivo. Similarly, manipulation of TMBIM3/GRINA levels in zebrafish embryos revealed an essential role in the control of apoptosis during neuronal development and in experimental models of ER stress. These findings suggest the existence of a conserved group of functionally related cell death regulators across species beyond the BCL-2 family of proteins operating at the ER membrane.

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....

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...

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...

Dynamic Regulation of Ero1α and Peroxiredoxin 4 Localization in the Secretory Pathway*

Science.gov (United States)

Kakihana, Taichi; Araki, Kazutaka; Vavassori, Stefano; Iemura, Shun-ichiro; Cortini, Margherita; Fagioli, Claudio; Natsume, Tohru; Sitia, Roberto; Nagata, Kazuhiro

2013-01-01

In the early secretory compartment (ESC), a network of chaperones and enzymes assists oxidative folding of nascent proteins. Ero1 flavoproteins oxidize protein disulfide isomerase (PDI), generating H2O2 as a byproduct. Peroxiredoxin 4 (Prx4) can utilize luminal H2O2 to oxidize PDI, thus favoring oxidative folding while limiting oxidative stress. Interestingly, neither ER oxidase contains known ER retention signal(s), raising the question of how cells prevent their secretion. Here we show that the two proteins share similar intracellular localization mechanisms. Their secretion is prevented by sequential interactions with PDI and ERp44, two resident proteins of the ESC-bearing KDEL-like motifs. PDI binds preferentially Ero1α, whereas ERp44 equally retains Ero1α and Prx4. The different binding properties of Ero1α and Prx4 increase the robustness of ER redox homeostasis. PMID:23979138

Håndbold er en praksis!

DEFF Research Database (Denmark)

Olsen, Poul Bitsch

2008-01-01

Dansk håndbold er en kæmpemæssig succeshistorie. Ser man snævert på den udvikling, elitedelen af sporten har gennemlevet de seneste 15 år, viser stort set alle tænkelige parametre fremgang. De internationale resultater for lands og klubhold er med få udfald blevet stadigt bedre, omsætningen i klu...

Crystal and molecular structure of the coordination compounds of Er3+ with 1-(methoxydiphenylphosphoryl)-2-diphenylphosphorylbenzene [ErL21(NO3)2]2[Er(NO3)2(H2O)5]0.333(NO3)2.333 · 2.833H2O and its ethyl substituted derivative [ErL22(NO3)2][Er(NO3)5]0.5 · 0.5H2O

International Nuclear Information System (INIS)

Polyakova, I. N.; Baulin, V. E.; Ivanova, I. S.; Pyatova, E. N.; Sergienko, V. S.; Tsivadze, A. Yu.

2015-01-01

The coordination compounds of Er 3+ with 1-(methoxydiphenylphosphoryl)-2-diphenylphosphorylbenzene [ErL 2 1 (NO 3 ) 2 ] 2 [Er(NO 3 ) 2 (H 2 O) 5 ] 0.333 (NO 3 ) 2.333 · 2.833H 2 O (I) and its ethyl substituted derivative [ErL 2 2 (NO 3 ) 2 ][Er(NO 3 ) 5 ] 0.5 · 0.5H 2 O (II) are synthesized and their crystal structures are studied. I and II contain [ErL 2 (NO 3 ) 2 ] + complex cations of identical composition and close structure. The eight-vertex polyhedron of the Er atom in the shape of a distorted octahedron with two split trans vertices is formed by the O atoms of the phosphoryl groups of L ligands and nitrate anions. L ligands close nine-membered metallocycles. The structures contain spacious channels which are populated differently, namely, by disordered [Er(NO 3 ) 2 (H 2 O) 5 ] + complex cations, NO 3 − anions, and crystallization water molecules in I and disordered [Er(NO 3 ) 5 ] 2− complex anions and crystallization water molecules in II. The IR spectra of I and II are studied

ER stress inhibitor attenuates hearing loss and hair cell death in Cdh23erl/erl mutant mice.

Science.gov (United States)

Hu, Juan; Li, Bo; Apisa, Luke; Yu, Heping; Entenman, Shami; Xu, Min; Stepanyan, Ruben; Guan, Bo-Jhih; Müller, Ulrich; Hatzoglou, Maria; Zheng, Qing Yin

2016-11-24

Hearing loss is one of the most common sensory impairments in humans. Mouse mutant models helped us to better understand the mechanisms of hearing loss. Recently, we have discovered that the erlong (erl) mutation of the cadherin23 (Cdh23) gene leads to hearing loss due to hair cell apoptosis. In this study, we aimed to reveal the molecular pathways upstream to apoptosis in hair cells to exploit more effective therapeutics than an anti-apoptosis strategy. Our results suggest that endoplasmic reticulum (ER) stress is the earliest molecular event leading to the apoptosis of hair cells and hearing loss in erl mice. We also report that the ER stress inhibitor, Salubrinal (Sal), could delay the progression of hearing loss and preserve hair cells. Our results provide evidence that therapies targeting signaling pathways in ER stress development prevent hair cell apoptosis at an early stage and lead to better outcomes than those targeting downstream factors, such as tip-link degeneration and apoptosis.

Exploring the cross talk between ER stress and inflammation in age-related macular degeneration.

Directory of Open Access Journals (Sweden)

Samira Kheitan

Full Text Available Increasing evidence demonstrates that inflammation and endoplasmic reticulum (ER stress is implicated in the development and progression of age-related macular degeneration (AMD, a multifactorial neurodegenerative disease. However the cross talk between these cellular mechanisms has not been clearly and fully understood. The present study investigates a possible intersection between ER stress and inflammation in AMD. In this study, we recruited two collections of involved protein markers to retrieve their interaction information from IMEx-curated databases, which are the most well- known protein-protein interaction collections, allowing us to design an intersection network for AMD that is unprecedented. In order to find expression activated subnetworks, we utilized AMD expression profiles in our network. In addition, we studied topological characteristics of the most expressed active subnetworks to identify the hubs. With regard to topological quantifications and expressional activity, we reported a list of the most pivotal hubs which are potentially applicable as probable therapeutic targets. Furthermore, we introduced MAPK signaling pathway as a significantly involved pathway in the association between ER stress and inflammation, leading to promising new directions in discovering AMD formation mechanisms and possible treatments.

Exploring the cross talk between ER stress and inflammation in age-related macular degeneration.

Science.gov (United States)

Kheitan, Samira; Minuchehr, Zarrin; Soheili, Zahra-Soheila

2017-01-01

Increasing evidence demonstrates that inflammation and endoplasmic reticulum (ER) stress is implicated in the development and progression of age-related macular degeneration (AMD), a multifactorial neurodegenerative disease. However the cross talk between these cellular mechanisms has not been clearly and fully understood. The present study investigates a possible intersection between ER stress and inflammation in AMD. In this study, we recruited two collections of involved protein markers to retrieve their interaction information from IMEx-curated databases, which are the most well- known protein-protein interaction collections, allowing us to design an intersection network for AMD that is unprecedented. In order to find expression activated subnetworks, we utilized AMD expression profiles in our network. In addition, we studied topological characteristics of the most expressed active subnetworks to identify the hubs. With regard to topological quantifications and expressional activity, we reported a list of the most pivotal hubs which are potentially applicable as probable therapeutic targets. Furthermore, we introduced MAPK signaling pathway as a significantly involved pathway in the association between ER stress and inflammation, leading to promising new directions in discovering AMD formation mechanisms and possible treatments.

Degradation Signals Recognized by the Ubc6p-Ubc7p Ubiquitin-Conjugating Enzyme Pair

Science.gov (United States)

Gilon, Tamar; Chomsky, Orna; Kulka, Richard G.

2000-01-01

Proteolysis by the ubiquitin-proteasome system is highly selective. Specificity is achieved by the cooperation of diverse ubiquitin-conjugating enzymes (Ubcs or E2s) with a variety of ubiquitin ligases (E3s) and other ancillary factors. These recognize degradation signals characteristic of their target proteins. In a previous investigation, we identified signals directing the degradation of β-galactosidase and Ura3p fusion proteins via a subsidiary pathway of the ubiquitin-proteasome system involving Ubc6p and Ubc7p. This pathway has recently been shown to be essential for the degradation of misfolded and regulated proteins in the endoplasmic reticulum (ER) lumen and membrane, which are transported to the cytoplasm via the Sec61p translocon. Mutant backgrounds which prevent retrograde transport of ER proteins (hrd1/der3Δ and sec61-2) did not inhibit the degradation of the β-galactosidase and Ura3p fusions carrying Ubc6p/Ubc7p pathway signals. We therefore conclude that the ubiquitination of these fusion proteins takes place on the cytosolic face of the ER without prior transfer to the ER lumen. The contributions of different sequence elements to a 16-amino-acid-residue Ubc6p-Ubc7p-specific signal were analyzed by mutation. A patch of bulky hydrophobic residues was an essential element. In addition, positively charged residues were found to be essential. Unexpectedly, certain substitutions of bulky hydrophobic or positively charged residues with alanine created novel degradation signals, channeling the degradation of fusion proteins to an unidentified proteasomal pathway not involving Ubc6p and Ubc7p. PMID:10982838

Reference hearing threshold levels for chirp signals delivered by an ER-3A insert earphone

DEFF Research Database (Denmark)

Gøtsche-Rasmussen, Kristian; Poulsen, Torben; Elberling, Claus

2012-01-01

back from a Tucker Davies Technologies System II, and a Matlab program controlled the test setup. The results are specified in dB peak-to-peak equivalent threshold sound pressure levels (dB peETSPL). Study sample: The test group consisted of 25 otologically-normal young adults (age 18–25 years......Objective: To establish reference hearing threshold levels for chirps and frequency-specific chirps. Design: Hearing thresholds were determined monaurally for broad-band chirps and octave-band chirps using the Etymotic Research, ER-3A insert earphone. The chirps were presented using two repetition...

Study of signal discrimination for timing measurements

CERN Document Server

Krepelkova, Marta

2017-01-01

The timing detectors of the CMS-TOTEM Precision Proton Spectrometer (CT-PPS) are currently read out using discrete components, separated into three boards; the first board hosts the sensors and the amplifiers, the second one hosts the discriminators and the third is dedicated to the Time to Digital Converter (TDC) and to the interface with the data acquisition system (DAQ). This work proposes a new front-end electronics for the timing detector, with sensors, amplifiers and discriminators integrated on the same board. We simulated an updated version of the amplifier together with a discriminator designed using commercial components. We decided to use an LVDS buffer as a discriminator, because of its cost, availability, speed and lo w power consumption. As a proof of concept, we used the LVDS input of an FPGA to discriminate signals produced by a detector prototype, using a radioactive source.

Binding of Signal Recognition Particle Gives Ribosome/Nascent Chain Complexes a Competitive Advantage in Endoplasmic Reticulum Membrane Interaction

Science.gov (United States)

Neuhof, Andrea; Rolls, Melissa M.; Jungnickel, Berit; Kalies, Kai-Uwe; Rapoport, Tom A.

1998-01-01

Most secretory and membrane proteins are sorted by signal sequences to the endoplasmic reticulum (ER) membrane early during their synthesis. Targeting of the ribosome-nascent chain complex (RNC) involves the binding of the signal sequence to the signal recognition particle (SRP), followed by an interaction of ribosome-bound SRP with the SRP receptor. However, ribosomes can also independently bind to the ER translocation channel formed by the Sec61p complex. To explain the specificity of membrane targeting, it has therefore been proposed that nascent polypeptide-associated complex functions as a cytosolic inhibitor of signal sequence- and SRP-independent ribosome binding to the ER membrane. We report here that SRP-independent binding of RNCs to the ER membrane can occur in the presence of all cytosolic factors, including nascent polypeptide-associated complex. Nontranslating ribosomes competitively inhibit SRP-independent membrane binding of RNCs but have no effect when SRP is bound to the RNCs. The protective effect of SRP against ribosome competition depends on a functional signal sequence in the nascent chain and is also observed with reconstituted proteoliposomes containing only the Sec61p complex and the SRP receptor. We conclude that cytosolic factors do not prevent the membrane binding of ribosomes. Instead, specific ribosome targeting to the Sec61p complex is provided by the binding of SRP to RNCs, followed by an interaction with the SRP receptor, which gives RNC–SRP complexes a selective advantage in membrane targeting over nontranslating ribosomes. PMID:9436994

Dietary toxins, endoplasmic reticulum (ER) stress and diabetes.

Science.gov (United States)

Hettiarachchi, Kalindi D; Zimmet, Paul Z; Myers, Mark A

2008-05-01

The incidence of Type 1 diabetes has been increasing at a rate too rapid to be due to changes in genetic risk. Instead changes in environmental factors are the likely culprit. The endoplasmic reticulum (ER) plays an important role in the production of newly synthesized proteins and interference with these processes leads to ER stress. The insulin-producing beta cells are particularly prone to ER stress as a result of their heavy engagement in insulin production. Increasing evidence suggests ER stress is central to initiation and progression of Type 1 diabetes. An early environmental exposure, such as toxins and viral infections, can impart a significant physiological load on beta cells to initiate abnormal processing of proinsulin, ER stress and insulin secretory defects. Release of altered proinsulin from the beta cells early in life may trigger autoimmunity in those with genetic susceptibility leading to cytokine-induced nitric oxide production and so exacerbating ER stress in beta cells, ultimately leading to apoptosis of beta cells and diabetes. Here we suggest that ER stress is an inherent cause of beta cell dysfunction and environmental factors, in particular dietary toxins derived from Streptomyces in infected root vegetables, can impart additional stress that aggravates beta cell death and progression to diabetes. Furthermore, we propose that the increasing incidence of Type 1 diabetes may be accounted for by increased dietary exposure to ER-stress-inducing Streptomyces toxins.

Contrasting hypoxic effects on breast cancer stem cell hierarchy is dependent on ER-α status.

Science.gov (United States)

Harrison, Hannah; Rogerson, Lynsey; Gregson, Hannah J; Brennan, Keith R; Clarke, Robert B; Landberg, Göran

2013-02-15

Tumor hypoxia is often linked to decreased survival in patients with breast cancer and current therapeutic strategies aim to target the hypoxic response. One way in which this is done is by blocking hypoxia-induced angiogenesis. Antiangiogenic therapies show some therapeutic potential with increased disease-free survival, but these initial promising results are short lived and followed by tumor progression. We hypothesized that this may be due to altered cancer stem cell (CSC) activity resulting from increased tumor hypoxia. We studied the effects of hypoxia on CSC activity, using in vitro mammosphere and holoclone assays as well as in vivo limiting dilution experiments, in 13 patient-derived samples and four cell lines. There was a HIF-1α-dependent CSC increase in ER-α-positive cancers following hypoxic exposure, which was blocked by inhibition of estrogen and Notch signaling. A contrasting decrease in CSC was seen in ER-α-negative cancers. We next developed a xenograft model of cell lines and patient-derived samples to assess the hypoxic CSC response. Varying sizes of xenografts were collected and analyzed for HIF1-α expression and CSC. The same ER-α-dependent contrasting hypoxic-CSC response was seen validating the initial observation. These data suggest that ER-α-positive and negative breast cancer subtypes respond differently to hypoxia and, as a consequence, antiangiogenic therapies will not be suitable for both subgroups.

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....

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......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...

Transformation of tobacco plant (Nicotiana tabacum L. with the recombinant hepatitis B virus genes 35SHBsAg and 35SHBsAgER

Directory of Open Access Journals (Sweden)

Juliana Martins Ribeiro

2010-03-01

Full Text Available The recombinant surface antigen of hepatitis B virus (HBsAg, purified from transgenic plants, proved to be efficient when utilized for raising anti-HB antibodies for the prevention of hepatitis B. Because of the important role of the HBsAg antigen in hepatitis B prevention, the coding sequence of HBsAg antigen, with or without the addition of the carboxi-terminus sequence for protein retention in the endoplasmatic reticulum, was linked to cauliflower mosaic virus 35S promoter, tobacco mosaic virus leader sequence Ω, and the transcription terminator sequence. The aim of this work was to clone the chimeric gene 35SHBsAgER in the plant expression vector pGPTV/Kan/Asc. The resulting plasmid, called pG35SHBsAgER, and another plasmid produced previously in our laboratory called pG35SHBsAg, were transferred to Agrobacterium tumefaciens, and tobacco leaves, of the SR1 cultivar were used as explants for genetic transformation. Twenty-one fully regenerated plants were obtained (10 for the pG35SHBsAg construction and 11 for the pG35SHBsAgER construction. The genomic DNA of all plants was analyzed by PCR, and the presence of the transgene was confirmed in all plants.

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.

Er nogen mere lige end andre?

DEFF Research Database (Denmark)

Møberg, Rasmus Juul

normativ fordring. Kohlis (2007) formulering af normalbiografien er en tredeling af livsforløbet (uddannelse – arbejdsliv - pension). En tredeling der bliver kritiseret for at være køns- og familieblind, hvorfor linked lives-begrebet bliver introduceret. Begrebet har den teoretiske implikation...... analyser tager højde for afhængighed over tid i den afhængige variabel. Overordnet set er det tre aspekter af datas karakteristika, der fordrer specielle metoder. Det er censurering af data, tidsmæssig variation i de uafhængige variable samt potentiel korrelation mellem målingerne af den afhængige variabel...... for disse ændringer, hvorved risikoen for en given transition beregnes mere præcist. Afhandlingens empiriske grundlag er registerdata for alle personer i Danmark, der tilhører fødselskohorterne 1968, 1972 og 1976. Data dækker over personlige, familiære forhold og oplysninger på arbejdspladsniveau, hvor den...

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.

Synthesis, crystal structure and electrical properties of A-site cation ordered BaErMn2O5 and BaErMn2O6

International Nuclear Information System (INIS)

Świerczek, Konrad; Klimkowicz, Alicja; Zheng, Kun; Dabrowski, Bogdan

2013-01-01

In this paper, we report on a synthesis procedure, structural and electrical properties of BaErMn 2 O 5 and BaErMn 2 O 6 , A-site double perovskites having layered arrangement of Ba and Er cations. These materials belong to a family of BaLnMn 2 O 5+δ oxides, which up to now were successfully synthesized for Ln=Y and La–Ho lanthanides. Up to our knowledge, this is the first report on the successful synthesis of BaErMn 2 O 5 and BaErMn 2 O 6 , yielding>95 wt% of the considered compounds. Structural characterization of the materials is given at room temperature, together with in situ XRD studies, performed during oxidation of BaErMn 2 O 5 in air, at elevated temperatures up to 500 °C. A complex structural behavior was observed, with oxidation process of BaErMn 2 O 5 occurring at around 300 °C. The oxidized BaErMn 2 O 6 shows a structural phase transition at about 225 °C. Results of structural studies are supported by thermogravimetric measurements of the oxidation process, performed in air, as well as reduction process, preformed in 5 vol% of H 2 in Ar. Additionally, isothermal oxidation/reduction cycles were measured at 500 °C, showing interesting properties of BaErMn 2 O 5+δ , from a point of view of oxygen storage technology. Electrical conductivity of BaErMn 2 O 5 is of the order of 10 −4 S cm −1 at room temperature and shows activated character on temperature with activation energy E a =0.30(1) eV. Positive sign of Seebeck coefficient for this material indicates holes as dominant charge carriers. Oxidized BaErMn 2 O 6 possesses much higher electrical conductivity, almost 0.2 S cm −1 at room temperature. Additional, about 10-fold increase of electrical conductivity, occurring in the vicinity of 225 °C for this material, can be associated with phase transition from charge/orbital-ordered insulator COI(CE) to paramagnetic metal PM phase. The highest conductivity for BaErMn 2 O 6 was measured near 500 °C and is almost equal to 40 S cm −1 , while

Multiple band structure in 156Er

International Nuclear Information System (INIS)

Sunyar, A.W.; Der Mateosian, E.; Kistner, O.C.; Johnson, A.; Lumpkin, A.H.; Thieberger, P.

1976-01-01

The 142 Nd( 18 O,4n) 156 Er reaction at 90-95 MeV was used to study 156 Er high-spin states to spin 24. In addition to the background ground-state band, two well developed off-spin side bands, one of each parity, were observed. (Auth.)

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...

Led strategisk med 3 F'er

DEFF Research Database (Denmark)

Klausen, Kurt Klaudi

2017-01-01

Artiklen gennemgår kort de tre F'er: at fremskrive, forudse og forestille som strategiske værktøjer til strategic forecast......Artiklen gennemgår kort de tre F'er: at fremskrive, forudse og forestille som strategiske værktøjer til strategic forecast...

Wise retained in the endoplasmic reticulum inhibits Wnt signaling by reducing cell surface LRP6.

Science.gov (United States)

Guidato, Sonia; Itasaki, Nobue

2007-10-15

The Wnt signaling pathway is tightly regulated by extracellular and intracellular modulators. Wise was isolated as a secreted protein capable of interacting with the Wnt co-receptor LRP6. Studies in Xenopus embryos revealed that Wise either enhances or inhibits the Wnt pathway depending on the cellular context. Here we show that the cellular localization of Wise has distinct effects on the Wnt pathway readout. While secreted Wise either synergizes or inhibits the Wnt signals depending on the partner ligand, ER-retained Wise consistently blocks the Wnt pathway. ER-retained Wise reduces LRP6 on the cell surface, making cells less susceptible to the Wnt signal. This study provides a cellular mechanism for the action of Wise and introduces the modulation of cellular susceptibility to Wnt signals as a novel mechanism of the regulation of the Wnt pathway.

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...

Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.

Science.gov (United States)

Perry, Ben D; Rahnert, Jill A; Xie, Yang; Zheng, Bin; Woodworth-Hobbs, Myra E; Price, S Russ

2018-01-01

Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4). Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides), palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242). Inflammatory indicators of TLR4 activation (IL-6 and TNFα) and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle in part by induction of ER stress.

Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.

Directory of Open Access Journals (Sweden)

Ben D Perry

Full Text Available Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4. Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides, palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242. Inflammatory indicators of TLR4 activation (IL-6 and TNFα and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle in part by induction of ER stress.

Hypermethylation pattern of ESR and PgR genes and lacking estrogen and progesterone receptors in human breast cancer tumors: ER/PR subtypes.

Science.gov (United States)

Pirouzpanah, Saeed; Taleban, Forough-Azam; Mehdipour, Parvin; Sabour, Siamak; Atri, Morteza

2018-02-14

The option of endocrine therapy in breast cancer remains conventionally promising. We aimed to investigate how accurately the pattern of hypermethylation at estrogen receptor (ESR) and progesterone receptor (PgR) genes may associate with relative expression and protein status of ER, PR and the combinative phenotype of ER/PR. In this consecutive case-series, we enrolled 139 primary diagnosed breast cancer. Methylation specific PCR was used to assess the methylation status (individual test). Tumor mRNA expression levels were evaluated using real-time RT-PCR. Immunohistochemistry data was used to present hormonal receptor status of a tumor (as test reference). Methylation at ESR1 was comparably frequent in ER-breast tumors (83.0%, PPR- conditions (Cramer's V= 0.44, PPR (77.1%, PPR expressions (55.6%, PPR- (64.4%, PPR-, the hypermethylation of PgRb seem another epigenetic signalling variable actively associate with methylated ESR1 to show lack of ER+/PR+ tumors in breast cancer.

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.

Generation of signaling specificity in Arabidopsis by spatially restricted buffering of ligand-receptor interactions.

Science.gov (United States)

Abrash, Emily B; Davies, Kelli A; Bergmann, Dominique C

2011-08-01

Core signaling pathways function in multiple programs during multicellular development. The mechanisms that compartmentalize pathway function or confer process specificity, however, remain largely unknown. In Arabidopsis thaliana, ERECTA (ER) family receptors have major roles in many growth and cell fate decisions. The ER family acts with receptor TOO MANY MOUTHS (TMM) and several ligands of the EPIDERMAL PATTERNING FACTOR LIKE (EPFL) family, which play distinct yet overlapping roles in patterning of epidermal stomata. Here, our examination of EPFL genes EPFL6/CHALLAH (CHAL), EPFL5/CHALLAH-LIKE1, and EPFL4/CHALLAH-LIKE2 (CLL2) reveals that this family may mediate additional ER-dependent processes. chal cll2 mutants display growth phenotypes characteristic of er mutants, and genetic interactions are consistent with CHAL family molecules acting as ER family ligands. We propose that different classes of EPFL genes regulate different aspects of ER family function and introduce a TMM-based discriminatory mechanism that permits simultaneous, yet compartmentalized and distinct, function of the ER family receptors in growth and epidermal patterning.

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?...

Quantification of PRL/Stat5 signaling with a novel pGL4-CISH reporter.

Science.gov (United States)

Fang, Feng; Antico, Giovanni; Zheng, Jiamao; Clevenger, Charles V

2008-02-06

Elevations of serum prolactin (PRL) are associated with an increased risk for breast cancer. PRL signaling through its prolactin receptor (PRLr) involves the Jak2/Stat5 pathway. Luciferase-based reporter assays have been widely used to evaluate the activity of this pathway. However, the existing reporters are often not sensitive enough to monitor the effect of PRL in this pathway. In this study, a new biologically relevant reporter, pGL4-CISH, was generated to study the PRL/Jak2/Stat5 signaling pathway. The sensitivity of pGL4-CISH to detect PRL was superior to that of several other commonly utilized Stat5-responsive reporters. Interestingly, the enhanced function pGL4-CISH was restricted to the estrogen receptor positive (ER+) human breast cancer cell lines T47D and MCF7, but not in the ER-MDA-231, BT-474, or MCF10A cell lines. Overexpression of Stat5 further enhanced the effect of PRL on pGL4-CISH. These studies demonstrate that pGL4-CISH is a novel and sensitive reporter for assessing the activity of the PRL/Stat5 signaling pathway in the ER+ human breast cancer cells.

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 -...... - så er selve trafikken og forventningerne blandt medtrafikanterne helt forskellige fra det, vi er vant til. Udgivelsesdato: Februar...

Interlayer exchange coupling in Er|Tb superlattices mediated by short range incommensurate Er order

International Nuclear Information System (INIS)

Pfuhl, E; Brueckel, T; Voigt, J; Mattauch, S; Korolkov, D

2010-01-01

We study the magnetic correlations in Er|Tb superlattices by means of off-specular scattering of polarized neutrons. We show here the co-existence of inhomogeneous magnetic states: i) ferromagnetic order of moments within the Tb layers below 230 K (FM), correlation length of about 10 bilayer, ii) an incommensurate modulated magnetic order, restricted to single Er layers and iii) antiferromagnetic coupling of ferromagnetic layers below 70K (AFC). Polarised off-specular neutron scattering under grazing incidence reveals that i) magnetic fluctuations appear when the sample is cooled below 70 K, ii) these fluctuations lead to AFC, when the sample is cooled to 10 K, which iii) persists, when the sample is subsequently heated up to 45 K, while the order is not present during the cooling cycle. Also the short range incommensurate order changes accordingly, implying that the magnetic order in the Er layers mediates the interlayer coupling between ferromagnetic Tb layers.

RNAi reduces expression and intracellular retention of mutant cartilage oligomeric matrix protein.

Directory of Open Access Journals (Sweden)

Karen L Posey

2010-04-01

Full Text Available Mutations in cartilage oligomeric matrix protein (COMP, a large extracellular glycoprotein expressed in musculoskeletal tissues, cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia. These mutations lead to massive intracellular retention of COMP, chondrocyte death and loss of growth plate chondrocytes that are necessary for linear growth. In contrast, COMP null mice have only minor growth plate abnormalities, normal growth and longevity. This suggests that reducing mutant and wild-type COMP expression in chondrocytes may prevent the toxic cellular phenotype causing the skeletal dysplasias. We tested this hypothesis using RNA interference to reduce steady state levels of COMP mRNA. A panel of shRNAs directed against COMP was tested. One shRNA (3B reduced endogenous and recombinant COMP mRNA dramatically, regardless of expression levels. The activity of the shRNA against COMP mRNA was maintained for up to 10 weeks. We also demonstrate that this treatment reduced ER stress. Moreover, we show that reducing steady state levels of COMP mRNA alleviates intracellular retention of other extracellular matrix proteins associated with the pseudoachondroplasia cellular pathology. These findings are a proof of principle and the foundation for the development of a therapeutic intervention based on reduction of COMP expression.

Er frygten for Kina vores eneste håb?

DEFF Research Database (Denmark)

Mehlsen, Camilla

2011-01-01

Man siger, at håbet er lysegrønt, men i det 21. århundrede er håbet rødt som riget i midten. Mens optimismen vinder frem i Asien med Kina som bannerfører, er Vesten ramt af frygt, og det forplanter sig negativt til uddannelsessystemet. Er positive følelser hemmeligheden bag, at asiatiske lande st...... stormer frem i internationale undersøgelser som PISA?...

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.

Operational durability of a giant ER valve for Braille display

Science.gov (United States)

Luning, Xu; Han, Li; Yufei, Li; Shen, Rong; Kunquan, Lu

2017-05-01

The compact configuration of giant ER (electrorheological) valves provides the possibility of realizing a full-page Braille display. The operational durability of ER valves is a key issue in fulfilling a Braille display. A giant ER valve was used to investigate the variations in pressure drops and critical pressure drops of the valves over a long period under some typical operational parameters. The results indicate that neither the pressure drops nor critical pressure drops of giant ER valves show apparent deterioration over a long period. Without ER fluid exchange, a blockage appears in the channel of the valve because the ER structures induced by an external electric field cannot be broken by the Brownian motion of hydraulic oil molecules when the external electric field is removed. Forcing ER fluid flow is an effective and necessary method to keep the channel of the valve unblocked. Thus the operational durability of the valve using giant ER fluids is able to meet the demands of Braille display.

Hvordan er det å leve med CRPS?

OpenAIRE

Hovind, Thomas

2014-01-01

Hensikten med denne studien er å se på hvordan pasienter med komplekst regionalt smertesyndrom (CRPS) opplever å leve med tilstanden og hvordan disse pasientene har opplevd å bli møtt i helsevesenet. CRPS er en langvarig tilstand med sterke smerter som kan medføre økt smerterespons, redusert funksjon og nedsatt livskvalitet hos pasientene. Studien er en kvalitativ undersøkelse basert på dybdeintervju av fire pasienter med CRPS. Pasientene ble rekruttert fra en smerteavdeling i Nord-Norge og u...

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...

Shikonin ameliorates isoproterenol (ISO)-induced myocardial damage through suppressing fibrosis, inflammation, apoptosis and ER stress.

Science.gov (United States)

Yang, Jun; Wang, Zhao; Chen, Dong-Lin

2017-09-01

Shikonin, isolated from the roots of herbal plant Lithospermum erythrorhizon, is a naphthoquinone. It has been reported to exert beneficial anti-inflammatory effects and anti-oxidant properties in various diseases. Isoproterenol (ISO) has been widely used to establish cardiac injury in vivo and in vitro. However, shikonin function in ISO-induced cardiac injury remains uncertain. In our study, we attempted to investigate the efficiency and possible molecular mechanism of shikonin in cardiac injury treatment induced by ISO. In vivo, C57BL6 mice were subcutaneously injected with 5mg/kg ISO to induce heart failure. And mice were given a gavage of shikonin (2 or 4mg/kg/d, for four weeks). Cardiac function, fibrosis indices, inflammation response, apoptosis and endoplasmic reticulum (ER) stress were calculated. Pathological alterations, fibrosis-, inflammation-, apoptosis- and ER stress-related molecules were examined. In ISO-induced cardiac injury, shikonin significantly ameliorated heart function, decreased myocardial fibrosis, suppressed inflammation, attenuated apoptosis and ER stress through impeding collagen accumulation, Toll like receptor 4/nuclear transcription factor κB (TLR4/NF-κB), Caspase-3 and glucose-regulated protein 78 (GRP78) signaling pathways activity, relieving heart failure in vivo. Also, in vitro, shikonin attenuated ISO-induced cardiac muscle cells by reducing fibrosis, inflammation, apoptosis and ER stress. Our findings indicated that shikonin treatment attenuated ISO-induced heart injury, providing an effective therapeutic strategy for heart failure treatment for future. Copyright © 2017. Published by Elsevier Masson SAS.

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...

"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....

Factors That Influence Enrolment and Retention in Ghana' National Health Insurance Scheme.

Science.gov (United States)

Kotoh, Agnes Millicent; Aryeetey, Genevieve Cecilia; Van der Geest, Sjaak

2017-10-17

The government of Ghana introduced the National Health Insurance Scheme (NHIS) in 2004 with the goal of achieving universal coverage within 5 years. Evidence, however, shows that expanding NHIS coverage and especially retaining members have remained a challenge. A multilevel perspective was employed as a conceptual framework and methodological tool to examine why enrolment and retention in the NHIS remains low. A household survey was conducted after 20 months educational and promotional activities aimed at improving enrolment and retention rates in 15 communities in the Central and Eastern Regions (ERs) of Ghana. Observation, indepth interviews and informal conversations were used to collect qualitative data. Forty key informants (community members, health providers and district health insurance schemes' [DHISs] staff) purposely selected from two casestudy communities in the Central Region (CR) were interviewed. Several community members, health providers and DHISs' staff were also engaged in informal conversations in the other five communities in the region. Also, four staff of the Ministry of Health (MoH), Ghana Health Service (GHS) and National Health Insurance Authority (NHIA) were engaged in in-depth interviews. Descriptive statistics was used to analyse quantitative data. Qualitative data was analysed using thematic content analysis. The results show that factors that influence enrolment and retention in the NHIS are multi-dimensional and cut across all stakeholders. People enrolled and renewed their membership because of NHIS' benefits and health providers' positive behaviour. Barriers to enrolment and retention included: poverty, traditional risk-sharing arrangements influence people to enrol or renew their membership only when they need healthcare, dissatisfaction about health providers' behaviour and service delivery challenges. Given the multi-dimensional nature of barriers to enrolment and retention, we suggest that the NHIA should engage DHISs, health

Two endoplasmic reticulum (ER) membrane proteins that facilitate ER-to-Golgi transport of glycosylphosphatidylinositol-anchored proteins.

Science.gov (United States)

Barz, W P; Walter, P

1999-04-01

Many eukaryotic cell surface proteins are anchored in the lipid bilayer through glycosylphosphatidylinositol (GPI). GPI anchors are covalently attached in the endoplasmic reticulum (ER). The modified proteins are then transported through the secretory pathway to the cell surface. We have identified two genes in Saccharomyces cerevisiae, LAG1 and a novel gene termed DGT1 (for "delayed GPI-anchored protein transport"), encoding structurally related proteins with multiple membrane-spanning domains. Both proteins are localized to the ER, as demonstrated by immunofluorescence microscopy. Deletion of either gene caused no detectable phenotype, whereas lag1Delta dgt1Delta cells displayed growth defects and a significant delay in ER-to-Golgi transport of GPI-anchored proteins, suggesting that LAG1 and DGT1 encode functionally redundant or overlapping proteins. The rate of GPI anchor attachment was not affected, nor was the transport rate of several non-GPI-anchored proteins. Consistent with a role of Lag1p and Dgt1p in GPI-anchored protein transport, lag1Delta dgt1Delta cells deposit abnormal, multilayered cell walls. Both proteins have significant sequence similarity to TRAM, a mammalian membrane protein thought to be involved in protein translocation across the ER membrane. In vivo translocation studies, however, did not detect any defects in protein translocation in lag1Delta dgt1Delta cells, suggesting that neither yeast gene plays a role in this process. Instead, we propose that Lag1p and Dgt1p facilitate efficient ER-to-Golgi transport of GPI-anchored proteins.

Die HECT-Ligase Hul5, eine neue Komponente der ER-assoziierten Proteindegradation

OpenAIRE

Kohlmann, Sonja

2007-01-01

Die meisten sekretorischen Proteine der eukaryontischen Zellen erreichen durch das endoplasmatische Retikulum (ER) den sekretorischen Signalweg. Sie gelangen vom Zytoplasma durch einen Kanal in der ER-Membran in das ER, wo sie ihre native Konformation erhalten. Das ER enthält ein strenges Qualitätskontrollsystem, welches fehlgefaltete Proteine erkennt, im ER zurückhält und letztendlich der ER-assoziierten Degradation (ERAD) zuführt. Die ER-Qualitätskontrolle und die ER-assoziierte Degradation...

Chelerythrine induced cell death through ROS-dependent ER stress in human prostate cancer cells

Directory of Open Access Journals (Sweden)

Wu S

2018-05-01

Full Text Available Songjiang Wu, Yanying Yang, Feiping Li, Lifu Huang, Zihua Han, Guanfu Wang, Hongyuan Yu, Haiping Li Department of Urology, Enze Hospital of Taizhou Enze Medical Center (Group, Taizhou, China Introduction: Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer-related mortality worldwide and the third in USA in 2017. Chelerythrine (CHE, a naturalbenzo[c]phenanthridine alkaloid, formerly identified as a protein kinase C inhibitor, has also shown anticancer effect through a number of mechanisms. Herein, effect and mechanism of the CHE-induced apoptosis via reactive oxygen species (ROS-mediated endoplasmic reticulum (ER stress in prostate cancer cells were studied for the first time. Methods: In our present study, we investigated whether CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a dose-dependent manner in PC-3 cells. In addition, we showed that CHE increases intracellular ROS and leads to ROS-dependent ER stress and cell apoptosis. Results: Pre-treatment with N-acetyl cysteine, an ROS scavenger, totally reversed the CHE-induced cancer cell apoptosis as well as ER stress activation, suggesting that the ROS generation was responsible for the anticancer effects of CHE. Conclusion: Taken together, our findings support one of the anticancer mechanisms by which CHE increased ROS accumulation in prostate cancer cells, thereby leading to ER stress and caused intrinsic apoptotic signaling. The study reveals that CHE could be a potential candidate for application in the treatment of prostate cancer. Keywords: chelerythrine, reactive oxygen species, endoplasmic reticulum stress, apoptosis, prostate cancer

The novel C-terminal KCNQ1 mutation M520R alters protein trafficking

DEFF Research Database (Denmark)

Schmitt, Nicole; Calloe, Kirstine; Nielsen, Nathalie Hélix

2007-01-01

The long QT-syndrome is characterized by a prolongation of the QT-interval and tachyarrhythmias causing syncopes and sudden death. We identified the missense mutation M520R in the calmodulin binding domain of the Kv7.1 channel from a German family with long QT-syndrome. Heterologous expression...... an immunopositive labeling of the plasma membrane. For M520R no plasma membrane staining was visible, instead a strong signal in the ER was observed. These results indicate that the LQT1 mutation M520R leads to ER-retention and dysfunctional trafficking of the mutant channel resulting in haploinsufficiency...

Crosstalk between mTORC1 and cAMP Signaling

Science.gov (United States)

2016-09-01

whether bidirectional inhibition of trafficking be- tween the endoplasmic reticulum (ER) and Golgi would affect Gln-induced activation of mTORC1 (23). We...Shimizu N, Matsumoto K, Itoh M, Ishitani T. 2012. NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor...L, Pan D, Edgar BA. 2003. Rheb promotes cell growth as a component of the insulin/ TOR signalling network . Nat Cell Biol 5: 566–571. Sengupta S

Mapping mesoscale variability of the Azores Current using TOPEX/POSEIDON and ERS 1 altimetry, together with hydrographic and Lagrangian measurements

Science.gov (United States)

Hernandez, Fabrice; Le Traon, Pierre-Yves; Morrow, Rosemary

1995-12-01

The SEMAPHORE mesoscale air/sea experiment was conducted in the Azores-Madeira region from July to November 1993. TOPEX/POSEIDON (T/P) and ERS 1 were flying simultaneously at that time. The main purposes of this paper are to evaluate the estimation of the oceanic mesoscale circulation from the two different sets of altimetric data (T/P and ERS 1) and to compare the results with in situ measurements provided by the SEMAPHORE hydrographic surveys and surface drifters (three expendable bathytermograph conductivity-temperature-depth surveys in a 500-km2 box and a set of 47 Lagrangian surface drifters drogued at 150 m). Comparisons are carried out through the maps obtained by objective analysis from the four data sets. The mapping accuracy of T/P, ERS 1, T/P and ERS 1 combined, and in situ data is investigated, as well as the sensitivity of the mapping to the correlation functions used. There is a good qualitative agreement between altimetric maps and corresponding drifter and hydrographic maps for the three hydrographic surveys. Correlations are about 0.8, and the regression fit is about 0.6-0.7; the lower values are due to the smooth climatology used to reference the altimetric maps. The correlation for time differences is better, with regression lines not significantly different from 1, especially when ERS 1 and T/P are combined. T/P mapping is almost as good as ERS 1 mapping, which was rather unexpected since the ERS 1 space-time sampling is better suited for the mesoscale. This may reflect the fact that the signal mapped by the hydrography and drifters does not contain the high frequency/wavenumber components. T/P and ERS 1 combined provide better results, although the improvement is not as large as expected, probably for the same reason.

Vejen til helvede er brolagt med frelste intentioner

DEFF Research Database (Denmark)

Vestenskov, David

2013-01-01

Det åbenlyse spørgsmål omkring, hvorfor vi er i Afghanistan (eller hvorfor vi bliver?) er bestemt et relevant spørgsmål, men at klæbe et prædikat på om krigens manglende moralske troværdighed kræver mere end blot sure opstød. Er vi netop ikke blevet i Afghanistan grundet moralske principper?...

In vitro study of demineralization resistance and fluoride retention in dental enamel irradiated with Er,Cr: YSGG laser

International Nuclear Information System (INIS)

Ana, Patricia Aparecida da.

2007-01-01

This study aimed to establish irradiation conditions of Er,Cr:YSGG laser (λ of 2.79 μm) which could propitiate changes on human dental enamel and increase its resistance to demineralization, when associated or not with topical application of acidulated phosphate fluoride (APF). Fluences of 2,8 J/cm 2 , 5,6 J/cm 2 e 8,5 J/cm 2 were selected; they were associated or not with previous application of a photo absorber (coal paste) and then APF was applied or not after laser irradiation. In a first step, the morphological findings, the surface temperatures, and the pupal temperatures were evaluated during laser irradiation. After that, the treated samples were submitted to a a ten-day pH-cycling model. After producing the incipient white-spots lesions, the following aspects were evaluated: the mineral loss, the loosely bound fluoride and the firmly bound fluoride. All the demineralizing and remineralizing pH-cycling solutions were evaluated with respect to their calcium (Ca), inorganic phosphorous (Pi) and fluoride (F - ) concentrations. The data had their normality and homogeneity distribution statistically evaluated, and it was chosen an appropriated statistical test for each performed analysis according to the obtained results, considering 5% significant level. The fluences selected for this study created ablated surfaces; the fluences of 5.6 J/cm 2 and 8.5 J/cm 2 promoted increments in surface temperature above 110 deg C. The intrapupal temperature changes revealed that laser irradiation did not increase the pulpal temperatures above the critical threshold for induction of pulpitis. The coal paste did not promote any changes on surface morphology or in the intrapulpal temperature changes; however, this paste increased the surface temperatures during laser irradiation. Only laser irradiation at 8.5 J/cm 2 was able to decrease the mineral loss when compared to the no-treatment group; although the association of coal paste + laser at 2.8 J/cm 2 + APF application

Elevated insulin-like growth factor 1 receptor signaling induces antiestrogen resistance through the MAPK/ERK and PI3K/Akt signaling routes

NARCIS (Netherlands)

Zhang, Y.; Moerkens, M.; Ramaiahgari, S.; Bont, de H.J.G.M.; Price, L.; Meerman, J.H.N.; Water, van de B.

2011-01-01

INTRODUCTION: Insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) is phosphorylated in all breast cancer subtypes. Past findings have shown that IGF-1R mediates antiestrogen resistance through cross-talk with estrogen receptor (ER) signaling and via its action upstream of the epidermal growth

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.

Fluorescent protein pair emit intracellular FRET signal suitable for FACS screening

International Nuclear Information System (INIS)

Johansson, Daniel X.; Brismar, Hjalmar; Persson, Mats A.A.

2007-01-01

The fluorescent proteins ECFP and HcRed were shown to give an easily resolved FRET-signal when expressed as a fusion inside mammalian cells. HeLa-tat cells expressing ECFP, pHcRed, or the fusion protein pHcRed-ECFP were analyzed by flow cytometry after excitation of ECFP. Cells expressing HcRed-ECFP, or ECFP and HcRed, were mixed and FACS-sorted for FRET positive cells: HcRed-ECFP cells were greatly enriched (72 times). Next, cloned human antibodies were fused with ECFP and expressed anchored to the ER membrane. Their cognate antigens (HIV-1 gp120 or gp41) were fused to HcRed and co-expressed in the ER. An increase of 13.5 ± 1.5% (mean ± SEM) and 8.0 ± 0.7% in ECFP fluorescence for the specific antibodies reacting with gp120 or gp41, respectively, was noted after photobleaching. A positive control (HcRed-ECFP) gave a 14.8 ± 2.6% increase. Surprisingly, the unspecific antibody (anti-TT) showed 12.1 ± 1.1% increase, possibly because overexpression in the limited ER compartment gave false FRET signals

ER-bound protein tyrosine phosphatase PTP1B interacts with Src at the plasma membrane/substrate interface.

Directory of Open Access Journals (Sweden)

Melisa C Monteleone

Full Text Available PTP1B is an endoplasmic reticulum (ER anchored enzyme whose access to substrates is partly dependent on the ER distribution and dynamics. One of these substrates, the protein tyrosine kinase Src, has been found in the cytosol, endosomes, and plasma membrane. Here we analyzed where PTP1B and Src physically interact in intact cells, by bimolecular fluorescence complementation (BiFC in combination with temporal and high resolution microscopy. We also determined the structural basis of this interaction. We found that BiFC signal is displayed as puncta scattered throughout the ER network, a feature that was enhanced when the substrate trapping mutant PTP1B-D181A was used. Time-lapse and co-localization analyses revealed that BiFC puncta did not correspond to vesicular carriers; instead they localized at the tip of dynamic ER tubules. BiFC puncta were retained in ventral membrane preparations after cell unroofing and were also detected within the evanescent field of total internal reflection fluorescent microscopy (TIRFM associated to the ventral membranes of whole cells. Furthermore, BiFC puncta often colocalized with dark spots seen by surface reflection interference contrast (SRIC. Removal of Src myristoylation and polybasic motifs abolished BiFC. In addition, PTP1B active site and negative regulatory tyrosine 529 on Src were primary determinants of BiFC occurrence, although the SH3 binding motif on PTP1B also played a role. Our results suggest that ER-bound PTP1B dynamically interacts with the negative regulatory site at the C-terminus of Src at random puncta in the plasma membrane/substrate interface, likely leading to Src activation and recruitment to adhesion complexes. We postulate that this functional ER/plasma membrane crosstalk could apply to a wide array of protein partners, opening an exciting field of research.

The new ternary pnictides Er12Ni30P21 and Er13Ni25As19: Crystal structures and magnetic properties

International Nuclear Information System (INIS)

Oryshchyn, Stepan; Babizhetskyy, Volodymyr; Zhak, Olga; Zelinska, Mariya; Pivan, Jean-Yves; Duppel, Viola; Simon, Arndt; Kienle, Lorenz

2010-01-01

The new ternary pnictides Er 12 Ni 30 P 21 and Er 13 Ni 25 As 19 have been synthesized from the elements. They crystallize with hexagonal structures determined from single-crystal X-ray data for Er 12 Ni 30 P 21 (space group P6 3 /m, a=1.63900(3) nm, c=0.37573(1) nm, Z=1, R F =0.062 for 1574 F-values and 74 variable parameters), and for Er 13 Ni 25 As 19 (Tm 13 Ni 25 As 19 -type structure, space group P6-bar , a=1.6208(1) nm, c=0.38847(2) nm, Z=1, R F =0.026 for 1549 F-values and 116 variable parameters). These compounds belong to a large family of hexagonal structures with a metal-metalloid ratio of 2:1. HRTEM investigations were conducted to probe for local ordering of the disordered structure at the nanoscale. The magnetic properties of the phosphide Er 12 Ni 30 P 21 have been studied in the temperature of range 2 eff =9.59 μ B corresponds to the theoretical value of Er 3+ . - Graphical abstract: The new ternary pnictides Er 12 Ni 30 P 21 and Er 13 Ni 25 As 19 have been synthesized from the elements. They crystallize with hexagonal structures determined from single-crystal X-ray data. The compounds belong to a large family of structures with a metal-metalloid ratio of 2:1. HRTEM investigations were conducted to probe for local ordering of the disordered structure at the nanoscale. Display Omitted

Overvågning af orkidéer 2000

DEFF Research Database (Denmark)

Wind, P.

resultaterne af orkidéovervågningen (Wind 2001). Hertil kommer præsentationen af projektet og dets resultater efter forløbet af de første tre år (Løjtnant 1991a) og en bearbejdning af projektets resultater for årene 1987-1995 (Wind 1997). I nærværende rapport undersøges skov-hullæbe for en eventuel sammenhæng...... mellem skudanlæggelsen udtrykt ved antallet af blomstrende og vegetative skud i et givet år og nedbørsmængder i august og september året før. Det er en udbredt antagelse at der er en sammenhæng mellem skudanlæggelse og mængden af nedbør det foregående år. Undersøgelser af skov-hullæbe populationer i...... 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...

Et kors er ikke bare et kors

DEFF Research Database (Denmark)

Bach-Nielsen, Carsten

2015-01-01

Om et kors, der er rejst uden for den danske kirke i Bruxelles; formodentlig en afledning af det såkaldte Brabanterkors.......Om et kors, der er rejst uden for den danske kirke i Bruxelles; formodentlig en afledning af det såkaldte Brabanterkors....

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.

Duplicate retention in signalling proteins and constraints from network dynamics.

Science.gov (United States)

Soyer, O S; Creevey, C J

2010-11-01

Duplications are a major driving force behind evolution. Most duplicates are believed to fix through genetic drift, but it is not clear whether this process affects all duplications equally or whether there are certain gene families that are expected to show neutral expansions under certain circumstances. Here, we analyse the neutrality of duplications in different functional classes of signalling proteins based on their effects on response dynamics. We find that duplications involving intermediary proteins in a signalling network are neutral more often than those involving receptors. Although the fraction of neutral duplications in all functional classes increase with decreasing population size and selective pressure on dynamics, this effect is most pronounced for receptors, indicating a possible expansion of receptors in species with small population size. In line with such an expectation, we found a statistically significant increase in the number of receptors as a fraction of genome size in eukaryotes compared with prokaryotes. Although not confirmative, these results indicate that neutral processes can be a significant factor in shaping signalling networks and affect proteins from different functional classes differently. © 2010 The Authors. Journal Compilation © 2010 European Society For Evolutionary Biology.

Broken bridges: a counter-example of the ER=EPR conjecture

International Nuclear Information System (INIS)

Chen, Pisin; Wu, Chih-Hung; Yeom, Dong-han

2017-01-01

In this paper, we provide a counter-example to the ER=EPR conjecture. In an anti-de Sitter space, we construct a pair of maximally entangled but separated black holes. Due to the vacuum decay of the anti-de Sitter background toward a deeper vacuum, these two parts can be trapped by bubbles. If these bubbles are reasonably large, then within the scrambling time, there should appear an Einstein-Rosen bridge between the two black holes. Now by tracing more details on the bubble dynamics, one can identify parameters such that one of the two bubbles either monotonically shrinks or expands. Because of the change of vacuum energy, one side of the black hole would evaporate completely. Due to the shrinking of the apparent horizon, a signal of one side of the Einstein-Rosen bridge can be viewed from the opposite side. We analytically and numerically demonstrate that within a reasonable semi-classical parameter regime, such process can happen. Bubbles are a non-perturbative effect, which is the crucial reason that allows the transmission of information between the two black holes through the Einstein-Rosen bridge, even though the probability is highly suppressed. Therefore, the ER=EPR conjecture cannot be generic in its present form and its validity maybe restricted.

Broken bridges: a counter-example of the ER=EPR conjecture

Energy Technology Data Exchange (ETDEWEB)

Chen, Pisin; Wu, Chih-Hung; Yeom, Dong-han, E-mail: pisinchen@phys.ntu.edu.tw, E-mail: b02202007@ntu.edu.tw, E-mail: innocent.yeom@gmail.com [Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, Taipei 10617, Taiwan (China)

2017-06-01

In this paper, we provide a counter-example to the ER=EPR conjecture. In an anti-de Sitter space, we construct a pair of maximally entangled but separated black holes. Due to the vacuum decay of the anti-de Sitter background toward a deeper vacuum, these two parts can be trapped by bubbles. If these bubbles are reasonably large, then within the scrambling time, there should appear an Einstein-Rosen bridge between the two black holes. Now by tracing more details on the bubble dynamics, one can identify parameters such that one of the two bubbles either monotonically shrinks or expands. Because of the change of vacuum energy, one side of the black hole would evaporate completely. Due to the shrinking of the apparent horizon, a signal of one side of the Einstein-Rosen bridge can be viewed from the opposite side. We analytically and numerically demonstrate that within a reasonable semi-classical parameter regime, such process can happen. Bubbles are a non-perturbative effect, which is the crucial reason that allows the transmission of information between the two black holes through the Einstein-Rosen bridge, even though the probability is highly suppressed. Therefore, the ER=EPR conjecture cannot be generic in its present form and its validity maybe restricted.

Egg retention and intrauterine embryonic development in Sceloporus aeneus (Reptilia: Phrynosomatidae: implications for the evolution of viviparity Retención de huevos y avance embrionario intrauterino en Sceloporus aeneus (Reptilia: Phrynosomatidae: implicaciones para la evolución de la viviparidad

Directory of Open Access Journals (Sweden)

Rodolfo García-Collazo

2012-09-01

Full Text Available Egg retention (ER and intrauterine embryonic development (IED have been considered intermediate steps in the evolution from oviparity to viviparity. Sceloporus aeneus is an oviparous lizard that is closely related to the viviparous species (Sceloporus bicanthalis. The present study addresses the following 2 questions: 1 Are intermediate stages of egg retention (ER and IED present in populations of Sceloporus aeneus? and 2 Are ER and/or IED explained by elevation, precipitation or phylogenetic effects? Results indicate that in S. aeneus, ER differs among populations. ER was negatively related to altitude and pluvial precipitation, whereas average environmental temperature had no effect on ER or IER. In contrast to previous observations of oviparous species related to viviparous species, populations of S. aeneus with advanced IED are associated with environmental factors such as low elevation and aridity instead of high elevation and cold climate, whereas the comparative analysis shows that there are no significative evolutionary changes throughout the phylogeny, which means that the altitude has no effect on the transition to the evolution of viviparity in S. aeneus-S bicanthalis.La retención de huevos (ER y el desarrollo embrionario intrauterino (IED han sido considerados pasos intermedios hacia la viviparidad. Sceloporus aeneus es un lacertilio ovíparo estrechamente relacionado a una especie vivípara (Sceloporus bicanthalis. El presente estudio derivó de las preguntas: ¿El ER y el IED presentes en las poblaciones de S. aeneus son estadios intermedios a la viviparidad? ¿ER y/o IED son explicados por la temperatura, altitud, precipitación pluvial o son un efecto filogenético? En S. aeneus, el ER y el IED fueron diferentes entre poblaciones. Los resultados indicaron que la ER se relacionó negativamente con la altitud y la precipitación pluvial, mientras que no se encontró efecto con la temperatura ambiental. En contraste con

Structural and electronic properties of Er-monopnictides under high pressure

International Nuclear Information System (INIS)

Pandit, Premlata; Srivastava, Vipul; Rajagopalan, M.; Sanyal, Sankar P.

2010-01-01

We present the results of theoretical calculations on the structural, magnetic and electronic properties of Er-monopnictides using self-consistent first principles tight-binding linear-muffin-tin-orbital (TB-LMTO) method within the atomic-sphere approximation (ASA). Both spin-polarized and non-spin-polarized calculations are performed to check the magnetic stability of these compounds. We find that ErN, ErP and ErAs are metallic in ferromagnetic (FM) phase in both the spin channels and stable in NaCl-type (B 1 ) structure at ambient pressure. We predict NaCl-type (B 1 ) to CsCl-type (B 2 ) structural phase transition in ErN, ErP and ErAs at pressures of 146.1, 60.2 and 53.2 GPa, respectively and remain metallic ferromagnetic at high pressure. We calculate equilibrium lattice constants (a), bulk modulus (B), magnetic moments (μ B ) and electronic properties of these compounds in B 1 and B 2 phases and compare with available experimental and theoretical results.

Bifunctional behavior of Er3+ ions as the sintering additive and the fluorescent agent in Er3+ single doped γ-AlON transparent ceramics

International Nuclear Information System (INIS)

Wang, Ying; Xie, Xiumin; Qi, Jianqi; Wang, Shanshan; Wei, Nian; Lu, Zhongwen; Chen, Xingtao; Lu, Tiecheng

2016-01-01

We report on the sintering promoting and fluorescent activator roles of Er 3+ in AlON:Er 3+ transparent ceramics prepared by pressureless sintering with Er 2 O 3 and AlON powder. There shows that the transparency of samples varied with the content of Er 2 O 3 additive. The AlON:Er 3+ ceramics showed upconversion luminescence peaking at 546 nm, 662 nm and 840 nm under the 980 nm excitation due to transition of 4 S 3/2 / 2 H 11/2 → 4 I 15/2 , 4 F 9/2 → 4 I 15/2 and 4 S 3/2 / 2 H 11/2 → 4 I 13/2 of Er 3+ ions, respectively. The infrared spectra exhibited strong emission at 1534 nm corresponds to 4 I 13/2 → 4 I 15/2 transition. The mechanism of the IR and visible emission bands in AlON:Er 3+ ceramics are discussed, which suggest it should be attractive for lighting and display devices applications.

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?...

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...

Optical energy gaps and photoluminescence peaks of BaGa2S4:Er3+ and BaGa2Se4:Er3+ single crystals

International Nuclear Information System (INIS)

Choe, Sung-Hyu; Jin, Moon-Seog; Kim, Wha-Tek

2005-01-01

BaGa 2 S 4 :Er 3+ and BaGa 2 Se 4 :Er 3+ single crystals were grown by using the chemical transport reaction method. The optical energy gaps of the BaGa 2 S 4 :Er 3+ and the BaGa 2 Se 4 :Er 3+ single crystals were found to be 4.045 eV and 3.073 eV, respectively, at 11 K. The temperature dependence of the optical energy gap was well fitted by the Varshni equation. Sharp emission peaks were observed in the photoluminescence spectra of the single crystals and assigned to radiation recombination between split Stark levels of the Er 3+ ion.

Er{sup 3+} Doping conditions of planar porous silicon waveguides

Energy Technology Data Exchange (ETDEWEB)

Najar, A. [Laboratoire d' Optronique UMR 6082-FOTON, Universite de Rennes 1, 6 rue de Kerampont, B. P. 80518, 22305 Lannion Cedex (France); Laboratoire de Spectroscopie Raman, Faculte des Sciences de Tunis, 2092 El Manar, Tunis (Tunisia); Lorrain, N., E-mail: nathalie.lorrain@univ-rennes1.fr [Laboratoire d' Optronique UMR 6082-FOTON, Universite de Rennes 1, 6 rue de Kerampont, B. P. 80518, 22305 Lannion Cedex (France); Ajlani, H. [Laboratoire de Spectroscopie Raman, Faculte des Sciences de Tunis, 2092 El Manar, Tunis (Tunisia); Charrier, J. [Laboratoire d' Optronique UMR 6082-FOTON, Universite de Rennes 1, 6 rue de Kerampont, B. P. 80518, 22305 Lannion Cedex (France); Oueslati, M. [Laboratoire de Spectroscopie Raman, Faculte des Sciences de Tunis, 2092 El Manar, Tunis (Tunisia); Haji, L. [Laboratoire d' Optronique UMR 6082-FOTON, Universite de Rennes 1, 6 rue de Kerampont, B. P. 80518, 22305 Lannion Cedex (France)

2009-11-15

EDX and infrared photoluminescence (IR PL) analyses performed on erbium-doped porous silicon waveguides (PSWG) were studied using different doping conditions. Both parameters of the cathodisation electrochemical method used for Er incorporation and parameters of thermal treatments required for Er optical activation were taken into consideration. Firstly, by varying the current density and the time of cathodisation, we have shown that a current density of 0.1 mA/cm{sup 2} for 10 min allows homogeneous Er doping to be achieved throughout the depth of the guiding layer. Then, the PL intensity at 1.53 {mu}m was studied as a function of the oxidation time at 900 deg. C and Er diffusion temperature for 60 min. Increasing the oxidation time up to 1 h allows PL to be enhanced due to active Si-O-Er complex formation whereas an oxidation time of 2 h induces a decrease in PL because of Er segregation. Moreover, an increase in the diffusion temperature induces an optimal distribution of optically active Si-Er-O complexes inside the crystallites. When the temperature is too high, a PSWG densification and Er segregation occurs inducing a decrease in PL due to energy transfer phenomena.

Forbruget af træer og buske i Danmark

DEFF Research Database (Denmark)

Jensen, Jan Svejgaard; Laursen, Allan Bach; Kjær, Erik Dahl

Træer og buske er vigtige elementer i byen og landskabet, og i Danmark bruges der mellem 60 og 80 millioner vedplanter hvert år. Forbruget har været konstant stigende og der er sket store forskydninger i forbrugsmønstret i retning af større fokus på mangfoldighed og autencitet. Undersøgelsen...... klarlægger forbrugsmønstret for træer og buske og undersøger, hvad brugerne lægger vægt på i deres valg af planter....

Preparation of Erbium-169 (169Er) Using Natural Erbium Target

International Nuclear Information System (INIS)

Azmairit Aziz; Nana Suherman

2009-01-01

The therapeutic radiopharmaceuticals which is labelled by β-particle emission are now increasingly used in nuclear medicine. Erbium-169 ('1 69 Er) is one of radioisotopes that can be used for radiation synovectomy (radio synovectomy) in the treatment of inflammatory joint diseases (arthritis) due to its β- particle emission (T 1/2 =9.4 days, E β maximum =0.34 MeV). The preliminary study on preparation of 169 Er by using natural erbium oxide (Er 2 O 3 ) target irradiated at TRIGA 2000 Bandung reactor has been carried out. The irradiated target was dissolved in hydrochloric acid solution and gentle warming. The optimum condition of 169 Er preparation was obtained by dissolution of 169 Er 2 O 3 by using 1N HCl solution. The radiochemical purity of 169 ErCl 3 was determined by paper chromatography, thin layer chromatography and paper electrophoresis techniques. The solution of 169 ErCl 3 formed was obtained with the pH of 1.5 – 2, clear, with the specific activity of 0.48 – 0.71 MBq/mg Er. The solution has the radiochemical purity of 98.32 ± 1.28% and the radionuclide purity of 99.98%. Study on the stability of 169 ErCl 3 solution showed that the solution was still stable for 4 days at room temperature with the radiochemical purity more than 95%. (author)

Gingival melanin depigmentation by Er:YAG laser: A literature review.

Science.gov (United States)

Pavlic, Verica; Brkic, Zlata; Marin, Sasa; Cicmil, Smiljka; Gojkov-Vukelic, Mirjana; Aoki, Akira

2018-04-01

Laser ablation is recently suggested as a most effective and reliable technique for depigmentation of melanin hyperpigmented gingiva. To date, different lasers have been used for gingival depigmentation (CO 2 , diode, Nd:YAG, Er:YAG and Er,Cr:YSGG lasers). The use of Er:YAG laser for depigmentation of melanin hyperpigmented gingiva has gained increasing importance in recent years. The purpose of this study was to report removal of gingival melanin pigmentation using an Er:YAG laser in a literature review. The main outcomes, such as improvement of signs (clinical parameters of bleeding, erythema, swelling and wound healing), symptoms (pain) and melanin recurrence/repigmentation were measured. The literature demonstrated that depigmentation of gingival melanin pigmentation can be performed safely and effectively by Er:YAG laser resulting in healing and an esthetically significant improvement of gingival discoloration. Thus, Er:YAG laser seems to be safe and useful in melanin depigmentation procedure. However, the main issue in giving the final conclusion of the optimal Er:YAG laser use in melanin depigmentation is that, to date, studies are offering completely discrepant Er:YAG laser procedure protocols (complex settings of laser parameters), and different criteria for the assessment of depigmentation and repigmentation (recurrence), thus hampering the comparison of the results. Therefore, further studies are necessary to give an optimal recommendation on the use of Er:YAG laser in gingival melanin hyperpigmentation.

Quantification of PRL/Stat5 signaling with a novel pGL4-CISH reporter

Directory of Open Access Journals (Sweden)

Zheng Jiamao

2008-02-01

Full Text Available Abstract Background Elevations of serum prolactin (PRL are associated with an increased risk for breast cancer. PRL signaling through its prolactin receptor (PRLr involves the Jak2/Stat5 pathway. Luciferase-based reporter assays have been widely used to evaluate the activity of this pathway. However, the existing reporters are often not sensitive enough to monitor the effect of PRL in this pathway. Results In this study, a new biologically relevant reporter, pGL4-CISH, was generated to study the PRL/Jak2/Stat5 signaling pathway. The sensitivity of pGL4-CISH to detect PRL was superior to that of several other commonly utilized Stat5-responsive reporters. Interestingly, the enhanced function pGL4-CISH was restricted to the estrogen receptor positive (ER+ human breast cancer cell lines T47D and MCF7, but not in the ER-MDA-231, BT-474, or MCF10A cell lines. Overexpression of Stat5 further enhanced the effect of PRL on pGL4-CISH. Conclusion These studies demonstrate that pGL4-CISH is a novel and sensitive reporter for assessing the activity of the PRL/Stat5 signaling pathway in the ER+ human breast cancer cells.

Urinary retention in women.

Science.gov (United States)

Juma, Saad

2014-07-01

This review is a summary of the most pertinent published studies in the literature in the last 18 months that address cause, diagnosis, and management of urinary retention in women. Symptoms, uroflow, and pressure-flow studies have a low predictive value for and do not correlate with elevated postvoid residual urine (PVR). Anterior and posterior colporrhaphy do not cause de-novo bladder outlet obstruction in the majority of patients with elevated PVR, and the cause of elevated PVR may be other factors such as pain or anxiety causing abnormal relaxation of the pelvic floor and contributing to voiding difficulty. The risk of urinary retention in a future pregnancy after mid-urethral sling (MUS) is small. The risk of urinary tract infection and urinary retention after chemodenervation of the bladder with onabotulinumtoxin-A (100 IU) in patients with non-neurogenic urge incontinence is 33 and 5%, respectively. There is a lack of consensus among experts on the timing of sling takedown in the management of acute urinary retention following MUS procedures. There has been a significant progress in the understanding of the causation of urinary retention. Important areas that need further research (basic and clinical) are post-MUS and pelvic organ prolapse repair urinary retention and obstruction, and urinary retention owing to detrusor underactivity.

Growth process and structure of Er/Si(100) thin film

International Nuclear Information System (INIS)

Fujii, S.; Michishita, Y.; Miyamae, N.; Suto, H.; Honda, S.; Okado, H.; Oura, K.; Katayama, M.

2006-01-01

The solid-phase reactive epitaxial growth processes and structures of Er/Si(100) thin films were investigated by coaxial impact-collision ion scattering spectroscopy (CAICISS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The as-deposited Er film grown at room temperature was transformed into crystalline rectangular-shaped islands after annealing at 900 deg. C. These islands have a hexagonal AlB 2 -type structure and the epitaxial relationship is determined to be ErSi 2 (011-bar0)[0001]//Si(100)[011-bar]. It has been revealed that the surface of the Er silicide island is terminated with an Er plane

Krigens første offer er også truet i fredstid

DEFF Research Database (Denmark)

Serritzlev, Jeanette

2018-01-01

Sandheden er krigens første offer, lyder det. Men informationskrig finder også sted i fredstid, og også her er sandheden jaget vildt. ’Fake News’ er det nye modeord, selv om det ikke er nyt. Det behøver ikke at være værre, end vi selv gør det. Det farlige opstår først, når vi er ligeglade....

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.

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" ....

Når mindset er nøglen til succes

DEFF Research Database (Denmark)

Nielsen, Jeppe Agger; Karlsmose, Jens; Kortnum, Allan

2016-01-01

Hvordan skaber man en arbejdspladskultur, hvor medarbejderne trives med forandringer, er udholdende og indstillede på at lære nyt? Det er for mange virksomheder et af de helt store aktuelle spørgsmål, og i flere af dem er svaret ledelse med mindsetbaserede principper. Læs her om mindset-tanketank...

Lace plant ethylene receptors, AmERS1a and AmERS1c, regulate ethylene-induced programmed cell death during leaf morphogenesis.

Science.gov (United States)

Rantong, Gaolathe; Evans, Rodger; Gunawardena, Arunika H L A N

2015-10-01

The lace plant, Aponogeton madagascariensis, is an aquatic monocot that forms perforations in its leaves as part of normal leaf development. Perforation formation occurs through developmentally regulated programmed cell death (PCD). The molecular basis of PCD regulation in the lace plant is unknown, however ethylene has been shown to play a significant role. In this study, we examined the role of ethylene receptors during perforation formation. We isolated three lace plant ethylene receptors AmERS1a, AmERS1b and AmERS1c. Using quantitative PCR, we examined their transcript levels at seven stages of leaf development. Through laser-capture microscopy, transcript levels were also determined in cells undergoing PCD and cells not undergoing PCD (NPCD cells). AmERS1a transcript levels were significantly lower in window stage leaves (in which perforation formation and PCD are occurring) as compared to all other leaf developmental stages. AmERS1a and AmERS1c (the most abundant among the three receptors) had the highest transcript levels in mature stage leaves, where PCD is not occurring. Their transcript levels decreased significantly during senescence-associated PCD. AmERS1c had significantly higher transcript levels in NPCD compared to PCD cells. Despite being significantly low in window stage leaves, AmERS1a transcripts were not differentially expressed between PCD and NPCD cells. The results suggested that ethylene receptors negatively regulate ethylene-controlled PCD in the lace plant. A combination of ethylene and receptor levels determines cell fate during perforation formation and leaf senescence. A new model for ethylene emission and receptor expression during lace plant perforation formation and senescence is proposed.

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

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....

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...

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

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.

DNA as a component of ER materials

Energy Technology Data Exchange (ETDEWEB)

Minagawa, K; Aoki, Y; Berber, M R [Institute of Technology and Science, University of Tokushima, Tokushima 770-8506 (Japan); Mori, T [Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka 819-0395 (Japan); Tanaka, M [Faculty of Pharmaceutical Science, Tokushima Bunri University, Tokushima 770-8514 (Japan)], E-mail: minagawa@chem.tokushima-u.ac.jp

2009-02-01

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.

Globular adiponectin protects rat hepatocytes against acetaminophen-induced cell death via modulation of the inflammasome activation and ER stress: Critical role of autophagy induction.

Science.gov (United States)

Kim, Eun Hye; Park, Pil-Hoon

2018-05-24

Acetaminophen (APAP) overdose treatment causes severe liver injury. Adiponectin, a hormone predominantly produced by adipose tissue, exhibits protective effects against APAP-induced hepatotoxicity. However, the underlying mechanisms are not clearly understood. In the present study, we examined the protective effect of globular adiponectin (gAcrp) on APAP-induced hepatocyte death and its underlying mechanisms. We found that APAP (2 mM)-induced hepatocyte death was prevented by inhibition of the inflammasome. In addition, treatment with gAcrp (0.5 and 1 μg/ml) inhibited APAP-induced activation of the inflammasome, judged by suppression of interleukin-1β maturation, caspase-1 activation, and apoptosis-associated speck-like protein (ASC) speck formation, suggesting that protective effects of gAcrp against APAP-induced hepatocyte death is mediated via modulation of the inflammasome. APAP also induced ER stress and treatment with tauroursodeoxycholic acid (TUDCA), an ER chaperone and inhibitor of ER stress, abolished APAP-induced inflammasomes activation, implying that ER stress acts as signaling event leading to the inflammasome activation in hepatocytes stimulated with APAP. Moreover, gAcrp significantly suppressed APAP-induced expression of ER stress marker genes. Finally, the modulatory effects of gAcrp on ER stress and inflammasomes activation were abrogated by treatment with autophagy inhibitors, while an autophagy inducer (rapamycin) suppressed APAP-elicited ER stress, demonstrating that autophagy induction plays a crucial role in the suppression of APAP-induced inflammasome activation and ER stress by gAcrp. Taken together, these results indicate that gAcrp protects hepatocytes against APAP-induced cell death by modulating ER stress and the inflammasome activation, at least in part, via autophagy induction. Copyright © 2018. Published by Elsevier Inc.

Ampelopsin-induced reactive oxygen species enhance the apoptosis of colon cancer cells by activating endoplasmic reticulum stress-mediated AMPK/MAPK/XAF1 signaling

Science.gov (United States)

Park, Ga Bin; Jeong, Jee-Yeong; Kim, Daejin

2017-01-01

Ampelopsin (Amp) is bioactive natural product and exerts anti-cancer effects against several cancer types. The present study investigated the anti-colon cancer activity of Amp and explored its mechanism of action. The treatment of colon cancer cells with Amp resulted in the dose- and time-dependent induction of apoptosis via the activation of endoplasmic reticulum (ER) stress, 5′ adenosine monophosphate-activated protein kinase (AMPK), and c-Jun N-terminal protein kinase (JNK)/p38 mitogen-activated protein kinases (MAPKs). Salubrinal, an ER stress inhibitor, prevented the upregulation of ER stress-associated proteins, including phosphorylated protein kinase RNA-like ER kinase, phosphorylated eukaryotic translation initiation factor 2α, glucose-regulated protein 78, and CCAAT/enhancer-binding protein homologous protein, as well as suppressing AMPK activation and the MAPK signaling pathway. Knockdown of AMPK by RNA interference failed to block ER stress. Additionally, SP600125 (a JNK inhibitor) and SB203580 (a p38-MAPK inhibitor) effectively inhibited apoptosis and attenuated the expression of X-linked IAP-associated factor 1 (XAF1) and apoptotic Bcl-2 family proteins (BCL2 antagonist/killer 1 and BCL2-associated X protein) in Amp-treated colon cancer cells. Furthermore, reactive oxygen species (ROS)-mediated ER stress/AMPK apoptotic signaling pathway in Amp-treated colon cancer cells were markedly inhibited by treatment with N-acetyl-L-cysteine, a ROS scavenger. These results demonstrate that treatment with Amp induces the apoptotic death of colon cancer cells through ER stress-initiated AMPK/MAPK/XAF1 signaling. These results also provide experimental information for developing Amp as therapeutic drug against colon cancer. PMID:29250183

Evaluating the potential bioactivity of a novel compound ER1626.

Science.gov (United States)

Wang, Lijun; Zeng, Yanyan; Wang, Tianling; Liu, Hongyi; Xiao, Hong; Xiang, Hua

2014-01-01

ER1626, a novel compound, is a derivate of indeno-isoquinoline ketone. This study was designed to evaluate the biological activity and potential anti-tumor mechanism of ER1626. MTT assay, scratch assay and flow cytometry were used to determine cell proliferation, cell migration and cell cycle distribution as well as cell apoptosis on human breast cancer MCF-7 cells and endometrial cancer Ishikawa cells. We also explored the antiangiogenic effect of ER1626 on HUVEC cells and chicken embryos. The expression of estrogen receptor protein was investigated with western-blot analysis. ER1626 down-regulated the expression of estrogen receptor α protein and up-regulated β protein in MCF-7 and Ishikawa cells. The value of IC50 of ER1626 on MCF-7 and Ishikawa cells were respectively 8.52 and 3.08 µmol/L. Meanwhile, ER1626 decreased VEGF secretion of MCF-7 and Ishikawa cells, disturbed the formation of VEGF-stimulated tubular structure in HUVEC cells, and inhibited the angiogenesis on the chicken chorioallantoic membrane. Scratch assay revealed that ER1626 suppressed the migration of MCF-7, Ishikawa and HUVEC cells. In addition to induction tumor cell apoptosis, ER1626 arrested cell cycle in G1/G0 phase in MCF-7 cells and G2/M phase in Ishikawa cells. In conclusion, our results demonstrated that ER1626 has favorable bioactivities to be a potential candidate against breast cancer and angiogenesis.

Evaluating the potential bioactivity of a novel compound ER1626.

Directory of Open Access Journals (Sweden)

Lijun Wang

Full Text Available ER1626, a novel compound, is a derivate of indeno-isoquinoline ketone. This study was designed to evaluate the biological activity and potential anti-tumor mechanism of ER1626.MTT assay, scratch assay and flow cytometry were used to determine cell proliferation, cell migration and cell cycle distribution as well as cell apoptosis on human breast cancer MCF-7 cells and endometrial cancer Ishikawa cells. We also explored the antiangiogenic effect of ER1626 on HUVEC cells and chicken embryos. The expression of estrogen receptor protein was investigated with western-blot analysis.ER1626 down-regulated the expression of estrogen receptor α protein and up-regulated β protein in MCF-7 and Ishikawa cells. The value of IC50 of ER1626 on MCF-7 and Ishikawa cells were respectively 8.52 and 3.08 µmol/L. Meanwhile, ER1626 decreased VEGF secretion of MCF-7 and Ishikawa cells, disturbed the formation of VEGF-stimulated tubular structure in HUVEC cells, and inhibited the angiogenesis on the chicken chorioallantoic membrane. Scratch assay revealed that ER1626 suppressed the migration of MCF-7, Ishikawa and HUVEC cells. In addition to induction tumor cell apoptosis, ER1626 arrested cell cycle in G1/G0 phase in MCF-7 cells and G2/M phase in Ishikawa cells.In conclusion, our results demonstrated that ER1626 has favorable bioactivities to be a potential candidate against breast cancer and angiogenesis.

Therapeutic Silencing of Bcl-2 by Systemically Administered siRNA Nanotherapeutics Inhibits Tumor Growth by Autophagy and Apoptosis and Enhances the Efficacy of Chemotherapy in Orthotopic Xenograft Models of ER (− and ER (+ Breast Cancer

Directory of Open Access Journals (Sweden)

Ibrahim Tekedereli

2013-01-01

Full Text Available Bcl-2 is overexpressed in about a half of human cancers and 50–70% of breast cancer patients, thereby conferring resistance to conventional therapies and making it an excellent therapeutic target. Small interfering RNA (siRNA offers novel and powerful tools for specific gene silencing and molecularly targeted therapy. Here, we show that therapeutic silencing of Bcl-2 by systemically administered nanoliposomal (NL-Bcl-2 siRNA (0.15 mg siRNA/kg, intravenous twice a week leads to significant antitumor activity and suppression of growth in both estrogen receptor-negative (ER(− MDA-MB-231 and ER-positive (+ MCF7 breast tumors in orthotopic xenograft models (P < 0.05. A single intravenous injection of NL-Bcl-2-siRNA provided robust and persistent silencing of the target gene expression in xenograft tumors. NL-Bcl-2-siRNA treatment significantly increased the efficacy of chemotherapy when combined with doxorubicin in both MDA-MB-231 and MCF-7 animal models (P < 0.05. NL-Bcl-2-siRNA treatment-induced apoptosis and autophagic cell death, and inhibited cyclin D1, HIF1α and Src/Fak signaling in tumors. In conclusion, our data provide the first evidence that in vivo therapeutic targeting Bcl-2 by systemically administered nanoliposomal-siRNA significantly inhibits growth of both ER(− and ER(+ breast tumors and enhances the efficacy of chemotherapy, suggesting that therapeutic silencing of Bcl-2 by siRNA is a viable approach in breast cancers.

Activity, splice variants, conserved peptide motifs, and phylogeny of two new alpha1,3-fucosyltransferase families (FUT10 and FUT11).

Science.gov (United States)

Mollicone, Rosella; Moore, Stuart E H; Bovin, Nicolai; Garcia-Rosasco, Marcela; Candelier, Jean-Jacques; Martinez-Duncker, Iván; Oriol, Rafael

2009-02-13

We report the cloning of three splice variants of the FUT10 gene, encoding for active alpha-l-fucosyltransferase-isoforms of 391, 419, and 479 amino acids, and two splice variants of the FUT11 gene, encoding for two related alpha-l-fucosyltransferases of 476 and 492 amino acids. The FUT10 and FUT11 appeared 830 million years ago, whereas the other alpha1,3-fucosyltransferases emerged 450 million years ago. FUT10-391 and FUT10-419 were expressed in human embryos, whereas FUT10-479 was cloned from adult brain and was not found in embryos. Recombinant FUT10-419 and FUT10-479 have a type II trans-membrane topology and are retained in the endoplasmic reticulum (ER) by a membrane retention signal at their NH(2) termini. The FUT10-479 has, in addition, a COOH-ER membrane retention signal. The FUT10-391 is a soluble protein without a trans-membrane domain or ER retention signal that transiently localizes to the Golgi and then is routed to the lysosome. After transfection in COS7 cells, the three FUT10s and at least one FUT11, link alpha-l-fucose onto conalbumin glycopeptides and biantennary N-glycan acceptors but not onto short lactosaminyl acceptor substrates as do classical monoexonic alpha1,3-fucosyltransferases. Modifications of the innermost core GlcNAc of the N-glycan, by substitution with ManNAc or with an opened GlcNAc ring or by the addition of an alpha1,6-fucose, suggest that the FUT10 transfer is performed on the innermost GlcNAc of the core chitobiose. We can exclude alpha1,3-fucosylation of the two peripheral GlcNAcs linked to the trimannosyl core of the acceptor, because the FUT10 fucosylated biantennary N-glycan product loses both terminal GlcNAc residues after digestion with human placenta alpha-N-acetylglucosaminidase.

Structural and electronic properties of Er-monopnictides under high pressure

Energy Technology Data Exchange (ETDEWEB)

Pandit, Premlata, E-mail: lataprem29@gmail.co [Department of Physics, Barkatullah University, Bhopal, Madhya Pradesh 462026 (India); Srivastava, Vipul [Department of Physics, Oriental Institute of Science and Technology, Thakral Nagar, Bhopal (India); Rajagopalan, M. [Crystal Growth Centre, Anna University, Chennai 600 025 (India); Sanyal, Sankar P. [Department of Physics, Barkatullah University, Bhopal, Madhya Pradesh 462026 (India)

2010-05-01

We present the results of theoretical calculations on the structural, magnetic and electronic properties of Er-monopnictides using self-consistent first principles tight-binding linear-muffin-tin-orbital (TB-LMTO) method within the atomic-sphere approximation (ASA). Both spin-polarized and non-spin-polarized calculations are performed to check the magnetic stability of these compounds. We find that ErN, ErP and ErAs are metallic in ferromagnetic (FM) phase in both the spin channels and stable in NaCl-type (B{sub 1}) structure at ambient pressure. We predict NaCl-type (B{sub 1}) to CsCl-type (B{sub 2}) structural phase transition in ErN, ErP and ErAs at pressures of 146.1, 60.2 and 53.2 GPa, respectively and remain metallic ferromagnetic at high pressure. We calculate equilibrium lattice constants (a), bulk modulus (B), magnetic moments (mu{sub B}) and electronic properties of these compounds in B{sub 1} and B{sub 2} phases and compare with available experimental and theoretical results.

Isothermal section of the Er-Cu-Ga ternary system at 973 K

Energy Technology Data Exchange (ETDEWEB)

Belgacem, B. [Unite de Recherche de Chimie des Materiaux et de l' Environnement (UR11ES25), ISSBAT, Universite de Tunis ElManar, 9 Avenue Dr. Zoheir Safi, 1006 Tunis (Tunisia); Pasturel, M., E-mail: mathieu.pasturel@univ-rennes1.fr [Institut des Sciences Chimiques de Rennes, Chimie du Solide et Materiaux, UMR CNRS 6226, Universite de Rennes 1, Campus de Beaulieu, 35042 Rennes (France); Tougait, O. [Institut des Sciences Chimiques de Rennes, Chimie du Solide et Materiaux, UMR CNRS 6226, Universite de Rennes 1, Campus de Beaulieu, 35042 Rennes (France); Nouri, S. [Unite de Recherche de Chimie des Materiaux et de l' Environnement (UR11ES25), ISSBAT, Universite de Tunis ElManar, 9 Avenue Dr. Zoheir Safi, 1006 Tunis (Tunisia); Bekkachi, H. El; Peron, I. [Institut des Sciences Chimiques de Rennes, Chimie du Solide et Materiaux, UMR CNRS 6226, Universite de Rennes 1, Campus de Beaulieu, 35042 Rennes (France); Hassen, R. Ben [Unite de Recherche de Chimie des Materiaux et de l' Environnement (UR11ES25), ISSBAT, Universite de Tunis ElManar, 9 Avenue Dr. Zoheir Safi, 1006 Tunis (Tunisia); Noeel, H. [Institut des Sciences Chimiques de Rennes, Chimie du Solide et Materiaux, UMR CNRS 6226, Universite de Rennes 1, Campus de Beaulieu, 35042 Rennes (France)

2012-08-05

Highlights: Black-Right-Pointing-Pointer The isothermal section at 973 K of the Er-Cu-Ga ternary phase diagram has been established for the first time. Black-Right-Pointing-Pointer Eight extensions of binary compounds in the ternary domain have been identified, as well as six ternary intermediate solid solutions characterized by an important Cu/Ga mutual substitution. Black-Right-Pointing-Pointer Magnetic properties of Er{sub 3}(Cu,Ga){sub 11} are reported for the first time and confirms the paramagnetic Curie-Weiss behavior of all the six intermediate intermetallics. - Abstract: Phase relations in the Er-Cu-Ga ternary system have been established at 973 K by means of powder X-ray diffraction complemented by energy dispersive spectroscopy coupled to scanning electron microscopy. The isothermal section of the phase diagram comprises eight extensions of binaries into the ternary system, ErCu{sub 1-x}Ga{sub x} (x {<=} 0.5), ErCu{sub 2-x}Ga{sub x} (x {<=} 1.1), ErCu{sub 5-x}Ga{sub x} (x {<=} 0.5), Er{sub 5}Cu{sub x}Ga{sub 3-x} (x {<=} 0.60), Er{sub 3}Cu{sub x}Ga{sub 2-x} (x {<=} 0.24), ErCu{sub x}Ga{sub 1-x} (x {<=} 0.10), ErCu{sub x}Ga{sub 2-x} (x {<=} 0.30) and ErCu{sub x}Ga{sub 3-x} (x {<=} 0.35), as well as six ternary intermediate phases, ErCu{sub x}Ga{sub 2-x} (0.4 {<=} x {<=} 0.7), Er{sub 14}Cu{sub 51-x}Ga{sub x} (5.5 {<=} x {<=} 11.0), ErCu{sub 5-x}Ga{sub x} (0.8 {<=} x {<=} 2.3), Er{sub 2}Cu{sub 17-x}Ga{sub x} (4.9 {<=} x {<=} 8.0), ErCu{sub 12-x}Ga{sub x} (5.7 {<=} x {<=} 6.7) and Er{sub 3}Cu{sub x}Ga{sub 11-x} (1.5 {<=} x {<=} 4.4), all deriving from binary structure-types.

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....

The influence of substrate on the properties of Er2O3 films grown by magnetron sputtering

International Nuclear Information System (INIS)

Miritello, M.; Lo Savio, R.; Iacona, F.; Franzo, G.; Bongiorno, C.; Irrera, A.; Priolo, F.

2006-01-01

The structural properties and the room temperature luminescence of Er 2 O 3 thin films deposited by RF magnetron sputtering have been studied. Films characterized by good morphological properties have been obtained by using a SiO 2 interlayer between the film and the Si substrate. The evolution of the properties of the Er 2 O 3 films due to rapid thermal annealing processes in O 2 ambient performed at temperatures in the range 800-1200 deg. C has been investigated in details. The existence of well-defined annealing conditions (temperature of 1100 deg. C or higher) allowing to avoid the occurrence of extensive chemical reactions with the oxidized substrate has been demonstrated and an increase of the photoluminescence (PL) intensity by about a factor of 40 with respect to the as deposited material has been observed. The enhanced efficiency of the photon emission process has been correlated with the longer lifetime of the PL signal. The same annealing processes are less effective when Er 2 O 3 is deposited on Si. In this latter case interfacial reactions and pit formation occur, leading to a material characterized by stronger non-radiative phenomena that limit the PL efficiency

The ER stress sensor PERK luminal domain functions as a molecular chaperone to interact with misfolded proteins

Energy Technology Data Exchange (ETDEWEB)

Wang, Peng; Li, Jingzhi; Sha, Bingdong

2016-11-29

PERK is one of the major sensor proteins which can detect the protein-folding imbalance generated by endoplasmic reticulum (ER) stress. It remains unclear how the sensor protein PERK is activated by ER stress. It has been demonstrated that the PERK luminal domain can recognize and selectively interact with misfolded proteins but not native proteins. Moreover, the PERK luminal domain may function as a molecular chaperone to directly bind to and suppress the aggregation of a number of misfolded model proteins. The data strongly support the hypothesis that the PERK luminal domain can interact directly with misfolded proteins to induce ER stress signaling. To illustrate the mechanism by which the PERK luminal domain interacts with misfolded proteins, the crystal structure of the human PERK luminal domain was determined to 3.2 Å resolution. Two dimers of the PERK luminal domain constitute a tetramer in the asymmetric unit. Superimposition of the PERK luminal domain molecules indicated that the β-sandwich domain could adopt multiple conformations. It is hypothesized that the PERK luminal domain may utilize its flexible β-sandwich domain to recognize and interact with a broad range of misfolded proteins.

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...

Peaked signals from dark matter velocity structures in direct detection experiments

Science.gov (United States)

Lang, Rafael F.; Weiner, Neal

2010-06-01

In direct dark matter detection experiments, conventional elastic scattering of WIMPs results in exponentially falling recoil spectra. In contrast, theories of WIMPs with excited states can lead to nuclear recoil spectra that peak at finite recoil energies ER. The peaks of such signals are typically fairly broad, with ΔER/Epeak ~ 1. We show that in the presence of dark matter structures with low velocity dispersion, such as streams or clumps, peaks from up-scattering can become extremely narrow with FWHM of a few keV only. This differs dramatically from the conventionally expected WIMP spectrum and would, once detected, open the possibility to measure the dark matter velocity structure with high accuracy. As an intriguing example, we confront the observed cluster of 3 events near 42 keV from the CRESST commissioning run with this scenario. Inelastic dark matter particles with a wide range of parameters are capable of producing such a narrow peak. We calculate the possible signals at other experiments, and find that such particles could also give rise to the signal at DAMA, although not from the same stream. Over some range of parameters, a signal would be visible at xenon experiments. We show that such dark matter peaks are a very clear signal and can be easily disentangled from potential backgrounds, both terrestrial or due to WIMP down-scattering, by an enhanced annual modulation in both the amplitude of the signal and its spectral shape.

Impact of incoherent pumping field and Er3+ ion concentration on group velocity and index of refraction in an Er3+-doped YAG crystal

International Nuclear Information System (INIS)

Jafarzadeh, Hossein; Asadpour, Seyyed Hossein; Soleimani, H Rahimpour

2015-01-01

The effect of Er 3+ ion concentration and incoherent pumping field on the refractive index and group index in an Er 3+ : YAG crystal is investigated. It is shown that under different concentrations of Er 3+ ion in the crystal, the index of refraction and absorption can be changed and a high index of refraction is accompanied by amplification in the medium. Also, it is shown that with the switching from subluminal to superluminal, or vice versa, light propagation can be obtained by different concentrations of Er 3+ ions in the crystal. (paper)

Er{sub 1.33}Pt{sub 3}Ga{sub 8}: A modulated variant of the Er{sub 4}Pt{sub 9}Al{sub 24}-structure type

Energy Technology Data Exchange (ETDEWEB)

Oswald, Iain W.H. [Department of Chemistry and Biochemistry, University of Texas at Dallas, Richardson, TX 75080 (United States); Gourdon, Olivier [Research and Development, ZS Pharma, Coppell, TX 75109 (United States); Bekins, Amy; Evans, Jess [Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, TX 76019 (United States); Treadwell, LaRico J. [Department of Chemistry and Biochemistry, University of Texas at Dallas, Richardson, TX 75080 (United States); Chan, Julia Y., E-mail: Julia.Chan@utdallas.edu [Department of Chemistry and Biochemistry, University of Texas at Dallas, Richardson, TX 75080 (United States); Macaluso, Robin T., E-mail: robin.macaluso@uta.edu [Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, TX 76019 (United States); Department of Chemistry and Biochemistry, University of Northern Colorado, Greeley, CO 80639 (United States)

2016-10-15

Single crystals of Er{sub 1.33}Pt{sub 3}Ga{sub 8} were synthesized in a molten Ga flux. Er{sub 1.33}Pt{sub 3}Ga{sub 8} can be considered to be a modulated variant of the Er{sub 4}Pt{sub 9}Al{sub 24}-structure type, where the partial occupancies are ordered. Indeed, the presence of weak satellite reflections indicates a complex organization and distribution of the Er and Ga atoms within the [ErGa] slabs. The structure has been solved based on single crystal X-ray diffraction data in the monoclinic superspace group X2/m(0β0)00 with a commensurate modulated vector q=1/3b*. Precession images also indicate diffusion in the perpendicular direction indicating a partial disorder of this arrangement from layer to layer. In addition, Er{sub 1.33}Pt{sub 3}Ga{sub 8} shows antiferromagnetic ordering at T{sub N}~5 K. - Graphical abstract: A precession image of the hk0 zone showing weak, periodic, unindexed reflections indicating modulation and representation of the commensurate [ErGa] layer showing the waving modulated occupation. - Highlights: • Single crystals of Er{sub 1.33}Pt{sub 3}Ga{sub 8} were grown from gallium flux. • The structure of Er{sub 1.33}Pt{sub 3}Ga{sub 8} is compared to Er{sub 4}Pt{sub 9}Al{sub 24}. • Structure has been solved in the monoclinic superspace group X2/m(0β0)00 with a commensurate modulated vector q=1/3b*.

Simplified tools for measuring retention in care in antiretroviral treatment program in Ethiopia: cohort and current retention in care.

Science.gov (United States)

Assefa, Yibeltal; Worku, Alemayehu; Wouters, Edwin; Koole, Olivier; Haile Mariam, Damen; Van Damme, Wim

2012-01-01

Patient retention in care is a critical challenge for antiretroviral treatment programs. This is mainly because retention in care is related to adherence to treatment and patient survival. It is therefore imperative that health facilities and programs measure patient retention in care. However, the currently available tools, such as Kaplan Meier, for measuring retention in care have a lot of practical limitations. The objective of this study was to develop simplified tools for measuring retention in care. Retrospective cohort data were collected from patient registers in nine health facilities in Ethiopia. Retention in care was the primary outcome for the study. Tools were developed to measure "current retention" in care during a specific period of time for a specific "ART-age group" and "cohort retention" in care among patients who were followed for the last "Y" number of years on ART. "Probability of retention" based on the tool for "cohort retention" in care was compared with "probability of retention" based on Kaplan Meier. We found that the new tools enable to measure "current retention" and "cohort retention" in care. We also found that the tools were easy to use and did not require advanced statistical skills. Both "current retention" and "cohort retention" are lower among patients in the first two "ART-age groups" and "ART-age cohorts" than in subsequent "ART-age groups" and "ART-age cohorts". The "probability of retention" based on the new tools were found to be similar to the "probability of retention" based on Kaplan Meier. The simplified tools for "current retention" and "cohort retention" will enable practitioners and program managers to measure and monitor rates of retention in care easily and appropriately. We therefore recommend that health facilities and programs start to use these tools in their efforts to improve retention in care and patient outcomes.

Simplified tools for measuring retention in care in antiretroviral treatment program in Ethiopia: cohort and current retention in care.

Directory of Open Access Journals (Sweden)

Yibeltal Assefa

Full Text Available INTRODUCTION: Patient retention in care is a critical challenge for antiretroviral treatment programs. This is mainly because retention in care is related to adherence to treatment and patient survival. It is therefore imperative that health facilities and programs measure patient retention in care. However, the currently available tools, such as Kaplan Meier, for measuring retention in care have a lot of practical limitations. The objective of this study was to develop simplified tools for measuring retention in care. METHODS: Retrospective cohort data were collected from patient registers in nine health facilities in Ethiopia. Retention in care was the primary outcome for the study. Tools were developed to measure "current retention" in care during a specific period of time for a specific "ART-age group" and "cohort retention" in care among patients who were followed for the last "Y" number of years on ART. "Probability of retention" based on the tool for "cohort retention" in care was compared with "probability of retention" based on Kaplan Meier. RESULTS: We found that the new tools enable to measure "current retention" and "cohort retention" in care. We also found that the tools were easy to use and did not require advanced statistical skills. Both "current retention" and "cohort retention" are lower among patients in the first two "ART-age groups" and "ART-age cohorts" than in subsequent "ART-age groups" and "ART-age cohorts". The "probability of retention" based on the new tools were found to be similar to the "probability of retention" based on Kaplan Meier. CONCLUSION: The simplified tools for "current retention" and "cohort retention" will enable practitioners and program managers to measure and monitor rates of retention in care easily and appropriately. We therefore recommend that health facilities and programs start to use these tools in their efforts to improve retention in care and patient outcomes.

ER stress proteins in autoimmune and inflammatory diseases

Directory of Open Access Journals (Sweden)

Daisuke eMorito

2012-03-01

Full Text Available Over the past two decades, heat shock proteins (HSPs have been implicated in inflammatory responses and autoimmunity. HSPs were originally believed to maintain protein quality control in the cytosol. However, they also exist extracellularly and appear to act as inflammatory factors. Recently, a growing body of evidence suggested that the other class of stress proteins such as, endoplasmic reticulum (ER stress proteins, which originally act as protein quality control factors in the secretory pathway and are induced by ER stress in inflammatory lesions, also participate in inflammation and autoimmunity. The immunoglobulin heavy-chain binding protein (Bip/glucose-regulated protein 78 (Grp78, homocysteine-induced ER protein (Herp, calnexin, calreticulin, glucose-regulated protein 94 (Grp94/gp96, oxygen-regulated protein 150 (ORP150 and heat shock protein 47 (Hsp47/Serpin H1, which are expressed not only in the ER but also occasionally at the cell surface play pathophysiological roles in autoimmune and inflammatory diseases as pro- or anti-inflammatory factors. Here we describe the accumulating evidence of the participation of ER stress proteins in autoimmunity and inflammation and discuss the critical differences between the two classes of stress proteins.

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.

Er det økologisk madordninger ofte sundere?

DEFF Research Database (Denmark)

He, Chen

Det europæiske skolemad system er under forandring, en forandring der er blevet kaldt den europæiske skolemad revolution af Morgan & Sonnino (2008). Forandringen består af to afgørende søjler/indsatsområder; 1) Krav til sundere kostvaner; 2) Flere økologiske fødevarer. Denne forskning harundersøg...

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....

SEC16 in COPII coat dynamics at ER exit sites

NARCIS (Netherlands)

Sprangers, Joep; Rabouille, Catherine

Protein export from the endoplasmic reticulum (ER), the first step in protein transport through the secretory pathway, is mediated by coatomer protein II (COPII)-coated vesicles at ER exit sites. COPII coat assembly on the ER is well understood and the conserved large hydrophilic protein Sec16

Æstetiseringen af forbruget: En undersøgelse af to udstillinger, hvor branding er kunst - og kunst er branding

DEFF Research Database (Denmark)

Hermansen, Judy

2008-01-01

Æstetiseringen af hverdagen er ét af de helt centrale træk ved det postmoderne forbrugersamfund. Og denne nedbrydning af grænserne mellem kunst og forbrug er det også vigtigt for marketingteorien at udforske. Artiklen analyserer to (kunst?)udstillinger i England, som på hver sin måde tematiserer,...

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.

Programming of Fetal Insulin Resistance in Pregnancies with Maternal Obesity by ER Stress and Inflammation

Science.gov (United States)

Sáez, Pablo J.; Villalobos-Labra, Roberto; Farías-Jofré, Marcelo

2014-01-01

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. PMID:25093191

Seed Implant Retention Score Predicts the Risk of Prolonged Urinary Retention After Prostate Brachytherapy

International Nuclear Information System (INIS)

Lee, Hoon K.; Adams, Marc T.; Shi, Qiuhu; Basillote, Jay; LaMonica, Joanne; Miranda, Luis; Motta, Joseph

2010-01-01

Purpose: To risk-stratify patients for urinary retention after prostate brachytherapy according to a novel seed implant retention score (SIRS). Patients and Methods: A total of 835 patients underwent transperineal prostate seed implant from March 1993 to January 2007; 197 patients had 125 I and 638 patients had 103 Pd brachytherapy. Four hundred ninety-four patients had supplemental external-beam radiation. The final downsized prostate volume was used for the 424 patients who had neoadjuvant hormone therapy. Retention was defined as reinsertion of a Foley catheter after the implant. Results: Retention developed in 7.4% of patients, with an average duration of 6.7 weeks. On univariate analysis, implant without supplemental external-beam radiation (10% vs. 5.6%; p = 0.02), neoadjuvant hormone therapy (9.4% vs. 5.4%; p = 0.02), baseline α-blocker use (12.5% vs. 6.3%; p = 0.008), and increased prostate volume (13.4% vs. 6.9% vs. 2.9%, >45 cm 3 , 25-45 cm 3 , 3 ; p = 0.0008) were significantly correlated with increased rates of retention. On multivariate analysis, implant without supplemental external-beam radiation, neoadjuvant hormone therapy, baseline α-blocker use, and increased prostate volume were correlated with retention. A novel SIRS was modeled as the combined score of these factors, ranging from 0 to 5. There was a significant correlation between the SIRS and retention (p < 0.0001). The rates of retention were 0, 4%, 5.6%, 9%, 20.9%, and 36.4% for SIRS of 0 to 5, respectively. Conclusions: The SIRS may identify patients who are at high risk for prolonged retention after prostate brachytherapy. A prospective validation study of the SIRS is planned.

The CDK inhibitor p21 is a novel target gene of ATF4 and contributes to cell survival under ER stress.

Science.gov (United States)

Inoue, Yasumichi; Kawachi, Shiori; Ohkubo, Tsubasa; Nagasaka, Mai; Ito, Shogo; Fukuura, Keishi; Itoh, Yuka; Ohoka, Nobumichi; Morishita, Daisuke; Hayashi, Hidetoshi

2017-11-01

Activating transcription factor 4 (ATF4) is well known for its role in the endoplasmic reticulum (ER) stress response. ATF4 also transcriptionally induces multiple effectors that determine cell fate depending on cellular context. In addition, ATF4 can communicate both pro-apoptotic and pro-survival signals. How ATF4 mediates its prosurvival roles, however, requires further investigation. Here, we report that the CDK inhibitor p21 is a novel target gene of ATF4. We identified two ATF4-responsive elements, one of which directly binds ATF4, within the first intron of the p21 gene. Importantly, overexpression of p21 enhances cell survival following ER stress induction, while p21 knockdown increases cell death. These results suggest that p21 induction plays a vital role in the cellular response to ER stress and indicate that p21 is a prosurvival effector of ATF4. © 2017 Federation of European Biochemical Societies.

Behaviour of Er/sup 3 +/ ion in tetragonal crystalline field

Energy Technology Data Exchange (ETDEWEB)

Kumar, V; Dass, N; Chandra, K [Roorkee Univ. (India). Dept. of Physics

1976-12-01

Crystal field parameters for ErGaG and Er/sup 3 +/ YAlG are used to compute the temperature dependence of Schottky specific heat, paramagnetic susceptibility, magnetic anisotropy, sup(..mu..)eff and quadrupole splitting in the range 10-400 K. The hyperfine interaction parameters A and B for /sup 16/ /sup 166/Er and /sup 167/Er in both the systems are also obtained and in turn used to estimate the nuclear specific heat contribution. The studied parameters compare well with the available experimental results.

Self-assembled infrared-luminescent Er-Si-O crystallites on silicon

International Nuclear Information System (INIS)

Isshiki, H.; Dood, M.J.A. de; Polman, A.; Kimura, T.

2004-01-01

Optically active and electrically excitable erbium complexes on silicon are made by wet-chemical synthesis. The single-crystalline Er-Si-O compound is formed by coating a Si(100) substrate with an ErCl 3 /ethanol solution, followed by rapid thermal oxidation and annealing. Room-temperature Er-related 1.53 μm photoluminescence is observed with a peak linewidth as small as 4 meV. The complexes can be excited directly into the Er intra-4f states, or indirectly, through photocarriers. Er concentrations as high as 14 at. % are achieved, incorporated in a crystalline lattice with a 0.9 nm periodicity. Thermal quenching at room temperature is only a factor 5, and the lifetime at 1.535 μm is 200 μs

The ER in 3D: a multifunctional dynamic membrane network.

Science.gov (United States)

Friedman, Jonathan R; Voeltz, Gia K

2011-12-01

The endoplasmic reticulum (ER) is a large, singular, membrane-bound organelle that has an elaborate 3D structure with a diversity of structural domains. It contains regions that are flat and cisternal, ones that are highly curved and tubular, and others adapted to form contacts with nearly every other organelle and with the plasma membrane. The 3D structure of the ER is determined by both integral ER membrane proteins and by interactions with the cytoskeleton. In this review, we describe some of the factors that are known to regulate ER structure and discuss how this structural organization and the dynamic nature of the ER membrane network allow it to perform its many different functions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes.

Science.gov (United States)

Liu, Xue-Ru; Cao, Lu; Li, Tao; Chen, Lin-Lin; Yu, Yi-Yan; Huang, Wen-Jun; Liu, Li; Tan, Xiao-Qiu

2017-05-01

Previous studies have shown that propofol, an intravenous anesthetic commonly used in clinical practice, protects the myocardium from injury. Mitochondria- and endoplasmic reticulum (ER)-mediated oxidative stress and apoptosis are two important signaling pathways involved in myocardial injury and protection. The present study aimed to test the hypothesis that propofol could exert a cardio-protective effect via the above two pathways. Cultured neonatal rat cardiomyocytes were treated with culture medium (control group), H 2 O 2 at 500 μM (H 2 O 2 group), propofol at 50 μM (propofol group), and H 2 O 2 plus propofol (H 2 O 2  + propofol group), respectively. The oxidative stress, mitochondrial membrane potential (ΔΨm) and apoptosis of the cardiomyocytes were evaluated by a series of assays including ELISA, flow cytometry, immunofluorescence microscopy and Western blotting. Propofol significantly suppressed the H 2 O 2 -induced elevations in the activities of caspases 3, 8, 9 and 12, the ratio of Bax/Bcl-2, and cell apoptosis. Propofol also inhibited the H 2 O 2 -induced reactive oxygen species (ROS) generation, lactic dehydrogenase (LDH) release and mitochondrial transmembrane potential (ΔΨm) depolarization, and restored the H 2 O 2 -induced reductions of glutathione (GSH) and superoxide dismutase (SOD). In addition, propofol decreased the expressions of glucose-regulated protein 78 kDa (Grp78) and inositol-requiring enzyme 1α (IRE1α), two important signaling molecules in the ER-mediated apoptosis pathway. Propofol protects cardiomyocytes from H 2 O 2 -induced injury by inhibiting the mitochondria- and ER-mediated apoptosis signaling pathways.

Magnetocaloric effect in textured rare earth intermetallic compound ErNi

Directory of Open Access Journals (Sweden)

Aparna Sankar

2018-05-01

Full Text Available Melt-spun ErNi crystallizes in orthorhombic FeB-type structure (Space group Pnma, no. 62 similar to the arc-melted ErNi compound. Room temperature X-ray diffraction (XRD experiments reveal the presence of texture and preferred crystal orientation in the melt-spun ErNi. The XRD data obtained from the free surface of the melt-spun ErNi show large intensity enhancement for (1 0 2 Bragg reflection. The scanning electron microscopy image of the free surface depicts a granular microstructure with grains of ∼1 μm size. The arc-melted and the melt-spun ErNi compounds order ferromagnetically at 11 K and 10 K (TC respectively. Field dependent magnetization (M-H at 2 K shows saturation behaviour and the saturation magnetization value is 7.2 μB/f.u. for the arc-melted ErNi and 7.4 μB/f.u. for the melt-spun ErNi. The isothermal magnetic entropy change (ΔSm close to TC has been calculated from the M-H data. The maximum isothermal magnetic entropy change, -ΔSmmax, is ∼27 Jkg-1K-1 and ∼24 Jkg-1K-1 for the arc-melted and melt-spun ErNi for 50 kOe field change, near TC. The corresponding relative cooling power values are ∼440 J/kg and ∼432 J/kg respectively. Although a part of ΔSm is lost to crystalline electric field (CEF effects, the magnetocaloric effect is substantially large at 10 K, thus rendering melt-spun ErNi to be useful in low temperature magnetic refrigeration applications such as helium gas liquefaction.

Magnetocaloric effect in textured rare earth intermetallic compound ErNi

Science.gov (United States)

Sankar, Aparna; Chelvane, J. Arout; Morozkin, A. V.; Nigam, A. K.; Quezado, S.; Malik, S. K.; Nirmala, R.

2018-05-01

Melt-spun ErNi crystallizes in orthorhombic FeB-type structure (Space group Pnma, no. 62) similar to the arc-melted ErNi compound. Room temperature X-ray diffraction (XRD) experiments reveal the presence of texture and preferred crystal orientation in the melt-spun ErNi. The XRD data obtained from the free surface of the melt-spun ErNi show large intensity enhancement for (1 0 2) Bragg reflection. The scanning electron microscopy image of the free surface depicts a granular microstructure with grains of ˜1 μm size. The arc-melted and the melt-spun ErNi compounds order ferromagnetically at 11 K and 10 K (TC) respectively. Field dependent magnetization (M-H) at 2 K shows saturation behaviour and the saturation magnetization value is 7.2 μB/f.u. for the arc-melted ErNi and 7.4 μB/f.u. for the melt-spun ErNi. The isothermal magnetic entropy change (ΔSm) close to TC has been calculated from the M-H data. The maximum isothermal magnetic entropy change, -ΔSmmax, is ˜27 Jkg-1K-1 and ˜24 Jkg-1K-1 for the arc-melted and melt-spun ErNi for 50 kOe field change, near TC. The corresponding relative cooling power values are ˜440 J/kg and ˜432 J/kg respectively. Although a part of ΔSm is lost to crystalline electric field (CEF) effects, the magnetocaloric effect is substantially large at 10 K, thus rendering melt-spun ErNi to be useful in low temperature magnetic refrigeration applications such as helium gas liquefaction.

Structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics for a-IGZO thin-film transistors.

Science.gov (United States)

Chen, Fa-Hsyang; Her, Jim-Long; Shao, Yu-Hsuan; Matsuda, Yasuhiro H; Pan, Tung-Ming

2013-01-08

In this letter, we investigated the structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics on the amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistor (TFT) devices. Compared with the Er2O3 dielectric, the a-IGZO TFT device incorporating an Er2TiO5 gate dielectric exhibited a low threshold voltage of 0.39 V, a high field-effect mobility of 8.8 cm2/Vs, a small subthreshold swing of 143 mV/decade, and a high Ion/Ioff current ratio of 4.23 × 107, presumably because of the reduction in the oxygen vacancies and the formation of the smooth surface roughness as a result of the incorporation of Ti into the Er2TiO5 film. Furthermore, the reliability of voltage stress can be improved using an Er2TiO5 gate dielectric.

Williams syndrome transcription factor (WSTF) acts as an activator of estrogen receptor signaling in breast cancer cells and the effect can be abrogated by 1α,25-dihydroxyvitamin D3

DEFF Research Database (Denmark)

Lundqvist, Johan; Kirkegaard, Tove; Laenkholm, Anne Vibeke

2018-01-01

A majority of estrogen receptor positive (ER+) breast cancers are growth stimulated by estrogens. The ability to inhibit the ER signaling pathway is therefore of critical importance in the current treatment of ER+ breast cancers. It has been reported that 1α,25-dihydroxyvitamin D3 down......-regulates the expression of the CYP19A1 gene, encoding the aromatase enzyme that catalyzes the synthesis of estradiol. Furthermore, 1α,25-dihydroxyvitamin D3 has also been reported to down-regulate the expression of estrogen receptor α (ERα), the main mediator of ER signaling.This study reports a novel transcription...... factor critical to 1α,25-dihydroxyvitamin D3-mediated regulation of estrogenic signaling in MCF-7 breast cancer cells. We have investigated the molecular mechanisms for the 1α,25-dihydroxyvitamin D3-mediated down-regulation of CYP19A1 and ERα gene expression in human MCF-7 breast cancer cells and found...

Analysis of erythema after Er:YAG laser skin resurfacing.

Science.gov (United States)

Ko, Na Young; Ahn, Hyo-Hyun; Kim, Soo-Nam; Kye, Young-Chul

2007-11-01

Postoperative erythema can be expected to occur in every patient after laser resurfacing, and pigmentary disturbances may be related to the intensity and the duration of erythema. This study was undertaken to assess the clinical features of erythema, the factors that influence its duration, and the relation between the duration of erythema and the incidence of hyperpigmentation and hypopigmentation in skin of Asian persons after Er:YAG laser resurfacing. A total of 218 patients (skin phototypes III to V) were recruited and treated with a short-pulsed Er:YAG laser, a variable-pulsed Er:YAG laser, or a dual-mode Er:YAG laser for skin resurfacing. Clinical assessments were performed retrospectively using medical charts and serial photographs. Postoperative erythema was observed in all patients after Er:YAG laser resurfacing with a mean duration of 4.72 months. In 98.2% of patients, erythema faded completely within 12 months. Postinflammatory hyperpigmentation was observed in 38.1% of patients after Er:YAG laser resurfacing. Skin phototype, level of ablation, and depth of thermal damage caused by a long-pulsed laser appear to be important factors that affect the duration of erythema. Moreover, prolonged erythema was related to the risk of postinflammatory hyperpigmentation.

Psyken er en grænseflade

DEFF Research Database (Denmark)

Hoffmeyer, Jesper

2011-01-01

En computer er i sig selv blot et stykke mekanik. Det afgørende sker i mødet mellem maskinen, mennesker og fællesskaber: på grænsefladen. Præcis som hos levende væsner......En computer er i sig selv blot et stykke mekanik. Det afgørende sker i mødet mellem maskinen, mennesker og fællesskaber: på grænsefladen. Præcis som hos levende væsner...

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....

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....

En isoleret verden er en bedre verden

DEFF Research Database (Denmark)

Enrum, Nils

2014-01-01

Man skal ikke kaste med sten, hvis man bor i et hus med energimærke D ... Men problemet med varmetab fra danske boliger er til at løse......Man skal ikke kaste med sten, hvis man bor i et hus med energimærke D ... Men problemet med varmetab fra danske boliger er til at løse...

Fluorescence lifetime imaging of microviscosity changes during ER autophagy in live cells

Science.gov (United States)

He, Ying; Samanta, Soham; Gong, Wanjun; Liu, Wufan; Pan, Wenhui; Yang, Zhigang; Qu, Junle

2018-02-01

Unfolded or misfolded protein accumulation inside Endoplasmic Reticulum (ER) will cause ER stress and subsequently will activate cellular autophagy to release ER stress, which would ultimately result in microviscosity changes. However, even though, it is highly significant to gain a quantitative assessment of microviscosity changes during ER autophagy to study ER stress and autophagy behaviors related diseases, it has rarely been reported yet. In this work, we have reported a BODIPY based fluorescent molecular rotor that can covalently bind with vicinal dithiols containing nascent proteins in ER and hence can result in ER stress through the inhibition of the folding of nascent proteins. The change in local viscosity, caused by the release of the stress in cells through autophagy, was quantified by the probe using fluorescence lifetime imaging. This work basically demonstrates the possibility of introducing synthetic chemical probe as a promising tool to diagnose ER-viscosity-related diseases.

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...

Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells.

Science.gov (United States)

Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

2016-04-19

The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin.

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....

Optimum Er concentration for in situ doped GaN visible and infrared luminescence

International Nuclear Information System (INIS)

Lee, D. S.; Heikenfeld, J.; Steckl, A. J.; Hommerich, U.; Seo, J. T.; Braud, A.; Zavada, J.

2001-01-01

GaN thin films have been doped with varying Er concentrations (0.01--10 at.%) during molecular-beam-epitaxy growth. As expected, the visible and infrared (IR) emissions, from photoluminescence (PL) and electroluminescence (EL), are a strong function of Er concentration. We report on the determination of an optimum Er doping level for PL and EL intensity. Secondary ion mass spectroscopy and Rutherford backscattering measurements showed that the Er concentration in GaN increased exponentially with Er cell temperature. PL and EL intensity of green emission at 537 and 558 nm, due to Er 4f--4f inner shell transitions, exhibited a maximum at ∼1 at.% Er. IR PL intensity at 1.54 μm, due to another Er transition, revealed the same maximum for ∼1 at.% Er concentration. PL lifetime measurements at 537 nm showed that samples with Er concentration <1 at.% had a lifetime of ∼5 μs. For Er concentration ≥1 at.%, the lifetime decreased rapidly to values below 1 μs. This concentration quenching is believed to be due to a combination of Er cross relaxation and energy transfer to GaN defects, eventually followed by precipitation. This conclusion is supported by x-ray diffraction measurements. As a result, we have determined that the optimum Er doping concentration into GaN is ∼1 at.%. Copyright 2001 American Institute of Physics

Isothermal section of the Er-Fe-Al ternary system at 800 oC

International Nuclear Information System (INIS)

Jemmali, M.; Walha, S.; Pasturel, M.; Tougait, O.; Ben Hassen, R.; Noel, H.

2010-01-01

Physico-chemical analysis techniques, including X-ray diffraction and Scanning Electron Microscope-Energy Dispersive X-ray Spectroscopy, were employed to construct the isothermal section of the Er-Fe-Al system at 800 o C. At this temperature, the phase diagram is characterized by the formation of five intermediate phases, ErFe 12-x Al x with 5 ≤ x ≤ 8 (ThMn 12 -type), ErFe 1+x Al 1-x with -0.2 ≤ x ≤ 0.75 (MgZn 2 -type), ErFe 3-x Al x with 0.5 2 Al-type), Er 2 Fe 17-x Al x with 4.74 ≤ x ≤ 5.7 (TbCu 7 -type) and Er 2 Fe 17-x Al x with 5.7 2 Zn 17 -type), seven extensions of binaries into the ternary system; ErFe x Al 3-x with x 3 Cu-type), ErFe x Al 2-x with x ≤ 0.68 (MgCu 2 -type), Er 2 Fe x Al 1-x with x ≤ 0.25 (Co 2 Si-type), ErFe 2-x Al x with x ≤ 0.5 (MgCu 2 -type), ErFe 3-x Al x with x ≤ 0.5 (Be 3 Nb-type), Er 6 Fe 23-x Al x with x ≤ 8 (Th 6 Mn 23 -type), and Er 2 Fe 17-x Al x with x ≤ 4.75 (Th 2 Ni 17 -type) and one intermetallic compound; the ErFe 2 Al 10 (YbFe 2 Al 10 -type).

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...

Measuring the Digital Divide with PingER

Energy Technology Data Exchange (ETDEWEB)

Cottrell, L.

2003-10-01

We introduce the PingER project/toolkit and show its relevance to monitoring sites in developing countries. We then show results from PingER that illustrate the extent of the Digital Divide in terms of Internet performance between developed and developing regions, which developing regions are catching up, keeping up, or falling behind and the magnitude of the differences in performance between developed regions and developing regions.

Temperature Effects of Dielectric Properties of ER Fluids

Science.gov (United States)

Qiu, Z. Y.; Hu, L.; Liu, M. W.; Bao, H. X.; Jiang, Y. G.; Zhou, L. W.; Tang, Y.; Gao, Z.; Sun, M.; Korobko, E. V.

Under the consideration of the role that energy transfer and dissipation play in ER effect, an improved theory frame for ER effects, polarization-dissipation-structure-rheology, is suggested. The theory frame is substantiated by the basic physical laws and certain critical experimental facts. The dielectric response of a diatomite ER fluid to temperature is measured in the temperature range of 140 K to 400 K. By comparison of the DC conductivity with the AC effective conductivity of the sample, we found that the AC dielectric loss consists of two parts. One part comes from the DC conductivity, the other from the response of the bound charges in scope of particle to AC field. It is suggested that the response of bound charges is very important to ER effects. Besides, the effect of temperature on shear stress is measured, and interpreted based on the dielectric measurements. The source of two loss peaks in the curve of the dielectric loss versus temperature is not clear.

On the enhancement of Er{sup 3+} diffusion in LiNbO{sub 3} crystals by Er{sup 3+}/Ti{sup 4+} co-diffusion

Energy Technology Data Exchange (ETDEWEB)

Almeida, José Manuel Marques Martins de, E-mail: jmmma@utad.pt [INESC-TEC, Rua do Campo Alegre, 687, Porto 4169-007 (Portugal); Department of Physics, School of Science and Technology, University of Trás-os-Montes e Alto Douro, PO. Box 1013, 5001-801 Vila Real (Portugal); Sada, Cinzia [Dipartimento di Fisica e Astronomia G. Galilei, Università di Padova, Via Marzolo 8, 35131 Padova (Italy)

2016-02-15

Highlights: • Enhancement of the diffusion of erbium ions (Er{sup 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{sup 3+}/Ti{sup 4+} ions into LiNbO{sub 3}. - Abstract: After carrying out a revision of the literature on the enhancement of Er{sup 3+} diffusion in LiNbO{sub 3} crystals by Er{sup 3+}/Ti{sup 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.

Tamoxifen reduces P-gp-mediated multidrug resistance via inhibiting the PI3K/Akt signaling pathway in ER-negative human gastric cancer cells.

Science.gov (United States)

Mao, Zonglei; Zhou, Jin; Luan, Junwei; Sheng, Weihua; Shen, Xiaochun; Dong, Xiaoqiang

2014-03-01

Multidrug resistance (MDR), mediated by overexpression of drug efflux transporters such as P-glycoprotein (P-gp), is a major problem limiting successful chemotherapy of gastric cancer. Tamoxifen (TAM), a triphenylethylene nonsteroidal antiestrogen agent, shows broad-spectrum antitumor properties. Emerging studies demonstrated that TAM could significantly reduce the MDR in a variety of human cancers. Here we investigated the effects and possible underlying mechanisms of action of TAM on the reversion of MDR in ER-negative human gastric cancer cells. Our results demonstrated that in MDR phenotype SGC7901/CDDP gastric cancer cells TAM dramatically lowered the IC50 of CDDP, 5-FU and ADM, increased the intracellular Rhodamine123 accumulation and induced G0/G1 phase arrest, while G2/M phase decreased accordingly. Furthermore, at the molecular level, TAM substantially decreased the expression of P-gp, p-Akt and the Akt-regulated downstream effectors such as p-GSK-3β, p-BAD, Bcl-XL and cyclinD1 proteins without affecting the expression of t-Akt, t-GSK-3β, t-BAD proteins in SGC7901/CDDP cells. Thus, our findings demonstrate that TAM reverses P-gp-mediated gastric cancer cell MDR via inhibiting the PI3K/Akt signaling pathway. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Enhanced magnetodielectric and multiferroic properties of Er-doped bismuth ferrite nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Mukherjee, A.; Banerjee, M. [Department of Physics, National Institute of Technology, Durgapur 713209 (India); Basu, S., E-mail: soumen.basu@phy.nitdgp.ac.in [Department of Physics, National Institute of Technology, Durgapur 713209 (India); Mukadam, M.D.; Yusuf, S.M. [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Pal, M. [CSIR-Central Glass & Ceramic Research Institute, Kolkata 700032 (India)

2015-07-15

An enhancement in multiferroic properties has been achieved for chemically prepared BFO nanoparticles by doping with erbium (Er). XRD along with electron microscopy study reveals the phase purity and nanocrystalline nature of BFO. Enhancement of both the magnetic moment and resistivity is observed by virtue of Er doping. The observed enhanced magnetic moment is considered to be associated with smaller crystallite whereas increase of resistivity may be attributed to a decrease of oxygen vacancies. Doping also display an improvement of leakage behaviour and dielectric constant in nanocrystalline BFO, reflected in well-developed P-E loop. In addition, large enhancement in magnetodielectric coefficient is observed because of Er doping. Therefore, the results provide interesting approaches to improve the multiferroic properties of BFO, which has great implication towards its applications. - Highlights: • Synthesis of pure Er-doped BFO nanoparticles by chemical route. • Large increase in magnetic moment and resistivity due to Er doping. • Er doping produce well developed P-E loop and enhance polarization. • Drastic increase in dielectric constant as well as magnetodielectric coefficient observes because of Er doping.

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...

Crosstalk between Wnt/β-catenin and estrogen receptor signaling synergistically promotes osteogenic differentiation of mesenchymal progenitor cells.

Directory of Open Access Journals (Sweden)

Yanhong Gao

Full Text Available Osteogenic differentiation from mesenchymal progenitor cells (MPCs are initiated and regulated by a cascade of signaling events. Either Wnt/β-catenin or estrogen signaling pathway has been shown to play an important role in regulating skeletal development and maintaining adult tissue homeostasis. Here, we investigate the potential crosstalk and synergy of these two signaling pathways in regulating osteogenic differentiation of MPCs. We find that the activation of estrogen receptor (ER signaling by estradiol (E2 or exogenously expressed ERα in MPCs synergistically enhances Wnt3A-induced early and late osteogenic markers, as well as matrix mineralization. The E2 or ERα-mediated synergy can be effectively blocked by ERα antagonist tamoxifen. E2 stimulation can enhance endochondral ossification of Wnt3A-transduced mouse fetal limb explants. Furthermore, exogenously expressed ERα significantly enhances the maturity and mineralization of Wnt3A-induced subcutaneous and intramuscular ectopic bone formation. Mechanistically, we demonstrate that E2 does not exert any detectable effect on β-catenin/Tcf reporter activity. However, ERα expression is up-regulated within the first 48h in AdWnt3A-transduced MPCs, whereas ERβ expression is significantly inhibited within 24h. Moreover, the key enzyme for the biosynthesis of estrogens aromatase is modulated by Wnt3A in a biphasic manner, up-regulated at 24h but reduced after 48h. Our results demonstrate that, while ER signaling acts synergistically with Wnt3A in promoting osteogenic differentiation, Wnt3A may crosstalk with ER signaling by up-regulating ERα expression and down-regulating ERβ expression in MPCs. Thus, the signaling crosstalk and synergy between these two pathways should be further explored as a potential therapeutic approach to combating bone and skeletal disorders, such as fracture healing and osteoporosis.

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)

Urinary Retention Associated with Stroke.

Science.gov (United States)

Umemura, Takeru; Ohta, Hirotsugu; Yokota, Akira; Yarimizu, Shiroh; Nishizawa, Shigeru

Patients often exhibit urinary retention following a stroke. Various neuropathological and animal studies have implicated the medulla oblongata, pons, limbic system, frontal lobe as areas responsible for micturition control, although the exact area responsible for urinary retention after stroke is not clear. The purpose of this study was to identify the stroke area responsible for urinary retention by localizing the areas where strokes occur. We assessed 110 patients with cerebral infarction and 27 patients with cerebral hemorrhage (78 men, 59 women; mean age, 73.0 years) who had been admitted to our hospital between October, 2012 and September, 2013. We used computed tomography (CT) and magnetic resonance imaging (MRI) to investigate the stroke location, and evaluated whether post-stroke urinary retention occurred. Twelve (8.8%) of the 137 patients (7 men, 5 women; mean age, 78.8 years) exhibited urinary retention after a stroke. Stroke occurred in the right/left dominant hemisphere in 7 patients; nondominant hemisphere in 1; cerebellum in 3; and brainstem in 1. Strokes in the dominant hemisphere were associated with urinary retention (P = 0.0314), particularly in the area of the insula (P < 0.01). We concluded that stroke affecting the insula of the dominant hemisphere tends to cause urinary retention.

Alcohol Dehydrogenase Protects against Endoplasmic Reticulum Stress-Induced Myocardial Contractile Dysfunction via Attenuation of Oxidative Stress and Autophagy: Role of PTEN-Akt-mTOR Signaling.

Directory of Open Access Journals (Sweden)

Jiaojiao Pang

Full Text Available The endoplasmic reticulum (ER plays an essential role in ensuring proper folding of the newly synthesized proteins. Aberrant ER homeostasis triggers ER stress and development of cardiovascular diseases. ADH is involved in catalyzing ethanol to acetaldehyde although its role in cardiovascular diseases other than ethanol metabolism still remains elusive. This study was designed to examine the impact of ADH on ER stress-induced cardiac anomalies and underlying mechanisms involved using cardiac-specific overexpression of alcohol dehydrogenase (ADH.ADH and wild-type FVB mice were subjected to the ER stress inducer tunicamycin (1 mg/kg, i.p., for 48 hrs. Myocardial mechanical and intracellular Ca(2+ properties, ER stress, autophagy and associated cell signaling molecules were evaluated.ER stress compromised cardiac contractile function (evidenced as reduced fractional shortening, peak shortening, maximal velocity of shortening/relengthening, prolonged relengthening duration and impaired intracellular Ca(2+ homeostasis, oxidative stress and upregulated autophagy (increased LC3B, Atg5, Atg7 and p62, along with dephosphorylation of PTEN, Akt and mTOR, all of which were attenuated by ADH. In vitro study revealed that ER stress-induced cardiomyocyte anomaly was abrogated by ADH overexpression or autophagy inhibition using 3-MA. Interestingly, the beneficial effect of ADH was obliterated by autophagy induction, inhibition of Akt and mTOR. ER stress also promoted phosphorylation of the stress signaling ERK and JNK, the effect of which was unaffected by ADH transgene.Taken together, these findings suggested that ADH protects against ER stress-induced cardiac anomalies possibly via attenuation of oxidative stress and PTEN/Akt/mTOR pathway-regulated autophagy.

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

ARM CLASIC ER2 CRS/EDOP

Energy Technology Data Exchange (ETDEWEB)

Gerald Heymsfield

2010-12-20

Data was taken with the NASA ER-2 aircraft with the Cloud Radar System and other instruments in conjunction with the DOE ARM CLASIC field campaign. The flights were near the SGP site in north Central Oklahoma and targeted small developing convection. The CRS is a 94 GHz nadir pointing Doppler radar. Also on board the ER-2 was the Cloud Physics Lidar (CPL). Seven science flights were conducted but the weather conditions did not cooperate in that there was neither developing convection, or there was heavy rain.

Harvard ER-2 OH laser-induced fluorescence instrument

Science.gov (United States)

Wennberg, Paul O.; Anderson, James G.

1994-01-01

The Harvard ER-2 OH instrument is scheduled to be integrated into the NASA ER-2 high altitude aircraft ozone payload in August 1992. Design and fabrication is presently underway. This experiment is a descendant of a balloon borne instrument designed and built in the mid-1980s. The ER-2 instrument is being designed to measure OH and HO2 as part of the NASA ozone payload for the investigation of processes controlling the concentration of stratospheric ozone. Although not specifically designed to do so, it is hoped that valid measurements of OH and HO2 can be made in the remote free troposphere with this instrument.

Computational modelling of Er(3+): Garnet laser materials

Science.gov (United States)

Spangler, Lee H.

1994-01-01

The Er(3+) ion has attracted a lot of interest for four reasons: (1) Its (4)I(sub 13/2) yields (4)I(sub 15/2) transition lases in the eyesafe region near 1.5 micron; (2) the (4)I(sub 13/2) transition lases near 2.8 micron, an important wavelength for surgical purposes; (3) it displays surprisingly efficient upconversion with lasing observed at 1.7, 1.2, 0.85, 0.56, 0.55, and 0.47 micron following 1.5 micron pumping; and (4) it has absorption bands at 0.96 and 0.81 micron and thus can be diode pumped. However, properties desirable for upconversion reduce the efficiency of 1.5 and 3 micron laser operation and vice versa. Since all of the processes are influenced by the host via the crystal field induced stark splittings in the Er levels, this project undertook modelling of the host influence on the Er lasinng behavior. While growth and measurement of all ten Er(3+) doped garnets is the surest way of identifying hosts which maximize upconversion (or conversly, 1.5 and 3 micron performance), it is also expensive - costing approximately $10,000/material or approximately $100,000 for the materials computationally investigated here. The calculations were performed using a quantum mechanical point charge model developed by Clyde Morrison at Harry Diamond Laboratories. The programs were used to fit the Er:YAG experimental energy levels so that the crystal field parameters, B(sub nm) could be extracted. From these radial factors, rho (sub n) were determined for Er(3+) in garnets. These, in combination with crystal field components, Anm, available from X-ray data, were used to predict energy levels for Er in the other nine garnet hosts. The levels in Er:YAG were fit with an rms error of 12.2/cm over a 22,000/cm range. Predicted levels for two other garnets for which literature values were available had rms errors of less than 17/cm , showing the calculations to be reliable. Based on resonances between pairs of calculated stark levels, the model predicts GSGG as the best host

Danske hæmatologer er foran de amerikanske. http://haematologisktidsskrift.dk/diagnostik/282-danske-haematologer-er-foran-de-amerikanske.html

DEFF Research Database (Denmark)

Hokland, Peter

2017-01-01

Amerikanske hæmatologer og hæmatopatologer har udarbejdet en ny guideline, der skal forbedre diagnosticeringen og dermed behandlingen af akut anæmi, De er på linje med, hvad de hæmatologiske afdelinger allerede gør i Danmark, hvor man arbejder tæt sammen og følger samme protokol. Og kvaliteten er...

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...

Modeller forudsiger klimarespons hos træer og buske

DEFF Research Database (Denmark)

Meilby, Henrik

2015-01-01

Modeller baseret på målinger af træer og buskes årringe afslører, hvilke klimatiske faktorer der lokalt er afgørende for deres vækst. Det kan hjælpe os med at forstå nogle af de ændringer, der sker i vegetationen, for eksempel i Grønland og i alpine områder. Med udgangspunkt i klimafrem- skrivnin......Modeller baseret på målinger af træer og buskes årringe afslører, hvilke klimatiske faktorer der lokalt er afgørende for deres vækst. Det kan hjælpe os med at forstå nogle af de ændringer, der sker i vegetationen, for eksempel i Grønland og i alpine områder. Med udgangspunkt i klimafrem...

Visible and infrared photoluminescence from Er-doped SiOx

International Nuclear Information System (INIS)

Wan, J.; Sheng, C.; Lu, F.; Yuan, S.; Gong, D.W.; Liao, L.S.; Fang, Y.L.; Lin, F.; Wang, X.

1998-01-01

The annealing behaviors of photoluminescence of SiO x and Er-doped SiO x grown by molecular beam epitaxy in the wavelength range of visible and infrared light are studied. For SiO x , four PL bands located at 510, 600, 716 and 810 nm, respectively, are observed. For Er-doped SiO x , the 716 nm band, which is believed to be originated from the electron-hole recombination at the interface between crystalline Si and amorphous SiO 2 , disappears in the annealing temperature range of 500-900C. It is suggested the enhancement of Er luminescence is partially due to the energy transfer from the recombination at the interface between crystalline Si and SiO 2 to Er ions. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Excitation mechanism of Er{sup 3+} in a-Si:H; Anregungsmechanismus von Er{sup 3+} in a-Si:H

Energy Technology Data Exchange (ETDEWEB)

Kuehne, H.

2004-07-01

The aim of this work is the examination of the optoelectronical material a-Si:H (Er). It is characterised in the good electronic properties of the a-Si:H and the emission wavelength of 1.5 micrometer of erbium which coincides with the absorbtion minimum of glasfibres. Photoluminescence measurements confirm the assumption that oxigen is necessary for the optical activation of Er{sup 3+} in addition to the symmetrical breaking of the crystal field. The flexible lattice of a-Si:H enables a high concentration of Erbium up to 5.10{sup 21}/cm{sup 3} with a quantum efficiency of the luminescence of 0.5-1.5.10{sup -4} at room temperature. Photoluminescence excitation and absorption measurements of a-Si:H (Er) show, that there is no direct excitation of the erbium ions because the absorption of the Er{sup 3+} ions is two orders of magnitude below the absorption of silicon. The excitation or the Er{sup 3+} ions takes place through the absorption in silicon with additional energy transfer to Erbium. Photoluminescence measurements are done in order to differentiate between the possible excitation channels, the intrinsic bond-bond channel and the excitation through defects. The different temperature dependence of the intensity of the intrinsic luminescence (77 K - 300 K >3 orders of magnitude) in comparison with the defect luminescence and the Erbium luminescence (both 1-1.5 orders of magnitude) shows that the energy transfer takes place over defects. Luminescence and absorption measurements with boron doped a-Si:H (Er) show no dependence of the Erbium luminescence in dependence of defect density or the electrical charge of the defects. The luminescence spectra show a break in the defect luminescence at 0.84 eV. This agrees with the first excited state of the Er{sup 3+} ion combined with a clearly smaller line width of the defect luminescence (0.18 eV in comparision with >0.3 eV in erbium free a-Si:H). This result shows the resonance of the energy transfer. The resonance is

Enhancement of Er optical efficiency through bismuth sensitization in yttrium oxide

Energy Technology Data Exchange (ETDEWEB)

Scarangella, Adriana [CNR IMM-MATIS, Via S. Sofia 64, 95123 Catania (Italy); Dipartimento di Fisica e Astronomia, Università di Catania, Via S. Sofia 64, 95123 Catania (Italy); Reitano, Riccardo [Dipartimento di Fisica e Astronomia, Università di Catania, Via S. Sofia 64, 95123 Catania (Italy); Franzò, Giorgia; Miritello, Maria, E-mail: maria.miritello@ct.infn.it [CNR IMM-MATIS, Via S. Sofia 64, 95123 Catania (Italy); Priolo, Francesco [CNR IMM-MATIS, Via S. Sofia 64, 95123 Catania (Italy); Dipartimento di Fisica e Astronomia, Università di Catania, Via S. Sofia 64, 95123 Catania (Italy); Scuola Superiore di Catania, Università di Catania, Via Valdisavoia 9, 95123 Catania (Italy)

2015-07-27

The process of energy transfer (ET) between optically active ions has been widely studied to improve the optical efficiency of a system for different applications, from lighting and photovoltaics to silicon microphotonics. In this work, we report the influence of Bi on the Er optical emission in erbium-yttrium oxide thin films synthesized by magnetron co-sputtering. We demonstrate that this host permits to well dissolve Er and Bi ions, avoiding their clustering, and thus to stabilize the optically active Er{sup 3+} and Bi{sup 3+} valence states. In addition, we establish the ET occurrence from Bi{sup 3+} to Er{sup 3+} by the observed Bi{sup 3+} PL emission decrease and the simultaneous Er{sup 3+} photoluminescence (PL) emission increase. This was further confirmed by the coincidence of the Er{sup 3+} and Bi{sup 3+} excitation bands, analyzed by PL excitation spectroscopy. By increasing the Bi content of two orders of magnitude inside the host, though the occurrence of Bi-Bi interactions becomes deleterious for Bi{sup 3+} optical efficiency, the ET process between Bi{sup 3+} and Er{sup 3+} is still prevalent. We estimate ET efficiency of 70% for the optimized Bi:Er ratio equal to 1:3. Moreover, we have demonstrated to enhance the Er{sup 3+} effective excitation cross section by more than three orders of magnitude with respect to the direct one, estimating a value of 5.3 × 10{sup −18} cm{sup 2}, similar to the expected Bi{sup 3+} excitation cross section. This value is one of the highest obtained for Er in Si compatible hosts. These results make this material very promising as an efficient emitter for Si-compatible photonics devices.

Fisetin induces apoptosis and endoplasmic reticulum stress in human non-small cell lung cancer through inhibition of the MAPK signaling pathway.

Science.gov (United States)

Kang, Kyoung Ah; Piao, Mei Jing; Madduma Hewage, Susara Ruwan Kumara; Ryu, Yea Seong; Oh, Min Chang; Kwon, Taeg Kyu; Chae, Sungwook; Hyun, Jin Won

2016-07-01

Fisetin (3,3',4',7-tetrahydroxyflavone), a dietary flavonoid compound, is currently being investigated for its anticancer effect in various cancer models, including lung cancer. Recent studies show that fisetin induces cell growth inhibition and apoptosis in the human non-small cell lung cancer line NCI-H460. In this study, we investigated whether fisetin can induce endoplasmic reticulum (ER) stress-mediated apoptosis in NCI-H460 cells. Fisetin induced mitochondrial reactive oxygen species (ROS) and characteristic signs of ER stress: ER staining; mitochondrial Ca(2+) overload; expression of ER stress-related proteins; glucose-regulated protein (GRP)-78, phosphorylation of protein kinase RNA (PKR)-like endoplasmic reticulum kinase (PERK) and phosphorylation of eukaryotic initiation factor-2 α subunit; cleavage of activating transcription factor-6; phosphorylation of inositol-requiring kinase-1 and splicing of X-box transcription factor-1; induction of C/EBP homologous protein and cleaved caspase-12. siRNA-mediated knockdown of CHOP and ATF-6 attenuated fisetin-induced apoptotic cell death. In addition, fisetin induced phosphorylation of ERK, JNK, and p38 MAPK. Moreover, silencing of the MAPK signaling pathway prevented apoptotic cell death. In summary, our results indicate that, in NCI-H460 cells, fisetin induces apoptosis and ER stress that is mediated by induction of the MAPK signaling pathway.

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer.

Science.gov (United States)

Ribas, Ricardo; Pancholi, Sunil; Rani, Aradhana; Schuster, Eugene; Guest, Stephanie K; Nikitorowicz-Buniak, Joanna; Simigdala, Nikiana; Thornhill, Allan; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dowsett, Mitch; Johnston, Stephen R; Martin, Lesley-Ann

2018-06-08

Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER + ) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. A panel of ER + BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1 wt or ESR1 Y537S , modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER

Does skill retention benefit from retentivity and symbolic rehearsal? - two studies with a simulated process control task.

Science.gov (United States)

Kluge, Annette; Frank, Barbara; Maafi, Sanaz; Kuzmanovska, Aleksandra

2016-05-01

Two experiments were designed to compare two symbolic rehearsal refresher interventions (imaginary practice, a hidden introspective process) and investigate the role of retentivity in skill retention. Retentivity is investigated as the ability to memorise and reproduce information and associations that were learned a short time ago. Both experiments comprised initial training (week 1), a symbolic rehearsal for the experimental group (week 2) and a retention assessment (week 3). In the first study, the experimental group received a symbolic rehearsal, while the control group received no rehearsal. In the second study, the experimental group received the same symbolic rehearsal used in study 1, enhanced with rehearsal tasks addressing human-computer interaction. The results showed that both symbolic rehearsal interventions were equally likely to mitigate skill decay. The retentivity showed medium to high correlations with skill retention in both studies, and the results suggest that subjects high in retentivity benefit more from a symbolic rehearsal refresher intervention. Practitioner Summary: Skill decay becomes a problem in situations in which jobs require the correct mastery of non-routine situations. Two experimental studies with simulated process control tasks showed that symbolic rehearsal and retentivity can significantly mitigate skill decay and that subjects higher in retentivity benefit more from refresher interventions.

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.

ER Consolidated Qtrly Rpt_April thru June 2015_October 2015

Energy Technology Data Exchange (ETDEWEB)

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

2015-10-01

This Sandia National Laboratories, New Mexico Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) fulfills all quarterly reporting requirements set forth in the Resource Conservation and Recovery Act Facility Operating Permit, and the Compliance Order on Consent. The 13 sites in the Corrective Action process are listed in Table I-1. Because the status of any Long-Term Stewardship (LTS) activity is detailed in other reports, Section I.3.0 (titled Long-Term Stewardship Work Completed) will not be presented in future ER Quarterly Reports. Section I.3.0 of this ER Quarterly Report identifies the other reports that detail LTS activities.

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.

Estradiol Membrane-Initiated Signaling in the Brain Mediates Reproduction.

Science.gov (United States)

Micevych, Paul E; Mermelstein, Paul G; Sinchak, Kevin

2017-11-01

Over the past few years our understanding of estrogen signaling in the brain has expanded rapidly. Estrogens are synthesized in the periphery and in the brain, acting on multiple receptors to regulate gene transcription, neural function, and behavior. Various estrogen-sensitive signaling pathways often operate in concert within the same cell, increasing the complexity of the system. In females, estrogen concentrations fluctuate over the estrous/menstrual cycle, dynamically modulating estrogen receptor (ER) expression, activity, and trafficking. These dynamic changes influence multiple behaviors but are particularly important for reproduction. Using the female rodent model, we review our current understanding of estradiol signaling in the regulation of sexual receptivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endoplasmic reticulum stress increases brain MAPK signaling, inflammation and renin-angiotensin system activity and sympathetic nerve activity in heart failure.

Science.gov (United States)

Wei, Shun-Guang; Yu, Yang; Weiss, Robert M; Felder, Robert B

2016-10-01

We previously reported that endoplasmic reticulum (ER) stress is induced in the subfornical organ (SFO) and the hypothalamic paraventricular nucleus (PVN) of heart failure (HF) rats and is reduced by inhibition of mitogen-activated protein kinase (MAPK) signaling. The present study further examined the relationship between brain MAPK signaling, ER stress, and sympathetic excitation in HF. Sham-operated (Sham) and HF rats received a 4-wk intracerebroventricular (ICV) infusion of vehicle (Veh) or the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 10 μg/day). Lower mRNA levels of the ER stress biomarkers GRP78, ATF6, ATF4, and XBP-1s in the SFO and PVN of TUDCA-treated HF rats validated the efficacy of the TUDCA dose. The elevated levels of phosphorylated p44/42 and p38 MAPK in SFO and PVN of Veh-treated HF rats, compared with Sham rats, were significantly reduced in TUDCA-treated HF rats as shown by Western blot and immunofluorescent staining. Plasma norepinephrine levels were higher in Veh-treated HF rats, compared with Veh-treated Sham rats, and were significantly lower in the TUDCA-treated HF rats. TUDCA-treated HF rats also had lower mRNA levels for angiotensin converting enzyme, angiotensin II type 1 receptor, tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and NF-κB p65, and a higher mRNA level of IκB-α, in the SFO and PVN than Veh-treated HF rats. These data suggest that ER stress contributes to the augmented sympathetic activity in HF by inducing MAPK signaling, thereby promoting inflammation and renin-angiotensin system activity in key cardiovascular regulatory regions of the brain.

Hvem er mest fornøyd med samlivet? : samlivskvalitet blant samboere og gifte

OpenAIRE

Wiik, Kenneth Aarskaug; Noack, Turid

2011-01-01

Artiklene i Samfunnsspeilet er tilgjengelige fra SSBs nettsider: http://www.ssb.no/ssp/ Norge og Sverige er land der samboerskap har en lang historie, og der denne samlivsformen er mest utbredt. I dag er et av fire samliv her til lands samboerskap. Men også her er det forskjeller mellom samboere og gifte. Hvis vi sammenlikner samlivskvaliteten blant samboere og gifte, finner vi at unge samboere i alderen 25 til 35 år er minst fornøyd med samlivet sitt. Samboere med planer om å gifte seg me...

Military Retention. A Comparative Outlook

Directory of Open Access Journals (Sweden)

Vasile Sminchise

2016-06-01

Full Text Available One of the main goals for human resources management structures and for armed forces leaders is to maintain all necessary personnel, both qualitatively and quantitatively for operational needs or for full required capabilities. The retention of military personnel is essential to keep morale and unit readiness and to reduce the costs for recruiting, training, replacement of manpower. Retention rates depend not only on money or other social measures. The goal for retention is to keep in use the most valuable resource that belongs to an organization: the human beings and their knowledge. The aim pf this paper is to provide a comparative analysis of retention measures in various countries based on Research and Technology Organisation report released in 2007 and, thus, provide more examples of retention measures as far as the Romanian military system is concerned.

Retention of Root Canal Posts

DEFF Research Database (Denmark)

Sahafi, A; Benetti, Ana Raquel; Flury, S

2015-01-01

The aim of this study was to investigate the effect of the cement film thickness of a zinc phosphate or a resin cement on retention of untreated and pretreated root canal posts. Prefabricated zirconia posts (CosmoPost: 1.4 mm) and two types of luting cements (a zinc phosphate cement [DeTrey Zinc...... received tribochemical silicate coating according to the manufacturer's instructions. Posts were then luted in the prepared root canals (n=30 per group). Following water storage at 37°C for seven days, retention of the posts was determined by the pull-out method. Irrespective of the luting cement......, pretreatment with tribochemical silicate coating significantly increased retention of the posts. Increased cement film thickness resulted in decreased retention of untreated posts and of pretreated posts luted with zinc phosphate cement. Increased cement film thickness had no influence on retention...

Er3+-Al2O3 nanoparticles doping of borosilicate glass

International Nuclear Information System (INIS)

Massera, Jonathan; Petit, Laeticia; Hupa, Leena; Hupa, Mikko; Koponen, Joona; Glorieux, Benoit

2015-01-01

Novel borosilicate glasses were developed by adding in the glass batch Er 3+ -Al 2 O 3 nanoparticles synthetized by using a soft chemical method. A similar nanoparticle doping with modified chemical vapour deposition (MCVD) process was developed to increase the efficiency of the amplifying silica fibre in comparison to using MCVD and solution doping. It was shown that with the melt quench technique, a Er 3+ -Al 2 O 3 nanoparticle doping neither leads to an increase in the Er 3+ luminescence properties nor allows one to control the rare-earth chemical environment in a borosilicate glass. The site of Er 3+ in the Er 3+ -Al 2 O 3 nanoparticle containing glass seems to be similar as in glasses with the same composition prepared using standard raw materials. We suspect the Er 3+ ions to diffuse from the nanoparticles into the glass matrix. There was no clear evidence of the presence of Al 2 O 3 nanoparticles in the glasses after melting. (author)

Detection of aseismic creep along the San Andreas fault near Parkfield, California with ERS-1 radar interferometry

Science.gov (United States)

Werner, Charles L.; Rosen, Paul; Hensley, Scott; Fielding, Eric; Buckley, Sean

1997-01-01

The differential interferometric analysis of ERS data from Parkfield (CA) observations revealed the wide area distribution of creep along the moving fault segment of the San Andreas fault over a 15 month interval. The removal of the interferometric phase related to the surface topography was carried out. The fault was clearly visible in the differential interferogram. The magnitude of the tropospheric water vapor phase distortions is greater than the signal and hinders quantitative analysis beyond order of magnitude calculations.

Job embeddedness and nurse retention.

Science.gov (United States)

Reitz, O Ed; Anderson, Mary Ann; Hill, Pamela D

2010-01-01

Nurse retention is a different way of conceptualizing the employer-employee relationship when compared with turnover. Job embeddedness (JE), a construct based on retention, represents the sum of reasons why employees remain at their jobs. However, JE has not been investigated in relation to locale (urban or rural) or exclusively with a sample of registered nurses (RNs). The purpose of this study was to determine what factors (JE, age, gender, locale, and income) help predict nurse retention. A cross-sectional mailed survey design was used with RNs in different locales (urban or rural). Job embeddedness was measured by the score on the composite, standardized instrument. Nurse retention was measured by self-report items concerning intent to stay. A response rate of 49.3% was obtained. The typical respondent was female (96.1%), white, non-Hispanic (87.4%), and married (74.9%). Age and JE were predictive of nurse retention and accounted for 26% of the explained variance in intent to stay. Although age was a significant predictor of intent to stay, it accounted for only 1.4% of the variance while JE accounted for 24.6% of the variance of nurse retention (as measured by intent to stay). Older, more "embedded" nurses are more likely to remain employed in their current organization. Based on these findings, JE may form the basis for the development of an effective nurse retention program.

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.

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....

Hvilke planter er hjemmehørende i Danmark?

DEFF Research Database (Denmark)

Erik, Buchwald,; Wind, Peter; Bruun, Hans Henrik

2013-01-01

Der har i de senere år været debat om, hvorvidt konkrete plantearter - fx Ær (Acer pseudoplatanus) og Gyvel (Cytisus scoparius) - er hjemmehørende arter i Danmark eller indførte fremmede (Buchwald 2008, 20110: Friis 2010: Møller 2011; Bruun2011). En medvirkende årsag til diskussionerne er, at derr...

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....

Calculation of retention time tolerance windows with absolute confidence from shared liquid chromatographic retention data.

Science.gov (United States)

Boswell, Paul G; Abate-Pella, Daniel; Hewitt, Joshua T

2015-09-18

Compound identification by liquid chromatography-mass spectrometry (LC-MS) is a tedious process, mainly because authentic standards must be run on a user's system to be able to confidently reject a potential identity from its retention time and mass spectral properties. Instead, it would be preferable to use shared retention time/index data to narrow down the identity, but shared data cannot be used to reject candidates with an absolute level of confidence because the data are strongly affected by differences between HPLC systems and experimental conditions. However, a technique called "retention projection" was recently shown to account for many of the differences. In this manuscript, we discuss an approach to calculate appropriate retention time tolerance windows for projected retention times, potentially making it possible to exclude candidates with an absolute level of confidence, without needing to have authentic standards of each candidate on hand. In a range of multi-segment gradients and flow rates run among seven different labs, the new approach calculated tolerance windows that were significantly more appropriate for each retention projection than global tolerance windows calculated for retention projections or linear retention indices. Though there were still some small differences between the labs that evidently were not taken into account, the calculated tolerance windows only needed to be relaxed by 50% to make them appropriate for all labs. Even then, 42% of the tolerance windows calculated in this study without standards were narrower than those required by WADA for positive identification, where standards must be run contemporaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

Phase relationships in the Er-Mn-Ti ternary system at 773 K

International Nuclear Information System (INIS)

Liu Jingqi; Wang Xina; Tang Mengqi; Su Kunpeng; Yang Xiaomao; Li Chunhui; Li Xueqiang

2009-01-01

The Phase relationship in the Er-Mn-Ti ternary system at 773 K has been investigated by X-ray powder diffraction analysis with the aid of differential thermal analysis and optical microanalysis techniques in this work. The existence of eight binary compounds Mn 15 Ti 85, αMnTi, βMnTi, Mn 2 Ti, Mn 5 Ti, ErMn 12, Er 6 Mn 23 and ErMn 2 has been confirmed at 773 K in this system. The maximum solid solubility of Ti in Mn is about 8 at%Ti. The homogeneity range of Mn 2 Ti extends from about 31 at% to 39 at% Ti. The maximum solid solubility of Er in Mn 2 Ti phase is about less than 1 at% Er. No ternary compounds were found in this ternary system at 773K. At 773 K, the isothermal section of phase diagram of Er-Mn-Ti ternary system consists of 11 single-phase regions, 19 two-phase regions and 9 three-phase regions.

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...

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.

Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity*

Science.gov (United States)

Marty, Caroline; Chaligné, Ronan; Lacout, Catherine; Constantinescu, Stefan N.; Vainchenker, William; Villeval, Jean-Luc

2009-01-01

The activating W515L mutation in the thrombopoietin receptor (MPL) has been identified in primary myelofibrosis and essential thrombocythemia. MPL belongs to a subset of the cytokine receptor superfamily that requires the JAK2 kinase for signaling. We examined whether the ligand-independent MPLW515L mutant could signal intracellularly. Addition of the endoplasmic reticulum (ER) retention KDEL sequence to the receptor C terminus efficiently locked MPLW515L within its natural ER/Golgi maturation pathway. In contrast to cells expressing the parental MPLW515L, MPLW515L-KDEL-expressing FDC-P1 cells were unable to grow autonomously and to produce tumors in nude mice. When observed, tumor nodules resulted from in vivo selection of cells leaking the receptor at their surface. JAK2 co-immunoprecipitated with MPLW515L-KDEL but was not phosphorylated. We generated disulfide-bonded MPLW515L homodimers by the S402C substitution, both in the normal and KDEL context. Unlike MPLW515L-KDEL, MPLW515L-S402C-KDEL signaled constitutively and exhibited cell surface localization. These data establish that MPLW515L with appended JAK2 matures through the ER/Golgi system in an inactive conformation and suggest that the MPLW515L/JAK2 complex requires membrane localization for JAK2 phosphorylation, resulting in autonomous receptor signaling. PMID:19261614

Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis.

Science.gov (United States)

Schneeberger, Marc; Gómez-Valadés, Alicia G; Altirriba, Jordi; Sebastián, David; Ramírez, Sara; Garcia, Ainhoa; Esteban, Yaiza; Drougard, Anne; Ferrés-Coy, Albert; Bortolozzi, Analía; Garcia-Roves, Pablo M; Jones, John G; Manadas, Bruno; Zorzano, Antonio; Gomis, Ramon; Claret, Marc

2015-07-21

Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

ER stress affects processing of MHC class I-associated peptides

Directory of Open Access Journals (Sweden)

Meloche Sylvain

2009-02-01

Full Text Available Abstract Background Viral infection and neoplastic transformation trigger endoplasmic reticulum (ER stress. Thus, a large proportion of the cells that must be recognized by the immune system are stressed cells. Cells respond to ER stress by launching the unfolded protein response (UPR. The UPR regulates the two key processes that control major histocompatibility complex class I (MHC I-peptide presentation: protein synthesis and degradation. We therefore asked whether and how the UPR impinges on MHC I-peptide presentation. Results We evaluated the impact of the UPR on global MHC I expression and on presentation of the H2Kb-associated SIINFEKL peptide. EL4 cells stably transfected with vectors coding hen egg lysozyme (HEL-SIINFEKL protein variants were stressed with palmitate or exposed to glucose deprivation. UPR decreased surface expression of MHC I but did not affect MHC I mRNA level nor the total amount of intracellular MHC I proteins. Impaired MHC I-peptide presentation was due mainly to reduced supply of peptides owing to an inhibition of overall protein synthesis. Consequently, generation of H2Kb-SIINFEKL complexes was curtailed during ER stress, illustrating how generation of MHC I peptide ligands is tightly coupled to ongoing protein synthesis. Notably, the UPR-induced decline of MHC I-peptide presentation was more severe when the protein source of peptides was localized in the cytosol than in the ER. This difference was not due to changes in the translation rates of the precursor proteins but to increased stability of the cytosolic protein during ER stress. Conclusion Our results demonstrate that ER stress impairs MHC I-peptide presentation, and that it differentially regulates expression of ER- vs. cytosol-derived peptides. Furthermore, this work illustrates how ER stress, a typical feature of infected and malignant cells, can impinge on cues for adaptive immune recognition.

Facets of operational performance in an emergency room (ER)

NARCIS (Netherlands)

van der Vaart, Taco; Vastag, Gyula; Wijngaard, Jacob

This paper, using detailed time measurements of patients complemented by interviews with hospital management and staff, examines three facets of an emergency room's (ER) operational performance: (1) effectiveness of the triage system in rationing patient treatment; (2) factors influencing ER's

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

Derfor er zoner en god idé for naturen og pengepungen

DEFF Research Database (Denmark)

Hansen, Anne Merrild; Dahl, Hjalmar

2014-01-01

I rapporten ”Til Gavn for Grønland” var en zoneinddeling af landet et tema. I den offentlige debat er zoneringstanken blevet opfattet, som en (urealistisk) friholdelse af arealer for industri-aktivitet. Men ideen bag zonerne er også til fordel for erhvervslivet og økonomien. Det er en prioriterin...

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

Prophylactic effects of alpha-blockers, Tamsulosin and Alfuzosin, on postoperative urinary retention in male patients undergoing urologic surgery under spinal anaesthesia.

Science.gov (United States)

Akkoc, Ali; Aydin, Cemil; Topaktas, Ramazan; Kartalmis, Mahir; Altin, Selcuk; Isen, Kenan; Metin, Ahmet

2016-01-01

Postoperative urinary retention (POUR) is one of the most common complications after surgical procedures under spinal anaesthesia. Recent studies have shown the beneficial effects of alpha-adrenergic blockers in preventing POUR. The aim of this prospective study was to investigate and compare the prophylactic effects of tamsulosin and alfuzosin on POUR after urologic surgical procedures under spinal anaesthesia. A total of 180 males who underwent elective urologic surgery were included in this study. The patients were randomly allocated into three Groups. The Group I received placebo. Patients in Group II were given 0.4mg of tamsulosin orally 14 and 2 hours before surgery. Patients in Group III were given 10mg of alfuzosin ER orally 10 and 2 hours before surgery. All patients were closely followed for 24 hours postoperatively and their episodes of urinary retentions were recorded. There were 60 patients in each Group. Their mean age was 35.95±15.16 years. Fifteen patients in Group I (25%), 3 patients in Group II (5%) and 4 patients in Group III (6.7%) required catheterization because of urinary retention. In tamsulosin group and alfuzosin group, there were a significantly lower proportion of patients with POUR compared with the placebo Group (p=0.002 and p=0.006). The beneficial effects of tamsulosin and alfuzosin on POUR were similar between both Groups (p=0.697). This study suggests that the use of prophylactic tamsulosin or alfuzosin can reduce the incidence of urinary retention and the need for catheterization after urologic surgical procedures under spinal anaesthesia.