PI3K class II α regulates δ-opioid receptor export from the trans-Golgi network.

Science.gov (United States)

Shiwarski, Daniel J; Darr, Marlena; Telmer, Cheryl A; Bruchez, Marcel P; Puthenveedu, Manojkumar A

2017-08-01

The interplay between signaling and trafficking by G protein-coupled receptors (GPCRs) has focused mainly on endocytic trafficking. Whether and how surface delivery of newly synthesized GPCRs is regulated by extracellular signals is less understood. Here we define a signaling-regulated checkpoint at the trans -Golgi network (TGN) that controls the surface delivery of the delta opioid receptor (δR). In PC12 cells, inhibition of phosphoinositide-3 kinase (PI3K) activity blocked export of newly synthesized δR from the Golgi and delivery to the cell surface, similar to treatment with nerve growth factor (NGF). Depletion of class II phosphoinositide-3 kinase α (PI3K C2A), but not inhibition of class I PI3K, blocked δR export to comparable levels and attenuated δR-mediated cAMP inhibition. NGF treatment displaced PI3K C2A from the Golgi and optogenetic recruitment of the PI3K C2A kinase domain to the TGN-induced δR export downstream of NGF. Of importance, PI3K C2A expression promotes export of endogenous δR in primary trigeminal ganglion neurons. Taken together, our results identify PI3K C2A as being required and sufficient for δR export and surface delivery in neuronal cells and suggest that it could be a key modulator of a novel Golgi export checkpoint that coordinates GPCR delivery to the surface. © 2017 Shiwarski et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Golgi-type I and Golgi-type II neurons in the ventral anterior thalamic nucleus of the adult human: morphological features and quantitative analysis.

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Al-Hussain Bani Hani, Saleh M; El-Dwairi, Qasim A; Bataineh, Ziad M; Al-Haidari, Mohammad S; Al-Alami, Jamil

2008-05-01

The morphological and quantitative features of neurons in the adult human ventral anterior thalamic nucleus were studied in Golgi preparations. Two neuronal types were found and their quantitative features were studied. Golgi-type I neurons were medium to large cells with dense dendritic trees and dendritic protrusions and short hair-like appendages. They have somatic mean diameter of 30.8 microm (+/-9.4, n = 85). They have an average 100.3 dendritic branches, 48.97 dendritic branching points, and 58.85 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 3.1 microm (+/-1, n = 80), 1.85 microm (+/-0.8, n = 145), and 1.5 microm (+/-0.4, n = 160), respectively. Golgi-type II neurons were small to medium cells with few sparsely branching dendrites and dendritic stalked appendages with or without terminal swellings. They have somatic mean diameters of 22.2 microm (+/-5.8, n = 120). They have an average 33.76 dendritic branches, 16.49 dendritic branching points, and 21.97 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 1.6 microm (+/-0.86, n = 70), 1.15 microm (+/-0.55, n = 118), and 1 microm (+/-0.70, n = 95), respectively. These quantitative data may form the basis for further quantitative studies involving aging or some degenerative diseases that may affect cell bodies and/or dendritic trees of the Golgi-type I and/or Golgi-type II thalamic neurons.

Newly-formed emotional memories guide selective attention processes: Evidence from event-related potentials.

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Schupp, Harald T; Kirmse, Ursula; Schmälzle, Ralf; Flaisch, Tobias; Renner, Britta

2016-06-20

Emotional cues can guide selective attention processes. However, emotional stimuli can both activate long-term memory representations reflecting general world knowledge and engage newly formed memory representations representing specific knowledge from the immediate past. Here, the self-completion feature of associative memory was utilized to assess the regulation of attention processes by newly-formed emotional memory. First, new memory representations were formed by presenting pictures depicting a person either in an erotic pose or as a portrait. Afterwards, to activate newly-built memory traces, edited pictures were presented showing only the head region of the person. ERP recordings revealed the emotional regulation of attention by newly-formed memories. Specifically, edited pictures from the erotic compared to the portrait category elicited an early posterior negativity and late positive potential, similar to the findings observed for the original pictures. A control condition showed that the effect was dependent on newly-formed memory traces. Given the large number of new memories formed each day, they presumably make an important contribution to the regulation of attention in everyday life.

Newly-formed emotional memories guide selective attention processes: Evidence from event-related potentials

Science.gov (United States)

Schupp, Harald T.; Kirmse, Ursula; Schmälzle, Ralf; Flaisch, Tobias; Renner, Britta

2016-01-01

Emotional cues can guide selective attention processes. However, emotional stimuli can both activate long-term memory representations reflecting general world knowledge and engage newly formed memory representations representing specific knowledge from the immediate past. Here, the self-completion feature of associative memory was utilized to assess the regulation of attention processes by newly-formed emotional memory. First, new memory representations were formed by presenting pictures depicting a person either in an erotic pose or as a portrait. Afterwards, to activate newly-built memory traces, edited pictures were presented showing only the head region of the person. ERP recordings revealed the emotional regulation of attention by newly-formed memories. Specifically, edited pictures from the erotic compared to the portrait category elicited an early posterior negativity and late positive potential, similar to the findings observed for the original pictures. A control condition showed that the effect was dependent on newly-formed memory traces. Given the large number of new memories formed each day, they presumably make an important contribution to the regulation of attention in everyday life. PMID:27321471

Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines

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Edismauro Garcia Freitas Filho

2016-01-01

Full Text Available Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators.

Golgi-associated Rab14, a new regulator for Chlamydia trachomatis infection outcome.

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Capmany, Anahí; Leiva, Natalia; Damiani, María Teresa

2011-09-01

Chlamydia trachomatis is the causing agent of the most frequent bacterial sexually-transmitted diseases worldwide and is an underlying cause of chronic pelvic inflammatory diseases and cervical cancer. It is an obligate intracellular bacterium that establishes a close relationship with the Golgi complex and parasites the biosynthetic machinery of host cells. In a recent study, we have demonstrated that Rab14, a newly-described Golgi-associated Rab, is involved in the delivery of sphingolipids to the growing bacteria-containing vacuole. The interference with Rab14-controlled trafficking pathways delays chlamydial inclusion enlargement, decreases bacterial lipid uptake, negatively impact on bacterial differentiation, and reduces bacterial progeny and infectivity. C. trachomatis manipulation of host trafficking pathways for the acquisition of endogenously-biosynthesized nutrients arises as one of the characteristics of this highly evolved pathogen. The development of therapeutic strategies targeted to interfere with bacterium-host cell interaction is a new challenge for pharmacological approaches to control chlamydial infections.

Xyloglucan biosynthesis by Golgi membranes from suspension-cultured sycamore (Acer pseudoplatanus) cells

International Nuclear Information System (INIS)

White, A.R.; Xin, Yi

1990-01-01

Xyloglucan is a major hemicellulose polysaccharide in plant cell walls. Biosynthesis of such cell wall polysaccharides is closely linked to the process of plant cell growth and development. Xyloglucan polysaccharides consist of a β-1,4 glucan backbone synthesized by xyloglucan synthase and sidechains of xylose, galactose, and fucose added by other transferase enzymes. Most plant Golgi and plasma membranes also contain glucan synthases I ampersand II, which make β-1,4 and β-1,3 glucans, respectively. All of these enzymes have very similar activities. Cell walls on suspension-cultured cells from Acer pseudoplatanus (sycamore maple) were enzymatically softened prior to cell disruption by passing through a 30 μm nylon screen. Cell membranes from homogenates were separated by ultracentrifugation on top-loaded or flotation sucrose density gradients. Samples were collected by gradient fractionation and assayed for membrane markers and xyloglucan and glucan synthase activities. Standard marker assays (cyt. c reductase for eR, IDPase ampersand UDPase for Golgi, and eosin 5'-malelmide binding for plasma membrane) showed partial separation of these three membrane types. Golgi and plasma membrane markers overlapped in most gradients. Incorporation of 14 C-labeled sugars from UDP-glucose and UDP-xylose was used to detect xyloglucan synthase, glucan synthases I ampersand II, and xylosyl transferase in Golgi membrane fractions. These activities overlapped, although distinct peaks of xyloglucan synthase and xylosyl transferase were found. Ca ++ had a stimulatory effect on glucan synthases I ampersand II, while Mn ++ had an inhibitory effect on glucan synthase I in the presence of Ca ++ . The similarity of these various synthase activities demonstrates the need for careful structural characterization of newly synthesized polysaccharides

Identification of a Golgi apparatus protein complex important for the asexual erythrocytic cycle of the malaria parasite Plasmodium falciparum.

Science.gov (United States)

Hallée, Stéphanie; Thériault, Catherine; Gagnon, Dominic; Kehrer, Jessica; Frischknecht, Friedrich; Mair, Gunnar R; Richard, Dave

2018-03-26

Compared with other eukaryotic cell types, malaria parasites appear to possess a more rudimentary Golgi apparatus being composed of dispersed, unstacked cis and trans-cisternae. Despite playing a central role in the secretory pathway of the parasite, few Plasmodium Golgi resident proteins have been characterised. We had previously identified a new Golgi resident protein of unknown function, which we had named Golgi Protein 1, and now show that it forms a complex with a previously uncharacterised transmembrane protein (Golgi Protein 2, GP2). The Golgi Protein complex localises to the cis-Golgi throughout the erythrocytic cycle and potentially also during the mosquito stages. Analysis of parasite strains where GP1 expression is conditionally repressed and/or the GP2 gene is inactivated reveals that though the Golgi protein complex is not essential at any stage of the parasite life cycle, it is important for optimal asexual development in the blood stages. © 2018 John Wiley & Sons Ltd.

Newly-formed emotional memories guide selective attention processes: Evidence from event-related potentials

OpenAIRE

Harald T. Schupp; Ursula Kirmse; Ralf Schmälzle; Tobias Flaisch; Britta Renner

2016-01-01

Emotional cues can guide selective attention processes. However, emotional stimuli can both activate long-term memory representations reflecting general world knowledge and engage newly formed memory representations representing specific knowledge from the immediate past. Here, the self-completion feature of associative memory was utilized to assess the regulation of attention processes by newly-formed emotional memory. First, new memory representations were formed by presenting pictures depi...

A novel Golgi retention signal RPWS for tumor suppressor UBIAD1.

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Xian Wang

Full Text Available UBIAD1 plays critical roles in physiology including vitamin K and CoQ10 biosynthesis as well as pathophysiology including dyslipimedia-induced SCD (Schnyder's corneal dystrophy, Parkinson's disease, cardiovascular disease and bladder carcinoma. Since the subcellular localization of UBIAD1 varies in different cell types, characterization of the exact subcellular localization of UBIAD1 in specific human disease is vital for understanding its molecular mechanism. As UBIAD1 suppresses bladder carcinoma, we studied its subcellular localization in human bladder carcinoma cell line T24. Since fluorescent images of UBIAD1-EGFP in T24, human prostate cancer cell line PC-3, human embryonic kidney cell line HEK293 and human hepatocyte cell line L02 are similar, these four cell lines were used for present study. Using a combination of fluorescent microscopy and immunohistochemistry, it was found that UBIAD1 localized on the Golgi and endoplasmic reticulum (ER, but not on the plasma membrane, of T24 and HEK293 cells. Using scanning electron microscopy and western blot analysis, we found that UBIAD1 is enriched in the Golgi fraction extracted from the L02 cells, verifying the Golgi localization of UBAID1. Site-directed mutagenesis showed that the RPWS motif, which forms an Arginine finger on the UBIAD1 N terminus, serves as the Golgi retention signal. With both cycloheximide and brefeldin A inhibition assays, it was shown that UBIAD1 may be transported from the endoplasmic reticulum (ER to the Golgi by a COPII-mediated mechanism. Based upon flow cytometry analysis, it is shown that mutation of the RPWS motif reduced the UBIAD1-induced apoptosis of T24 cells, indicating that the proper Golgi localization of UBIAD1 influences its tumor suppressant activity. This study paves the way for further understanding the molecular mechanism of UBIAD1 in human diseases.

Sequential phosphorylation of GRASP65 during mitotic Golgi disassembly

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Danming Tang

2012-09-01

GRASP65 phosphorylation during mitosis and dephosphorylation after mitosis are required for Golgi disassembly and reassembly during the cell cycle. At least eight phosphorylation sites on GRASP65 have been identified, but whether they are modified in a coordinated fashion during mitosis is so far unknown. In this study, we raised phospho-specific antibodies that recognize phosphorylated T220/T224, S277 and S376 residues of GRASP65, respectively. Biochemical analysis showed that cdc2 phosphorylates all three sites, while plk1 enhances the phosphorylation. Microscopic studies using these antibodies for double and triple labeling demonstrate sequential phosphorylation and dephosphorylation during the cell cycle. S277 and S376 are phosphorylated from late G2 phase through metaphase until telophase when the new Golgi is reassembled. T220/224 is not modified until prophase, but is highly modified from prometaphase to anaphase. In metaphase, phospho-T220/224 signal localizes on both Golgi haze and mitotic Golgi clusters that represent dispersed Golgi vesicles and Golgi remnants, respectively, while phospho-S277 and S376 labeling is more concentrated on mitotic Golgi clusters. Expression of a phosphorylation-resistant GRASP65 mutant T220A/T224A inhibited mitotic Golgi fragmentation to a much larger extent than the expression of the S277A and S376A mutants. In cytokinesis, T220/224 dephosphorylation occurs prior to that of S277, but after S376. This study provides evidence that GRASP65 is sequentially phosphorylated and dephosphorylated during mitosis at different sites to orchestrate Golgi disassembly and reassembly during cell division, with phosphorylation of the T220/224 site being most critical in the process.

A smart drug: a pH-responsive photothermal ablation agent for Golgi apparatus activated cancer therapy.

Science.gov (United States)

Xue, Fengfeng; Wen, Ying; Wei, Peng; Gao, Yilin; Zhou, Zhiguo; Xiao, Shuzhang; Yi, Tao

2017-06-13

We report a pH-responsive photothermal ablation agent (pH-PTT) based on cyanine dyes for photothermal therapy (PTT). The nanoparticles formed by BSA and pH-PTT preferentially accumulated in the Golgi apparatus of cancer cells compared to normal cells, and thus can be specifically activated by the acidic Golgi apparatus in cancer cells for effective PTT both ex vivo and in vivo.

The small G protein Arl5 contributes to endosome-to-Golgi traffic by aiding the recruitment of the GARP complex to the Golgi

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Cláudia Rosa-Ferreira

2015-03-01

Full Text Available The small G proteins of the Arf family play critical roles in membrane trafficking and cytoskeleton organization. However, the function of some members of the family remains poorly understood including Arl5 which is widely conserved in eukaryotes. Humans have two closely related Arl5 paralogues (Arl5a and Arl5b, and both Arl5a and Arl5b localize to the trans-Golgi with Arl5b being involved in retrograde traffic from endosomes to the Golgi apparatus. To investigate the function of Arl5, we have used Drosophila melanogaster as a model system. We find that the single Arl5 orthologue in Drosophila also localizes to the trans-Golgi, but flies lacking the Arl5 gene are viable and fertile. By using both liposome and column based affinity chromatography methods we find that Arl5 interacts with the Golgi-associated retrograde protein (GARP complex that acts in the tethering of vesicles moving from endosomes to the trans-Golgi network (TGN. In Drosophila tissues the GARP complex is partially displaced from the Golgi when Arl5 is absent, and the late endosomal compartment is enlarged. In addition, in HeLa cells GARP also becomes cytosolic upon depletion of Arl5b. These phenotypes are consistent with a role in endosome-to-Golgi traffic, but are less severe than loss of GARP itself. Thus it appears that Arl5 is one of the factors that directs the recruitment of the GARP complex to the trans-Golgi, and this function is conserved in both flies and humans.

Blocking variant surface glycoprotein synthesis alters endoplasmic reticulum exit sites/Golgi homeostasis in Trypanosoma brucei.

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Ooi, Cher-Pheng; Smith, Terry K; Gluenz, Eva; Wand, Nadina Vasileva; Vaughan, Sue; Rudenko, Gloria

2018-06-01

The predominant secretory cargo of bloodstream form Trypanosoma brucei is variant surface glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre-cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post-mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of endoplasmic reticulum exit sites (ERES) in post-mitotic cells dropped from 3.9 ± 0.6 to 2.7 ± 0.1 eight hours after blocking VSG synthesis. The secretory pathway was still functional in these stalled cells, as monitored using Cathepsin L. Rates of phospholipid and glycosylphosphatidylinositol-anchor biosynthesis remained relatively unaffected, except for the level of sphingomyelin which increased. However, both endoplasmic reticulum and Golgi morphology became distorted, with the Golgi cisternae becoming significantly dilated, particularly at the trans-face. Membrane accumulation in these structures is possibly caused by reduced budding of nascent vesicles due to the drastic reduction in the total amount of secretory cargo, that is, VSG. These data argue that the total flux of secretory cargo impacts upon the biogenesis and maintenance of secretory structures and organelles in T. brucei, including the ERES and Golgi. © 2018 The Authors. Traffic published by John Wiley & Sons Ltd.

Galacturonomannan and Golgi-derived membrane linked to growth and shaping of biogenic calcite

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Marsh, M. E.; Ridall, A. L.; Azadi, P.; Duke, P. J.

2002-01-01

The coccolithophores are valuable models for the design and synthesis of composite materials, because the cellular machinery controlling the nucleation, growth, and patterning of their calcitic scales (coccoliths) can be examined genetically. The coccoliths are formed within the Golgi complex and are the major CaCO(3) component in limestone sediments-particularly those of the Cretaceous period. In this study, we describe mutants lacking a sulfated galacturonomannan and show that this polysaccharide in conjunction with the Golgi-derived membrane is directly linked to the growth and shaping of coccolith calcite but not to the initial orientated nucleation of the mineral phase.

The role of Golgi reassembly and stacking protein 65 phosphorylation in H2O2-induced cell death and Golgi morphological changes.

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Ji, Guang; Zhang, Weiwei; Quan, Moyuan; Chen, Yang; Qu, Hui; Hu, Zhiping

2016-12-01

This study aimed to investigate the effects of H 2 O 2 -induced oxidative stress on cell viability and survival, as well as changes in the distribution of Golgi apparatus and in the level of Golgi reassembly and stacking protein 65 (GRASP65). Cell viability of cultured N2a cells treated with H 2 O 2 was measured by the MTT assay. Apoptosis was measured by flow cytometry analyses. Cells labeled by indirect immunofluorescence were observed under confocal microscope to detect any Golgi morphological alterations; electron microscopy of Golgi apparatus was also done. Expression of GRASP65 and phospho-GRASP65 was examined by immunoblotting. H 2 O 2 treatment reduced the cell viability and raised the cell mortality of N2a cells in a time-dependent manner. Notable changes were only observed in the distribution and morphology of Golgi apparatus at 6 h after H 2 O 2 treatment. The expression of GRASP65 showed no significant changes at different time points; the phosphorylated GRASP65 level was significantly increased after H 2 O 2 treatment, peaked at 3 h, and finally dropped at 6 h. Taken together, GRASP65 phosphorylation may have a critical role in inducing cell death at the early stage after H 2 O 2 treatment, while its role in H 2 O 2 -induced Golgi morphological changes may be complex.

Phosphorylation of p37 is important for Golgi disassembly at mitosis

International Nuclear Information System (INIS)

Kaneko, Yayoi; Tamura, Kaori; Totsukawa, Go; Kondo, Hisao

2010-01-01

Research highlights: → p37 is phosphorylated on Serine-56 and Threonine-59 by Cdc2 at mitosis. → Phosphorylated p37 does not bind to Golgi membranes. → p37 phosphorylation inhibits p97/p37-mediated Golgi membrane fusion. -- Abstract: In mammals, the Golgi apparatus is disassembled at early mitosis and reassembled at the end of mitosis. For Golgi disassembly, membrane fusion needs to be blocked. Golgi biogenesis requires two distinct p97ATPase-mediated membrane fusion, the p97/p47 and p97/p37 pathways. We previously reported that p47 phosphorylation on Serine-140 by Cdc2 results in mitotic inhibition of the p97/p47 pathway . In this study, we demonstrate that p37 is phosphorylated on Serine-56 and Threonine-59 by Cdc2 at mitosis, and this phosphorylated p37 does not bind to Golgi membranes. Using an in vitro Golgi reassembly assay, we show that mutated p37(S56D, T59D), which mimics mitotic phosphorylation, does not cause any cisternal regrowth, indicating that p37 phosphorylation inhibits the p97/p37 pathway. Our results demonstrate that p37 phosphorylation on Serine-56 and Threonine-59 is important for Golgi disassembly at mitosis.

The Cirque du Soleil of Golgi membrane dynamics.

Science.gov (United States)

Bankaitis, Vytas A

2009-07-27

The role of lipid metabolic enzymes in Golgi membrane remodeling is a subject of intense interest. Now, in this issue, Schmidt and Brown (2009. J. Cell Biol. doi:10.1083/jcb.200904147) report that lysophosphatidic acid-specific acyltransferase, LPAAT3, contributes to Golgi membrane dynamics by suppressing tubule formation.

The Cirque du Soleil of Golgi membrane dynamics

OpenAIRE

Bankaitis, Vytas A.

2009-01-01

The role of lipid metabolic enzymes in Golgi membrane remodeling is a subject of intense interest. Now, in this issue, Schmidt and Brown (2009. J. Cell Biol. doi:10.1083/jcb.200904147) report that lysophosphatidic acid?specific acyltransferase, LPAAT3, contributes to Golgi membrane dynamics by suppressing tubule formation.

A Comparison of Traditional and Newly Emerging Forms of Cooperative Capitalization

OpenAIRE

Barton, David G.

2004-01-01

This paper compares the traditional forms of capitalization used by American co-ops to newly emerging forms. It is based on an in-depth review of several case co-ops. A broad framework is provided that may be beneficial in more extensive studies of capitalization practices of cooperatives and similar organizations. It is divided into three parts. Part One outlines the alternative capitalization forms being used by cooperatives and their antecedents, where conversions to other structures and f...

A catechol oxidase AcPPO from cherimoya (Annona cherimola Mill.) is localized to the Golgi apparatus.

Science.gov (United States)

Olmedo, Patricio; Moreno, Adrián A; Sanhueza, Dayan; Balic, Iván; Silva-Sanzana, Christian; Zepeda, Baltasar; Verdonk, Julian C; Arriagada, César; Meneses, Claudio; Campos-Vargas, Reinaldo

2018-01-01

Cherimoya (Annona cherimola) is an exotic fruit with attractive organoleptic characteristics. However, it is highly perishable and susceptible to postharvest browning. In fresh fruit, browning is primarily caused by the polyphenol oxidase (PPO) enzyme catalyzing the oxidation of o-diphenols to quinones, which polymerize to form brown melanin pigment. There is no consensus in the literature regarding a specific role of PPO, and its subcellular localization in different plant species is mainly described within plastids. The present work determined the subcellular localization of a PPO protein from cherimoya (AcPPO). The obtained results revealed that the AcPPO- green fluorescent protein co-localized with a Golgi apparatus marker, and AcPPO activity was present in Golgi apparatus-enriched fractions. Likewise, transient expression assays revealed that AcPPO remained active in Golgi apparatus-enriched fractions obtained from tobacco leaves. These results suggest a putative function of AcPPO in the Golgi apparatus of cherimoya, providing new perspectives on PPO functionality in the secretory pathway, its effects on cherimoya physiology, and the evolution of this enzyme. Copyright © 2017. Published by Elsevier B.V.

Non-synaptic signaling from cerebellar climbing fibers modulates Golgi cell activity.

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Nietz, Angela K; Vaden, Jada H; Coddington, Luke T; Overstreet-Wadiche, Linda; Wadiche, Jacques I

2017-10-13

Golgi cells are the principal inhibitory neurons at the input stage of the cerebellum, providing feedforward and feedback inhibition through mossy fiber and parallel fiber synapses. In vivo studies have shown that Golgi cell activity is regulated by climbing fiber stimulation, yet there is little functional or anatomical evidence for synapses between climbing fibers and Golgi cells. Here, we show that glutamate released from climbing fibers activates ionotropic and metabotropic receptors on Golgi cells through spillover-mediated transmission. The interplay of excitatory and inhibitory conductances provides flexible control over Golgi cell spiking, allowing either excitation or a biphasic sequence of excitation and inhibition following single climbing fiber stimulation. Together with prior studies of spillover transmission to molecular layer interneurons, these results reveal that climbing fibers exert control over inhibition at both the input and output layers of the cerebellar cortex.

Newly formed skeletal muscle fibers are prone to false positive immunostaining by rabbit antibodies

DEFF Research Database (Denmark)

Andersen, Ditte C; Kliem, Anette; Schrøder, Henrik Daa

2011-01-01

rely on controls that reveal non-specific binding by the secondary antibody and neglect that the primary rabbit antibody itself may cause false positive staining of the muscle. We suggest that reliable immuno-based protein detection in newly formed muscle fibers at least requires a nonsense rabbit......Reports on muscle biology and regeneration often implicate immuno(cyto/histo)chemical protein characterization using rabbit polyclonal antibodies. In this study we demonstrate that newly formed myofibers are especially prone to false positive staining by rabbit antibodies and this unwanted staining...

The Arf-GDP-regulated recruitment of GBF1 to Golgi membranes requires domains HDS1 and HDS2 and a Golgi-localized protein receptor.

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Quilty, Douglas; Chan, Calvin J; Yurkiw, Katherine; Bain, Alexandra; Babolmorad, Ghazal; Melançon, Paul

2018-04-19

We previously proposed a novel mechanism by which the enzyme Golgi-specific Brefeldin A resistance factor 1 (GBF1) is recruited to the membranes of the cis -Golgi, based on in vivo experiments. Here, we extended our in vivo analysis on the production of regulatory Arf-GDP and observed that ArfGAP2 and ArfGAP3 do not play a role in GBF1 recruitment. We confirm that Arf-GDP localization is critical, as a TGN-localized Arf-GDP mutant protein fails to promote GBF1 recruitment. We also reported the establishment of an in vitro GBF1 recruitment assay that supports the regulation of GBF1 recruitment by Arf-GDP. This in vitro assay yielded further evidence for the requirement of a Golgi-localized protein because heat denaturation or protease treatment of Golgi membranes abrogated GBF1 recruitment. Finally, combined in vivo and in vitro measurements indicated that the recruitment to Golgi membranes via a putative receptor requires only the HDS1 and HDS2 domains in the C-terminal half of GBF1. © 2018. Published by The Company of Biologists Ltd.

Assessment of the Quality of Newly Formed Bone around Titanium Alloy Implants by Using X-Ray Photoelectron Spectroscopy

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Hiroshi Nakada

2012-01-01

Full Text Available The aim of this study was to evaluate differences in bones quality between newly formed bone and cortical bone formed around titanium alloy implants by using X-ray photoelectron spectroscopy. As a result of narrow scan measurement at 4 weeks, the newly formed bone of C1s, P2p, O1s, and Ca2p were observed at a different peak range and strength compared with a cortical bone. At 8 weeks, the peak range and strength of newly formed bone were similar to those of cortical bone at C1s, P2p, and Ca2p, but not O1s. The results from this analysis indicate that the peaks and quantities of each element of newly formed bone were similar to those of cortical bone at 8 weeks, suggestive of a strong physicochemical resemblance.

Neutral sphingomyelinase (SMPD3) deficiency disrupts the Golgi secretory pathway and causes growth inhibition

Science.gov (United States)

Stoffel, Wilhelm; Hammels, Ina; Jenke, Bitta; Binczek, Erika; Schmidt-Soltau, Inga; Brodesser, Susanne; Schauss, Astrid; Etich, Julia; Heilig, Juliane; Zaucke, Frank

2016-01-01

Systemic loss of neutral sphingomyelinase (SMPD3) in mice leads to a novel form of systemic, juvenile hypoplasia (dwarfism). SMPD3 deficiency in mainly two growth regulating cell types contributes to the phenotype, in chondrocytes of skeletal growth zones to skeletal malformation and chondrodysplasia, and in hypothalamic neurosecretory neurons to systemic hypothalamus–pituitary–somatotropic hypoplasia. The unbiased smpd3−/− mouse mutant and derived smpd3−/− primary chondrocytes were instrumental in defining the enigmatic role underlying the systemic and cell autonomous role of SMPD3 in the Golgi compartment. Here we describe the unprecedented role of SMPD3. SMPD3 deficiency disrupts homeostasis of sphingomyelin (SM), ceramide (Cer) and diacylglycerol (DAG) in the Golgi SMPD3-SMS1 (SM-synthase1) cycle. Cer and DAG, two fusogenic intermediates, modify the membrane lipid bilayer for the initiation of vesicle formation and transport. Dysproteostasis, unfolded protein response, endoplasmic reticulum stress and apoptosis perturb the Golgi secretory pathway in the smpd3−/− mouse. Secretion of extracellular matrix proteins is arrested in chondrocytes and causes skeletal malformation and chondrodysplasia. Similarly, retarded secretion of proteo-hormones in hypothalamic neurosecretory neurons leads to hypothalamus induced combined pituitary hormone deficiency. SMPD3 in the regulation of the protein vesicular secretory pathway may become a diagnostic target in the etiology of unknown forms of juvenile growth and developmental inhibition. PMID:27882938

Golgi organization and the apical extension of fungal hyphae: an essential relationship.

Science.gov (United States)

Harris, Steven D

2013-07-01

The Golgi apparatus performs crucial functions in the sorting and processing of proteins destined for secretion from eukaryotic cells. In filamentous fungi, organization of the Golgi apparatus reflects the unique challenges brought about by the highly polarized nature of hyphal growth. Recent results show that Golgi compartments are spatially segregated within hyphal tip cells in a manner that depends upon the integrity of the cytoskeleton. Moreover, loss of normal Golgi organization stops polarized hyphal extension and triggers de-polarization of the hyphal tip. These results emphasize the point that a spatially organized and dynamic Golgi apparatus represents an adaptation that is as important for hyphal extension as is the presence of a Spitzenkörper. In addition, they also identify regulatory mechanisms that could enable controlled de-polarization of hyphae during development or infection-related morphogenesis. © 2013 John Wiley & Sons Ltd.

Synthesis of cell wall xylans and glucans by golgi membranes

International Nuclear Information System (INIS)

Gibeaut, D.M.; Carpita, N.C.

1989-01-01

We investigated the biosynthesis of mixed-linkage β-D-glucan and glucuronoarabinoxylans which make up the hemicellulosic matrix of the primary cell walls of maize and other cereal grasses. The Golgi apparatus was enriched from plasma membrane and other organelles by flotation density gradient centrifugation. Glucan synthase I and II, which are established markers for Golgi and plasma membrane, respectively, displayed considerable overlap in conventional separations with sucrose density gradients. Flotation gradients improved separation of the membranes substantially, but the different synthases themselves also incorporated radioactivity from either 10 μM or 1 mM UDP-[ 14 C]-glucose into polymer. Relative incorporation of radioactivity into polymers from UDP-[ 14 C]-xylose by the various membrane fractions was nearly identical to relative IDPase activities, indicating that combined xylosyl transferase-xylan synthase represents a new, unequivocal marker for the Golgi apparatus. We also have developed techniques of gas-liquid chromatography and radiogas proportional counting to achieve capillary quality separation of partially methylated alditol acetates with simultaneous determination of radioactivity in the derivatives. Digestion of polymeric products by specific endo-glycanohydrolases to diagnostic oligosaccharides also reveal specific kinds of polysaccharides synthesized by the Golgi membranes. A combination of these techniques provides unequivocal determination of the linkage structure of specific polymers synthesized by the purified Golgi apparatus

Proteomic characterization of golgi membranes enriched from Arabidopsis suspension cell cultures

DEFF Research Database (Denmark)

Hansen, Sara Fasmer; Ebert, Berit; Rautengarten, Carsten

2016-01-01

The plant Golgi apparatus has a central role in the secretory pathway and is the principal site within the cell for the assembly and processing of macromolecules. The stacked membrane structure of the Golgi apparatus along with its interactions with the cytoskeleton and endoplasmic reticulum has...... historically made the isolation and purification of this organelle difficult. Density centrifugation has typically been used to enrich Golgi membranes from plant microsomal preparations, and aside from minor adaptations, the approach is still widely employed. Here we outline the enrichment of Golgi membranes...... from an Arabidopsis cell suspension culture that can be used to investigate the proteome of this organelle. We also provide a useful workflow for the examination of proteomic data as the result of multiple analyses. Finally, we highlight a simple technique to validate the subcellular localization...

The asymmetrical structure of Golgi apparatus membranes revealed by in situ atomic force microscope.

Directory of Open Access Journals (Sweden)

Haijiao Xu

Full Text Available The Golgi apparatus has attracted intense attentions due to its fascinating morphology and vital role as the pivot of cellular secretory pathway since its discovery. However, its complex structure at the molecular level remains elusive due to limited approaches. In this study, the structure of Golgi apparatus, including the Golgi stack, cisternal structure, relevant tubules and vesicles, were directly visualized by high-resolution atomic force microscope. We imaged both sides of Golgi apparatus membranes and revealed that the outer leaflet of Golgi membranes is relatively smooth while the inner membrane leaflet is rough and covered by dense proteins. With the treatment of methyl-β-cyclodextrin and Triton X-100, we confirmed the existence of lipid rafts in Golgi apparatus membrane, which are mostly in the size of 20 nm -200 nm and appear irregular in shape. Our results may be of significance to reveal the structure-function relationship of the Golgi complex and pave the way for visualizing the endomembrane system in mammalian cells at the molecular level.

CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation.

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Jansen, Jos C; Cirak, Sebahattin; van Scherpenzeel, Monique; Timal, Sharita; Reunert, Janine; Rust, Stephan; Pérez, Belén; Vicogne, Dorothée; Krawitz, Peter; Wada, Yoshinao; Ashikov, Angel; Pérez-Cerdá, Celia; Medrano, Celia; Arnoldy, Andrea; Hoischen, Alexander; Huijben, Karin; Steenbergen, Gerry; Quelhas, Dulce; Diogo, Luisa; Rymen, Daisy; Jaeken, Jaak; Guffon, Nathalie; Cheillan, David; van den Heuvel, Lambertus P; Maeda, Yusuke; Kaiser, Olaf; Schara, Ulrike; Gerner, Patrick; van den Boogert, Marjolein A W; Holleboom, Adriaan G; Nassogne, Marie-Cécile; Sokal, Etienne; Salomon, Jody; van den Bogaart, Geert; Drenth, Joost P H; Huynen, Martijn A; Veltman, Joris A; Wevers, Ron A; Morava, Eva; Matthijs, Gert; Foulquier, François; Marquardt, Thorsten; Lefeber, Dirk J

2016-02-04

Disorders of Golgi homeostasis form an emerging group of genetic defects. The highly heterogeneous clinical spectrum is not explained by our current understanding of the underlying cell-biological processes in the Golgi. Therefore, uncovering genetic defects and annotating gene function are challenging. Exome sequencing in a family with three siblings affected by abnormal Golgi glycosylation revealed a homozygous missense mutation, c.92T>C (p.Leu31Ser), in coiled-coil domain containing 115 (CCDC115), the function of which is unknown. The same mutation was identified in three unrelated families, and in one family it was compound heterozygous in combination with a heterozygous deletion of CCDC115. An additional homozygous missense mutation, c.31G>T (p.Asp11Tyr), was found in a family with two affected siblings. All individuals displayed a storage-disease-like phenotype involving hepatosplenomegaly, which regressed with age, highly elevated bone-derived alkaline phosphatase, elevated aminotransferases, and elevated cholesterol, in combination with abnormal copper metabolism and neurological symptoms. Two individuals died of liver failure, and one individual was successfully treated by liver transplantation. Abnormal N- and mucin type O-glycosylation was found on serum proteins, and reduced metabolic labeling of sialic acids was found in fibroblasts, which was restored after complementation with wild-type CCDC115. PSI-BLAST homology detection revealed reciprocal homology with Vma22p, the yeast V-ATPase assembly factor located in the endoplasmic reticulum (ER). Human CCDC115 mainly localized to the ERGIC and to COPI vesicles, but not to the ER. These data, in combination with the phenotypic spectrum, which is distinct from that associated with defects in V-ATPase core subunits, suggest a more general role for CCDC115 in Golgi trafficking. Our study reveals CCDC115 deficiency as a disorder of Golgi homeostasis that can be readily identified via screening for abnormal

Characterization of the human GARP (Golgi associated retrograde protein) complex

International Nuclear Information System (INIS)

Liewen, Heike; Meinhold-Heerlein, Ivo; Oliveira, Vasco; Schwarzenbacher, Robert; Luo Guorong; Wadle, Andreas; Jung, Martin; Pfreundschuh, Michael; Stenner-Liewen, Frank

2005-01-01

The Golgi associated retrograde protein complex (GARP) or Vps fifty-three (VFT) complex is part of cellular inter-compartmental transport systems. Here we report the identification of the VFT tethering factor complex and its interactions in mammalian cells. Subcellular fractionation shows that human Vps proteins are found in the smooth membrane/Golgi fraction but not in the cytosol. Immunostaining of human Vps proteins displays a vesicular distribution most concentrated at the perinuclear envelope. Co-staining experiments with endosomal markers imply an endosomal origin of these vesicles. Significant accumulation of VFT complex positive endosomes is found in the vicinity of the Trans Golgi Network area. This is in accordance with a putative role in Golgi associated transport processes. In Saccharomyces cerevisiae, GARP is the main effector of the small GTPase Ypt6p and interacts with the SNARE Tlg1p to facilitate membrane fusion. Accordingly, the human homologue of Ypt6p, Rab6, specifically binds hVps52. In human cells, the 'orphan' SNARE Syntaxin 10 is the genuine binding partner of GARP mediated by hVps52. This reveals a previously unknown function of human Syntaxin 10 in membrane docking and fusion events at the Golgi. Taken together, GARP shows significant conservation between various species but diversification and specialization result in important differences in human cells

TCR¿ is transported to and retained in the Golgi apparatus independently of other TCR chains: implications for TCR assembly

DEFF Research Database (Denmark)

Dietrich, J; Kastrup, J; Lauritsen, Jens Peter Holst

1999-01-01

. This study focused on the intracellular localization and transport of partially assembled TCR complexes as determined by confocal microscopy analyses. We found that none of the TCR chains except for TCRzeta were allowed to exit the ER in T cell variants in which the hexameric CD3gammaepsilonTi alphabetaCD3...... deltaepsilon complex was not formed. Interestingly, TCRzeta was exported from the ER independently of other TCR chains and was predominantly located in a compartment identified as the Golgi apparatus. Furthermore, in the TCRzeta-negative cell line MA5.8, the hexameric CD3gammaepsilonTi alphabetaCD3...... the ER to the Golgi apparatus independently of each other and that these partial TCR complexes are unable to be efficiently expressed at the cell surface suggest that final TCR assembly occurs in the Golgi apparatus....

Restoration of compact Golgi morphology in advanced prostate cancer enhances susceptibility to galectin-1-induced apoptosis by modifying mucin O-glycan synthesis.

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Petrosyan, Armen; Holzapfel, Melissa S; Muirhead, David E; Cheng, Pi-Wan

2014-12-01

Prostate cancer progression is associated with upregulation of sialyl-T antigen produced by β-galactoside α-2,3-sialyltransferase-1 (ST3Gal1) but not with core 2-associated polylactosamine despite expression of core 2 N-acetylglucosaminyltransferase-L (C2GnT-L/GCNT1). This property allows androgen-refractory prostate cancer cells to evade galectin-1 (LGALS1)-induced apoptosis, but the mechanism is not known. We have recently reported that Golgi targeting of glycosyltransferases is mediated by golgins: giantin (GOLGB1) for C2GnT-M (GCNT3) and GM130 (GOLGA2)-GRASP65 (GORASP1) or GM130-giantin for core 1 synthase. Here, we show that for Golgi targeting, C2GnT-L also uses giantin exclusively whereas ST3Gal1 uses either giantin or GM130-GRASP65. In addition, the compact Golgi morphology is detected in both androgen-sensitive prostate cancer and normal prostate cells, but fragmented Golgi and mislocalization of C2GnT-L are found in androgen-refractory cells as well as primary prostate tumors (Gleason grade 2-4). Furthermore, failure of giantin monomers to be phosphorylated and dimerized prevents Golgi from forming compact morphology and C2GnT-L from targeting the Golgi. On the other hand, ST3Gal1 reaches the Golgi by an alternate site, GM130-GRASP65. Interestingly, inhibition or knockdown of non-muscle myosin IIA (MYH9) motor protein frees up Rab6a GTPase to promote phosphorylation of giantin by polo-like kinase 3 (PLK3), which is followed by dimerization of giantin assisted by protein disulfide isomerase A3 (PDIA3), and restoration of compact Golgi morphology and targeting of C2GnT-L. Finally, the Golgi relocation of C2GnT-L in androgen-refractory cells results in their increased susceptibility to galectin-1-induced apoptosis by replacing sialyl-T antigen with polylactosamine. This study demonstrates the importance of Golgi morphology and regulation of glycosylation and provides insight into how the Golgi influences cancer progression and metastasis. ©2014 American

Physiological Roles of Plant Post-Golgi Transport Pathways in Membrane Trafficking.

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Uemura, Tomohiro

2016-10-01

Membrane trafficking is the fundamental system through which proteins are sorted to their correct destinations in eukaryotic cells. Key regulators of this system include RAB GTPases and soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs). Interestingly, the numbers of RAB GTPases and SNAREs involved in post-Golgi transport pathways in plant cells are larger than those in animal and yeast cells, suggesting that plants have evolved unique and complex post-Golgi transport pathways. The trans-Golgi network (TGN) is an important organelle that acts as a sorting station in the post-Golgi transport pathways of plant cells. The TGN also functions as the early endosome, which is the first compartment to receive endocytosed proteins. Several endocytosed proteins on the plasma membrane (PM) are initially targeted to the TGN/EE, then recycled back to the PM or transported to the vacuole for degradation. The recycling and degradation of the PM localized proteins is essential for the development and environmental responses in plant. The present review describes the post-Golgi transport pathways that show unique physiological functions in plants. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Inheritance of the Golgi Apparatus and Cytokinesis Are Controlled by Degradation of GBF1

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Roberto Magliozzi

2018-06-01

Full Text Available Summary: Although much is known about how chromosome segregation is coupled to cell division, how intracellular organelles partition during mitotic division is poorly understood. We report that the phosphorylation-dependent degradation of the ARFGEF GBF1 regulates organelle trafficking during cell division. We show that, in mitosis, GBF1 is phosphorylated on Ser292 and Ser297 by casein kinase-2 allowing recognition by the F-box protein βTrCP. GBF1 interaction with βTrCP recruits GBF1 to the SCFβTrCP ubiquitin ligase complex, triggering its degradation. Phosphorylation and degradation of GBF1 occur along microtubules at the intercellular bridge of telophase cells and are required for Golgi membrane positioning and postmitotic Golgi reformation. Indeed, expression of a non-degradable GBF1 mutant inhibits the transport of the Golgi cluster adjacent to the midbody toward the Golgi twin positioned next to the centrosome and results in defective Golgi reassembly and cytokinesis failure. These findings define a mechanism that controls postmitotic Golgi reassembly and inheritance. : Magliozzi et al. demonstrate that, in mitosis, the ARFGEF GBF1 is targeted for ubiquitin-dependent degradation by casein kinase-2 and the SCFβTrCP ubiquitin ligase and show that GBF1 proteolysis is required for Golgi inheritance and accurate cell division. Keywords: cell division, cytokinesis, mitosis, Golgi apparatus, GBF1, ubiquitin-proteasome system, protein degradation, Cullin-RING ubiquitin ligase

Mitotic phosphorylation of VCIP135 blocks p97ATPase-mediated Golgi membrane fusion

Energy Technology Data Exchange (ETDEWEB)

Totsukawa, Go; Matsuo, Ayaka; Kubota, Ayano; Taguchi, Yuya; Kondo, Hisao, E-mail: hk228@med.kyushu-u.ac.jp

2013-04-05

Highlights: •VCIP135 is mitotically phosphorylated on Threonine-760 and Serine-767 by Cdc2. •Phosphorylated VCIP135 does not bind to p97ATPase. •The phosphorylation of VCIP135 inhibits p97ATPase-mediated Golgi membrane fusion. -- Abstract: In mammals, the Golgi apparatus is disassembled early mitosis and reassembled at the end of mitosis. For Golgi disassembly, membrane fusion needs to be blocked. Golgi biogenesis requires two distinct p97ATPase-mediated membrane fusion, the p97/p47 and p97/p37 pathways. We previously reported that p47 phosphorylation on Serine-140 and p37 phosphorylation on Serine-56 and Threonine-59 result in mitotic inhibition of the p97/p47 and the p97/p37 pathways, respectively [11,14]. In this study, we show another mechanism of mitotic inhibition of p97-mediated Golgi membrane fusion. We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97. An in vitro Golgi reassembly assay revealed that VCIP135(T760E, S767E), which mimics mitotic phosphorylation, caused no cisternal regrowth. Our results indicate that the phosphorylation of VCIP135 on Threonine-760 and Serine-767 inhibits p97-mediated Golgi membrane fusion at mitosis.

Depletion of the human N-terminal acetyltransferase hNaa30 disrupts Golgi integrity and ARFRP1 localization.

Science.gov (United States)

Starheim, Kristian K; Kalvik, Thomas V; Bjørkøy, Geir; Arnesen, Thomas

2017-04-30

The organization of the Golgi apparatus (GA) is tightly regulated. Golgi stack scattering is observed in cellular processes such as apoptosis and mitosis, and has also been associated with disruption of cellular lipid metabolism and neurodegenerative diseases. Our studies show that depletion of the human N-α-acetyltransferase 30 (hNaa30) induces fragmentation of the Golgi stack in HeLa and CAL-62 cell lines. The GA associated GTPase ADP ribosylation factor related protein 1 (ARFRP1) was previously shown to require N-terminal acetylation for membrane association and based on its N-terminal sequence, it is likely to be a substrate of hNaa30. ARFRP1 is involved in endosome-to- trans -Golgi network (TGN) traffic. We observed that ARFRP1 shifted from a predominantly cis -Golgi and TGN localization to localizing both Golgi and non-Golgi vesicular structures in hNaa30-depleted cells. However, we did not observe loss of membrane association of ARFRP1. We conclude that hNaa30 depletion induces Golgi scattering and induces aberrant ARFRP1 Golgi localization. © 2017 The Author(s).

Study of ethanol-induced Golgi disorganization reveals the potential mechanism of alcohol-impaired N-glycosylation

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Casey, Carol A.; Bhat, Ganapati; Holzapfel, Melissa S.; Petrosyan, Armen

2016-01-01

Background It is known that ethanol (EtOH) and its metabolites have a negative effect on protein glycosylation. The fragmentation of the Golgi apparatus induced by alteration of the structure of largest Golgi matrix protein, giantin, is the major consequence of damaging effects of EtOH-metabolism on the Golgi, however, the link between this and abnormal glycosylation remains unknown. Because previously we have shown that Golgi morphology dictates glycosylation, we examined the effect EtOH administration has on function of Golgi residential enzymes involved in N-glycosylation. Methods HepG2 cells transfected with mouse ADH1 (VA-13 cells) were treated with 35 mM ethanol for 72 h. Male Wistar rats were pair-fed Lieber-DeCarli diets for 5 to 8 weeks. Characterization of Golgi-associated mannosyl (α-1,3-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase (MGAT1), α-1,2-mannosidase (Man-I) and α-mannosidase II (Man-II) were performed in VA-13 cells and rat hepatocytes followed by 3D Structured Illumination Microscopy (SIM). Results First, we detected that EtOH administration results in the loss of sialylated N-glycans on asialoglycoprotein receptor, however the high mannose-type N-glycans are increased. Further analysis by 3D SIM microscopy revealed that EtOH treatment despite Golgi disorganization does not change cis-Golgi localization for Man-I, but does induce medial-to-cis relocation of MGAT1 and Man-II. Using different approaches, including electron microscopy, we revealed that EtOH treatment results in dysfunction of Arf1 GTPase followed by a deficiency in COPI vesicles at the Golgi. Silencing beta-COP or expression of GDP-bound mutant Arf1(T31N) mimics the EtOH effect on retaining MGAT1 and Man-II at the cis-Golgi, suggesting that (a) EtOH specifically blocks activation of Arf1, and (b) EtOH alters the proper localization of Golgi enzymes through impairment of COPI. Importantly, the level of MGAT1 was reduced, because likely MGAT1, contrary to Man-I and Man

A small-molecule switch for Golgi sulfotransferases.

Science.gov (United States)

de Graffenried, Christopher L; Laughlin, Scott T; Kohler, Jennifer J; Bertozzi, Carolyn R

2004-11-30

The study of glycan function is a major frontier in biology that could benefit from small molecules capable of perturbing carbohydrate structures on cells. The widespread role of sulfotransferases in modulating glycan function makes them prime targets for small-molecule modulators. Here, we report a system for conditional activation of Golgi-resident sulfotransferases using a chemical inducer of dimerization. Our approach capitalizes on two features shared by these enzymes: their requirement of Golgi localization for activity on cellular substrates and the modularity of their catalytic and localization domains. Fusion of these domains to the proteins FRB and FKBP enabled their induced assembly by the natural product rapamycin. We applied this strategy to the GlcNAc-6-sulfotransferases GlcNAc6ST-1 and GlcNAc6ST-2, which collaborate in the sulfation of L-selectin ligands. Both the activity and specificity of the inducible enzymes were indistinguishable from their WT counterparts. We further generated rapamycin-inducible chimeric enzymes comprising the localization domain of a sulfotransferase and the catalytic domain of a glycosyltransferase, demonstrating the generality of the system among other Golgi enzymes. The approach provides a means for studying sulfate-dependent processes in cellular systems and, potentially, in vivo.

Role of myristoylation in membrane attachment and function of G alpha i-3 on Golgi membranes.

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Brand, S H; Holtzman, E J; Scher, D A; Ausiello, D A; Stow, J L

1996-05-01

Heterotrimeric G protein alpha-subunits localized on the cytoplasmic face of Golgi membranes are involved in regulating vesicle trafficking and protein secretion. We investigated the role of myristoylation in attachment of the G alpha i-3 subunit to Golgi membranes. G alpha i-3 was epitope-tagged by insertion of a FLAG sequence at an NH2-terminal site predicted to interfere with myristoylation, and the resulting NT-alpha i-3 construct was stably transfected and expressed in polarized epithelial LLC-PK1 cells. Metabolic labeling confirmed that the translation product of NT-alpha i-3 was not myristoylated. In contrast to endogenous G alpha 1-3, which is tightly bound to Golgi membranes, the unmyristoylated FLAG-tagged NT-alpha i-3 did not attach to membranes; it was localized by immunofluorescence in the cytoplasm of LLC-PK1 cells and was detected only in the cytosol fraction of cell homogenates. Pertussis toxin-dependent ADP-ribosylation was used to test the ability of NT-alpha i-3 to interact with membrane-bound beta gamma-subunits. In both in vitro and in vivo assays, cytosolic NT-alpha i-3 alone was not ADP-ribosylated, although in the presence of membranes it could interact with G beta gamma-subunits to form heterotrimers. The expression of NT-alpha i-3 in LLC-PK1 cells altered the rate of basolateral secretion of sulfated proteoglycans, consistent with the demonstrated function of endogenous G alpha i-3. These data are consistent with a model in which G alpha i-3 utilizes NH2-terminal myristoylation to bind to Golgi membranes and to maximize its interaction with G beta gamma-subunits. Furthermore, our results show that stable attachment of G alpha i-3 to Golgi membranes is not required for it to participate as a regulatory element in vesicle trafficking in the secretory pathway.

Oxysterol-binding Protein Activation at Endoplasmic Reticulum-Golgi Contact Sites Reorganizes Phosphatidylinositol 4-Phosphate Pools*

Science.gov (United States)

Goto, Asako; Charman, Mark; Ridgway, Neale D.

2016-01-01

Oxysterol-binding protein (OSBP) exchanges cholesterol and phosphatidylinositol 4-phosphate (PI-4P) at contact sites between the endoplasmic reticulum (ER) and the trans-Golgi/trans-Golgi network. 25-Hydroxycholesterol (25OH) competitively inhibits this exchange reaction in vitro and causes the constitutive localization of OSBP at the ER/Golgi interface and PI-4P-dependent recruitment of ceramide transfer protein (CERT) for sphingomyelin synthesis. We used PI-4P probes and mass analysis to determine how OSBP controls the availability of PI-4P for this metabolic pathway. Treatment of fibroblasts or Chinese hamster ovary (CHO) cells with 25OH caused a 50–70% reduction in Golgi-associated immunoreactive PI-4P that correlated with Golgi localization of OSBP. In contrast, 25OH caused an OSBP-dependent enrichment in Golgi PI-4P that was detected with a pleckstrin homology domain probe. The cellular mass of phosphatidylinositol monophosphates and Golgi PI-4P measured with an unbiased PI-4P probe (P4M) was unaffected by 25OH and OSBP silencing, indicating that OSBP shifts the distribution of PI-4P upon localization to ER-Golgi contact sites. The PI-4P and sterol binding activities of OSBP were both required for 25OH activation of sphingomyelin synthesis, suggesting that 25OH must be exchanged for PI-4P to be concentrated at contact sites. We propose a model wherein 25OH activation of OSBP promotes the binding and retention of PI-4P at ER-Golgi contact sites. This pool of PI-4P specifically recruits pleckstrin homology domain-containing proteins involved in lipid transfer and metabolism, such as CERT. PMID:26601944

Nonrandom γ-TuNA-dependent spatial pattern of microtubule nucleation at the Golgi.

Science.gov (United States)

Sanders, Anna A W M; Chang, Kevin; Zhu, Xiaodong; Thoppil, Roslin J; Holmes, William R; Kaverina, Irina

2017-11-07

Noncentrosomal microtubule (MT) nucleation at the Golgi generates MT network asymmetry in motile vertebrate cells. Investigating the Golgi-derived MT (GDMT) distribution, we find that MT asymmetry arises from nonrandom nucleation sites at the Golgi (hotspots). Using computational simulations, we propose two plausible mechanistic models of GDMT nucleation leading to this phenotype. In the "cooperativity" model, formation of a single GDMT promotes further nucleation at the same site. In the "heterogeneous Golgi" model, MT nucleation is dramatically up-regulated at discrete and sparse locations within the Golgi. While MT clustering in hotspots is equally well described by both models, simulating MT length distributions within the cooperativity model fits the data better. Investigating the molecular mechanism underlying hotspot formation, we have found that hotspots are significantly smaller than a Golgi subdomain positive for scaffolding protein AKAP450, which is thought to recruit GDMT nucleation factors. We have further probed potential roles of known GDMT-promoting molecules, including γ-TuRC-mediated nucleation activator (γ-TuNA) domain-containing proteins and MT stabilizer CLASPs. While both γ-TuNA inhibition and lack of CLASPs resulted in drastically decreased GDMT nucleation, computational modeling revealed that only γ-TuNA inhibition suppressed hotspot formation. We conclude that hotspots require γ-TuNA activity, which facilitates clustered GDMT nucleation at distinct Golgi sites. © 2017 Sanders et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

The cerebellar Golgi cell and spatiotemporal organization of granular layer activity

Directory of Open Access Journals (Sweden)

Egidio eD‘Angelo

2013-05-01

Full Text Available The cerebellar granular layer has been suggested to perform a complex spatiotemporal reconfiguration of incoming mossy fiber signals. Central to this role is the inhibitory action exerted by Golgi cells over granule cells: Golgi cells inhibit granule cells through double feedforward and feedback inhibitory loops and generate a broad lateral inhibition that extends beyond the afferent synaptic field. This characteristic connectivity has recently been investigated in great detail and been correlated with specific functional properties of the neuron. These include theta-frequency pacemaking, network entrainment into coherent oscillations and phase resetting. Important advances have also been made in terms of determining the membrane and synaptic properties of the neuron, and clarifying the mechanisms of activation by input bursts. Moreover, voltage sensitive dye imaging and multi-electrode array recordings, combined with mathematical simulations based on realistic computational models, have improved our understanding of the impact of Golgi cell activity on granular layer circuit computations. These investigations have highlighted the critical role of Golgi cells in: generating dense clusters of granule cell activity organized in center-surround structures, implementing combinatorial operations on multiple mossy fiber inputs, regulating transmission gain and cut-off frequency, controlling spike timing and burst transmission, and determining the sign, intensity and extension of long-term synaptic plasticity at the mossy fiber-granule cell relay. This review considers recent advances in the field, highlighting the functional implications of Golgi cells for granular layer network computation and indicating new challenges for cerebellar research.

Protogalaxy interactions in newly formed clusters: Galaxy luminosities, colors, and intergalactic gas

International Nuclear Information System (INIS)

Silk, J.

1978-01-01

The role of protogalaxy interactions in galactic evolution is studied during the formation of galaxy clusters. In the early stages of the collapse, coalescent encounters of protogalaxies lead to the development of a galactic luminosity function. Once galaxies acquire appreciable random motions, mutual collisions between galaxies in rich clusters will trigger the collapse of interstellar clouds to form stars. This provides both a source for enriched intracluster gas and an interpretation of the correlation between luminosity and color for cluster elliptical galaxies. Other observational consequences that are considered include optical, X-ray, and diffuse nonthermal radio emission from newly formed clusters of galaxies

Oxysterol-binding Protein Activation at Endoplasmic Reticulum-Golgi Contact Sites Reorganizes Phosphatidylinositol 4-Phosphate Pools.

Science.gov (United States)

Goto, Asako; Charman, Mark; Ridgway, Neale D

2016-01-15

Oxysterol-binding protein (OSBP) exchanges cholesterol and phosphatidylinositol 4-phosphate (PI-4P) at contact sites between the endoplasmic reticulum (ER) and the trans-Golgi/trans-Golgi network. 25-Hydroxycholesterol (25OH) competitively inhibits this exchange reaction in vitro and causes the constitutive localization of OSBP at the ER/Golgi interface and PI-4P-dependent recruitment of ceramide transfer protein (CERT) for sphingomyelin synthesis. We used PI-4P probes and mass analysis to determine how OSBP controls the availability of PI-4P for this metabolic pathway. Treatment of fibroblasts or Chinese hamster ovary (CHO) cells with 25OH caused a 50-70% reduction in Golgi-associated immunoreactive PI-4P that correlated with Golgi localization of OSBP. In contrast, 25OH caused an OSBP-dependent enrichment in Golgi PI-4P that was detected with a pleckstrin homology domain probe. The cellular mass of phosphatidylinositol monophosphates and Golgi PI-4P measured with an unbiased PI-4P probe (P4M) was unaffected by 25OH and OSBP silencing, indicating that OSBP shifts the distribution of PI-4P upon localization to ER-Golgi contact sites. The PI-4P and sterol binding activities of OSBP were both required for 25OH activation of sphingomyelin synthesis, suggesting that 25OH must be exchanged for PI-4P to be concentrated at contact sites. We propose a model wherein 25OH activation of OSBP promotes the binding and retention of PI-4P at ER-Golgi contact sites. This pool of PI-4P specifically recruits pleckstrin homology domain-containing proteins involved in lipid transfer and metabolism, such as CERT. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

3D Printing of Plant Golgi Stacks from Their Electron Tomographic Models.

Science.gov (United States)

Mai, Keith Ka Ki; Kang, Madison J; Kang, Byung-Ho

2017-01-01

Three-dimensional (3D) printing is an effective tool for preparing tangible 3D models from computer visualizations to assist in scientific research and education. With the recent popularization of 3D printing processes, it is now possible for individual laboratories to convert their scientific data into a physical form suitable for presentation or teaching purposes. Electron tomography is an electron microscopy method by which 3D structures of subcellular organelles or macromolecular complexes are determined at nanometer-level resolutions. Electron tomography analyses have revealed the convoluted membrane architectures of Golgi stacks, chloroplasts, and mitochondria. But the intricacy of their 3D organizations is difficult to grasp from tomographic models illustrated on computer screens. Despite the rapid development of 3D printing technologies, production of organelle models based on experimental data with 3D printing has rarely been documented. In this chapter, we present a simple guide to creating 3D prints of electron tomographic models of plant Golgi stacks using the two most accessible 3D printing technologies.

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

International Nuclear Information System (INIS)

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

2010-01-01

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

STED Imaging of Golgi Dynamics with Cer-SiR: A Two-Component, Photostable, High-Density Lipid Probe for Live Cells.

Science.gov (United States)

Erdmann, Roman S; Toomre, Derek; Schepartz, Alanna

2017-01-01

Long time-lapse super-resolution imaging in live cells requires a labeling strategy that combines a bright, photostable fluorophore with a high-density localization probe. Lipids are ideal high-density localization probes, as they are >100 times more abundant than most membrane-bound proteins and simultaneously demark the boundaries of cellular organelles. Here, we describe Cer-SiR, a two-component, high-density lipid probe that is exceptionally photostable. Cer-SiR is generated in cells via a bioorthogonal reaction of two components: a ceramide lipid tagged with trans-cyclooctene (Cer-TCO) and a reactive, photostable Si-rhodamine dye (SiR-Tz). These components assemble within the Golgi apparatus of live cells to form Cer-SiR. Cer-SiR is benign to cellular function, localizes within the Golgi at a high density, and is sufficiently photostable to enable visualization of Golgi structure and dynamics by 3D confocal or long time-lapse STED microscopy.

Quantifying Golgi structure using EM: combining volume-SEM and stereology for higher throughput.

Science.gov (United States)

Ferguson, Sophie; Steyer, Anna M; Mayhew, Terry M; Schwab, Yannick; Lucocq, John Milton

2017-06-01

Investigating organelles such as the Golgi complex depends increasingly on high-throughput quantitative morphological analyses from multiple experimental or genetic conditions. Light microscopy (LM) has been an effective tool for screening but fails to reveal fine details of Golgi structures such as vesicles, tubules and cisternae. Electron microscopy (EM) has sufficient resolution but traditional transmission EM (TEM) methods are slow and inefficient. Newer volume scanning EM (volume-SEM) methods now have the potential to speed up 3D analysis by automated sectioning and imaging. However, they produce large arrays of sections and/or images, which require labour-intensive 3D reconstruction for quantitation on limited cell numbers. Here, we show that the information storage, digital waste and workload involved in using volume-SEM can be reduced substantially using sampling-based stereology. Using the Golgi as an example, we describe how Golgi populations can be sensed quantitatively using single random slices and how accurate quantitative structural data on Golgi organelles of individual cells can be obtained using only 5-10 sections/images taken from a volume-SEM series (thereby sensing population parameters and cell-cell variability). The approach will be useful in techniques such as correlative LM and EM (CLEM) where small samples of cells are treated and where there may be variable responses. For Golgi study, we outline a series of stereological estimators that are suited to these analyses and suggest workflows, which have the potential to enhance the speed and relevance of data acquisition in volume-SEM.

The Golgin GMAP210/TRIP11 anchors IFT20 to the Golgi complex.

Directory of Open Access Journals (Sweden)

John A Follit

2008-12-01

Full Text Available Eukaryotic cells often use proteins localized to the ciliary membrane to monitor the extracellular environment. The mechanism by which proteins are sorted, specifically to this subdomain of the plasma membrane, is almost completely unknown. Previously, we showed that the IFT20 subunit of the intraflagellar transport particle is localized to the Golgi complex, in addition to the cilium and centrosome, and hypothesized that the Golgi pool of IFT20 plays a role in sorting proteins to the ciliary membrane. Here, we show that IFT20 is anchored to the Golgi complex by the golgin protein GMAP210/Trip11. Mice lacking GMAP210 die at birth with a pleiotropic phenotype that includes growth restriction, ventricular septal defects of the heart, omphalocele, and lung hypoplasia. Cells lacking GMAP210 have normal Golgi structure, but IFT20 is no longer localized to this organelle. GMAP210 is not absolutely required for ciliary assembly, but cilia on GMAP210 mutant cells are shorter than normal and have reduced amounts of the membrane protein polycystin-2 localized to them. This work suggests that GMAP210 and IFT20 function together at the Golgi in the sorting or transport of proteins destined for the ciliary membrane.

Localization of foot-and-mouth disease - RNA synthesis on newly formed cellular smooth membranous vacuoles

International Nuclear Information System (INIS)

Polatnick, J.; Wool, S.H.

1982-01-01

Viral RNA synthesis in foot-and-mouth disease infected bovine kidney cell cultures was associated throughout the infectious period with newly formed smooth membranous vacuoles. Membrane formation was measured by choline uptake. The site of RNA synthesis was determined by electron microscopic examination of autoradiograms of incorporated [ 3 H] uridine. Both membrane formation and RNA synthesis became signifcant at 2.5 hours postinfection, but membrane formation increased steadily to 4.5 hours while RNA synthesis peaked at 3.5 hours. Percent density distributions of developed silver grains on autoradiograms showed that almost all RNA synthesis was concentrated on the smooth vacuoles of infected cells. Histogram analysis of grain density distributions established that the site of RNA synthesis was the vacuolar membrane. The newly formed smooth membrane-bound vacuoles were not seen to coalesce into the large vacuolated areas typical of poliovirus cytopathogenicity. (Author)

Localization of foot-and-mouth disease - RNA synthesis on newly formed cellular smooth membranous vacuoles

Energy Technology Data Exchange (ETDEWEB)

Polatnick, J.; Wool, S.H. (United States Department of Agriculture, Science and Education, Greenport, New York (USA). Agricultural Research, Plum Island Animal Disease Center)

1982-01-01

Viral RNA synthesis in foot-and-mouth disease infected bovine kidney cell cultures was associated throughout the infectious period with newly formed smooth membranous vacuoles. Membrane formation was measured by choline uptake. The site of RNA synthesis was determined by electron microscopic examination of autoradiograms of incorporated (/sup 3/H) uridine. Both membrane formation and RNA synthesis became signifcant at 2.5 hours postinfection, but membrane formation increased steadily to 4.5 hours while RNA synthesis peaked at 3.5 hours. Percent density distributions of developed silver grains on autoradiograms showed that almost all RNA synthesis was concentrated on the smooth vacuoles of infected cells. Histogram analysis of grain density distributions established that the site of RNA synthesis was the vacuolar membrane. The newly formed smooth membrane-bound vacuoles were not seen to coalesce into the large vacuolated areas typical of poliovirus cytopathogenicity.

TMEM199 Deficiency Is a Disorder of Golgi Homeostasis Characterized by Elevated Aminotransferases, Alkaline Phosphatase, and Cholesterol and Abnormal Glycosylation

NARCIS (Netherlands)

Jansen, Jos C.; Timal, Sharita; van Scherpenzeel, Monique; Michelakakis, Helen; Vicogne, Dorothée; Ashikov, Angel; Moraitou, Marina; Hoischen, Alexander; Huijben, Karin; Steenbergen, Gerry; van den Boogert, Marjolein A. W.; Porta, Francesco; Calvo, Pier Luigi; Mavrikou, Mersyni; Cenacchi, Giovanna; van den Bogaart, Geert; Salomon, Jody; Holleboom, Adriaan G.; Rodenburg, Richard J.; Drenth, Joost P. H.; Huynen, Martijn A.; Wevers, Ron A.; Morava, Eva; Foulquier, François; Veltman, Joris A.; Lefeber, Dirk J.

2016-01-01

Congenital disorders of glycosylation (CDGs) form a genetically and clinically heterogeneous group of diseases with aberrant protein glycosylation as a hallmark. A subgroup of CDGs can be attributed to disturbed Golgi homeostasis. However, identification of pathogenic variants is seriously

EXPERIMENTAL INVESTIGATION OF THE ORTHO/PARA RATIO OF NEWLY FORMED MOLECULAR HYDROGEN ON AMORPHOUS SOLID WATER

International Nuclear Information System (INIS)

Gavilan, L.; Lemaire, J. L.; Dulieu, F.; Congiu, E.; Chaabouni, H.; Vidali, G.; Chehrouri, M.; Fillion, J.-H.

2012-01-01

Several astronomical observations have shown that the ortho/para ratio (OPR) of H 2 can differ from the expected statistical value of 3 or the local thermodynamic equilibrium (LTE) value at the gas or dust temperature. It is thus important to know the OPR of H 2 newly formed on dust grain surfaces, in order to clarify the dependence of the observed OPR in space on the formation process. Using an experimental setup designed to mimic interstellar medium environments, we measured the OPR of H 2 and D 2 formed on the surface of porous amorphous water ice held at 10 K. We report for the first time the OPR value for newly formed D 2 , consistent with the expected LTE value at the high-temperature limit found by previous theoretical and experimental works on the determination of the OPR upon H 2 formation on surfaces at low temperature.

Golgi coiled-coil proteins contain multiple binding sites for Rab family G proteins

NARCIS (Netherlands)

Sinka, Rita; Gillingham, Alison K.; Kondylis, Vangelis; Munro, Sean

2008-01-01

Vesicles and other carriers destined for the Golgi apparatus must be guided to the correct cisternae. Golgins, long coiled-coil proteins that localize to particular Golgi subdomains via their C termini, are candidate regulators of vesicle sorting. In this study, we report that the GRIP domain

Defects in the COG complex and COG-related trafficking regulators affect neuronal Golgi function.

Directory of Open Access Journals (Sweden)

Leslie K Climer

2015-10-01

Full Text Available The Conserved Oligomeric Golgi (COG complex is an evolutionarily conserved hetero-octameric protein complex that has been proposed to organize vesicle tethering at the Golgi apparatus. Defects in seven of the eight COG subunits are linked to Congenital Disorders of Glycosylation (CDG-type II, a family of rare diseases involving misregulation of protein glycosylation, alterations in Golgi structure, variations in retrograde trafficking through the Golgi and system-wide clinical pathologies. A troublesome aspect of these diseases are the neurological pathologies such as low IQ, microcephaly and cerebellar atrophy. The essential function of the COG complex is dependent upon interactions with other components of trafficking machinery, such as Rab-GTPases and SNAREs. COG-interacting Rabs and SNAREs have been implicated in neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease. Defects in Golgi maintenance disrupts trafficking and processing of essential proteins, frequently associated with and contributing to compromised neuron function and human disease. Despite the recent advances in molecular neuroscience, the subcellular bases for most neurodegenerative diseases are poorly understood. This article gives an overview of the potential contributions of the COG complex and its Rab and SNARE partners in the pathogenesis of different neurodegenerative disorders.

Transport of soluble proteins through the Golgi occurs by diffusion via continuities across cisternae

Science.gov (United States)

Beznoussenko, Galina V; Parashuraman, Seetharaman; Rizzo, Riccardo; Polishchuk, Roman; Martella, Oliviano; Di Giandomenico, Daniele; Fusella, Aurora; Spaar, Alexander; Sallese, Michele; Capestrano, Maria Grazia; Pavelka, Margit; Vos, Matthijn R; Rikers, Yuri GM; Helms, Volkhard; Mironov, Alexandre A; Luini, Alberto

2014-01-01

The mechanism of transport through the Golgi complex is not completely understood, insofar as no single transport mechanism appears to account for all of the observations. Here, we compare the transport of soluble secretory proteins (albumin and α1-antitrypsin) with that of supramolecular cargoes (e.g., procollagen) that are proposed to traverse the Golgi by compartment progression–maturation. We show that these soluble proteins traverse the Golgi much faster than procollagen while moving through the same stack. Moreover, we present kinetic and morphological observations that indicate that albumin transport occurs by diffusion via intercisternal continuities. These data provide evidence for a transport mechanism that applies to a major class of secretory proteins and indicate the co-existence of multiple intra-Golgi trafficking modes. DOI: http://dx.doi.org/10.7554/eLife.02009.001 PMID:24867214

Proteomic identification of S-nitrosylated Golgi proteins: new insights into endothelial cell regulation by eNOS-derived NO.

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Panjamaporn Sangwung

Full Text Available Endothelial nitric oxide synthase (eNOS is primarily localized on the Golgi apparatus and plasma membrane caveolae in endothelial cells. Previously, we demonstrated that protein S-nitrosylation occurs preferentially where eNOS is localized. Thus, in endothelial cells, Golgi proteins are likely to be targets for S-nitrosylation. The aim of this study was to identify S-nitrosylated Golgi proteins and attribute their S-nitrosylation to eNOS-derived nitric oxide in endothelial cells.Golgi membranes were isolated from rat livers. S-nitrosylated Golgi proteins were determined by a modified biotin-switch assay coupled with mass spectrometry that allows the identification of the S-nitrosylated cysteine residue. The biotin switch assay followed by Western blot or immunoprecipitation using an S-nitrosocysteine antibody was also employed to validate S-nitrosylated proteins in endothelial cell lysates.Seventy-eight potential S-nitrosylated proteins and their target cysteine residues for S-nitrosylation were identified; 9 of them were Golgi-resident or Golgi/endoplasmic reticulum (ER-associated proteins. Among these 9 proteins, S-nitrosylation of EMMPRIN and Golgi phosphoprotein 3 (GOLPH3 was verified in endothelial cells. Furthermore, S-nitrosylation of these proteins was found at the basal levels and increased in response to eNOS stimulation by the calcium ionophore A23187. Immunofluorescence microscopy and immunoprecipitation showed that EMMPRIN and GOLPH3 are co-localized with eNOS at the Golgi apparatus in endothelial cells. S-nitrosylation of EMMPRIN was notably increased in the aorta of cirrhotic rats.Our data suggest that the selective S-nitrosylation of EMMPRIN and GOLPH3 at the Golgi apparatus in endothelial cells results from the physical proximity to eNOS-derived nitric oxide.

EXPERIMENTAL INVESTIGATION OF THE ORTHO/PARA RATIO OF NEWLY FORMED MOLECULAR HYDROGEN ON AMORPHOUS SOLID WATER

Energy Technology Data Exchange (ETDEWEB)

Gavilan, L.; Lemaire, J. L.; Dulieu, F.; Congiu, E.; Chaabouni, H. [LERMA, UMR 8112 du CNRS, de l' Observatoire de Paris et de l' Universite de Cergy Pontoise, 5 mail Gay Lussac, F-95000 Cergy Pontoise Cedex (France); Vidali, G. [Visiting Professor. Permanent address: Physics Department, Syracuse University, Syracuse, NY 13244-1320 (United States); Chehrouri, M. [Permanent address: LEPC Universite de Saida, BP138, ENSAR, 20002 Saida (Algeria); Fillion, J.-H., E-mail: lisseth.gavilan@obspm.fr [Permanent address: LPMAA, UMR 7092, Universite Pierre et Marie Curie, F-75252 Paris Cedex 05 (France)

2012-11-20

Several astronomical observations have shown that the ortho/para ratio (OPR) of H{sub 2} can differ from the expected statistical value of 3 or the local thermodynamic equilibrium (LTE) value at the gas or dust temperature. It is thus important to know the OPR of H{sub 2} newly formed on dust grain surfaces, in order to clarify the dependence of the observed OPR in space on the formation process. Using an experimental setup designed to mimic interstellar medium environments, we measured the OPR of H{sub 2} and D{sub 2} formed on the surface of porous amorphous water ice held at 10 K. We report for the first time the OPR value for newly formed D{sub 2}, consistent with the expected LTE value at the high-temperature limit found by previous theoretical and experimental works on the determination of the OPR upon H{sub 2} formation on surfaces at low temperature.

PERMANGANATE FIXATION OF THE GOLGI COMPLEX AND OTHER CYTOPLASMIC STRUCTURES OF MAMMALIAN TESTES

Science.gov (United States)

Mollenhauer, Hilton H.; Zebrun, William

1960-01-01

Observations on the fine structure of KMnO4-fixed testes of small mammals (guinea pig, rat, and mouse) reveal certain morphological differences between the spermatogenic and Sertoli cells which have not been demonstrated in the same tissue fixed with OsO4. Aggregates of minute circular profiles, much smaller than the spherical Golgi vesicles, are described in close association with the Golgi complex of developing spermatids. Groups of dense flattened vesicles, individually surrounded by a membrane of different dimensions than that which bounds most of the other cell organelles, appear dispersed within the cytoplasm of some spermatogenic cells. Flattened vesicles of greater density than those belonging to the Golgi complex are reported confined to the inner Golgi zone of developing guinea pig spermatids between the Golgi cisternae and the head cap. The profiles of endoplasmic reticulum within spermatocytes appear shorter, wider, and more tortuous than those of Sertoli cells. Minute cytoplasmic particles approximately 300 A in diameter and of high electron opacity appear randomly disposed in some Sertoli cells. Groups of irregular-shaped ovoid bodies within the developing spermatids are described as resembling portions of cytoplasm from closely adjacent spermatids. Interpretation is presented regarding the fine structure of KMnO4-fixed testes in view of what has already been reported for mammalian testes fixed in OsO4. PMID:13771855

Oxysterol-binding Protein Activation at Endoplasmic Reticulum-Golgi Contact Sites Reorganizes Phosphatidylinositol 4-Phosphate Pools*

OpenAIRE

Goto, Asako; Charman, Mark; Ridgway, Neale D.

2015-01-01

Oxysterol-binding protein (OSBP) exchanges cholesterol and phosphatidylinositol 4-phosphate (PI-4P) at contact sites between the endoplasmic reticulum (ER) and the trans-Golgi/trans-Golgi network. 25-Hydroxycholesterol (25OH) competitively inhibits this exchange reaction in vitro and causes the constitutive localization of OSBP at the ER/Golgi interface and PI-4P-dependent recruitment of ceramide transfer protein (CERT) for sphingomyelin synthesis. We used PI-4P probes and mass analysis to de...

Vibration sensitivity of human muscle spindles and Golgi tendon organs.

Science.gov (United States)

Fallon, James B; Macefield, Vaughan G

2007-07-01

The responses of the various muscle receptors to vibration are more complicated than a naïve categorization into stretch (muscle spindle primary ending), length (muscle spindle secondary endings), and tension (Golgi tendon organs) receptors. To emphasize the similarity of responses to small length changes, we recorded from 58 individual muscle afferents subserving receptors in the ankle or toe dorsiflexors of awake human subjects (32 primary endings, 20 secondary endings, and six Golgi tendon organs). Transverse sinusoidal vibration was applied to the distal tendon of the receptor-bearing muscle, while subjects either remained completely relaxed or maintained a weak isometric contraction of the appropriate muscle. In relaxed muscle, few units responded in a 1:1 manner to vibration, and there was no evidence of a preferred frequency of activation. In active muscle the response profiles of all three receptor types overlapped, with no significant difference in threshold between receptor types. These results emphasize that when intramuscular tension increases during a voluntary contraction, Golgi tendon organs and muscle spindle secondary endings, not just muscle spindle primary endings, can effectively encode small imposed length changes.

La técnica de impregnación argéntica de Golgi. Conmemoración del centenario del premio nobel de Medicina (1906 compartido por Camillo Golgi y Santiago Ramón y Cajal

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Orlando Torres-Fernández

2006-12-01

Full Text Available La técnica de Golgi es un sencillo procedimiento histológico que revela la morfología neuronal completa en tres dimensiones. Este método se fundamenta en la formación de depósitos opacos intracelulares de cromato argéntico, producto de la reacción entre el bicromato de potasio y el nitrato de plata (reacción negra. Camillo Golgi, su descubridor, y Santiago Ramón y Cajal, su principal exponente, recibieron el premio nobel de Medicina y Fisiología en 1906 por su contribución al conocimiento de la estructura del sistema nervioso. Gran parte de sus logros se obtuvieron a través de la aplicación del método de impregnación argéntica. Sin embargo, Golgi y Cajal tenían interpretaciones diferentes sobre la estructura del tejido nervioso. Golgi era defensor de la teoría reticular, la cual proponía que el sistema nervioso estaba conformado por una red de células fusionadas a través de los axones a manera de un sincitio. Por el contrario, la doctrina neuronal, defendida por Cajal, sostenía que las neuronas eran células independientes. También se debe a Golgi y su reazione nera el descubrimiento del organelo celular conocido como ‘aparato de Golgi'. La microscopía electrónica confirmó los postulados de la doctrina neuronal, así como la existencia del complejo de Golgi, y contribuyó al resurgimiento de la técnica de impregnación argéntica. Aunque existen métodos modernos de tinción intracelular que revelan imágenes excelentes de la morfología neuronal, la técnica de Golgi se mantiene vigente por ser un método más práctico y menos costoso para el estudio de la morfología normal y patológica de las neuronas.

Foot-and-mouth disease virus-induced RNA polymerase is associated with Golgi apparatus.

OpenAIRE

Polatnick, J; Wool, S H

1985-01-01

Electrophoretic analysis of the Golgi apparatus isolated by differential centrifugation from radiolabeled cells infected with foot-and-mouth disease virus showed about 10 protein bands. The virus-induced RNA polymerase was identified by immunoprecipitation and electron microscope staining procedures. Pulse-chase experiments indicated that the polymerase passed through the Golgi apparatus in less than 1 h.

Stathmin 1/2-triggered microtubule loss mediates Golgi fragmentation in mutant SOD1 motor neurons

NARCIS (Netherlands)

Bellouze, Sarah; Baillat, Gilbert; Buttigieg, Dorothée; de la Grange, Pierre; Rabouille, Catherine; Haase, Georg

2016-01-01

BACKGROUND: Pathological Golgi fragmentation represents a constant pre-clinical feature of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) but its molecular mechanisms remain hitherto unclear. RESULTS: Here, we show that the severe Golgi fragmentation in transgenic

Inducible Inhibition of Gβγ Reveals Localization-dependent Functions at the Plasma Membrane and Golgi*

Science.gov (United States)

Klayman, Lauren M.; Wedegaertner, Philip B.

2017-01-01

Heterotrimeric G proteins signal at a variety of endomembrane locations, in addition to their canonical function at the cytoplasmic surface of the plasma membrane (PM), where they are activated by cell surface G protein-coupled receptors. Here we focus on βγ signaling at the Golgi, where βγ activates a signaling cascade, ultimately resulting in vesicle fission from the trans-Golgi network (TGN). To develop a novel molecular tool for inhibiting endogenous βγ in a spatial-temporal manner, we take advantage of a lipid association mutant of the widely used βγ inhibitor GRK2ct (GRK2ct-KERE) and the FRB/FKBP heterodimerization system. We show that GRK2ct-KERE cannot inhibit βγ function when expressed in cells, but recruitment to a specific membrane location recovers the ability of GRK2ct-KERE to inhibit βγ signaling. PM-recruited GRK2ct-KERE inhibits lysophosphatidic acid-induced phosphorylation of Akt, whereas Golgi-recruited GRK2ct-KERE inhibits cargo transport from the TGN to the PM. Moreover, we show that Golgi-recruited GRK2ct-KERE inhibits model basolaterally targeted but not apically targeted cargo delivery, for both PM-destined and secretory cargo, providing the first evidence of selectivity in terms of cargo transport regulated by βγ. Last, we show that Golgi fragmentation induced by ilimaquinone and nocodazole is blocked by βγ inhibition, demonstrating that βγ is a key regulator of multiple pathways that impact Golgi morphology. Thus, we have developed a new molecular tool, recruitable GRK2ct-KERE, to modulate βγ signaling at specific subcellular locations, and we demonstrate novel cargo selectivity for βγ regulation of TGN to PM transport and a novel role for βγ in mediating Golgi fragmentation. PMID:27994056

Inducible Inhibition of Gβγ Reveals Localization-dependent Functions at the Plasma Membrane and Golgi.

Science.gov (United States)

Klayman, Lauren M; Wedegaertner, Philip B

2017-02-03

Heterotrimeric G proteins signal at a variety of endomembrane locations, in addition to their canonical function at the cytoplasmic surface of the plasma membrane (PM), where they are activated by cell surface G protein-coupled receptors. Here we focus on βγ signaling at the Golgi, where βγ activates a signaling cascade, ultimately resulting in vesicle fission from the trans-Golgi network (TGN). To develop a novel molecular tool for inhibiting endogenous βγ in a spatial-temporal manner, we take advantage of a lipid association mutant of the widely used βγ inhibitor GRK2ct (GRK2ct-KERE) and the FRB/FKBP heterodimerization system. We show that GRK2ct-KERE cannot inhibit βγ function when expressed in cells, but recruitment to a specific membrane location recovers the ability of GRK2ct-KERE to inhibit βγ signaling. PM-recruited GRK2ct-KERE inhibits lysophosphatidic acid-induced phosphorylation of Akt, whereas Golgi-recruited GRK2ct-KERE inhibits cargo transport from the TGN to the PM. Moreover, we show that Golgi-recruited GRK2ct-KERE inhibits model basolaterally targeted but not apically targeted cargo delivery, for both PM-destined and secretory cargo, providing the first evidence of selectivity in terms of cargo transport regulated by βγ. Last, we show that Golgi fragmentation induced by ilimaquinone and nocodazole is blocked by βγ inhibition, demonstrating that βγ is a key regulator of multiple pathways that impact Golgi morphology. Thus, we have developed a new molecular tool, recruitable GRK2ct-KERE, to modulate βγ signaling at specific subcellular locations, and we demonstrate novel cargo selectivity for βγ regulation of TGN to PM transport and a novel role for βγ in mediating Golgi fragmentation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Endoplasmic reticulum-to-Golgi transitions upon herpes virus infection [version 2; referees: 1 approved, 3 approved with reservations

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Peter Wild

2018-02-01

Full Text Available Background: Herpesvirus capsids are assembled in the nucleus, translocated to the perinuclear space by budding, acquiring tegument and envelope, or released to the cytoplasm via impaired nuclear envelope. One model proposes that envelopment, “de-envelopment” and “re-envelopment” is essential for production of infectious virus. Glycoproteins gB/gH were reported to be essential for de-envelopment, by fusion of the “primary” envelope with the outer nuclear membrane. Yet, a high proportion of enveloped virions generated from genomes with deleted gB/gH were found in the cytoplasm and extracellular space, suggesting the existence of alternative exit routes. Methods: We investigated the relatedness between the nuclear envelope and membranes of the endoplasmic reticulum and Golgi complex, in cells infected with either herpes simplex virus 1 (HSV-1 or a Us3 deletion mutant thereof, or with bovine herpesvirus 1 (BoHV-1 by transmission and scanning electron microscopy, employing freezing technique protocols. Results:  The Golgi complex is a compact entity in a juxtanuclear position covered by a membrane on the cis face. Golgi membranes merge with membranes of the endoplasmic reticulum forming an entity with the perinuclear space. All compartments contained enveloped virions. After treatment with brefeldin A, HSV-1 virions aggregated in the perinuclear space and endoplasmic reticulum, while infectious progeny virus was still produced. Conclusions: The data suggest that virions derived by budding at nuclear membranes are intraluminally transported from the perinuclear space via Golgi -endoplasmic reticulum transitions into Golgi cisternae for packaging. Virions derived by budding at nuclear membranes are infective like Us3 deletion mutants, which  accumulate in the perinuclear space. Therefore, i de-envelopment followed by re-envelopment is not essential for production of infective progeny virus, ii the process taking place at the outer nuclear

The Arabidopsis Golgi-localized GDP-L-fucose transporter is required for plant development

DEFF Research Database (Denmark)

Rautengarten, Carsten; Ebert, Berit; Liu, Lifeng

2016-01-01

assays, we show that GFT preferentially transports GDP-L-fucose over other nucleotide sugars in vitro, while GFT1-silenced plants are almost devoid of L-fucose in cell wall-derived xyloglucan and rhamnogalacturonan II. Furthermore, these lines display reduced L-fucose content in N-glycan structures......Nucleotide sugar transport across Golgi membranes is essential for the luminal biosynthesis of glycan structures. Here we identify GDP-fucose transporter 1 (GFT1), an Arabidopsis nucleotide sugar transporter that translocates GDP-L-fucose into the Golgi lumen. Using proteo-liposome-based transport...... accompanied by severe developmental growth defects. We conclude that GFT1 is the major nucleotide sugar transporter for import of GDP-L-fucose into the Golgi and is required for proper plant growth and development....

The Arabidopsis Golgi-localized GDP-L-fucose transporter is required for plant development.

Science.gov (United States)

Rautengarten, Carsten; Ebert, Berit; Liu, Lifeng; Stonebloom, Solomon; Smith-Moritz, Andreia M; Pauly, Markus; Orellana, Ariel; Scheller, Henrik Vibe; Heazlewood, Joshua L

2016-07-06

Nucleotide sugar transport across Golgi membranes is essential for the luminal biosynthesis of glycan structures. Here we identify GDP-fucose transporter 1 (GFT1), an Arabidopsis nucleotide sugar transporter that translocates GDP-L-fucose into the Golgi lumen. Using proteo-liposome-based transport assays, we show that GFT preferentially transports GDP-L-fucose over other nucleotide sugars in vitro, while GFT1-silenced plants are almost devoid of L-fucose in cell wall-derived xyloglucan and rhamnogalacturonan II. Furthermore, these lines display reduced L-fucose content in N-glycan structures accompanied by severe developmental growth defects. We conclude that GFT1 is the major nucleotide sugar transporter for import of GDP-L-fucose into the Golgi and is required for proper plant growth and development.

A novel, modernized Golgi-Cox stain optimized for CLARITY cleared tissue.

Science.gov (United States)

Kassem, Mustafa S; Fok, Sandra Y Y; Smith, Kristie L; Kuligowski, Michael; Balleine, Bernard W

2018-01-15

High resolution neuronal information is extraordinarily useful in understanding the brain's functionality. The development of the Golgi-Cox stain allowed observation of the neuron in its entirety with unrivalled detail. Tissue clearing techniques, e.g., CLARITY and CUBIC, provide the potential to observe entire neuronal circuits intact within tissue and without previous restrictions with regard to section thickness. Here we describe an improved Golgi-Cox stain method, optimised for use with CLARITY and CUBIC that can be used in both fresh and fixed tissue. Using this method, we were able to observe neurons in their entirety within a fraction of the time traditionally taken to clear tissue (48h). We were also able to show for the first-time that Golgi stained tissue is fluorescent when visualized using a multi-photon microscope, allowing us to image synaptic spines with a detail previously unachievable. These novel methods provide cheap and easy to use techniques to investigate the morphology of cellular processes in the brain at a new-found depth, speed, utility and detail, without previous restrictions of time, tissue type and section thickness. This is the first application of a Golgi-Cox stain to cleared brain tissue, it is investigated and discussed in detail, describing different methodologies that may be used, a comparison between the different clearing techniques and lastly the novel interaction of these techniques with this ultra-rapid stain. Copyright © 2017 Elsevier B.V. All rights reserved.

Trafficking of human ADAM 12-L: retention in the trans-Golgi network

DEFF Research Database (Denmark)

Hougaard, S; Loechel, F; Xu, X

2000-01-01

We have investigated the trafficking of the membrane-anchored form of human ADAM 12 (ADAM 12-L) fused to a green fluorescence protein tag. Subcellular localization of the protein in transiently transfected cells was determined by fluorescence microscopy and trypsin sensitivity. Full-length ADAM 12...... the cytoplasmic and transmembrane domains, but not the Src homology 3 domain (SH3) binding sites. These results raise the possibility that a trafficking checkpoint in the trans-Golgi network is one of the cellular mechanisms for regulation of ADAM 12-L function, by allowing a rapid release of ADAM 12-L...

The critical role of Golgi cells in regulating spatio-temporal integration and plasticity at the cerebellum input stage

Directory of Open Access Journals (Sweden)

2008-07-01

Full Text Available After the discovery at the end of the 19th century (Golgi, 1883, the Golgi cell was precisely described by S.R. y Cajal (see Cajal, 1987, 1995 and functionally identified as an inhibitory interneuron 50 years later by J.C. Eccles and colleagues (Eccles e al., 1967. Then, its role has been casted by Marr (1969 within the Motor Learning Theory as a codon size regulator of granule cell activity. It was immediately clear that Golgi cells had to play a critical role, since they are the main inhibitory interneuron of the granular layer and control activity of as many as 100 millions granule cells. In vitro, Golgi cells show pacemaking, resonance, phase-reset and rebound-excitation in the theta-frequency band. These properties are likely to impact on their activity in vivo, which shows irregular spontaneous beating modulated by sensory inputs and burst responses to punctuate stimulation followed by a silent pause. Moreover, investigations have given insight into Golgi cells connectivity within the cerebellar network and on their impact on the spatio-temporal organization of activity. It turns out that Golgi cells can control both the temporal dynamics and the spatial distribution of information transmitted through the cerebellar network. Moreover, Golgi cells regulate the induction of long-term synaptic plasticity at the mossy fiber - granule cell synapse. Thus, the concept is emerging that Golgi cells are of critical importance for regulating granular layer network activity bearing important consequences for cerebellar computation as a whole.

Localization of three human polypeptide GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation throughout the Golgi apparatus

DEFF Research Database (Denmark)

Röttger, S; White, J; Wandall, H H

1998-01-01

O-glycosylation of proteins is initiated by a family of UDP-N-acetylgalactosamine:polypeptide N-acetylgalactos-aminyltransferases (GalNAc-T). In this study, we have localized endogenous and epitope-tagged human GalNAc-T1, -T2 and -T3 to the Golgi apparatus in HeLa cells by subcellular fractionation......, immunofluorescence and immunoelectron microscopy. We show that all three GalNAc-transferases are concentrated about tenfold in Golgi stacks over Golgi associated tubular-vesicular membrane structures. Surprisingly, we find that GalNAc-T1, -T2 and -T3 are present throughout the Golgi stack suggesting that initiation...... of O-glycosylation may not be restricted to the cis Golgi, but occur at multiple sites within the Golgi apparatus. GalNAc-T1 distributes evenly across the Golgi stack whereas GalNAc-T2 and -T3 reside preferentially on the trans side and in the medial part of the Golgi stack, respectively. Moreover, we...

Post-Golgi anterograde transport requires GARP-dependent endosome-to-TGN retrograde transport

Science.gov (United States)

Hirata, Tetsuya; Fujita, Morihisa; Nakamura, Shota; Gotoh, Kazuyoshi; Motooka, Daisuke; Murakami, Yoshiko; Maeda, Yusuke; Kinoshita, Taroh

2015-01-01

The importance of endosome-to–trans-Golgi network (TGN) retrograde transport in the anterograde transport of proteins is unclear. In this study, genome-wide screening of the factors necessary for efficient anterograde protein transport in human haploid cells identified subunits of the Golgi-associated retrograde protein (GARP) complex, a tethering factor involved in endosome-to-TGN transport. Knockout (KO) of each of the four GARP subunits, VPS51–VPS54, in HEK293 cells caused severely defective anterograde transport of both glycosylphosphatidylinositol (GPI)-anchored and transmembrane proteins from the TGN. Overexpression of VAMP4, v-SNARE, in VPS54-KO cells partially restored not only endosome-to-TGN retrograde transport, but also anterograde transport of both GPI-anchored and transmembrane proteins. Further screening for genes whose overexpression normalized the VPS54-KO phenotype identified TMEM87A, encoding an uncharacterized Golgi-resident membrane protein. Overexpression of TMEM87A or its close homologue TMEM87B in VPS54-KO cells partially restored endosome-to-TGN retrograde transport and anterograde transport. Therefore GARP- and VAMP4-dependent endosome-to-TGN retrograde transport is required for recycling of molecules critical for efficient post-Golgi anterograde transport of cell-surface integral membrane proteins. In addition, TMEM87A and TMEM87B are involved in endosome-to-TGN retrograde transport. PMID:26157166

Acyl-CoA-binding protein (ACBP) localizes to the endoplasmic reticulum and Golgi in a ligand-dependent manner in mammalian cells

DEFF Research Database (Denmark)

Hansen, Jesper S; Færgeman, Nils J; Kragelund, Birthe B

2008-01-01

showed that ACBP targeted to the ER (endoplasmic reticulum) and Golgi in a ligand-binding-dependent manner. A variant Y28F/K32A-FACI-50, which is unable to bind acyl-CoA, did no longer show association with the ER and became segregated from the Golgi, as analysed by intensity correlation calculations....... Depletion of fatty acids from cells by addition of FAFBSA (fatty-acid-free BSA) significantly decreased FACI-50 association with the Golgi, whereas fatty acid overloading increased Golgi association, strongly supporting that ACBP associates with the Golgi in a ligand-dependent manner. FRAP (fluorescence...... recovery after photobleaching) showed that the fatty-acid-induced targeting of FACI-50 to the Golgi resulted in a 5-fold reduction in FACI-50 mobility. We suggest that ACBP is targeted to the ER and Golgi in a ligand-binding-dependent manner in living cells and propose that ACBP may be involved...

Direct interaction of the Golgi V-ATPase a-subunit isoform with PI(4)P drives localization of Golgi V-ATPases in yeast.

Science.gov (United States)

Banerjee, Subhrajit; Kane, Patricia M

2017-09-15

Luminal pH and phosphoinositide content are fundamental features of organelle identity. Vacuolar H + -ATPases (V-ATPases) drive organelle acidification in all eukaryotes, and membrane-bound a-subunit isoforms of the V-ATPase are implicated in organelle-specific targeting and regulation. Earlier work demonstrated that the endolysosomal lipid PI(3,5)P 2 activates V-ATPases containing the vacuolar a-subunit isoform in Saccharomyces cerevisiae Here we demonstrate that PI(4)P, the predominant Golgi phosphatidylinositol (PI) species, directly interacts with the cytosolic amino terminal (NT) domain of the yeast Golgi V-ATPase a-isoform Stv1. Lysine-84 of Stv1NT is essential for interaction with PI(4)P in vitro and in vivo, and interaction with PI(4)P is required for efficient localization of Stv1-containing V-ATPases. The cytosolic NT domain of the human V-ATPase a2 isoform specifically interacts with PI(4)P in vitro, consistent with its Golgi localization and function. We propose that NT domains of V o a-subunit isoforms interact specifically with PI lipids in their organelles of residence. These interactions can transmit organelle-specific targeting or regulation information to V-ATPases. © 2017 Banerjee and Kane. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Role of the Small GTPase Rho3 in Golgi/Endosome trafficking through functional interaction with adaptin in Fission Yeast.

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Ayako Kita

Full Text Available BACKGROUND: We had previously identified the mutant allele of apm1(+ that encodes a homolog of the mammalian µ1A subunit of the clathrin-associated adaptor protein-1 (AP-1 complex, and we demonstrated the role of Apm1 in Golgi/endosome trafficking, secretion, and vacuole fusion in fission yeast. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we isolated rho3(+, which encodes a Rho-family small GTPase, an important regulator of exocystosis, as a multicopy-suppressor of the temperature-sensitive growth of the apm1-1 mutant cells. Overexpression of Rho3 suppressed the Cl(- sensitivity and immunosuppressant sensitivity of the apm1-1 mutant cells. Overexpression of Rho3 also suppressed the fragmentation of vacuoles, and the accumulation of v-SNARE Syb1 in Golgi/endosomes and partially suppressed the defective secretion associated with apm1-deletion cells. Notably, electron microscopic observation of the rho3-deletion cells revealed the accumulation of abnormal Golgi-like structures, vacuole fragmentation, and accumulation of secretory vesicles; these phenotypes were very similar to those of the apm1-deletion cells. Furthermore, the rho3-deletion cells and apm1-deletion cells showed very similar phenotypic characteristics, including the sensitivity to the immunosuppressant FK506, the cell wall-damaging agent micafungin, Cl(-, and valproic acid. Green fluorescent protein (GFP-Rho3 was localized at Golgi/endosomes as well as the plasma membrane and division site. Finally, Rho3 was shown to form a complex with Apm1 as well as with other subunits of the clathrin-associated AP-1 complex in a GTP- and effector domain-dependent manner. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings reveal a novel role of Rho3 in the regulation of Golgi/endosome trafficking and suggest that clathrin-associated adaptor protein-1 and Rho3 co-ordinate in intracellular transport in fission yeast. To the best of our knowledge, this study provides the first evidence

Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans-Golgi

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Antonio Galindo

2016-07-01

Full Text Available The GTPase Arf1 is the major regulator of vesicle traffic at both the cis- and trans-Golgi. Arf1 is activated at the cis-Golgi by the guanine nucleotide exchange factor (GEF GBF1 and at the trans-Golgi by the related GEF BIG1 or its paralog, BIG2. The trans-Golgi-specific targeting of BIG1 and BIG2 depends on the Arf-like GTPase Arl1. We find that Arl1 binds to the dimerization and cyclophilin binding (DCB domain in BIG1 and report a crystal structure of human Arl1 bound to this domain. Residues in the DCB domain that bind Arl1 are required for BIG1 to locate to the Golgi in vivo. DCB domain-binding residues in Arl1 have a distinct conformation from those in known Arl1-effector complexes, and this plasticity allows Arl1 to interact with different effectors of unrelated structure. The findings provide structural insight into how Arf1 GEFs, and hence active Arf1, achieve their correct subcellular distribution.

Autometallographic (AMG) technique used for enhancement of the Golgi-Cox staining gives good contrast andhigh resolution of dendrites and spines

DEFF Research Database (Denmark)

Orlowski, Dariusz

Despite the existence of many newer staining methods, Golgi staining still remains the primary method forvisualization of the dendrites and spines. The black deposit in the Golgi-Cox impregnated cells is a Mercuricsulphide, therefore autometallographic (AMG) technique which is used for visualizat...... of dendrites and spines in the rat hippocampus. The describedmethod will be of value for future behavioural-anatomical studies, examining changes in dendrite branching andspine density caused by brain diseases and their subsequent treatment.......Despite the existence of many newer staining methods, Golgi staining still remains the primary method forvisualization of the dendrites and spines. The black deposit in the Golgi-Cox impregnated cells is a Mercuricsulphide, therefore autometallographic (AMG) technique which is used...... for visualization of the metals and metalsulphides/selenides in tissue may be used to enhance the Golgi-Cox staining. We demonstrated accordingly thatuse of AMG enhancement method on the Golgi-Cox staining gives good contrast and high resolution of dendritesand spines. Moreover, this method is cheaper and more...

The Prenylated Rab GTPase Receptor PRA1.F4 Contributes to Protein Exit from the Golgi Apparatus.

Science.gov (United States)

Lee, Myoung Hui; Yoo, Yun-Joo; Kim, Dae Heon; Hanh, Nguyen Hong; Kwon, Yun; Hwang, Inhwan

2017-07-01

Prenylated Rab acceptor1 (PRA1) functions in the recruitment of prenylated Rab proteins to their cognate organelles. Arabidopsis ( Arabidopsis thaliana ) contains a large number of proteins belonging to the AtPRA1 family. However, their physiological roles remain largely unknown. Here, we investigated the physiological role of AtPRA1.F4, a member of the AtPRA1 family. A T-DNA insertion knockdown mutant of AtPRA1.F4 , atpra1.f4 , was smaller in stature than parent plants and possessed shorter roots, whereas transgenic plants overexpressing HA:AtPRA1.F4 showed enhanced development of secondary roots and root hairs. However, both overexpression and knockdown plants exhibited increased sensitivity to high-salt stress, lower vacuolar Na + /K + -ATPase and plasma membrane ATPase activities, lower and higher pH in the vacuole and apoplast, respectively, and highly vesiculated Golgi apparatus. HA:AtPRA1.F4 localized to the Golgi apparatus and assembled into high-molecular-weight complexes. atpra1.f4 plants displayed a defect in vacuolar trafficking, which was complemented by low but not high levels of HA : AtPRA1.F4 Overexpression of HA:AtPRA1.F4 also inhibited protein trafficking at the Golgi apparatus, albeit differentially depending on the final destination or type of protein: trafficking of vacuolar proteins, plasma membrane proteins, and trans-Golgi network (TGN)-localized SYP61 was strongly inhibited; trafficking of TGN-localized SYP51 was slightly inhibited; and trafficking of secretory proteins and TGN-localized SYP41 was negligibly or not significantly inhibited. Based on these results, we propose that Golgi-localized AtPRA1.F4 is involved in the exit of many but not all types of post-Golgi proteins from the Golgi apparatus. Additionally, an appropriate level of AtPRA1.F4 is crucial for its function at the Golgi apparatus. © 2017 American Society of Plant Biologists. All Rights Reserved.

A model for the self-organization of vesicular flux and protein distributions in the Golgi apparatus.

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Iaroslav Ispolatov

Full Text Available The generation of two non-identical membrane compartments via exchange of vesicles is considered to require two types of vesicles specified by distinct cytosolic coats that selectively recruit cargo, and two membrane-bound SNARE pairs that specify fusion and differ in their affinities for each type of vesicles. The mammalian Golgi complex is composed of 6-8 non-identical cisternae that undergo gradual maturation and replacement yet features only two SNARE pairs. We present a model that explains how distinct composition of Golgi cisternae can be generated with two and even a single SNARE pair and one vesicle coat. A decay of active SNARE concentration in aging cisternae provides the seed for a cis[Formula: see text]trans SNARE gradient that generates the predominantly retrograde vesicle flux which further enhances the gradient. This flux in turn yields the observed inhomogeneous steady-state distribution of Golgi enzymes, which compete with each other and with the SNAREs for incorporation into transport vesicles. We show analytically that the steady state SNARE concentration decays exponentially with the cisterna number. Numerical solutions of rate equations reproduce the experimentally observed SNARE gradients, overlapping enzyme peaks in cis, medial and trans and the reported change in vesicle nature across the Golgi: Vesicles originating from younger cisternae mostly contain Golgi enzymes and SNAREs enriched in these cisternae and extensively recycle through the Endoplasmic Reticulum (ER, while the other subpopulation of vesicles contains Golgi proteins prevalent in older cisternae and hardly reaches the ER.

Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network

DEFF Research Database (Denmark)

Klemm, Robin W; Ejsing, Christer S.; Surma, Michal A

2009-01-01

The trans-Golgi network (TGN) is the major sorting station in the secretory pathway of all eukaryotic cells. How the TGN sorts proteins and lipids to generate the enrichment of sphingolipids and sterols at the plasma membrane is poorly understood. To address this fundamental question in membrane...... trafficking, we devised an immunoisolation procedure for specific recovery of post-Golgi secretory vesicles transporting a transmembrane raft protein from the TGN to the cell surface in the yeast Saccharomyces cerevisiae. Using a novel quantitative shotgun lipidomics approach, we could demonstrate that TGN...... than the late Golgi membrane, as measured by C-Laurdan spectrophotometry, strongly suggests that lipid rafts play a role in the TGN-sorting machinery....

OSCILLATION OF NEWLY FORMED LOOPS AFTER MAGNETIC RECONNECTION IN THE SOLAR CHROMOSPHERE

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Yang, Shuhong [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China); Xiang, Yongyuan, E-mail: shuhongyang@nao.cas.cn [Fuxian Solar Observatory, Yunnan Observatories, Chinese Academy of Sciences, Kunming 650011 (China)

2016-03-10

With the high spatial and temporal resolution Hα images from the New Vacuum Solar Telescope, we focus on two groups of loops with an X-shaped configuration in the dynamic chromosphere. We find that the anti-directed loops approach each other and reconnect continually. The connectivity of the loops is changed and new loops are formed and stack together. The stacked loops are sharply bent, implying that they are greatly impacted by the magnetic tension force. When another reconnection process takes place, one new loop is formed and stacks with the previously formed ones. Meanwhile, the stacked loops retract suddenly and move toward the balance position, performing an overshoot movement, which led to an oscillation with an average period of about 45 s. The oscillation of newly formed loops after magnetic reconnection in the chromosphere is observed for the first time. We suggest that the stability of the stacked loops is destroyed due to the attachment of the last new loop and then suddenly retract under the effect of magnetic tension. Because of the retraction, another lower loop is pushed outward and performs an oscillation with a period of about 25 s. The different oscillation periods may be due to their difference in three parameters, i.e., loop length, plasma density, and magnetic field strength.

Socket Preservation with d-PTFE Membrane: Histologic Analysis of the Newly Formed Matrix at Membrane Removal.

Science.gov (United States)

Laurito, Domenico; Cugnetto, Riccardo; Lollobrigida, Marco; Guerra, Fabrizio; Vestri, Annarita; Gianno, Francesca; Bosco, Sandro; Lamazza, Luca; De Biase, Alberto

This study aimed to evaluate the efficacy of an exposed high-density polytetrafluoroethylene (d-PTFE) membrane in preventing epithelial migration in postextraction sockets. For this purpose, a histologic description of the newly formed soft tissue underlying the membrane is presented. The periodontal status of the adjacent teeth was also evaluated to assess the gingival response. Ten premolar extraction sockets were treated. After tooth extraction, the sockets were filled with nanocrystalline hydroxyapatite and covered with d-PTFE membranes. Subperiosteal pockets were created to ensure the stability of the membranes. Membranes were left intentionally exposed and were atraumatically removed after 28 days. At that time, a bioptic specimen of the newly formed soft tissue under the membranes was taken. All the histologic samples showed a dense connective tissue without epithelial cells and no signs of foreign body reaction. No significant variation of the periodontal indices was observed on the teeth adjacent to the extraction sites. The study results indicate that exposed d-PTFE membranes can prevent epithelial migration in healing sockets without consequences on the periodontal health.

A rapid method combining Golgi and Nissl staining to study neuronal morphology and cytoarchitecture.

Science.gov (United States)

Pilati, Nadia; Barker, Matthew; Panteleimonitis, Sofoklis; Donga, Revers; Hamann, Martine

2008-06-01

The Golgi silver impregnation technique gives detailed information on neuronal morphology of the few neurons it labels, whereas the majority remain unstained. In contrast, the Nissl staining technique allows for consistent labeling of the whole neuronal population but gives very limited information on neuronal morphology. Most studies characterizing neuronal cell types in the context of their distribution within the tissue slice tend to use the Golgi silver impregnation technique for neuronal morphology followed by deimpregnation as a prerequisite for showing that neuron's histological location by subsequent Nissl staining. Here, we describe a rapid method combining Golgi silver impregnation with cresyl violet staining that provides a useful and simple approach to combining cellular morphology with cytoarchitecture without the need for deimpregnating the tissue. Our method allowed us to identify neurons of the facial nucleus and the supratrigeminal nucleus, as well as assessing cellular distribution within layers of the dorsal cochlear nucleus. With this method, we also have been able to directly compare morphological characteristics of neuronal somata at the dorsal cochlear nucleus when labeled with cresyl violet with those obtained with the Golgi method, and we found that cresyl violet-labeled cell bodies appear smaller at high cellular densities. Our observation suggests that cresyl violet staining is inadequate to quantify differences in soma sizes.

Golgi bypass: skirting around the heart of classical secretion

NARCIS (Netherlands)

Grieve, A.; Rabouille, C.

2011-01-01

Classical secretion consists of the delivery of transmembrane and soluble proteins to the plasma membrane and the extracellular medium, respectively, and is mediated by the organelles of the secretory pathway, the Endoplasmic Reticulum (ER), the ER exit sites, and the Golgi, as described by the

Voltage-Dependent Intrinsic Bursting in Olfactory Bulb Golgi Cells

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Pressler, R. Todd; Rozman, Peter A.; Strowbridge, Ben W.

2013-01-01

In the mammalian olfactory bulb (OB), local synaptic circuits modulate the evolving pattern of activity in mitral and tufted cells following olfactory sensory stimulation. GABAergic granule cells, the most numerous interneuron subtype in this brain region, have been extensively studied. However, classic studies using Golgi staining methods…

OSBP-related protein 11 (ORP11) dimerizes with ORP9 and localizes at the Golgi-late endosome interface

International Nuclear Information System (INIS)

Zhou, You; Li, Shiqian; Maeyraenpaeae, Mikko I.; Zhong, Wenbin; Baeck, Nils; Yan, Daoguang; Olkkonen, Vesa M.

2010-01-01

We characterize here ORP11, a member of the oxysterol-binding protein family. ORP11 is present at highest levels in human ovary, testis, kidney, liver, stomach, brain, and adipose tissue. Immunohistochemistry demonstrates abundant ORP11 in the epithelial cells of kidney tubules, testicular tubules, caecum, and skin. ORP11 in HEK293 cells resides on Golgi complex and LE, co-localizing with GFP-Rab9, TGN46, GFP-Rab7, and a fluorescent medial-trans-Golgi marker. Under electron microscopic observation, cells overexpressing ORP11 displayed lamellar lipid bodies associated with vacuolar structures or the Golgi complex, indicating a disturbance of lipid trafficking. N-terminal fragment of ORP11 (aa 1-292) localized partially to Golgi, but displayed enhanced localization on Rab7- and Rab9-positive LE, while the C-terminal ligand-binding domain (aa 273-747) was cytosolic, demonstrating that the membrane targeting determinants are N-terminal. Yeast two-hybrid screen revealed interaction of ORP11 with the related ORP9. The interacting region was delineated within aa 98-372 of ORP9 and aa 154-292 of ORP11. Overexpressed ORP9 was able to recruit EGFP-ORP11 to membranes, and ORP9 silencing inhibited ORP11 Golgi association. The results identify ORP11 as an OSBP homologue distributing at the Golgi-LE interface and define the ORP9-ORP11 dimer as a functional unit that may act as an intracellular lipid sensor or transporter.

OSBP-related protein 11 (ORP11) dimerizes with ORP9 and localizes at the Golgi-late endosome interface

Energy Technology Data Exchange (ETDEWEB)

Zhou, You [Minerva Foundation Institute for Medical Research, Biomedicum 2U, and National Institute for Health and Welfare/Public Health Genomics Unit, Biomedicum 1, FI-00290, Helsinki (Finland); Li, Shiqian [Department of Biology, Jinan University, Guangzhou 510632 (China); Maeyraenpaeae, Mikko I. [Wihuri Research Institute, FI-00140 Helsinki, and the Department of Forensic Medicine, FI-00014 University of Helsinki (Finland); Zhong, Wenbin [Department of Biology, Jinan University, Guangzhou 510632 (China); Baeck, Nils [Institute of Biomedicine/Anatomy, FI-00014 University of Helsinki, Helsinki (Finland); Yan, Daoguang [Department of Biology, Jinan University, Guangzhou 510632 (China); Olkkonen, Vesa M., E-mail: vesa.olkkonen@helsinki.fi [Minerva Foundation Institute for Medical Research, Biomedicum 2U, and National Institute for Health and Welfare/Public Health Genomics Unit, Biomedicum 1, FI-00290, Helsinki (Finland); Institute of Biomedicine/Anatomy, FI-00014 University of Helsinki, Helsinki (Finland)

2010-11-15

We characterize here ORP11, a member of the oxysterol-binding protein family. ORP11 is present at highest levels in human ovary, testis, kidney, liver, stomach, brain, and adipose tissue. Immunohistochemistry demonstrates abundant ORP11 in the epithelial cells of kidney tubules, testicular tubules, caecum, and skin. ORP11 in HEK293 cells resides on Golgi complex and LE, co-localizing with GFP-Rab9, TGN46, GFP-Rab7, and a fluorescent medial-trans-Golgi marker. Under electron microscopic observation, cells overexpressing ORP11 displayed lamellar lipid bodies associated with vacuolar structures or the Golgi complex, indicating a disturbance of lipid trafficking. N-terminal fragment of ORP11 (aa 1-292) localized partially to Golgi, but displayed enhanced localization on Rab7- and Rab9-positive LE, while the C-terminal ligand-binding domain (aa 273-747) was cytosolic, demonstrating that the membrane targeting determinants are N-terminal. Yeast two-hybrid screen revealed interaction of ORP11 with the related ORP9. The interacting region was delineated within aa 98-372 of ORP9 and aa 154-292 of ORP11. Overexpressed ORP9 was able to recruit EGFP-ORP11 to membranes, and ORP9 silencing inhibited ORP11 Golgi association. The results identify ORP11 as an OSBP homologue distributing at the Golgi-LE interface and define the ORP9-ORP11 dimer as a functional unit that may act as an intracellular lipid sensor or transporter.

Retrograde transport of protein toxins through the Golgi apparatus

DEFF Research Database (Denmark)

Sandvig, Kirsten; Skotland, Tore; van Deurs, Bo

2013-01-01

at the cell surface, and they are endocytosed both by clathrin-dependent and clathrin-independent mechanisms. Sorting to the Golgi and retrograde transport to the endoplasmic reticulum (ER) are common to these toxins, but the exact mechanisms turn out to be toxin and cell-type dependent. In the ER...

Cleavage of ST6Gal I by Radiation-Induced BACE1 Inhibits Golgi-Anchored ST6Gal I-Mediated Sialylation of Integrin β1 and Migration in Colon Cancer Cells

International Nuclear Information System (INIS)

Lee, Minyoung; Park, Jung-Jin; Ko, Young-Gyu; Lee, Yun-Sil

2012-01-01

Previously, we found that β-galactoside α2,6-sialyltransferase (ST6Gal I), an enzyme that adds sialic acids to N-linked oligosaccharides of glycoproteins and is frequently overexpressed in cancer cells, is up-regulated by ionizing radiation (IR) and cleaved to a form possessing catalytic activity comparable to that of the Golgi-localized enzyme. Moreover, this soluble form is secreted into the culture media. Induction of ST6Gal I significantly increased the migration of colon cancer cells via sialylation of integrin β1. Here, we further investigated the mechanisms underlying ST6Gal I cleavage, solubilization and release from cells, and addressed its functions, focusing primarily on cancer cell migration. We performed immunoblotting and lectin affinity assay to analyze the expression of ST6 Gal I and level of sialylated integrin β1. After ionizing radiation, migration of cells was measured by in vitro migration assay. α2, 6 sialylation level of cell surface was analyzed by flow cytometry. Cell culture media were concentrated and then analyzed for soluble ST6Gal I levels using an α2, 6 sialyltransferase sandwich ELISA. We found that ST6Gal I was cleaved by BACE1 (β-site amyloid precursor protein-cleaving enzyme), which was specifically overexpressed in response to IR. The soluble form of ST6Gal I, which also has sialyltransferase enzymatic activity, was cleaved from the Golgi membrane and then released into the culture media. Both non-cleaved and cleaved forms of ST6Gal I significantly increased colon cancer cell migration in a sialylation-dependent manner. The pro-migratory effect of the non-cleaved form of ST6Gal I was dependent on integrin β1 sialylation, whereas that of the cleaved form of ST6Gal I was not, suggesting that other intracellular sialylated molecules apart from cell surface molecules such as integrin β1 might be involved in mediating the pro-migratory effects of the soluble form of ST6Gal I. Moreover, production of soluble form ST6Gal I by

G-rich, a Drosophila selenoprotein, is a Golgi-resident type III membrane protein

International Nuclear Information System (INIS)

Chen, Chang Lan; Shim, Myoung Sup; Chung, Jiyeol; Yoo, Hyun-Seung; Ha, Ji Min; Kim, Jin Young; Choi, Jinmi; Zang, Shu Liang; Hou, Xiao; Carlson, Bradley A.; Hatfield, Dolph L.; Lee, Byeong Jae

2006-01-01

G-rich is a Drosophila melanogaster selenoprotein, which is a homologue of human and mouse SelK. Subcellular localization analysis using GFP-tagged G-rich showed that G-rich was localized in the Golgi apparatus. The fusion protein was co-localized with the Golgi marker proteins but not with an endoplasmic reticulum (ER) marker protein in Drosophila SL2 cells. Bioinformatic analysis of G-rich suggests that this protein is either type II or type III transmembrane protein. To determine the type of transmembrane protein experimentally, GFP-G-rich in which GFP was tagged at the N-terminus of G-rich, or G-rich-GFP in which GFP was tagged at the C-terminus of G-rich, were expressed in SL2 cells. The tagged proteins were then digested with trypsin, and analyzed by Western blot analysis. The results showed that the C-terminus of the G-rich protein was exposed to the cytoplasm indicating it is a type III microsomal membrane protein. G-rich is First selenoprotein identified in the Golgi apparatus

Pathological changes of Golgi complex in hemocytoblasts of spleen of young axolotls after x-irradiation

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Turska, R.

1975-01-01

The data available up to now concerning the structure of Golgi complex in different types of normal and pathologically changed cells are very divergent. Results are reported from detailed studies on changes occurring within the Golgi complex in the spleen of three-month old axolotls after x-ray irradiation with a single dose of 1,200 R and killed by decapitation 15, 30, 60 minutes and 3, 6, and 12 hours after irradiation.

Golgi apparatus-localized synaptotagmin 2 is required for unconventional secretion in Arabidopsis.

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Haiyan Zhang

Full Text Available BACKGROUND: Most secretory proteins contain signal peptides that direct their sorting to the ER and secreted via the conventional ER/Golgi transport pathway, while some signal-peptide-lacking proteins have been shown to export through ER/Golgi independent secretory pathways. Hygromycin B is an aminoglycoside antibiotic produced by Streptomyces hygroscopicus that is active against both prokaryotic and eukaryotic cells. The hygromycin phosphotransferase (HYG(R can phosphorylate and inactivate the hygromycin B, and has been widely used as a positive selective marker in the construction of transgenic plants. However, the localization and trafficking of HYG(R in plant cells remain unknown. Synaptotagmins (SYTs are involved in controlling vesicle endocytosis and exocytosis as calcium sensors in animal cells, while their functions in plant cells are largely unclear. METHODOLOGY/PRINCIPAL FINDINGS: We found Arabidopsis synaptotagmin SYT2 was localized on the Golgi apparatus by immunofluorescence and immunogold labeling. Surprisingly, co-expression of SYT2 and HYG(R caused hypersensitivity of the transgenic Arabidopsis plants to hygromycin B. HYG(R, which lacks a signal sequence, was present in the cytoplasm as well as in the extracellular space in HYG(R-GFP transgenic Arabidopsis plants and its secretion is not sensitive to brefeldin A treatment, suggesting it is not secreted via the conventional secretory pathway. Furthermore, we found that HYG(R-GFP was truncated at carboxyl terminus of HYG(R shortly after its synthesis, and the cells deficient SYT2 failed to efficiently truncate HYG(R-GFP,resulting in HYG(R-GFP accumulated in prevacuoles/vacuoles, indicating that SYT2 was involved in HYG(R-GFP trafficking and secretion. CONCLUSION/SIGNIFICANCE: These findings reveal for the first time that SYT2 is localized on the Golgi apparatus and regulates HYG(R-GFP secretion via the unconventional protein transport from the cytosol to the extracelluar matrix in

Golgi bypass for local delivery of axonal proteins, fact or fiction?

Science.gov (United States)

González, Carolina; Cornejo, Víctor Hugo; Couve, Andrés

2018-04-06

Although translation of cytosolic proteins is well described in axons, much less is known about the synthesis, processing and trafficking of transmembrane and secreted proteins. A canonical rough endoplasmic reticulum or a stacked Golgi apparatus has not been detected in axons, generating doubts about the functionality of a local route. However, axons contain mRNAs for membrane and secreted proteins, translation factors, ribosomal components, smooth endoplasmic reticulum and post-endoplasmic reticulum elements that may contribute to local biosynthesis and plasma membrane delivery. Here we consider the evidence supporting a local secretory system in axons. We discuss exocytic elements and examples of autonomous axonal trafficking that impact development and maintenance. We also examine whether unconventional post-endoplasmic reticulum pathways may replace the canonical Golgi apparatus. Copyright © 2018. Published by Elsevier Ltd.

Secretory granule formation and membrane recycling by the trans-Golgi network in adipokinetic cells of Locusta migratoria in relation to flight and rest.

Science.gov (United States)

Diederen, J H; Vullings, H G

1995-03-01

The influence of flight activity on the formation of secretory granules and the concomitant membrane recycling by the trans-Golgi network in the peptidergic neurosecretory adipokinetic cells of Locusta migratoria was investigated by means of ultrastructural morphometric methods. The patterns of labelling of the trans-Golgi network by the exogenous adsorptive endocytotic tracer wheat-germ agglutinin-conjugated horse-radish peroxidase and by the endogenous marker enzyme acid phosphatase were used as parameters and were measured by an automatic image analysis system. The results show that endocytosed fragments of plasma membrane with bound peroxidase label were transported to the trans-Golgi network and used to build new secretory granules. The amounts of peroxidase and especially of acid phosphatase within the trans-Golgi network showed a strong tendency to be smaller in flight-stimulated cells than in non-stimulated cells. The amounts of acid phosphatase in the immature secretory granules originating from the trans-Golgi network were significantly smaller in stimulated cells. The number of immature secretory granules positive for acid phosphatase tended to be higher in stimulated cells. Thus, flight stimulation of adipokinetic cells for 1 h influences the functioning of the trans-Golgi network; this most probably results in a slight enhancement of the production of secretory granules by the trans-Golgi network.

Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication.

Directory of Open Access Journals (Sweden)

Anahí Capmany

2010-11-01

Full Text Available Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation.

Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication.

Science.gov (United States)

Capmany, Anahí; Damiani, María Teresa

2010-11-22

Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation.

Relationship between the isotopic composition of strontium in newly formed continental clay minerals and their source material

International Nuclear Information System (INIS)

Clauer, N.

1979-01-01

The 87 Sr/ 86 Sr ratios of recent montmorillonites and kaolinites newly formed in weathering profiles of western and central Africa and of Nosy Be and La Reunion islands near Madagascar are directly related to the composition and age of the parent rocks or minerals. They may, therefore, be used as a genetic tracer. The 87 Sr/ 86 Sr ratios are about 0.704 when these clays crystallise from recent basalts and they are higher than 0.715 when the parent rocks are of sialic composition and old in age. Kaolinites newly formed in situ from feldspars contain small amounts of Sr with abnormally high 87 Sr/ 86 Sr ratios: in this study they are higher than 1.094. When these minerals crystallize from biotites, their 87 Sr/ 86 Sr ratios are much lower and can be close to the value of the primary Sr trapped in the biotites during their crystallization. On the other hand, the 87 Sr/ 86 Sr of continental montmorillonites are less scattered: they range, in this study, between 0.704 and 0.722. These low values, as well as the high adsorption capacities of these minerals in the sedimentary environment, allow the assumption that they frequently have 87 Sr/ 86 Sr ratios close to that of marine Sr during sedimentation. Therefore, montmorillonites are able to form homogeneous authigenic minerals by synsedimentary alterations. (Auth.)

Membrane topology of Golgi-localized probable S-adenosylmethionine-dependent methyltransferase in tobacco (Nicotiana tabacum) BY-2 cells.

Science.gov (United States)

Liu, Jianping; Hayashi, Kyoko; Matsuoka, Ken

2015-01-01

S-adenosylmethionine (SAM)-dependent methyltransferases (MTases) transfer methyl groups to substrates. In this study, a novel putative tobacco SAM-MTase termed Golgi-localized methyl transferase 1 (GLMT1) has been characterized. GLMT1 is comprised of 611 amino acids with short N-terminal region, putative transmembrane region, and C-terminal SAM-MTase domain. Expression of monomeric red fluorescence protein (mRFP)-tagged protein in tobacco BY-2 cell indicated that GLMT1 is a Golgi-localized protein. Analysis of the membrane topology by protease digestion suggested that both C-terminal catalytic region and N-terminal region seem to be located to the cytosolic side of the Golgi apparatus. Therefore, GLMT1 might have a different function than the previously studied SAM-MTases in plants.

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

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

2013-09-01

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

Adiponectin release and insulin receptor targeting share trans-Golgi-dependent endosomal trafficking routes

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Maria Rödiger

2018-02-01

Full Text Available Objective: Intracellular vesicle trafficking maintains cellular structures and functions. The assembly of cargo-laden vesicles at the trans-Golgi network is initiated by the ARF family of small GTPases. Here, we demonstrate the role of the trans-Golgi localized monomeric GTPase ARFRP1 in endosomal-mediated vesicle trafficking of mature adipocytes. Methods: Control (Arfrp1flox/flox and inducible fat-specific Arfrp1 knockout (Arfrp1iAT−/− mice were metabolically characterized. In vitro experiments on mature 3T3-L1 cells and primary mouse adipocytes were conducted to validate the impact of ARFRP1 on localization of adiponectin and the insulin receptor. Finally, secretion and transferrin-based uptake and recycling assays were performed with HeLa and HeLa M-C1 cells. Results: We identified the ARFRP1-based sorting machinery to be involved in vesicle trafficking relying on the endosomal compartment for cell surface delivery. Secretion of adiponectin from fat depots was selectively reduced in Arfrp1iAT−/− mice, and Arfrp1-depleted 3T3-L1 adipocytes revealed an accumulation of adiponectin in Rab11-positive endosomes. Plasma adiponectin deficiency of Arfrp1iAT−/− mice resulted in deteriorated hepatic insulin sensitivity, increased gluconeogenesis and elevated fasting blood glucose levels. Additionally, the insulin receptor, undergoing endocytic recycling after ligand binding, was less abundant at the plasma membrane of adipocytes lacking Arfrp1. This had detrimental effects on adipose insulin signaling, followed by insufficient suppression of basal lipolytic activity and impaired adipose tissue expansion. Conclusions: Our findings suggest that adiponectin secretion and insulin receptor surface targeting utilize the same post-Golgi trafficking pathways that are essential for an appropriate systemic insulin sensitivity and glucose homeostasis. Keywords: Adiponectin, ARFRP1, Exocytosis, Insulin receptor, trans-Golgi

Transport According to GARP: Receiving Retrograde Cargo at the Trans-Golgi Network

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Bonifacino, Juan S.; Hierro, Aitor

2010-01-01

Tethering factors are large protein complexes that capture transport vesicles and enable their fusion with acceptor organelles at different stages of the endomembrane system. Recent studies have shed new light on the structure and function of a heterotetrameric tethering factor named Golgi-associated retrograde protein (GARP), which promotes fusion of endosome-derived, retrograde transport carriers to the trans-Golgi network (TGN). X-ray crystallography of the Vps53 and Vps54 subunits of GARP has revealed that this complex is structurally related to other tethering factors such as the exocyst, COG and Dsl1, indicating that they all might work by a similar mechanism. Loss of GARP function compromises the growth, fertility and/or viability of the defective organisms, underscoring the essential nature of GARP-mediated retrograde transport. PMID:21183348

Live-cell imaging of post-golgi transport vesicles in cultured hippocampal neurons

DEFF Research Database (Denmark)

Jensen, Camilla Stampe; Misonou, Hiroaki

2015-01-01

compartments of neurons. In the past two decades, the establishment and advancement of fluorescent protein technology have provided us with opportunities to study how proteins are trafficked in living cells. However, live imaging of trafficking processes in neurons necessitate imaging tools to distinguish...... the several different routes that neurons use for protein trafficking. Here we provide a novel protocol to selectively visualize post-Golgi transport vesicles carrying fluorescent-labeled ion channel proteins in living neurons. Further, we provide a number of analytical tools we developed to quantify...... mechanisms by which post-Golgi vesicles are trafficked in neurons. Our protocol uniquely combines the classic temperature-block with close monitoring of the transient expression of transfected protein tagged with fluorescent proteins, and provides a quick and easy way to study protein trafficking in living...

Multidimensional fractionation is a requirement for quantitation of Golgi-resident glycosylation enzymes from cultured human cells.

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Lin, Chi-Hung; Chik, Jenny H L; Packer, Nicolle H; Molloy, Mark P

2015-02-06

Glycosylation results from the concerted action of glycosylation enzymes in the secretory pathway. In general, gene expression serves as the primary control mechanism, but post-translational fine-tuning of glycosylation enzyme functions is often necessary for efficient synthesis of specific glycan epitopes. While the field of glycomics has rapidly advanced, there lacks routine proteomic methods to measure expression of specific glycosylation enzymes needed to fill the gap between mRNA expression and the glycomic profile in a "reverse genomics" workflow. Toward developing this workflow we enriched Golgi membranes from two human colon cancer cell lines by sucrose density centrifugation and further mass-based fractionation by SDS-PAGE. We then applied mass spectrometry to demonstrate a doubling in the number of Golgi resident proteins identified, compared to the unenriched, low speed centrifuged supernatant of lysed cells. A total of 35 Golgi-resident glycosylation enzymes, of which 23 were glycosyltransferases, were identified making this the largest protein database so far of Golgi resident glycosylation enzymes experimentally identified in cultured human cells. We developed targeted mass spectrometry assays for specific quantitation of many of these glycosylation enzymes. Our results show that alterations in abundance of glycosylation enzymes at the protein level were generally consistent with the resultant glycomic profiles, but not necessarily with the corresponding glycosyltransferase mRNA expression as exemplified by the case of O-glycan core 1 T synthase.

Monocrotaline pyrrole-induced megalocytosis of lung and breast epithelial cells: Disruption of plasma membrane and Golgi dynamics and an enhanced unfolded protein response

International Nuclear Information System (INIS)

Mukhopadhyay, Somshuvra; Shah, Mehul; Patel, Kirit; Sehgal, Pravin B.

2006-01-01

The pyrrolizidine alkaloid monocrotaline (MCT) initiates pulmonary hypertension by inducing a 'megalocytosis' phenotype in target pulmonary arterial endothelial, smooth muscle and Type II alveolar epithelial cells. In cultured endothelial cells, a single exposure to the pyrrolic derivative of monocrotaline (MCTP) results in large cells with enlarged endoplasmic reticulum (ER) and Golgi and increased vacuoles. However, these cells fail to enter mitosis. Largely based upon data from endothelial cells, we proposed earlier that a disruption of the trafficking and mitosis-sensor functions of the Golgi (the 'Golgi blockade' hypothesis) may represent the subcellular mechanism leading to MCTP-induced megalocytosis. In the present study, we investigated the applicability of the Golgi blockade hypothesis to epithelial cells. MCTP induced marked megalocytosis in cultures of lung A549 and breast MCF-7 cells. This was associated with a change in the distribution of the cis-Golgi scaffolding protein GM130 from a discrete juxtanuclear localization to a circumnuclear distribution consistent with an anterograde block of GM130 trafficking to/through the Golgi. There was also a loss of plasma membrane caveolin-1 and E-cadherin, cortical actin together with a circumnuclear accumulation of clathrin heavy chain (CHC) and α-tubulin. Flotation analyses revealed losses/alterations in the association of caveolin-1, E-cadherin and CHC with raft microdomains. Moreover, megalocytosis was accompanied by an enhanced unfolded protein response (UPR) as evidenced by nuclear translocation of Ire1α and glucose regulated protein 58 (GRP58/ER-60/ERp57) and a circumnuclear accumulation of PERK kinase and protein disulfide isomerase (PDI). These data further support the hypothesis that an MCTP-induced Golgi blockade and enhanced UPR may represent the subcellular mechanism leading to enlargement of ER and Golgi and subsequent megalocytosis

Live-cell imaging of dual-labeled Golgi stacks in tobacco BY-2 cells reveals similar behaviors for different cisternae during movement and brefeldin A treatment.

Science.gov (United States)

Madison, Stephanie L; Nebenführ, Andreas

2011-09-01

In plant cells, the Golgi apparatus consists of numerous stacks that, in turn, are composed of several flattened cisternae with a clear cis-to-trans polarity. During normal functioning within living cells, this unusual organelle displays a wide range of dynamic behaviors such as whole stack motility, constant membrane flux through the cisternae, and Golgi enzyme recycling through the ER. In order to further investigate various aspects of Golgi stack dynamics and integrity, we co-expressed pairs of established Golgi markers in tobacco BY-2 cells to distinguish sub-compartments of the Golgi during monensin treatments, movement, and brefeldin A (BFA)-induced disassembly. A combination of cis and trans markers revealed that Golgi stacks remain intact as they move through the cytoplasm. The Golgi stack orientation during these movements showed a slight preference for the cis side moving ahead, but trans cisternae were also found at the leading edge. During BFA treatments, the different sub-compartments of about half of the observed stacks fused with the ER sequentially; however, no consistent order could be detected. In contrast, the ionophore monensin resulted in swelling of trans cisternae while medial and particularly cis cisternae were mostly unaffected. Our results thus demonstrate a remarkable equivalence of the different cisternae with respect to movement and BFA-induced fusion with the ER. In addition, we propose that a combination of dual-label fluorescence microscopy and drug treatments can provide a simple alternative approach to the determination of protein localization to specific Golgi sub-compartments.

Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors.

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Tantra, M; Guo, L; Kim, J; Zainolabidin, N; Eulenburg, V; Augustine, G J; Chen, A I

2018-02-15

Inhibitory interneurons mediate the gating of synaptic transmission and modulate the activities of neural circuits. Disruption of the function of inhibitory networks in the forebrain is linked to impairment of social and cognitive behaviors, but the involvement of inhibitory interneurons in the cerebellum has not been assessed. We found that Cadherin 13 (Cdh13), a gene implicated in autism spectrum disorder and attention-deficit hyperactivity disorder, is specifically expressed in Golgi cells within the cerebellar cortex. To assess the function of Cdh13 and utilize the manipulation of Cdh13 expression in Golgi cells as an entry point to examine cerebellar-mediated function, we generated mice carrying Cdh13-floxed alleles and conditionally deleted Cdh13 with GlyT2::Cre mice. Loss of Cdh13 results in a decrease in the expression/localization of GAD67 and reduces spontaneous inhibitory postsynaptic current (IPSC) in cerebellar Golgi cells without disrupting spontaneous excitatory postsynaptic current (EPSC). At the behavioral level, loss of Cdh13 in the cerebellum, piriform cortex and endopiriform claustrum have no impact on gross motor coordination or general locomotor behaviors, but leads to deficits in cognitive and social abilities. Mice lacking Cdh13 exhibit reduced cognitive flexibility and loss of preference for contact region concomitant with increased reciprocal social interactions. Together, our findings show that Cdh13 is critical for inhibitory function of Golgi cells, and that GlyT2::Cre-mediated deletion of Cdh13 in non-executive centers of the brain, such as the cerebellum, may contribute to cognitive and social behavioral deficits linked to neurological disorders. © 2018 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

A Quantitative Golgi Study of Dendritic Morphology in the Mice Striatal Medium Spiny Neurons

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Ana Hladnik

2017-04-01

Full Text Available In this study we have provided a detailed quantitative morphological analysis of medium spiny neurons (MSNs in the mice dorsal striatum and determined the consistency of values among three groups of animals obtained in different set of experiments. Dendritic trees of 162 Golgi Cox (FD Rapid GolgiStain Kit impregnated MSNs from 15 adult C57BL/6 mice were 3-dimensionally reconstructed using Neurolucida software, and parameters of dendritic morphology have been compared among experimental groups. The parameters of length and branching pattern did not show statistically significant difference and were highly consistent among groups. The average neuronal soma surface was between 160 μm2 and 180 μm2, and the cells had 5–6 primary dendrites with close to 40 segments per neuron. Sholl analysis confirmed regular pattern of dendritic branching. The total length of dendrites was around 2100 μm with the average length of individual branching (intermediate segment around 22 μm and for the terminal segment around 100 μm. Even though each experimental group underwent the same strictly defined protocol in tissue preparation and Golgi staining, we found inconsistency in dendritic volume and soma surface. These changes could be methodologically influenced during the Golgi procedure, although without affecting the dendritic length and tree complexity. Since the neuronal activity affects the dendritic thickness, it could not be excluded that observed volume inconsistency was related with functional states of neurons prior to animal sacrifice. Comprehensive analyses of tree complexity and dendritic length provided here could serve as an additional tool for understanding morphological variability in the most numerous neuronal population of the striatum. As reference values they could provide basic ground for comparisons with the results obtained in studies that use various models of genetically modified mice in explaining different pathological conditions that

Phospholipase D is involved in the formation of Golgi associated clathrin coated vesicles in human parotid duct cells.

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Lorena Brito de Souza

Full Text Available Phospholipase D (PLD has been implicated in many cellular functions, such as vesicle trafficking, exocytosis, differentiation, and proliferation. The aim of this study was to characterize the role of PLD in HSY cells, a human cell line originating from the intercalated duct of the parotid gland. As the function and intracellular localization of PLD varies according to cell type, initially, the intracellular localization of PLD1 and PLD2 was determined. By immunofluorescence, PLD1 and PLD2 both showed a punctate cytoplasmic distribution with extensive co-localization with TGN-46. PLD1 was also found in the nucleus, while PLD2 was associated with the plasma membrane. Treatment of cells with the primary alcohol 1-butanol inhibits the hydrolysis of phosphatidylcoline by PLD thereby suppressing phosphatidic acid (PA production. In untreated HSY cells, there was only a slight co-localization of PLD with the clathrin coated vesicles. When HSY cells were incubated with 1-butanol the total number of clathrin coated vesicles increased, especially in the juxtanuclear region and the co-localization of PLD with the clathrin coated vesicles was augmented. Transmission electron microscopy confirmed that the number of Golgi-associated coated vesicles was greater. Treatment with 1-butanol also affected the Golgi apparatus, increasing the volume of the Golgi saccules. The decrease in PA levels after treatment with 1-butanol likewise resulted in an accumulation of enlarged lysosomes in the perinuclear region. Therefore, in HSY cells PLD appears to be involved in the formation of Golgi associated clathrin coated vesicles as well as in the structural maintenance of the Golgi apparatus.

Ceramide transport from endoplasmic reticulum to Golgi apparatus is not vesicle-mediated

NARCIS (Netherlands)

Kok, JW; Babia, T; Klappe, K; Egea, G; Hoekstra, D

1998-01-01

Ceramide (Cer) transfer from the endoplasmic reticulum (ER) to the Golgi apparatus was measured under conditions that block vesicle-mediated protein transfer. This was done either in intact cells by reducing the incubation temperature to 15 degrees C, or in streptolysin O-permeabilized cells by

Proliferation of the Golgi apparatus in tobacco BY-2 cells during cell proliferation after release from the stationary phase of growth.

Science.gov (United States)

Abiodun, Moses; Matsuoka, Ken

2013-08-01

We have recently developed a new method aimed at mass photo-conversion of photo-convertible fluorescence protein (PFP) fluorescence in transformed tobacco BY-2 cells. Using this method we reported recently that the Golgi apparatus is generated by the de novo formation from ER and the division of pre-existing Golgi stacks with similar extents In this work we report that the proliferation of the Golgi apparatus in tobacco cells that enter the growing cycle from the non-dividing cycle is quite similar to that in rapidly growing cells and that de novo formation from the ER and division of pre-existing stacks seems to contribute almost equally to the proliferation.

Polarized trafficking: the palmitoylation cycle distributes cytoplasmic proteins to distinct neuronal compartments.

Science.gov (United States)

Tortosa, Elena; Hoogenraad, Casper C

2018-02-01

In neurons, polarized cargo distribution occurs mainly between the soma and axonal and dendritic compartments, and requires coordinated regulation of cytoskeletal remodeling and membrane trafficking. The Golgi complex plays a critical role during neuronal polarization and secretory trafficking has been shown to differentially transport proteins to both axons and dendrites. Besides the Golgi protein sorting, recent data revealed that palmitoylation cycles are an efficient mechanism to localize cytoplasmic, non-transmembrane proteins to particular neuronal compartments, such as the newly formed axon. Palmitoylation allows substrate proteins to bind to and ride with Golgi-derived secretory vesicles to all neuronal compartments. By allowing cytoplasmic proteins to 'hitchhike' on transport carriers in a non-polarized fashion, compartmentalized depalmitoylation may act as a selective retention mechanism. Copyright © 2018 Elsevier Ltd. All rights reserved.

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....

Asparagus IRX9, IRX10, and IRX14A Are Components of an Active Xylan Backbone Synthase Complex that Forms in the Golgi Apparatus.

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Zeng, Wei; Lampugnani, Edwin R; Picard, Kelsey L; Song, Lili; Wu, Ai-Min; Farion, Isabela M; Zhao, Jia; Ford, Kris; Doblin, Monika S; Bacic, Antony

2016-05-01

Heteroxylans are abundant components of plant cell walls and provide important raw materials for the food, pharmaceutical, and biofuel industries. A number of studies in Arabidopsis (Arabidopsis thaliana) have suggested that the IRREGULAR XYLEM9 (IRX9), IRX10, and IRX14 proteins, as well as their homologs, are involved in xylan synthesis via a Golgi-localized complex termed the xylan synthase complex (XSC). However, both the biochemical and cell biological research lags the genetic and molecular evidence. In this study, we characterized garden asparagus (Asparagus officinalis) stem xylan biosynthesis genes (AoIRX9, AoIRX9L, AoIRX10, AoIRX14A, and AoIRX14B) by heterologous expression in Nicotiana benthamiana We reconstituted and partially purified an active XSC and showed that three proteins, AoIRX9, AoIRX10, and AoIRX14A, are necessary for xylan xylosyltranferase activity in planta. To better understand the XSC structure and its composition, we carried out coimmunoprecipitation and bimolecular fluorescence complementation analysis to show the molecular interactions between these three IRX proteins. Using a site-directed mutagenesis approach, we showed that the DxD motifs of AoIRX10 and AoIRX14A are crucial for the catalytic activity. These data provide, to our knowledge, the first lines of biochemical and cell biological evidence that AoIRX9, AoIRX10, and AoIRX14A are core components of a Golgi-localized XSC, each with distinct roles for effective heteroxylan biosynthesis. © 2016 American Society of Plant Biologists. All Rights Reserved.

Seizures beget seizures in temporal lobe epilepsies: the boomerang effects of newly formed aberrant kainatergic synapses.

Science.gov (United States)

Ben-Ari, Yehezkel; Crepel, Valérie; Represa, Alfonso

2008-01-01

Do temporal lobe epilepsy (TLE) seizures in adults promote further seizures? Clinical and experimental data suggest that new synapses are formed after an initial episode of status epilepticus, however their contribution to the transformation of a naive network to an epileptogenic one has been debated. Recent experimental data show that newly formed aberrant excitatory synapses on the granule cells of the fascia dentate operate by means of kainate receptor-operated signals that are not present on naive granule cells. Therefore, genuine epileptic networks rely on signaling cascades that differentiate them from naive networks. Recurrent limbic seizures generated by the activation of kainate receptors and synapses in naive animals lead to the formation of novel synapses that facilitate the emergence of further seizures. This negative, vicious cycle illustrates the central role of reactive plasticity in neurological disorders.

Hsp20 Protects against Oxygen-Glucose Deprivation/Reperfusion-Induced Golgi Fragmentation and Apoptosis through Fas/FasL Pathway

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Bingwu Zhong

2015-01-01

Full Text Available Cerebral ischemia-reperfusion injury plays an important role in the development of tissue injury after acute ischemic stroke. Finding effective neuroprotective agents has become a priority in the treatment of ischemic stroke. The Golgi apparatus (GA is a pivotal organelle and its protection is an attractive target in the treatment of cerebral ischemia-reperfusion injury. Protective effects of Hsp20, a potential cytoprotective agent due to its chaperone-like activity and involvement in regulation of many vital processes, on GA were assessed in an ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR insult. OGDR induces Golgi fragmentation, apoptosis, and p115 cleavage in N2a cells. However, transfection with Hsp20 significantly attenuates OGDR-induced Golgi fragmentation and apoptosis. Hsp20 interacts with Bax, decreases FasL and Bax expression, and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. Our data demonstrate that increased Hsp20 expression protects against OGDR-induced Golgi fragmentation and apoptosis, likely through interaction with Bax and subsequent amelioration of the OGDR-induced elevation in p115 cleavage via the Fas/FasL signaling pathway. This neuroprotective potential of Hsp20 against OGDR insult and the underlying mechanism will pave the way for its potential clinical application for cerebral ischemia-reperfusion related disorders.

Overexpression of Rab22a hampers the transport between endosomes and the Golgi apparatus

International Nuclear Information System (INIS)

Mesa, Rosana; Magadan, Javier; Barbieri, Alejandro; Lopez, Cecilia; Stahl, Philip D.; Mayorga, Luis S.

2005-01-01

The transport and sorting of soluble and membrane-associated macromolecules arriving at endosomal compartments require a complex set of Rab proteins. Rab22a has been localized to the endocytic compartment; however, very little is known about the function of Rab22a and inconsistent results have been reported in studies performed in different cell lines. To characterize the function of Rab22a in endocytic transport, the wild-type protein (Rab22a WT), a hydrolysis-deficient mutant (Rab22a Q64L), and a mutant with reduced affinity for GTP (Rab22a S19N) were expressed in CHO cells. None of the three Rab22a constructs affected the transport of rhodamine-dextran to lysosomes, the digestion of internalized proteins, or the lysosomal localization of cathepsin D. In contrast with the mild effect of Rab22a on the endosome-lysosome route, cells expressing Rab22a WT and Rab22a Q64L presented a strong delay in the retrograde transport of cholera toxin from endosomes to the Golgi apparatus. Moreover, these cells accumulated the cation independent mannose 6-phosphate receptor in endosomes. These observations indicate that Rab22a can affect the trafficking from endosomes to the Golgi apparatus probably by promoting fusion among endosomes and impairing the proper segregation of membrane domains required for targeting to the trans-Golgi network (TGN)

Dynamin-like protein 1 at the Golgi complex: A novel component of the sorting/targeting machinery en route to the plasma membrane

International Nuclear Information System (INIS)

Bonekamp, Nina A.; Vormund, Kerstin; Jacob, Ralf; Schrader, Michael

2010-01-01

The final step in the liberation of secretory vesicles from the trans-Golgi network (TGN) involves the mechanical action of the large GTPase dynamin as well as conserved dynamin-independent fission mechanisms, e.g. mediated by Brefeldin A-dependent ADP-ribosylated substrate (BARS). Another member of the dynamin family is the mammalian dynamin-like protein 1 (DLP1/Drp1) that is known to constrict and tubulate membranes, and to divide mitochondria and peroxisomes. Here, we examined a potential role for DLP1 at the Golgi complex. DLP1 localized to the Golgi complex in some but not all cell lines tested, thus explaining controversial reports on its cellular distribution. After silencing of DLP1, an accumulation of the apical reporter protein YFP-GL-GPI, but not the basolateral reporter VSVG-SP-GFP at the Golgi complex was observed. A reduction in the transport of YFP-GL-GPI to the plasma membrane was confirmed by surface immunoprecipitation and TGN-exit assays. In contrast, YFP-GL-GPI trafficking was not disturbed in cells silenced for BARS, which is involved in basolateral sorting and trafficking of VSVG-SP-GFP in COS-7 cells. Our data indicate a new role for DLP1 at the Golgi complex and thus a role for DLP1 as a novel component of the apical sorting machinery at the TGN is discussed.

Determinants for membrane association and permeabilization of the coxsackievirus 2B protein and the identification of the Golgi complex as the target organelle.

Science.gov (United States)

de Jong, Arjan S; Wessels, Els; Dijkman, Henri B P M; Galama, Jochem M D; Melchers, Willem J G; Willems, Peter H G M; van Kuppeveld, Frank J M

2003-01-10

The 2B protein of enterovirus is responsible for the alterations in the permeability of secretory membranes and the plasma membrane in infected cells. The structural requirements for the membrane association and the subcellular localization of this essential virus protein, however, have not been defined. Here, we provide evidence that the 2B protein is an integral membrane protein in vivo that is predominantly localized at the Golgi complex upon individual expression. Addition of organelle-specific targeting signals to the 2B protein revealed that the Golgi localization is an absolute prerequisite for the ability of the protein to modify plasma membrane permeability. Expression of deletion mutants and heterologous proteins containing specific domains of the 2B protein demonstrated that each of the two hydrophobic regions could mediate membrane binding individually. However, the presence of both hydrophobic regions was required for the correct membrane association, efficient Golgi targeting, and the membrane-permeabilizing activity of the 2B protein, suggesting that the two hydrophobic regions are cooperatively involved in the formation of a membrane-integral complex. The formation of membrane-integral pores by the 2B protein in the Golgi complex and the possible mechanism by which a Golgi-localized virus protein modifies plasma membrane permeability are discussed.

Short length transmembrane domains having voluminous exoplasmic halves determine retention of Type II membrane proteins in the Golgi complex

OpenAIRE

Quiroga, Rodrigo; Trenchi, Alejandra; Gonzalez Montoro, Ayelén; Valdez, Javier Esteban; Maccioni, Hugo Jose Fernando

2017-01-01

It is still unclear why some proteins that travel along the secretory pathway are retained in the Golgi complex whereas others make their way to the plasma membrane. Recent bioinformatic analyses on a large number of single-spanning membrane proteins support the hypothesis that specific features of the transmembrane domain (TMD) are relevant to the sorting of these proteins to particular organelles. Here we experimentally test this hypothesis for Golgi and plasma membrane proteins. Using the ...

GABARAP activates ULK1 and traffics from the centrosome dependent on Golgi partners WAC and GOLGA2/GM130

OpenAIRE

Joachim, Justin; Tooze, Sharon A.

2016-01-01

ABSTRACT WAC and GOLGA2/GM130 are 2 Golgi proteins that affect autophagy; however, their mechanism of action was unknown. We have shown that WAC binding to GOLGA2 at the Golgi displaces GABARAP from GOLGA2 to allow the maintenance of a nonlipidated centrosomal GABARAP pool. Centrosomal GABARAP can traffic to autophagic structures during starvation. In addition GABARAP specifically promotes ULK1 activation and this is independent of GABARAP lipidation but likely requires a LIR-mediated GABARAP...

Characterization of the sterol and phosphatidylinositol 4-phosphate binding properties of Golgi-associated OSBP-related protein 9 (ORP9.

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Xinwei Liu

Full Text Available Oxysterol binding protein (OSBP and OSBP-related proteins (ORPS have a conserved lipid-binding fold that accommodates cholesterol, oxysterols and/or phospholipids. The diversity of OSBP/ORPs and their potential ligands has complicated the analysis of transfer and signalling properties of this mammalian gene family. In this study we explored the use of the fluorescent sterol cholestatrienol (CTL to measure sterol binding by ORP9 and competition by other putative ligands. Relative to cholesterol, CTL and dehydroergosterol (DHE were poor ligands for OSBP. In contrast, both long (ORP9L and short (ORP9S variants of ORP9 rapidly extracted CTL, and to a lesser extent DHE, from liposomes. ORP9L and ORP9S also extracted [32P]phosphatidylinositol 4-phosphate (PI-4P from liposomes, which was inhibited by mutating two conserved histidine residues (HH488,489AA at the entrance to the binding pocket but not by a mutation in the lid region that inhibited cholesterol binding. Results of direct binding and competition assays showed that phosphatidylserine was poorly extracted from liposomes by ORP9 compared to CTL and PI-4P. ORP9L and PI-4P did not co-localize in the trans-Golgi/TGN of HeLa cells, and siRNA silencing of ORP9L expression did not affect PI-4P distribution in the Golgi apparatus. However, transient overexpression of ORP9L or ORP9S in CHO cells, but not the corresponding PI-4P binding mutants, prevented immunostaining of Golgi-associated PI-4P. The apparent sequestration of Golgi PI-4P by ORP9S was identified as a possible mechanism for its growth inhibitory effects. These studies identify ORP9 as a dual sterol/PI-4P binding protein that could regulate PI-4P in the Golgi apparatus.

Characterization of the sterol and phosphatidylinositol 4-phosphate binding properties of Golgi-associated OSBP-related protein 9 (ORP9).

Science.gov (United States)

Liu, Xinwei; Ridgway, Neale D

2014-01-01

Oxysterol binding protein (OSBP) and OSBP-related proteins (ORPS) have a conserved lipid-binding fold that accommodates cholesterol, oxysterols and/or phospholipids. The diversity of OSBP/ORPs and their potential ligands has complicated the analysis of transfer and signalling properties of this mammalian gene family. In this study we explored the use of the fluorescent sterol cholestatrienol (CTL) to measure sterol binding by ORP9 and competition by other putative ligands. Relative to cholesterol, CTL and dehydroergosterol (DHE) were poor ligands for OSBP. In contrast, both long (ORP9L) and short (ORP9S) variants of ORP9 rapidly extracted CTL, and to a lesser extent DHE, from liposomes. ORP9L and ORP9S also extracted [32P]phosphatidylinositol 4-phosphate (PI-4P) from liposomes, which was inhibited by mutating two conserved histidine residues (HH488,489AA) at the entrance to the binding pocket but not by a mutation in the lid region that inhibited cholesterol binding. Results of direct binding and competition assays showed that phosphatidylserine was poorly extracted from liposomes by ORP9 compared to CTL and PI-4P. ORP9L and PI-4P did not co-localize in the trans-Golgi/TGN of HeLa cells, and siRNA silencing of ORP9L expression did not affect PI-4P distribution in the Golgi apparatus. However, transient overexpression of ORP9L or ORP9S in CHO cells, but not the corresponding PI-4P binding mutants, prevented immunostaining of Golgi-associated PI-4P. The apparent sequestration of Golgi PI-4P by ORP9S was identified as a possible mechanism for its growth inhibitory effects. These studies identify ORP9 as a dual sterol/PI-4P binding protein that could regulate PI-4P in the Golgi apparatus.

Hepatic trans-Golgi action coordinated by the GTPase ARFRP1 is crucial for lipoprotein lipidation and assembly[S

Science.gov (United States)

Hesse, Deike; Radloff, Katrin; Jaschke, Alexander; Lagerpusch, Merit; Chung, Bomee; Tailleux, Anne; Staels, Bart; Schürmann, Annette

2014-01-01

The liver is a major organ in whole body lipid metabolism and malfunctioning can lead to various diseases including dyslipidemia, fatty liver disease, and type 2 diabetes. Triglycerides and cholesteryl esters are packed in the liver as very low density lipoproteins (VLDLs). Generation of these lipoproteins is initiated in the endoplasmic reticulum and further maturation likely occurs in the Golgi. ADP-ribosylation factor-related protein 1 (ARFRP1) is a small trans-Golgi-associated guanosine triphosphatase (GTPase) that regulates protein sorting and is required for chylomicron lipidation and assembly in the intestine. Here we show that the hepatocyte-specific deletion of Arfrp1 (Arfrp1liv−/−) results in impaired VLDL lipidation leading to reduced plasma triglyceride levels in the fasted state as well as after inhibition of lipoprotein lipase activity by Triton WR-1339. In addition, the concentration of ApoC3 that comprises 40% of protein mass of secreted VLDLs is markedly reduced in the plasma of Arfrp1liv−/− mice but accumulates in the liver accompanied by elevated triglycerides. Fractionation of Arfrp1liv−/− liver homogenates reveals more ApoB48 and a lower concentration of triglycerides in the Golgi compartments than in the corresponding fractions from control livers. In conclusion, ARFRP1 and the Golgi apparatus play an important role in lipoprotein maturation in the liver by influencing lipidation and assembly of proteins to the lipid particles. PMID:24186947

Role of the AP-5 adaptor protein complex in late endosome-to-Golgi retrieval.

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Jennifer Hirst

2018-01-01

Full Text Available The AP-5 adaptor protein complex is presumed to function in membrane traffic, but so far nothing is known about its pathway or its cargo. We have used CRISPR-Cas9 to knock out the AP-5 ζ subunit gene, AP5Z1, in HeLa cells, and then analysed the phenotype by subcellular fractionation profiling and quantitative mass spectrometry. The retromer complex had an altered steady-state distribution in the knockout cells, and several Golgi proteins, including GOLIM4 and GOLM1, were depleted from vesicle-enriched fractions. Immunolocalisation showed that loss of AP-5 led to impaired retrieval of the cation-independent mannose 6-phosphate receptor (CIMPR, GOLIM4, and GOLM1 from endosomes back to the Golgi region. Knocking down the retromer complex exacerbated this phenotype. Both the CIMPR and sortilin interacted with the AP-5-associated protein SPG15 in pull-down assays, and we propose that sortilin may act as a link between Golgi proteins and the AP-5/SPG11/SPG15 complex. Together, our findings suggest that AP-5 functions in a novel sorting step out of late endosomes, acting as a backup pathway for retromer. This provides a mechanistic explanation for why mutations in AP-5/SPG11/SPG15 cause cells to accumulate aberrant endolysosomes, and highlights the role of endosome/lysosome dysfunction in the pathology of hereditary spastic paraplegia and other neurodegenerative disorders.

The emergence of shared leadership in newly-formed teams with an initial structure of vertical leadership: A longitudinal analysis

OpenAIRE

Fransen, Katrien; Delvaux, Ellen; Mesquita, Batja; Van Puyenbroeck, Stef

2018-01-01

The importance of high-quality leadership for team effectiveness is widely recognized, with recent viewpoints arguing shared leadership to be a more powerful predictor than vertical leadership. To identify changes in leadership structures over time, we longitudinally tracked the leadership structure of 27 newly-formed teams (N = 195), all having an initial structure of vertical leadership. Our findings demonstrated that the average team leadership strengthened over the course of the 24-week p...

GABARAP activates ULK1 and traffics from the centrosome dependent on Golgi partners WAC and GOLGA2/GM130.

Science.gov (United States)

Joachim, Justin; Tooze, Sharon A

2016-05-03

WAC and GOLGA2/GM130 are 2 Golgi proteins that affect autophagy; however, their mechanism of action was unknown. We have shown that WAC binding to GOLGA2 at the Golgi displaces GABARAP from GOLGA2 to allow the maintenance of a nonlipidated centrosomal GABARAP pool. Centrosomal GABARAP can traffic to autophagic structures during starvation. In addition GABARAP specifically promotes ULK1 activation and this is independent of GABARAP lipidation but likely requires a LIR-mediated GABARAP-ULK1 interaction.

Use of newly developed standardized form for interpretation of high-resolution CT in screening for pneumoconiosis

International Nuclear Information System (INIS)

Julien, P.J.; Sider, L.; Silverman, J.M.; Dahlgren, J.; Harber, P.; Bunn, W.

1991-01-01

This paper reports that although the International Labour Office (ILO) standard for interpretation of the posteroanterior chest radiograph has been available for 10 years, there has been no attempt to standardize the high-resolution CT (HRTC) readings for screening of pneumoconiosis. An integrated respirator surveillance program for 87 workers exposed to inorganic dust was conducted. This program consisted of a detailed occupational exposure history, physical symptoms and signs, spirometry, chest radiography, and HRCT. Two groups of workers with known exposure were studied with HRCT. Group 1 had normal spirometry results and chest radiographs, and group 2 had abnormalities at spirometry or on chest radiographs. The HRCT scans were read independently of the clinical findings and chest radiographs. The HRCT scans were interpreted by using an ILO-based standard form developed by the authors for this project. With the newly developed HRCT form, individual descriptive abnormality localized severity, and overall rating systems have been developed and compared for inter- and intraobserver consistency

FAM21 directs SNX27–retromer cargoes to the plasma membrane by preventing transport to the Golgi apparatus

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Lee, Seongju; Chang, Jaerak; Blackstone, Craig

2016-01-01

The endosomal network maintains cellular homeostasis by sorting, recycling and degrading endocytosed cargoes. Retromer organizes the endosomal sorting pathway in conjunction with various sorting nexin (SNX) proteins. The SNX27–retromer complex has recently been identified as a major endosomal hub that regulates endosome-to-plasma membrane recycling by preventing lysosomal entry of cargoes. Here, we show that SNX27 directly interacts with FAM21, which also binds retromer, within the Wiskott–Aldrich syndrome protein and SCAR homologue (WASH) complex. This interaction is required for the precise localization of SNX27 at an endosomal subdomain as well as for recycling of SNX27-retromer cargoes. Furthermore, FAM21 prevents cargo transport to the Golgi apparatus by controlling levels of phosphatidylinositol 4-phosphate, which facilitates cargo dissociation at the Golgi. Together, our results demonstrate that the SNX27–retromer–WASH complex directs cargoes to the plasma membrane by blocking their transport to lysosomes and the Golgi. PMID:26956659

The Golgi localized bifunctional UDP-rhamnose/UDP-galactose transporter family of Arabidopsis

DEFF Research Database (Denmark)

Rautengarten, Carsten; Ebert, Berit; Moreno, Ignacio

2014-01-01

Delivery of nucleotide sugar substrates into the Golgi apparatus and endoplasmic reticulum for processes such as cell wall biosynthesis and protein glycosylation is critical for plant growth and development. Plant genomes encode large families of uncharacterized nucleotide sugar transporters that...

Characterization of p28, a novel ERGIC/"cis"-Golgi protein, required for Golgi ribbon formation. pH measurements in the early secretory pathway "in vivo"

OpenAIRE

Kögler, Eva Jutta

2008-01-01

The secretory pathway of mammalian cells consists of several compartments. Transport between these organelles is accomplished via vesicular carriers or maturation. For non abundant proteins it is thought that transport receptors help the proteins to exit the ER in an effective way. The best characterized mammalian cargo receptor is ERGIC-53, which transports blood coagulation factor V and VIII, cathespin C and Z as well as alpha1-antitrypsin. It localizes to the ER Golgi intermediate compartm...

Selectivity of neuronal [3H]GABA accumulation in the visual cortex as revealed by Golgi staining of the labeled neurons

International Nuclear Information System (INIS)

Somogyi, P.; Freund, T.F.; Kisvarday, Z.F.; Halasz, N.

1981-01-01

[ 3 H]GABA was injected into the visual cortex of rats in vivo. The labeled amino acid was demonstrated by autoradiography using semithin sections of Golgi material. Selective accumulation was seen in the perikarya of Golgi-stained, gold-toned, aspinous stellate neurons. Spine-laden pyramidal-like cells did not show labeling. This method gives direct information about the dendritic arborization of a neuron, and its putative transmitter, and allows the identification of its synaptic connections. (Auth.)

Asparagus IRX9, IRX10, and IRX14A Are Components of an Active Xylan Backbone Synthase Complex that Forms in the Golgi Apparatus1[OPEN

Science.gov (United States)

Zeng, Wei; Picard, Kelsey L.; Song, Lili; Wu, Ai-Min; Farion, Isabela M.; Zhao, Jia; Ford, Kris; Bacic, Antony

2016-01-01

Heteroxylans are abundant components of plant cell walls and provide important raw materials for the food, pharmaceutical, and biofuel industries. A number of studies in Arabidopsis (Arabidopsis thaliana) have suggested that the IRREGULAR XYLEM9 (IRX9), IRX10, and IRX14 proteins, as well as their homologs, are involved in xylan synthesis via a Golgi-localized complex termed the xylan synthase complex (XSC). However, both the biochemical and cell biological research lags the genetic and molecular evidence. In this study, we characterized garden asparagus (Asparagus officinalis) stem xylan biosynthesis genes (AoIRX9, AoIRX9L, AoIRX10, AoIRX14A, and AoIRX14B) by heterologous expression in Nicotiana benthamiana. We reconstituted and partially purified an active XSC and showed that three proteins, AoIRX9, AoIRX10, and AoIRX14A, are necessary for xylan xylosyltranferase activity in planta. To better understand the XSC structure and its composition, we carried out coimmunoprecipitation and bimolecular fluorescence complementation analysis to show the molecular interactions between these three IRX proteins. Using a site-directed mutagenesis approach, we showed that the DxD motifs of AoIRX10 and AoIRX14A are crucial for the catalytic activity. These data provide, to our knowledge, the first lines of biochemical and cell biological evidence that AoIRX9, AoIRX10, and AoIRX14A are core components of a Golgi-localized XSC, each with distinct roles for effective heteroxylan biosynthesis. PMID:26951434

Shifted Golgi targeting of glycosyltransferases and α-mannosidase IA from giantin to GM130-GRASP65 results in formation of high mannose N-glycans in aggressive prostate cancer cells.

Science.gov (United States)

Bhat, Ganapati; Hothpet, Vishwanath-Reddy; Lin, Ming-Fong; Cheng, Pi-Wan

2017-11-01

There is a pressing need for biomarkers that can distinguish indolent from aggressive prostate cancer to prevent over-treatment of patients with indolent tumor. Golgi targeting of glycosyltransferases was characterized by confocal microscopy after knockdown of GM130, giantin, or both. N-glycans on a trans-Golgi enzyme β4galactosyltransferase-1 isolated by immunoprecipitation from androgen-sensitive and independent prostate cancer cells were determined by matrix-assisted laser desorption-time of flight-mass spectrometry. In situ proximity ligation assay was employed to determine co-localization of (a) α-mannosidase IA, an enzyme required for processing Man 8 GlcNAc 2 down to Man 5 GlcNAc 2 to enable synthesis of complex-type N-glycans, with giantin, GM130, and GRASP65, and (b) trans-Golgi glycosyltransferases with high mannose N-glycans terminated with α3-mannose. Defective giantin in androgen-independent prostate cancer cells results in a shift of Golgi targeting of glycosyltransferases and α-mannosidase IA from giantin to GM130-GRASP65. Consequently, trans-Golgi enzymes and cell surface glycoproteins acquire high mannose N-glycans, which are absent in cells with functional giantin. In situ proximity ligation assays of co-localization of α-mannosidase IA with GM130 and GRASP65, and trans-Golgi glycosyltransferases with high mannose N-glycans are negative in androgen-sensitive LNCaP C-33 cells but positive in androgen-independent LNCaP C-81 and DU145 cells, and LNCaP C-33 cells devoid of giantin. In situ proximity ligation assays of Golgi localization of α-mannosidase IA at giantin versus GM130-GRASP65 site, and absence or presence of N-glycans terminated with α3-mannose on trans-Golgi glycosyltransferases may be useful for distinguishing indolent from aggressive prostate cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Nerve growth factor induced changes in the Golgi apparatus of PC-12 rat pheochromocytoma cells as studied by ligand endocytosis, cytochemical and morphometric methods.

Science.gov (United States)

Hickey, W F; Stieber, A; Hogue-Angeletti, R; Gonatas, J; GOnatas, N K

1983-10-01

Cells of the PC-12 rat pheochromocytoma cell line respond to nerve growth factor (NGF) by sprouting neurites and biochemically differentiating into sympathetic ganglion-like cells. NGF-stimulated ('differentiated') and unstimulated ('undifferentiated') cells were studied by cytochemical techniques for the localization of the enzymes acid phosphatase (ACPase) and thiamine pyrophosphatase (TPPase), and by a morphometric analysis of the distribution of endocytosed wheat-germ agglutinin labelled with horseradish peroxidase (WGA-HRP). Both cytochemical stains showed the enzymes to be distributed in lysosomes and certain cisternae of the Golgi apparatus in both NGF stimulated and unstimulated cells. ACPase was not confined to GERL (Golgi-endoplasmic reticulum-lysosome) as in certain other cells. The morphometric studies demonstrated that the reaction product of the internalized WGA-HRP occupied 4.7% of the cytoplasmic area in unstimulated cells and 4.5% in NGF-stimulated ones. Despite this similarity, the distribution of the WGA-HRP among the studied intracellular compartments in these two cell groups varied. In the NGF-stimulated cells 3.3% of the WGA-HRP reaction product was found in the innermost Golgi cisterna(e) while in unstimulated cells only 0.3% was seen in this compartment. Similarly, 4.3% of the WGA-HRP stain was found in small vesicles at the 'trans' aspect of the Golgi apparatus in stimulated cells, when only 0.3% of the stain occupied this compartment in 'undifferentiated' cells. The morphometric analysis also revealed that when the PC-12 cells were stimulated with NGF, the Golgi apparatus increased in area by approximately 70%. These findings are consistent with the hypothesis that NGF induced differentiation of PC-12 cells is coupled with enhanced endocytosis of WGA and probably of its 'receptor' to the innermost Golgi cisterna(e) and the closely associated vesicles.

Proton accumulation and ATPase activity in Golgi apparatus-enriched vesicles from rat liver

International Nuclear Information System (INIS)

Yeh, H.I.; van Rossum, G.D.

1991-01-01

We have studied the mechanism by which liver Golgi apparatus maintains the acidity of its contents, using a subcellular fraction from rat liver highly enriched in Golgi marker enzymes. Proton accumulation (measured by quenching of acridine-orange fluorescence) and anion-dependent ATPase were characterized and compared. Maximal ATPase and proton accumulation required ATP; GTP and other nucleotides gave 10% to 30% of maximal activity. Among anions, Cl- and Br- approximately doubled the activities; others were much less effective. Half-maximal increase of ATPase and H+ uptake required 55 mmol/L and 27 mmol/L Cl-, respectively. In predominantly chloride media, SCN- and NO3- markedly inhibited H+ uptake. Nitrate competitively inhibited both the chloride-dependent ATPase (apparent Ki 6 mmol/L) and proton uptake (apparent Ki 2 mmol/L). Nitrate and SCN- also inhibited uptake of 36Cl. Replacing K+ with Na+ had no effect on the initial rate of proton uptake but somewhat reduced the steady state attained. Replacement of K+ with NH4+ and choline reduced proton uptake without affecting ATPase. The ATPase and H+ uptake were supported equally well by Mg2+ or Mn2+. The ATPase was competitively inhibited by 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonic acid (apparent Ki 39 mumol/L). Other agents inhibiting both H+ uptake and ATPase were N-ethylmaleimide, N,N'-dicyclohexylcarbodiimide, chlorpromazine, diethylstilbestrol, Zn2+, Co2+ and Cu2+. In the Cl- medium, accumulated protons were released by ionophores at the relative rates, monensin = nigericin greater than valinomycin greater than carbonyl cyanide mchlorophenylhydrazone; the last of these also reduced ATPase activity. In the absence of Cl-, monensin and valinomycin both stimulated the ATPase. These results show a close association between ATPase activity and acidification of liver Golgi vesicles

Morphometric golgi study of some cortical locations in wag/rij and aci rat strains

NARCIS (Netherlands)

Karpova, A.V.; Bikbaev, A.F.; Coenen, A.M.L.; Luijtelaar, E.L.J.M. van; Luijtelaar, E.L.J.M. van; Kuznetsova, G.D.; Coenen, A.M.L.; Chepurnov, S.A.

2004-01-01

The present study was aimed to investigate the neuronal organization of two neocortical frontal zones using a Golgi staining technique in genetic epileptic rats, WAG/Rij's. One cortical zone was a specific part of the somatosensory cortex, which was recently proposed to contain a cortical epileptic

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.

FMNL2 and -3 regulate Golgi architecture and anterograde transport downstream of Cdc42

DEFF Research Database (Denmark)

Kage, Frieda; Steffen, Anika; Ellinger, Adolf

2017-01-01

The Rho-family small GTPase Cdc42 localizes at plasma membrane and Golgi complex and aside from protrusion and migration operates in vesicle trafficking, endo- and exocytosis as well as establishment and/or maintenance of cell polarity. The formin family members FMNL2 and -3 are actin assembly fa...

Retention in the Golgi apparatus and expression on the cell surface of Cfr/Esl-1/Glg-1/MG-160 are regulated by two distinct mechanisms.

Science.gov (United States)

Miyaoka, Yuichiro; Kato, Hidenori; Ebato, Kazuki; Saito, Shigeru; Miyata, Naoko; Imamura, Toru; Miyajima, Atsushi

2011-11-15

Cfr (cysteine-rich fibroblast growth factor receptor) is an Fgf (fibroblast growth factor)-binding protein without a tyrosine kinase. We have shown previously that Cfr is involved in Fgf18 signalling via Fgf receptor 3c. However, as Cfr is also known as Glg (Golgi apparatus protein)-1 or MG-160 and occurs in the Golgi apparatus, it remains unknown how the distribution of Cfr is regulated. In the present study, we performed a mutagenic analysis of Cfr to show that two distinct regions contribute to its distribution and stability. First, the C-terminal region retains Cfr in the Golgi apparatus. Secondly, the Cfr repeats in the extracellular juxtamembrane region destabilizes Cfr passed through the Golgi apparatus. This destabilization does not depend on the cleavage and secretion of the extracellular domain of Cfr. Furthermore, we found that Cfr with a GPI (glycosylphosphatidylinositol) anchor was predominantly expressed on the cell surface in Ba/F3 cells and affected Fgf18 signalling in a similar manner to the full-length Cfr, indicating that the interaction of Cfr with Fgfs on the cell surface is important for its function in Fgf signalling. These results suggest that the expression of Cfr in the Golgi apparatus and on the plasma membrane is finely tuned through two distinct mechanisms for exhibiting different functions.

Dual pulse-chase microscopy reveals early divergence in the biosynthetic trafficking of the Na,K-ATPase and E-cadherin

Science.gov (United States)

Farr, Glen A.; Hull, Michael; Stoops, Emily H.; Bateson, Rosalie; Caplan, Michael J.

2015-01-01

Recent evidence indicates that newly synthesized membrane proteins that share the same distributions in the plasma membranes of polarized epithelial cells can pursue a variety of distinct trafficking routes as they travel from the Golgi complex to their common destination at the cell surface. In most polarized epithelial cells, both the Na,K-ATPase and E-cadherin are localized to the basolateral domains of the plasma membrane. To examine the itineraries pursued by newly synthesized Na,K-ATPase and E-cadherin in polarized MDCK epithelial cells, we used the SNAP and CLIP labeling systems to fluorescently tag temporally defined cohorts of these proteins and observe their behaviors simultaneously as they traverse the secretory pathway. These experiments reveal that E-cadherin is delivered to the cell surface substantially faster than is the Na,K-ATPase. Furthermore, the surface delivery of newly synthesized E-cadherin to the plasma membrane was not prevented by the 19°C temperature block that inhibits the trafficking of most proteins, including the Na,K-ATPase, out of the trans-Golgi network. Consistent with these distinct behaviors, populations of newly synthesized E-cadherin and Na,K-ATPase become separated from one another within the trans-Golgi network, suggesting that they are sorted into different carrier vesicles that mediate their post-Golgi trafficking. PMID:26424804

Disturbed neuronal ER-Golgi sorting of unassembled glycine receptors suggests altered subcellular processing is a cause of human hyperekplexia.

Science.gov (United States)

Schaefer, Natascha; Kluck, Christoph J; Price, Kerry L; Meiselbach, Heike; Vornberger, Nadine; Schwarzinger, Stephan; Hartmann, Stephanie; Langlhofer, Georg; Schulz, Solveig; Schlegel, Nadja; Brockmann, Knut; Lynch, Bryan; Becker, Cord-Michael; Lummis, Sarah C R; Villmann, Carmen

2015-01-07

Recent studies on the pathogenic mechanisms of recessive hyperekplexia indicate disturbances in glycine receptor (GlyR) α1 biogenesis. Here, we examine the properties of a range of novel glycine receptor mutants identified in human hyperekplexia patients using expression in transfected cell lines and primary neurons. All of the novel mutants localized in the large extracellular domain of the GlyR α1 have reduced cell surface expression with a high proportion of receptors being retained in the ER, although there is forward trafficking of glycosylated subpopulations into the ER-Golgi intermediate compartment and cis-Golgi compartment. CD spectroscopy revealed that the mutant receptors have proportions of secondary structural elements similar to wild-type receptors. Two mutants in loop B (G160R, T162M) were functional, but none of those in loop D/β2-3 were. One nonfunctional truncated mutant (R316X) could be rescued by coexpression with the lacking C-terminal domain. We conclude that a proportion of GlyR α1 mutants can be transported to the plasma membrane but do not necessarily form functional ion channels. We suggest that loop D/β2-3 is an important determinant for GlyR trafficking and functionality, whereas alterations to loop B alter agonist potencies, indicating that residues here are critical elements in ligand binding. Copyright © 2015 the authors 0270-6474/15/350422-16$15.00/0.

Retromer guides STxB and CD8-M6PR from early to recycling endosomes, EHD1 guides STxB from recycling endosome to Golgi

Science.gov (United States)

McKenzie, Jenna E.; Raisley, Brent; Zhou, Xin; Naslavsky, Naava; Taguchi, Tomohiko; Caplan, Steve; Sheff, David

2012-01-01

Retrograde trafficking transports proteins, lipids and toxins from the plasma membrane to the Golgi and ER. To reach the Golgi, these cargos must transit the endosomal system, consisting of early endosomes, recycling endosomes, late endosomes and lysosomes. All cargos pass through early endosomes, but may take different routes to the Golgi. Retromer dependent cargos bypass the late endosomes to reach the Golgi. We compared how two very different retromer dependent cargos negotiate the endosomal sorting system. Shiga toxin B, bound to the external layer of the plasma membrane, and chimeric CD8-Mannose-6-Phosphate Receptor, which is anchored via a transmembrane domain. Both appear to pass through the recycling endosome. Ablation of the recycling endosome diverted both of these cargos to an aberrant compartment and prevented them from reaching the Golgi. Once in the recycling endosome, Shiga toxin required EHD1 to traffic to the TGN, while the CD8-Mannose-6-Phosphate Receptor was not significantly dependent on EHD1. Knockdown of retromer components left cargo in the early endosomes, suggesting that it is required for retrograde exit from this compartment. This work establishes the recycling endosome as a required step in retrograde traffic of at least these two retromer dependent cargos. Along this pathway, retromer is associated with EE to recycling endosome traffic, while EHD1 is associated with recycling endosome to TGN traffic of STxB. PMID:22540229

The organization of the Golgi complex and microtubules in skeletal muscle is fiber type-dependent

DEFF Research Database (Denmark)

Ralston, E; Lu, Z; Ploug, Thorkil

1999-01-01

Skeletal muscle has a nonconventional Golgi complex (GC), the organization of which has been a subject of controversy in the past. We have now examined the distribution of the GC by immunofluorescence and immunogold electron microscopy in whole fibers from different rat muscles, both innervated a...

Plasma Membrane Targeting of Protocadherin 15 Is Regulated by the Golgi-Associated Chaperone Protein PIST

Directory of Open Access Journals (Sweden)

Hongyun Nie

2016-01-01

Full Text Available Protocadherin 15 (PCDH15 is a core component of hair cell tip-links and crucial for proper function of inner ear hair cells. Mutations of PCDH15 gene cause syndromic and nonsyndromic hearing loss. At present, the regulatory mechanisms responsible for the intracellular transportation of PCDH15 largely remain unknown. Here we show that PIST, a Golgi-associated, PDZ domain-containing protein, interacts with PCDH15. The interaction is mediated by the PDZ domain of PIST and the C-terminal PDZ domain-binding interface (PBI of PCDH15. Through this interaction, PIST retains PCDH15 in the trans-Golgi network (TGN and reduces the membrane expression of PCDH15. We have previously showed that PIST regulates the membrane expression of another tip-link component, cadherin 23 (CDH23. Taken together, our finding suggests that PIST regulates the intracellular trafficking and membrane targeting of the tip-link proteins CDH23 and PCDH15.

A spatially-supported forced-choice recognition test reveals children’s long-term memory for newly learned word forms

Directory of Open Access Journals (Sweden)

Katherine R. Gordon

2014-03-01

Full Text Available Children’s memories for the link between a newly trained word and its referent have been the focus of extensive past research. However, memory for the word form itself is rarely assessed among preschool-age children. When it is, children are typically asked to verbally recall the forms, and they generally perform at floor on such tests. To better measure children’s memory for word forms, we aimed to design a more sensitive test that required recognition rather than recall, provided spatial cues to off-set the phonological memory demands of the test, and allowed pointing rather than verbal responses. We taught 12 novel word-referent pairs via ostensive naming to sixteen 4-to-6-year-olds and measured their memory for the word forms after a week-long retention interval using the new spatially-supported form recognition test. We also measured their memory for the word-referent links and the generalization of the links to untrained referents with commonly used recognition tests. Children demonstrated memory for word forms at above chance levels; however, their memory for forms was poorer than their memory for trained or generalized word-referent links. When in error, children were no more likely to select a foil that was a close neighbor to the target form than a maximally different foil. Additionally, they more often selected correct forms that were among the first six than the last six to be trained. Overall, these findings suggest that children are able to remember word forms after a limited number of ostensive exposures and a long-term delay. However, word forms remain more difficult to learn than word-referent links and there is an upper limit on the number of forms that can be learned within a given period of time.

Appearance of newly formed mRNA and rRNA as ribonucleoprotein-particles in the cytoplasmic subribosomal fraction of pea embryos

International Nuclear Information System (INIS)

Takahashi, Noribumi; Takaiwa, Fumio; Fukuei, Keisuke; Sakamaki, Tadashi; Tanifuji, Shigeyuki

1977-01-01

Incorporation studies with 3 H-uridine or 3 H-adenosine showed that germinating pea embryos synthesize all types of poly A(+) RNA, rRNA and 4-5S RNA at the early stage of germination. After the pulse labeling for 30 min, only heterodisperse RNA and 4-5S RNA appeared in the cytoplasm as labeled RNA species. At this time the radioactivity was associated with cytoplasmic structures heavier than 80S and RNP particles of 68-70S, 52-55S, 36-38S and 20-22S which are presumed to be free mRNP particles in plants. When the pulse-labeled embryos were incubated for a further 60 min in an isotope-free medium, the labeled 17S and 25S rRNA emerged in the cytoplasm, together with labeled heterodisperse and 4-5S RNAs. More radioactivity accumulated in the regions of the polysome, 62-65S and 38-42S particles. The results of analysis of RNAs extracted from the whole cytoplasm, polysome or subribosomal fractions indicated that small subunits of newly formed ribosomes appear more rapidly in the cytoplasm than new large subunits, which accumulate for a while as free particles in the cytoplasm than are incorporated into polysomes. The actinomycin treatment which caused preferential inhibition of rRNA synthesis reduced the accumulation of free, newly formed ribosome subunits and partially permitted detection of the presumed mRNP particles in the subribosomal region even after the chase treatment. (auth.)

Nucleocytoplasmic shuttling of STK16 (PKL12), a Golgi-resident serine/threonine kinase involved in VEGF expression regulation

International Nuclear Information System (INIS)

Guinea, Barbara; Ligos, Jose Manuel; Lain de Lera, Teresa; Martin-Caballero, Juan; Flores, Juana; Gonzalez de la Pena, Manuel; Garcia-Castro, Javier; Bernad, Antonio

2006-01-01

PKL12/STK16 protein is the first identified mammalian member of a ser/thr kinase subfamily that is conserved across several kingdoms, with a broad expression pattern in murine tissues and cell types. Endogenous STK16 subcellular localization was evaluated by indirect immunofluorescence in NIH/3T3 and NRK cells, demonstrating a Golgi-associated pattern that appears to be independent of signals provided by integrin pathways. When cells were treated with brefeldin A (BFA) or nocodazole, drugs that promote Golgi disorganization, we observed STK16 translocation to the nuclear compartment. Constitutive overexpression of this protein by retroviral vectors also promotes accumulation of STK16 in the nuclear compartment, as shown by subfractionation studies. A kinase-dead STK16 mutant (E202A) was used to demonstrate that both the Golgi association and the nuclear translocation capabilities seem to be independent of the STK16 kinase activity. In addition, we show that STK16 overexpression in several cell lines enhances their capacity to produce and secrete VEGF. To confirm these data in vivo, we injected tumor cells overexpressing STK16 into immunodeficient BALBc/SCID mice. HT1080-derived tumors overexpressing STK16 showed increased volume and number of blood vessels compared to controls. Altogether, these data concur with previous reports suggesting a potential role for STK16 as a transcriptional co-activator

Role of the Conserved Ologomeric Golgi Complex in the Abnormalities of Glycoprotein Processing in Breast Cancer Cells

National Research Council Canada - National Science Library

Zolov, Sergey

2004-01-01

.... We propose that the COG3 protein plays one of the main roles in these processes. We utilized RNA interference assay to knockdown COG3p in HeLa cells to determine the effect of its depletion on Golgi proteins localization...

Ramón y Cajal erroneously identified as Camillo Golgi on a souvenir postage stamp.

Science.gov (United States)

Triarhou, Lazaros C; del Cerro, Manuel

2012-01-01

Focusing on a philatelic oddity that erringly identifies a picture of Santiago Ramón y Cajal as that of Camillo Golgi, this brief article examines official and unofficial stamp issues honoring the two great neuroanatomists, one from Spain and the other from Italy, who were early Nobel Prize winners in Physiology or Medicine.

Analysis of thick brain sections by obverse-reverse computer microscopy: application of a new, high clarity Golgi-Nissl stain.

Science.gov (United States)

Glaser, E M; Van der Loos, H

1981-08-01

Exceptionally clear Golgi-Nissl sections of 300 micron thickness have been morphometrically studied by light microscopy using oil immersion objectives. The clarity results from a new variation of a staining procedure that combines Golgi and Nissl images in one section. A viewing technique has been developed that permits a histologic preparation to be examined from its obverse (or normally viewed) side and its reverse (or under) side. The technique was designed for use with a computer microscope but can be employed with any light microscope whose stage position can be measured within 100 micron. Sections thicker than 300 micron can be studied dependent on the working distance of the objective lens, provided that the clarity of the material permits it.

Modulating Endoplasmic Reticulum-Golgi Cargo Receptors for Improving Secretion of Carrier-Fused Heterologous Proteins in the Filamentous Fungus Aspergillus oryzae

Science.gov (United States)

Hoang, Huy-Dung; Maruyama, Jun-ichi

2014-01-01

Filamentous fungi are excellent hosts for industrial protein production due to their superior secretory capacity; however, the yield of heterologous eukaryotic proteins is generally lower than that of fungal or endogenous proteins. Although activating protein folding machinery in the endoplasmic reticulum (ER) improves the yield, the importance of intracellular transport machinery for heterologous protein secretion is poorly understood. Here, using Aspergillus oryzae as a model filamentous fungus, we studied the involvement of two putative lectin-like cargo receptors, A. oryzae Vip36 (AoVip36) and AoEmp47, in the secretion of heterologous proteins expressed in fusion with the endogenous enzyme α-amylase as the carrier. Fluorescence microscopy revealed that mDsRed-tagged AoVip36 localized in the Golgi compartment, whereas AoEmp47 showed localization in both the ER and the Golgi compartment. Deletion of AoVip36 and AoEmp47 improved heterologous protein secretion, but only AoVip36 deletion had a negative effect on the secretion of α-amylase. Analysis of ER-enriched cell fractions revealed that AoVip36 and AoEmp47 were involved in the retention of heterologous proteins in the ER. However, the overexpression of each cargo receptor had a different effect on heterologous protein secretion: AoVip36 enhanced the secretion, whereas AoEmp47 promoted the intracellular retention. Taken together, our data suggest that AoVip36 and AoEmp47 hinder the secretion of heterologous proteins by promoting their retention in the ER but that AoVip36 also promotes the secretion of heterologous proteins. Moreover, we found that genetic deletion of these putative ER-Golgi cargo receptors significantly improves heterologous protein production. The present study is the first to propose that ER-Golgi transport is a bottleneck for heterologous protein production in filamentous fungi. PMID:25362068

Cutis laxa and fatal pulmonary hypertension: a newly recognized syndrome?

Science.gov (United States)

Brunetti-Pierri, Nicola; Piccolo, Pasquale; Morava, Eva; Wevers, Ron A.; McGuirk, Megan; Johnson, Yvette R.; Urban, Zsolt; Dishop, Megan K.; Potocki, Lorraine

2015-01-01

Cutis laxa is a connective tissue disorder with distinctive lax, redundant, and inelastic skin. It is a genetically heterogenous disorder with autosomal dominant and recessive patterns of inheritance. We report a patient with cutis laxa supported by clinical, microscopic, and ultrastructural findings. Molecular analysis of fibulin-4 and -5, of the α2 subunit of the V-type H+ ATPase, and of the component of the oligomeric Golgi complex 7 (COG7) genes excluded the type I and type II autosomal recessive forms of cutis laxa, and congenital disorders of glycosylation associated with cutis laxa. Remarkably, our patient also presented severe and lethal pulmonary hypertension as a newborn. This case with cutis laxa, severe pulmonary hypertension, and no detectable mutations in fibulin-4 and -5 genes may represent a previously unrecognized syndrome. PMID:21285876

Evaluation of interim and final waste forms for the newly generated liquid low-level waste flowsheet

International Nuclear Information System (INIS)

Abotsi, G.M.K.; Bostick, D.T.; Beck, D.E.

1996-05-01

The purpose of this review is to evaluate the final forms that have been proposed for radioactive-containing solid wastes and to determine their application to the solid wastes that will result from the treatment of newly generated liquid low-level waste (NGLLLW) and Melton Valley Storage Tank (MVST) supernate at the Oak Ridge National Laboratory (ORNL). Since cesium and strontium are the predominant radionuclides in NGLLLW and MVST supernate, this review is focused on the stabilization and solidification of solid wastes containing these radionuclides in cement, glass, and polymeric materials-the principal waste forms that have been tested with these types of wastes. Several studies have shown that both cesium and strontium are leached by distilled water from solidified cement, although the leachabilities of cesium are generally higher than those of strontium under similar conditions. The situation is exacerbated by the presence of sulfates in the solution, as manifested by cracking of the grout. Additives such as bentonite, blast-furnace slag, fly ash, montmorillonite, pottery clay, silica, and zeolites generally decrease the cesium and strontium release rates. Longer cement curing times (>28 d) and high ionic strengths of the leachates, such as those that occur in seawater, also decrease the leach rates of these radionuclides. Lower cesium leach rates are observed from vitrified wastes than from grout waste forms. However, significant quantities of cesium are volatilized due to the elevated temperatures required to vitrify the waste. Hence, vitrification will generally require the use of cleanup systems for the off-gases to prevent their release into the atmosphere

Phospho-eNOS Ser-1176 is associated with the nucleoli and the Golgi complex in C6 rat glioma cells.

Science.gov (United States)

Klinz, Franz-Josef; Herberg, Natalie; Arnhold, Stefan; Addicks, Klaus; Bloch, Wilhelm

2007-06-29

Enzymatic activity of endothelial nitric oxide synthase (eNOS) is controlled by posttranslational modifications, protein-protein interactions, and subcellular localization. For example, N-terminal fatty acid modifications target eNOS to the Golgi complex where it becomes phosphorylated. We show here by immunofluorescence analysis that phospho-eNOS Ser-1176 is enriched in the perinuclear region of interphase C6 rat glioma cells. Confocal double immunofluorescence microscopy with the Golgi marker protein 58K revealed that phospho-eNOS Ser-1176 is associated with the Golgi complex. Surprisingly, we observed several spots in the nucleus of C6 cells that were positive for phospho-eNOS Ser-1176. Confocal double immunofluorescence analysis with the nucleolus marker protein fibrillarin revealed that within the nucleus phospho-eNOS Ser-1176 is exclusively associated with the nucleoli. It is known that in mitotic cells nucleoli are lost during prophase and rebuild during telophase. In agreement with this, we find no nucleoli-like distribution of phospho-eNOS Ser-1176 in metaphase and anaphase C6 glioma cells. Our finding that phospho-eNOS Ser-1176 is selectively associated with the nucleoli points to a so far unknown role for eNOS in interphase glioma cells.

Endogenous glycosphingolipid acceptor specificity of sialosyltransferase systems in intact golgi membranes, synaptosomes, and synaptic plasma membranes from rat brain

International Nuclear Information System (INIS)

Durrie, R.; Saito, M.; Rosenberg, A.

1988-01-01

Preparations highly enriched in Golgi complex membranes, synaptosomes, and synaptic plasma membranes (SPM) by marker enzyme analysis and electron microscopic morphology were made from the brains of 28-day-old rats. These were incubated with cytidine 5'-monophosphate-N-acetyl[ 14 C]neuraminic acid (CMP-NeuAc) in a physiologic buffer, without detergents. Glycolipid sialosyltransferase activities (SATs) were measured by analyzing incorporation of radiolabeled NeuAc into endogenous membrane gangliosides. Golgi SAT was diversified in producing all the various molecular species of labeled gangliosides. Synaptosomal SAT exhibited a lower activity, but it was highly specific in its labeling pattern, with a marked preference for labeling NeuAcα2 → 8NeuAcα2 → 3Galβ1 → 4Glcβ1 → 1Cer (GD3 ganglioside). SPM prepared from the synaptosomes retained the GD3-related SAT (or SAT-2), and the total specific activity increased, which suggests that the location of the synaptosomal activity is in the SPM. These results indicate that SAT activity in Golgi membranes differs from that in synaptosomes with regard to endogenous acceptor substrate specificity and SAT activity of synaptosomes should be located in the synaptosomal plasma membrane. This SAT could function as an ectoenzyme in concert with ecto-sialidase to modulate the GD3 and other ganglioside population in situ at the SPM of the central nervous system

Activation of a remote (1-year old) emotional memory interferes with the retrieval of a newly formed hippocampus-dependent memory in rats.

Science.gov (United States)

Zoladz, Phillip R; Woodson, James C; Haynes, Vernon F; Diamond, David M

2010-01-01

The persistent intrusion of remote traumatic memories in people with post-traumatic stress disorder (PTSD) may contribute to the impairment of their ongoing hippocampal and prefrontal cortical functioning. In the current work, we have developed a rodent analogue of the intrusive memory phenomenon. We studied the influence of the activation of a remote traumatic memory in rats on their ability to retrieve a newly formed hippocampus-dependent memory. Adult male Sprague-Dawley rats were given inhibitory avoidance (IA) training, and then 24 h or 1, 6 or 12 months later, the same rats were trained to learn, and then remember across a 30-min delay period, the location of a hidden escape platform in the radial-arm water maze (RAWM). When IA-trained rats spent the 30-min delay period in the IA apparatus, they exhibited intact remote (1-year old) memory of the shock experience. More importantly, activation of the rats' memory of the shock experience profoundly impaired their ability to retrieve the newly formed spatial memory of the hidden platform location in the RAWM. Our finding that reactivation of a remote emotional memory exerted an intrusive effect on new spatial memory processing in rats provides a novel approach toward understanding how intrusive memories of traumatic experiences interfere with ongoing cognitive processing in people with PTSD.

Mutations in TRAPPC12 Manifest in Progressive Childhood Encephalopathy and Golgi Dysfunction.

Science.gov (United States)

Milev, Miroslav P; Grout, Megan E; Saint-Dic, Djenann; Cheng, Yong-Han Hank; Glass, Ian A; Hale, Christopher J; Hanna, David S; Dorschner, Michael O; Prematilake, Keshika; Shaag, Avraham; Elpeleg, Orly; Sacher, Michael; Doherty, Dan; Edvardson, Simon

2017-08-03

Progressive childhood encephalopathy is an etiologically heterogeneous condition characterized by progressive central nervous system dysfunction in association with a broad range of morbidity and mortality. The causes of encephalopathy can be either non-genetic or genetic. Identifying the genetic causes and dissecting the underlying mechanisms are critical to understanding brain development and improving treatments. Here, we report that variants in TRAPPC12 result in progressive childhood encephalopathy. Three individuals from two unrelated families have either a homozygous deleterious variant (c.145delG [p.Glu49Argfs ∗ 14]) or compound-heterozygous variants (c.360dupC [p.Glu121Argfs ∗ 7] and c.1880C>T [p. Ala627Val]). The clinical phenotypes of the three individuals are strikingly similar: severe disability, microcephaly, hearing loss, spasticity, and characteristic brain imaging findings. Fibroblasts derived from all three individuals showed a fragmented Golgi that could be rescued by expression of wild-type TRAPPC12. Protein transport from the endoplasmic reticulum to and through the Golgi was delayed. TRAPPC12 is a member of the TRAPP protein complex, which functions in membrane trafficking. Variants in several other genes encoding members of the TRAPP complex have been associated with overlapping clinical presentations, indicating shared and distinct functions for each complex member. Detailed understanding of the TRAPP-opathies will illuminate the role of membrane protein transport in human disease. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Chimeric forms of furin and TGN38 are transported with the plasma membrane in the trans-Golgi network via distinct endosomal pathways.

Science.gov (United States)

Mallet, W G; Maxfield, F R

1999-07-26

Furin and TGN38 are menbrane proteins that cycle between the plasma membrane and the trans-Golgi network (TGN), each maintaining a predominant distribution in the TGN. We have used chimeric proteins with an extracellular Tac domain and the cytoplasmic domain of TGN38 or furin to study the trafficking of these proteins in endosomes. Previously, we demonstrated that the postendocytic trafficking of Tac-TGN38 to the TGN is via the endocytic recycling pathway (Ghosh, R.N.,W.G. Mallet,T.T. Soe,T.E.McGraw, and F.R. Maxfield.1998.J. Cell Biol.142:923-936). Here we show that internalized Tac-furin is delivered to the TGN through late endosomes, bypassing the endocytic recycling compartment. The transport of Tac-furin from late endosomes to the TGN appears to proceed via an efficient, single-pass mechanism. Delivery of Tac-furin but not Tac-TGN38 to the TGN is blocked by nocodazole, and the two pathways are also differentially affected by wortmannin. These studies demonstrate the existence of two independentpathways for endosomal transport of proteins to the TGN from the plasma membrane.

Golgi Study of Medium Spiny Neurons from Dorsolateral Striatum of the Turtle Trachemys scripta elegans.

Science.gov (United States)

González, Carolina; Mendoza, Janeth; Avila-Costa, María Rosa; Arias, Juan M; Barral, Jaime

2013-10-25

Comparative anatomy has shown similarities between reptilian and mammalian basal ganglia. Here the morphological characteristics of the medium spiny neurons (MSN) in the dorsolateral striatum (DLS) of the turtle are described after staining them with the Golgi technique. The soma of MSN in DLS showed three main forms: spherical, ovoid, and fusiform. The number of primary dendritic branches (3-4 dendrites/cell) was less than observed in mammals. The MSN axon originates mainly from the soma, and randomly it emerges at the beginning of the primary dendrite. The main differences between turtle and mammalian MSN were detected on dendritic spines. Short, thin, bifurcated and fungiform types of dendritic spines were observed in the turtle's MSN, according to their shape. In most of the analyzed spines, it was found that its length considerably exceeded that reported in mammals, with dendritic spines up to 8μm in length. These differences could play an important role in the modulation of motor networks preserved along the vertebrate evolution. Copyright © 2013. Published by Elsevier Ireland Ltd.

Golgi twins in late mitosis revealed by genetically encoded tags for live cell imaging and correlated electron microscopy

NARCIS (Netherlands)

Gaietta, Guido M; Giepmans, Ben N G; Deerinck, Thomas J; Smith, W Bryan; Ngan, Lucy; Llopis, Juan; Adams, Stephen R; Tsien, Roger Y; Ellisman, Mark H

2006-01-01

Combinations of molecular tags visible in light and electron microscopes become particularly advantageous in the analysis of dynamic cellular components like the Golgi apparatus. This organelle disassembles at the onset of mitosis and, after a sequence of poorly understood events, reassembles after

Different selective pressures lead to different genomic outcomes as newly-formed hybrid yeasts evolve

Directory of Open Access Journals (Sweden)

Piotrowski Jeff S

2012-04-01

Full Text Available Abstract Background Interspecific hybridization occurs in every eukaryotic kingdom. While hybrid progeny are frequently at a selective disadvantage, in some instances their increased genome size and complexity may result in greater stress resistance than their ancestors, which can be adaptively advantageous at the edges of their ancestors' ranges. While this phenomenon has been repeatedly documented in the field, the response of hybrid populations to long-term selection has not often been explored in the lab. To fill this knowledge gap we crossed the two most distantly related members of the Saccharomyces sensu stricto group, S. cerevisiae and S. uvarum, and established a mixed population of homoploid and aneuploid hybrids to study how different types of selection impact hybrid genome structure. Results As temperature was raised incrementally from 31°C to 46.5°C over 500 generations of continuous culture, selection favored loss of the S. uvarum genome, although the kinetics of genome loss differed among independent replicates. Temperature-selected isolates exhibited greater inherent and induced thermal tolerance than parental species and founding hybrids, and also exhibited ethanol resistance. In contrast, as exogenous ethanol was increased from 0% to 14% over 500 generations of continuous culture, selection favored euploid S. cerevisiae x S. uvarum hybrids. Ethanol-selected isolates were more ethanol tolerant than S. uvarum and one of the founding hybrids, but did not exhibit resistance to temperature stress. Relative to parental and founding hybrids, temperature-selected strains showed heritable differences in cell wall structure in the forms of increased resistance to zymolyase digestion and Micafungin, which targets cell wall biosynthesis. Conclusions This is the first study to show experimentally that the genomic fate of newly-formed interspecific hybrids depends on the type of selection they encounter during the course of evolution

Golgi localized barley MTP8 proteins facilitate Mn transport

DEFF Research Database (Denmark)

Pedas, Pai Rosager; Schiller, Michaela; Hegelund, Josefine Nymark

2014-01-01

Many metabolic processes in plants are regulated by manganese (Mn) but limited information is available on the molecular mechanisms controlling cellular Mn homeostasis. In this study, a yeast assay was used to isolate and characterize two genes, MTP8.1 and MTP8.2 , which encode membrane...... in yeast, MTP8.1 and MTP8.2 were found to be Mn transporters catalysing Mn efflux in a similar manner as the Golgi localized endogenous yeast protein Pmr1p. The level of MTP8.1 transcripts in barley roots increased with external Mn supply ranging from deficiency to toxicity, while MTP8.2 transcripts...

3D Structure and Interaction of p24β and p24δ Golgi Dynamics Domains: Implication for p24 Complex Formation and Cargo Transport.

Science.gov (United States)

Nagae, Masamichi; Hirata, Tetsuya; Morita-Matsumoto, Kana; Theiler, Romina; Fujita, Morihisa; Kinoshita, Taroh; Yamaguchi, Yoshiki

2016-10-09

The p24 family consists of four subfamilies (p24α, p24β, p24γ, and p24δ), and the proteins are thought to form hetero-oligomeric complexes for efficient transport of cargo proteins from the endoplasmic reticulum to the Golgi apparatus. The proteins possess a conserved luminal Golgi dynamics (GOLD) domain, whose functions are largely unknown. Here, we present structural and biochemical studies of p24β1 and p24δ1 GOLD domains. Use of GOLD domain-deleted mutants revealed that the GOLD domain of p24δ1 is required for proper p24 hetero-oligomeric complex formation and efficient transport of GPI-anchored proteins. The p24β1 and p24δ1 GOLD domains share a common β-sandwich fold with a characteristic intrasheet disulfide bond. The GOLD domain of p24δ1 crystallized as dimers, allowing the analysis of a homophilic interaction site. Surface plasmon resonance and solution NMR analyses revealed that p24β1 and p24δ1 GOLD domains interact weakly (K d = ~10 -4 M). Bi-protein titration provided interaction site maps. We propose that the heterophilic interaction of p24 GOLD domains contributes to the formation of the p24 hetero-oligomeric complex and to efficient cargo transport. Copyright © 2016 Elsevier Ltd. All rights reserved.

Function of the Golgi-located phosphate transporter PHT4;6 is critical for senescence-associated processes in Arabidopsis

Czech Academy of Sciences Publication Activity Database

Hassler, S.; Jung, B.; Lemke, L.; Novák, Ondřej; Strnad, Miroslav; Martinoia, E.; Neuhaus, H.E.

2016-01-01

Roč. 67, č. 15 (2016), s. 4671-4684 ISSN 0022-0957 R&D Projects: GA ČR GA15-22322S; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : ammonium * cytokinin * golgi Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.830, year: 2016

Orf virus interferes with MHC class I surface expression by targeting vesicular transport and Golgi

Directory of Open Access Journals (Sweden)

Rohde Jörg

2012-07-01

Full Text Available Abstract Background The Orf virus (ORFV, a zoonotic Parapoxvirus, causes pustular skin lesions in small ruminants (goat and sheep. Intriguingly, ORFV can repeatedly infect its host, despite the induction of a specific immunity. These immune modulating and immune evading properties are still unexplained. Results Here, we describe that ORFV infection of permissive cells impairs the intracellular transport of MHC class I molecules (MHC I as a result of structural disruption and fragmentation of the Golgi apparatus. Depending on the duration of infection, we observed a pronounced co-localization of MHC I and COP-I vesicular structures as well as a reduction of MHC I surface expression of up to 50%. These subversion processes are associated with early ORFV gene expression and are accompanied by disturbed carbohydrate trimming of post-ER MHC I. The MHC I population remaining on the cell surface shows an extended half-life, an effect that might be partially controlled also by late ORFV genes. Conclusions The presented data demonstrate that ORFV down-regulates MHC I surface expression in infected cells by targeting the late vesicular export machinery and the structure and function of the Golgi apparatus, which might aid to escape cellular immune recognition.

ECA3, a Golgi-localized P_2A-type-ATPase, plays a crucial role in manganese nutrition in Arabidopsis

DEFF Research Database (Denmark)

Mills, Rebecca F.; Doherty, Melissa Louise; Lopez Marques, Rosa Laura

2008-01-01

and development, and transport processes play a key role in regulating their cellular levels. Arabidopsis (Arabidopsis thaliana) contains four P(2A)-type ATPase genes, AtECA1 to AtECA4, which are expressed in all major organs of Arabidopsis. To elucidate the physiological role of AtECA2 and AtECA3 in Arabidopsis...... not so striking because in this case all plants were severely affected. ECA3 partially restored the growth defect on high Mn of the yeast (Saccharomyces cerevisiae) pmr1 mutant, which is defective in a Golgi Ca/Mn pump (PMR1), and the yeast K616 mutant (Deltapmc1 Deltapmr1 Deltacnb1), defective in Golgi...

Structural Basis for the Interaction of the Golgi-Associated Retrograde Protein (GARP) Complex with the t-SNARE Syntaxin 6

Science.gov (United States)

Abascal-Palacios, Guillermo; Schindler, Christina; Rojas, Adriana L; Bonifacino, Juan S.; Hierro, Aitor

2016-01-01

Summary The Golgi-Associated Retrograde Protein (GARP) is a tethering complex involved in the fusion of endosome-derived transport vesicles to the trans-Golgi network through interaction with components of the Syntaxin 6/Syntaxin 16/Vti1a/VAMP4 SNARE complex. The mechanisms by which GARP and other tethering factors engage the SNARE fusion machinery are poorly understood. Herein we report the structural basis for the interaction of the human Ang2 subunit of GARP with Syntaxin 6 and the closely related Syntaxin 10. The crystal structure of Syntaxin 6 Habc domain in complex with a peptide from the N terminus of Ang2 shows a novel binding mode in which a di-tyrosine motif of Ang2 interacts with a highly conserved groove in Syntaxin 6. Structure-based mutational analyses validate the crystal structure and support the phylogenetic conservation of this interaction. The same binding determinants are found in other tethering proteins and syntaxins, suggesting a general interaction mechanism. PMID:23932592

Association of the golgi UDP-galactose transporter with UDP-galactose: ceramide galactosyltransferase allows UDP-galactose import in the endoplasmic reticulum

NARCIS (Netherlands)

Sprong, H.; Degroote, S.; Nilsson, T.; Kawakita, M.; Ishida, N.; van der Sluijs, P.; van Meer, G.

2003-01-01

UDP-galactose reaches the Golgi lumen through the UDP-galactose transporter (UGT) and is used for the galactosylation of proteins and lipids. Ceramides and diglycerides are galactosylated within the endoplasmic reticulum by the UDP-galactose: ceramide galactosyltransferase. It is not known how

Identification of rice cornichon as a possible cargo receptor for the Golgi-localized sodium transporter OsHKT1;3

Czech Academy of Sciences Publication Activity Database

Rosas-Santiago, P.; Lagunas-Goméz, D.; Barkla, B. J.; Vera-Estrella, R.; Lalonde, S.; Jones, A.; Frommer, W. B.; Zimmermannová, Olga; Sychrová, Hana; Pantoja, O.

2015-01-01

Roč. 66, č. 9 (2015), s. 2733-2748 ISSN 0022-0957 R&D Projects: GA MŠk(CZ) LD13037 Institutional support: RVO:67985823 Keywords : Cornichon * endoplasmic reticulum * Golgi * OsHKT1-3 * protein–protein interaction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.677, year: 2015

GOLGA2/GM130, cis-Golgi Matrix Protein, is a Novel Target of Anticancer Gene Therapy

OpenAIRE

Chang, Seung-Hee; Hong, Seong-Ho; Jiang, Hu-Lin; Minai-Tehrani, Arash; Yu, Kyeong-Nam; Lee, Jae-Ho; Kim, Ji-Eun; Shin, Ji-Young; Kang, Bitna; Park, Sungjin; Han, Kiwon; Chae, Chanhee; Cho, Myung-Haing

2012-01-01

Achievement of long-term survival of patients with lung cancer treated with conventional chemotherapy is still difficult for treatment of metastatic and advanced tumors. Despite recent progress in investigational therapies, survival rates are still disappointingly low and novel adjuvant and systemic therapies are urgently needed. A recently elucidated secretory pathway is attracting considerable interest as a promising anticancer target. The cis-Golgi matrix protein, GOLGA2/GM130, plays an im...

Phosphorylation in the C-terminal domain of Aquaporin-4 is required for Golgi transition in primary cultured astrocytes

International Nuclear Information System (INIS)

Kadohira, Ikuko; Abe, Yoichiro; Nuriya, Mutsuo; Sano, Kazumi; Tsuji, Shoji; Arimitsu, Takeshi; Yoshimura, Yasunori; Yasui, Masato

2008-01-01

Aquaporin-4 (AQP4) is expressed in the perivascular and subpial astrocytes end-feet in mammalian brain, and plays a critical component of an integrated water and potassium homeostasis. Here we examine whether AQP4 is phosphorylated in primary cultured mouse astrocytes. Astrocytes were metabolically labeled with [ 32 P]phosphoric acid, then AQP4 was immunoprecipitated with anti-AQP4 antibody. We observed that AQP4 was constitutively phosphorylated, which is reduced by treatment with protein kinase CK2 inhibitors. To elucidate the phosphorylation of AQP4 by CK2, myc-tagged wild-type or mutant AQP4 was transiently transfected in primary cultured astrocytes. Substitution of Ala residues for four putative CK2 phosphorylation sites in the C terminus abolished the phosphorylation of AQP4. Immunofluorescent microscopy revealed that the quadruple mutant was localized in the Golgi apparatus. These observations indicate that the C-terminal domain of AQP4 is constitutively phosphorylated at least in part by protein kinase CK2 and it is required for Golgi transition.

A membrane-anchored E-type endo-1,4-beta-glucanase is localized on Golgi and plasma membranes of higher plants.

Science.gov (United States)

Brummell, D A; Catala, C; Lashbrook, C C; Bennett, A B

1997-04-29

Endo-1,4-beta-D-glucanases (EGases, EC 3.2.1.4) are enzymes produced in bacteria, fungi, and plants that hydrolyze polysaccharides possessing a 1,4-beta-D-glucan backbone. All previously identified plant EGases are E-type endoglucanases that possess signal sequences for endoplasmic reticulum entry and are secreted to the cell wall. Here we report the characterization of a novel E-type plant EGase (tomato Cel3) with a hydrophobic transmembrane domain and structure typical of type II integral membrane proteins. The predicted protein is composed of 617 amino acids and possesses seven potential sites for N-glycosylation. Cel3 mRNA accumulates in young vegetative tissues with highest abundance during periods of rapid cell expansion, but is not hormonally regulated. Antibodies raised to a recombinant Cel3 protein specifically recognized three proteins, with apparent molecular masses of 93, 88, and 53 kDa, in tomato root microsomal membranes separated by sucrose density centrifugation. The 53-kDa protein comigrated in the gradient with plasma membrane markers, the 88-kDa protein with Golgi membrane markers, and the 93-kDa protein with markers for both Golgi and plasma membranes. EGase enzyme activity was also found in regions of the density gradient corresponding to both Golgi and plasma membranes, suggesting that Cel3 EGase resides in both membrane systems, the sites of cell wall polymer biosynthesis. The in vivo function of Cel3 is not known, but the only other known membrane-anchored EGase is present in Agrobacterium tumefaciens where it is required for cellulose biosynthesis.

[Principles of nutrition in patients with newly appointed stoma].

Science.gov (United States)

Pachocka, Lucyna Małgorzata; Urbanik, Anna

2016-01-01

The treatment of intestinal stoma is often a difficult experience for patients and results in numerous problems in the physical, psychological and social aspects. Therefore, post-operative care of the patient with the newly appointed stoma should be taken by therapeutic team consisting of doctors, nurses, physiotherapists, dieticians, psychologists and social workers. Appropriate nutritional education of patients aims to improve their quality of life and to prevent from unpleasant ailments formed after the operation. The specific type of stoma may decide about certain dietary recommendations. The presented work provides a practical dietary recommendations for patients with newly appointed stoma.

Genetic, structural, and chemical insights into the dual function of GRASP55 in germ cell Golgi remodeling and JAM-C polarized localization during spermatogenesis.

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Amandine Cartier-Michaud

2017-06-01

Full Text Available Spermatogenesis is a dynamic process that is regulated by adhesive interactions between germ and Sertoli cells. Germ cells express the Junctional Adhesion Molecule-C (JAM-C, encoded by Jam3, which localizes to germ/Sertoli cell contacts. JAM-C is involved in germ cell polarity and acrosome formation. Using a proteomic approach, we demonstrated that JAM-C interacted with the Golgi reassembly stacking protein of 55 kDa (GRASP55, encoded by Gorasp2 in developing germ cells. Generation and study of Gorasp2-/- mice revealed that knock-out mice suffered from spermatogenesis defects. Acrosome formation and polarized localization of JAM-C in spermatids were altered in Gorasp2-/- mice. In addition, Golgi morphology of spermatocytes was disturbed in Gorasp2-/- mice. Crystal structures of GRASP55 in complex with JAM-C or JAM-B revealed that GRASP55 interacted via PDZ-mediated interactions with JAMs and induced a conformational change in GRASP55 with respect of its free conformation. An in silico pharmacophore approach identified a chemical compound called Graspin that inhibited PDZ-mediated interactions of GRASP55 with JAMs. Treatment of mice with Graspin hampered the polarized localization of JAM-C in spermatids, induced the premature release of spermatids and affected the Golgi morphology of meiotic spermatocytes.

Reactions of newly formed fission products in the gas phase

International Nuclear Information System (INIS)

Strickert, R.G.

1976-01-01

A dynamic gas-flow system was constructed which stopped fission products in the gas phase and rapidly separated (in less than 2 sec) volatile compounds from non-volatile ones. The filter assembly designed and used was shown to stop essentially all non-volatile fission products. Between 5 percent and 20 percent of tellurium fission-product isotopes reacted with several hydrocarbon gases to form volatile compounds, which passed through the filter. With carbon monoxide gas, volatile tellurium compound(s) (probably TeCO) were also formed with similar efficiencies. The upper limits for the yields of volatile compounds formed between CO and tin and antimony fission products were shown to be less than 0.3 percent, so tellurium nuclides, not their precursors, reacted with CO. It was found that CO reacted preferentially with independently produced tellurium atoms; the reaction efficiency of beta-produced atoms was only 27 +- 3 percent of that of the independently formed atoms. The selectivity, which was independent of the over-all reaction efficiency, was shown to be due to reaction of independently formed atoms in the gas phase. The gas phase reactions are believed to occur mainly at thermal energies because of the independence of the yield upon argon moderator mole-fraction (up to 80 percent). It was shown in some experiments that about one-half of the TeCO decomposed in passing through a filter and that an appreciable fraction (approximately 20 percent) of the tellurium atoms deposited on the filter reacted agin with CO. Other tellurium atoms on the filter surface (those formed by beta decay and those formed independently but not reacting in the gas phase) also reacted with CO, but probably somewhat less efficiently than atoms formed by TeCO decomposition. No evidence was found for formation of TeCO as a direct result of beta-decay

The Golgi localization of phosphatidylinositol transfer protein beta requires the protein kinase C-dependent phosphorylation of serine 262 and is essential for maintaining plasma membrane sphingomyelin levels.

Science.gov (United States)

van Tiel, Claudia M; Westerman, Jan; Paasman, Marten A; Hoebens, Martha M; Wirtz, Karel W A; Snoek, Gerry T

2002-06-21

Recombinant mouse phosphatidylinositol transfer protein (PI-TP)beta is a substrate for protein kinase C (PKC)-dependent phosphorylation in vitro. Based on site-directed mutagenesis and two-dimensional tryptic peptide mapping, Ser(262) was identified as the major site of phosphorylation and Ser(165) as a minor phosphorylation site. The phospholipid transfer activities of wild-type PI-TP beta and PI-TP beta(S262A) were identical, whereas PI-TP beta(S165A) was completely inactive. PKC-dependent phosphorylation of Ser(262) also had no effect on the transfer activity of PI-TP beta. To investigate the role of Ser(262) in the functioning of PI-TP beta, wtPI-TP beta and PI-TP beta(S262A) were overexpressed in NIH3T3 fibroblast cells. Two-dimensional PAGE analysis of cell lysates was used to separate PI-TP beta from its phosphorylated form. After Western blotting, wtPI-TP beta was found to be 85% phosphorylated, whereas PI-TP beta(S262A) was not phosphorylated. In the presence of the PKC inhibitor GF 109203X, the phosphorylated form of wtPI-TP beta was strongly reduced. Immunolocalization showed that wtPI-TP beta was predominantly associated with the Golgi membranes. In the presence of the PKC inhibitor, wtPI-TP beta was distributed throughout the cell similar to what was observed for PI-TP beta(S262A). In contrast to wtPI-TP beta overexpressors, cells overexpressing PI-TP beta(S262A) were unable to rapidly replenish sphingomyelin in the plasma membrane upon degradation by sphingomyelinase. This implies that PKC-dependent association with the Golgi complex is a prerequisite for PI-TP beta to express its effect on sphingomyelin metabolism.

Discrimination between Newly Formed and Aged Thrombi Using Empirical Mode Decomposition of Ultrasound B-Scan Image

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Jui Fang

2015-01-01

Full Text Available Ultrasound imaging is a first-line diagnostic method for screening the thrombus. During thrombus aging, the proportion of red blood cells (RBCs in the thrombus decreases and therefore the signal intensity of B-scan can be used to detect the thrombus age. To avoid the effect of system gain on the measurements, this study proposed using the empirical mode decomposition (EMD of ultrasound image as a strategy to classify newly formed and aged thrombi. Porcine blood samples were used for the in vitro induction of fresh and aged thrombi (at hematocrits of 40%. Each thrombus was imaged using an ultrasound scanner at different gains (15, 20, and 30 dB. Then, EMD of ultrasound signals was performed to obtain the first and second intrinsic mode functions (IMFs, which were further used to calculate the IMF-based echogenicity ratio (IER. The results showed that the performance of using signal amplitude of B-scan to reflect the thrombus age depends on gain. However, the IER is less affected by the gain in discriminating between fresh and aged thrombi. In the future, ultrasound B-scan combined with the EMD may be used to identify the thrombus age for the establishment of thrombolytic treatment planning.

Yeast Interacting Proteins Database: YHL002W, YNR006W [Yeast Interacting Proteins Database

Lifescience Database Archive (English)

Full Text Available ycling of Golgi proteins and formation of lumenal membranes Rows with this bait as bait (1) Rows with this b...required for recycling Golgi proteins, forming lumenal membranes and sorting ubiquitinated proteins destined...on, as well as for recycling of Golgi proteins and formation of lumenal membranes...ith Hse1p; required for recycling Golgi proteins, forming lumenal membranes and sorting ubiquitinated protei

Yeast Interacting Proteins Database: YNR006W, YHL002W [Yeast Interacting Proteins Database

Lifescience Database Archive (English)

Full Text Available ling Golgi proteins, forming lumenal membranes and sorting ubiquitinated proteins destined for degradation; ..., as well as for recycling of Golgi proteins and formation of lumenal membranes Rows with this prey as prey ...1p; required for recycling Golgi proteins, forming lumenal membranes and sorting ubiquitinated proteins dest...degradation, as well as for recycling of Golgi proteins and formation of lumenal membranes

Being a team leader: newly registered nurses relate their experiences.

Science.gov (United States)

Ekström, Louise; Idvall, Ewa

2015-01-01

This paper presents a study that explores how newly qualified registered nurses experience their leadership role in the ward-based nursing care team. A nurse's clinical leadership affects the quality of care provided. Newly qualified nurses experience difficulties during the transition period from student to qualified professional and find it challenging to lead nursing care. Twelve nurses were interviewed and the transcribed texts analysed using qualitative content analysis to assess both manifest and latent content. Five themes were identified: feeling stranded; forming well-functioning teams; learning to lead; having the courage, strength, and desire to lead; and ensuring appropriate care. The findings indicate that many factors limit nurses' leadership but some circumstances are supportive. The leadership prerequisites for newly registered nurses need to improve, emphasizing different ways to create a supportive atmosphere that promotes professional development and job satisfaction. To increase nurse retention and promote quality of care, nurse managers need to clarify expectations and guide and support newly qualified nurses in a planned way. © 2013 John Wiley & Sons Ltd.

Functional genomics indicates yeast requires Golgi/ER transport, chromatin remodeling, and DNA repair for low dose DMSO tolerance

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Brandon David Gaytán

2013-08-01

Full Text Available Dimethyl sulfoxide (DMSO is frequently utilized as a solvent in toxicological and pharmaceutical investigations. It is therefore important to establish the cellular and molecular targets of DMSO in order to differentiate its intrinsic effects from those elicited by a compound of interest. We performed a genome-wide functional screen in Saccharomyces cerevisiae to identify deletion mutants exhibiting sensitivity to 1% DMSO, a concentration standard to yeast chemical profiling studies. We report that mutants defective in Golgi/ER transport are sensitive to DMSO, including those lacking components of the conserved oligomeric Golgi (COG complex. Moreover, strains deleted for members of the SWR1 histone exchange complex are hypersensitive to DMSO, with additional chromatin remodeling mutants displaying a range of growth defects. We also identify DNA repair genes important for DMSO tolerance. Finally, we demonstrate that overexpression of histone H2A.Z, which replaces chromatin-associated histone H2A in a SWR1-catalyzed reaction, confers resistance to DMSO. Many yeast genes described in this study have homologs in more complex organisms, and the data provided is applicable to future investigations into the cellular and molecular mechanisms of DMSO toxicity.

Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis.

Science.gov (United States)

Partridge, Emily A; Le Roy, Christine; Di Guglielmo, Gianni M; Pawling, Judy; Cheung, Pam; Granovsky, Maria; Nabi, Ivan R; Wrana, Jeffrey L; Dennis, James W

2004-10-01

The Golgi enzyme beta1,6 N-acetylglucosaminyltransferase V (Mgat5) is up-regulated in carcinomas and promotes the substitution of N-glycan with poly N-acetyllactosamine, the preferred ligand for galectin-3 (Gal-3). Here, we report that expression of Mgat5 sensitized mouse cells to multiple cytokines. Gal-3 cross-linked Mgat5-modified N-glycans on epidermal growth factor and transforming growth factor-beta receptors at the cell surface and delayed their removal by constitutive endocytosis. Mgat5 expression in mammary carcinoma was rate limiting for cytokine signaling and consequently for epithelial-mesenchymal transition, cell motility, and tumor metastasis. Mgat5 also promoted cytokine-mediated leukocyte signaling, phagocytosis, and extravasation in vivo. Thus, conditional regulation of N-glycan processing drives synchronous modification of cytokine receptors, which balances their surface retention against loss via endocytosis.

Flagellation of Pseudomonas aeruginosa in newly divided cells

Science.gov (United States)

Zhao, Kun; Lee, Calvin; Anda, Jaime; Wong, Gerard

2015-03-01

For monotrichous bacteria, Pseudomonas aeruginosa, after cell division, one daughter cell inherits the old flagellum from its mother cell, and the other grows a new flagellum during or after cell division. It had been shown that the new flagellum grows at the distal pole of the dividing cell when the two daughter cells haven't completely separated. However, for those daughter cells who grow new flagella after division, it still remains unknown at which pole the new flagellum will grow. Here, by combining our newly developed bacteria family tree tracking techniques with genetic manipulation method, we showed that for the daughter cell who did not inherit the old flagellum, a new flagellum has about 90% chances to grow at the newly formed pole. We proposed a model for flagellation of P. aeruginosa.

Identification and functional analysis of two Golgi-localized UDP-galactofuranose transporters with overlapping functions in Aspergillus niger.

Science.gov (United States)

Park, Joohae; Tefsen, Boris; Heemskerk, Marc J; Lagendijk, Ellen L; van den Hondel, Cees A M J J; van Die, Irma; Ram, Arthur F J

2015-11-02

Galactofuranose (Galf)-containing glycoconjugates are present in numerous microbes, including filamentous fungi where they are important for morphology, virulence and maintaining cell wall integrity. The incorporation of Galf-residues into galactomannan, galactomannoproteins and glycolipids is carried out by Golgi-localized Galf transferases. The nucleotide sugar donor used by these transferases (UDP-Galf) is produced in the cytoplasm and has to be transported to the lumen of the Golgi by a dedicated nucleotide sugar transporter. Based on homology with recently identified UDP-Galf-transporters in A. fumigatus and A. nidulans, two putative UDP-Galf-transporters in A. niger were found. Their function and localization was determined by gene deletions and GFP-tagging studies, respectively. The two putative UDP-Galf-transporters in A. niger are homologous to each other and are predicted to contain eleven transmembrane domains (UgtA) or ten transmembrane domains (UgtB) due to a reduced length of the C-terminal part of the UgtB protein. The presence of two putative UDP-Galf-transporters in the genome was not unique for A. niger. From the twenty Aspergillus species analysed, nine species contained two additional putative UDP-Galf-transporters. Three of the nine species were outside the Aspergillus section nigri, indication an early duplication of UDP-Galf-transporters and subsequent loss of the UgtB copy in several aspergilli. Deletion analysis of the single and double mutants in A. niger indicated that the two putative UDP-Galf-transporters (named UgtA and UgtB) have a redundant function in UDP-Galf-transport as only the double mutant displayed a Galf-negative phenotype. The Galf-negative phenotype of the double mutant could be complemented by expressing either CFP-UgtA or CFP-UgtB fusion proteins from their endogenous promoters, indicating that both CFP-tagged proteins are functional. Both Ugt proteins co-localize with each other as well as with the GDP

Force estimation from ensembles of Golgi tendon organs

Science.gov (United States)

Mileusnic, M. P.; Loeb, G. E.

2009-06-01

Golgi tendon organs (GTOs) located in the skeletal muscles provide the central nervous system with information about muscle tension. The ensemble firing of all GTO receptors in the muscle has been hypothesized to represent a reliable measure of the whole muscle force but the precision and accuracy of that information are largely unknown because it is impossible to record activity simultaneously from all GTOs in a muscle. In this study, we combined a new mathematical model of force sampling and transduction in individual GTOs with various models of motor unit (MU) organization and recruitment simulating various normal, pathological and neural prosthetic conditions. Our study suggests that in the intact muscle the ensemble GTO activity accurately encodes force information according to a nonlinear, monotonic relationship that has its steepest slope for low force levels and tends to saturate at the highest force levels. The relationship between the aggregate GTO activity and whole muscle tension under some pathological conditions is similar to one seen in the intact muscle during rapidly modulated, phasic excitation of the motor pool (typical for many natural movements) but quite different when the muscle is activated slowly or held at a given force level. Substantial deviations were also observed during simulated functional electrical stimulation.

Further obsrvations on a newly located prawn fishery off Saurashtra coast

Digital Repository Service at National Institute of Oceanography (India)

Gopalan, U.K.

The abundance of prawns in a newly located ground off Saurashtra has been described Catch omposition showed that Metapenaeus affinis formed the bulk of the catches Previously this species was thought to be of not much commercial importance...

Regulation of traffic and organelle architecture of the ER-Golgi interface by signal transduction.

Science.gov (United States)

Tillmann, Kerstin D; Millarte, Valentina; Farhan, Hesso

2013-09-01

The components that control trafficking between organelles of the secretory pathway as well as their architecture were uncovered to a reasonable extent in the past decades. However, only recently did we begin to explore the regulation of the secretory pathway by cellular signaling. In the current review, we focus on trafficking between the endoplasmic reticulum and the Golgi apparatus. We highlight recent advances that have been made toward a better understanding of how the secretory pathway is regulated by signaling and discuss how this knowledge is important to obtain an integrative view of secretion in the context of other homeostatic processes such as growth and proliferation.

Evaluation of a magnetic particles-based chemiluminescence enzyme immunoassay for Golgi protein 73 in human serum.

Science.gov (United States)

Liu, Xiangyi; Wan, Xiaohua; Lu, Sheng; Zhang, Lijun; Yu, Shaohua; Lu, Xinxin

2015-05-20

Golgi protein 73 (GP73) is regarded as a potential serum biomarker for early diagnosis of hepatocellular carcinoma (HCC). We developed a rapid magnetic particles-based chemiluminescence enzyme immunoassay (MPs-CLEIA) for the determination of serum GP73. Fluorescein isothiocyanate (FITC) and alkaline phosphatase (ALP) were used to label 2 different monoclonal antibodies to GP73. Serum GP73 was captured with labeled antibodies and formed a sandwiched immunoreaction. The magnetic particles (MPs) coated with anti-FITC antibody were used as a means of separation of the GP73 protein from other serum proteins. After adding the enzyme substrate solution, the relative light unit (RLU) was measured. A MPs-CLEIA for serum GP73 was established and evaluated. The RLU was directly proportional to the concentration of GP73. The method linearity was 5-600 μg/l. Limit of the blank was 2.19 μg/l. The intra- and inter-assay imprecision was 73-0.89), and the sensitivity and specificity, with cut-off value of 115.6 μg/l, were 75.4% and 92.1%, respectively. The proposed method demonstrates an acceptable performance for quantifying serum GP73. This assay could be appropriate for routine use in clinical laboratories. Copyright © 2015 Elsevier B.V. All rights reserved.

Forms of newly retained phosphorus in mineral soils

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Armi Kaila

1964-01-01

Full Text Available The distribution of soluble phosphate in various fractions of soil phosphorus was studied by treating 1 g-samples of 180 mineral soils with 50 ml of a KH2PO4- solution containing P 5 mg/l for 24 hours, and carrying out the fractionation by the method of CHANG and JACKSON after the solution was removed and the moist samples had stood for 3 days at room temperature. The amount of retained phosphorus in the different fractions was computed by taking the difference between the treated and check samples. In the 70 samples of clay soils, the mean proportion of the retained phosphorus was 57 per cent of the 250 mg/kg applied, in the 62 samples of the sand and fine sand soils the corresponding part was 45 per cent, and in the 48 samples of loam and silt soils it was 44 per cent. The higher retention in the clay soils was mainly due to a higher retention in the alkali-soluble fraction. The net increase in the fluoride-soluble forms was of the same order in these three soil groups. On the average, more than 95 per cent of the sorbed phosphorus was found in the fluoride-soluble and alkali-soluble fractions. In one third of the samples a low net increase in the acid soluble fraction was detected, but this may be partly due to changes in the solubility of the native phosphorus in the treated samples. Owing to the fairly large variation, the tendency to somewhat higher mean values for the sorption in the subsoils compared with those of the topsoils was not statistically significant. The ratio between the sorbed amounts of fluoride-soluble and alkali soluble forms was higher in the sand and fine sand soils than in the clay soils. Only in 15 samples, most of them Litorina-soils, the net increase in the alkali-soluble forms was higher than in the fluoride-soluble fraction. Probably, because an equilibrium in the phosphorus conditions was not yet reached at the end of the treatment, the attempt failed to find any clear connection between the distribution of the

The trans-Golgi SNARE syntaxin 10 is required for optimal development of Chlamydia trachomatis

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Andrea L Lucas

2015-09-01

Full Text Available Chlamydia trachomatis, an obligate intracellular pathogen, grows inside of a vacuole, termed the inclusion. Within the inclusion, the organisms differentiate from the infectious elementary body (EB into the reticulate body (RB. The RB communicates with the host cell through the inclusion membrane to obtain the nutrients necessary to divide, thus expanding the chlamydial population. At late time points within the developmental cycle, the RBs respond to unknown molecular signals to redifferentiate into infectious EBs to perpetuate the infection cycle. One strategy for Chlamydia to obtain necessary nutrients and metabolites from the host is to intercept host vesicular trafficking pathways. In this study we demonstrate that a trans-Golgi soluble N-ethylmaleimide–sensitive factor attachment protein (SNARE, syntaxin 10, and/or syntaxin10-associated Golgi elements colocalize with the chlamydial inclusion. We hypothesized that Chlamydia utilizes the molecular machinery of syntaxin 10 at the inclusion membrane to intercept specific vesicular trafficking pathways in order to create and maintain an optimal intra-inclusion environment. To test this hypothesis, we used siRNA knockdown of syntaxin 10 to examine the impact of the loss of syntaxin 10 on chlamydial growth and development. Our results demonstrate that loss of syntaxin 10 leads to defects in normal chlamydial maturation including: variable inclusion size with fewer chlamydial organisms per inclusion, fewer infectious progeny, and delayed or halted RB-EB differentiation. These defects in chlamydial development correlate with an overabundance of NBD-lipid retained by inclusions cultured in syntaxin 10 knockdown cells. Overall, loss of syntaxin 10 at the inclusion membrane negatively affects Chlamydia. Understanding host machinery involved in maintaining an optimal inclusion environment to support chlamydial growth and development is critical towards understanding the molecular signals involved in

Hepatitis C virus replication and Golgi function in brefeldin a-resistant hepatoma-derived cells.

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Rayan Farhat

Full Text Available Recent reports indicate that the replication of hepatitis C virus (HCV depends on the GBF1-Arf1-COP-I pathway. We generated Huh-7-derived cell lines resistant to brefeldin A (BFA, which is an inhibitor of this pathway. The resistant cell lines could be sorted into two phenotypes regarding BFA-induced toxicity, inhibition of albumin secretion, and inhibition of HCV infection. Two cell lines were more than 100 times more resistant to BFA than the parental Huh-7 cells in these 3 assays. This resistant phenotype was correlated with the presence of a point mutation in the Sec7 domain of GBF1, which is known to impair the binding of BFA. Surprisingly, the morphology of the cis-Golgi of these cells remained sensitive to BFA at concentrations of the drug that allowed albumin secretion, indicating a dichotomy between the phenotypes of secretion and Golgi morphology. Cells of the second group were about 10 times more resistant than parental Huh-7 cells to the BFA-induced toxicity. The EC50 for albumin secretion was only 1.5-1.8 fold higher in these cells than in Huh-7 cells. However their level of secretion in the presence of inhibitory doses of BFA was 5 to 15 times higher. Despite this partially effective secretory pathway in the presence of BFA, the HCV infection was almost as sensitive to BFA as in Huh-7 cells. This suggests that the function of GBF1 in HCV replication does not simply reflect its role of regulator of the secretory pathway of the host cell. Thus, our results confirm the involvement of GBF1 in HCV replication, and suggest that GBF1 might fulfill another function, in addition to the regulation of the secretory pathway, during HCV replication.

The role of the active site Zn in the catalytic mechanism of the GH38 Golgi alpha-mannosidase II: Implications from noeuromycin inhibition

DEFF Research Database (Denmark)

Bols, Mikael; Kuntz, Douglas A.; Rose, David R.

2006-01-01

Golgi alpha-mannosidase II (GMII) is a Family 38 glycosyl hydrolase involved in the eukaryotic N-glycosylation pathway in protein synthesis. Understanding of its catalytic mechanism has been of interest for the development of specific inhibitors that could lead to novel anti-metastatic or anti-in...

UAV observation of newly formed volcanic island, Nishinoshima, Japan, from a ship

Science.gov (United States)

Ohminato, T.; Kaneko, T.; Takagi, A.

2016-12-01

We conducted an aerial observation at Nishinoshima island, south of Japan, from Jun 7 to Jun 9, 2016 by using an Unmanned Aerial Vehicle (UAV), a radio controlled small helicopter. Takeoff and landing of the UAV was conducted on a ship. Nishinoshima is a small island, 130km west of Chichijima in Ogasawara Islands, Japan. New eruption started in November 2013 in a shallow sea approximately 400 m southeast of the existing Nishinoshima Island. It started from a small islet and evolved with 1-5 × 105 m3/day discharge rate (Maeno et al, 2016). In late December 2013, the islet coalesced with the existing Nishinoshima. In 16 month, the lava field reached 2.6×106 m2and covered almost all of the existing Nishinoshima. Human landing upon the newly formed part of the island has still been prohibited due to the danger of sudden eruptions. Before our mission, some pumice or rock samples had been taken from the island but their amount was not enough to conduct detailed petrological analyses. The evolution of the lava field from the central cone has been well documented by using images taken from satellites and airplanes. However, due to the limited resolution of satellite images or photos taken from distant airplanes, there still be uncertainties in detailed morphological evolution of lava flows. The purpose of our observation includes, 1) sampling of pyroclasts near the central cone in order to investigate the condition of magma chamber and magma ascent process, and 2) taking high resolution 4K images in order to clarify the characteristic morphology of the lava flow covering the island. During the three days operation, we were successfully able to sample 250g of pyroclasts and to take 1.5TB of 4K movies. Conducting UAV's takeoff and landing on a ship was not an easy task. We used a marine research ship, Keifu-Maru, operated by Japan Meteorological Agency. The ship size is 1483 tons. On the ship deck, there are several structures which can interfere with the helicopter

Research advances in association between Golgi protein 73 and liver diseases

Directory of Open Access Journals (Sweden)

WEI Fengxian

2017-08-01

Full Text Available Golgi protein 73 (GP73 has a very low expression level in normal people, while it has a significantly higher expression level in patients with liver diseases and hepatocellular carcinoma (HCC, and therefore, it may become a new marker for HCC. This article introduces the distribution of GP73 in human body and definitions of different subtypes of GP73 and elaborates on its association with benign/malignant liver diseases and surgical operation based on the subtypes of GP73, as well as the application of GP73 in the differentiation of benign/malignant liver diseases. Since GP73 is closely associated with the development, progression, and prognosis of liver diseases, this article summarizes the latest advances in basic research, introduces the structural basis of fucosylated GP73 and proliferation, migration, and invasion of hepatoma cells and known signaling pathways, and lists the factors which affect the expression of GP73.

GOLGA2, Encoding A Master Regulator of Golgi Apparatus, Is Mutated in A Patient with A Neuromuscular Disorder

OpenAIRE

Shamseldin, Hanan E; Bennett, Alexis H; Alfadhel, Majid; Gupta, Vandana; Alkuraya, Fowzan S

2016-01-01

Golgi apparatus (GA) is a membrane-bound organelle that serves a multitude of critical cellular functions including protein secretion and sorting, and cellular polarity. Many Mendelian diseases are caused by mutations in genes encoding various components of GA. GOLGA2 encodes GM130, a necessary component for the assembly of GA as a single complex, and its deficiency has been found to result in severe cellular phenotypes. We describe the first human patient with a homozygous apparently loss of...

Immunomicroscopic localization of aminopeptidase N in the pig enterocyte. Implications for the route of intracellular transport

DEFF Research Database (Denmark)

Hansen, Gert Helge; Sjöström, H; Norén, Ove

1987-01-01

The subcellular localization of aminopeptidase N (EC 3.4.11.2) in the pig enterocyte was investigated by immunofluorescence and immunoelectron microscopy (immunogold staining). By indirect immunofluorescence on either frozen or paraffin-embedded sections, a very intense staining in the microvillar....... Labelling was demonstrated in the Golgi apparatus and in a minor fraction of the intracellular smooth vesicles positioned between the Golgi apparatus and the microvillar membrane. These observations are compatible with the view that newly synthesized aminopeptidase N is delivered directly to the microvillar...

Influence of copper on the Golgi apparatus of the meristematic cells of the horse-bean - Vicia faba c. v. Povazsky

Energy Technology Data Exchange (ETDEWEB)

Kostal, L

1974-01-01

The influence of copper on the Golgi apparatus of beans was investigated. At 1 mg/l copper was toxic within 24 hours. After application of 1 mg/l Cu, a striking increase in the number of split vesicles was noted together with a significant decrease in the number of cisterns. The endoplasmic reticulum is often fragmented after application of Cu, showing separation of membrane.

Form Filling with Self-Compacting Concrete

DEFF Research Database (Denmark)

Thrane, Lars Nyholm

2002-01-01

This paper describes a newly started Ph.D. project with the aim of simulating the form filling ability of Self-Compacting Concrete (SCC) taking into account the form geometry, reinforcement configuration, casting technique, and the rheological properties of the concrete. Comparative studies...

Apoptosis-linked Gene-2 (ALG-2)/Sec31 Interactions Regulate Endoplasmic Reticulum (ER)-to-Golgi Transport

Science.gov (United States)

Helm, Jared R.; Bentley, Marvin; Thorsen, Kevin D.; Wang, Ting; Foltz, Lauren; Oorschot, Viola; Klumperman, Judith; Hay, Jesse C.

2014-01-01

Luminal calcium released from secretory organelles has been suggested to play a regulatory role in vesicle transport at several steps in the secretory pathway; however, its functional roles and effector pathways have not been elucidated. Here we demonstrate for the first time that specific luminal calcium depletion leads to a significant decrease in endoplasmic reticulum (ER)-to-Golgi transport rates in intact cells. Ultrastructural analysis revealed that luminal calcium depletion is accompanied by increased accumulation of intermediate compartment proteins in COPII buds and clusters of unfused COPII vesicles at ER exit sites. Furthermore, we present several lines of evidence suggesting that luminal calcium affected transport at least in part through calcium-dependent interactions between apoptosis-linked gene-2 (ALG-2) and the Sec31A proline-rich region: 1) targeted disruption of ALG-2/Sec31A interactions caused severe defects in ER-to-Golgi transport in intact cells; 2) effects of luminal calcium and ALG-2/Sec31A interactions on transport mutually required each other; and 3) Sec31A function in transport required luminal calcium. Morphological phenotypes of disrupted ALG-2/Sec31A interactions were characterized. We found that ALG-2/Sec31A interactions were not required for the localization of Sec31A to ER exit sites per se but appeared to acutely regulate the stability and trafficking of the cargo receptor p24 and the distribution of the vesicle tether protein p115. These results represent the first outline of a mechanism that connects luminal calcium to specific protein interactions regulating vesicle trafficking machinery. PMID:25006245

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.

Drosophila egghead encodes a beta 1,4-mannosyltransferase predicted to form the immediate precursor glycosphingolipid substrate for brainiac

DEFF Research Database (Denmark)

Wandall, Hans H; Pedersen, Johannes W; Park, Chaeho

2002-01-01

-N-acetylglucosamine:beta Man beta 1,3-N-acetylglucosaminyltransferase (beta 3GlcNAc-transferase) tentatively assigned a key role in biosynthesis of arthroseries glycosphingolipids and forming the trihexosylceramide, GlcNAc beta 1-3Man beta 1-4Glc beta 1-1Cer. In the present study we demonstrate that egghead encodes a Golgi......-located GDP-mannose:beta Glc beta 1,4-mannosyltransferase tentatively assigned a biosynthetic role to form the precursor arthroseries glycosphingolipid substrate for Brainiac, Man beta 1-4Glc beta 1-1Cer. Egghead is unique among eukaryotic glycosyltransferase genes in that homologous genes are limited...

The regulation of ER export and Golgi retention of ST3Gal5 (GM3/GM4 synthase) and B4GalNAcT1 (GM2/GD2/GA2 synthase) by arginine/lysine-based motif adjacent to the transmembrane domain.

Science.gov (United States)

Uemura, Satoshi; Shishido, Fumi; Kashimura, Madoka; Inokuchi, Jin-ichi

2015-12-01

In the Golgi maturation model, the Golgi cisternae dynamically mature along a secretory pathway. In this dynamic process, glycosyltransferases are transported from the endoplasmic reticulum (ER) to the Golgi apparatus where they remain and function. The precise mechanism behind this maturation process remains unclear. We investigated two glycosyltransferases, ST3Gal5 (ST3G5) and B4GalNAcT1 (B4GN1), involved in ganglioside synthesis and examined their signal sequences for ER export and Golgi retention. Reports have suggested that the [R/K](X)[R/K] motif functions as an ER exporting signal; however, this signal sequence is insufficient in stably expressed, full-length ST3G5. Through further analysis, we have clarified that the (2)R(3)R(X)(5) (9)K(X)(3) (13)K sequence in ST3G5 is essential for ER export. We have named the sequence the R/K-based motif. On the other hand, for ER export of B4GN1, the homodimer formation in addition to the R/K-based motif is required for ER export suggesting the importance of unidentified lumenal side interaction. We found that ST3G5 R2A/R3A and K9A/K13A mutants localized not only in Golgi apparatus but also in endosomes. Furthermore, the amounts of mature type asparagine-linked (N)-glycans in ST3G5 R2A/R3A and K9A/K13A mutants were decreased compared with those in wild-type proteins, and the stability of the mutants was lower. These results suggest that the R/K-based motif is necessary for the Golgi retention of ST3G5 and that the retention is involved in the maturation of N-glycans and in stability. Thus, several basic amino acids located on the cytoplasmic tail of ST3G5 play important roles in both ER export and Golgi retention. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Localization and biosynthesis of aminopeptidase N in pig fetal small intestine

DEFF Research Database (Denmark)

Danielsen, E M; Niels-Christiansen, L L; Hansen, Gert Helge

1995-01-01

BACKGROUND & AIMS: Little is known about the expression of brush border enzymes in fetal enterocytes. The aim of this study was to describe the localization and biosynthesis of porcine fetal aminopeptidase N. METHODS: This study was performed using histochemistry and immunoelectron microscopy......, and large vacuoles in the apical cytoplasm. The transient high mannose-glycosylated form of fetal aminopeptidase N was processed to the mature complex-glycosylated form at a markedly slower rate than the enzyme in adult intestine. Likewise, dimerization occurred slowly compared with the adult form...... of aminopeptidase N, and it took place mainly after the Golgi-associated complex glycosylation. The enzyme had a biphasic appearance in the Mg(2+)-precipitated and microvillar fractions, indicating that the bulk of newly made aminopeptidase N is transported to the brush border membrane before appearing...

Metallic nanomaterials formed by exerting large plastic strains

International Nuclear Information System (INIS)

Richert, M; Richert, J.; Zasadzinski, J.; Hawrylkiewicz, S.

2002-01-01

The investigations included pure Al and Cu single crystals, AlMg5 alloy and AlCuZr alloy have been presented. The materials were deformed by the cyclic extrusion compression method (CEC) within the range of true strains φ = 0.4-59.8 (1 to 67 deformation cycles by the CEC method). In all examined materials a strong tendency to form banded was observed. Within the range of very large plastic strains there was observed intensive rebuilding of the banded microstructure into subgrains, at first of rhombic shape, and next into equiaxial subgrains. A characteristic feature of the newly formed subgrains, not encountered in the range of conventional deformations, was the occurrence of large misorientation angles between the newly formed subgrains. The proportion of large misorientation angles in the microstructure varied, and it increased with increasing deformation. Reduction of the recovery process in AlMg5 and AlCuZr alloys preserved the growth of the newly formed nanograins, favoring the retaining of the nanomeric dimensions. This results show that there is the effective possibility of production of metallic nanomaterials by exerting of very large nonconventional plastic strains. (author)

Prostaglandin E (dmPGE{sub 2}) action in vitro on the activity of rat liver Golgi apparatus galactosyltransferase

Energy Technology Data Exchange (ETDEWEB)

Kordowiak, A.M.; Tomecki, J.; Procyk, K.; Kapusta, P. [Uniwersytet Jagiellonski, Cracow (Poland)

1993-12-31

In vitro addition of 16,16`-dimethyl prostaglandin E{sub 2} to Golgi-rich membrane fraction in final concentration of 0.1 {mu}g/1 mg of protein increased generally the activity of galactosyltransferase in comparison with control. The percentage of phospholipids in the whole fraction was similar in both investigated groups, only the sum of phosphatidylenoamine + phosphatidic acid was significantly lower after addition of dmPGE{sub 2} than in the control (0.001 < P < 0.01). (author). 25 refs, 2 figs, 1 tab.

VvGONST-A and VvGONST-B are Golgi-localised GDP-sugar transporters in grapevine (Vitis vinifera L.).

Science.gov (United States)

Utz, Daniella; Handford, Michael

2015-02-01

Plant nucleotide-sugar transporters (NSTs) are responsible for the import of nucleotide-sugar substrates into the Golgi lumen, for subsequent use in glycosylation reactions. NSTs are specific for either GDP- or UDP-sugars, and almost all transporters studied to date have been isolated from Arabidopsis thaliana L. In order to determine the conservation of the import mechanism in other higher plant species, here we report the identification and characterisation of VvGONST-A and VvGONST-B from grapevine (Vitis vinifera L. cv. Thompson Seedless), which are the orthologues of the GDP-sugar transporters GONST3 and GONST4 in Arabidopsis. Both grapevine NSTs possess the molecular features characteristic of GDP-sugar transporters, including a GDP-binding domain (GXL/VNK) towards the C-terminal. VvGONST-A and VvGONST-B expression is highest at berry setting and decreases throughout berry development and ripening. Moreover, we show using green fluorescent protein (GFP) tagged versions and brefeldin A treatments, that both are localised in the Golgi apparatus. Additionally, in vitro transport assays after expression of both NSTs in tobacco leaves indicate that VvGONST-A and VvGONST-B are capable of transporting GDP-mannose and GDP-glucose, respectively, but not a range of other UDP- and GDP-sugars. The possible functions of these NSTs in glucomannan synthesis and/or glycosylation of sphingolipids are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries

Directory of Open Access Journals (Sweden)

Meritxell Reverter

2014-05-01

Full Text Available Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN. Here, using Chinese hamster ovary (CHO Niemann-Pick type C1 (NPC1 mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6 accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs. This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion.

Cutis laxa and fatal pulmonary hypertension: a newly recognized syndrome?

OpenAIRE

Brunetti-Pierri, N; Piccolo, P; Morava, Eva; Wevers, RA; McGuirk, M; Johnson, YR; Urban, Z; Dishop, MK; Potocki, L

2011-01-01

Cutis laxa is a connective tissue disorder with distinctive lax, redundant, and inelastic skin. It is a genetically heterogenous disorder with autosomal dominant and recessive patterns of inheritance. We report a patient with cutis laxa supported by clinical, microscopic, and ultrastructural findings. Molecular analysis of fibulin-4 and -5, of the α2 subunit of the V-type H+ ATPase, and of the component of the oligomeric Golgi complex 7 (COG7) genes excluded the type I and type II autosomal r...

The Golgi-Localized γ-Ear-Containing ARF-Binding (GGA Proteins Alter Amyloid-β Precursor Protein (APP Processing through Interaction of Their GAE Domain with the Beta-Site APP Cleaving Enzyme 1 (BACE1.

Directory of Open Access Journals (Sweden)

Bjoern von Einem

Full Text Available Proteolytic processing of amyloid-β precursor protein (APP by beta-site APP cleaving enzyme 1 (BACE1 is the initial step in the production of amyloid beta (Aβ, which accumulates in senile plaques in Alzheimer's disease (AD. Essential for this cleavage is the transport and sorting of both proteins through endosomal/Golgi compartments. Golgi-localized γ-ear-containing ARF-binding (GGA proteins have striking cargo-sorting functions in these pathways. Recently, GGA1 and GGA3 were shown to interact with BACE1, to be expressed in neurons, and to be decreased in AD brain, whereas little is known about GGA2. Since GGA1 impacts Aβ generation by confining APP to the Golgi and perinuclear compartments, we tested whether all GGAs modulate BACE1 and APP transport and processing. We observed decreased levels of secreted APP alpha (sAPPα, sAPPβ, and Aβ upon GGA overexpression, which could be reverted by knockdown. GGA-BACE1 co-immunoprecipitation was impaired upon GGA-GAE but not VHS domain deletion. Autoinhibition of the GGA1-VHS domain was irrelevant for BACE1 interaction. Our data suggest that all three GGAs affect APP processing via the GGA-GAE domain.

Practicing on Newly Dead

Directory of Open Access Journals (Sweden)

Jewel Abraham

2015-07-01

Full Text Available A newly dead cadaver simulation is practiced on the physical remains of the dead before the onset of rigor mortis. This technique has potential benefits for providing real-life in-situ experience for novice providers in health care practices. Evolving ethical views in health care brings into question some of the ethical aspects associated with newly dead cadaver simulation in terms of justification for practice, autonomy, consent, and the need of disclosure. A clear statement of policies and procedures on newly dead cadaver simulation has yet to be implemented. Although there are benefits and disadvantages to an in-situ cadaver simulation, such practices should not be carried out in secrecy as there is no compelling evidence that suggests such training as imperative. Secrecy in these practices is a violation of honor code of nursing ethics. As health care providers, practitioners are obliged to be ethically honest and trustworthy to their patients. The author explores the ethical aspects of using newly dead cadaver simulation in training novice nursing providers to gain competency in various lifesaving skills, which otherwise cannot be practiced on a living individual. The author explores multiple views on cadaver simulation in relation to ethical theories and practices such as consent and disclosure to family.

Forms of Knowledge Incorporated in Clinical Decision-making among Newly-Graduated Nurses: A Metasynthesis

DEFF Research Database (Denmark)

Voldbjerg, Siri; Elgaard Sørensen, Erik; Grønkjær, Mette

2014-01-01

Clinical-decision-making is of decisive importance to how evidence-based practice is put into practice. Schools of Nursing have a responsibility to teach and train nursing students to make clinical decisions within a frame of evidence-based practice. Clinical decision-making among nurses has been...... explored from numerous angles using a diversity of methodologies. Existing research has mainly focused on promoting and inhibiting factors for implementation of evidence-based practice and incorporation of research evidence in the clinical-decision. Little attention has been given to the nurses' behavior......, including the knowledge that actually informs the newly graduated nurses’ clinical decision. The aim of the study is to combine and synthesize results from qualitative research. Noblit and Hare’s meta-ethnographic approach is used to conduct a metasynthesis of qualitative research that has studied...

In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the enzymes involved in GDP-L-fucose synthesis and Golgi import.

Science.gov (United States)

Peterson, Nathan A; Anderson, Tavis K; Wu, Xiao-Jun; Yoshino, Timothy P

2013-07-09

Carbohydrate structures of surface-expressed and secreted/excreted glycoconjugates of the human blood fluke Schistosoma mansoni are key determinants that mediate host-parasite interactions in both snail and mammalian hosts. Fucose is a major constituent of these immunologically important glycans, and recent studies have sought to characterize fucosylation-associated enzymes, including the Golgi-localized fucosyltransferases that catalyze the transfer of L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. Importantly, GDP-L-fucose is the only nucleotide-sugar donor used by fucosyltransferases and its availability represents a bottleneck in fucosyl-glycotope expression. A homology-based genome-wide bioinformatics approach was used to identify and molecularly characterize the enzymes that contribute to GDP-L-fucose synthesis and Golgi import in S. mansoni. Putative functions were further investigated through molecular phylogenetic and immunocytochemical analyses. We identified homologs of GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (GMER), which constitute a de novo pathway for GDP-L-fucose synthesis, in addition to a GDP-L-fucose transporter (GFT) that putatively imports cytosolic GDP-L-fucose into the Golgi. In silico primary sequence analyses identified characteristic Rossman loop and short-chain dehydrogenase/reductase motifs in GMD and GMER as well as 10 transmembrane domains in GFT. All genes are alternatively spliced, generating variants of unknown function. Observed quantitative differences in steady-state transcript levels between miracidia and primary sporocysts may contribute to differential glycotope expression in early larval development. Additionally, analyses of protein expression suggest the occurrence of cytosolic GMD and GMER in the ciliated epidermal plates and tegument of miracidia and primary sporocysts, respectively, which is consistent with previous localization of highly

Newly graduated nurses' use of knowledge sources

DEFF Research Database (Denmark)

Voldbjerg, Siri Lygum; Grønkjaer, Mette; Sørensen, Erik Elgaard

2016-01-01

AIM: To advance evidence on newly graduated nurses' use of knowledge sources. BACKGROUND: Clinical decisions need to be evidence-based and understanding the knowledge sources that newly graduated nurses use will inform both education and practice. Qualitative studies on newly graduated nurses' use...... underscoring progression in knowledge use and perception of competence and confidence among newly graduated nurses. CONCLUSION: The transition phase, feeling of confidence and ability to use critical thinking and reflection, has a great impact on knowledge sources incorporated in clinical decisions....... The synthesis accentuates that for use of newly graduated nurses' qualifications and skills in evidence-based practice, clinical practice needs to provide a supportive environment which nurtures critical thinking and questions and articulates use of multiple knowledge sources....

Alteraciones de la morfología dendrítica neuronal en la corteza cerebral de ratones infectados con rabia: un estudio con la técnica de Golgi

Directory of Open Access Journals (Sweden)

Orlando Torres-Fernández

2007-12-01

Conclusiones. Estos resultados son evidencia de que el virus de la rabia sí puede inducir daño neuronal estructural. Además, esta infección aparentemente interfiere con los mecanismos de impregnación argéntica del método de Golgi.

Los Alamos Plutonium Facility newly generated TRU waste certification

International Nuclear Information System (INIS)

Gruetzmacher, K.; Montoya, A.; Sinkule, B.; Maez, M.

1997-01-01

This paper presents an overview of the activities being planned and implemented to certify newly generated contact handled transuranic (TRU) waste produced by Los Alamos National Laboratory's (LANL's) Plutonium Facility. Certifying waste at the point of generation is the most important cost and labor saving step in the WIPP certification process. The pedigree of a waste item is best known by the originator of the waste and frees a site from expensive characterization activities such as those associated with legacy waste. Through a cooperative agreement with LANLs Waste Management Facility and under the umbrella of LANLs WIPP-related certification and quality assurance documents, the Plutonium Facility will be certifying its own newly generated waste. Some of the challenges faced by the Plutonium Facility in preparing to certify TRU waste include the modification and addition of procedures to meet WIPP requirements, standardizing packaging for TRU waste, collecting processing documentation from operations which produce TRU waste, and developing ways to modify waste streams which are not certifiable in their present form

Cytoarchitectonic and quantitative Golgi study of the hedgehog supraoptic nucleus.

Science.gov (United States)

Caminero, A A; Machín, C; Sanchez-Toscano, F

1992-02-01

A cytoarchitectural study was made of the supraoptic nucleus (SON) of the hedgehog with special attention to the quantitative comparison of its main neuronal types. The main purposes were (1) to relate the characteristics of this nucleus in the hedgehog (a primitive mammalian insectivorous brain) with those in the SONs of more evolutionarily advanced species; (2) to identify quantitatively the dendritic fields of the main neuronal types in the hedgehog SON and to study their synaptic connectivity. From a descriptive standpoint, 3 neuronal types were found with respect to the number of dendritic stems arising from the neuronal soma: bipolar neurons (48%), multipolar neurons (45.5%) and monopolar neurons (6.5%). Within the multipolar type 2 subtypes could be distinguished, taking into account the number of dendritic spines: (a) with few spines (93%) and (b) very spiny (7%). These results indicate that the hedgehog SON is similar to that in other species except for the very spiny neurons, the significance of which is discussed. In order to characterise the main types more satisfactorily (bipolar and multipolars with few spines) we undertook a quantitative Golgi study of their dendritic fields. Although the patterns of the dendritic field are similar in both neuronal types, the differences in the location of their connectivity can reflect functional changes and alterations in relation to the synaptic afferences.

Manganese modified CdTe/CdS quantum dots as an immunoassay biosensor for the detection of Golgi protein-73.

Science.gov (United States)

Liu, Wei; Zhang, Aixia; Xu, Guanhong; Wei, Fangdi; Yang, Jing; Hu, Qin

2016-01-05

In this paper, a new fluorescence bioassay for Golgi protein-73 (GP73), a promising marker for monitoring liver tumor, was developed by using anti-GP73 antibody (GP73 Ab) capped quantum dots (QDs) coupled with protein A/G agarose beads in an attempt to improve the analysis time, cost and operation. First, carboxylic-functionalized Mn modified CdTe/CdS QDs were synthesized and covalently conjugated with GP73 Ab, then protein A/G agarose beads were specifically combined with the QDs-conjugated Ab to form the QDs-Ab-beads conjugate, which could capture and separate GP73 from the sample through simple centrifugation. It was found that the fluorescence intensity of the above QDs-Ab-beads biosensor could be specifically quenched by GP73 added. A simple, rapid and specific quantitative method for GP73 protein was proposed using the as-prepared QDs-Ab-beads as a biosensor. Under the optimized conditions, the calibration curve of the proposed assay showed good linearity with a correlation coefficient of 0.9935 in the concentration range of 20-150 ng/mL of GP73 protein. The limit of detection (defined as 3σ/K) was 10 ng/mL. The method built exhibited a great potential in the clinic test of GP73. Copyright © 2015 Elsevier B.V. All rights reserved.

Neutral Sphingomyelinase (SMPD3) Deficiency Causes a Novel Form of Chondrodysplasia and Dwarfism That Is Rescued by Col2A1-Driven smpd3 Transgene Expression

OpenAIRE

Stoffel, Wilhelm; Jenke, Britta; Holz, Barbara; Binczek, Erika; Günter, Robert Heinz; Knifka, Jutta; Koebke, Jürgen; Niehoff, Anja

2007-01-01

Neutral sphingomyelinase SMPD3 (nSMase2), a sphingomyelin phosphodiesterase, resides in the Golgi apparatus and is ubiquitously expressed. Gene ablation of smpd3 causes a generalized prolongation of the cell cycle that leads to late embryonic and juvenile hypoplasia because of the SMPD3 deficiency in hypothalamic neurosecretory neurons. We show here that this novel form of combined pituitary hormone deficiency is characterized by the perturbation of the hypothalamus-pituitary growth axis, ass...

Newly Homeless Youth Typically Return Home

OpenAIRE

Milburn, Norweeta G.; Rosenthal, Doreen; Rotheram-Borus, Mary Jane; Mallett, Shelley; Batterham, Philip; Rice, Eric; Solorio, Rosa

2007-01-01

165 newly homeless adolescents from Melbourne, Australia and 261 from Los Angeles, United States were surveyed and followed for two years. Most newly homeless adolescents returned home (70% U.S., 47% Australia) for significant amounts of time (39% U.S., 17% Australia more than 12 months) within two years of becoming homeless.

Restoration of Compact Golgi Morphology in Advanced Prostate Cancer Enhances Susceptibility to Galectin-1-induced Apoptosis by Modifying Mucin O-glycan Synthesis

OpenAIRE

Petrosyan, Armen; Holzapfel, Melissa S.; Muirhead, David E.; Cheng, Pi-Wan

2014-01-01

Prostate cancer progression is associated with up-regulation of sialyl-T antigen produced by β-galactoside α-2,3-sialyltransferase-1 (ST3Gal1) but not with core 2-associated polylactosamine despite expression of core 2 N-acetylglucosaminyltransferase-L (C2GnT-L/GCNT1). This property allows androgen-refractory prostate cancer cells to evade galectin-1 (LGALS1)-induced apoptosis, but the mechanism is not known. We have recently reported that Golgi targeting of glycosyltransferases is mediated b...

Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding.

Science.gov (United States)

Huang, Kai-Fa; Liaw, Su-Sen; Huang, Wei-Lin; Chia, Cho-Yun; Lo, Yan-Chung; Chen, Yi-Ling; Wang, Andrew H-J

2011-04-08

Aberrant pyroglutamate formation at the N terminus of certain peptides and proteins, catalyzed by glutaminyl cyclases (QCs), is linked to some pathological conditions, such as Alzheimer disease. Recently, a glutaminyl cyclase (QC) inhibitor, PBD150, was shown to be able to reduce the deposition of pyroglutamate-modified amyloid-β peptides in brain of transgenic mouse models of Alzheimer disease, leading to a significant improvement of learning and memory in those transgenic animals. Here, we report the 1.05-1.40 Å resolution structures, solved by the sulfur single-wavelength anomalous dispersion phasing method, of the Golgi-luminal catalytic domain of the recently identified Golgi-resident QC (gQC) and its complex with PBD150. We also describe the high-resolution structures of secretory QC (sQC)-PBD150 complex and two other gQC-inhibitor complexes. gQC structure has a scaffold similar to that of sQC but with a relatively wider and negatively charged active site, suggesting a distinct substrate specificity from sQC. Upon binding to PBD150, a large loop movement in gQC allows the inhibitor to be tightly held in its active site primarily by hydrophobic interactions. Further comparisons of the inhibitor-bound structures revealed distinct interactions of the inhibitors with gQC and sQC, which are consistent with the results from our inhibitor assays reported here. Because gQC and sQC may play different biological roles in vivo, the different inhibitor binding modes allow the design of specific inhibitors toward gQC and sQC.

Cytoarchitectonic and quantitative Golgi study of the hedgehog supraoptic nucleus.

Science.gov (United States)

Caminero, A A; Machín, C; Sanchez-Toscano, F

1992-01-01

A cytoarchitectural study was made of the supraoptic nucleus (SON) of the hedgehog with special attention to the quantitative comparison of its main neuronal types. The main purposes were (1) to relate the characteristics of this nucleus in the hedgehog (a primitive mammalian insectivorous brain) with those in the SONs of more evolutionarily advanced species; (2) to identify quantitatively the dendritic fields of the main neuronal types in the hedgehog SON and to study their synaptic connectivity. From a descriptive standpoint, 3 neuronal types were found with respect to the number of dendritic stems arising from the neuronal soma: bipolar neurons (48%), multipolar neurons (45.5%) and monopolar neurons (6.5%). Within the multipolar type 2 subtypes could be distinguished, taking into account the number of dendritic spines: (a) with few spines (93%) and (b) very spiny (7%). These results indicate that the hedgehog SON is similar to that in other species except for the very spiny neurons, the significance of which is discussed. In order to characterise the main types more satisfactorily (bipolar and multipolars with few spines) we undertook a quantitative Golgi study of their dendritic fields. Although the patterns of the dendritic field are similar in both neuronal types, the differences in the location of their connectivity can reflect functional changes and alterations in relation to the synaptic afferences. Images Fig. 2 Fig. 3 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:1452481

Active Dendrites and Differential Distribution of Calcium Channels Enable Functional Compartmentalization of Golgi Cells.

Science.gov (United States)

Rudolph, Stephanie; Hull, Court; Regehr, Wade G

2015-11-25

Interneurons are essential to controlling excitability, timing, and synaptic integration in neuronal networks. Golgi cells (GoCs) serve these roles at the input layer of the cerebellar cortex by releasing GABA to inhibit granule cells (grcs). GoCs are excited by mossy fibers (MFs) and grcs and provide feedforward and feedback inhibition to grcs. Here we investigate two important aspects of GoC physiology: the properties of GoC dendrites and the role of calcium signaling in regulating GoC spontaneous activity. Although GoC dendrites are extensive, previous studies concluded they are devoid of voltage-gated ion channels. Hence, the current view holds that somatic voltage signals decay passively within GoC dendrites, and grc synapses onto distal dendrites are not amplified and are therefore ineffective at firing GoCs because of strong passive attenuation. Using whole-cell recording and calcium imaging in rat slices, we find that dendritic voltage-gated sodium channels allow somatic action potentials to activate voltage-gated calcium channels (VGCCs) along the entire dendritic length, with R-type and T-type VGCCs preferentially located distally. We show that R- and T-type VGCCs located in the dendrites can boost distal synaptic inputs and promote burst firing. Active dendrites are thus critical to the regulation of GoC activity, and consequently, to the processing of input to the cerebellar cortex. In contrast, we find that N-type channels are preferentially located near the soma, and control the frequency and pattern of spontaneous firing through their close association with calcium-activated potassium (KCa) channels. Thus, VGCC types are differentially distributed and serve specialized functions within GoCs. Interneurons are essential to neural processing because they modulate excitability, timing, and synaptic integration within circuits. At the input layer of the cerebellar cortex, a single type of interneuron, the Golgi cell (GoC), carries these functions. The

Immunoparesis in newly diagnosed Multiple Myeloma patients

DEFF Research Database (Denmark)

Sorrig, Rasmus; Klausen, Tobias W.; Salomo, Morten

2017-01-01

Immunoparesis (hypogammaglobulinemia) is associated to an unfavorable prognosis in newly diagnosed Multiple myeloma (MM) patients. However, this finding has not been validated in an unselected population-based cohort. We analyzed 2558 newly diagnosed MM patients in the Danish Multiple Myeloma...

Phase transitions of antibiotic clarithromycin forms I, IV and new form VII crystals.

Science.gov (United States)

Ito, Masataka; Shiba, Rika; Watanabe, Miteki; Iwao, Yasunori; Itai, Shigeru; Noguchi, Shuji

2018-06-01

Metastable crystal form I of the antibiotic clarithromycin has a pharmaceutically valuable characteristic that its crystalline phase transition can be applied for its sustained release from tablets. The phase transition of form I was investigated in detail by single crystal and powder X-ray analyses, dynamic vapor sorption analysis and thermal analysis. The single crystal structure of form I revealed that form I was not an anhydrate crystal but contained a partially occupied water molecule in the channel-like void space. Dynamic vapor sorption (DVS) analysis demonstrated that form I crystals reversibly sorbed water molecules in two steps when the relative humidity (RH) increased and finally transited to hydrate form IV at 95% RH. DVS analysis also showed that when the RH decreased form IV crystals lost water molecules at 40% RH and transited to the newly identified anhydrate crystal form VII. Form VII reversibly transited to form IV at lower RH than form I, suggesting that form I is more suitable for manufacturing a sustained-release tablet of CAM utilizing the crystalline phase transition. Copyright © 2018 Elsevier B.V. All rights reserved.

On the Matching of Seen and Felt Shape by Newly Sighted Subjects

Directory of Open Access Journals (Sweden)

John Schwenkler

2012-04-01

Full Text Available How do we recognize identities between seen shapes and felt ones? Is this due to associative learning, or intrinsic connections these sensory modalities? We can address this question by testing the capacities of newly sighted subjects to match seen and felt shapes, but only if the subjects can see the objects well enough to form adequate visual representations of their shapes. In light of this, a recent study by R. Held and colleagues fails to demonstrate that their newly sighted subjects' inability to match seen and felt shape was due to a lack of intermodal connections rather than a purely visual deficit, as the subjects may not have been able visually to represent 3D shape in the perspective-invariant manner required for intermodal matching. However, the study could be modified in any of several ways to help avoid this problem.

Pineapple Fruit Collapse: Newly Emerging Disease of Pineapple Fruit in Lampung, Indonesia

OpenAIRE

Joko Prasetyo; Titik Nur Aeny

2014-01-01

ABSTRACT Pineapple fruit collapse: newly emerging disease of pineapple fruit in Lampung, Indonesia Recently, a new disease on pineapple fruit has occurred in Lampung. Symptoms of the disease are complex. Fruits rotted and exuded copious liquid from the inter- fruitlet tissues accompanied by gas bubbles. Open spaces were formed inside the rotten fruit. Dissection of diseased fruit showed many cavities within its sceletal fibres and bad odour was exerted from the rotten tissues. A bacterial...

Somal and dendritic development of human CA3 pyramidal neurons from midgestation to middle childhood: a quantitative Golgi study.

Science.gov (United States)

Lu, Dahua; He, Lixin; Xiang, Wei; Ai, Wei-Min; Cao, Ye; Wang, Xiao-Sheng; Pan, Aihua; Luo, Xue-Gang; Li, Zhiyuan; Yan, Xiao-Xin

2013-01-01

The CA3 area serves a key relay on the tri-synaptic loop of the hippocampal formation which supports multiple forms of mnemonic processing, especially spatial learning and memory. To date, morphometric data about human CA3 pyramidal neurons are relatively rare, with little information available for their pre- and postnatal development. Herein, we report a set of developmental trajectory data, including somal growth, dendritic elongation and branching, and spine formation, of human CA3 pyramidal neurons from midgestation stage to middle childhood. Golgi-impregnated CA3 pyramidal neurons in fetuses at 19, 20, 26, 35, and 38 weeks of gestation (GW) and a child at 8 years of age (Y) were analyzed by Neurolucida morphometry. Somal size of the impregnated CA3 cells increased age-dependently among the cases. The length of the apical and basal dendrites of these neurons increased between 26 GW to 38 GW, and appeared to remain stable afterward until 8 Y. Dendritic branching points increased from 26 GW to 38 GW, with that on the apical dendrites slightly reduced at 8 Y. Spine density on the apical and basal dendrites increased progressively from 26 GW to 8 Y. These data suggest that somal growth and dendritic arborization of human CA3 pyramidal neurons occur largely during the second to third trimester. Spine development and likely synaptogenesis on CA3 pyramidal cells progress during the third prenatal trimester and may continue throughout childhood. Copyright © 2012 Wiley Periodicals, Inc.

Generational differences among newly licensed registered nurses.

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Keepnews, David M; Brewer, Carol S; Kovner, Christine T; Shin, Juh Hyun

2010-01-01

Responses of 2369 newly licensed registered nurses from 3 generational cohorts-Baby Boomers, Generation X, and Generation Y-were studied to identify differences in their characteristics, work-related experiences, and attitudes. These responses revealed significant differences among generations in: job satisfaction, organizational commitment, work motivation, work-to-family conflict, family-to-work conflict, distributive justice, promotional opportunities, supervisory support, mentor support, procedural justice, and perceptions of local job opportunities. Health organizations and their leaders need to anticipate intergenerational differences among newly licensed nurses and should provide for supportive working environments that recognize those differences. Orientation and residency programs for newly licensed nurses should be tailored to the varying needs of different generations. Future research should focus on evaluating the effectiveness of orientation and residency programs with regard to different generations so that these programs can be tailored to meet the varying needs of newly licensed nurses at the start of their careers. Copyright 2010 Mosby, Inc. All rights reserved.

Hope in newly diagnosed cancer patients.

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Duggleby, Wendy; Ghosh, Sunita; Cooper, Dan; Dwernychuk, Lynne

2013-11-01

Hope is important to cancer patients as it helps them deal with their diagnosis. Little is known about hope in newly diagnosed cancer patients. Based on the Transcending Possibilities conceptual model of hope, the purpose of this study was to examine the relationship of hope with pain, energy, and psychological and demographic characteristics in newly diagnosed adult oncology outpatients. Data from 310 New Patient Assessment Forms from cancer outpatients' health records were collected. Health records from the first six months of 2009 were reviewed and data were collected on hope, energy, pain, depression, anxiety, feeling overwhelmed, and demographic variables. A generalized linear modeling approach was used to study the relationship of hope scores with these variables. Hypothesized variables and variables that were significant at the P = 0.01 level from the univariate analysis were entered into the multivariate model, with hope scores as the dependent variable. Hope scores were significantly negatively related to age (P = 0.02). More specifically, oncology patients who were 65 years of age or older had significantly less hope than those under the age of 65 years (P = 0.01). Gender (P = 0.009) also was a significant factor, with men having higher hope scores than women. No other variables were significant. Older adults comprise the majority of persons in Canada with cancer. The lower hope scores found in this age group compared with their younger counterparts underscore the importance of further research. This study provides a foundation for future research in this important area for oncology patients. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Health-related quality of life of children with newly diagnosed specific learning disability.

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Karande, Sunil; Bhosrekar, Kirankumar; Kulkarni, Madhuri; Thakker, Arpita

2009-06-01

The objective of this study was to measure health-related quality of life (HRQL) of children with newly diagnosed specific learning disability (SpLD) using the Child Health Questionnaire-Parent Form 50. We detected clinically significant deficits (effect size > or = -0.5) in 9 out of 12 domains: limitations in family activities, emotional impact on parents, social limitations as a result of emotional-behavioral problems, time impact on parents, general behavior, physical functioning, social limitations as a result of physical health, general health perceptions and mental health; and in both summary scores (psychosocial > physical). Multivariate analysis revealed having > or = 1 non-academic problem(s) (p or =1 non-academic problem(s) (p = 0.006) or first-born status (p = 0.035) predicted a poor physical summary score. HRQL is significantly compromised in children having newly diagnosed SpLD.

Maintaining Professional Commitment as a Newly Credentialed Athletic Trainer in the Secondary School Setting.

Science.gov (United States)

Mazerolle, Stephanie M; Myers, Sarah L; Walker, Stacy E; Kirby, Jessica

2018-03-01

  Professional commitment, or one's affinity and loyalty to a career, has become a topic of interest in athletic training. The expanding research on the topic, however, has omitted newly credentialed athletic trainers (ATs). For an impressionable group of practitioners, transitioning to clinical practice can be stressful.   To explore the professional commitment of newly credentialed ATs in the secondary school setting.   Secondary school.   Qualitative study.   A total of 31 newly credentialed ATs (6 men, 25 women; mean age = 24 ± 3 years) participated. Of these, 17 ATs (4 men, 13 women; mean age = 25 ± 4 years) were employed full time in the secondary school setting, and 14 ATs (2 men, 12 women; mean age = 23.0 ± 2.0 years) were graduate assistant students in the secondary school setting.   All participants completed semistructured interviews, which focused on their experiences in the secondary school setting and transitioning into the role and setting. Transcripts were analyzed using the phenomenologic approach. Creditability was established by peer review, member checks, and researcher triangulation.   Four main findings related to the professional commitment of newly credentialed ATs in the secondary school setting were identified. Work-life balance, professional relationships formed with the student-athletes, enjoyment gained from working in the secondary school setting, and professional responsibility emerged as factors facilitating commitment.   Affective commitment is a primary facilitator of professional commitment. Newly credentialed ATs who enjoy their jobs and have time to engage in nonwork roles are able to maintain a positive professional commitment. Our findings align with the previous literature and help strengthen our understanding that rejuvenation and passion are important to professional commitment.

Michael Maier--nine newly discovered letters.

Science.gov (United States)

Lenke, Nils; Roudet, Nicolas; Tilton, Hereward

2014-02-01

The authors provide a transcription, translation, and evaluation of nine newly discovered letters from the alchemist Michael Maier (1568-1622) to Gebhardt Johann von Alvensleben (1576-1631), a noble landholder in the vicinity of Magdeburg. Stemming from the final year of his life, this correspondence casts new light on Maier's biography, detailing his efforts to secure patronage amid the financial crisis of the early Thirty Years' War. While his ill-fated quest to perfect potable gold continued to form the central focus of his patronage suits, Maier also offered his services in several arts that he had condemned in his printed works, namely astrology and "supernatural" magic. Remarks concerning his previously unknown acquaintance with Heinrich Khunrath call for a re-evaluation of Maier's negotiation of the discursive boundaries between Lutheran orthodoxy and Paracelsianism. The letters also reveal Maier's substantial contribution to a work previously ascribed solely to the English alchemist Francis Anthony.

Establishment probability in newly founded populations

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Gusset Markus

2012-06-01

Full Text Available Abstract Background Establishment success in newly founded populations relies on reaching the established phase, which is defined by characteristic fluctuations of the population’s state variables. Stochastic population models can be used to quantify the establishment probability of newly founded populations; however, so far no simple but robust method for doing so existed. To determine a critical initial number of individuals that need to be released to reach the established phase, we used a novel application of the “Wissel plot”, where –ln(1 – P0(t is plotted against time t. This plot is based on the equation P0t=1–c1e–ω1t, which relates the probability of extinction by time t, P0(t, to two constants: c1 describes the probability of a newly founded population to reach the established phase, whereas ω1 describes the population’s probability of extinction per short time interval once established. Results For illustration, we applied the method to a previously developed stochastic population model of the endangered African wild dog (Lycaon pictus. A newly founded population reaches the established phase if the intercept of the (extrapolated linear parts of the “Wissel plot” with the y-axis, which is –ln(c1, is negative. For wild dogs in our model, this is the case if a critical initial number of four packs, consisting of eight individuals each, are released. Conclusions The method we present to quantify the establishment probability of newly founded populations is generic and inferences thus are transferable to other systems across the field of conservation biology. In contrast to other methods, our approach disaggregates the components of a population’s viability by distinguishing establishment from persistence.

GOLGA2, encoding a master regulator of golgi apparatus, is mutated in a patient with a neuromuscular disorder.

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Shamseldin, Hanan E; Bennett, Alexis H; Alfadhel, Majid; Gupta, Vandana; Alkuraya, Fowzan S

2016-02-01

Golgi apparatus (GA) is a membrane-bound organelle that serves a multitude of critical cellular functions including protein secretion and sorting, and cellular polarity. Many Mendelian diseases are caused by mutations in genes encoding various components of GA. GOLGA2 encodes GM130, a necessary component for the assembly of GA as a single complex, and its deficiency has been found to result in severe cellular phenotypes. We describe the first human patient with a homozygous apparently loss of function mutation in GOLGA2. The phenotype is a neuromuscular disorder characterized by developmental delay, seizures, progressive microcephaly, and muscular dystrophy. Knockdown of golga2 in zebrafish resulted in severe skeletal muscle disorganization and microcephaly recapitulating loss of function human phenotype. Our data suggest an important developmental role of GM130 in humans and zebrafish.

The impossible interview with the man of the hidden biological structures. Interview by Paolo Mazzarello.

Science.gov (United States)

Golgi, Camillo

2006-12-01

This paper presents an "impossible interview" to Professor Camillo Golgi, placed in time in December 1906. The Italian Professor Golgi from Pavia has been awarded the Nobel Prize for Physiology or Medicine ex aequo with the Spanish anatomist Santiago Ramón y Cajal. Both scientists have obtained the award for their work on the anatomy of the nervous system. However, they have opposite views on the mechanisms underlying nervous functions. Golgi believes that the axons stained by his "black reaction" form a continuous anatomical or functional network along which nervous impulses propagate. Ramón y Cajal is the paladin of the neuron theory, a hypothesis questioned by Golgi in his Nobel lecture of Tuesday, December 11. After the ceremony, an independent journalist has interviewed Professor Golgi in the Grand Hotel in Stockholm. Excerpts about his education, his main scientific discoveries, and his personal life are here given (reconstructing the "impossible interview" on the basis of Golgi's original writings).

Video Views and Reviews: Golgi Export, Targeting, and Plasma Membrane Caveolae

Science.gov (United States)

Watters, Christopher

2004-01-01

In this article, the author reviews videos from "Molecular Biology of the Cell (MBC)" depicting various aspects of plasma membrane (PM) dynamics, including the targeting of newly synthesized components and the organization of those PM invaginations called caveolae. The papers accompanying these videos describe, respectively, the constitutive…

Historical biogeography and diversification of truffles in the Tuberaceae and their newly identified Southern hemisphere sister lineage

Science.gov (United States)

Gregory Bonito; Matthew E. Smith; Michael Nowak; Rosanne A. Healy; Gonzalo Guevara; Efren Cazares; Akihiko Kinoshita; Eduardo R. Nouhra; Laura S. Dominguez; Leho Tedersoo; Claude Murat; Yun Wang; Baldomero Arroyo Moreno; Donald H. Pfister; Kazuhide Nara; Alessandra Zambonelli; James M. Trappe; Rytas. Vilgalys

2013-01-01

In this study we reassessed the biogeography and origin of the Tuberaceae and their relatives using multiple loci and a global sampling of taxa. Multiple independent transitions from an aboveground to a belowground truffie fruiting body form have occurred in the Tuberaceae and in its newly recognized sister lineage...

Superplastic forming and diffusion bonding: Progress and trends

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Zhiqiang Li

2015-01-01

Full Text Available This paper summarized recent progress in metal superplasticity and the application of Superplastic Forming/Diffusion Bonding (SPF/DB or SPF/Welding in typical structures. Various aerospace components such as three dimensional lattice structures made by SPF/DB have been demonstrated. In addition, some newly developed technologies, such as melt droplet spreading/thermo-mechanical forming (MDS/TMF, were also included. Finally, the future potential of SPF/DB technology was predicted.

The Drosophila Neurally Altered Carbohydrate Mutant Has a Defective Golgi GDP-fucose Transporter*

Science.gov (United States)

Geisler, Christoph; Kotu, Varshika; Sharrow, Mary; Rendić, Dubravko; Pöltl, Gerald; Tiemeyer, Michael; Wilson, Iain B. H.; Jarvis, Donald L.

2012-01-01

Studying genetic disorders in model organisms can provide insights into heritable human diseases. The Drosophila neurally altered carbohydrate (nac) mutant is deficient for neural expression of the HRP epitope, which consists of N-glycans with core α1,3-linked fucose residues. Here, we show that a conserved serine residue in the Golgi GDP-fucose transporter (GFR) is substituted by leucine in nac1 flies, which abolishes GDP-fucose transport in vivo and in vitro. This loss of function is due to a biochemical defect, not to destabilization or mistargeting of the mutant GFR protein. Mass spectrometry and HPLC analysis showed that nac1 mutants lack not only core α1,3-linked, but also core α1,6-linked fucose residues on their N-glycans. Thus, the nac1 Gfr mutation produces a previously unrecognized general defect in N-glycan core fucosylation. Transgenic expression of a wild-type Gfr gene restored the HRP epitope in neural tissues, directly demonstrating that the Gfr mutation is solely responsible for the neural HRP epitope deficiency in the nac1 mutant. These results validate the Drosophila nac1 mutant as a model for the human congenital disorder of glycosylation, CDG-IIc (also known as LAD-II), which is also the result of a GFR deficiency. PMID:22745127

Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons

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Chang Geon Chung

2017-07-01

Full Text Available Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs and a decreased supply of plasma membrane (PM in Drosophila class IV dendritic arborization (da (C4 da neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis. Transcription factor enrichment analysis identified CREB3L1/CrebA, which regulates COPII gene expression. CrebA overexpression in C4 da neurons restores the dysregulation of COPII genes, GOP synthesis, and PM supply. Chromatin immunoprecipitation (ChIP-PCR revealed that CrebA expression is regulated by CREB-binding protein (CBP, which is sequestered by polyQ proteins. Furthermore, co-overexpression of CrebA and Rac1 synergistically restores the polyQ-induced dendrite pathology. Collectively, our results suggest that GOPs impaired by polyQ proteins contribute to dendrite pathology through the CBP-CrebA-COPII pathway.

Kidney-differentiated cells derived from Lowe Syndrome patient's iPSCs show ciliogenesis defects and Six2 retention at the Golgi complex.

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Wen-Chieh Hsieh

Full Text Available Lowe syndrome is an X-linked condition characterized by congenital cataracts, neurological abnormalities and kidney malfunction. This lethal disease is caused by mutations in the OCRL1 gene, which encodes for the phosphatidylinositol 5-phosphatase Ocrl1. While in the past decade we witnessed substantial progress in the identification and characterization of LS patient cellular phenotypes, many of these studies have been performed in knocked-down cell lines or patient's cells from accessible cell types such as skin fibroblasts, and not from the organs affected. This is partially due to the limited accessibility of patient cells from eyes, brain and kidneys. Here we report the preparation of induced pluripotent stem cells (iPSCs from patient skin fibroblasts and their reprogramming into kidney cells. These reprogrammed kidney cells displayed primary cilia assembly defects similar to those described previously in cell lines. Additionally, the transcription factor and cap mesenchyme marker Six2 was substantially retained in the Golgi complex and the functional nuclear-localized fraction was reduced. These results were confirmed using different batches of differentiated cells from different iPSC colonies and by the use of the human proximal tubule kidney cell line HK2. Indeed, OCRL1 KO led to both ciliogenesis defects and Six2 retention in the Golgi complex. In agreement with Six2's role in the suppression of ductal kidney lineages, cells from this pedigree were over-represented among patient kidney-reprogrammed cells. We speculate that this diminished efficacy to produce cap mesenchyme cells would cause LS patients to have difficulties in replenishing senescent or damaged cells derived from this lineage, particularly proximal tubule cells, leading to pathological scenarios such as tubular atrophy.

Factors Associated with Newly Diagnosed Children with Diabetic Ketoacidosis

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Raheleh Mirsadraee

2016-09-01

Full Text Available Background Diabetes mellitus type 1 is one of the most prevalent endocrine diseases in pediatrics. Diabetic ketoacidosis is considered as one of the most threatening clinical pictures of DM1, especially if occurred as the first presentation of DM1 in children. Objectives The current study aimed to identify factors which may play a role in DKA onset in children. Methods This case-control study included all patients under 18 years old who referred to department of pediatrics endocrinology at Mashhad University Hospital (Imam Reza from January 2013 to December 2015 as newly diagnosed patients with DM1. Patients who fulfilled DKA criteria at diagnosis were considered as DKA group and those who referred with other presentations were considered as control group (non-DKA group. Data were analyzed by SPSS software ver. 16. Results During the study period, 97 (39.2% male newly diagnosed patients were included as DKA group. Accordingly 97 gender- and age-matched patients were added as non-DKA group. The most prevalent symptoms in both groups were polyuria (91.88% and polydipsia (88.66%. Fever and cold symptoms were significantly higher in the DKA group (P < 0.001 and P =0.005, respectively. Hemoglobin A1c level was significantly higher in the DKA group (P = 0.001, while body mass index was significantly lower in the DKA group (P = 0.045. Fever and father’s education level were the most important risk and protective factors in the DKA onset in newly diagnosed patients with DM1 (adjusted OR = 10.1, 95% CI = 2.9-35.3; P < 0.001 and adjusted OR = 0.5, 95% CI = 0.3 - 0.9 and P = 0.019, respectively. Conclusions In conclusion, a recent febrile illness was found as the strongest risk factor and father’s education level as the main protective factor in the DKA to diagnose children with DM1. The study findings suggested that DKA is a severe form of DM1 instead of a neglected or misdiagnosed disease.

Tetrahymena gene encodes a protein that is homologous with the liver-specific F-antigen and associated with membranes of the Golgi apparatus and transport vesicles

DEFF Research Database (Denmark)

Hummel, R; Nørgaard, P; Andreasen, P H

1992-01-01

The F-antigen is a prominent liver protein which has been extensively used in studies on natural and induced immunological tolerance. However, its intracellular localization and biological function have remained elusive. It has generally been assumed that the F-antigen is confined phylogenetically...... of the Golgi apparatus and transport vesicles pointing to a role of TF-ag in membrane trafficking. Transcription of the TF-ag gene, as determined by run-on analyses, was only detectable in growing cells, and following transfer to starvation condition pre-existing TF-ag mRNA was rapidly degraded. The abundance...

Education through fiction: acquiring opinion-forming skills in the context of genomics

NARCIS (Netherlands)

Knippels, M.C.P.J.; Severiens, S.E.; Klop, T.

2009-01-01

The present study examined the outcomes of a newly designed four-lesson science module on opinion-forming in the context of genomics in upper secondary education. The lesson plan aims to foster 16-year-old students’ opinion-forming skills in the context of genomics and to test the effect of the use

Confidence in leadership among the newly qualified.

Science.gov (United States)

Bayliss-Pratt, Lisa; Morley, Mary; Bagley, Liz; Alderson, Steven

2013-10-23

The Francis report highlighted the importance of strong leadership from health professionals but it is unclear how prepared those who are newly qualified feel to take on a leadership role. We aimed to assess the confidence of newly qualified health professionals working in the West Midlands in the different competencies of the NHS Leadership Framework. Most respondents felt confident in their abilities to demonstrate personal qualities and work with others, but less so at managing or improving services or setting direction.

The small GTPase Cdc42 modulates the number of exocytosis-competent dense-core vesicles in PC12 cells

Energy Technology Data Exchange (ETDEWEB)

Sato, Mai [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan); Kitaguchi, Tetsuya [Cell Signaling Group, Waseda Bioscience Research Institute in Singapore (WABOIS), Waseda University, 11 Biopolis Way, 05-01/02 Helios, Singapore 138667 (Singapore); Numano, Rika [The Electronics-Inspired Interdisciplinary Research Institute (EIIRIS), Toyohashi University of Technology, 1-1 Hibarigaoka, Tennpaku-cho, Toyohashi, Aichi 441-8580 (Japan); Ikematsu, Kazuya [Forensic Pathology and Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kakeyama, Masaki [Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033 (Japan); Murata, Masayuki; Sato, Ken [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan); Tsuboi, Takashi, E-mail: takatsuboi@bio.c.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan)

2012-04-06

Highlights: Black-Right-Pointing-Pointer Regulation of exocytosis by Rho GTPase Cdc42. Black-Right-Pointing-Pointer Cdc42 increases the number of fusion events from newly recruited vesicles. Black-Right-Pointing-Pointer Cdc42 increases the number of exocytosis-competent dense-core vesicles. -- Abstract: Although the small GTPase Rho family Cdc42 has been shown to facilitate exocytosis through increasing the amount of hormones released, the precise mechanisms regulating the quantity of hormones released on exocytosis are not well understood. Here we show by live cell imaging analysis under TIRF microscope and immunocytochemical analysis under confocal microscope that Cdc42 modulated the number of fusion events and the number of dense-core vesicles produced in the cells. Overexpression of a wild-type or constitutively-active form of Cdc42 strongly facilitated high-KCl-induced exocytosis from the newly recruited plasma membrane vesicles in PC12 cells. By contrast, a dominant-negative form of Cdc42 inhibited exocytosis from both the newly recruited and previously docked plasma membrane vesicles. The number of intracellular dense-core vesicles was increased by the overexpression of both a wild-type and constitutively-active form of Cdc42. Consistently, activation of Cdc42 by overexpression of Tuba, a Golgi-associated guanine nucleotide exchange factor for Cdc42 increased the number of intracellular dense-core vesicles, whereas inhibition of Cdc42 by overexpression of the Cdc42/Rac interactive binding domain of neuronal Wiskott-Aldrich syndrome protein decreased the number of them. These findings suggest that Cdc42 facilitates exocytosis by modulating both the number of exocytosis-competent dense-core vesicles and the production of dense-core vesicles in PC12 cells.

The small GTPase Cdc42 modulates the number of exocytosis-competent dense-core vesicles in PC12 cells

International Nuclear Information System (INIS)

Sato, Mai; Kitaguchi, Tetsuya; Numano, Rika; Ikematsu, Kazuya; Kakeyama, Masaki; Murata, Masayuki; Sato, Ken; Tsuboi, Takashi

2012-01-01

Highlights: ► Regulation of exocytosis by Rho GTPase Cdc42. ► Cdc42 increases the number of fusion events from newly recruited vesicles. ► Cdc42 increases the number of exocytosis-competent dense-core vesicles. -- Abstract: Although the small GTPase Rho family Cdc42 has been shown to facilitate exocytosis through increasing the amount of hormones released, the precise mechanisms regulating the quantity of hormones released on exocytosis are not well understood. Here we show by live cell imaging analysis under TIRF microscope and immunocytochemical analysis under confocal microscope that Cdc42 modulated the number of fusion events and the number of dense-core vesicles produced in the cells. Overexpression of a wild-type or constitutively-active form of Cdc42 strongly facilitated high-KCl-induced exocytosis from the newly recruited plasma membrane vesicles in PC12 cells. By contrast, a dominant-negative form of Cdc42 inhibited exocytosis from both the newly recruited and previously docked plasma membrane vesicles. The number of intracellular dense-core vesicles was increased by the overexpression of both a wild-type and constitutively-active form of Cdc42. Consistently, activation of Cdc42 by overexpression of Tuba, a Golgi-associated guanine nucleotide exchange factor for Cdc42 increased the number of intracellular dense-core vesicles, whereas inhibition of Cdc42 by overexpression of the Cdc42/Rac interactive binding domain of neuronal Wiskott–Aldrich syndrome protein decreased the number of them. These findings suggest that Cdc42 facilitates exocytosis by modulating both the number of exocytosis-competent dense-core vesicles and the production of dense-core vesicles in PC12 cells.

The Prion-like Domain in the Exomer-Dependent Cargo Pin2 Serves as a trans-Golgi Retention Motif

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Alicja M. Ritz

2014-04-01

Full Text Available Prion and prion-like domains (PLDs are found in many proteins throughout the animal kingdom. We found that the PLD in the S. cerevisiae exomer-dependent cargo protein Pin2 is involved in the regulation of protein transport and localization. The domain serves as a Pin2 retention signal in the trans-Golgi network (TGN. Pin2 is localized in a polarized fashion at the plasma membrane of the bud early in the cell cycle and the bud neck at cytokinesis. This polarized localization is dependent on both exo- and endocytosis. Upon environmental stress, Pin2 is rapidly endocytosed, and the PLD aggregates and causes sequestration of Pin2. The aggregation of Pin2 is reversible upon stress removal and Pin2 is rapidly re-exported to the plasma membrane. Altogether, these data uncover a role for PLDs as protein localization elements.

A traffic signal for heterodimeric amino acid transporters to transfer from the ER to the Golgi.

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Ganapathy, Vadivel

2009-01-15

Heterodimeric amino acid transporters represent a unique class of transport systems that consist of a light chain that serves as the 'transporter proper' and a heavy chain that is necessary for targeting the complex to the plasma membrane. The currently prevailing paradigm assigns no role for the light chains in the cellular processing of these transporters. In this issue of the Biochemical Journal, Sakamoto et al. provide evidence contrary to this paradigm. Their studies with the rBAT -b(0,+)AT (related to b(0,+) amino acid transporter-b(0,+)-type amino acid transporter) heterodimeric amino acid transporter show that the C-terminus of the light chain b(0,+)AT contains a sequence motif that serves as the traffic signal for the transfer of the heterodimeric complex from the endoplasmic reticulum to the Golgi. This is a novel function for the light chain in addition to its already established role as the subunit responsible for the transport activity. These new findings also seem to be applicable to other heterodimeric amino acid transporters as well.

Problems faced by newly diagnosed diabetes mellitus patients at ...

African Journals Online (AJOL)

Diabetes mellitus can be a frightening experience for newly diagnosed patients. The aim of this study was to determine and describe the problems faced by newly diagnosed diabetes mellitus patients at primary healthcare facilities at Mopani district, Limpopo Province. A qualitative, descriptive and contextual research ...

Newly graduated nurses' use of knowledge sources in clinical decision-making

DEFF Research Database (Denmark)

Voldbjerg, Siri Lygum; Grønkjaer, Mette; Wiechula, Rick

2017-01-01

AIMS AND OBJECTIVES: To explore which knowledge sources newly graduated nurses' use in clinical decision-making and why and how they are used. BACKGROUND: In spite of an increased educational focus on skills and competencies within evidence based practice newly graduated nurses' ability to use...... approaches to strengthen the knowledgebase used in clinical decision-making. DESIGN AND METHODS: Ethnographic study using participant-observation and individual semi-structured interviews of nine Danish newly graduated nurses in medical and surgical hospital settings. RESULTS: Newly graduates use...... in clinical decision-making. If newly graduates are to be supported in an articulate and reflective use of a variety of sources, they have to be allocated to experienced nurses who model a reflective, articulate and balanced use of knowledge sources. This article is protected by copyright. All rights reserved....

Value of a newly sequenced bacterial genome

DEFF Research Database (Denmark)

Barbosa, Eudes; Aburjaile, Flavia F; Ramos, Rommel Tj

2014-01-01

and annotation will not be undertaken. It is important to know what is lost when we settle for a draft genome and to determine the "scientific value" of a newly sequenced genome. This review addresses the expected impact of newly sequenced genomes on antibacterial discovery and vaccinology. Also, it discusses...... heightened expectations that NGS would boost antibacterial discovery and vaccine development. Although many possible drug and vaccine targets have been discovered, the success rate of genome-based analysis has remained below expectations. Furthermore, NGS has had consequences for genome quality, resulting...

Dsc E3 ligase localization to the Golgi requires the ATPase Cdc48 and cofactor Ufd1 for activation of sterol regulatory element-binding protein in fission yeast.

Science.gov (United States)

Burr, Risa; Ribbens, Diedre; Raychaudhuri, Sumana; Stewart, Emerson V; Ho, Jason; Espenshade, Peter J

2017-09-29

Sterol regulatory element-binding proteins (SREBPs) in the fission yeast Schizosaccharomyces pombe regulate lipid homeostasis and the hypoxic response under conditions of low sterol or oxygen availability. SREBPs are cleaved in the Golgi through the combined action of the Dsc E3 ligase complex, the rhomboid protease Rbd2, and the essential ATPases associated with diverse cellular activities (AAA + ) ATPase Cdc48. The soluble SREBP N-terminal transcription factor domain is then released into the cytosol to enter the nucleus and regulate gene expression. Previously, we reported that Cdc48 binding to Rbd2 is required for Rbd2-mediated SREBP cleavage. Here, using affinity chromatography and mass spectrometry experiments, we identified Cdc48-binding proteins in S. pombe , generating a list of many previously unknown potential Cdc48-binding partners. We show that the established Cdc48 cofactor Ufd1 is required for SREBP cleavage but does not interact with the Cdc48-Rbd2 complex. Cdc48-Ufd1 is instead required at a step prior to Rbd2 function, during Golgi localization of the Dsc E3 ligase complex. Together, these findings demonstrate that two distinct Cdc48 complexes, Cdc48-Ufd1 and Cdc48-Rbd2, are required for SREBP activation and low-oxygen adaptation in S. pombe . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Disturbed vesicular trafficking of membrane proteins in prion disease.

Science.gov (United States)

Uchiyama, Keiji; Miyata, Hironori; Sakaguchi, Suehiro

2013-01-01

The pathogenic mechanism of prion diseases remains unknown. We recently reported that prion infection disturbs post-Golgi trafficking of certain types of membrane proteins to the cell surface, resulting in reduced surface expression of membrane proteins and abrogating the signal from the proteins. The surface expression of the membrane proteins was reduced in the brains of mice inoculated with prions, well before abnormal symptoms became evident. Prions or pathogenic prion proteins were mainly detected in endosomal compartments, being particularly abundant in recycling endosomes. Some newly synthesized membrane proteins are delivered to the surface from the Golgi apparatus through recycling endosomes, and some endocytosed membrane proteins are delivered back to the surface through recycling endosomes. These results suggest that prions might cause neuronal dysfunctions and cell loss by disturbing post-Golgi trafficking of membrane proteins via accumulation in recycling endosomes. Interestingly, it was recently shown that delivery of a calcium channel protein to the cell surface was impaired and its function was abrogated in a mouse model of hereditary prion disease. Taken together, these results suggest that impaired delivery of membrane proteins to the cell surface is a common pathogenic event in acquired and hereditary prion diseases.

A Newly Improved Modified Method Development and Validation of Bromofenac Sodium Sesquihydrate in Bulk Drug Manufacturing

OpenAIRE

Sunil Kumar Yelamanchi V; Useni Reddy Mallu; I. V Kasi Viswanath; D. Balasubramanyam; G. Narshima Murthy

2016-01-01

The main objective of this study was to develop a simple, efficient, specific, precise and accurate newly improved modified Reverse Phase High Performance Liquid Chromatographic Purity (or) Related substance method for bromofenac sodium sesquihydrate active pharmaceuticals ingredient dosage form. Validation of analytical method is the confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled as per ICH, USP...

The construction of social identity in newly recruited nuclear engineering staff: A longitudinal study

International Nuclear Information System (INIS)

Nguyen, Lynda; Murphy, Glen; Chang, Artemis

2014-01-01

This study examines the process by which newly recruited nuclear engineering and technical staff came to understand, define, think, feel and behave within a distinct group that has a direct contribution to the organization's overall emphasis on a culture of reliability and system safety. In the field of organizational behavior the interactive model of social identity formation has been recently proposed to explain the process by which the internalization of shared norms and values occurs, an element critical in identity formation. Using this rich model of organizational behavior we analyzed multiple sources of data from nine new hires over a period of three years. This was done from the time they were employed to investigate the construction of social identity by new entrants entering into a complex organizational setting reflected in the context of a nuclear facility. Informed by our data analyses, we found support for the interactive model of social identity development and report the unexpected finding that a newly appointed member's age and level of experience appears to influence the manner in which they adapt, and assimilate into their surroundings. This study represents an important contribution to the safety and reliability literature as it provides a rich insight into the way newly recruited employees enact the process by which their identities are formed and hence act, particularly under conditions of duress or significant organizational disruption in complex organizational settings. - Highlights: • We examined how newly recruited nuclear engineer staff develop their social identity. • The study empirically examined the interactive model of social identity formation. • Innovative research strategies were used to capture rich primary data for all case studies. • Age and experience moderated internalization route and the social identity formation process

Newly Generated Liquid Waste Processing Alternatives Study, Volume 1

Energy Technology Data Exchange (ETDEWEB)

Landman, William Henry; Bates, Steven Odum; Bonnema, Bruce Edward; Palmer, Stanley Leland; Podgorney, Anna Kristine; Walsh, Stephanie

2002-09-01

This report identifies and evaluates three options for treating newly generated liquid waste at the Idaho Nuclear Technology and Engineering Center of the Idaho National Engineering and Environmental Laboratory. The three options are: (a) treat the waste using processing facilities designed for treating sodium-bearing waste, (b) treat the waste using subcontractor-supplied mobile systems, or (c) treat the waste using a special facility designed and constructed for that purpose. In studying these options, engineers concluded that the best approach is to store the newly generated liquid waste until a sodium-bearing waste treatment facility is available and then to co-process the stored inventory of the newly generated waste with the sodium-bearing waste. After the sodium-bearing waste facility completes its mission, two paths are available. The newly generated liquid waste could be treated using the subcontractor-supplied system or the sodium-bearing waste facility or a portion of it. The final decision depends on the design of the sodium-bearing waste treatment facility, which will be completed in coming years.

Golgi protein 73 as a biomarker for hepatocellular carcinoma: A diagnostic meta-analysis.

Science.gov (United States)

Yang, Jing; Li, Jingjing; Dai, Weiqi; Wang, Fan; Shen, Miao; Chen, Kan; Cheng, Ping; Zhang, Yan; Wang, Chengfen; Zhu, Rong; Zhang, Huawei; Zheng, Yuanyuan; Wang, Junshan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Guo, Chuanyong

2015-04-01

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer-related mortality worldwide. Conflicting results have been reported regarding the use of serum Golgi protein 73 (GP73) as a promising serum marker for the diagnosis of HCC; therefore, the aim of the present study was to provide a systematic review of the diagnostic performance of GP73 for HCC. Following a systematic review of the relevant studies, a number of indices associated with the accuracy of the diagnostic performance of GP73, including the sensitivity and specificity, were pooled using Meta Disc 1.4 software. Data were presented as forest plots, and summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance. Eleven studies were included in this meta-analysis. The summary estimates for serum GP73 in diagnosing HCC were as follows: Sensitivity, 77% [95% confidence interval (CI), 75-79%]; specificity, 91% (95% CI, 90-92%); positive likelihood ratio, 4.34 (95% CI, 2.19-8.59); negative likelihood ratio, 0.30 (95% CI, 0.26-0.36) and diagnostic odds ratio, 15.78 (95% CI, 6.95-35.83). The area under the SROC curve was 0.8638, and the Q index was 0.7944. Significant heterogeneity was found. This meta-analysis indicates a moderate diagnostic value of GP73 in HCC; however, further studies with rigorous design, large sample size and multiregional cooperation are required.

Remunicipalisation and Foundation of Municipal Utilities in the German Energy Sector: Details about Newly Established Enterprises

Directory of Open Access Journals (Sweden)

Oliver Wagner

2017-09-01

Full Text Available Since the majority of network concession contracts in Germany were set to expire some time between 2005 and 2016, a window of opportunity arose in which to rebuild and remunicipalise the local energy supply. As a result, 72 new local power companies were established in Germany within the space of just seven years (between early 2005 and late 2012. This paper provides an introduction to the topic of establishing municipal utilities in Germany. The findings were identified on the basis of the comprehensive screening of all newly established municipal utilities in Germany. Our analysis provides information about regional concentration, the size of municipalities, the legal forms of the newly founded municipal public utilities and the role of strategic partnerships. The key findings are that remunicipalisation is not a question of size and that knowledge gaps may be closed by entering into close strategic partnerships.

The practical skills of newly qualified nurses.

Science.gov (United States)

Danbjørg, Dorthe Boe; Birkelund, Regner

2011-02-01

This paper reports the findings from a study of newly qualified nurses and which subjects the nurses regarded as the most important in order to be able to live up to the requirements of clinical practice, and how they experience their potential for developing practical and moral skills, after the decrease in practical training. A qualitative approach guided the research process and the analysis of the data. The data was collected by participant observation and qualitative interviews with four nurses as informants. The conclusions made in this study are based on the statements and the observations of the newly qualified nurses. Our findings are discussed in relation to the Aristotelian concept and other relevant literature. The main message is that the newly qualified nurses did not feel equipped when they finished their training. This could be interpreted as a direct consequence of the decrease in practical training. Our study also underlines that the way nursing theory is perceived and taught is problematic. The interviews revealed that the nurses think that nursing theories should be applied directly in practice. This misunderstanding is probably also applicable to the teachers of the theories. Copyright © 2010 Elsevier Ltd. All rights reserved.

Newly graduated nurses' use of knowledge sources: a meta-ethnography.

Science.gov (United States)

Voldbjerg, Siri Lygum; Grønkjaer, Mette; Sørensen, Erik Elgaard; Hall, Elisabeth O C

2016-08-01

To advance evidence on newly graduated nurses' use of knowledge sources. Clinical decisions need to be evidence-based and understanding the knowledge sources that newly graduated nurses use will inform both education and practice. Qualitative studies on newly graduated nurses' use of knowledge sources are increasing though generated from scattered healthcare contexts. Therefore, a metasynthesis of qualitative research on what knowledge sources new graduates use in decision-making was conducted. Meta-ethnography. Nineteen reports, representing 17 studies, published from 2000-2014 were identified from iterative searches in relevant databases from May 2013-May 2014. Included reports were appraised for quality and Noblit and Hare's meta-ethnography guided the interpretation and synthesis of data. Newly graduated nurses' use of knowledge sources during their first 2-year postgraduation were interpreted in the main theme 'self and others as knowledge sources,' with two subthemes 'doing and following' and 'knowing and doing,' each with several elucidating categories. The metasynthesis revealed a line of argument among the report findings underscoring progression in knowledge use and perception of competence and confidence among newly graduated nurses. The transition phase, feeling of confidence and ability to use critical thinking and reflection, has a great impact on knowledge sources incorporated in clinical decisions. The synthesis accentuates that for use of newly graduated nurses' qualifications and skills in evidence-based practice, clinical practice needs to provide a supportive environment which nurtures critical thinking and questions and articulates use of multiple knowledge sources. © 2016 John Wiley & Sons Ltd.

COPA mutations impair ER-Golgi transport causing hereditary autoimmune-mediated lung disease and arthritis

Science.gov (United States)

Watkin, Levi B.; Jessen, Birthe; Wiszniewski, Wojciech; Vece, Timothy; Jan, Max; Sha, Youbao; Thamsen, Maike; Santos-Cortez, Regie L. P.; Lee, Kwanghyuk; Gambin, Tomasz; Forbes, Lisa; Law, Christopher S.; Stray-Petersen, Asbjørg; Cheng, Mickie H.; Mace, Emily M.; Anderson, Mark S.; Liu, Dongfang; Tang, Ling Fung; Nicholas, Sarah K.; Nahmod, Karen; Makedonas, George; Canter, Debra; Kwok, Pui-Yan; Hicks, John; Jones, Kirk D.; Penney, Samantha; Jhangiani, Shalini N.; Rosenblum, Michael D.; Dell, Sharon D.; Waterfield, Michael R.; Papa, Feroz R.; Muzny, Donna M.; Zaitlen, Noah; Leal, Suzanne M.; Gonzaga-Jauregui, Claudia; Boerwinkle, Eric; Eissa, N. Tony; Gibbs, Richard A.; Lupski, James R.; Orange, Jordan S.; Shum, Anthony K.

2015-01-01

Advances in genomics have allowed unbiased genetic studies of human disease with unexpected insights into the molecular mechanisms of cellular immunity and autoimmunity1. We performed whole exome sequencing (WES) and targeted sequencing in patients with an apparent Mendelian syndrome of autoimmune disease characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease (ILD). In five families, we identified four unique deleterious variants in the Coatomer subunit alpha (COPA) gene all located within the same functional domain. We hypothesized that mutant COPA leads to a defect in intracellular transport mediated by coat protein complex I (COPI)2–4. We show that COPA variants impair binding of proteins targeted for retrograde Golgi to ER transport and demonstrate that expression of mutant COPA leads to ER stress and the upregulation of Th17 priming cytokines. Consistent with this pattern of cytokine expression, patients demonstrated a significant skewing of CD4+ T cells toward a T helper 17 (Th17) phenotype, an effector T cell population implicated in autoimmunity5,6. Our findings uncover an unexpected molecular link between a vesicular transport protein and a syndrome of autoimmunity manifested by lung and joint disease. These findings provide a unique opportunity to understand how alterations in cellular homeostasis caused by a defect in the intracellular trafficking pathway leads to the generation of human autoimmune disease. PMID:25894502

Hsp47 and cyclophilin B traverse the endoplasmic reticulum with procollagen into pre-Golgi intermediate vesicles. A role for Hsp47 and cyclophilin B in the export of procollagen from the endoplasmic reticulum.

Science.gov (United States)

Smith, T; Ferreira, L R; Hebert, C; Norris, K; Sauk, J J

1995-08-04

Hsp47 and cyclophilin B (CyPB) are residents of the endoplasmic reticulum (ER). Both of these proteins are closely associated with polysome-associated alpha 1(I) procollagen chains. Hsp47 possesses chaperone properties early during the translation of procollagen while the cis/trans-isomerase properties of CyPB facilitate procollagen folding. In this report, we further investigate the interaction of these proteins with procollagen I during export from the ER. To inhibit vesicular budding and retain procollagen within the ER, cells were treated with the heterotrimeric G protein inhibitor mastoparan or calphostin C, a specific inhibitor of diacylglycerol/phorbol ester binding proteins. To arrest procollagen in pre-Golgi intermediate vesicles, cells were treated with guanosine 5'-3-O-(thio)triphosphate. Pulse-chase experiments of cells labeled with [35S]methionine followed by immunoprecipitation during the chase period with anti-procollagen, anti-Hsp47, and anti-CyPB antibodies were performed to reveal the relationship between Hsp47/CyPB/procollagen I. The distribution of procollagen, Hsp47, and CyPB to the ER and/or pre-Golgi vesicles was verified by immunofluorescence. Hsp47 and CyPB remained associated with procollagen retained within the ER. Hsp47 and CyPB were also associated with procollagen exported from the ER into pre-Golgi intermediate vesicles. Treatment of cells with cyclosporin A diminished the levels of CyPB bound to procollagen and diminished the rate of Hsp47 released from procollagen and the rate of procollagen secretion, suggesting that Hsp47 release from procollagen may be driven by helix formation. Also, these studies suggest that Hsp47 may resemble protein disulfide isomerase and possess both chaperone and anti-chaperone properties. During translation, high levels of Hsp47 are seen to limit protein aggregation and facilitate chain registration. Later, Hsp47 and/or CyPB and protein disulfide isomerase act as anti-chaperones and provide the basis for

The impact of organisational culture on the adaptation of newly ...

African Journals Online (AJOL)

Usually newly employed nurses find adjusting to a work setting a challenging experience. Their successful adaptation to their work situation is greatly influenced by the socialisation process inherent in the organisational culture. The newly employed nurse often finds that the norms are unclear, confusing and restrictive.

GABA regulates synaptic integration of newly generated neurons in the adult brain

Science.gov (United States)

Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

2006-02-01

Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

Direct measurement of newly synthesized ATP dissociation kinetics in sarcoplasmic reticulum ATPase

International Nuclear Information System (INIS)

Teruel-Puche, J.; Kurzmack, M.; Inesi, G.

1987-01-01

Incubation of SR vesicles with Ca 2+ and ( 32 P)acetylphosphate, yields steady state levels of ( 32 P)phosphorylated enzyme (ATPase) intermediate and high concentrations of Ca 2+ in the lumen of the vesicles. At this time, addition of ADP (and EGTA to lower the Ca 2+ concentration in the medium outside the vesicles) results in single cycle formation of (γ- 32 P)ATP by transfer of ( 32 P)phosphate from the enzyme intermediate to ADP. The phosphoenzyme decay and ATP formation exhibit a fast component within the first 20 msec following addition of ADP, and a slower component reaching an asymptote in approximately 100 msec. They have now measured by a rapid filtration method the fraction of newly synthesized ATP which is bound to the enzyme, as opposed to the fraction dissociated into the medium. They find that nearly all the ATP formed during the initial burst is still bound to the enzyme within the initial 20 msec of reaction. Dissociation of newly synthesized ATP occurs then with approximately 13 sec -1 rate constant, permitting reequilibration of the system and further formation of ATP. The rate limiting effect of ATP dissociation and other partial reactions on the slow component of single cycle ATP synthesis is evaluated by appropriate kinetic simulations

Assessment for markers of nephropathy in newly diagnosed type 2 ...

African Journals Online (AJOL)

Objective: To assess for markers of nephropathy in newly diagnosed type 2 diabetics, using blood pressure levels, endogenous creatinine clearance and urinary protein excretion as markers of renal disease. Study design: Ninety newly diagnosed type 2 diabetics were studied within 6 weeks of diagnosis. They were in ...

Structure and formation of egg membranes in Aedes aegypti. (L. ) (Diptera:Culicidae)

Energy Technology Data Exchange (ETDEWEB)

Mathew, G; Rai, K S

1975-01-01

An ultrastructural study of mosquito ovarioles reveals that both the vitelline membrane and the endochorion are secreted by the follicular epithelium. The presecretory phase is characterized by the hypertrophy of endoplasmic reticulum and Golgi complex in the follicle cells. Synthesis of vitelline membrane precursors begins immediately after yolk protein uptake by micropinocytosis. Secretory droplets are budded off Golgi cisternae and released into the follicle cell--oocyte interface by exocytosis. The vitelline membrane first appears as dense plaques which eventually fuse to form a single homogeneous layer. Two types of secretory material are identified in the follicle cells prior to the formation of the endochorion. Golgi cisternae bud off small droplets similar in size and appearance to the precursors of the vitelline membrane. These migrate to the apical surface and accumulate between surface folds in the plasma membrane. The second type is a fibrous material formed in endoplasmic reticulum. When fully secreted, the endochorion is a 2-layered structure. The lower layer is comprised of pillar-like structures alternating with fibrous mesh-like areas. The pillars are formed by the coalescence of droplets released from Golgi, while the mesh-like areas presumably arise from the fibrous material. The outer layer is also fibrous. The follicle cells degenerate once the endochorion is laid down. endochorion is laid down.

Hepatitis C virus translation preferentially depends on active RNA replication.

Directory of Open Access Journals (Sweden)

Helene Minyi Liu

Full Text Available Hepatitis C virus (HCV RNA initiates its replication on a detergent-resistant membrane structure derived from the endoplasmic reticulum (ER in the HCV replicon cells. By performing a pulse-chase study of BrU-labeled HCV RNA, we found that the newly-synthesized HCV RNA traveled along the anterograde-membrane traffic and moved away from the ER. Presumably, the RNA moved to the site of translation or virion assembly in the later steps of viral life cycle. In this study, we further addressed how HCV RNA translation was regulated by HCV RNA trafficking. When the movement of HCV RNA from the site of RNA synthesis to the Golgi complex was blocked by nocodazole, an inhibitor of ER-Golgi transport, HCV protein translation was surprisingly enhanced, suggesting that the translation of viral proteins occurred near the site of RNA synthesis. We also found that the translation of HCV proteins was dependent on active RNA synthesis: inhibition of viral RNA synthesis by an NS5B inhibitor resulted in decreased HCV viral protein synthesis even when the total amount of intracellular HCV RNA remained unchanged. Furthermore, the translation activity of the replication-defective HCV replicons or viral RNA with an NS5B mutation was greatly reduced as compared to that of the corresponding wildtype RNA. By performing live cell labeling of newly synthesized HCV RNA and proteins, we further showed that the newly synthesized HCV proteins colocalized with the newly synthesized viral RNA, suggesting that HCV RNA replication and protein translation take place at or near the same site. Our findings together indicate that the translation of HCV RNA is coupled to RNA replication and that the both processes may occur at the same subcellular membrane compartments, which we term the replicasome.

14 CFR 26.39 - Newly produced airplanes: Fuel tank flammability.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Newly produced airplanes: Fuel tank... Tank Flammability § 26.39 Newly produced airplanes: Fuel tank flammability. (a) Applicability: This... Series 767 Series (b) Any fuel tank meeting all of the criteria stated in paragraphs (b)(1), (b)(2) and...

Layer 6 cortical neurons require Reelin-Dab1 signaling for cellular orientation, Golgi deployment, and directed neurite growth into the marginal zone.

Science.gov (United States)

O'Dell, Ryan S; Ustine, Candida J M; Cameron, David A; Lawless, Sean M; Williams, Rebecca M; Zipfel, Warren R; Olson, Eric C

2012-07-07

The secreted ligand Reelin is believed to regulate the translocation of prospective layer 6 (L6) neocortical neurons into the preplate, a loose layer of pioneer neurons that overlies the ventricular zone. Recent studies have also suggested that Reelin controls neuronal orientation and polarized dendritic growth during this period of early cortical development. To explicitly characterize and quantify how Reelin controls this critical aspect of neurite initiation and growth we used a new ex utero explant model of early cortical development to selectively label a subset of L6 cortical neurons for complete 3-D reconstruction. The total neurite arbor sizes of neurons in Reelin-deficient (reeler mutant) and Dab1-deficient (Reelin-non-responsive scrambler mutant) cortices were quantified and unexpectedly were not different than control arbor lengths (p = 0.51). For each mutant, however, arbor organization was markedly different: mutant neurons manifested more primary processes (neurites emitted directly from the soma) than wild type, and these neurites were longer and displayed less branching. Reeler and scrambler mutant neurites extended tangentially rather than radially, and the Golgi apparatus that normally invests the apical neurite was compact in both reeler and scrambler mutants. Mutant cortices also exhibited a neurite "exclusion zone" which was relatively devoid of L6 neuron neurites and extended at least 15 μm beneath the pial surface, an area corresponding to the marginal zone (MZ) in the wild type explants. The presence of an exclusion zone was also indicated in the orientation of mutant primary neurite and neuronal somata, which failed to adopt angles within ~20˚ of the radial line to the pial surface. Injection of recombinant Reelin to reeler, but not scrambler, mutant cortices fully rescued soma orientation, Golgi organization, and dendritic projection defects within four hrs. These findings indicate Reelin promotes directional dendritic growth into

Chrysosplenium japonicum (Saxifragaceae, Newly Recorded from Taiwan

Directory of Open Access Journals (Sweden)

Tian-Chuan Hsu

2011-11-01

Full Text Available Chrysosplenium japonicum (Maxim. Makino (Saxifragaceae is newly recorded from northeastern Taiwan. Description, color photos and a key to the Chrysosplenium species in Taiwan are provided.

Papel del diacilglicerol en el tráfico de membranas en la zona entre el retículo endoplasmático y el complejo de Golgi, El

OpenAIRE

Fernández Ulibarri, Inés

2008-01-01

DE LA TESIS:El DAG es esencial para formar los intermediarios de transporte que se dirigen a la membrana plasmática. Sin embargo, no existen evidencias de su posible participación en las etapas tempranas de la vía secretora. Por tanto, nos centramos en averiguar la implicación del DAG en el transporte de proteínas en la zona del ER/Golgi. Para ello, utilizamos una variedad de fármacos conocidos que inhiben las enzimas responsables de la producción del DAG. Nuestros datos indican que el DAG es...

El Papel del diacilglicerol en el tráfico de membranas en la zona entre el retículo endoplasmático y el complejo de Golgi

OpenAIRE

Fernández Ulibarri, Inés

2008-01-01

[spa] DE LA TESIS: El DAG es esencial para formar los intermediarios de transporte que se dirigen a la membrana plasmática. Sin embargo, no existen evidencias de su posible participación en las etapas tempranas de la vía secretora. Por tanto, nos centramos en averiguar la implicación del DAG en el transporte de proteínas en la zona del ER/Golgi. Para ello, utilizamos una variedad de fármacos conocidos que inhiben las enzimas responsables de la producción del DAG. Nuestros datos indican que el...

Newly developed chitosan-silver hybrid nanoparticles: biosafety and apoptosis induction in HepG2 cells

International Nuclear Information System (INIS)

El-Sherbiny, Ibrahim M.; Salih, Ehab; Yassin, Abdelrahman M.; Hafez, Elsayed E.

2016-01-01

The present study reports the biosafety assessment, the exact molecular effects, and apoptosis induction of newly developed chitosan-silver hybrid nanoparticles (Cs–Ag NPs) in HepG2 cells. The investigated hybrid NPs were green synthesized using Cs/grape leaves aqueous extract (Cs/GLE) or Cs/GLE NPs as reducing and stabilizing agents. The successful formation of Cs/GLE NPs and Cs–Ag hybrid NPs has been confirmed by UV–Vis spectrophotometry, FTIR spectroscopy, XRD, and HRTEM. From the TEM analysis, the prepared Cs/GLE NPs are uniform and spherical with an average size of 150 nm, and the AgNPs (5–10 nm) were formed mainly on their surface. The UV–Vis spectra of Cs–Ag NPs showed a surface plasmon resonance (SPR) peak at about 450 nm confirming their formation. The synthesized Cs–Ag NPs were found to be crystalline as shown by XRD patterns with fcc phase oriented along the (111), (200), (220), and (311) planes. The cytotoxicity patterns, the antiproliferative activities, and the possible mechanisms of anticancer activity at molecular level of the newly developed Cs–Ag hybrid NPs were investigated. Cytotoxicity patterns of all the preparations demonstrated that the nontoxic treatment concentrations are ranged from 0.39 to 50 %, and many of the newly prepared Cs–Ag hybrid NPs showed high anticancer activities against HpG2 cells, and induced cellular apoptosis by downregulating BCL2 gene and upregulating P53.Graphical Abstract

Newly developed chitosan-silver hybrid nanoparticles: biosafety and apoptosis induction in HepG2 cells

Energy Technology Data Exchange (ETDEWEB)

El-Sherbiny, Ibrahim M., E-mail: ielsherbiny@Zewailcity.edu.eg; Salih, Ehab [Zewail City of Science and Technology, Center for Materials Science (Egypt); Yassin, Abdelrahman M. [Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technology Applications, Biopharmaceutical Product Research Department (Egypt); Hafez, Elsayed E. [City of Scientific Research and Technology Applications, Plant Protection and Biomolecular Diagnosis Department (Egypt)

2016-07-15

The present study reports the biosafety assessment, the exact molecular effects, and apoptosis induction of newly developed chitosan-silver hybrid nanoparticles (Cs–Ag NPs) in HepG2 cells. The investigated hybrid NPs were green synthesized using Cs/grape leaves aqueous extract (Cs/GLE) or Cs/GLE NPs as reducing and stabilizing agents. The successful formation of Cs/GLE NPs and Cs–Ag hybrid NPs has been confirmed by UV–Vis spectrophotometry, FTIR spectroscopy, XRD, and HRTEM. From the TEM analysis, the prepared Cs/GLE NPs are uniform and spherical with an average size of 150 nm, and the AgNPs (5–10 nm) were formed mainly on their surface. The UV–Vis spectra of Cs–Ag NPs showed a surface plasmon resonance (SPR) peak at about 450 nm confirming their formation. The synthesized Cs–Ag NPs were found to be crystalline as shown by XRD patterns with fcc phase oriented along the (111), (200), (220), and (311) planes. The cytotoxicity patterns, the antiproliferative activities, and the possible mechanisms of anticancer activity at molecular level of the newly developed Cs–Ag hybrid NPs were investigated. Cytotoxicity patterns of all the preparations demonstrated that the nontoxic treatment concentrations are ranged from 0.39 to 50 %, and many of the newly prepared Cs–Ag hybrid NPs showed high anticancer activities against HpG2 cells, and induced cellular apoptosis by downregulating BCL2 gene and upregulating P53.Graphical Abstract.

Estimating the impact of newly arrived foreign-born persons on tuberculosis in the United States.

Directory of Open Access Journals (Sweden)

Yecai Liu

Full Text Available Among approximately 163.5 million foreign-born persons admitted to the United States annually, only 500,000 immigrants and refugees are required to undergo overseas tuberculosis (TB screening. It is unclear what extent of the unscreened nonimmigrant visitors contributes to the burden of foreign-born TB in the United States.We defined foreign-born persons within 1 year after arrival in the United States as "newly arrived", and utilized data from U.S. Department of Homeland Security, U.S. Centers for Disease Control and Prevention, and World Health Organization to estimate the incidence of TB among newly arrived foreign-born persons in the United States. During 2001 through 2008, 11,500 TB incident cases, including 291 multidrug-resistant TB incident cases, were estimated to occur among 20,989,738 person-years for the 1,479,542,654 newly arrived foreign-born persons in the United States. Of the 11,500 estimated TB incident cases, 41.6% (4,783 occurred among immigrants and refugees, 36.6% (4,211 among students/exchange visitors and temporary workers, 13.8% (1,589 among tourists and business travelers, and 7.3% (834 among Canadian and Mexican nonimmigrant visitors without an I-94 form (e.g., arrival-departure record. The top 3 newly arrived foreign-born populations with the largest estimated TB incident cases per 100,000 admissions were immigrants and refugees from high-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of ≥100 cases/100,000 population/year; 235.8 cases/100,000 admissions, 95% confidence interval [CI], 228.3 to 243.3, students/exchange visitors and temporary workers from high-incidence countries (60.9 cases/100,000 admissions, 95% CI, 58.5 to 63.3, and immigrants and refugees from medium-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of 15-99 cases/100,000 population/year; 55.2 cases/100,000 admissions, 95% CI, 51.6 to 58.8.Newly arrived nonimmigrant visitors contribute substantially to the burden of

Estimating the impact of newly arrived foreign-born persons on tuberculosis in the United States.

Science.gov (United States)

Liu, Yecai; Painter, John A; Posey, Drew L; Cain, Kevin P; Weinberg, Michelle S; Maloney, Susan A; Ortega, Luis S; Cetron, Martin S

2012-01-01

Among approximately 163.5 million foreign-born persons admitted to the United States annually, only 500,000 immigrants and refugees are required to undergo overseas tuberculosis (TB) screening. It is unclear what extent of the unscreened nonimmigrant visitors contributes to the burden of foreign-born TB in the United States. We defined foreign-born persons within 1 year after arrival in the United States as "newly arrived", and utilized data from U.S. Department of Homeland Security, U.S. Centers for Disease Control and Prevention, and World Health Organization to estimate the incidence of TB among newly arrived foreign-born persons in the United States. During 2001 through 2008, 11,500 TB incident cases, including 291 multidrug-resistant TB incident cases, were estimated to occur among 20,989,738 person-years for the 1,479,542,654 newly arrived foreign-born persons in the United States. Of the 11,500 estimated TB incident cases, 41.6% (4,783) occurred among immigrants and refugees, 36.6% (4,211) among students/exchange visitors and temporary workers, 13.8% (1,589) among tourists and business travelers, and 7.3% (834) among Canadian and Mexican nonimmigrant visitors without an I-94 form (e.g., arrival-departure record). The top 3 newly arrived foreign-born populations with the largest estimated TB incident cases per 100,000 admissions were immigrants and refugees from high-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of ≥100 cases/100,000 population/year; 235.8 cases/100,000 admissions, 95% confidence interval [CI], 228.3 to 243.3), students/exchange visitors and temporary workers from high-incidence countries (60.9 cases/100,000 admissions, 95% CI, 58.5 to 63.3), and immigrants and refugees from medium-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of 15-99 cases/100,000 population/year; 55.2 cases/100,000 admissions, 95% CI, 51.6 to 58.8). Newly arrived nonimmigrant visitors contribute substantially to the burden of foreign

People newly in love are more responsive to positive feedback.

Science.gov (United States)

Brown, Cassandra L; Beninger, Richard J

2012-06-01

Passionate love is associated with increased activity in dopamine-rich regions of the brain. Increased dopamine in these regions is associated with a greater tendency to learn from reward in trial-and-error learning tasks. This study examined the prediction that individuals who were newly in love would be better at responding to reward (positive feedback). In test trials, people who were newly in love selected positive outcomes significantly more often than their single (not in love) counterparts but were no better at the task overall. This suggests that people who are newly in love show a bias toward responding to positive feedback, which may reflect a general bias towards reward-seeking.

78 kDa receptor for Man6P-independent lysosomal enzyme targeting: Biosynthetic transport from endoplasmic reticulum to 'high-density vesicles'

International Nuclear Information System (INIS)

Gonzalez-Noriega, Alfonso; Ortega Cuellar, Daniel D.; Michalak, Colette

2006-01-01

Recent work has shown that the cation-independent mannose 6-phosphate and the 78 kDa receptors for lysosomal enzyme targeting are located in different cell compartments. While the mannose 6-phosphate receptor is enriched in the Percoll fractions that contain Golgi apparatus, most of the 78 kDa receptor is localized in a heavy fraction at the bottom of the Percoll gradient. This report presents the biosynthetic transport of the 78 kDa receptor. Newly synthesized 78 kDa receptor was transported to Golgi from endoplasmic reticulum with a half life of 5 min. From the Golgi apparatus, the receptor takes two routes; about 15-25% is transported to the plasma membrane, and the rest migrates to late endosomes, subsequently to prelysosomes and finally to the dense vesicles. The 78 kDa receptor starts appearing at the dense vesicles 120 min after biosynthesis and reaches a maximum of 40-50% of the total receptor. Treatment of cells with NH 4 Cl causes depletion of the receptor from the dense vesicles and prelysosomes and corresponding augmentation in endosomes and plasma membrane. These results suggest that the 78 kDa receptor cycles between compartments and that the dense vesicles seem to represent the most distal compartment in the biosynthetic pathway of this receptor

Effect of colchicine on the transport of precursor enamel protein in secretory ameloblasts studied by 3H-proline radioautography in vitro

International Nuclear Information System (INIS)

Matsuo, S.; Takano, Y.; Wakisaka, S.; Ichikawa, H.; Nishikawa, S.; Akai, M.

1988-01-01

The incorporation of 3H-proline into the secretory ameloblasts of rat molar tooth germs cultured with or without colchicine was studied by light and electron microscope radioautography to determine the function of microtubules in the transport of precursor enamel protein from the rough-surfaced endoplasmic reticulum (rER) to the Golgi cisternae. The grain counts over the transitional vesicles, which accumulated in various cellular regions with colchicine treatment, continued to increase with chase time, unlike in controls. At 30 and 90 min chase, these counts were significantly higher than in controls. Moreover, the total grain count over the organelles (rER, pale granules, and transitional vesicles), which are positioned before the Golgi cisternae in the synthetic pathway, maintained a significantly higher level at 90 min chase in colchicine-treated tooth germs than in controls. The transport of synthesized protein to the Golgi cisternae via transitional vesicles was suppressed in colchicine-treated tooth germs. Some grains appeared with time over pale granular materials that appeared in the intercellular spaces of secretory ameloblasts with colchicine treatment. However, at each chase period, the grain count over pale granular materials was not so high as the count over the enamel in control. The present results indicate that colchicine affects the transport of newly synthesized protein from the rER to the Golgi cisterna via transitional vesicles, probably by interfering with the oriented transport related to microtubular function. It is suggested that the microtubular system may be concerned with the movement of the transitional vesicles

Workplace Violence and Job Outcomes of Newly Licensed Nurses

OpenAIRE

Chang, Hyoung Eun; Cho, Sung-Hyun

2016-01-01

Purpose: The purpose of this study was to examine the prevalence of workplace violence toward newly licensed nurses and the relationship between workplace violence and job outcomes. Methods: An online survey was conducted of newly licensed registered nurses who had obtained their license in 2012 or 2013 in South Korea and had been working for 5–12 months after first being employed. The sample consisted of 312 nurses working in hospitals or clinics. The Copenhagen Psychosocial Questionnaire...

A NEWLY FORMING COLD FLOW PROTOGALACTIC DISK, A SIGNATURE OF COLD ACCRETION FROM THE COSMIC WEB

International Nuclear Information System (INIS)

Martin, D. Christopher; Matuszewski, Mateusz; Morrissey, Patrick; Neill, James D.; Moore, Anna; Steidel, Charles C.; Trainor, Ryan

2016-01-01

How galaxies form from, and are fueled by, gas from the intergalactic medium (IGM) remains one of the major unsolved problems in galaxy formation. While the classical Cold Dark Matter paradigm posits galaxies forming from cooling virialized gas, recent theory and numerical simulations have highlighted the importance of cold accretion flows—relatively cool ( T ∼ few × 104 K) unshocked gas streaming along filaments into dark matter halos, including hot, massive, high-redshift halos. These flows are thought to deposit gas and angular momentum into the circumgalactic medium resulting in disk- or ring-like structures, eventually coalescing into galaxies forming at filamentary intersections. We earlier reported a bright, Ly α emitting filament near the QSO HS1549+19 at redshift z = 2.843 discovered with the Palomar Cosmic Web Imager. We now report that the bright part of this filament is an enormous ( R > 100 kpc) rotating structure of hydrogen gas with a disk-like velocity profile consistent with a 4 × 10"1"2 M _⊙ halo. The orbital time of the outer part of the what we term a “protodisk” is comparable to the virialization time and the age of the universe at this redshift. We propose that this protodisk can only have recently formed from cold gas flowing directly from the cosmic web.

A NEWLY FORMING COLD FLOW PROTOGALACTIC DISK, A SIGNATURE OF COLD ACCRETION FROM THE COSMIC WEB

Energy Technology Data Exchange (ETDEWEB)

Martin, D. Christopher; Matuszewski, Mateusz; Morrissey, Patrick; Neill, James D. [Cahill Center for Astrophysics, California Institute of Technology, 1216 East California Boulevard, Mail Code 278-17, Pasadena, California 91125 (United States); Moore, Anna [Caltech Optical Observatories, Cahill Center for Astrophysics, California Institute of Technology, 1216 East California Boulevard, Mail Code 11-17, Pasadena, California 91125 (United States); Steidel, Charles C. [Cahill Center for Astrophysics, California Institute of Technology, 1216 East California Boulevard, Mail Code 249-17, Pasadena, California 91125 (United States); Trainor, Ryan, E-mail: cmartin@srl.caltech.edu [Department of Astronomy, University of California, Berkeley, 501 15 Campbell Hall, Berkeley, CA 94720 (United States)

2016-06-10

How galaxies form from, and are fueled by, gas from the intergalactic medium (IGM) remains one of the major unsolved problems in galaxy formation. While the classical Cold Dark Matter paradigm posits galaxies forming from cooling virialized gas, recent theory and numerical simulations have highlighted the importance of cold accretion flows—relatively cool ( T ∼ few × 104 K) unshocked gas streaming along filaments into dark matter halos, including hot, massive, high-redshift halos. These flows are thought to deposit gas and angular momentum into the circumgalactic medium resulting in disk- or ring-like structures, eventually coalescing into galaxies forming at filamentary intersections. We earlier reported a bright, Ly α emitting filament near the QSO HS1549+19 at redshift z = 2.843 discovered with the Palomar Cosmic Web Imager. We now report that the bright part of this filament is an enormous ( R > 100 kpc) rotating structure of hydrogen gas with a disk-like velocity profile consistent with a 4 × 10{sup 12} M {sub ⊙} halo. The orbital time of the outer part of the what we term a “protodisk” is comparable to the virialization time and the age of the universe at this redshift. We propose that this protodisk can only have recently formed from cold gas flowing directly from the cosmic web.

Exercise recommendations in patients with newly diagnosed fibromyalgia.

Science.gov (United States)

Wilson, Brad; Spencer, Horace; Kortebein, Patrick

2012-04-01

To evaluate exercise recommendations in patients newly diagnosed with fibromyalgia. A retrospective chart review. A public university rheumatology clinic. Patients newly diagnosed with fibromyalgia (N = 122). Frequency and type of exercise recommendations. The mean (standard deviation) age of these patients with fibromyalgia was 45 ± 12 years; 91% were women. Exercise was recommended as part of the documented treatment plan in 47% of these patients (57/122); only 3 patients had a documented contraindication for exercise. Aquatic exercise was most frequently recommended (56% [32/57]), followed by combined aquatic-aerobic exercise (26% [15/57]), and, infrequently, aerobic exercise only (5% [3/57]); only 7% of these patients (4/57) were referred for physical therapy. The primary method of communication was verbal discussion (94% [54/57]). Although there is well-documented evidence that exercise is beneficial for patients with fibromyalgia, we found that less than half of patients with newly diagnosed fibromyalgia in our study were provided recommendations to initiate an exercise program as part of their treatment plan. Further investigation of these findings are warranted, including evaluation of other university and community rheumatology practices as well as that of other physicians caring for patients with fibromyalgia. However, our findings indicate that there appears to be an opportunity to provide more specific and practical education regarding the implementation of an exercise regimen for patients with newly diagnosed fibromyalgia. Physiatrists may be particularly well suited to manage the exercise component of patients with fibromyalgia because of their specialized training in exercise prescription. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

DEFF Research Database (Denmark)

Saglio, Giuseppe; Kim, Dong-Wook; Issaragrisil, Surapol

2010-01-01

Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase.......Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase....

Transformation of organic N newly added to red soil treated with different cultural practices

Institute of Scientific and Technical Information of China (English)

ZhangQin－Zheng; YeQing－Fu; 等

1998-01-01

By using 15N tracer method,transformation of organic N,which wqas newly added to red soil treated with different cultural practices,was studied under thelaboratory incubation condition.The experimental results showed that the transformation of N from newly added organic matter and soil native pool during incubation was influenced by cultural practice treatment beforeincubation.Fallow was favorable to the mineralization of newly added organic N and soil N compared with the planting wheat treatment.Planting wheat greatly increased the loss of soil N.Application of fertilizers stimulated the mineralization of newly added organic N and application of organic matter reduced the mineralization,but stimulated microbialtransformation of newly adde4d organic N.

Savannah River Certification Plan for newly generated, contact-handled transuranic waste

International Nuclear Information System (INIS)

Wierzbicki, K.S.

1986-01-01

This Certification Plan document describes the necessary processes and methods for certifying unclassified, newly generated, contact-handled solid transuranic (TRU) waste at the Savannah River Plant and Laboratory (SRP, SRL) to comply with the Waste Isolation Pilot Plant Waste Acceptance Criteria (WIPP-WAC). Section 2 contains the organizational structure as related to waste certification including a summary of functional responsibilities, levels of authority, and lines of communication of the various organizations involved in certification activities. Section 3 describes general plant operations and TRU waste generation. Included is a description of the TRU Waste classification system. Section 4 contains the SR site TRU Waste Quality Assurance Program Plan. Section 5 describes waste container procurement, inspection, and certification prior to being loaded with TRU waste. Certification of waste packages, after package closure in the waste generating areas, is described in Section 6. The packaging and certification of individual waste forms is described in Attachments 1-5. Included in each attachment is a description of controls used to ensure that waste packages meet all applicable waste form compliance requirements for shipment to the WIPP. 3 figs., 3 tabs

GRASP55 Senses Glucose Deprivation through O-GlcNAcylation to Promote Autophagosome-Lysosome Fusion.

Science.gov (United States)

Zhang, Xiaoyan; Wang, Leibin; Lak, Behnam; Li, Jie; Jokitalo, Eija; Wang, Yanzhuang

2018-04-23

The Golgi apparatus is the central hub for protein trafficking and glycosylation in the secretory pathway. However, how the Golgi responds to glucose deprivation is so far unknown. Here, we report that GRASP55, the Golgi stacking protein located in medial- and trans-Golgi cisternae, is O-GlcNAcylated by the O-GlcNAc transferase OGT under growth conditions. Glucose deprivation reduces GRASP55 O-GlcNAcylation. De-O-GlcNAcylated GRASP55 forms puncta outside of the Golgi area, which co-localize with autophagosomes and late endosomes/lysosomes. GRASP55 depletion reduces autophagic flux and results in autophagosome accumulation, while expression of an O-GlcNAcylation-deficient mutant of GRASP55 accelerates autophagic flux. Biochemically, GRASP55 interacts with LC3-II on the autophagosomes and LAMP2 on late endosomes/lysosomes and functions as a bridge between LC3-II and LAMP2 for autophagosome and lysosome fusion; this function is negatively regulated by GRASP55 O-GlcNAcylation. Therefore, GRASP55 senses glucose levels through O-GlcNAcylation and acts as a tether to facilitate autophagosome maturation. Copyright © 2018 Elsevier Inc. All rights reserved.

Detection of Overreported Psychopathology with the MMPI-2 RF Form Validity Scales

Science.gov (United States)

Sellbom, Martin; Bagby, R. Michael

2010-01-01

We examined the utility of the validity scales on the recently released Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2 RF; Ben-Porath & Tellegen, 2008) to detect overreported psychopathology. This set of validity scales includes a newly developed scale and revised versions of the original MMPI-2 validity scales. We…

TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER-Golgi intermediate compartments.

Science.gov (United States)

Hanna, Michael G; Block, Samuel; Frankel, E B; Hou, Feng; Johnson, Adam; Yuan, Lin; Knight, Gavin; Moresco, James J; Yates, John R; Ashton, Randolph; Schekman, Randy; Tong, Yufeng; Audhya, Anjon

2017-09-12

The conserved coat protein complex II (COPII) mediates the initial steps of secretory protein trafficking by assembling onto subdomains of the endoplasmic reticulum (ER) in two layers to generate cargo-laden transport carriers that ultimately fuse with an adjacent ER-Golgi intermediate compartment (ERGIC). Here, we demonstrate that Trk-fused gene (TFG) binds directly to the inner layer of the COPII coat. Specifically, the TFG C terminus interacts with Sec23 through a shared interface with the outer COPII coat and the cargo receptor Tango1/cTAGE5. Our findings indicate that TFG binding to Sec23 outcompetes these other associations in a concentration-dependent manner and ultimately promotes outer coat dissociation. Additionally, we demonstrate that TFG tethers vesicles harboring the inner COPII coat, which contributes to their clustering between the ER and ERGIC in cells. Together, our studies define a mechanism by which COPII transport carriers are retained locally at the ER/ERGIC interface after outer coat disassembly, which is a prerequisite for fusion with ERGIC membranes.

Validation of an Adapted French Form of the Career Adapt-Abilities Scale in Four Francophone Countries

Science.gov (United States)

Johnston, Claire S.; Broonen, Jean-Paul; Stauffer, Sarah D.; Hamtiaux, Armanda; Pouyaud, Jacques; Zecca, Gregory; Houssemand, Claude; Rossier, Jerome

2013-01-01

This study presents the validation of a French version of the Career Adapt-Abilities Scale in four Francophone countries. The aim was to re-analyze the item selection and then compare this newly developed French-language form with the international form 2.0. Exploratory factor analysis was used as a tool for item selection, and confirmatory factor…

Possible origin of Saturn's newly discovered outer ring

International Nuclear Information System (INIS)

Moehlmann, D.

1986-01-01

Within a planetogonic model the self-gravitationally caused formation of pre-planetary and pre-satellite rings from an earlier thin disk is reported. The theoretically derived orbital radii of these rings are compared with the orbital levels in the planetary system and the satellite systems of Jupiter, Saturn and Uranus. From this comparison it is concluded that at the radial position of Saturn's newly discovered outer ring an early pre-satellite ring of more or less evolved satellites could have existed. These satellites should have been disturbed in their evolution by the gravitation of the neighbouring massive satellite Titan. The comparison also may indicate similarities between the asteroidal belt and the newly discovered outer ring of Saturn

Oral Cancer Knowledge Assessment: Newly Graduated versus Senior Dental Clinicians

Science.gov (United States)

Salgado de Souza, Ricardo; Gallego Arias Pecorari, Vanessa; Lauria Dib, Luciano

2018-01-01

The present study assessed the level of dentists' knowledge regarding oral cancer in the city of São Paulo, Brazil. A questionnaire was used to compare the level of knowledge among newly graduated and senior clinicians. A total of 20,154 e-mails were correctly delivered to the dentists registered in the database of the Regional Dentistry Council of São Paulo, and 477 (2.36%) responses were received. This sample consisted of 84 newly graduated clinicians and 105 senior clinicians. For the statistical analysis, the chi-square test and the logistic regression analysis were performed with α = 0.05, and the results were described herein. According to their knowledge level, the results were statistically different between the groups, since 19% of the newly graduated clinicians were evaluated with knowledge grade A (excellent) in comparison to 6.7% of the senior clinicians. In spite of the results indicated that newly graduated clinicians' knowledge regarding oral cancer was 2.1 times higher, 34.5% of the professionals in this group had regular or poor knowledge on the subject, and several questions relating to clinical characteristics and risk factors indicated that there still exist some knowledge gaps, demonstrating that there is a need for further studies and information activities addressing oral cancer. PMID:29666649

Career Motivation in Newly Licensed Registered Nurses: What Makes Them Remain

Science.gov (United States)

Banks, Zarata Mann; Bailey, Jessica H.

2010-01-01

Despite vast research on newly licensed registered nurses (RNs), we don't know why some newly licensed registered nurses remain in their current jobs and others leave the nursing profession early in their career. Job satisfaction, the most significant factor emerging from the literature, plays a significant role in nurses' decisions to remain in…

Meeting and activating the newly unemployed

DEFF Research Database (Denmark)

Rotger, Gabriel Pons

-demanding activity. As intensive activation is usually accompanied by intensive search monitoring, it is important to disentangling the contribution of the costly activation programs from that of caseworker meetings. Using Danish data for the period 2010-13, the paper shows that requiring newly unemployed intensive...... activation, contrary to job search meetings, reduces employment and increases sickness benefit claims....

Competence of newly qualified registered nurses from a nursing college

Directory of Open Access Journals (Sweden)

BG Morolong

2005-09-01

Full Text Available The South African education and training system, through its policy of outcomesbased education and training, has made competency a national priority. In compliance to this national requirement of producing competent learners, the South African Nursing Council ( 1999 B require that the beginner professional nurse practitioners and midwives have the necessary knowledge, skills, attitudes and values which will enable them to render efficient professional service. The health care system also demands competent nurse practitioners to ensure quality in health care. In the light of competency being a national priority and a statutory demand, the research question that emerges is, how competent are the newly qualified registered nurses from a specific nursing college in clinical nursing education? A quantitative, non-experimental contextual design was used to evaluate the competence of newly qualified registered nurses from a specific nursing college. The study was conducted in two phases. The first phase dealt with the development of an instrument together with its manual through the conceptualisation process. The second phase focused on the evaluation of the competency of newly qualified nurses using the instrument based on the steps of the nursing process. A pilot study was conducted to test the feasibility of the items of the instrument. During the evaluation phase, a sample of twenty-six newly qualified nurses was selected by simple random sampling from a target population of thirty-six newly qualified registered nurses. However, six participants withdrew from the study. Data was collected in two general hospitals where the newly qualified registered nurses were working. Observation and questioning were used as data collection techniques in accordance with the developed instrument. Measures were taken to ensure internal validity and reliability of the results. To protect the rights of the participants, the researcher adhered to DENOSA’S (1998

Different patterns of motor activity induce differential plastic changes in pyramidal neurons in the motor cortex of rats: A Golgi study.

Science.gov (United States)

Vázquez-Hernández, Nallely; González-Tapia, Diana C; Martínez-Torres, Nestor I; González-Tapia, David; González-Burgos, Ignacio

2017-09-14

Rehabilitation is a process which favors recovery after brain damage involving motor systems, and neural plasticity is the only real resource the brain has for inducing neurobiological events in order to bring about re-adaptation. Rats were placed on a treadmill and made to walk, in different groups, at different velocities and with varying degrees of inclination. Plastic changes in the spines of the apical and basal dendrites of fifth-layer pyramidal neurons in the motor cortices of the rats were detected after study with the Golgi method. Numbers of dendritic spines increased in the three experimental groups, and thin, mushroom, stubby, wide, and branched spines increased or decreased in proportion depending on the motor demands made of each group. Along with the numerical increase of spines, the present findings provide evidence that dendritic spines' geometrical plasticity is involved in the differential performance of motor activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical heterogeneity in newly diagnosed Parkinson's disease

NARCIS (Netherlands)

Post, Bart; Speelman, Johannes D.; de Haan, Rob J.

2008-01-01

OBJECTIVE: To determine clinical heterogeneity in newly diagnosed Parkinson's disease using cluster analysis and to describe the subgroups in terms of impairment, disability, perceived quality of life, and use of dopaminergic therapy. METHODS: We conducted a k-means cluster analysis in a prospective

The membrane-associated form of α(s1-casein interacts with cholesterol-rich detergent-resistant microdomains.

Directory of Open Access Journals (Sweden)

Annabelle Le Parc

Full Text Available Caseins, the main milk proteins, interact with colloidal calcium phosphate to form the casein micelle. The mesostructure of this supramolecular assembly markedly influences its nutritional and technological functionalities. However, its detailed molecular organization and the cellular mechanisms involved in its biogenesis have been only partially established. There is a growing body of evidence to support the concept that α(s1-casein takes center stage in casein micelle building and transport in the secretory pathway of mammary epithelial cells. Here we have investigated the membrane-associated form of α(s1-casein in rat mammary epithelial cells. Using metabolic labelling we show that α(s1-casein becomes associated with membranes at the level of the endoplasmic reticulum, with no subsequent increase at the level of the Golgi apparatus. From morphological and biochemical data, it appears that caseins are in a tight relationship with membranes throughout the secretory pathway. On the other hand, we have observed that the membrane-associated form of α(s1-casein co-purified with detergent-resistant membranes. It was poorly solubilised by Tween 20, partially insoluble in Lubrol WX, and substantially insoluble in Triton X-100. Finally, we found that cholesterol depletion results in the release of the membrane-associated form of α(s1-casein. These experiments reveal that the insolubility of α(s1-casein reflects its partial association with a cholesterol-rich detergent-resistant microdomain. We propose that the membrane-associated form of α(s1-casein interacts with the lipid microdomain, or lipid raft, that forms within the membranes of the endoplasmic reticulum, for efficient forward transport and sorting in the secretory pathway of mammary epithelial cells.

The Membrane-Associated Form of αs1-Casein Interacts with Cholesterol-Rich Detergent-Resistant Microdomains

Science.gov (United States)

Le Parc, Annabelle; Honvo Houéto, Edith; Pigat, Natascha; Chat, Sophie; Leonil, Joëlle; Chanat, Eric

2014-01-01

Caseins, the main milk proteins, interact with colloidal calcium phosphate to form the casein micelle. The mesostructure of this supramolecular assembly markedly influences its nutritional and technological functionalities. However, its detailed molecular organization and the cellular mechanisms involved in its biogenesis have been only partially established. There is a growing body of evidence to support the concept that αs1-casein takes center stage in casein micelle building and transport in the secretory pathway of mammary epithelial cells. Here we have investigated the membrane-associated form of αs1-casein in rat mammary epithelial cells. Using metabolic labelling we show that αs1-casein becomes associated with membranes at the level of the endoplasmic reticulum, with no subsequent increase at the level of the Golgi apparatus. From morphological and biochemical data, it appears that caseins are in a tight relationship with membranes throughout the secretory pathway. On the other hand, we have observed that the membrane-associated form of αs1-casein co-purified with detergent-resistant membranes. It was poorly solubilised by Tween 20, partially insoluble in Lubrol WX, and substantially insoluble in Triton X-100. Finally, we found that cholesterol depletion results in the release of the membrane-associated form of αs1-casein. These experiments reveal that the insolubility of αs1-casein reflects its partial association with a cholesterol-rich detergent-resistant microdomain. We propose that the membrane-associated form of αs1-casein interacts with the lipid microdomain, or lipid raft, that forms within the membranes of the endoplasmic reticulum, for efficient forward transport and sorting in the secretory pathway of mammary epithelial cells. PMID:25549363

The membrane-associated form of α(s1)-casein interacts with cholesterol-rich detergent-resistant microdomains.

Science.gov (United States)

Le Parc, Annabelle; Honvo Houéto, Edith; Pigat, Natascha; Chat, Sophie; Leonil, Joëlle; Chanat, Eric

2014-01-01

Caseins, the main milk proteins, interact with colloidal calcium phosphate to form the casein micelle. The mesostructure of this supramolecular assembly markedly influences its nutritional and technological functionalities. However, its detailed molecular organization and the cellular mechanisms involved in its biogenesis have been only partially established. There is a growing body of evidence to support the concept that α(s1)-casein takes center stage in casein micelle building and transport in the secretory pathway of mammary epithelial cells. Here we have investigated the membrane-associated form of α(s1)-casein in rat mammary epithelial cells. Using metabolic labelling we show that α(s1)-casein becomes associated with membranes at the level of the endoplasmic reticulum, with no subsequent increase at the level of the Golgi apparatus. From morphological and biochemical data, it appears that caseins are in a tight relationship with membranes throughout the secretory pathway. On the other hand, we have observed that the membrane-associated form of α(s1)-casein co-purified with detergent-resistant membranes. It was poorly solubilised by Tween 20, partially insoluble in Lubrol WX, and substantially insoluble in Triton X-100. Finally, we found that cholesterol depletion results in the release of the membrane-associated form of α(s1)-casein. These experiments reveal that the insolubility of α(s1)-casein reflects its partial association with a cholesterol-rich detergent-resistant microdomain. We propose that the membrane-associated form of α(s1)-casein interacts with the lipid microdomain, or lipid raft, that forms within the membranes of the endoplasmic reticulum, for efficient forward transport and sorting in the secretory pathway of mammary epithelial cells.

Response of sesame to population densities and nitrogen fertilization on newly reclaimed sandy soils

International Nuclear Information System (INIS)

Noorka, I.R.; Hafiz, S.I.

2011-01-01

Two field experiments were conducted at the Experimental Farm of Faculty of Agriculture, Suez Canal University at Ismailia during 2008 and 2009 seasons to study the effect of nitrogen fertilization and planting density on growth , yield, its attributes as well as seed quality of new sesame variety (Taka 2 cv.). On newly reclaimed sandy soils of Ismailia Governorate, Egypt, experimental design in split plots form with four replications was used. Four levels of nitrogen fertilization 55, 105, 155 and 205 Kg/ha were arranged randomly in the main plots and three planting distances between hills (10, 15 and 20 cm, respectively) were distributed at random in the sub plots. Increasing N fertilizer level up to 205 Kg/ha significantly increased plant height, fruiting zone length, height of the first fruiting branch, number of branches and capsules/plant, 1000-seed weight, seed weight/plant, seed oil content (%) and seed and oil yields /ha. Decreasing planting distance from 20 to 15 and 10 cm consistently and significantly increased plant height, height of the first fruiting branch and seed and oil yields /ha. The reverse was true regarding the yield components. These results were expected, since experiment soil was newly reclaimed sandy soil and very poor in the nutrients and organic matter. (author)

Golgi protein 73 versus alpha-fetoprotein as a biomarker for hepatocellular carcinoma: a diagnostic meta- analysis

International Nuclear Information System (INIS)

Zhou, Ying; Yin, Xin; Ying, Jun; Zhang, BoHeng

2012-01-01

There have been conflicting reports about serum golgi protein 73 (GP73) as one of the most promising serum markers for the diagnosis of hepatocellular carcinoma (HCC). This study was to make a systematic review about the diagnostic accuracy of serum GP73 versus alpha-fetoprotein (AFP) for HCC. After a systematic review of related studies, sensitivity, specificity and other measures about the accuracy of serum GP73 and AFP in the diagnosis of HCC were pooled using random-effects models. Summary receiver operating characteristic curve analysis was used to summarize the overall test performance. Eight studies were included in our meta-analysis. The summary estimates for serum GP73 and AFP in diagnosing HCC in the studies included were as follows: sensitivity, 76% (95% confidence interval (CI) 51-91%) vs. 70% (47-86%); specificity, 86% (95%CI 65-95%) vs. 89% (69-96%); diagnostic odds ratio (DOR), 18.59 (95%CI 5.33-64.91) vs. 18.00(9.41-34.46); and area under sROC, 0.88 (95%CI 0.77-0.99) vs. 0.86 (95%CI 0.84-0.87). The current evidence indicates that serum GP73 has a comparable accuracy to AFP for the diagnosis of HCC, while the value of serum GP73 in combination with AFP for HCC detection deserves further investigation

GOLGA2/GM130, cis-Golgi matrix protein, is a novel target of anticancer gene therapy.

Science.gov (United States)

Chang, Seung-Hee; Hong, Seong-Ho; Jiang, Hu-Lin; Minai-Tehrani, Arash; Yu, Kyeong-Nam; Lee, Jae-Ho; Kim, Ji-Eun; Shin, Ji-Young; Kang, Bitna; Park, Sungjin; Han, Kiwon; Chae, Chanhee; Cho, Myung-Haing

2012-11-01

Achievement of long-term survival of patients with lung cancer treated with conventional chemotherapy is still difficult for treatment of metastatic and advanced tumors. Despite recent progress in investigational therapies, survival rates are still disappointingly low and novel adjuvant and systemic therapies are urgently needed. A recently elucidated secretory pathway is attracting considerable interest as a promising anticancer target. The cis-Golgi matrix protein, GOLGA2/GM130, plays an important role in glycosylation and transport of protein in the secretory pathway. In this study, the effects of short hairpin RNA (shRNA) constructs targeting GOLGA2/GM130 (shGOLGA2) on autophagy and lung cancer growth were evaluated in vitro and in vivo. Downregulation of GOLGA2/GM130 led to induction of autophagy and inhibition of glycosylation in A549 cells and in the lungs of K-ras(LA1) mice. Furthermore, downregulation of GOLGA2/GM130 decreased angiogenesis and cancer cell invasion in vitro and suppressed tumorigenesis in lung cancer mice model. The tumor specificity of sequence targeting GOLGA2/GM130 was also demonstrated. Taken together, these results suggest that induction of autophagy by shGOLGA2 may induce cell death rather than cell survival. Therefore, downregulation of GOLGA2/GM130 may be a potential therapeutic option for lung cancer.

Structural rearrangements detected in newly-formed hexaploid ...

Indian Academy of Sciences (India)

signals were observed on the Epifluorescence microscope ... Images were cap- ... the chromosome pairs 1B and 6B in durum wheat (figure. 1e). The number and physical location ... 6B chromosome probably experienced an inverted pericen-.

Structural rearrangements detected in newly-formed hexaploid

Indian Academy of Sciences (India)

Institute of Biotechnology and Bioengineering (IBB), Centre of Genomics and Biotechnology (CGB), University of Tras-os-Montes and Alto Douro (UTAD), P.O. Box 1013, 5001-801 VilaReal, Portugal; Instituto de Agricultura Sostenible (IAS), Consejo Superior de Investigaciones Científicas (CSIC), Apartado 4084, 14080 ...

Ultrastructural investigation and in vitro recapitulation of spermatid differentiation in a potential bio-indicator species - The marine invertebrate Galeolaria gemineoa (Polychaeta: Serpulidae.

Directory of Open Access Journals (Sweden)

Yonggang Lu

Full Text Available Galeolaria gemineoa is a sessile broadcast-spawning marine invertebrate, whose spermatozoa have been regarded as a sensitive indicator for water quality monitoring. In this study, 10 steps of spermiogenesis have been identified at the ultrastructural level and this differentiation process has been recapitulated in vitro up to the point of spermiogenesis (step 7-9 spermatids. On completion of the second meiosis, newly formed spermatids were detached from the seminiferous epithelium and released to the lumen of each germinal chamber. These spermatids were present in pairs and interconnected by a cytoplasmic bridge throughout the entire spermiogenic process. On the basis of morphological events such as formation of the acrosome, elongation of the flagellum, and condensation of the nucleus, spermiogenesis has been temporally divided into Golgi phase, acrosomal phase and maturation phase. During the Golgi phase, proacrosomal vesicles appeared at the posterior pole of the spermatids and gradually fused into a proacrosomal vacuole. Simultaneously, the distal centriole docked onto the plasma membrane and gave rise to a formative flagellum. The acrosomal phase was characterised by differentiation of the acrosome, condensation of the chromatin and formation of a mitochondrial sheath surrounding the initial portion of the flagellum. During the maturation phase, the fully differentiated acrosome migrated to the anterior pole and excess cytoplasm was extruded from the spermatids in the form of residual bodies. In addition, we successfully induced step 1-3 spermatids to differentiate into the step 7-9 spermatids in both male germinal fluid and 10% foetal bovine serum in RPMI 1640 medium, but failed to replicate this process in female or boiled male germinal fluids. This finding supports our concept that spermatid differentiation in this species is dependent on intrinsic developmental programming and does not require input from accompanying nurse cells.

Two Newly Discovered Plants in Taiwan

OpenAIRE

Tian-Chuan Hsu; Jia-Jung Lin; Shih-Wen Chung

2009-01-01

Two herbs are newly discovered in Taiwan. Limnophila fragrans (G. Forst.) Seem. (Scrophulariaceae), native in SE Asia, is recognized from southern lowlands. Anagallis minima (L.) E. H. L. Krause (Primulaceae), native in N America and Europe, was found from northern mountainous region at low altitudes. In this study, descriptions, line drawings, color photos and a distribution map of the two species are provided.

A golgi study of the optic tectum of the tegu lizard, Tupinambis nigropunctatus.

Science.gov (United States)

Butler, A B; Ebbesson, O E

1975-06-01

The dendritic patterns of cells in the optic tectum of the tegu lizard, Tupinambis nigropunctatus, were analyzed with the Ramon-Moliner modification of the Golgi-Cox technique. Cell types were compared with those described by other authors in the tectum of other reptiles; particular comparisons of our results were made with the description of cell types in the chameleon (Ramń, 1896), as the latter is the most complete analysis in the literature. The periventricular gray layers 3 and 5 consist primarily of two cell types--piriform or pyramidal shaped cells and horizontal cells. Cells in the medial portion of the tectum, in an area coextensive with the bilateral spinal projection zone, possess dendrites that extend across the midline. The latter cells have either fusiform or pyramidal shaped somas. The central white zone, layer 6, contains fibers, large fusiform or pyramidal shaped cells, fusiform cells, and small horizontal cells. The central gray zone, layer 7, is composed predominately of fusiform cells which have dendrites extending to the superficial optic layers, large polygonal cells, and horizontal cells. The superficial gray and white layers, layers 8-13, contain polygonal, fusiform, stellate, and horizontal elements. Layer 14 is composed solely of afferent optic tract fibers. Several differences in the occurrence and distribution of cell types between the tegu and the other reptiles studied are noted. Additionally, the laminar distribution of retinal, tectotectal, telencephalic, and spinal projections in the tegutectum can be related to the distribution of cell types, and those cells which may be postsynaptic to specific inputs can be identified. The highly differentiated laminar structure of the reptilian optic tectum, both in regard to cell type and to afferent and efferent connections, may serve as a model for studying some functional properties of lamination common to cortical structures.

Pollen parameters estimates of genetic variability among newly ...

African Journals Online (AJOL)

Pollen parameters estimates of genetic variability among newly selected Nigerian roselle (Hibiscus sabdariffa L.) genotypes. ... Estimates of some pollen parameters where used to assess the genetic diversity among ... HOW TO USE AJOL.

Tricks of the trade: time management tips for newly qualified doctors.

Science.gov (United States)

Offiah, Gozie; Doherty, Eva

2018-03-01

The transition from medical student to doctor is an important milestone. The discovery that their time is no longer their own and that the demands of their job are greater than the time they have available is extremely challenging. At a recent surgical boot camp training programme, 60 first-year surgical trainees who had just completed their internship were invited to reflect on the lessons learnt regarding effective time management and to recommend tips for their newly qualified colleagues. They were asked to identify clinical duties that were considered urgent and important using the time management matrix and the common time traps encountered by newly qualified doctors. The surgical trainees identified several practical tips that ranged from writing a priority list to working on relationships within the team. These tips are generic and so applicable to all newly qualified medial doctors. We hope that awareness of these tips from the outset as against learning them through experience will greatly assist newly qualified doctors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chest Radiographic Findings in Newly Diagnosed Pulmonary ...

African Journals Online (AJOL)

Five hundred newly diagnosed cases of Pulmonary Tuberculosis were treated with directly observed short-course treatment and 100 of them had chest radiographic examination done. The various chest radiographic patterns in the 100 subjects were studied and included: Fluffy exudative changes 80(80%), fibrosis 70(70%) ...

Newly graduated nurses' empowerment regarding professional competence and other work-related factors.

Science.gov (United States)

Kuokkanen, Liisa; Leino-Kilpi, Helena; Numminen, Olivia; Isoaho, Hannu; Flinkman, Mervi; Meretoja, Riitta

2016-01-01

Although both nurse empowerment and competence are fundamental concepts of describing newly graduated nurses' professional development and job satisfaction, only few studies exist on the relationship between these concepts. Therefore, the purpose of this study was to determine how newly graduated nurses assess their empowerment and to clarify professional competence compared to other work-related factors. A descriptive, cross-sectional and correlational design was applied. The sample comprised newly graduated nurses (n = 318) in Finland. Empowerment was measured using the 19-item Qualities of an Empowered Nurse scale and the Nurse Competence Scale measured nurses' self-assessed generic competence. In addition to demographic data, the background data included employment sector (public/private), job satisfaction, intent to change/leave job, work schedule (shifts/business hours) and assessments of the quality of care in the workplace. The data were analysed statistically by using Spearman's correlation coefficient as well as the One-Way and Multivariate Analysis of Variance. Cronbach's alpha coefficient was used to estimate the internal consistency. Newly graduated nurses perceived their level of empowerment and competence fairly high. The association between nurse empowerment and professional competence was statistically significant. Other variables correlating positively to empowerment included employment sector, age, job satisfaction, intent to change job, work schedule, and satisfaction with the quality of care in the work unit. The study indicates competence had the strongest effect on newly graduated nurses' empowerment. New graduates need support and career opportunities. In the future, nurses' further education and nurse managers' resources for supporting and empowering nurses should respond to the newly graduated nurses' requisites for attractive and meaningful work.

Two Newly Discovered Plants in Taiwan

Directory of Open Access Journals (Sweden)

Tian-Chuan Hsu

2009-11-01

Full Text Available Two herbs are newly discovered in Taiwan. Limnophila fragrans (G. Forst. Seem. (Scrophulariaceae, native in SE Asia, is recognized from southern lowlands. Anagallis minima (L. E. H. L. Krause (Primulaceae, native in N America and Europe, was found from northern mountainous region at low altitudes. In this study, descriptions, line drawings, color photos and a distribution map of the two species are provided.

Diabetes education and self-management for ongoing and newly diagnosed (DESMOND)

DEFF Research Database (Denmark)

Skinner, T. Chas; Carey, Marian E.; Cradock, Sue

2006-01-01

diagnosed with Type 2 diabetes changes key illness beliefs and that these changes predict quality of life and metabolic control at 3-month follow-up. Practice implications: Newly diagnosed individuals are open to attending self-management programs and, if the program is theoretically driven, can......Objective: To determine the effects of a structured education program on illness beliefs, quality of life and physical activity in people newly diagnosed with Type 2 diabetes. Methods: Individuals attending a diabetes education and self-management for ongoing and newly diagnosed (DESMOND) program...... in 12 Primary Care Trusts completed questionnaire booklets assessing illness beliefs and quality of life at baseline and 3-month follow-up, metabolic control being assessed through assay of HbA1c. Results: Two hundred and thirty-six individuals attended the structured self-management education sessions...

Perceptions of the clinical competence of newly registered nurses in the North West province

Directory of Open Access Journals (Sweden)

M.R. Moeti

2004-09-01

Full Text Available The clinical competence of newly registered nurses relating to the care of individual Clients, depends on their ability to correlate theoretical knowledge learned in the classroom with practice and the development of clinical skills. Its foundation lies in the ability to identify and solve problems that emanate from critical thinking, analytical reasoning and reflective practice. It is clear that the quality of clinical exposure plays a leading role in the development of nursing professionals. Nursing skills alone cannot ensure quality care of clients without the application of theory. Facilitation of this theory to practice therefore remains an essential component of nursing education. This study was aimed at identifying areas of incompetence of newly registered nurses (1998- 2001 in the clinical area by determining the newly registered nurses1 and professional nurses1 perceptions of the competence of the newly registered nurses. A quantitative, non-experimental, descriptive survey was used to collect the data regarding the clinical competence of newly registered nurses (1998-2001.

Serum Golgi protein 73 is a prognostic rather than diagnostic marker in hepatocellular carcinoma.

Science.gov (United States)

Dong, Min; Chen, Zhan-Hong; Li, Xing; Li, Xiao-Yun; Wen, Jing-Yun; Lin, Qu; Ma, Xiao-Kun; Wei, Li; Chen, Jie; Ruan, Dan-Yun; Lin, Ze-Xiao; Wang, Tian-Tian; Wu, Dong-Hao; Wu, Xiang-Yuan

2017-11-01

Serum Golgi protein 73 (sGP73) is a candidate diagnostic biomarker for hepatocellular carcinoma (HCC). However, current evidence of its diagnostic value is conflicting, primarily due to the small sample sizes of previous studies, and its prognostic role in HCC also remains unclear. In the present study, sGP73 levels in 462 patients with HCC, 186 patients with liver cirrhosis, and 83 healthy controls were evaluated using ELISA, and it was identified that the median sGP73 levels were significantly higher in the HCC (18.7 ng/ml) and liver cirrhosis (18.5 ng/ml) patients than in the healthy controls (0 ng/ml; both P<0.001); however, the levels did not significantly differ between the HCC and liver cirrhosis groups (P=0.632). sGP73 had an inferior sensitivity and specificity for HCC diagnosis (27.79 and 77.96%, respectively) compared with α-fetoprotein (57.36 and 90.96%, respectively; P<0.001). In the HCC group, a high level of sGP73 was associated with aggressive clinicopathological features and independently predicted poor overall survival (OS) time (P<0.001). Additionally, in patients with resectable HCC, a high level of sGP73 was associated with significantly decreased disease-free survival (P<0.001) and OS (P=0.039) times compared with a low level of sGP73. This study demonstrated that sGP73 is unsuitable as a diagnostic marker for the early detection of HCC; however, it is an independent negative prognostic marker, providing a novel risk stratification factor and a potential therapeutic molecular target for HCC.

'Practising under your own Pin'- a description of the transition experiences of newly qualified midwives.

Science.gov (United States)

Avis, Mark; Mallik, Maggie; Fraser, Diane M

2013-11-01

Transition experiences of newly qualified midwives were examined in depth during the third phase of a UK evaluation study of midwifery education. The fitness to practise and the retention of newly qualified nursing and midwifery graduates are pressing concerns for health care managers. The advantages of preceptorship are reported in the literature but the content and timing of schemes remain unclear. A semi-structured diary was kept for up to 6 months by 35 newly qualified midwives in 18 work sites covering all countries in the UK. The preceptor and supervisor of midwives for each newly qualified midwife completed short questionnaires about their preceptee's performance, and a further sub-sample of newly qualified midwives and preceptors participated in a semi-structured interview. Data were analysed to elicit aspects of newly qualified midwives transition experiences. Findings confirm that structured preceptorship schemes are not widely available. Newly qualified midwives primarily obtained transition support from members of the midwifery team. Although perceived as competent, there is no demarcation point in becoming confident to practise as a registered practitioner. Implications for managers include the importance of a supportive culture within clinical teams for successful transition and the introduction of structured preceptorship schemes facilitated by appropriate rotation patterns. © 2012 John Wiley & Sons Ltd.

Assessment of FUN-1 vital dye staining: Yeast with a block in the vacuolar sorting pathway have impaired ability to form CIVS when stained with FUN-1 fluorescent dye.

Science.gov (United States)

Essary, Brandin D; Marshall, Pamela A

2009-08-01

FUN-1 [2-chloro-4-(2,3-dihydro-3-methyl-(benzo-1,3-thiazol-2-yl)-methylidene)-1-phenylquinolinium iodide] is a fluorescent dye used in studies of yeast and other fungi to monitor cell viability in the research lab and to assay for active fungal infection in the clinical setting. When the plasma membrane is intact, fungal cells internalize FUN-1 and the dye is seen as diffuse green cytosolic fluorescence. FUN-1 is then transported to the vacuole in metabolically active wild type cells and subsequently is compacted into fluorescent red cylindrical intravacuolar structures (CIVS) by an unknown transport pathway. This dye is used to determine yeast viability, as only live cells form CIVS. However, in live Saccharomyces cerevisiae with impaired protein sorting to the yeast vacuole, we report decreased to no CIVS formation, depending on the cellular location of the block in the sorting pathway. Cells with a block in vesicle-mediated transport from the Golgi to prevacuolar compartment (PVC) or with a block in recycling from the PVC to the Golgi demonstrate a substantial impairment in CIVS formation. Instead, the FUN-1 dye is seen either in small punctate structures under fluorescence or as diffuse red cytosol under white light. Thus, researchers using FUN-1 should be cognizant of the limitations of this procedure in determining cell viability as there are viable yeast mutants with impaired CIVS formation.

Combustion, performance and emissions characteristics of a newly ...

Indian Academy of Sciences (India)

of a newly developed CRDI single cylinder diesel engine. AVINASH ... In case of unit injector and unit pump systems, fuel injection pressure depends on ... nozzle hole diameters were effective in reducing smoke and PM emissions. However ...

Yield and Adaptability Evaluation of Newly Introduced Tomato ...

African Journals Online (AJOL)

High yield is a major ambition to tomato plant breeders and farmers. The purpose of the ... Tabora Region on the growth and yield of newly introduced tomato varieties. The tested ..... (1985). Evaluation of some American tomatocultivars grown.

Mentorship for newly appointed physicians: a strategy for enhancing patient safety?

Science.gov (United States)

Harrison, Reema; McClean, Serwaa; Lawton, Rebecca; Wright, John; Kay, Clive

2014-09-01

Mentorship is an increasingly popular innovation from business and industry that is being applied in health-care contexts. This paper explores the concept of mentorship for newly appointed physicians in their first substantive senior post, and specifically its utilization to enhance patient safety. Semi-structured face to face and telephone interviews with Medical Directors (n = 5), Deputy Medical Directors (n = 4), and Clinical Directors (n = 6) from 9 acute NHS Trusts in the Yorkshire and Humber region in the north of England. A focused thematic analysis was used. A number of beneficial outcomes were associated with mentorship for newly appointed physicians including greater personal and professional support, organizational commitment, and general well-being. Providing newly appointed senior physicians with support through mentorship was considered to enhance the safety of patient care. Mentorship may prevent or reduce active failures, be used to identify threats in the local working environment, and in the longer term, address latent threats to safety within the organization by encouraging a healthier safety culture. Offering mentorship to all newly appointed physicians in their first substantive post in health care may be a useful strategy to support the development of their clinical, professional, and personal skills in this transitional period that may also enhance the safety of patient care.

Newly elected IAEA Board of Governors

International Nuclear Information System (INIS)

2000-01-01

The document gives information about the election of 11 Member States to the IAEA Board of Governors, the 35-member policy-making body, during the 44th regular session of the IAEA's General Conference (18 - 22 September 2000, Austria Center, Vienna). The newly elected Member States are: Argentina, Egypt, Ghana, Ireland, Libyan Arab Jamahiriya, Mexico, Pakistan, Peru, Switzerland, Thailand, Ukraine. The other 24 Member States of the Board are also given

A newly developed snack effective for enhancing bone volume

Directory of Open Access Journals (Sweden)

Hayashi Hidetaka

2009-07-01

Full Text Available Abstract Background The incidence of primary osteoporosis is higher in Japan than in USA and European countries. Recently, the importance of preventive medicine has been gradually recognized in the field of orthopaedic surgery with a concept that peak bone mass should be increased in childhood as much as possible for the prevention of osteoporosis. Under such background, we have developed a new bean snack with an aim to improve bone volume loss. In this study, we examined the effects of a newly developed snack on bone volume and density in osteoporosis model mice. Methods Orchiectomy (ORX and ovariectomy (OVX were performed for C57BL/6J mice of twelve-week-old (Jackson Laboratory, Bar Harbar, ME, USA were used in this experiment. We prepared and given three types of powder diet e.g.: normal calcium diet (NCD, Ca: 0.9%, Clea Japan Co., Tokyo, Japan, low calcium diet (LCD, Ca: 0.63%, Clea Japan Co., and special diet (SCD, Ca: 0.9%. Eighteen weeks after surgery, all the animals were sacrified and prepared for histomorphometric analysis to quantify bone density and bone mineral content. Results As a result of histomorphometric examination, SCD was revealed to enhance bone volume irrespective of age and sex. The bone density was increased significantly in osteoporosis model mice fed the newly developmental snack as compared with the control mice. The bone mineral content was also enhanced significantly. These phenomena were revealed in both sexes. Conclusion It is shown that the newly developed bean snack is highly effective for the improvement of bone volume loss irrespective of sex. We demonstrated that newly developmental snack supplements may be a useful preventive measure for Japanese whose bone mineral density values are less than the ideal condition.

Clinical evaluation of a newly designed orthodontic tooth brush - A clinical study

Directory of Open Access Journals (Sweden)

C S Saimbi

2009-01-01

In this study, the newly designed orthodontic tooth brush is compared with an ordinary tooth brush. Results of this study show that the newly designed orthodontic tooth brush is superior in its cleaning efficiency as compared to the ordinary tooth brush. The results show that plaque removing capacity of orthodontic tooth brush is nearly 95-99%.

Newly qualified teachers´ possibilities to get foothold in a lifelong career course

DEFF Research Database (Denmark)

Krøjgaard, Frede; Frederiksen, Lisbeth Angela Lunde

Keyword: Induction program, newly qualified teachers, NQT, retention, professional development In Contrary to many other countries in Europe Denmark does not have any kind of national program regarding teacher induction program (TIP) or support in general to newly qualified teachers what so ever...

Design of an oval-form cathode for the precision etching process of e-paper surface

International Nuclear Information System (INIS)

Pa, P.S.

2009-01-01

A newly designed oval-form cathode using electroetching for indium-tin-oxide (ITO) microstructure removal from the surface of e-paper polymer PET films is presented. Through ultra-precise microstructural etching, the semiconductor industry can effectively reclaim defective products, thereby reducing production costs. The design features for the ITO removal process and the tool design of oval-form cathodes are of significant interest. A smaller oval-form cathode minor axis, a higher cathode rotational speed, a higher concentration, or a higher electrolyte temperature corresponds to a higher ITO etching rate.

Critical thinking dispositions among newly graduated nurses

Science.gov (United States)

Wangensteen, Sigrid; Johansson, Inger S; Björkström, Monica E; Nordström, Gun

2010-01-01

wangensteen s., johansson i.s., björkström m.e. & nordström g. (2010) Critical thinking dispositions among newly graduated nurses. Journal of Advanced Nursing66(10), 2170–2181. Aim The aim of the study was to describe critical thinking dispositions among newly graduated nurses in Norway, and to study whether background data had any impact on critical thinking dispositions. Background Competence in critical thinking is one of the expectations of nursing education. Critical thinkers are described as well-informed, inquisitive, open-minded and orderly in complex matters. Critical thinking competence has thus been designated as an outcome for judging the quality of nursing education programmes and for the development of clinical judgement. The ability to think critically is also described as reducing the research–practice gap and fostering evidence-based nursing. Methods A cross-sectional descriptive study was performed. The data were collected between October 2006 and April 2007 using the California Critical Thinking Disposition Inventory. The response rate was 33% (n= 618). Pearson’s chi-square tests were used to analyse the data. Results Nearly 80% of the respondents reported a positive disposition towards critical thinking. The highest mean score was on the Inquisitiveness subscale and the lowest on the Truth-seeking subscale. A statistically significant higher proportion of nurses with high critical thinking scores were found among those older than 30 years, those with university education prior to nursing education, and those working in community health care. Conclusion Nurse leaders and nurse teachers should encourage and nurture critical thinking among newly graduated nurses and nursing students. The low Truth-seeking scores found may be a result of traditional teaching strategies in nursing education and might indicate a need for more student-active learning models. PMID:20384637

Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic HBV infection.

Science.gov (United States)

Cao, Zhujun; Li, Ziqiang; Wang, Hui; Liu, Yuhan; Xu, Yumin; Mo, Ruidong; Ren, Peipei; Chen, Lichang; Lu, Jie; Li, Hong; Zhuang, Yan; Liu, Yunye; Wang, Xiaolin; Zhao, Gangde; Tang, Weiliang; Xiang, Xiaogang; Cai, Wei; Liu, Longgen; Bao, Shisan; Xie, Qing

2017-11-01

Serum Golgi protein 73 (GP73) is a potential biomarker for fibrosis assessment. We aimed to develop an algorithm based on GP73 and liver stiffness (LS) for further improvement of accuracy for significant fibrosis in patients with antiviral-naïve chronic hepatitis B virus (HBV) infection. Diagnostic accuracy evaluation of GP73 and development of GP73-LS algorithm was performed in training cohort (n = 267) with an independent cohort (n = 133) for validation. A stepwise increasing pattern of serum GP73 was observed across fibrosis stages in patients with antiviral-naïve chronic HBV infection. Serum GP73 significantly correlated (rho = 0.48, P 73, accuracy: 63.6%). Using GP73-LS algorithm, GP73 < 63 in agreement with LS < 8.5 provided accuracy of 81.7% to excluded significant fibrosis. GP73 ≥ 63 in agreement with LS ≥ 8.5 provided accuracy of 93.3% to confirm significant fibrosis. Almost 64% or 68% of patients in the training or validation cohort could be accurately classified. Serum GP73 is a robust biomarker for significant fibrosis diagnosis. GP73-LS algorithm provided better diagnostic accuracy than currently available approaches. More than 60% antiviral naïve CHB patients could use this algorithm without resorting to liver biopsy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Violacein induces death of resistant leukaemia cells via kinome reprogramming, endoplasmic reticulum stress and Golgi apparatus collapse.

Directory of Open Access Journals (Sweden)

Karla C S Queiroz

Full Text Available It is now generally recognised that different modes of programmed cell death (PCD are intimately linked to the cancerous process. However, the mechanism of PCD involved in cancer chemoprevention is much less clear and may be different between types of chemopreventive agents and tumour cell types involved. Therefore, from a pharmacological view, it is crucial during the earlier steps of drug development to define the cellular specificity of the candidate as well as its capacity to bypass dysfunctional tumoral signalling pathways providing insensitivity to death stimuli. Studying the cytotoxic effects of violacein, an antibiotic dihydro-indolone synthesised by an Amazon river Chromobacterium, we observed that death induced in CD34(+/c-Kit(+/P-glycoprotein(+/MRP1(+ TF1 leukaemia progenitor cells is not mediated by apoptosis and/or autophagy, since biomarkers of both types of cell death were not significantly affected by this compound. To clarify the working mechanism of violacein, we performed kinome profiling using peptide arrays to yield comprehensive descriptions of cellular kinase activities. Pro-death activity of violacein is actually carried out by inhibition of calpain and DAPK1 and activation of PKA, AKT and PDK, followed by structural changes caused by endoplasmic reticulum stress and Golgi apparatus collapse, leading to cellular demise. Our results demonstrate that violacein induces kinome reprogramming, overcoming death signaling dysfunctions of intrinsically resistant human leukaemia cells.

Electron microscopical study of non-specific cholinesterase activity in simple lamellar corpuscles of glabrous skin from cat rhinarium: a histochemical evidence for the presence of collagenase-sensitive molecular forms and their secretion.

Science.gov (United States)

Dubový, P

1989-01-01

The distribution of nCHE activity was studied histochemically in simple lamellar corpuscles (SLCs) of glabrous skin from cat rhinarium. The Schwann cells forming myelin sheaths in preterminal part of SCLs exhibited no positive reaction for nCHE activity. Prevalent reaction product was localized extracellularly in the inne core enveloping terminal portion of unmyelinated sensory axon. A dot-like shaped reaction product was deposited in the basal lamina of the inner core cells and their cytoplasmic lamellae or was scattered in enlarged interlamellar spaces. Only small amount of fine end product was found to be associated with the plasma membrane of inner core lamellae. Fine reaction product for nCHE activity was consistently localized in perinuclear and rER cisternae and saccules of the Golgi apparatus of inner core cells. Some vesicles around rER and the Golgi apparatus, ones beneath the plasma membrane, and tubular-like cisternal profiles oriented towards the surface contained nCHE end product, as well. The intracellular and extracellular localization of nCHE reaction product suggests that this enzyme behaves in cat SLCs as a secreted rather than as an integral membrane protein. A large amount of dot-like reaction product in the interlamellar spaces disappeared if the skin sections were treated with collagenase before incubation in the medium for histochemical detection of nCHE activity. The decrease of nCHE end product in SLCs of the skin sections after collagenase digestion was corroborated by means of light microdensitometer and electrometrical measurement. The histochemical detection and electrometrical measurement revealed that the majority of the reaction product in the interlamellar spaces of inner core corresponds with the nCHE molecules sensitive to collagenase treatment and they are probably counted among asymmetrical molecular forms.

Newly elected IAEA Board of Governors

International Nuclear Information System (INIS)

2001-01-01

The document gives information about the election of 11 Member States to the IAEA Board of Governors, the 35-member policy-making body, during the 45th regular session of the IAEA's General Conference (17-21 September 2001, Austria Center, Vienna). The newly elected Member States are: Bulgaria, Burkina Faso, Chile, Colombia, Islamic Republic of Iran, Kuwait, Morocco, Philippines, Romania, Spain, and Turkey. The other 24 Member States of the Board are also given

Health problems of newly arrived migrants and refugees in Europe.

Science.gov (United States)

Pavli, Androula; Maltezou, Helena

2017-07-01

The number of migrants and refugees in Europe in the past few years has increased dramatically due to war, violence or prosecutions in their homeland. Migration may affect physical, mental and social health. The objective of this article is to assess migrants and refugees' health problems, and to recommend appropriate interventions. A PubMed search of published articles on health problems of newly arrived migrants and refugees was conducted from 2003 through 2016, focusing on the current refugee crisis in Europe. In addition to communicable diseases, such as respiratory, gastrointestinal and dermatologic infections, non-communicable diseases, including chronic conditions, mental and social problems, account for a significant morbidity burden in newly arrived migrants and refugees. Vaccine-preventable diseases are also of outmost importance. The appropriate management of newly arrived refugees and migrants' health problems is affected by barriers to access to health care including legal, communication, cultural and bureaucratic difficulties. There is diversity and lack of integration regarding health care provision across Europe due to policy differences between health care systems and social services. There is a notable burden of communicable and non-communicable diseases among newly arrived migrants and refugees. Provision of health care at reception and temporary centres should be integrated and provided by a multidisciplinary team Appropriate health care of migrants and refugees could greatly enhance their health and social status which will benefit also the host countries at large. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

New large-Nc relations for the electromagnetic nucleon-to-Δ form factors

International Nuclear Information System (INIS)

Vladimir Pascalutsa; Marc Vanderhaeghen

2006-01-01

We establish relations which express the three N → Δ transition form factors in terms of the nucleon form factors. These relations are based on the known large-N c relation between the N → Δ electric quadrupole moment and the neutron charge radius, and a newly derived large-N c relation between the electric quadrupole (E2) and Coulomb quadrupole (C2) transitions. Namely, in the large-N c limit we find C2=E2. We show that these relations provide predictions for the N → Δ electromagnetic form factors which are found to be in very good agreement with experiment for moderate momentum transfers. They also provide constraints for the N → Δ GPDs

The cyclic nucleotide gated cation channel AtCNGC10 traffics from the ER via Golgi vesicles to the plasma membrane of Arabidopsis root and leaf cells

Directory of Open Access Journals (Sweden)

Andres Marilou A

2007-09-01

Full Text Available Abstract Background The cyclic nucleotide-gated ion channels (CNGCs maintain cation homeostasis essential for a wide range of physiological processes in plant cells. However, the precise subcellular locations and trafficking of these membrane proteins are poorly understood. This is further complicated by a general deficiency of information about targeting pathways of membrane proteins in plants. To investigate CNGC trafficking and localization, we have measured Atcngc5 and Atcngc10 expression in roots and leaves, analyzed AtCNGC10-GFP fusions transiently expressed in protoplasts, and conducted immunofluorescence labeling of protoplasts and immunoelectron microscopic analysis of high pressure frozen leaves and roots. Results AtCNGC10 mRNA and protein levels were 2.5-fold higher in roots than leaves, while AtCNGC5 mRNA and protein levels were nearly equal in these tissues. The AtCNGC10-EGFP fusion was targeted to the plasma membrane in leaf protoplasts, and lightly labeled several intracellular structures. Immunofluorescence microscopy with affinity purified CNGC-specific antisera indicated that AtCNGC5 and AtCNGC10 are present in the plasma membrane of protoplasts. Immunoelectron microscopy demonstrated that AtCNGC10 was associated with the plasma membrane of mesophyll, palisade parenchyma and epidermal cells of leaves, and the meristem, columella and cap cells of roots. AtCNCG10 was also observed in the endoplasmic reticulum and Golgi cisternae and vesicles of 50–150 nm in size. Patch clamp assays of an AtCNGC10-GFP fusion expressed in HEK293 cells measured significant cation currents. Conclusion AtCNGC5 and AtCNGC10 are plasma membrane proteins. We postulate that AtCNGC10 traffics from the endoplasmic reticulum via the Golgi apparatus and associated vesicles to the plasma membrane. The presence of the cation channel, AtCNGC10, in root cap meristem cells, cell plate, and gravity-sensing columella cells, combined with the previously reported

Anatomy and histology of the newly discovered adipose sac structure within the labia majora: international original research.

Science.gov (United States)

Ostrzenski, Adam; Krajewski, Pawel; Davis, Kern

2016-09-01

To determine whether there is any new anatomical structure present within the labia majora. A case serial study was executed on eleven consecutive fresh human female cadavers. Stratum-by-stratum dissections of the labia majora were performed. Twenty-two anatomic dissections of labia majora were completed. Eosin and Hematoxylin agents were used to stain newly discovered adipose sac's tissues of the labia majora and the cylinder-like structures, which cover condensed adipose tissues. The histology of these two structures was compared. All dissected labia majora demonstrated the presence of the anatomic existence of the adipose sac structure. Just under the dermis of the labia majora, the adipose sac was located, which was filled with lobules containing condensed fatty tissues in the form of cylinders. The histological investigation established that the well-organized fibro-connective-adipose tissues represented the adipose sac. The absence of descriptions of the adipose sac within the labia majora in traditional anatomic and gynecologic textbooks was noted. In this study group, the newly discovered adipose sac is consistently present within the anatomical structure of the labia majora. The well-organized fibro-connective-adipose tissue represents microscopic characteristic features of the adipose sac.

Radiation therapy of newly diagnosed, advanced prostatic cancer and hormonally relapsed prostatic cancer

International Nuclear Information System (INIS)

Suzuki, Minoru; Fujiwara, Kazuhisa; Hayakawa, Katsumi; Hida, Shuichi

1994-01-01

Ten patients with newly diagnosed, advanced prostatic cancer were treated with radiotherapy and hormone therapy to improve tumor control and survival. Eight patients with hormonally relapsed prostatic cancer were treated with radiotherapy to improve their quality of life. Local control of the tumor was achieved in 9 of 10 patients with newly diagnosed, advanced prostatic cancer. Five of eight patients with hormonally relapsed prostatic cancer obtained improved quality of life. Combined radiotherapy and hormone therapy were effective in the treatment of newly diagnosed, advanced prostatic cancer, and radiotherapy was useful for improving the quality of life of patients with hormonally relapsed prostatic cancer. (author)

Three Newly Naturalized Plants in Taiwan

Directory of Open Access Journals (Sweden)

Ming-Jer Jung

2009-11-01

Full Text Available Three newly naturalized plants are reported in this paper. Hypochaeris microcephala (Sch. Bip. Cabrera var. albiflora (Kuntze Cabrera (Asteraceae is naturalized in urban areas of northern Taiwan. Indigofera pseudo-tinctoria Matsum. (Leguminosae is naturalized in low elevations of northern and southern Taiwan and in middle elevations of central Taiwan. Lamium purpureum L. (Laminaceae has become naturalized locally in middle elevations of central Taiwan. Descriptions, illustrations and color photos of these plants are provided.

Activation of Rab GTPase Sec4 by its GEF Sec2 is required for prospore membrane formation during sporulation in yeast Saccharomyces cerevisiae.

Science.gov (United States)

Suda, Yasuyuki; Tachikawa, Hiroyuki; Inoue, Ichiro; Kurita, Tomokazu; Saito, Chieko; Kurokawa, Kazuo; Nakano, Akihiko; Irie, Kenji

2018-02-01

Sec2 activates Sec4 Rab GTPase as a guanine nucleotide exchange factor for the recruitment of downstream effectors to facilitate tethering and fusion of post-Golgi vesicles at the plasma membrane. During the meiosis and sporulation of budding yeast, post-Golgi vesicles are transported to and fused at the spindle pole body (SPB) to form a de novo membrane, called the prospore membrane. Previous studies have revealed the role of the SPB outer surface called the meiotic outer plaque (MOP) in docking and fusion of post-Golgi vesicles. However, the upstream molecular machinery for post-Golgi vesicular fusion that facilitates prospore membrane formation remains enigmatic. Here, we demonstrate that the GTP exchange factor for Sec4, Sec2, participates in the formation of the prospore membrane. A conditional mutant in which the SEC2 expression is shut off during sporulation showed sporulation defects. Inactivation of Sec2 caused Sec4 targeting defects along the prospore membranes, thereby causing insufficient targeting of downstream effectors and cargo proteins to the prospore membrane. These results suggest that the activation of Sec4 by Sec2 is required for the efficient supply of post-Golgi vesicles to the prospore membrane and thus for prospore membrane formation/extension and subsequent deposition of spore wall materials. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Intracellular and transcellular transport of secretory and membrane proteins in the rat hepatocyte

International Nuclear Information System (INIS)

Sztul, E.S.

1984-01-01

The intra- and transcellular transport of hepatic secretory and membrane proteins was studied in rats in vivo using [ 3 H]fucose and [ 35 S]cyteine as metabolic precursors. Incorporated radioactivity in plasma, bile, and liver subcellular fractions was measured and the labeled proteins of the Golgi complex, bile and plasma were separated by SDS-PAGE and identified by fluorography. 3 H-radioactivity in Golgi fractions peaked at 10 min post injection (p.i.) and then declined concomitantly with the appearance of labeled glycoproteins in plasma. Maximal secretion of secretory fucoproteins from the Golgi complex occurred between 10 and 20 min p.i. In contrast, the clearance of labeled proteins from Golgi membrane subfractions occurred past 30 min p.i., indicating that membrane proteins leave the Golgi complex at least 10 min later than the bulk of content proteins. A major 80K form of Secretory Component (SC) was identified in the bile by precipitation with an anti IgA antibody. A comparative study of kinetics of transport of 35 S-labeled SC and 35 S-labeled albumin showed that albumin peaked in bile at ∼45 min p.i., whereas the SC peak occurred at 80 min p.i., suggesting that the transit time differs for plasma and membrane proteins which are delivered to the bile canaliculus (BC)

Validation of mentorship model for newly qualified professional ...

African Journals Online (AJOL)

Newly qualified professional nurses (NQPNs) allocated to community health care services require the use of validated model to practice independently. Validation was done to adapt and assess if the model is understood and could be implemented by NQPNs and mentors employed in community health care services.

Predictive value of serum Golgi protein 73 for prominent hepatic necroinflammation in chronic HBV infection.

Science.gov (United States)

Xu, Zhengju; Shen, Jiankun; Pan, Xingnan; Wei, Meijuan; Liu, Liguan; Wei, Kaipeng; Liu, Lifei; Yang, Huanwen; Huang, Jinfa

2018-06-01

As a noninvasive marker, serum alanine aminotransferase (ALT) has limitations, because a large proportion of patients chronically infected with hepatitis B virus (HBV) suffer from severe hepatic necroinflammation, but have normal or mildly elevated ALT. In the present study, we aimed to investigate the potential value of serum Golgi protein 73 (GP73) in predicting significant hepatic necroinflamation among chronic HBV infected patients. A cohort of 497 chronic HBV infected patients was retrospectively recruited. Liver biopsy was performed in all patients and serum GP73 levels were measured by enzyme-linked immunosorbent assay. Serum GP73 increased in parallel with the increase in hepatic necroinflammatory activity grade (r = 0.682) and the stage of liver fibrosis (r = 0.539). The positive correlation of serum GP73 with the degree of hepatic necroinflammatory activity was statistically significant, while serum GP73 with the stage of liver fibrosis was weaker than that with hepatic necroinflammation. Furthermore, serum GP73 levels were significantly greater in patients with normal or mildly elevated ALT and significant hepatic necroinflammation (≥G2) than in patients with minimal to mild hepatic necroinflammation. The sensitivity and specificity of GP73 for the diagnosis of G2 hepatic necroinflammation was 42.35% and 95.0%, respectively, at a cut-off value of 88.38 ng/mL. When the cut-off value was set at 124.76 ng/mL, the sensitivity and specificity of GP73 for the diagnosis of G3 hepatic necroinflammation was 55.56% and 97.29%, respectively. These findings indicate that GP73 holds promise as an important candidate for diagnosing significant hepatic necroinflammation. © 2018 Wiley Periodicals, Inc.

Newly divided eosinophils limit ozone-induced airway hyperreactivity in nonsensitized guinea pigs.

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Wicher, Sarah A; Jacoby, David B; Fryer, Allison D

2017-06-01

Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory cells were harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day after ozone, mature eosinophils dominate the inflammatory response and potentiate vagally induced bronchoconstriction. However, by 3 days, newly divided eosinophils have reached the lungs, where they inhibit ozone-induced airway hyperreactivity because depleting them with antibody to IL-5 or a TNF-α antagonist worsened vagally induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs 3 days later failed to occur. Thus mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs, where 3 days later, newly divided eosinophils attenuate vagally mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNF-α antagonist or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus interventions targeting eosinophils, although beneficial in atopic individuals, may delay resolution of airway hyperreactivity in nonatopic individuals. Copyright �

A newly-recognized galactic supernova remnant with shell-type and filled-center features

International Nuclear Information System (INIS)

Barnes, D.J.; Turtle, A.J.

1988-01-01

While the number of galactic supernova remnants (SNRs) now known is fairly large (>150), the subset among these that are known to resemble the Crab Nebula is still distressingly small, about 15 or so. Thus any object that can be unambiguously included in this exclusive club forms a valuable addition to knowledge of this class. The authors report observations of a newly recognized nonthermal galactic object, G18.94-1.06, having all the hallmarks of the classical shell-type SNRs, while also appearing to have a filled-centre component located inside the shell. Among the known Crab-like remnants, about one third show this dual nature. This diagnosis of G18.94-1.06 is supported mainly by the variations in spectral index across the source, as seen between the two observation frequencies, 408 MHz and 5.0 GHz

Neuropsychological and psychological interventions for people with newly diagnosed epilepsy.

Science.gov (United States)

Jackson, Cerian F; Makin, Selina M; Baker, Gus A

2015-07-22

Many people with epilepsy report experiencing psychological difficulties such as anxiety, depression and neuropsychological deficits including memory problems. Research has shown that these difficulties are often present not only for people with chronic epilepsy but also for people with newly diagnosed epilepsy. Despite this, there are very few published interventions that detail means to help people with newly diagnosed epilepsy manage these problems. To identify and assess possible psychological and neuropsychological interventions for adults with newly diagnosed epilepsy. We searched the following databases on 30 June 2015: the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), SCOPUS, PsycINFO, CINAHL, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). This review includes all randomised controlled trials, quasi-randomised controlled trials, prospective cohort controlled studies, and prospective before and after studies which include psychological or neuropsychological interventions for people with newly diagnosed epilepsy. We excluded studies that included people with epilepsy and any other psychological disorder or neurological condition. We excluded studies carried out which recruited only children. We used the standard methodological procedure expected by The Cochrane Collaboration. Two authors independently completed data extraction and risk of bias analysis. The results of this were cross-checked and third author resolved any discrepancies. In the event of missing data, we contacted the study authors. Meta-analysis was not completed due to differences in the intervention and outcomes reported in the two studies. We included two randomised controlled trials assessing psychological interventions for people with newly diagnosed epilepsy. One study assessed a cognitive behavioural intervention (CBI) in an adolescent

Frequency of Ketoacidosis in Newly Diagnosed Type 1 Diabetic Children

Science.gov (United States)

Razavi, Zahra

2010-01-01

Objectives Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). Many patients with newly diagnosed type 1 diabetes present with DKA. The aim of this study is to determine the frequency and the clinical presentation of diabetic ketoacidosis at the diagnosis of type 1 diabetes mellitus in youths in hamadan, Western Province of Iran. Methods The Clinical and laboratory data of a total of 200 patients under 19 years of age with newly diagnosed type 1 diabetes mellitus between 1995-2005 were retrospectively reviewed. Statistical analysis was performed using SPSS 11. Results 48 (24%)of the children were presented in a state of ketoacidosis. Sever form of DKA (pH≤7.2) was observed in 54.5% of patients. The mean age at diagnosis was 7.3±5.15 years in DKA group and 8.59±3.07 in non-DKA group (p=0.22). 60.4% of patient with DKA were female whereas in the non-DKA group, 53.3% of patients were female, the difference was not significant (p=0.38). The duration of symptoms before diagnosis was 14.84±8.19 days in patients with DKA and 22.39±2.27 in the non-DKA group, (p=0.11). No significant difference was found between the age, sex and duration of the symptoms and occurance of DKA. Polydipsia (85.4) polyuria (83.3%), weakness (68.8%) and abdominal pain (52.1%) were the most frequently notified symptoms among the patients. In two cases, diagnosis of DKA was preceded by as appendicitis and the patient underwent appendectomy. Conclusion Frequency of DKA at onset of type 1 diabetes mellitus was significant in the studied region. However, it was lower than other regions in Asia. Polydipsia, polyuria, fatigue and abdominal pain were the most common symptoms on presentation. PMID:22125712

Frequency of Ketoacidosis in Newly Diagnosed Type 1 Diabetic Children

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Zahra Razavi

2010-04-01

Full Text Available ABSTRACTObjectives: Diabetic ketoacidosis (DKA is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM. Many patients with newly diagnosed type 1 diabetes present with DKA. The aim of this study is to determine the frequency and the clinical presentation of diabetic ketoacidosis at the diagnosis of type 1 diabetes mellitus in youths in hamadan, Western Province of Iran.Methods: The Clinical and laboratory data of a total of 200 patients under 19 years of age with newly diagnosed type 1 diabetes mellitus between 1995-2005 were retrospectively reviewed. Statistical analysis was performed using SPSS 11.Results: 48 (24%of the children were presented in a state of ketoacidosis. Sever form of DKA (pH≤7.2 was observed in 54.5% of patients. The mean age at diagnosis was 7.3±5.15 years in DKA group and 8.59±3.07 in non-DKA group (p=0.22. 60.4% of patient with DKA were female whereas in the non-DKA group, 53.3% of patients were female, the difference was not significant (p=0.38. The duration of symptoms before diagnosis was 14.84±8.19 days in patients with DKA and 22.39±2.27 in the non-DKA group, (p=0.11. No significant difference was found between the age, sex and duration of the symptoms and occurance of DKA. Polydipsia (85.4 polyuria (83.3%, weakness (68.8% and abdominal pain (52.1% were the most frequently notified symptoms among the patients. In two cases, diagnosis of DKA was preceded by as appendicitis and the patient underwent appendectomy.Conclusion: Frequency of DKA at onset of type 1 diabetes mellitus was significant in the studied region. However, it was lower than other regions in Asia. Polydipsia, polyuria, fatigue and abdominal pain were the most common symptoms on presentation.

Enantioselective hydrolysis of racemic styrene oxide and its substituted derivatives using newly-isolated Sphingopyxis sp. exhibiting a novel epoxide hydrolase activity.

Science.gov (United States)

Woo, Jung-Hee; Lee, Eun Yeol

2014-02-01

(S)-Styrene oxide, (S)-2-chlorostyrene oxide (CSO), (S)-3-CSO and (S)-4-CSO with 99.9 %ee were obtained with a yield of 20.6, 39.3, 28.7 and 26.8 % from 4 mM corresponding racemic substrates using 10 mg cells of a newly-isolated Sphingopyxis sp. at pH 8.0 and 25 °C in 1 ml 100 mM Tris/HCl buffer after 420, 100, 120 and 55 min, respectively. For racemic 2CSO, well-known for one of the racemates that is difficult to obtained in enantiomerically pure form, (S)-2-CSO with 99.9 %ee, 39.3 % yield (theoretical yield 50 %) and enantiomeric ratio of 42.1 was obtained. The newly-isolated strain can thus be used as whole-cell biocatalyst in the production of various (S)-CSO with a chlorine group at different positions.

Anticipating the free amino acid concentrations in newly hatched pelagic fish larvae based on recently fertilized eggs and temperature

DEFF Research Database (Denmark)

Rayner, Thomas Allan; Hwang, Jiang-Shiou; Hansen, Benni Winding

2017-01-01

between the species for different FAAs was low, and the most outstanding essential FAAs were leucine, lysine, valine and isoleucine while alanine and serine dominated non-essential FAAs. Overall, leucine could be regarded as the most important among all species due to its common occurrence in newly...... spawned eggs and fast rate of decay. Based on the functions considered in the present study, it is possible to anticipate the availability of FAA diet needed in the form of live feed for pelagic first feeding marine fish larvae in aquaculture at different temperatures....

Hope, emotion regulation, and psychosocial well-being in patients newly diagnosed with cancer.

Science.gov (United States)

Peh, Chao Xu; Kua, Ee Heok; Mahendran, Rathi

2016-05-01

Patients newly diagnosed with cancer are often confronted with feelings of uncertainty and life threat. A significant proportion may report impairments in psychosocial well-being. Previous studies examining protective psychological factors such as hope and emotion regulation (ER) have yet to investigate these processes concurrently within a common self-regulation framework and/or focus on newly diagnosed patients. The present study aimed to examine how hope and ER may relate to psychosocial outcomes of patients newly diagnosed with cancer. The present study used a cross-sectional design with self-report questionnaires. Participants were newly diagnosed patients (N = 101) recruited from three cancer therapy clinics in a hospital. Patients completed measures of hope, ER (cognitive reappraisal and expressive suppression), and psychosocial well-being (life satisfaction and negative affectivity). Findings showed that (1) hope and reappraisal, but not suppression, were associated with well-being and (2) the interaction between hope and reappraisal was associated with well-being; reappraisal was not associated with well-being in high hope patients, while high reappraisal was associated with better well-being in low hope patients. Individual differences in hope and reappraisal appeared to be associated with psychosocial outcomes in newly diagnosed cancer patients. Hopeful thinking appeared to benefit patients' psychosocial well-being. In addition, an interaction effect between hope and reappraisal suggested that reappraisal as an ER strategy may be particularly adaptive for patients with low hope.

DISABILITIES OF HANDS, FEET AND EYES IN NEWLY-DIAGNOSED LEPROSY PATIENTS IN EASTERN NEPAL

NARCIS (Netherlands)

SCHIPPER, A; LUBBERS, WJ; HOGEWEG, M; DESOLDENHOFF, R

The objective of the study was to determine the magnitude of hand/feet/eye disabilities in newly diagnosed leprosy patients by examining all newly diagnosed leprosy patients who presented at the Eastern Leprosy Control Project (supported by The Netherlands Leprosy Relief Association), made up of a

Delivering the diabetes education and self management for ongoing and newly diagnosed (DESMOND) programme for people with newly diagnosed type 2 diabetes

DEFF Research Database (Denmark)

Gillett, M.; Dallosso, H. M.; Dixon, S.

2010-01-01

intervention is £82 (-£831 to £1010) and the mean incremental cost per QALY gained is £2092. A probabilistic sensitivity analysis indicated that the likelihood that the DESMOND programme is cost effective at a threshold of £20 000 per QALY is 66% using trial based intervention costs and 70% using "real world......Objectives: To assess the long term clinical and cost effectiveness of the diabetes education and self management for ongoing and newly diagnosed (DESMOND) intervention compared with usual care in people with newly diagnosed type 2 diabetes. Design: We undertook a cost-utility analysis that used...... data from a 12 month, multicentre, cluster randomised controlled trial and, using the Sheffield type 2 diabetes model, modelled long term outcomes in terms of use of therapies, incidence of complications, mortality, and associated effect on costs and health related quality of life. A further cost...

Newly-graduated midwives transcending barriers: a grounded theory study.

Science.gov (United States)

Barry, Michele J; Hauck, Yvonne L; O'Donoghue, Thomas; Clarke, Simon

2013-12-01

Midwifery has developed its own philosophy to formalise its unique identity as a profession. Newly-graduated midwives are taught, and ideally embrace, this philosophy during their education. However, embarking in their career within a predominantly institutionalised and the medically focused health-care model may challenge this application. The research question guiding this study was as follows: 'How do newly graduated midwives deal with applying the philosophy of midwifery in their first six months of practice?' The aim was to generate a grounded theory around this social process. This Western Australian grounded theory study is conceptualised within the social theory of symbolic interactionism. Data were collected by means of in-depth, semi-structured interviews with 11 recent midwifery graduates. Participant and interviewer's journals provided supplementary data. The 'constant comparison' approach was used for data analysis. The substantive theory of transcending barriers was generated. Three stages in transcending barriers were identified: Addressing personal attributes, Understanding the 'bigger picture', and finally, 'Evaluating, planning and acting' to provide woman-centred care. An overview of these three stages provides the focus of this article. The theory of transcending barriers provides a new perspective on how newly-graduated midwives deal with applying the philosophy of midwifery in their first six months of practice. A number of implications for pre and post registration midwifery education and policy development are suggested, as well as recommendations for future research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Morphological and functional changes in the enterocyte induced by fructose

DEFF Research Database (Denmark)

Danielsen, E M; Hansen, Gert Helge; Wetterberg, L L

1991-01-01

In the presence of 10-50 mM-fructose, enterocytes of organ-cultured pig intestinal-mucosal explants fail to glycosylate correctly their newly synthesized microvillar enzymes, and instead degrade them [Danielsen (1989) J. Biol. Chem. 264, 13726-13729]. In the present work, this degradation was shown....... Thus the stack of Golgi cisternae was condensed and devoid of dilated rims, and the secretion of a non-glycosylated protein, apolipoprotein A-1, was almost completely blocked in the presence of fructose, showing that transport through the secretory pathway is disturbed even for proteins unaffected...... by the defective glycosylation. The microvilli of the brush-border membrane were markedly shortened (by about 40%) in the presence of fructose, and incorporation of newly made actin into the microvillar cytoskeleton was similarly decreased. By affecting membrane glycoprotein synthesis, the common dietary sugar...

Pineapple Fruit Collapse: Newly Emerging Disease of Pineapple Fruit in Lampung, Indonesia

Directory of Open Access Journals (Sweden)

Joko Prasetyo

2014-03-01

Full Text Available ABSTRACT Pineapple fruit collapse: newly emerging disease of pineapple fruit in Lampung, Indonesia Recently, a new disease on pineapple fruit has occurred in Lampung. Symptoms of the disease are complex. Fruits rotted and exuded copious liquid from the inter- fruitlet tissues accompanied by gas bubbles. Open spaces were formed inside the rotten fruit. Dissection of diseased fruit showed many cavities within its sceletal fibres and bad odour was exerted from the rotten tissues. A bacterial entity was isolated  from the diseased materials. In a pathogenicity test, the isolated bacteria caused the same symptom as mentioned. In the growing-on test the crown of the heavily infected fruit  showed  heart rot symptom.  Those  indicated that the disease was pineapple fruit collapse. Both symptoms were known related to the same causal agent, Erwinia chrysanthemi (pineapple strain Dickeya sp.. In our opinion, this is the first report of pineapple fruit collapse in Indonesia.

Physico-chemical forms and migration in continental waters of radium from uranium mining and milling

International Nuclear Information System (INIS)

Benes, P.

1982-01-01

Recent advances in knowledge of the physico-chemical forms and migration of radium in continental waters are reviewed and recommendations for future research in this field are given. Computations of solution equilibria based on the reported and newly determined stability constants and solubilities of radium compounds show that a significant percentage of dissolved radium can exist in some waste and natural waters as an RaSO 4 ion pair, besides a significant percentage of Ra 2+ ions. The formation of a solid phase consisting mainly of sparingly soluble radium compounds can be excluded in waste and natural waters. Model experiments revealed that radium can be bound in complexes with some as yet unidentified ligands, probably of organic nature. Direct determinations of the physico-chemical forms of radium in surface and groundwaters were mostly confined to the analysis of the ratio of dissolved to particulate forms of radium. Ratios from 0.01 to 100 were found, depending on the type of water examined. Recently a newly suggested method of selective dissolution was applied to characterize the nature of particulate forms of radium in surface waters. Migration of radium is reviewed, covering the release of radium from its source, its transport in ground and surface waters and its deposition in various sinks. Factors influencing radium release from the sources into the hydrosphere are discussed. The following processes affecting radium migration are discussed: adsorption of dissolved radium on suspended solids and bottom sediments, coprecipitation of radium with solids formed in waste waters or in natural waters, sedimentation of particulate forms of radium in reservoirs and streams, resuspension of bottom sediments and dissolution of radium from suspended solids or bottom sediments

Exploring selection and recruitment processes for newly qualified nurses: a sequential-explanatory mixed-method study.

Science.gov (United States)

Newton, Paul; Chandler, Val; Morris-Thomson, Trish; Sayer, Jane; Burke, Linda

2015-01-01

To map current selection and recruitment processes for newly qualified nurses and to explore the advantages and limitations of current selection and recruitment processes. The need to improve current selection and recruitment practices for newly qualified nurses is highlighted in health policy internationally. A cross-sectional, sequential-explanatory mixed-method design with 4 components: (1) Literature review of selection and recruitment of newly qualified nurses; and (2) Literature review of a public sector professions' selection and recruitment processes; (3) Survey mapping existing selection and recruitment processes for newly qualified nurses; and (4) Qualitative study about recruiters' selection and recruitment processes. Literature searches on the selection and recruitment of newly qualified candidates in teaching and nursing (2005-2013) were conducted. Cross-sectional, mixed-method data were collected from thirty-one (n = 31) individuals in health providers in London who had responsibility for the selection and recruitment of newly qualified nurses using a survey instrument. Of these providers who took part, six (n = 6) purposively selected to be interviewed qualitatively. Issues of supply and demand in the workforce, rather than selection and recruitment tools, predominated in the literature reviews. Examples of tools to measure values, attitudes and skills were found in the nursing literature. The mapping exercise found that providers used many selection and recruitment tools, some providers combined tools to streamline process and assure quality of candidates. Most providers had processes which addressed the issue of quality in the selection and recruitment of newly qualified nurses. The 'assessment centre model', which providers were adopting, allowed for multiple levels of assessment and streamlined recruitment. There is a need to validate the efficacy of the selection tools. © 2014 John Wiley & Sons Ltd.

Newly graduated nurses' occupational commitment and its associations with professional competence and work-related factors.

Science.gov (United States)

Numminen, Olivia; Leino-Kilpi, Helena; Isoaho, Hannu; Meretoja, Riitta

2016-01-01

To explore newly graduated nurses' occupational commitment and its associations with their self-assessed professional competence and other work-related factors. As a factor affecting nurse turnover, newly graduated nurses' occupational commitment and its associations with work-related factors needs exploring to retain adequate workforce. Nurses' commitment has mainly been studied as organisational commitment, but newly graduated nurses' occupational commitment and its association with work-related factors needs further studying. This study used descriptive, cross-sectional, correlation design. A convenience sample of 318 newly graduated nurses in Finland participated responding to an electronic questionnaire. Statistical software, NCSS version 9, was used in data analysis. Frequencies, percentages, ranges, means and standard deviations summarised the data. Multivariate Analyses of Variance estimated associations between occupational commitment and work-related variables. IBM SPSS Amos version 22 estimated the model fit of Occupational Commitment Scale and Nurse Competence Scale. Newly graduated nurses' occupational commitment was good, affective commitment reaching the highest mean score. There was a significant difference between the nurse groups in favour of nurses at higher competence levels in all subscales except in limited alternatives occupational commitment. Multivariate analyses revealed significant associations between subscales of commitment and competence, turnover intentions, job satisfaction, earlier professional education and work sector, competence counting only through affective dimension. The association between occupational commitment and low turnover intentions and satisfaction with nursing occupation was strong. Higher general competence indicated higher overall occupational commitment. Managers' recognition of the influence of all dimensions of occupational commitment in newly graduated nurses' professional development is important. Follow

Identifying Malnutrition: Nutritional Status in Newly Diagnosed Patients With Cancer.

Science.gov (United States)

Krishnasamy, Karthikayini; Li Yoong, Tang; Mei Chan, Chong; Peng Choong, Lau; Chinna, Karuthan

2017-02-01

Malnutrition is common among patients with cancer, but little attention is given to its risks and consequences. The aim of this study is to assess the nutritional status and identify the factors associated with malnutrition among newly diagnosed patients with cancer. Patients admitted with newly diagnosed cancer at a teaching hospital in Malaysia were recruited from January to April 2015. Nutritional status was assessed before treatment initiation, and patients were classified into three categories. A total of 132 pretreatment patients were recruited into the study. About half were severely malnourished. Patients with stage III cancer had the highest prevalence of severe malnourishment. Clinical parameters and disease characteristics were significantly associated with nutritional status. Demographic variables were also statistically significantly associated with severe nutritional status.

Assessment of metal retention in newly constructed highway embankments.

Science.gov (United States)

Werkenthin, Moritz; Kluge, Björn; Wessolek, Gerd

2016-12-01

Newly constructed embankments should provide both a specific bearing capacity to enable trafficability in emergency cases and a sufficient pollutant retention capacity to protect the groundwater. A number of lysimeters were installed along the A115 highway to determine total and dissolved metal concentrations in road runoff and in the soil solution of newly constructed embankments. Dissolved concentrations in soil solution of the embankments did not exceed the trigger values of the German legislation. Depending on the metal, total concentrations in soil solution were more than twice as high as dissolved concentrations. The high infiltration rates lead to increased groundwater recharge beneath the embankments (up to 4100 mm a -1 ). Although metal concentrations were not problematic from the legislators' point of view, the elevated infiltration rates beside the road facilitated the transfer of high metal loads into deeper soil layers and potentially into the groundwater as well.

Sizing Performance of the Newly Developed Eddy Current System

Energy Technology Data Exchange (ETDEWEB)

Cho, Chan Hee; Lee, Hee Jong; Yoo, Hyun Ju; Moon, Gyoon Young; Lee, Tae Hoon [Korea Hydro and Nuclear Power Co., Ltd., Daejeon (Korea, Republic of)

2013-10-15

This paper describes the comparison results of sizing performance for two systems. The KHNP developed a new eddy current testing system for the inspection of steam generator tubing in domestic nuclear power plants. The equivalency assessment of the newly developed system with the EPRI-qualified system was already carried out. In this paper, the comparisons of depth-sizing performance for the artificial flaws between two systems were performed. The results show that the newly developed system is in good agreement with the qualified system. Therefore, it is expected that the newly developed eddy current system can be used for the inspection of steam generator tubing in nuclear power plants. There are some non-destructive examination (NDE) methods for the inspection of components in nuclear power plants, such as ultrasonic, radiographic, eddy current testing, etc. The eddy current testing is widely used for the inspection of steam generator (SG) tubing because it offers a relatively low cost approach for high speed, large scale testing of metallic materials in high pressure and temperature engineering systems. The Korea Hydro and Nuclear Power Co., Ltd. (KHNP) developed an eddy current testing system for the inspection of steam generator tubing in nuclear power plants. This system includes not only hardware but software such as the frequency generator and data acquisition-analysis program. The foreign eddy current system developed by ZETEC is currently used for the inspection of steam generator tubing in domestic nuclear power plants. The equivalency assessment between two systems was already carried out in accordance with the EPRI steam generator examination guidelines.

Workplace Violence and Job Outcomes of Newly Licensed Nurses.

Science.gov (United States)

Chang, Hyoung Eun; Cho, Sung-Hyun

2016-12-01

The purpose of this study was to examine the prevalence of workplace violence toward newly licensed nurses and the relationship between workplace violence and job outcomes. An online survey was conducted of newly licensed registered nurses who had obtained their license in 2012 or 2013 in South Korea and had been working for 5-12 months after first being employed. The sample consisted of 312 nurses working in hospitals or clinics. The Copenhagen Psychosocial Questionnaire II was used to measure violence and nurse job outcomes. Multiple linear and logistic regression analyses were conducted to examine the relationship between violence and job outcomes. Verbal abuse was most prevalent (59.6%), followed by threats of violence (36.9%), physical violence (27.6%), bullying (25.6%), and sexual harassment (22.4%). Approximately three quarters of the nurses had experienced at least one type of violence. The main perpetrators were patients and nurse colleagues, although the distribution of perpetrators varied depending on the type of violence. Bullying had a significant relationship with all four job outcomes (job satisfaction, burnout, commitment to the workplace, and intent to leave), while verbal abuse was associated with all job outcomes except for intent to leave. Violence perpetrated by nurse colleagues had a significant relationship with all four job outcomes, while violence by physicians had a significant inverse relationship with job satisfaction. Workplace violence is experienced by a high percentage of newly licensed nurses, and is associated with their job outcomes. Copyright © 2016. Published by Elsevier B.V.

Effects of brefeldin A on the endomembrane system and germ tube formation of the tetraspore of Gelidium floridanum (Rhodophyta, Florideophyceae).

Science.gov (United States)

Simioni, Carmen; Rover, Ticiane; Schmidt, Éder C; de L Felix, Marthiellen R; Polo, Luz Karime; Santos, Rodrigo Dos; Costa, Giulia Burle; Kreusch, Marianne; Pereira, Debora T; Ouriques, Luciane C; Bouzon, Zenilda L

2014-06-01

Gelidium floridanum W.R. Taylor tetraspores are units of dispersal and are responsible for substrate attachment. This study aimed to examine evidence of direct interaction between germ tube formation and Golgi activity during tetraspore germination of G. floridanum. After release, the tetraspores were incubated with brefeldin A (BFA) in concentrations of 4 and 8 μM over a 6 h period. The controls and treatments were analyzed with light, fluorescence (FM4-64 dye) and transmission electron microscopy. In the control samples, the Golgi bodies were responsible for germ tube formation. In contrast, BFA-treated samples were observed to inhibit spore adhesion and germ tube formation. These tetraspores also showed an increase in volume (≥30 μm width). BFA treatment also resulted in the disassembly of Golgi cisternae and the formation of vesiculated areas of the cytoplasm, blocking the secretion of protein and amorphous matrix polysaccharides. When stained with FM4-64, the control samples showed fluorescence in the apical region of the germ tube, but the treated samples showed an intense fluorescence throughout the cytoplasm. From these results, we can conclude that the germ tube is formed by the incorporation of vesicles derived from Golgi. Thus, vesicle secretion and Golgi organization are basic processes and essential in adhesion and tube formation. By blocking the secretion of protein and amorphous matrix polysaccharides, BFA treatment precluded tetraspore germination. © 2014 Phycological Society of America.

Chenodeoxycholic acid reduces intestinal permeability in newly weaned piglets

NARCIS (Netherlands)

Meer, van der Y.; Gerrits, W.J.J.; Bosch, van den M.; Holst, J.J.; Moreto, M.; Buurman, W.A.; Kulik, W.; Kempen, van T.A.T.G.

2012-01-01

Piglets are highly susceptible to gut health-related problems. Intravenously administered chenodeoxycholic acid (CDCA) affects gut health mediated through glucagon-like peptide 2 (GLP-2). To test whether CDCA is a suitable feed additive for improving gut health, a trial was performed with newly

Electroconvulsive stimulation results in long-term survival of newly generated hippocampal neurons in rats

DEFF Research Database (Denmark)

Olesen, Mikkel Vestergaard; Wörtwein, Gitta; Folke, Jonas

2017-01-01

Electroconvulsive stimulation (ECS) is one of the strongest stimulators of hippocampal neurogenesis in rodents that represents a plausible mechanism for the efficacy of electroconvulsive therapy (ECT) in major depressive disorder. Using design-based stereological cell counting, we recently...... in neurogenesis facilitates the behavioral outcome of the forced swim test (FST), an animal model of depression. The results showed that ECS in conjunction with CRS stimulates hippocampal neurogenesis, and that a significant quantity of the newly formed hippocampal neurons survives up to 12 months. The new Brd......U-positive neurons showed time-dependent attrition of ∼40% from day 1 to 3 months, with no further decline between 3 and 12 months. ECS did not affect the number of pre-existing dentate granule neurons or the volume of the dentate granule cell layer, suggesting no damaging effect of the treatment. Finally, we found...

Timing of revenue streams from newly recruited faculty: implications for faculty retention.

Science.gov (United States)

Joiner, Keith A; Hiteman, Sarah; Wormsley, Steven; St Germain, Patricia

2007-12-01

To determine the timing and magnitude of revenues generated by newly recruited faculty, to facilitate configuration of recruitment packages appropriately matched to expected financial returns. The aggregate of all positive cash flows to central college of medicine administration -- from research, clinical care, tuition, philanthropy, and royalties and patents, from all faculty newly recruited to the University of Arizona College of Medicine between 1998 and 2004 -- was quantified using the net present value (npv) methodology, which incorporates the time value of money. Tenure-track faculty and, in particular, those with laboratory research programs, generated the highest positive central cash flows. The npv for positive cash flows (npv[+]) during 6 and 10 years for newly recruited assistant professors with laboratory research programs were $118,600 and $255,400, respectively, and, for professors with laboratory research programs, $172,600 and $298,000, respectively (associate professors were not analyzed because of limited numbers). Faculty whose appointments at the University of Arizona College of Medicine exceeded 15 years in duration were the most productive in central revenue generation, far in excess of their numbers proportionate to the total. The results emphasize the critical importance of faculty retention, because even those newly recruited faculty who are most successful in central revenue generation (tenure track with laboratory research programs) must be retained for periods well in excess of 10 years to recoup the initial central investment required for their recruitment.

Korean Red Ginseng Improves Glucose Control in Subjects with Impaired Fasting Glucose, Impaired Glucose Tolerance, or Newly Diagnosed Type 2 Diabetes Mellitus

OpenAIRE

Bang, Hyangju; Kwak, Jung Hyun; Ahn, Hyeon Yeong; Shin, Dong Yeob; Lee, Jong Ho

2014-01-01

This study was designed to evaluate the effect of Korean red ginseng (KRG) supplementation on glucose control in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or newly diagnosed type 2 diabetes mellitus (T2DM). The study was a 12-week randomized, double-blinded, placebo-controlled (5 g of KRG [n=21] or placebo [n=20] in tablet form) trial. Glucose-related biomarkers, including serum and whole blood levels of glucose, insulin, and C-peptide, were measured by 2...

Scandinavian exceptionalism? Civic integration and labour market activation for newly arrived immigrants

DEFF Research Database (Denmark)

Breidahl, Karen Nielsen

2017-01-01

models have been resilient: Based on an in-depth historical and comparative analysis of labour market activation policies targeting newly arrived immigrants in Sweden, Norway, and Denmark since the early 1990s, the article contributes to the overall question: To what extent do the institutional pathways...... of the Scandinavian welfare states prevail when confronted with newcomers? Activation policies targeting newly arrived immigrants exemplifies how the ambition of states to promote functional, individual autonomy is also an important, ongoing process in diverse policy areas of the welfare state and not restricted...

Distinguishing Newly Born Strange Stars from Neutron Stars with g-Mode Oscillations

International Nuclear Information System (INIS)

Fu Weijie; Wei Haiqing; Liu Yuxin

2008-01-01

The gravity-mode (g-mode) eigenfrequencies of newly born strange quark stars (SQSs) and neutron stars (NSs) are studied. It is found that the eigenfrequencies in SQSs are much lower than those in NSs by almost 1 order of magnitude, since the components of a SQS are all extremely relativistic particles while nucleons in a NS are nonrelativistic. We therefore propose that newly born SQSs can be distinguished from the NSs by detecting the eigenfrequencies of the g-mode pulsations of supernovae cores through gravitational radiation by LIGO-class detectors

Functional assays for the assessment of the pathogenicity of variants of GOSR2, an ER-to-Golgi SNARE involved in progressive myoclonus epilepsies

Directory of Open Access Journals (Sweden)

Jörn M. Völker

2017-12-01

Full Text Available Progressive myoclonus epilepsies (PMEs are inherited disorders characterized by myoclonus, generalized tonic-clonic seizures, and ataxia. One of the genes that is associated with PME is the ER-to-Golgi Qb-SNARE GOSR2, which forms a SNARE complex with syntaxin-5, Bet1 and Sec22b. Most PME patients are homo­zygous for a p.Gly144Trp mutation and develop similar clinical presentations. Recently, a patient who was compound heterozygous for p.Gly144Trp and a previously unseen p.Lys164del mutation was identified. Because this patient presented with a milder disease phenotype, we hypothesized that the p.Lys164del mutation may be less severe compared to p.Gly144Trp. To characterize the effect of the p.Gly144Trp and p.Lys164del mutations, both of which are present in the SNARE motif of GOSR2, we examined the corresponding mutations in the yeast ortholog Bos1. Yeasts expressing the orthologous mutants in Bos1 showed impaired growth, suggesting a partial loss of function, which was more severe for the Bos1 p.Gly176Trp mutation. Using anisotropy and gel filtration, we report that Bos1 p.Gly176Trp and p.Arg196del are capable of complex formation, but with partly reduced activity. Molecular dynamics (MD simulations showed that the hydrophobic core, which triggers SNARE complex formation, is compromised due to the glycine-to-tryptophan substitution in both GOSR2 and Bos1. In contrast, the deletion of residue p.Lys164 (or p.Arg196del in Bos1 interferes with the formation of hydrogen bonds between GOSR2 and syntaxin-5. Despite these perturbations, all SNARE complexes stayed intact during longer simulations. Thus, our data suggest that the milder course of disease in compound heterozygous PME is due to less severe impairment of the SNARE function.

Newly democratic Mongolia offering exploration contracts

International Nuclear Information System (INIS)

Penttila, W.C.

1992-01-01

This paper reports that Mongolia, formerly the Mongolian People's Republic, is working to open its exploration prospects to international operators as it emerges as the world's 15th largest independent nation. The country, about the same size as Alaska with a population of 2 million, held its first free election in July 1990. The newly elected government drafted a constitution that took effect Feb. 12, 1992. The document modifies the previous government's structures to eliminate bureaucracy and allows for political pluralism. At the same time, the government is formulating energy policies, state oil company structure, and resource development philosophy

Nitrogen-containing bisphosphonate induces a newly discovered hematopoietic structure in the omentum of an anemic mouse model by stimulating G-CSF production.

Science.gov (United States)

Otsuka, Hirotada; Yagi, Hideki; Endo, Yasuo; Soeta, Satoshi; Nonaka, Naoko; Nakamura, Masanori

2017-02-01

We previously reported that the injection of nitrogen-containing bisphosphonate (NBP) induced the site of erythropoiesis to shift from the bone marrow (BM) to the spleen. Our previous study established a severely anemic mouse model that was treated with a combination of NBP with phenylhydrazine (PHZ), which induced newly discovered hematopoietic organs in the omentum. No reports have shown that new hematopoietic organs form under any condition. We characterized the structures and factors related to the formation of these new organs. Splenectomized mice were treated with NBP to inhibit erythropoiesis in the BM and then injected with PHZ to induce hemolytic anemia. The mice showed severe anemia and wine-colored structures appeared in the omentum. Some hematopoietic cells, including megakaryocytes, and well-developed sinuses were observed in these structures. Numerous TER119-positive erythroblasts were located with cells positive for PCNA, a cell proliferation marker. C-kit-positive cells were detected and mRNAs related to hematopoiesis were expressed in these structures. Moreover, TER119-positive erythroblasts emerged and formed clusters and hematopoiesis-related factors were detected in the omentum of mice treated with NBP and PHZ. The levels of G-CSF in the serum and hematopoietic progenitor cells (HPCs) in the peripheral blood were increased upon treatment with both NBP and PHZ. These results suggest that the induced hematopoietic structures act as the sites of erythropoiesis and that NBP-induced G-CSF production causes HPC mobilization, homing and colonization in the omentum because they constitutively express some factors, including SDF-1; thus, the newly discovered hematopoietic structure in this study might be formed.

Duplex ultrasound: Indications and findings in a newly created ...

African Journals Online (AJOL)

Duplex ultrasound: Indications and findings in a newly created facility at the University of Calabar Teaching Hospital, Calabar. ... It is recommended that timely referrals be made, and mobile Doppler units be acquired to save more lives and limbs in the developing world. Keywords: Calabar, deep venous thrombosis, duplex ...

Mapping subsurface in proximity to newly-developed sinkhole along roadway.

Science.gov (United States)

2013-02-01

MS&T acquired electrical resistivity tomography profiles in immediate proximity to a newly-developed sinkhole in Nixa Missouri : The sinkhole has closed a well-traveled municipal roadway and threatens proximal infrastructure. The intent of this inves...

Ultrastructural analysis of bone nodules formed in vitro by isolated fetal rat calvaria cells

International Nuclear Information System (INIS)

Bhargava, U.; Bar-Lev, M.; Bellows, C.G.; Aubin, J.E.

1988-01-01

When cells enzymatically digested from 21 d fetal rat calvaria are grown in ascorbic acid and Na beta-glycerophosphate, they form discrete three-dimensional nodular structures with the histological and immunohistochemical appearance of woven bone. The present investigation was undertaken to verify that bone-like features were identifiable at the ultrastructural level. The nodules formed on top of a fibroblast-like multilayer of cells. The upper surface of the nodules was lined by a continuous layer of cuboidal osteoblastic cells often seen to be joined by adherens junctions. Numerous microvilli, membrane protrusions, and coated pits could be seen on the upper surface of these cells, their cytoplasm contained prominent RER and Golgi membranes, and processes extended from their lower surfaces into a dense, highly organized collagenous matrix. Some osteocyte-like cells were completely embedded within this matrix; they also displayed RER and prominent processes which extended through the matrix and often made both adherens and gap junctional contacts with the processes of other cells. The fibroblastic cells not participating in nodule formation were surrounded by a less dense collagenous matrix and, in contrast to the matrix of the nodules, it did not mineralize. An unmineralized osteoid-like layer was seen directly below the cuboidal top layer of cells. A mineralization front was detectable below this in which small, discrete structures resembling matrix vesicles and feathery mineral crystals were evident and frequently associated with the collagen fibrils. More heavily mineralized areas were seen further into the nodule. Electron microprobe and electron and X-ray diffraction analysis confirmed the mineral to be hydroxyapatite

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

Science.gov (United States)

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

Enhanced SCAP glycosylation by inflammation induces macrophage foam cell formation.

Directory of Open Access Journals (Sweden)

Chao Zhou

Full Text Available Inflammatory stress promotes foam cell formation by disrupting LDL receptor feedback regulation in macrophages. Sterol Regulatory Element Binding Proteins (SREBPs Cleavage-Activating Protein (SCAP glycosylation plays crucial roles in regulating LDL receptor and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR feedback regulation. The present study was to investigate if inflammatory stress disrupts LDL receptor and HMGCoAR feedback regulation by affecting SCAP glycosylation in THP-1 macrophages. Intracellular cholesterol content was assessed by Oil Red O staining and quantitative assay. The expression of molecules controlling cholesterol homeostasis was examined using real-time quantitative RT-PCR and Western blotting. The translocation of SCAP from the endoplasmic reticulum (ER to the Golgi was detected by confocal microscopy. We demonstrated that exposure to inflammatory cytokines increased lipid accumulation in THP-1 macrophages, accompanying with an increased SCAP expression even in the presence of a high concentration of LDL. These inflammatory cytokines also prolonged the half-life of SCAP by enhancing glycosylation of SCAP due to the elevated expression of the Golgi mannosidase II. This may enhance translocation and recycling of SCAP between the ER and the Golgi, escorting more SREBP2 from the ER to the Golgi for activation by proteolytic cleavages as evidenced by an increased N-terminal of SREBP2 (active form. As a consequence, the LDL receptor and HMGCoAR expression were up-regulated. Interestingly, these effects could be blocked by inhibitors of Golgi mannosidases. Our results indicated that inflammation increased native LDL uptake and endogenous cholesterol de novo synthesis, thereby causing foam cell formation via increasing transcription and protein glycosylation of SCAP in macrophages. These data imply that inhibitors of Golgi processing enzymes might have a potential vascular-protective role in prevention of atherosclerotic foam

The nuclear retention signal of HPV16 L2 protein is essential for incoming viral genome to transverse the trans-Golgi network

International Nuclear Information System (INIS)

DiGiuseppe, Stephen; Bienkowska-Haba, Malgorzata; Hilbig, Lydia; Sapp, Martin

2014-01-01

The Human papillomavirus (HPV) capsid is composed of the major and minor capsid proteins, L1 and L2, respectively. Infectious entry requires a complex series of conformational changes in both proteins that lead to uptake and allow uncoating to occur. During entry, the capsid is disassembled and host cyclophilins dissociate L1 protein from the L2/DNA complex. Herein, we describe a mutant HPV16 L2 protein (HPV16 L2-R302/5A) that traffics pseudogenome to the trans-Golgi network (TGN) but fails to egress. Our data provide further evidence that HPV16 traffics through the TGN and demonstrates that L2 is essential for TGN egress. Furthermore, we show that cyclophilin activity is required for the L2/DNA complex to be transported to the TGN which is accompanied by a reduced L1 protein levels. - Highlights: • mNLS mutant HPV16 L2 protein traffics pseudogenome to the TGN but fails to egress. • Cyclophilin activity is required for trafficking of the L2/DNA complex to the TGN. • Majority of L1 protein is shed from the L2/DNA complex prior to reaching the TGN

The nuclear retention signal of HPV16 L2 protein is essential for incoming viral genome to transverse the trans-Golgi network

Energy Technology Data Exchange (ETDEWEB)

DiGiuseppe, Stephen; Bienkowska-Haba, Malgorzata; Hilbig, Lydia; Sapp, Martin, E-mail: msapp1@lsuhsc.edu

2014-06-15

The Human papillomavirus (HPV) capsid is composed of the major and minor capsid proteins, L1 and L2, respectively. Infectious entry requires a complex series of conformational changes in both proteins that lead to uptake and allow uncoating to occur. During entry, the capsid is disassembled and host cyclophilins dissociate L1 protein from the L2/DNA complex. Herein, we describe a mutant HPV16 L2 protein (HPV16 L2-R302/5A) that traffics pseudogenome to the trans-Golgi network (TGN) but fails to egress. Our data provide further evidence that HPV16 traffics through the TGN and demonstrates that L2 is essential for TGN egress. Furthermore, we show that cyclophilin activity is required for the L2/DNA complex to be transported to the TGN which is accompanied by a reduced L1 protein levels. - Highlights: • mNLS mutant HPV16 L2 protein traffics pseudogenome to the TGN but fails to egress. • Cyclophilin activity is required for trafficking of the L2/DNA complex to the TGN. • Majority of L1 protein is shed from the L2/DNA complex prior to reaching the TGN.

[Psycho-social factors of sexual failure among newly married Uyghur young males].

Science.gov (United States)

Erkin, Ashim; Hamrajan, Memtili; Kadirjan, Mijit; Adil, Eli; Elijan, Abdureshit; Ibrahim, Ubul; Abdulla, Tursun; Hasanjan, Abdurehim; Turgun, Hekim; Eli, Ablet; Eset, Metmusa

2016-08-01

To study the psycho-social risk factors of sexual failure among newly married young males in the Uyghur population. We conducted a paired case control study of 186 newly married Uyghur young males (aged 17－30 ［23.4±2.9］ yr) with sexual failure and another 186 (aged 18－34 ［24.0±3.1］ yr) with no such problem as controls. We performed a logistic regression analysis on the possible psycho-social risk factors of this condition. Logistic regression analysis showed that the risk factors of sexual failure among the newly married men included personality (OR=0.271, 95% CI 0.176－0.420), income (OR=0.391, 95% CI 0.264－0.580), history of masturbation (OR=0.824, 95% CI 0.710－0.956), premarital sex (OR=0.757, 95% CI 0.677－0.847), sense of obligation (OR=1.756, 95% CI 1.157－2.693), equality of the social status (OR=0.574, 95% CI 0.435－0.756), degree of mutual care (OR=1.605, 95% CI 1.268－2.032), female's psychological obstacle (OR=2.832, 95% CI 1.221－6.569), and religion (OR=0.643, 95% CI 0.472－0.967). There was a statistical significance in the correlation between these factors and sexual failure in the newly married males (all Ppsycho-social factors, which necessitates sexual education among young males and particularly pre-marriage sexual education and psychological guide among both males and females.

CAMS newly detected meteor showers and the sporadic background

Science.gov (United States)

Jenniskens, P.; Nénon, Q.; Gural, P. S.; Albers, J.; Haberman, B.; Johnson, B.; Morales, R.; Grigsby, B. J.; Samuels, D.; Johannink, C.

2016-03-01

The Cameras for Allsky Meteor Surveillance (CAMS) video-based meteoroid orbit survey adds 60 newly identified showers to the IAU Working List of Meteor Showers (numbers 427, 445-446, 506-507, and part of 643-750). 28 of these are also detected in the independent SonotaCo survey. In total, 230 meteor showers and shower components are identified in CAMS data, 177 of which are detected in at least two independent surveys. From the power-law size frequency distribution of detected showers, we extrapolate that 36% of all CAMS-observed meteors originated from ∼700 showers above the N = 1 per 110,000 shower limit. 71% of mass falling to Earth from streams arrives on Jupiter-family type orbits. The transient Geminids account for another 15%. All meteoroids not assigned to streams form a sporadic background with highest detected numbers from the apex source, but with 98% of mass falling in from the antihelion source. Even at large ∼7-mm sizes, a Poynting-Robertson drag evolved population is detected, which implies that the Grün et al. collisional lifetimes at these sizes are underestimated by about a factor of 10. While these large grains survive collisions, many fade on a 104-y timescale, possibly because they disintegrate into smaller particles by processes other than collisions, leaving a more resilient population to evolve.

Three newly recorded Linyphiid spiders (Araneae: Linyphiidae from Korea

Directory of Open Access Journals (Sweden)

Sue Yeon Lee

2018-03-01

Full Text Available Three Linyphiid spiders, Caviphantes pseudosaxetorum Wunderlich, 1979, Erigone edentata Saito and Ono, 2001, and Savignia kawachiensis Oi, 1960, are reported for the first time from Korea with taxonomic illustrations and redescription. In this study, the genus Caviphantes Oi, 1960 is also newly recorded to Korean spider fauna.

[Impact of Increased Supply of Newly Licensed Nurses on Hospital Nurse Staffing and Policy Implications].

Science.gov (United States)

Kim, Yunmi; You, Sunju; Kim, Jinhyun

2017-12-01

This study aimed to analyze the impact of increasing the supply of newly licensed nurses on improving the hospital nurse staffing grades for the period of 2009~2014. Using public administrative data, we analyzed the effect of newly licensed nurses on staffing in 1,594 hospitals using Generalized Estimating Equation (GEE) ordered logistic regression, and of supply variation on improving staffing grades in 1,042 hospitals using GEE logistic regression. An increase of one newly licensed nurse per 100 beds in general units had significantly lower odds of improving staffing grades (grades 6~0 vs. 7) (odds ratio=0.95, p=.005). The supply of newly licensed nurses increased by 32% from 2009 to 2014, and proportion of hospitals whose staffing grade had improved, not changed, and worsened was 19.1%, 70.1%, and 10.8% respectively. Compared to 2009, the supply variation of newly licensed nurses in 2014 was not significantly related to the increased odds of improving staffing grades in the region (OR=1.02, p=.870). To achieve a balance in the regional supply and demand for hospital nurses, compliance with nurse staffing legislation and revisions in the nursing fee differentiation policy are needed. Rather than relying on increasing nurse supply, retention policies for new graduate nurses are required to build and sustain competent nurse workforce in the future. © 2017 Korean Society of Nursing Science

Simulation of an Aspheric Glass Lens Forming Behavior in Progressive GMP Process

International Nuclear Information System (INIS)

Chang, Sung Ho; Lee, Young Min; Kang, Jeong Jin; Hong, Seok Kwan; Shin, Gwang Ho; Heo, Young Moo; Jung, Tae Sung

2007-01-01

Recently, GMP(Glass Molding Press) process is mainly used to produce aspheric glass lenses. Because glass lens is heated at high temperature above Tg (Transformation Temperature) for forming the glass, the quality of aspheric glass lens is deteriorated by residual stresses which are generated in a aspheric glass lens after forming. In this study, as a fundamental study to develop the mold for progressive GMP process, we conducted a aspheric glass lens forming simulation. Prior to a aspheric glass lens forming simulation, compression and thermal conductivity tests were carried out to obtain mechanical and thermal properties of K-PBK40 which is newly developed material for precision molding, and flow characteristics of K-PBK40 were obtained at high temperature. Then, using the flow characteristics obtained, compression simulation was carried out and compared with the experimental result for the purpose of verifying the obtained flow characteristics. Finally, a glass lens press simulation in progressive GMP process was carried out and we could forecast the shape of deformed glass lenses and residual stresses contribution in the structure of deformed glass lenses after forming

Different Pathophysiological Phenotypes among Newly Diagnosed Type 2 Diabetes Patients

DEFF Research Database (Denmark)

Stidsen, Jacob

2013-01-01

Type 2 diabetes (T2D) can be considered a syndrome with several different pathophysiological mechanisms leading to hyperglycemia. Nonetheless, T2D is treated according to algorithms as if it was one disease entity. Methods: We investigated the prevalence of different pathophysiological phenotypes...... or secondary diabetes), classic obesity-associated insulin resistant diabetes ( f-P-C-peptide >= 568 pmol/l) and a normoinsulinopenic group (333 age of our new T2D patients was 61 years (range 21-95 years), 57% were men. We found that 3.0% newly diagnosed T2D patients...... suffered from LADA, 3.9% from secondary diabetes, 6.0% from steroid induced diabetes 5.9% had insulinopenic diabetes, whereas 56.7% presented the classic obesity-associated insulin-resistant phenotype. 24.6% was classified as normoinsulinopenic patients. Conclusion: We conclude that newly diagnosed T2D...

deep-orange and carnation define distinct stages in late endosomal biogenesis in Drosophila melanogaster.

Science.gov (United States)

Sriram, V; Krishnan, K S; Mayor, Satyajit

2003-05-12

Endosomal degradation is severely impaired in primary hemocytes from larvae of eye color mutants of Drosophila. Using high resolution imaging and immunofluorescence microscopy in these cells, products of eye color genes, deep-orange (dor) and carnation (car), are localized to large multivesicular Rab7-positive late endosomes containing Golgi-derived enzymes. These structures mature into small sized Dor-negative, Car-positive structures, which subsequently fuse to form tubular lysosomes. Defective endosomal degradation in mutant alleles of dor results from a failure of Golgi-derived vesicles to fuse with morphologically arrested Rab7-positive large sized endosomes, which are, however, normally acidified and mature with wild-type kinetics. This locates the site of Dor function to fusion of Golgi-derived vesicles with the large Rab7-positive endocytic compartments. In contrast, endosomal degradation is not considerably affected in car1 mutant; fusion of Golgi-derived vesicles and maturation of large sized endosomes is normal. However, removal of Dor from small sized Car-positive endosomes is slowed, and subsequent fusion with tubular lysosomes is abolished. Overexpression of Dor in car1 mutant aggravates this defect, implicating Car in the removal of Dor from endosomes. This suggests that, in addition to an independent role in fusion with tubular lysosomes, the Sec1p homologue, Car, regulates Dor function.

Biogenesis of the demarcation membrane system (DMS) in megakaryocytes.

Science.gov (United States)

Eckly, Anita; Heijnen, Harry; Pertuy, Fabien; Geerts, Willie; Proamer, Fabienne; Rinckel, Jean-Yves; Léon, Catherine; Lanza, François; Gachet, Christian

2014-02-06

The demarcation membrane system (DMS) in megakaryocytes forms the plasma membrane (PM) of future platelets. Using confocal microscopy, electron tomography, and large volume focused ion beam/scanning electron microscopy (FIB/SEM), we determined the sequential steps of DMS formation. We identified a pre-DMS that initiated at the cell periphery and was precisely located between the nuclear lobes. At all developmental stages, the DMS remained continuous with the cell surface. The number of these connections correlated well with the nuclear lobulation, suggesting a relationship with cleavage furrow formation and abortive cytokinesis. On DMS expansion, Golgi complexes assembled around the pre-DMS, and fusion profiles between trans-golgi network-derived vesicles and the DMS were observed. Brefeldin-A reduced DMS expansion, indicating that the exocytic pathway is essential for DMS biogenesis. Close contacts between the endoplasmic reticulum (ER) and the DMS were detected, suggesting physical interaction between the 2 membrane systems. FIB/SEM revealed that the DMS forms an intertwined tubular membrane network resembling the platelet open canalicular system. We thus propose the following steps in DMS biogenesis: (1) focal membrane assembly at the cell periphery; (2) PM invagination and formation of a perinuclear pre-DMS; (3) expansion through membrane delivery from Golgi complexes; and (4) ER-mediated lipid transfer.

ORF Sequence: NC_001141 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available NC_001141 gi|6322114 >gi|6322114|ref|NP_012189.1| Part of a heptameric protein complex that regulates retro...grade Golgi-to-ER protein traffic in eukaryotic cells; coatomer forms the COP I ves

Higher incidence of hip fracture in newly diagnosed schizophrenic ...

African Journals Online (AJOL)

Higher incidence of hip fracture in newly diagnosed schizophrenic patients in Taiwan. Hip fracture is a major public health concern due to its poor outcome and serious socioeconomic burden in older people (1). Evidence has shown that many factors are related to increased risk of hip fracture, but psychiatric diseases are ...

Death Concerns among Individuals Newly Diagnosed with Lung Cancer

Science.gov (United States)

Lehto, Rebecca; Therrien, Barbara

2010-01-01

Confronting the reality of death is an important challenge for individuals facing life-threatening illness such as lung cancer, the leading cause of cancer death. Few studies, however, document the nature of death-related concerns in individuals newly diagnosed with lung cancer. The aims of this exploratory study were to examine unsolicited…

Patients with newly diagnosed Rheumatoid Arthritis are at increased risk of Diabetes Mellitus

DEFF Research Database (Denmark)

Emamifar, Amir; Levin, Klaus; Jensen Hansen, Inger Marie

2018-01-01

-C-reactive protein (DAS28-CRP) at the time of diagnosis and after 4 months (±1-2 months) of treatment initiation were extracted from Danbio Registry. To reveal the presence of DM, patients' electronic medical records were reviewed. The prevalence of DM in our patients was compared (using an age- and gender......-matched analysis) with that expected from Danish population. RESULTS: of 439 included patients, 60.1% were female, mean of age 64.6±15.0 years and RA disease duration 2.6±1.7 years. Prevalence of DM was 57/439 (12.9%), herein type II DM 52 (91.2%) and type I DM 5 (8.8%). Except for two patients, diagnosis of DM......AIMS: To reveal the prevalence of Diabetes Mellitus (DM) in patients with newly diagnosed Rheumatoid Arthritis (RA) and evaluate the association between clinical characteristics of RA and DM as well as treatment response in newly diagnosed RA patients with DM. METHODS: Newly diagnosed, adult, RA...

Changes in immunological status among newly-diagnosed HIV-infected in Denmark 1995-2005

DEFF Research Database (Denmark)

Hoegh, S.; Lohse, N.; Hansen, A.B.

2008-01-01

INTRODUCTION: The incidence of new HIV diagnoses in Denmark has remained stable since 1991, but it has increased among the subgroup of homosexual men in recent years. This may reflect an actual increase in newly infected, e.g. as a result of increased risk behaviour, or it may reflect increased HIV....... MATERIALS AND METHODS: Observational study based on the Danish HIV Cohort Study, which includes all adults seen at Danish HIV clinics since 1995. RESULTS: From 2000 to 2004 the number of newly-infected homosexual men increased (from 69 to 123), particularly in persons under 30 years (from 5 to 42......). The median CD4 cell count at the time of diagnosis increased in this group (median 19.1 cells/microL per year [95% CI: 3.7-11.3]), while it remained stable among heterosexually infected. The number of newly-diagnosed homosexually infected under 30 years with a CD4 cell count over 400 cells/microL increased...

Step-function increase of significance of waste form in RWM strategy

International Nuclear Information System (INIS)

Roy, R.

1979-01-01

Radioactive waste management on the technical side is composed of four subsystems: storage, radionuclide immobilization, isolation, and post-emplacement. Thus far, emphasis has been on the isolation subsystem, with the assumption that all the radionuclides placed in the geological formation would be released. Findings by a committee of the National Academy of Science on the types of solid forms for radioactive wastes are summarized. The most important research findings of the last two or three years are evaluated, findings which impinge on the role of the newly developed radionuclide immobilization subsystems. 24 refs

Intracellular transport and sorting of mutant human proinsulins that fail to form hexamers.

Science.gov (United States)

Quinn, D; Orci, L; Ravazzola, M; Moore, H P

1991-06-01

Human proinsulin and insulin oligomerize to form dimers and hexamers. It has been suggested that the ability of prohormones to self associate and form aggregates may be responsible for the sorting process at the trans-Golgi. To examine whether insulin oligomerization is required for proper sorting into regulated storage granules, we have constructed point mutations in human insulin B chain that have been previously shown to prevent formation of insulin hexamers (Brange, J., U. Ribel, J. F. Hansen, G. Dodson, M. T. Hansen, S. Havelund, S. G. Melberg, F. Norris, K. Norris, L. Snel, A. R. Sorensen, and H. O. Voight. 1988. Nature [Lond.]. 333:679-682). One mutant (B10His----Asp) allows formation of dimers but not hexamers and the other (B9Ser----Asp) prevents formation of both dimers and hexamers. The mutants were transfected into the mouse pituitary AtT-20 cells, and their ability to be sorted into regulated secretory granules was compared to wild-type insulin. We found that while B10His----Asp is sorted somewhat less efficiently than wild-type insulin as reported previously (Carroll, R. J., R. E. Hammer, S. J. Chan, H. H. Swift, A. H. Rubenstein, and D. F. Steiner. 1988. Proc. Natl. Acad. Sci. USA. 85:8943-8947; Gross, D. J., P. A. Halban, C. R. Kahn, G. C. Weir, and L. Villa-Kumaroff. 1989. Proc. Natl. Acad. Sci. USA. 86:4107-4111). B9Ser----Asp is targeted to granules as efficiently as wild-type insulin. These results indicate that self association of proinsulin into hexamers is not required for its targeting to the regulated secretory pathway.

Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input

Directory of Open Access Journals (Sweden)

Paolo eBotta

2014-02-01

Full Text Available Golgi cells (GoCs are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generation tonic GABAA receptor-mediated currents in granule cells. In turn, granule cell axons provide feedback glutamatergic input to GoCs. It has been shown that high frequency stimulation of granule cell axons induces a transient pause in GoC firing in a type 2-metabotropic glutamate receptor (mGluR2-dependent manner. Here, we investigated the effect ethanol on the pause of GoC firing induced by high frequency stimulation of granule cell axons. GoC electrophysiological recordings were performed in parasagittal cerebellar vermis slices from postnatal day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40 mM reversibly decreases the pause duration. An antagonist of mGluR2 reduced the pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp recordings showed that currents evoked by an mGluR2 agonist were not significantly affected by ethanol. Perforated-patch experiments in which hyperpolarizing and depolarizing currents were injected into GoCs demonstrated that there is an inverse relationship between spontaneous firing and pause duration. Slight inhibition of the Na+/K+ pump mimicked the effect of ethanol on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated feedback mechanism by reducing the input responsiveness of GoCs. This would result in a transient increase of GABAA receptor-mediated inhibition of granule cells, limiting information flow at the input stage of the cerebellar cortex.

Study on mid and long-term strategic plan formulation for newly-constructed NPP

International Nuclear Information System (INIS)

Song Lin

2014-01-01

Mid and Long-term strategic plan plays a key role for the management of a newly constructed nuclear power company. Among others, process, goals, and risk management, are the primary concerns during plan preparing. The article analyzed these three areas for Fuqing NPP, including the formulating process for the plan, the mid and long-term goal setting of the company, the major risk analysis and countermeasure selection therefore. Through that solutions and suggestions for strategic plan formulation were concluded for newly-constructed NPP. (author)

The monomeric GTPase RabA2 is required for progression and maintenance of membrane integrity of infection threads during root nodule symbiosis.

Science.gov (United States)

Dalla Via, Virginia; Traubenik, Soledad; Rivero, Claudio; Aguilar, O Mario; Zanetti, María Eugenia; Blanco, Flavio Antonio

2017-04-01

Progression of the infection canal that conducts rhizobia to the nodule primordium requires a functional Rab GTPase located in Golgi/trans-Golgi that also participate in root hair polar growth. Common bean (Phaseolus vulgaris) symbiotically associates with its partner Rhizobium etli, resulting in the formation of root nitrogen-fixing nodules. Compatible bacteria can reach cortical cells in a tightly regulated infection process, in which the specific recognition of signal molecules is a key step to select the symbiotic partner. In this work, we show that RabA2, a monomeric GTPase from common bean, is required for the progression of the infection canal, referred to as the infection thread (IT), toward the cortical cells. Expression of miss-regulated mutant variants of RabA2 resulted in an increased number of abortive infection events, including bursting of ITs and a reduction in the number of nodules. Nodules formed in these plants were small and contained infected cells with disrupted symbiosome membranes, indicating either early senescence of these cells or defects in the formation of the symbiosome membrane during bacterial release. RabA2 localized to mobile vesicles around the IT, but mutations that affect GTP hydrolysis or GTP/GDP exchange modified this localization. Colocalization of RabA2 with ArfA1 and a Golgi marker indicates that RabA2 localizes in Golgi stacks and the trans-Golgi network. Our results suggest that RabA2 is part of the vesicle transport events required to maintain the integrity of the membrane during IT progression.

Newly velocity field of Sulawesi Island from GPS observation

Science.gov (United States)

Sarsito, D. A.; Susilo, Simons, W. J. F.; Abidin, H. Z.; Sapiie, B.; Triyoso, W.; Andreas, H.

2017-07-01

Sulawesi microplate Island is located at famous triple junction area of the Eurasian, India-Australian, and Philippine Sea plates. Under the influence of the northward moving Australian plate and the westward motion of the Philippine plate, the island at Eastern part of Indonesia is collide and with the Eurasian plate and Sunda Block. Those recent microplate tectonic motions can be quantitatively determine by GNSS-GPS measurement. We use combine GNSS-GPS observation types (campaign type and continuous type) from 1997 to 2015 to derive newly velocity field of the area. Several strategies are applied and tested to get the optimum result, and finally we choose regional strategy to reduce error propagation contribution from global multi baseline processing using GAMIT/GLOBK 10.5. Velocity field are analyzed in global reference frame ITRF 2008 and local reference frame by fixing with respect alternatively to Eurasian plate - Sunda block, India-Australian plate and Philippine Sea plates. Newly results show dense distribution of velocity field. This information is useful for tectonic deformation studying in geospatial era.

The Effect of Pollution on Newly-Formed Particle Composition in Boreal Forest

Science.gov (United States)

Vaattovaara, Petri

2010-05-01

Petri Vaattovaara (1), Tuukka Petäjä (2), Jorma Joutsensaari (1), Pasi Miettinen (1), Boris Zaprudin (1,6), Aki Kortelainen (1), Juha Heijari (3,7), Pasi Yli-Pirilä (3), Pasi Aalto (2), Doug R. Worsnop (4), and Ari Laaksonen(1,5) (1) University of Eastern Finland, Finland (2) University of Helsinki, Finland (3) University of Eastern Finland, Finland (4) Aerodyne Research Inc., USA (5) Finnish Meteorological Institute, Finland (6) Currently at University of Turku, Finland (7) Currently at Maritime Research Centre, Finland Email address of the Corresponding author: Petri.Vaattovaara@uef.fi The geographical extent of the tropical, temperate and boreal forests is about 30% of the Earth's land surface. Those forests are located around the world in different climate zones effecting widely on atmospheric composition via new particle formation. The Boreal forests solely cover one third of the forests extent and are one of the largest vegetation environments, forming a circumpolar band throughout the northern hemisphere continents, with a high potential to affect climate processes [1]. In order to more fully understand the possible climatic effects of the forests, the properties of secondary organic aerosols (SOA) in varying conditions (e.g. a change in meteorological parameters or in the concentrations of biogenic and antropogenic trace gases) need to be better known. In this study, we applied the UFO-TDMA (ultrafine organic tandem differential mobility analyzer [2]) and the UFH-TDMA (ultrafine hygroscopicity tandem differential mobility analyzer [3]) methods parallel to shed light on the evolution of the nucleation and Aitken mode particle compositions (via physic-chemical properties) at a virgin boreal forest site in varying conditions. The measurements were carried out at Hyytiälä forest station in Northern Europe (Finland) during 15 spring nucleation events. We also carried out a statistical analysis using linear correlations in order to explain the variability in

Degradation of dibenzofuran via multiple dioxygenation by a newly isolated Agrobacterium sp. PH-08.

Science.gov (United States)

Le, T T; Murugesan, K; Nam, I-H; Jeon, J-R; Chang, Y-S

2014-03-01

To demonstrate the biodegradation of dibenzofuran (DF) and its structural analogs by a newly isolated Agrobacterium sp. PH-08. To assess the biodegradation potential of newly isolated Agrobacterium sp. PH-08, various substrates were evaluated as sole carbon sources in growth and biotransformation experiments. ESI LC-MS/MS analysis revealed the presence of angular degrading by-products as well as lateral dioxygenation metabolites in the upper pathway. The metabolites in the lower pathway also were detected. In addition, the cometabolically degraded daughter compounds of DF-related compounds such as BP and dibenzothiophene (DBT) in dual substrate degradation were observed. Strain PH-08 exhibited the evidence of meta-cleavage pathway as confirmed by the activity and gene expression of catechol-2,3-dioxygenase. Newly isolated bacterial strain, Agrobacterium sp. PH-08, grew well with and degraded DF via both angular and lateral dioxygenation as demonstrated by metabolites identified through ESI LC-MS/MS and GC-MS analyses. The other heterocyclic pollutants were also cometabolically degraded. Few reports have described the complete degradation of DF by a cometabolic lateral pathway. Our study demonstrates the novel results that the newly isolated strain utilized the DF as a sole carbon source and mineralized it via multiple dioxygenation. © 2013 The Society for Applied Microbiology.

Star-forming galaxy models: Blending star formation into TREESPH

Science.gov (United States)

Mihos, J. Christopher; Hernquist, Lars

1994-01-01

We have incorporated star-formation algorithms into a hybrid N-body/smoothed particle hydrodynamics code (TREESPH) in order to describe the star forming properties of disk galaxies over timescales of a few billion years. The models employ a Schmidt law of index n approximately 1.5 to calculate star-formation rates, and explicitly include the energy and metallicity feedback into the Interstellar Medium (ISM). Modeling the newly formed stellar population is achieved through the use of hybrid SPH/young star particles which gradually convert from gaseous to collisionless particles, avoiding the computational difficulties involved in creating new particles. The models are shown to reproduce well the star-forming properties of disk galaxies, such as the morphology, rate of star formation, and evolution of the global star-formation rate and disk gas content. As an example of the technique, we model an encounter between a disk galaxy and a small companion which gives rise to a ring galaxy reminiscent of the Cartwheel (AM 0035-35). The primary galaxy in this encounter experiences two phases of star forming activity: an initial period during the expansion of the ring, and a delayed phase as shocked material in the ring falls back into the central regions.

Newly graduated nurses use of knowledge sources in clinical decison-making - a qualitative study

DEFF Research Database (Denmark)

Voldbjerg, Siri

of clinical decisions, based on transparent, articulate and reflective use of knowledge sources. Furthermore, it is implied that nurses are able to retrieve, asses, implement and evaluate research evidence. To meet these requirements, nursing educations around the world have organised curricula to educate...... graduated nurses do not work within a framework of evidence-based practice. The overall aim of this thesis was to explore which knowledge sources newly graduated nurses’ use in their clinical decision-making and why they use them in order to understand why newly graduated nurses use research and components...... within evidence-based practice to a limited extent. The thesis is based on a synthesis of findings from two studies. The aim of the first study was to explore which knowledge sources newly graduated nurses use in clinical decision making as reported within international qualitative research. The purpose...

Characterization of newly isolated lytic bacteriophages active against Acinetobacter baumannii.

Directory of Open Access Journals (Sweden)

Maia Merabishvili

Full Text Available Based on genotyping and host range, two newly isolated lytic bacteriophages, myovirus vB_AbaM_Acibel004 and podovirus vB_AbaP_Acibel007, active against Acinetobacter baumannii clinical strains, were selected from a new phage library for further characterization. The complete genomes of the two phages were analyzed. Both phages are characterized by broad host range and essential features of potential therapeutic phages, such as short latent period (27 and 21 min, respectively, high burst size (125 and 145, respectively, stability of activity in liquid culture and low frequency of occurrence of phage-resistant mutant bacterial cells. Genomic analysis showed that while Acibel004 represents a novel bacteriophage with resemblance to some unclassified Pseudomonas aeruginosa phages, Acibel007 belongs to the well-characterized genus of the Phikmvlikevirus. The newly isolated phages can serve as potential candidates for phage cocktails to control A. baumannii infections.

[Bioethical analysis of the use of newly dead patients in medical learning].

Science.gov (United States)

Gomes, Andréia Patrícia; Rego, Sergio; Palácios, Marisa; Siqueira-Batista, Rodrigo

2010-01-01

The purpose of this article is to carry out, a discussion on the subject of bioethics and cadavers based upon a critic review of literature. A review of literature, was made with a survey of articles between 1977 and 2007 in the sites 'Biblioteca Virtual de Saúde', PubMed and SciElo, utilizing the keywords: newly deceased patients, newly dead patients, simulators,. This was complemented by a critical evaluation of books published in the area of ethics and bioethics. The possibility to develop learning without orientation by a supervisor is doubtful.. The utilization of newly dead for learning invasive procedures is very frequent and seldom admitted. These procedures, are usually, carried out secretly, without the knowledge and consent of the family. The ethical aspects of these practices are not discussed in the practical medical education. It essential that the ethics of use of recent deceased become a necessary content of graduate education. Performance of these procedures by students should always be authorized by family members. The simulators meet the requirements of training. Discussions about the ethical and bioethical aspects cannot be separated from practical considerations during the students learning time.

Bone histomorphometry in children with newly diagnosed acute lymphoblastic leukemia

NARCIS (Netherlands)

Leeuw, JA; Koudstaal, J; Wiersema-Buist, J; Kamps, WA; Timens, W

2003-01-01

The objective of this study was to obtain insight into bone formation and resorption in children with newly diagnosed untreated acute lymphoblastic leukemia (ALL). In 23 consecutive children with ALL, a bone biopsy was taken from the crista iliaca posterior under ketamine anesthesia, together with

Cultural characters of a newly recognized group of hospital staphylococci.

Science.gov (United States)

Jevons, M P; John, M; Parker, M T

1966-07-01

Members of a newly recognized group of hospital staphylococci, which are believed to have arisen from 83A staphylococci by lysogenization, differ from them in several cultural characters. Some but not all of these characters appear to be determined by the carriage of phage.

Assessment of Knowledge and Attitudes of Newly-Qualified Doctors Towards AIDS Infection

Directory of Open Access Journals (Sweden)

Thomais Kalogirou

2010-01-01

Full Text Available Background: Health-care professionals are at a high risk of AIDS infection, among hospitalized HIV infectedpatients. Proper training and knowledge accompanied by necessary preventive measures are by all means, the mostsignificant factors which ensure low accident rates and furthermore lower contamination rates of the health-carepersonnel.Objective: Screening and assessment of knowledge and attitudes of newly-qualified doctors towards AIDSinfection.Methodology: We conducted a cohort study with a screening questionnaire, which included demographic data and16 questions associated with AIDS infection. 51 forms were filled in by specializing and rural doctors. Thestatistical analysis was conducted using the statistical program SPSS 13.Results: 25,5% (n=13 of the participants in this reserch have treated at least one patient for HIV infection, 19%(n=10, of them would willingly specialize in intense care of HIV patients and lastly 90.2%(n=46 believe that weshould preserve the medical confidential for HIV patients. 96.1% (n=49 of the participants doctors knew thatAIDS disease is caused by Human Immunodeficiency Virus (HIV, 88.2%(n=45 is aware that HIV virus damagesthe immune system and finally 92% (n=47 recognize HIV symptomatology.The vast majority of the doctors(98%,n=50 is aware that HIV infection is spread through sexual intercourse, blood contact and by sharing needlesor syringes. Nevertheless, a percentage of 13.7% (n=7 believe that HIV transmission is feasible through kissingand 7.8% (n=15 through insects’ bites. At last 85-98% of the personnel refer that it’s familiar with the generalpreventive measures, which are usually applied to all HIV positive inpatients.Conclusions: Knowledge and attitude of new doctors towards AIDS infection is, in general terms satisfactory.Nevertheless, it’s imperative that we constantly inform and update newly-qualified doctors about AIDS infection,in order to minimize their inhibitions and compensate for the

Mineralogy and Physico-Chemical Data of Two Newly Discovered Halloysite in China and Their Contrasts with Some Typical Minerals

Directory of Open Access Journals (Sweden)

Jing Ouyang

2018-03-01

Full Text Available We report in this article the systematical acquisition of physico-chemical parameters for two newly discovered halloysite (Hal minerals from Shiyan and Tongling in China. As the comparative reference, the data from Hal in Linfen, Chenxi, and the salt lake in Australia (samples were abbreviated as Hal-AU, Hal-SY, Hal-LF, Hal-CX and Hal-TL, respectively were also investigated using X-ray diffraction (XRD, scanning electronic microscopy (SEM, transmission electron microscopy (TEM, Fourier transformation infrared spectroscopy (FTIR, differential scanning calorimetry-thermogravimetry (DSC-TG, X-ray fluorescence, surface zeta potential measurements and N2 adsorption-desorption isotherms. The newly found minerals were probably formed in hydrothermal leaching and sedimentary circumstances. The Hal-SY contains 7 Å-halloysite and dickite, while Hal-TL contains 10 Å-halloysite with some alunite (similar with Hal-CX. Other impurities found in the samples include quartz, gibbsite, iron oxide and anatase. All of them showed tubular morphology with diameter in the range of 30–90 nm and a length of 300–2500 nm, while the Hal-SY has the largest inner diameter to about 150 nm. Specific surface areas varied from 26.0~59.0 m2·g−1. In addition, maximum CEC (cation exchange capacity of the newly found Hal was about 40 cmol/kg, while that of Hal-AU was relatively low (8 cmol/kg due to the sedimentary nature of Salt Lake circumstances. The surface charge was predominantly negative over most of the relevant pH range (>2.0. It can be concluded that the different morphology and impurity content of halloysite will greatly affect the surface area, pore volume, and cationic exchange capacity (CEC of the minerals.

The effect of preceptor role effectiveness on newly licensed registered nurses' perceived psychological empowerment and professional autonomy.

Science.gov (United States)

Watkins, Chanell; Hart, Patricia L; Mareno, Nicole

2016-03-01

The first year turnover rate for newly licensed registered nurses is roughly 30% and increases to about 57% in the second year (Twibell et al., 2012). An effective preceptorship has been shown to better facilitate the first year transition (Hodges et al., 2008) and increase retention rates (Pine and Tart, 2007). The purpose of this study was to examine the relationships between newly licensed registered nurses' perceived preceptor role effectiveness, psychological empowerment and professional autonomy. A prospective, cross-sectional, descriptive research design was used. Sixty-nine newly licensed registered nurses were recruited and surveyed. Newly licensed registered nurses were found to have moderately high levels of perceived preceptor role effectiveness, psychological empowerment, and professional autonomy. Preceptor role effectiveness had significant, moderately, positive relationships with professional autonomy and psychological empowerment. There was also a significant relationship found between professional autonomy and psychological empowerment. Results show that preceptor role effectiveness is linked to increased professional autonomy and psychological empowerment. Therefore, effective preceptorships are necessary in easing the newly licensed registered nurse's transition to practice. Strategies to ensure effective preceptorships and enhance the NRLN's transition to practice are proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Management of Newly Diagnosed Atrial Fibrillation in an Outpatient Clinic Setting

DEFF Research Database (Denmark)

Thrysoee, Lars; Strömberg, Anna; Brandes, Axel

2018-01-01

fibrillation is not a fatal disease in itself was very important for patients. At the same time, visiting the clinic was overwhelming, information was difficult to understand, and patients found it difficult to be involved in decision-making. CONCLUSIONS: This study indicates that patients were uncertain......AIMS: To gain in-depth knowledge of patients' experiences of the consultation processes at a multidisciplinary atrial fibrillation outpatient clinic in a university hospital in Denmark. BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia associated with morbidity and mortality...... if not diagnosed and treated as recommended. Patients with newly diagnosed atrial fibrillation preferably should be managed in an outpatient setting which includes medical examination, patient education and decision making on medical therapy. DESIGN: This is a qualitative study of 14 patients newly diagnosed...

Sequence Classification: 891407 [

Lifescience Database Archive (English)

Full Text Available ive stress, forms LMA1 complex with Pbi2p, acts as a cofactor for Tsa1p, required for ER-Golgi transport and vacuole inheritance; Trx2p || http://www.ncbi.nlm.nih.gov/protein/6321648 ...

QR encoded smart oral dosage forms by inkjet printing.

Science.gov (United States)

Edinger, Magnus; Bar-Shalom, Daniel; Sandler, Niklas; Rantanen, Jukka; Genina, Natalja

2018-01-30

The use of inkjet printing (IJP) technology enables the flexible manufacturing of personalized medicine with the doses tailored for each patient. In this study we demonstrate, for the first time, the applicability of IJP in the production of edible dosage forms in the pattern of a quick response (QR) code. This printed pattern contains the drug itself and encoded information relevant to the patient and/or healthcare professionals. IJP of the active pharmaceutical ingredient (API)-containing ink in the pattern of QR code was performed onto a newly developed porous and flexible, but mechanically stable substrate with a good absorption capacity. The printing did not affect the mechanical properties of the substrate. The actual drug content of the printed dosage forms was in accordance with the encoded drug content. The QR encoded dosage forms had a good print definition without significant edge bleeding. They were readable by a smartphone even after storage in harsh conditions. This approach of efficient data incorporation and data storage combined with the use of smart devices can lead to safer and more patient-friendly drug products in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Importance of circulating tumor cells in newly diagnosed colorectal cancer

NARCIS (Netherlands)

van Dalum, Guus; Stam, Gerrit-Jan; Scholten, Loes F.A.; Mastboom, Walter J.B.; Vermes, I.; Tibbe, Arjan G.J.; De Groot, Marco R.; Terstappen, Leonardus Wendelinus Mathias Marie

2015-01-01

Presence of circulating tumor cells (CTC) is associated with poor prognosis in patients with metastatic colorectal cancer (CRC). The present study was conducted to determine if the presence of CTC prior to surgery and during follow‑up in patients with newly diagnosed non-metastatic CRC can identify

Physiological evaluation of a newly designed lever mechanism for wheelchairs

NARCIS (Netherlands)

van der Woude, L H; Veeger, DirkJan (H. E. J.); de Boer, Y; Rozendal, R H

1993-01-01

Lever-propelled wheelchairs have been described as more efficient and less physically demanding than hand-rim-propelled wheelchairs. To evaluate a newly designed lever mechanism (MARC) in both one- and two-arm use, a series of wheelchair exercise tests were performed on a motor-driven treadmill.

EYE DISEASE IN NEWLY-DIAGNOSED LEPROSY PATIENTS IN EASTERN NEPAL

NARCIS (Netherlands)

LUBBERS, WJ; SCHIPPER, A; HOGEWEG, M; DESOLDENHOFF, R

To determine the magnitude of eye lesions in newly diagnosed leprosy patients we examined their eyes. The Eastern Leprosy Control Project was supported by The Netherlands Leprosy Relief Association; we used the regional clinic in Biratnagar and 5 mobile clinics in surrounding districts as our survey

Parental influences on sperm banking attempts among adolescent males newly diagnosed with cancer.

Science.gov (United States)

Klosky, James L; Flynn, Jessica S; Lehmann, Vicky; Russell, Kathryn M; Wang, Fang; Hardin, Robin N; Eddinger, Jasmine R; Zhang, Hui; Schenck, Lauren A-M; Schover, Leslie R

2017-12-01

To investigate the influence of parental sociodemographic, communication, and psychological factors on sperm collection attempts among at-risk adolescent males newly diagnosed with cancer. Prospective, single group, observational study design. Pediatric oncology centers. Parents (N = 144) of 122 newly diagnosed adolescent males at increased risk for infertility secondary to cancer therapy. Survey-based assessment of parent factors associated with adolescent collection attempts. Attempt of manual collection of sperm. Parental recommendation to bank sperm (odds ratio [OR] 3.72; 95% confidence interval [CI] 1.18-11.76) and perceived self-efficacy to facilitate banking (OR 1.20; 95% CI 1.02-1.41) were associated with an increased likelihood of making a collection attempt. Parental recommendation to bank is a critical influence for sperm banking among adolescent males newly diagnosed with cancer. These findings highlight the importance of effective communication between parents, patients, and health-care teams when discussing preservation options. Parent perceptions of their ability to facilitate sperm banking at the time of diagnosis should also be targeted in future interventions. NCT01152268. Copyright © 2017. Published by Elsevier Inc.

Quality of life of elderly persons with newly diagnosed cancer

DEFF Research Database (Denmark)

Esbensen, B A; Osterlind, K; Roer, O

2004-01-01

The aim was to investigate quality of life (QoL) in elderly persons newly diagnosed with cancer (65+ years) in relation to age, contact with the health-care system, ability to perform activities of daily living (ADL), hope, social network and support, and to identify which factors were associated...... with low QoL. The sample consisted of 101 patients (75 women and 26 men) newly diagnosed with cancer. EORTC QLQ-C30, Nowotny's Hope Scale, Katz ADL and the Interview Schedule for Social Interaction (ISSI) were used. The analysis was carried out in four age groups and revealed no significant differences...... in QoL. Compared with the other age groups, those of a high age (80+ years) more often lived alone, used more home-help service and had a smaller social network. Factors associated with low QoL were 'no other incomes than retirement pension', 'low level of hope' and 'lung cancer'. In addition, 'being...

HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

Science.gov (United States)

Lu, Xinli; Kang, Xianjiang; Liu, Yongjian; Cui, Ze; Guo, Wei; Zhao, Cuiying; Li, Yan; Chen, Suliang; Li, Jingyun; Zhang, Yuqi; Zhao, Hongru

2017-01-01

New human immunodeficiency virus type 1 (HIV-1) diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF)01_AE (53.4%), CRF07_BC (23.4%), subtype B (15.9%), and unique recombinant forms URFs (4.9%). Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx), unknown before in Hebei, were first found among men who have sex with men (MSM). All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%), CRF01_AE/B (23.3%), B/C (16.7%), CRF01_AE/C (13.3%), CRF01_AE/B/A2 (3.3%) and CRF01_AE/BC/A2 (3.3%), plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China.

HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

Directory of Open Access Journals (Sweden)

Xinli Lu

Full Text Available New human immunodeficiency virus type 1 (HIV-1 diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF01_AE (53.4%, CRF07_BC (23.4%, subtype B (15.9%, and unique recombinant forms URFs (4.9%. Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx, unknown before in Hebei, were first found among men who have sex with men (MSM. All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%, CRF01_AE/B (23.3%, B/C (16.7%, CRF01_AE/C (13.3%, CRF01_AE/B/A2 (3.3% and CRF01_AE/BC/A2 (3.3%, plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China.

Quality of life of elderly persons with newly diagnosed cancer

DEFF Research Database (Denmark)

Esbensen, B A; Osterlind, K; Roer, O

2004-01-01

The aim was to investigate quality of life (QoL) in elderly persons newly diagnosed with cancer (65+ years) in relation to age, contact with the health-care system, ability to perform activities of daily living (ADL), hope, social network and support, and to identify which factors were associated...

Breeding of newly licensed wheat variety Huapei 8 and improved ...

African Journals Online (AJOL)

ajl yemi

2011-12-28

Dec 28, 2011 ... Full Length Research Paper. Breeding of newly licensed wheat variety Huapei 8 and improved breeding strategy by anther culture ... more efficient in pure line selection rather than the hete- .... Regional and productivity tests showed that Huapei 8 had .... Large-scale production of wheat and triticale double.

Who Is Doing Well? A Typology of Newly Homeless Adolescents

Science.gov (United States)

Milburn, Norweeta; Liang, Li-Jung; Lee, Sung-Jae; Rotheram-Borus, Mary Jane; Rosenthal, Doreen; Mallett, Shelley; Lightfoot, Marguerita; Lester, Patricia

2009-01-01

There is growing evidence to support developing new typologies for homeless adolescents. Current typologies focus on the risks associated with being homeless, with less consideration of the positive attributes of homeless adolescents. The authors examined both risk and protective factors in a sample of newly homeless adolescents. Using cluster…

Clinical Prediction Model for Time in Therapeutic Range While on Warfarin in Newly Diagnosed Atrial Fibrillation.

Science.gov (United States)

Williams, Brent A; Evans, Michael A; Honushefsky, Ashley M; Berger, Peter B

2017-10-12

Though warfarin has historically been the primary oral anticoagulant for stroke prevention in newly diagnosed atrial fibrillation (AF), several new direct oral anticoagulants may be preferred when anticoagulation control with warfarin is expected to be poor. This study developed a prediction model for time in therapeutic range (TTR) among newly diagnosed AF patients on newly initiated warfarin as a tool to assist decision making between warfarin and direct oral anticoagulants. This electronic medical record-based, retrospective study included newly diagnosed, nonvalvular AF patients with no recent warfarin exposure receiving primary care services through a large healthcare system in rural Pennsylvania. TTR was estimated as the percentage of time international normalized ratio measurements were between 2.0 and 3.0 during the first year following warfarin initiation. Candidate predictors of TTR were chosen from data elements collected during usual clinical care. A TTR prediction model was developed and temporally validated and its predictive performance was compared with the SAMe-TT 2 R 2 score (sex, age, medical history, treatment, tobacco, race) using R 2 and c-statistics. A total of 7877 newly diagnosed AF patients met study inclusion criteria. Median (interquartile range) TTR within the first year of starting warfarin was 51% (32, 67). Of 85 candidate predictors evaluated, 15 were included in the final validated model with an R 2 of 15.4%. The proposed model showed better predictive performance than the SAMe-TT 2 R 2 score ( R 2 =3.0%). The proposed prediction model may assist decision making on the proper mode of oral anticoagulant among newly diagnosed AF patients. However, predicting TTR on warfarin remains challenging. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Wide-field Infrared Survey Explorer Observations of the Evolution of Massive Star-forming Regions

OpenAIRE

Koenig, X. P.; Leisawitz, D. T.; Benford, D. J.; Rebull, L. M.; Padgett, D. L.; Assef, R. J.

2012-01-01

We present the results of a mid-infrared survey of 11 outer Galaxy massive star-forming regions and 3 open clusters with data from the Wide-field Infrared Survey Explorer (WISE). Using a newly developed photometric scheme to identify young stellar objects and exclude extragalactic contamination, we have studied the distribution of young stars within each region. These data tend to support the hypothesis that latter generations may be triggered by the interaction of winds and radiation from th...

33 CFR 150.515 - What are the requirements for weight testing of newly installed or relocated craft?

Science.gov (United States)

2010-07-01

... weight testing of newly installed or relocated craft? 150.515 Section 150.515 Navigation and Navigable... testing of newly installed or relocated craft? (a) The operator must perform installation weight testing... (a) of this section, when survival crafts are relocated to another deepwater port. ...

18 CFR 347.1 - Material to support request for newly established or changed property account depreciation studies.

Science.gov (United States)

2010-04-01

... request for newly established or changed property account depreciation studies. 347.1 Section 347.1... REGULATIONS UNDER THE INTERSTATE COMMERCE ACT OIL PIPELINE DEPRECIATION STUDIES § 347.1 Material to support request for newly established or changed property account depreciation studies. (a) Means of filing...

Health related quality of life in patients with newly diagnosed anti-neutrophil cytoplasm antibody associated vasculitis

Science.gov (United States)

Walsh, Michael; Mukhtyar, Chetan; Mahr, Alfred; Herlyn, Karen; Luqmani, Raashid; Merkel, Peter A.; Jayne, David R. W.

2011-01-01

Background Anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) can present with a broad spectrum of signs and symptoms. The relative effects of different manifestations on health related quality of life (HRQOL) is unknown. Methods We conducted an individual patient data meta-analysis of baseline Short Form 36 (SF-36) scores from four randomized controlled trials of patients with newly diagnosed AAV. We determined the associations between organ manifestations at trial entry and the SF-36 Physical Composite Score (PCS) and Mental Composite Score (MCS) using mixed effects models adjusted for demographic factors. Associations with each of the 8 domains of the SF-36 were further explored using multivariate multiple regression. Results SF-36 data was available from 346 patients. Older age (−0.11 points/year; 95% Confidence Interval [CI] −0.21 to −0.012; p=0.029) and neurologic involvement (−5.84, p<0.001) at baseline were associated with lower Physical Composite Scores. Physical Function scores were the most affected and older age (−0.25 points per year, 95% Confidence Interval [CI] −0.38 to −0.11; p<0.001) scores and neurologic involvement (−8.48 points, 95% CI −12.90 to −4.06; p<0.001) had the largest effects. The MCS was negatively affected only by chest involvement (p=0.027) but this effect was not exerted in any particular domain. Conclusions HRQOL in patients with newly diagnosed AAV are complex and incompletely explained by their organ system manifestations. PMID:21452254

Hope pictured in drawings by women newly diagnosed with gynecological cancer

DEFF Research Database (Denmark)

Hammer, Kristianna; Hall, Elisabeth; Mogensen, Ole

2013-01-01

BACKGROUND:: In mysterious ways, hope makes life meaningful even in chaotic and uncontrolled situations. When a woman is newly diagnosed with gynecologic cancer, hope is ineffable and needs exploring. Drawings help express ineffable phenomena. OBJECTIVE:: The aim of the study was to explore how...... women newly diagnosed with gynecologic cancer express the meaning of hope in drawings. METHOD:: Participants were 15 women who on the same day had received the diagnosis of gynecologic cancer. They were between 24 and 87 years (median, 52 years) with a variety of gynecologic cancer diagnoses. Data from...... 15 drawings and postdrawing interviews with the women were analyzed using visual and hermeneutic phenomenology. RESULTS:: Three themes emerged: hope as a spirit to move on, hope as energy through nature, and hope as a communion with families. CONCLUSION:: Hope as pictured in drawings often appears...

Clinical and immunological status of a newly diagnosed HIV positive ...

African Journals Online (AJOL)

Objective: To evaluate the clinical and the immune status of newly HIV diagnosed patients, in Marrakech city and its neighboring area, in Morocco. Methods: We performed a retrospective study on 235 patients who have been previously confirmed for HIV infection, and underwent a CD4 T cells using flow cytometry ...

At the Bridging Point: Tutoring Newly Arrived Students in Sweden

Science.gov (United States)

Avery, Helen

2017-01-01

In Sweden, tutoring in the mother tongue is a special support measure primarily intended for newly arrived students to facilitate their transition into the Swedish school system. Tutoring is premised on the collaboration between the class teacher, responsible for subject-related expertise, and the tutor, who contributes with knowledge of the…

Ethical climate and nurse competence - newly graduated nurses' perceptions.

Science.gov (United States)

Numminen, Olivia; Leino-Kilpi, Helena; Isoaho, Hannu; Meretoja, Riitta

2015-12-01

Nursing practice takes place in a social framework, in which environmental elements and interpersonal relations interact. Ethical climate of the work unit is an important element affecting nurses' professional and ethical practice. Nevertheless, whatever the environmental circumstances, nurses are expected to be professionally competent providing high-quality care ethically and clinically. This study examined newly graduated nurses' perception of the ethical climate of their work environment and its association with their self-assessed professional competence, turnover intentions and job satisfaction. Descriptive, cross-sectional, correlational research design was applied. Participants consisted of 318 newly graduated nurses. Data were collected electronically and analysed statistically. Ethical approval and permissions to use instruments and conduct the study were obtained according to required procedures. Data were rendered anonymous to protect participant confidentiality. Completing the questionnaire was interpreted as consent to participate. Nurses' overall perception of the ethical climate was positive. More positive perceptions related to peers, patients and physicians, and less positive to hospitals and managers. Strong associations were found between perceived ethical climate and self-assessed competence, turnover intentions in terms of changing job, and job satisfaction in terms of quality of care. Nurses at a higher competence level with positive views of job satisfaction and low turnover intentions perceived the climate significantly more positively. Nursing management responsible for and having the power to implement changes should understand their contribution in ethical leadership, as well as the multidimensional nature of nurses' work environment and the interaction between work-related factors in planning developmental measures. Future research should focus on issues in nurse managers' ethical leadership in creating ethical work environments. There

Global transgenerational gene expression dynamics in two newly synthesized allohexaploid wheat (Triticum aestivum lines

Directory of Open Access Journals (Sweden)

Qi Bao

2012-01-01

Full Text Available Abstract Background Alteration in gene expression resulting from allopolyploidization is a prominent feature in plants, but its spectrum and extent are not fully known. Common wheat (Triticum aestivum was formed via allohexaploidization about 10,000 years ago, and became the most important crop plant. To gain further insights into the genome-wide transcriptional dynamics associated with the onset of common wheat formation, we conducted microarray-based genome-wide gene expression analysis on two newly synthesized allohexaploid wheat lines with chromosomal stability and a genome constitution analogous to that of the present-day common wheat. Results Multi-color GISH (genomic in situ hybridization was used to identify individual plants from two nascent allohexaploid wheat lines between Triticum turgidum (2n = 4x = 28; genome BBAA and Aegilops tauschii (2n = 2x = 14; genome DD, which had a stable chromosomal constitution analogous to that of common wheat (2n = 6x = 42; genome BBAADD. Genome-wide analysis of gene expression was performed for these allohexaploid lines along with their parental plants from T. turgidum and Ae. tauschii, using the Affymetrix Gene Chip Wheat Genome-Array. Comparison with the parental plants coupled with inclusion of empirical mid-parent values (MPVs revealed that whereas the great majority of genes showed the expected parental additivity, two major patterns of alteration in gene expression in the allohexaploid lines were identified: parental dominance expression and non-additive expression. Genes involved in each of the two altered expression patterns could be classified into three distinct groups, stochastic, heritable and persistent, based on their transgenerational heritability and inter-line conservation. Strikingly, whereas both altered patterns of gene expression showed a propensity of inheritance, identity of the involved genes was highly stochastic, consistent with the involvement of diverse Gene Ontology (GO

Biosynthesis of intestinal microvillar proteins. Dimerization of aminopeptidase N and lactase-phlorizin hydrolase

DEFF Research Database (Denmark)

Danielsen, E M

1990-01-01

of dimers of this enzyme therefore occurs prior to the Golgi-associated processing, and the slow rate of dimerization may be the rate-limiting step in the transport from the endoplasmic reticulum to the Golgi complex. For lactase-phlorizin hydrolase, the posttranslational processing includes a proteolytic......The pig intestinal brush border enzymes aminopeptidase N (EC 3.4.11.2) and lactase-phlorizin hydrolase (EC 3.2.1.23-62) are present in the microvillar membrane as homodimers. Dimethyl adipimidate was used to cross-link the two [35S]methionine-labeled brush border enzymes from cultured mucosal...... explants. For aminopeptidase N, dimerization did not begin until 5-10 min after synthesis, and maximal dimerization by cross-linking of the transient form of the enzyme required 1 h, whereas the mature form of aminopeptidase N cross-linked with unchanged efficiency from 45 min to 3 h of labeling. Formation...

High acceptability of a newly developed urological practical skills training program.

NARCIS (Netherlands)

Vries, A.H. de; Luijk, S.J. van; Scherpbier, A.J.J.A.; Hendrikx, A.J.M.; Koldewijn, E.L.; Wagner, C.; Schout, B.M.A.

2015-01-01

Background: Benefits of simulation training are widely recognized, but its structural implementation into urological curricula remains challenging. This study aims to gain insight into current and ideal urological practical skills training and presents the outline of a newly developed skills

High acceptability of a newly developed urological practical skills training program

NARCIS (Netherlands)

de Vries, A.H.; van Luijk, S.J.; Scherpbier, A.J.J.A.; Hendrikx, A.J.M.; Koldewijn, E.L.; Wagner, C.; Schout, B.M.A.

2015-01-01

Background: Benefits of simulation training are widely recognized, but its structural implementation into urological curricula remains challenging. This study aims to gain insight into current and ideal urological practical skills training and presents the outline of a newly developed skills

Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation

NARCIS (Netherlands)

Camm, A.J.; Accetta, G.; Ambrosio, G.; Atar, D.; Bassand, J.P.; Berge, E. van de; Cools, F.; Fitzmaurice, D.A.; Goldhaber, S.Z.; Goto, S.; Haas, S.; Kayani, G.; Koretsune, Y.; Mantovani, L.G.; Misselwitz, F.; Oh, S.; Turpie, A.G.G.; Verheugt, F.W.A.; Kakkar, A.K.

2017-01-01

OBJECTIVE: We studied evolving antithrombotic therapy patterns in patients with newly diagnosed non-valvular atrial fibrillation (AF) and >/=1 additional stroke risk factor between 2010 and 2015. METHODS: 39 670 patients were prospectively enrolled in four sequential cohorts in the Global

Shrinkage of Newly Formed Particles in an Urban Environment

Czech Academy of Sciences Publication Activity Database

Škrabalová, Lenka; Zíková, Naděžda; Ždímal, Vladimír

2015-01-01

Roč. 15, č. 4 (2015), s. 1313-1324 ISSN 1680-8584 R&D Projects: GA ČR GAP209/11/1342 Institutional support: RVO:67985858 Keywords : aerosol dynamics * ultrafine particles * particle shrinkage Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.393, year: 2015

GPR107, a G-protein-coupled receptor essential for intoxication by Pseudomonas aeruginosa exotoxin A, localizes to the Golgi and is cleaved by furin.

Science.gov (United States)

Tafesse, Fikadu G; Guimaraes, Carla P; Maruyama, Takeshi; Carette, Jan E; Lory, Stephen; Brummelkamp, Thijn R; Ploegh, Hidde L

2014-08-29

A number of toxins, including exotoxin A (PE) of Pseudomonas aeruginosa, kill cells by inhibiting protein synthesis. PE kills by ADP-ribosylation of the translation elongation factor 2, but many of the host factors required for entry, membrane translocation, and intracellular transport remain to be elucidated. A genome-wide genetic screen in human KBM7 cells was performed to uncover host factors used by PE, several of which were confirmed by CRISPR/Cas9-gene editing in a different cell type. Several proteins not previously implicated in the PE intoxication pathway were identified, including GPR107, an orphan G-protein-coupled receptor. GPR107 localizes to the trans-Golgi network and is essential for retrograde transport. It is cleaved by the endoprotease furin, and a disulfide bond connects the two cleaved fragments. Compromising this association affects the function of GPR107. The N-terminal region of GPR107 is critical for its biological function. GPR107 might be one of the long-sought receptors that associates with G-proteins to regulate intracellular vesicular transport. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

A Newly Naturalized Species in Taiwan: Phytolacca icosandra L. (Phytolaccaceae

Directory of Open Access Journals (Sweden)

Szu-I Hsieh

2012-12-01

Full Text Available Phytolacca icosandra L. (Phytolaccaceae, native to the South America has been found recently in central Taiwan. This newly naturalized species is distinguished by its erect spike-like racemes and 12–20 stamens. This paper describes the morphology of the species and provides line drawing and photographs for identification.

The impact of female genital cutting on health of newly married women.

Science.gov (United States)

Elnashar, A; Abdelhady, R

2007-06-01

To detect the rate of female genital cutting among a sample of newly married women in Benha city, and make a comparison between circumcised and non-circumcised women regarding long-term health problems. Randomly selected (264) newly married women were the subjects of this work. Circumcised group constitutes 75.8% of the sample. All non-circumcised women were living in an urban area. Dysmenorrhea was more common among circumcised rather than non-circumcised, with statistically significant difference (Pwomen. Obstetric problems such as tears, episiotomy and consequently distressed babies were more events among circumcised mothers with statistical significance. Circumcised females had significant mental problems such as somatization, anxiety and phobia (Pwomen's life particularly the time of consummation of marriage and the time of childbirth.

Depression and cognitive impairment among newly admitted nursing home residents in the USA.

Science.gov (United States)

Ulbricht, Christine M; Rothschild, Anthony J; Hunnicutt, Jacob N; Lapane, Kate L

2017-11-01

The objective of this study is to describe the prevalence of depression and cognitive impairment among newly admitted nursing home residents in the USA and to describe the treatment of depression by level of cognitive impairment. We identified 1,088,619 newly admitted older residents between 2011 and 2013 with an active diagnosis of depression documented on the Minimum Data Set 3.0. The prevalence of receiving psychiatric treatment was estimated by cognitive impairment status and depression symptoms. Binary logistic regression using generalized estimating equations provided adjusted odds ratios and 95% confidence intervals for the association between level of cognitive impairment and receipt of psychiatric treatment, adjusted for clustering of residents within nursing homes and resident characteristics. Twenty-six percent of newly admitted residents had depression; 47% of these residents also had cognitive impairment. Of those who had staff assessments of depression, anhedonia, impaired concentration, psychomotor disturbances, and irritability were more commonly experienced by residents with cognitive impairment than residents without cognitive impairment. Forty-eight percent of all residents with depression did not receive any psychiatric treatment. Approximately one-fifth of residents received a combination of treatment. Residents with severe cognitive impairment were less likely than those with intact cognition to receive psychiatric treatment (adjusted odds ratio = 0.95; 95% confidence interval: 0.93-0.98). Many newly admitted residents with an active diagnosis of depression are untreated, potentially missing an important window to improve symptoms. The extent of comorbid cognitive impairment and depression and lack of treatment suggest opportunities for improved quality of care in this increasingly important healthcare setting. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Molecular detection of HIV-1 subtype B, CRF01_AE, CRF33_01B, and newly emerging recombinant lineages in Malaysia.

Science.gov (United States)

Chook, Jack Bee; Ong, Lai Yee; Takebe, Yutaka; Chan, Kok Gan; Choo, Martin; Kamarulzaman, Adeeba; Tee, Kok Keng

2015-03-01

A molecular genotyping assay for human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia is difficult to design because of the high level of genetic diversity. We developed a multiplex real-time polymerase chain reaction (PCR) assay to detect subtype B, CRF01_AE, CRF33_01B, and three newly described circulating recombinant forms, (CRFs) (CRF53_01B, CRF54_01B, and CRF58_01B). A total of 785 reference genomes were used for subtype-specific primers and TaqMan probes design targeting the gag, pol, and env genes. The performance of this assay was compared and evaluated with direct sequencing and phylogenetic analysis. A total of 180 HIV-infected subjects from Kuala Lumpur, Malaysia were screened and 171 samples were successfully genotyped, in agreement with the phylogenetic data. The HIV-1 genotype distribution was as follows: subtype B (16.7%); CRF01_AE (52.8%); CRF33_01B (24.4%); CRF53_01B (1.1%); CRF54_01B (0.6%); and CRF01_AE/B unique recombinant forms (4.4%). The overall accuracy of the genotyping assay was over 95.0%, in which the sensitivities for subtype B, CRF01_AE, and CRF33_01B detection were 100%, 100%, and 97.7%, respectively. The specificity of genotyping was 100%, inter-subtype specificities were > 95% and the limit of detection of 10(3) copies/mL for plasma. The newly developed real-time PCR assay offers a rapid and cost-effective alternative for large-scale molecular epidemiological surveillance for HIV-1. © The American Society of Tropical Medicine and Hygiene.

Golgi Analysis of Neuron Morphology in the Presumptive Somatosensory Cortex and Visual Cortex of the Florida Manatee (Trichechus manatus latirostris).

Science.gov (United States)

Reyes, Laura D; Harland, Tessa; Reep, Roger L; Sherwood, Chet C; Jacobs, Bob

2016-01-01

The current study investigates neuron morphology in presumptive primary somatosensory (S1) and primary visual (V1) cortices of the Florida manatee (Trichechus manatus latirostris) as revealed by Golgi impregnation. Sirenians, including manatees, have an aquatic lifestyle, a large body size, and a relatively large lissencephalic brain. The present study examines neuron morphology in 3 cortical areas: in S1, dorsolateral cortex area 1 (DL1) and cluster cortex area 2 (CL2) and in V1, dorsolateral cortex area 4 (DL4). Neurons exhibited a variety of morphological types, with pyramidal neurons being the most common. The large variety of neuron types present in the manatee cortex was comparable to that seen in other eutherian mammals, except for rodents and primates, where pyramid-shaped neurons predominate. A comparison between pyramidal neurons in S1 and V1 indicated relatively greater dendritic branching in S1. Across all 3 areas, the dendritic arborization pattern of pyramidal neurons was also similar to that observed previously in the afrotherian rock hyrax, cetartiodactyls, opossums, and echidnas but did not resemble the widely bifurcated dendrites seen in the large-brained African elephant. Despite adaptations for an aquatic environment, manatees did not share specific neuron types such as tritufted and star-like neurons that have been found in cetaceans. Manatees exhibit an evolutionarily primitive pattern of cortical neuron morphology shared with most other mammals and do not appear to have neuronal specializations for an aquatic niche. © 2016 S. Karger AG, Basel.

Secretion of 35SO4-labeled proteins from isolated rat hepatocytes

International Nuclear Information System (INIS)

von Wuertemberg, M.M.F.; Fries, E.

1989-01-01

Sulfation is a Golgi-specific modification of secretory proteins. We have characterized the proteins that are labeled with 35 SO 4 in cultures of rat hepatocytes and studied their transport to the medium. Analysis by polyacrylamide gel electrophoresis showed that of the five most heavily labeled proteins, four had well-defined mobilities--apparent molecular masses of 188, 142, 125, and 82 kDa--whereas one was electrophoretically heterogeneous--apparent molecular mass of 35-45 kDa. Judging by their relatively high resistance to acid treatment, the sulfate residues in the 125- and 35-45-kDa proteins were linked to carbohydrate. Some of the secreted proteins were sialylated. In samples of pulse-labeled cells, there appeared to be no unsialylated forms, indicating that sulfation occurred after sialylation, presumably in the trans Golgi. Kinetic experiments showed that the cellular half-life was the same for all the sulfated proteins--about 8 min--consistent with the idea that transport from the Golgi complex to the cell surface occurs by liquid bulk flow

Fitness, daily activity and body composition in children with newly diagnosed, untreated asthma

DEFF Research Database (Denmark)

Vahlkvist, S; Pedersen, S

2009-01-01

Background: Information about how the asthma disease affects the life style and health in children is sparse. Aim: To measure fitness, daily physical activity and body composition in children with newly diagnosed, untreated asthma and healthy controls, and to assess the association between...... the level of asthma control and these parameters. Methods: Daily physical activity measured using accelerometry, cardiovascular fitness and body composition (per cent fat, per cent lean tissue and bone mineral density) were measured in 57 children with newly diagnosed, untreated asthma and in 157 healthy...... fitness and daytime spent in intensive activity. Overweight children are physically less active than normal weight children....

Critical thinking dispositions among newly graduated nurses.

Science.gov (United States)

Wangensteen, Sigrid; Johansson, Inger S; Björkström, Monica E; Nordström, Gun

2010-10-01

The aim of the study was to describe critical thinking dispositions among newly graduated nurses in Norway, and to study whether background data had any impact on critical thinking dispositions. Competence in critical thinking is one of the expectations of nursing education. Critical thinkers are described as well-informed, inquisitive, open-minded and orderly in complex matters. Critical thinking competence has thus been designated as an outcome for judging the quality of nursing education programmes and for the development of clinical judgement. The ability to think critically is also described as reducing the research-practice gap and fostering evidence-based nursing. A cross-sectional descriptive study was performed. The data were collected between October 2006 and April 2007 using the California Critical Thinking Disposition Inventory. The response rate was 33% (n = 618). Pearson's chi-square tests were used to analyse the data. Nearly 80% of the respondents reported a positive disposition towards critical thinking. The highest mean score was on the Inquisitiveness subscale and the lowest on the Truth-seeking subscale. A statistically significant higher proportion of nurses with high critical thinking scores were found among those older than 30 years, those with university education prior to nursing education, and those working in community health care. Nurse leaders and nurse teachers should encourage and nurture critical thinking among newly graduated nurses and nursing students. The low Truth-seeking scores found may be a result of traditional teaching strategies in nursing education and might indicate a need for more student-active learning models. © 2010 The Authors. Journal of Advanced Nursing © 2010 Blackwell Publishing Ltd.

Identification of rice cornichon as a possible cargo receptor for the Golgi-localized sodium transporter OsHKT1;3

Science.gov (United States)

Rosas-Santiago, Paul; Lagunas-Gómez, Daniel; Barkla, Bronwyn J.; Vera-Estrella, Rosario; Lalonde, Sylvie; Jones, Alexander; Frommer, Wolf B.; Zimmermannova, Olga; Sychrová, Hana; Pantoja, Omar

2015-01-01

Membrane proteins are synthesized and folded in the endoplasmic reticulum (ER), and continue their path to their site of residence along the secretory pathway. The COPII system has been identified as a key player for selecting and directing the fate of membrane and secretory cargo proteins. Selection of cargo proteins within the COPII vesicles is achieved by cargo receptors. The cornichon cargo receptor belongs to a conserved protein family found in eukaryotes that has been demonstrated to participate in the selection of integral membrane proteins as cargo for their correct targeting. Here it is demonstrated at the cellular level that rice cornichon OsCNIH1 interacts with OsHKT1;3 and, in yeast cells, enables the expression of the sodium transporter to the Golgi apparatus. Physical and functional HKT–cornichon interactions are confirmed by the mating-based split ubiquitin system, bimolecular fluorescence complementation, and Xenopus oocyte and yeast expression systems. The interaction between the two proteins occurs in the ER of plant cells and their co-expression in oocytes leads to the sequestration of the transporter in the ER. In the yeast cornichon mutant erv14, OsHKT1;3 is mistargeted, preventing the toxic effects of sodium transport in the cell observed in wild-type cells or in the erv14 mutant that co-expressed OsHKT1;3 with either OsCNIH1 or Erv14p. Identification and characterization of rice cornichon as a possible cargo receptor opens up the opportunity to improve our knowledge on membrane protein targeting in plant cells. PMID:25750424

Coping strategies among patients with newly diagnosed amyotrophic lateral sclerosis.

Science.gov (United States)

Jakobsson Larsson, Birgitta; Nordin, Karin; Askmark, Håkan; Nygren, Ingela

2014-11-01

To prospectively identify different coping strategies among newly diagnosed amyotrophic lateral sclerosis patients and whether they change over time and to determine whether physical function, psychological well-being, age and gender correlated with the use of different coping strategies. Amyotrophic lateral sclerosis is a fatal disease with impact on both physical function and psychological well-being. Different coping strategies are used to manage symptoms and disease progression, but knowledge about coping in newly diagnosed amyotrophic lateral sclerosis patients is scarce. This was a prospective study with a longitudinal and descriptive design. A total of 33 patients were included and evaluation was made at two time points, one to three months and six months after diagnosis. Patients were asked to complete the Motor Neuron Disease Coping Scale and the Hospital Anxiety and Depression Scale. Physical function was estimated using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale. The most commonly used strategies were support and independence. Avoidance/venting and information seeking were seldom used at both time points. The use of information seeking decreased between the two time points. Men did not differ from women, but patients ≤64 years used positive action more often than older patients. Amyotrophic Lateral Sclerosis Functional Rating Scale was positively correlated with positive action at time point 1, but not at time point 2. Patients' psychological well-being was correlated with the use of different coping strategies. Support and independence were the most used coping strategies, and the use of different strategies changed over time. Psychological well-being was correlated with different coping strategies in newly diagnosed amyotrophic lateral sclerosis patients. The knowledge about coping strategies in early stage of the disease may help the nurses to improve and develop the care and support for these patients. © 2014 John Wiley

A Newly Naturalized Species in Taiwan: Rauvolfia tetraphylla L. (Apocynaceae)

OpenAIRE

Yung-Nan Ko; Fu-Shan Chou; Chun-Kuei Liao

2011-01-01

A newly naturalized plant, Rauvolfia tetraphylla L., a native species of the Apocynaceae distributed in the tropical Americas, has recently been found in southern Taiwan. It is a new record for this species to the flora of this island. A detailed description, line-drawings, photographs and geographic distribution are provided for identification of this species.

Dilemmas of a Newly Recruited Academic Qualified Professor: A Case

Science.gov (United States)

Agrawal, Anand

2015-01-01

This case describes the situation of a newly recruited academic professor who volunteered to teach a course on Research Methods to first-term MBA students in a practitioner-oriented case method Business School. Research Methods is a unique course due to its relevance not only in business but also across all graduate programs. Instructional and…

Sedum sarmentosum Bunge (Crassulaceae, a Newly Naturalized Herb in Taiwan

Directory of Open Access Journals (Sweden)

Mong-Huai Su

2014-03-01

Full Text Available Sedum sarmentosum Bunge (Crassulaceae, a newly naturalized fleshy herb in Taiwan, is reported here. The taxonomic description, line drawing, and photographs are provided. The population is colonized on Mt. Tatun, Yangmingshan National Park, north Taiwan. Since this species was reported being invasive, its impacts on the local ecosystem should be concerned.

Visual System Involvement in Patients with Newly Diagnosed Parkinson Disease.

Science.gov (United States)

Arrigo, Alessandro; Calamuneri, Alessandro; Milardi, Demetrio; Mormina, Enricomaria; Rania, Laura; Postorino, Elisa; Marino, Silvia; Di Lorenzo, Giuseppe; Anastasi, Giuseppe Pio; Ghilardi, Maria Felice; Aragona, Pasquale; Quartarone, Angelo; Gaeta, Michele

2017-12-01

Purpose To assess intracranial visual system changes of newly diagnosed Parkinson disease in drug-naïve patients. Materials and Methods Twenty patients with newly diagnosed Parkinson disease and 20 age-matched control subjects were recruited. Magnetic resonance (MR) imaging (T1-weighted and diffusion-weighted imaging) was performed with a 3-T MR imager. White matter changes were assessed by exploring a white matter diffusion profile by means of diffusion-tensor imaging-based parameters and constrained spherical deconvolution-based connectivity analysis and by means of white matter voxel-based morphometry (VBM). Alterations in occipital gray matter were investigated by means of gray matter VBM. Morphologic analysis of the optic chiasm was based on manual measurement of regions of interest. Statistical testing included analysis of variance, t tests, and permutation tests. Results In the patients with Parkinson disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density (F, -8.28; P Parkinson disease and that the entire intracranial visual system can be involved. © RSNA, 2017 Online supplemental material is available for this article.

Technical Equivalency Documentation for a Newly Acquired Alpha Spectroscopy System

International Nuclear Information System (INIS)

Hickman, D P; Fisher, S K; Hann, P R; Hume, R

2007-01-01

The response of a recently acquired Canberra(trademark) Alpha Analyst 'Blue' system (Chamber Number's 173-208) used by the Hazards Control, Radiation Safety Section, WBC/Spectroscopy Team has been studied with respect to an existing Canberra system. The existing Canberra system consists of thirty Alpha Analyst dual chambers Model XXXX comprising a total of sixty detectors (Chambers Number's 101-124 and 137-172). The existing chambers were previously compared to an older system consisting of thirty-six Model 7401 alpha spectrometry chambers (Chamber Number's 1-36) Chambers 101-124 and 137-172 are DOELAP accredited. The older system was previously DOELAP accredited for the routine Alpha Spectroscopy program used in LLNL's in vitro bioassay program. The newly acquired Alpha Analyst system operates on a network with software that controls and performs analysis of the current Alpha Analyst system (Chamber Number's 101-124 and 137-172). This exact same software is used for the current system and the newly acquired system and is DOELAP accredited. This document compares results from the existing Alpha System with the newer Alpha Analyst system

Scandinavian exceptionalism? Civic integration and labour market activation for newly arrived immigrants.

Science.gov (United States)

Breidahl, Karen N

2017-01-01

Since the late 1990s, a wide range of so-called new civic integration policies aimed at civilizing or disciplining newcomers have been introduced. Consequently, migration scholars have discussed whether a converging restrictive 'civic turn' has taken place in Western Europe or whether national models have been resilient: Based on an in-depth historical and comparative analysis of labour market activation policies targeting newly arrived immigrants in Sweden, Norway, and Denmark since the early 1990s, the article contributes to the overall question: To what extent do the institutional pathways of the Scandinavian welfare states prevail when confronted with newcomers? Activation policies targeting newly arrived immigrants exemplifies how the ambition of states to promote functional, individual autonomy is also an important, ongoing process in diverse policy areas of the welfare state and not restricted to early integration instruments. While the Scandinavian welfare states differ on a number of counts with respect to immigration control, national integration philosophies and citizenship policies, the article outlines how activation policies aimed at newly arrived immigrants share several features. One of the key factors in this turn involves path dependency from, among others, a lengthy tradition for strong state involvement and norms about employment. Another factor in this turn involves transnational policy learning. On some points, national versions of these policies are also found due to country-specific citizenship traditions, integration philosophies and party political constellations.

Newly introduced sample preparation techniques: towards miniaturization.

Science.gov (United States)

Costa, Rosaria

2014-01-01

Sampling and sample preparation are of crucial importance in an analytical procedure, representing quite often a source of errors. The technique chosen for the isolation of analytes greatly affects the success of a chemical determination. On the other hand, growing concerns about environmental and human safety, along with the introduction of international regulations for quality control, have moved the interest of scientists towards specific needs. Newly introduced sample preparation techniques are challenged to meet new criteria: (i) miniaturization, (ii) higher sensitivity and selectivity, and (iii) automation. In this survey, the most recent techniques introduced in the field of sample preparation will be described and discussed, along with many examples of applications.

Sequence Classification: 891113 [

Lifescience Database Archive (English)

Full Text Available zed to the ER, involved in retrograde traffic from the Golgi to the ER; forms a complex with the SNAREs Sec22p, Sec20p and Ufe1p; Use1p || http://www.ncbi.nlm.nih.gov/protein/6321340 ...

Depth-variable settlement patterns and predation influence on newly settled reef fishes (Haemulon spp., Haemulidae.

Directory of Open Access Journals (Sweden)

Lance K B Jordan

Full Text Available During early demersal ontogeny, many marine fishes display complex habitat-use patterns. Grunts of the speciose genus Haemulon are among the most abundant fishes on western North Atlantic coral reefs, with most species settling to shallow habitats (≤12 m. To gain understanding into cross-shelf distributional patterns exhibited by newly settled stages of grunts (<2 cm total length, we examined: 1 depth-specific distributions of congeners at settlement among sites at 8 m, 12 m, and 21 m, and 2 depth-variable predation pressure on newly settled individuals (species pooled. Of the six species identified from collections of newly settled specimens (n = 2125, Haemulon aurolineatum (tomtate, H. flavolineatum (French grunt, and H. striatum (striped grunt comprised 98% of the total abundance; with the first two species present at all sites. Prevalence of H. aurolineatum and H. flavolineatum decreased substantially from the 8-m site to the two deeper sites. In contrast, H. striatum was absent from the 8-m site and exhibited its highest frequency at the 21-m site. Comparison of newly settled grunt delta density for all species on caged (predator exclusion and control artificial reefs at the shallowest site (8-m revealed no difference, while the 12-m and 21-m sites exhibited significantly greater delta densities on the caged treatment. This result, along with significantly higher abundances of co-occurring piscivorous fishes at the deeper sites, indicated lower predation pressure at the 8-m site. This study suggests habitat-use patterns of newly settled stages of some coral reef fishes that undergo ontogenetic shifts are a function of depth-variable predation pressure while, for at least one deeper-water species, proximity to adult habitat appears to be an important factor affecting settlement distribution.

A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among children.

Science.gov (United States)

Stassijns, Jorgen; Bollaerts, Kaatje; Baay, Marc; Verstraeten, Thomas

2016-02-03

New adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a large body of evidence on their clinical safety in children. We carried out a systematic search for safety data from published clinical trials on newly adjuvanted vaccines in children ≤10 years of age. Serious adverse events (SAEs), solicited AEs, unsolicited AEs and AEs of special interest were evaluated for four new adjuvants: the immuno-stimulants containing adjuvant systems AS01 and AS02, and the squalene containing oil-in-water emulsions AS03 and MF59. Relative risks (RR) were calculated, comparing children receiving newly adjuvanted vaccines to children receiving other vaccines with a variety of antigens, both adjuvanted and unadjuvanted. Twenty-nine trials were included in the meta-analysis, encompassing 25,056 children who received at least one dose of the newly adjuvanted vaccines. SAEs did not occur more frequently in adjuvanted groups (RR 0.85, 95%CI 0.75-0.96). Our meta-analyses showed higher reactogenicity following administration of newly adjuvanted vaccines, however, no consistent pattern of solicited AEs was observed across adjuvant systems. Pain was the most prevalent AE, but often mild and of short duration. No increased risks were found for unsolicited AEs, febrile convulsions, potential immune mediated diseases and new onset of chronic diseases. Our meta-analysis did not show any safety concerns in clinical trials of the newly adjuvanted vaccines in children ≤10 years of age. An unexplained increase of meningitis in one Phase III AS01-adjuvanted malaria trial and the link between narcolepsy and the AS03-adjuvanted pandemic vaccine illustrate that continued safety monitoring is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Database marketing practices and opportunities in a newly emerging African market

NARCIS (Netherlands)

Paas, L.J.

2009-01-01

In this paper, qualitative research is conducted to gain insight into the current application and potential of database marketing in a newly emerging African economy, Tanzania. It is found that database marketing applications in Tanzania are currently limited, but that there is potential. The most

Yield evaluation and stability analysis in newly selected `KSA' cotton ...

African Journals Online (AJOL)

Yield evaluation and stability analysis in newly selected `KSA' cotton cultivars in Western Kenya. R M Opondo, G A Ombakho. Abstract. (African Crop Science Journal, 1997 5(2): 119-126). http://dx.doi.org/10.4314/acsj.v5i2.27854 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

A Newly Naturalized Species in Taiwan: Rauvolfia tetraphylla L. (Apocynaceae

Directory of Open Access Journals (Sweden)

Yung-Nan Ko

2011-06-01

Full Text Available A newly naturalized plant, Rauvolfia tetraphylla L., a native species of the Apocynaceae distributed in the tropical Americas, has recently been found in southern Taiwan. It is a new record for this species to the flora of this island. A detailed description, line-drawings, photographs and geographic distribution are provided for identification of this species.

Rivina humilis L. (Phytolaccaceae, a Newly Naturalized Plant in Taiwan

Directory of Open Access Journals (Sweden)

Yen-Hsueh Tseng

2008-12-01

Full Text Available A newly naturalized plant, Rivina humilis L., was found recently in the central part of Taiwan. This plant represents a new record of this genus and species for Taiwan. This Neotropical plant, native to the southern USA, Mexico, the Caribbean islands, and Central and South America, is described and illustrated in this report.

The subject of pedagogy from theory to practice--the view of newly registered nurses.

Science.gov (United States)

Ivarsson, Bodil; Nilsson, Gunilla

2009-07-01

The aim was to describe, from the newly registered nurses' perspective, specific events when using their pedagogical knowledge in their everyday clinical practice. The design was qualitative and the critical incident technique was used. Data was collected via interviews with ten newly registered nurses who graduated from the same University program 10 months earlier and are now employed at a university hospital. Two categories emerged in the analyses. The first category was "Pedagogical methods in theory" with the sub-categories Theory and the application of the course in practice, Knowledge of pedagogy and Information as a professional competence. The second category was "Pedagogical methods in everyday clinical practice" with sub-categories Factual knowledge versus pedagogical knowledge, Information and relatives, Difficulties when giving information, Understanding information received, Pedagogical tools, Collaboration in teams in pedagogical situations, and Time and giving information. By identifying specific events regarding pedagogical methods the findings can be useful for everyone from teachers and health-care managers to nurse students and newly registered nurses, to improve teaching methods in nurse education.

Cell wall accumulation of fluorescent proteins derived from a trans-Golgi cisternal membrane marker and paramural bodies in interdigitated Arabidopsis leaf epidermal cells.

Science.gov (United States)

Akita, Kae; Kobayashi, Megumi; Sato, Mayuko; Kutsuna, Natsumaro; Ueda, Takashi; Toyooka, Kiminori; Nagata, Noriko; Hasezawa, Seiichiro; Higaki, Takumi

2017-01-01

In most dicotyledonous plants, leaf epidermal pavement cells develop jigsaw puzzle-like shapes during cell expansion. The rapid growth and complicated cell shape of pavement cells is suggested to be achieved by targeted exocytosis that is coordinated with cytoskeletal rearrangement to provide plasma membrane and/or cell wall materials for lobe development during their morphogenesis. Therefore, visualization of membrane trafficking in leaf pavement cells should contribute an understanding of the mechanism of plant cell morphogenesis. To reveal membrane trafficking in pavement cells, we observed monomeric red fluorescent protein-tagged rat sialyl transferases, which are markers of trans-Golgi cisternal membranes, in the leaf epidermis of Arabidopsis thaliana. Quantitative fluorescence imaging techniques and immunoelectron microscopic observations revealed that accumulation of the red fluorescent protein occurred mostly in the curved regions of pavement cell borders and guard cell ends during leaf expansion. Transmission electron microscopy observations revealed that apoplastic vesicular membrane structures called paramural bodies were more frequent beneath the curved cell wall regions of interdigitated pavement cells and guard cell ends in young leaf epidermis. In addition, pharmacological studies showed that perturbations in membrane trafficking resulted in simple cell shapes. These results suggested possible heterogeneity of the curved regions of plasma membranes, implying a relationship with pavement cell morphogenesis.

Age-stratified 5-year risks of cervical precancer among women with enrollment and newly detected HPV infection.

Science.gov (United States)

Gage, Julia C; Katki, Hormuzd A; Schiffman, Mark; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas; Cheung, Li C; Castle, Philip E; Kinney, Walter K

2015-04-01

It is unclear whether a woman's age influences her risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) upon detection of HPV. A large change in risk as women age would influence vaccination and screening policies. Among 972,029 women age 30-64 undergoing screening with Pap and HPV testing (Hybrid Capture 2, Qiagen, Germantown, MD) at Kaiser Permanente Northern California (KPNC), we calculated age-specific 5-year CIN3+ risks among women with HPV infections detected at enrollment, and among women with "newly detected" HPV infections at their second screening visit. Women (57,899, 6.0%) had an enrollment HPV infection. Among the women testing HPV negative at enrollment with a second screening visit, 16,724 (3.3%) had a newly detected HPV infection at their second visit. Both enrollment and newly detected HPV rates declined with age (p < 0.001). Women with enrollment versus newly detected HPV infection had higher 5-year CIN3+ risks: 8.5% versus 3.9%, (p < 0.0001). Risks did not increase with age but declined slightly from 30-34 years to 60-64 years: 9.4% versus 7.4% (p = 0.017) for enrollment HPV and 5.1% versus 3.5% (p = 0.014) for newly detected HPV. Among women age 30-64 in an established screening program, women with newly detected HPV infections were at lower risk than women with enrollment infections, suggesting reduced benefit vaccinating women at older ages. Although the rates of HPV infection declined dramatically with age, the subsequent CIN3+ risks associated with HPV infection declined only slightly. The CIN3+ risks among older women are sufficiently elevated to warrant continued screening through age 65. © 2014 UICC.

MGMT inactivation and clinical response in newly diagnosed GBM patients treated with Gliadel.

Science.gov (United States)

Grossman, Rachel; Burger, Peter; Soudry, Ethan; Tyler, Betty; Chaichana, Kaisorn L; Weingart, Jon; Olivi, Alessandro; Gallia, Gary L; Sidransky, David; Quiñones-Hinojosa, Alfredo; Ye, Xiaobu; Brem, Henry

2015-12-01

We examined the relationship between the O(6)-methylguanine-methyltransferase (MGMT) methylation status and clinical outcomes in newly diagnosed glioblastoma multiforme (GBM) patients who were treated with Gliadel wafers (Eisai, Tokyo, Japan). MGMT promoter methylation has been associated with increased survival among patients with GBM who are treated with various alkylating agents. MGMT promoter methylation, in DNA from 122 of 160 newly diagnosed GBM patients treated with Gliadel, was determined by a quantitative methylation-specific polymerase chain reaction, and was correlated with overall survival (OS) and recurrence-free survival (RFS). The MGMT promoter was methylated in 40 (32.7%) of 122 patients. The median OS was 13.5 months (95% confidence interval [CI] 11.0-14.5) and RFS was 9.4 months (95% CI 7.8-10.2). After adjusting for age, Karnofsky performance score, extent of resection, temozolomide (TMZ) and radiation therapy (RT), the newly diagnosed GBM patients with MGMT methylation had a 15% reduced mortality risk, compared to patients with unmethylated MGMT (hazard ratio 0.85; 95% CI 0.56-1.31; p=0.46). The patients aged over 70 years with MGMT methylation had a significantly longer median OS of 13.5 months, compared to 7.6 months in patients with unmethylated MGMT (p=0.027). A significant difference was also found in older patients, with a median RFS of 13.1 versus 7.6 months for methylated and unmethylated MGMT groups, respectively (p=0.01). Methylation of the MGMT promoter in newly diagnosed GBM patients treated with Gliadel, RT and TMZ, was associated with significantly improved OS compared to the unmethylated population. In elderly patients, methylation of the MGMT promoter was associated with significantly better OS and RFS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy

Science.gov (United States)

Wei, Lu; Yu, Yong; Shen, Yihui; Wang, Meng C.; Min, Wei

2013-01-01

Synthesis of new proteins, a key step in the central dogma of molecular biology, has been a major biological process by which cells respond rapidly to environmental cues in both physiological and pathological conditions. However, the selective visualization of a newly synthesized proteome in living systems with subcellular resolution has proven to be rather challenging, despite the extensive efforts along the lines of fluorescence staining, autoradiography, and mass spectrometry. Herein, we report an imaging technique to visualize nascent proteins by harnessing the emerging stimulated Raman scattering (SRS) microscopy coupled with metabolic incorporation of deuterium-labeled amino acids. As a first demonstration, we imaged newly synthesized proteins in live mammalian cells with high spatial–temporal resolution without fixation or staining. Subcellular compartments with fast protein turnover in HeLa and HEK293T cells, and newly grown neurites in differentiating neuron-like N2A cells, are clearly identified via this imaging technique. Technically, incorporation of deuterium-labeled amino acids is minimally perturbative to live cells, whereas SRS imaging of exogenous carbon–deuterium bonds (C–D) in the cell-silent Raman region is highly sensitive, specific, and compatible with living systems. Moreover, coupled with label-free SRS imaging of the total proteome, our method can readily generate spatial maps of the quantitative ratio between new and total proteomes. Thus, this technique of nonlinear vibrational imaging of stable isotope incorporation will be a valuable tool to advance our understanding of the complex spatial and temporal dynamics of newly synthesized proteome in vivo. PMID:23798434

Sport as a context for integration:newly arrived immigrant children in Sweden drawing sporting experiences

OpenAIRE

Hertting, Krister; Karlefors, Inger

2013-01-01

Sport is a global phenomenon, which can make sport an important arena for integration into new societies. However, sport is also an expression of national culture and identities. The aim of this study is to explore images and experiences that newly-arrived immigrant children in Sweden have about sport in their country of origin, and challenges that can arise in processes of integration through sport. We asked 20 newly arrived children aged 10 to 13 to make drawings about sporting experiences ...

Alterations found with computerized tomography in newly diagnosed type 2 diabetics

International Nuclear Information System (INIS)

Bruna, J.

1989-01-01

In 28 newly diagnosed type 2 diabetic patients (insulin-independent), computerized tomography (CT) was used to determine the density of the pancreas and the kidneys, densities of the liver, spleen and blood in the abdominal aorta, and to investigate pathological changes in the tissues mentioned above. The results were correlated with laboratory findings. The following changes were found: decreased density of the pancreas (29.4 H) and the liver (49.1 H) and increased density of the spleen (56.3 H) and blood in the abdominal aorta (43.7 H). The decreased density of the pancreas appears to be connected with disorders of lipoprotein metabolism. The decreased liver density was related to increased energy intake by food and to overweight evaluated by Broc's index. Other CT findings in the newly diagnosed type 2 diabetics (changes in the size of the pancreas, and kidneys, kidney cysts, nephrolithiasis, sclerotic plaques on aorta) were not significant. (author). 2 tabs., 11 refs

Shared decision making in the management of children with newly diagnosed immune thrombocytopenia.

Science.gov (United States)

Beck, Carolyn E; Boydell, Katherine M; Stasiulis, Elaine; Blanchette, Victor S; Llewellyn-Thomas, Hilary; Birken, Catherine S; Breakey, Vicky R; Parkin, Patricia C

2014-10-01

This study aimed to examine the treatment decision-making process for children hospitalized with newly diagnosed immune thrombocytopenia (ITP). Using focus groups, we studied children with ITP, parents of children with ITP, and health care professionals, inquiring about participants' experience with decision support and decision making in newly diagnosed ITP. Data were examined using thematic analysis. Themes that emerged from children were feelings of "anxiety, fear, and confusion"; the need to "understand information"; and "treatment choice," the experience of which was age dependent. For parents, "anxiety, fear, and confusion" was a dominant theme; "treatment choice" revealed that participants felt directed toward intravenous immune globulin (IVIG) for initial treatment. For health care professionals, "comfort level" highlighted factors contributing to professionals' comfort with offering options; "assumptions" were made about parental desire for participation in shared decision making (SDM) and parental acceptance of treatment options; "providing information" was informative regarding modes of facilitating SDM; and "treatment choice" revealed a discrepancy between current practice (directed toward IVIG) and the ideal of SDM. At our center, families of children with newly diagnosed ITP are not experiencing SDM. Our findings support the implementation of SDM to facilitate patient-centered care for the management of pediatric ITP.

Serum lipid profile of newly diagnosed hypertensive patients in nnewi, South-East Nigeria.

Science.gov (United States)

Osuji, Charles U; Omejua, Emeka G; Onwubuya, Emmanuel I; Ahaneku, Gladys I

2012-01-01

Abnormalities in serum lipid and lipoprotein levels are recognized major modifiable cardiovascular disease and essential hypertension risk factors. The objective of this study was to examine the serum lipid patterns of newly diagnosed hypertensive patients attending a tertiary healthcare centre in South East Nigeria. Methods. Two hundred and fifty newly diagnosed adult hypertensive patients and an equal number of age- and sex-matched controls without hypertension were consecutively recruited from the Medical and General Outpatient Clinics of Nnamdi Azikiwe University Teaching Hospital, Nnewi. Result. 126 males and 124 females were in each of the two groups. Mean age was comparable in both groups. Hypertensives had significantly higher mean systolic blood pressure, diastolic blood pressure, body mass index, waist circumference, waist-hip ratio, and fasting blood sugar than the controls. The mean TC, TG, and LDL-C were significantly higher among the hypertensives. The mean HDL-C was comparable; P = 0.8. Among the hypertensive subjects, there was statistically significant positive correlation between BMI and TC; LDL-C and TG; WC and TG; FBS and TC; LDL-C and TG. HDL-C showed a statistically significant inverse correlation with WHR in hypertensives. Conclusion. This study showed that lipid abnormalities are highly prevalent among newly diagnosed hypertensives in South-East Nigeria.

A longitudinal, mixed methods investigation of newly qualified nurses' workplace stressors and stress experiences during transition.

Science.gov (United States)

Halpin, Yvonne; Terry, Louise M; Curzio, Joan

2017-11-01

To investigate transition in newly qualified nurses through an exploration of their stressors and stress experiences during their first 12 months postqualifying. Globally, thousands of new nurses qualify annually. They are crucial for the profession and healthcare service delivery. Work-related stress has multiple serious consequences, yet there is a lack of robust, empirical evidence that directly analyses newly qualified nurses and the stress they feel and experience in the workplace. Understanding what causes newly qualified nurses' stress is vital to retaining and nurturing this vital component of the workforce. Longitudinal, explanatory sequential mixed methods, cohort study. At the point of qualification (n = 288), 6 months postqualifying (n = 107) and 12 months postqualifying (n = 86), newly qualified nurses completed the Nursing Stress Scale, with 14 completing a one-to-one interview at 12 months postqualifying. Data were collected from 2010 - 2012. Inferential statistics, "thematic analysis" and "side-by-side comparisons in a discussion" were used for analysis. Workload was consistently the highest reported stressor with inadequate staffing and managing multiple role demands given as explanations. Incivility within the workplace was a noted stressor. Conversely, being part of "a good team" provided a civil, supportive, facilitative work environment. Entering nurse education with previous healthcare experience had a mediating effect on the reported frequency of stressors. Newly qualified nurses encounter multiple work-related stressors over their first 12 months postqualifying, which are intrinsically entwined with their transition. Employing organizations need to be more proactive in managing their workload and addressing workplace incivility. © 2017 John Wiley & Sons Ltd.

Newly Qualified Teachers' Professional Digital Competence: Implications for Teacher Education

Science.gov (United States)

Gudmundsdottir, Greta Björk; Hatlevik, Ove Edvard

2018-01-01

The professional digital competence (PDC) of teachers is of growing importance in classrooms, now that digital resources and digital media are becoming important parts of teachers' everyday practice. This study explores how newly qualified teachers are prepared to use information and communication technology (ICT) in their initial teacher…

Drag resistance measurements for newly applied antifouling coatings and welding seams on ship hull surface

DEFF Research Database (Denmark)

Wang, Xueting; Olsen, S. M.; Andres, E.

Drag resistances of newly applied antifouling coatings and welding seams on ship hull surface have been investigated using a pilot-scale rotary setup. Both conventional biocide-based antifouling (AF) coatings and silicone-based fouling release (FR) coatings have been studied and compared in their......Drag resistances of newly applied antifouling coatings and welding seams on ship hull surface have been investigated using a pilot-scale rotary setup. Both conventional biocide-based antifouling (AF) coatings and silicone-based fouling release (FR) coatings have been studied and compared...